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SK 12-15-15/BioWorld on AZN: “We save probably as much as we're spending because of the cost of these drugs.”
12-15-15/BioWorld: “If You Can't Beat 'em, Join 'em; Looking for Immuno-onc Boost”
By Brian Orelli, BioWorld Staff Writer
...
Earlier this year, Peregrine partnered up with Astrazeneca to test the pharma's anti-PD-L1 immune checkpoint inhibitor, durvalumab, with bavituximab, after preclinical data suggested that the combination might help even if tumors don't initially express PD-L1. By removing the phosphatidylserine checkpoint, the immune system is activated, but the tumor can then use PD-L1 to inhibit the immune system. Durvalumab should help perpetuate the bavituximab-induced immune response, while boosting the opportunity for durvalumab in tumors that are not expressing PD-L1 until the bavituximab treatment. "It's sort of a win-win situation," King said. ...
King said he thinks that bavituximab will likely work with any of the drugs targeting the PD-1 pathway, but decided to work with London-based Astrazeneca rather than one of the FDA-approved drugs, in part, because Astrazeneca was willing to provide the drug free of charge. "We save probably as much as we're spending because of the cost of these drugs," King said.
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=119200003
12-15-15: BioWorld quotes Steve.King in “Immuno-onc Boost” article
12-15-15/BioWorld: “If You Can't Beat 'em, Join 'em; Looking for Immuno-onc Boost”
By Brian Orelli, BioWorld Staff Writer
http://www.bioworld.com/content/if-you-cant-beat-em-join-em-looking-immuno-onc-boost-1
Last week, Threshold Pharmaceuticals Inc. announced the failure of 2 phase III evofosfamide trials (See BioWorld Today, Dec. 8, 2015)…
ENHANCING ACTIVITY - Aduro Biotech's CRS-207...
MULTIPLE CHECKPOINTS
Likewise, Peregrine Pharmaceuticals Inc. said it makes sense to test its drug, bavituximab, with a drug targeting the PD-1 pathway. Bavituximab targets phosphatidylserine, a molecule released during apoptosis that down-regulates the immune cells to keep the immune system from mounting a major response against a few cells that have died.
"Tumors hijack this pathway," Steven King, President & CEO of Tustin, Calif.-based Peregrine told BioWorld Insight. Tumors can outgrow their blood supply causing cells to die, but phosphatidylserine acts as a checkpoint, dampening the immune response against a tumor.
Peregrine is currently testing bavituximab with docetaxel compared to docetaxel alone in SUNRISE, a phase III trial in previously treated NSCLC patients that is scheduled to read out next year.
Earlier this year, Peregrine partnered up with Astrazeneca to test the pharma's anti-PD-L1 immune checkpoint inhibitor, durvalumab, with bavituximab, after preclinical data suggested that the combination might help even if tumors don't initially express PD-L1. By removing the phosphatidylserine checkpoint, the immune system is activated, but the tumor can then use PD-L1 to inhibit the immune system. Durvalumab should help perpetuate the bavituximab-induced immune response, while boosting the opportunity for durvalumab in tumors that are not expressing PD-L1 until the bavituximab treatment. "It's sort of a win-win situation," King said.
King said he thinks that bavituximab will likely work with any of the drugs targeting the PD-1 pathway, but decided to work with London-based Astrazeneca rather than one of the FDA-approved drugs, in part, because Astrazeneca was willing to provide the drug free of charge. "We save probably as much as we're spending because of the cost of these drugs," King said.
CHANGING COURSE - Heat Biologics's HS-110...
WE LIKE YOU A LOT - Bavarian Nordic's Prostvac...
*end*
Avid's New Customer – hints from 9/2014 on – definitely hit the revenue stream in Q2. We do not know who this new customer is at this point (at least I don't!). ...And now on 12-10-15, Rob Garnick discloses, “We are already contemplating our options to increase further our mfg. capacity [beyond Myford=Avid II]”, due to ”what appears to be a growing opportunity in this important area of our business.”
Q/E10-31-15 Q/E7-31-15 FY4-30-15 FY4-30-14
Halozyme 56% 84% 79% 91%
Cust-A U.S. 41% 15% 12% 1%
Other Custs 3% 1% 9% 8%
AVID PROFITABILITY (GROSS*) BY QTR:
QTR Avid-Rev$ CostofMfg$ Gross-Profit$ GP%
FY13Q1 7-31-12 4,135,000 2,024,000 2,111,000 51%
FY13Q2 10-31-12 6,061,000 3,703,000 2,358,000 39%
FY13Q3 1-31-13 6,961,000 3,651,000 3,310,000 47%
FY13Q4 4-30-13 4,176,000 3,217,000 959,000 23%
FY14Q1 7-31-13 4,581,000 2,670,000 1,911,000 42%
FY14Q2 10-31-13 7,354,000 4,195,000 3,159,000 43%
FY14Q3 1-31-14 3,885,000 2,416,000 1,469,000 38%
FY14Q4 4-30-14 6,474,000 3,829,000 2,645,000 41%
FY15Q1 7-31-14 5,496,000 3,583,000 1,913,000 35%
FY15Q2 10-31-14 6,263,000 4,139,000 2,124,000 34%
FY15Q3 1-31-15 5,677,000 3,113,000 2,564,000 45%
FY15Q4 4-30-15 9,308,000 4,758,000 4,550,000 49%
FY16Q1 7-31-15 9,379,000 4,608,000 4,771,000 51%
FY16Q2 10-31-15 9,523,000 4,741,000 4,782,000 50%
FY13 TOTAL: 21,333,000 12,595,000 8,738,000 41%*
FY14 TOTAL: 22,294,000 13,110,000 9,184,000 41%*
FY15 TOTAL: 26,744,000 15,393,000 11,151,000 42%*
12-10-15 Qtly CC-Transcript, PR(Fins/Devs Q2FY16/qe10-31-15), updated Avid Revenues History Table By Quarter…
=> Total Revs May06-Oct15: $148.1mm/Avid + $24.1mm/Govt + $2.4mm/Lic. = $174.7mm. Cash at 10-31-15: $72.0mm
As of Dec. 9, 2015, there were 229,701,808 shares outstanding.
This large post has 3 sections:
I. 12-10-15 Q2/FY16 Qtly. Earnings Conf. Call TRANSCRIPT (q/e 10-31-15)
II. 12-10-15 PPHM Press Release: Q2/FY16 Earnings & Developments
III. Updated Table of Avid Revenues By Quarter (May’06-Current)
…Recall: Peregrine’s FY runs May-Apr, so FY’16 = May’15-Apr’16.
((( Orig. transcript from SeekingAlpha.com [ http://tinyurl.com/zq52d5w ], with numerous corrections made. )))
Link to webcast replay:
http://ir.peregrineinc.com/events.cfm => http://edge.media-server.com/m/p/jigxfb5c
FULL TRANSCRIPT…
12-10-2015 FY’16/Q2 Earnings Conf. Call (q/e 10-31-15)
WELCOME & FWD-LOOKING STATEMENTS: Tim Brons, Vida Strategic Partners (IR) http://www.peregrineinc.com
Speakers: Steve King, Joe Shan, Stephen Worsley, Rob Garnick, Paul Lytle; Q&A session.
CEO STEVE KING – OPENING COMMENTS:
Thanks as always to all of you who have dialed in, and to all of you who are participating via webcast today. I’ll start by saying that we are making great progress in our broad overall development strategy for bavituximab. The strategy is to establish the potential of bavituximab in combination with current & evolving standard of care drugs, with both chemotherapy and immuno-oncology combinations in multiple cancer indications. Our goal is to drive to meaningful clinical data points in each of these areas by early 2017. In accordance, today’s development discussions will focus on these efforts, including upcoming completion enrollment in the SUNRISE trial which is evaluating a chemotherapy combination, and, as SUNRISE wraps up, our plans for a smooth transition of the key SUNRISE clinical sites directly to the next Phase II lung cancer trial evaluating an IO combination. In addition, we are expanding our potential cancer indications through initiation of a Phase II/III metastatic breast cancer study. All of this while continuing to work through several other clinical trial concepts actively under development or initiation in the new year.
On the development front, I’m pleased to report today that we are nearing completion of enrollment in the cornerstone of our bavituximab development strategy, our Phase III SUNRISE trial. In fact, with over 90% of the expected enrollment complete, we currently have sufficient patient enrollment based on the assumptions of the study to allow the trial’s planned interim evaluations and final readout based on the primary endpoint of overall survival. Having said that, we do expect to complete enrollment of at least the pre-specified 582 patients over the coming weeks. At this point, the next big milestones really are the interim data analysis from the study, expected to take place during early & mid 2016, with trial unblinding expected toward the end of 2016. Joe will add little more color to the up coming milestones for the SUNRISE trial during his prepared remarks.
For me, what has now become the most important thing at this point in our broader strategy is to engage our best enrolling sites from the SUNRISE trial toward a smooth transition to the new Phase II study that will evaluate bavi in combination with AstraZeneca’s anti-PD-L1 antibody durvalumab. We have a golden opportunity here to maintain continuity for our lung cancer program by continuing almost seamlessly working with our high enrolling sites and key investigators in essentially the same, even in extended, patient population with the inclusion of squamous non-small cell lung cancer patients. I have personally had the opportunity to meet with key investigators all over the globe and there is a lot of enthusiasm for continuing to work with Peregrine and bavituximab in the new study. Based on feedback so far, we expect that the new study could enroll even more quickly than the SUNRISE trial and the best way to ensure that is to get off to a quick start, again keeping us on track for data from the new study by early 2017. This would give us two nice sets of data in NSCLC to work with.
Equally exciting is the Phase II/III metastatic HER2- breast cancer study that we are looking forward to starting by year-end. I say exciting because the new trial design has a solid clinical data basis, and our previously completed Phase I & II trials in a patient population in these new treatment options. While we don’t have the same benefit as we do for the lung cancer program of rolling right from one study into another, the team has been working diligently to get the study started by the year-end, giving us additional enrollment months, which again can put us on track for some meaningful clinical data from the study by early 2017.
The company is also working diligently on a number of other studies, including our other collaboration with AstraZeneca, evaluating a combination of bavi with chemotherapy and adding in again their durvalumab antibody in multiple solid tumor indications. So, conceptually, “get an immune response going with chemotherapy & Bavi, and then keep it going with durvalumab”.
In addition, we are working toward initiating an earlier stage breast cancer study, as well as a number of other concepts that are in development. So, stay tuned for future clinical developments. Taken together, these clinical efforts, along with the plethora of preclinical & translation collaborations evaluating new combinations, new potential indications, and further validating our immune mechanism of action has a potential to add substantial value over the coming year. We expect a steady flow of scientific & clinical presentations over the coming year as we continue to learn to more about the potential bavituximab.
Oh, and by the way, today we also announced another record revenue quarter from our biomanufacturing business, with our new Myford manufacturing facility just ready for GMP production, which can help spur even more future growth for the business, not the least of which is getting ready for bavi commercial production. Rob & Paul will add more detail and discuss the continued growth for our mfg. business shortly. To say that these are busy times at Peregrine is an understatement.
JOE SHAN (VP/Clin.&Reg. Affairs) – CLINICAL TRIALS:
I’d like to start by quickly addressing our Phase III SUNRISE trial, which is evaluating the use of bavituximab & docetaxel in patients with previously treated locally advanced or metastatic non-squamous NSCLC. As Steve stated, we have already enrolled the number of patients required to achieve the trial’s main objectives, and expect to complete enrollment of the target sample size of 582 in the coming weeks. The next milestones are the interim analyses that will be conducted when 33% & 50% of the targeted number of deaths are reached. While these are event driven, it is our expectation that the 1st interim analysis will read out in early 2016 and the 2nd interim analysis around mid-2016. The final analysis, which will trigger study unblinding, is currently projected to occur at the end of 2016.
With the SUNRISE enrollment nearing completion, the Peregrine clinical team is shifting focus to a number of new clinical projects, including those just referenced by Steve. In each case, our goal is to generate clinical evidence of bavituximab’s ability to improve patient outcomes when combined with chemotherapy and immuno-oncology agents. With this goal in mind, we are very pleased to be collaborating with AstraZeneca. Through this partnership, we will be conducting 2 clinical trials, both of which will be initiated in 2016. One trial, which we expect to initiate early 2016, is a global randomized Phase II study in approx. 200 patients with previously treated NSCLC. This trial will evaluate the combination of bavituximab and AZ’s anti-PD-L1 immune checkpoint inhibitor durvalumab, or MEDI4736. As part of this combination trial, patients will also be evaluated retrospectively for the correlation between their PD-L1 levels & clinical outcomes. As the remaining patients are enrolled into SUNRISE, we have already begin laying the groundwork to quickly initiate this new Phase II combination study at a number of our most active sites participating in SUNRISE. These investigators are very familiar with bavituximab and have access to the appropriate patient populations, and we believe this experience will greatly benefit our new study.
The other trial with AstraZeneca will be a Phase I/Ib trial evaluating bavituximab in combination with chemotherapy & durvalumab in multiple solid tumors. The Phase I part of the trial will confirm the tolerability of the 2 IO agents and establish a recommended dose regimen for the Phase 1b part of the trial, which will assess safety & activity of the triple combination, which includes standard chemotherapy.
We’re particularly excited about these trials because we believe that bavituximab & durvalumab have different and potentially complementary mechanisms. Bavituximab, by targeting exposed PS, a highly immuno-suppressive molecule exposed on the surface of cells in the tumor microenvironment, has been shown to trigger macrophage re-polarization and tumor specific T-Cell activation. Durvalumab is a monoclonal antibody directed against programmed cell death ligand1, or PD-L1, and signals from PD-L1 help tumors avoid detection by the immune system. It’s become apparent that check inhibitors like durvalumab are most effective when there is a preexisting T-Cell response in tumors, as it provides those check inhibitors with the immune active environment they need to work best. Importantly, we have demonstrated in preclinical models the ability of bavituximab to activate CD8+ T-Cells and the anti-tumor activity PD-L1 checkpoint blockade is greatly enhanced when combined with bavituximab. Another important observation we recently made is that our PS signaling pathway inhibitors demonstrate multiple signs of immune activation in the low or negative PD-L1 tumors. We believe that this holds great potential to increase the number of patients able to respond to checkpoint therapy as well as traditional chemotherapy. Based on these observations, we believe that by combining these 2 approaches, the potential exists for a more complete & durable anti-tumor immune response. We look forward to getting both trials in our AstraZeneca collaboration underway.
Now, beyond lung cancer, we plan to initiate addl. clinical trials in breast cancer based on our clinical experience to-date. Data from a Phase I IST of bavituximab+paclitaxel published in Cancer Medicine earlier this year [3-31-15/A.Stopeck, N=13: PFS=7.3mos, ORR=85%, 2 CR's http://tinyurl.com/nm5oog4 ] demonstrated an impressive 85% response rate of patients with HER2- metastatic breast cancer. Data from this IST, together with 2 prior Peregrine-sponsored trials of bavituximab with taxane-based chemotherapy, which yielded between 61-74% response rates and a MOS of over 20mos. in patients with advanced or metastatic breast cancer, provides strong rationale to advance this indication. Importantly, taxanes continue to be a key std. treatment option for different stages of breast cancer. Accordingly, we plan to initiate a Phase II/III trial in patients with HER2- metastatic breast cancer, with all patients receiving physicians’ choice of paclitaxel or docetaxel, either alone or in combination with bavituximab. The Phase II part of the trial will enroll approx. 150 patients with a primary end point from overall response rate. The first sites in this Phase II/III breast cancer trial are scheduled to be initiated before the end of the year. Furthermore, we're planning a trial evaluating neoadjuvant paclitaxel with or without bavituximab, in the hopes of further elucidating bavituximab’s immune modulating mechanism and look for clinical signals in early stage breast cancer. That concludes my comments today I’d like to turn the call over to Steve Worsley to give an overview of business development activity.
STEPHEN WORSLEY (VP/Business Dev.):
We were very pleased to announce our collaboration with AstraZeneca in August [8-24-15: http://tinyurl.com/owlxpsf ] and were even more delighted to announce the expansion of that agreement in October [10-15-15: http://tinyurl.com/q79bkam ]. We believe that AstraZeneca’s enthusiasm for this program is based on the promise & potential of bavituximab. Copious amounts of positive data have consistently demonstrated bavituximab’s therapeutic value & ability to provide solutions to the limitations of currently available treatments. Today, checkpoint inhibitors are primarily effective in patients with high PD-L1 expression, a minority of all patients being treated. However, translational findings have demonstrated that bavituximab is effective in patients with the lowest PD-L1, PD-1 expressions, highlighting the potential bavituximab to convert patients with the low expression levels who do not respond to anti-PD-1 treatments into responders.
In addition to AstraZeneca, such data have also been the impetus for our ongoing collaboration with Memorial Sloan Kettering Cancer [5-21-15: http://tinyurl.com/qxu4w2x ], which is evaluating combinations of bavituximab with other checkpoint inhibitors & immune stimulatory agents for the purpose of developing new & increasingly effective anti-cancer treatments. It has also been the driver for our ongoing work with the Univ. of Texas SW, as well as a number of other ISTs.
Peregrine’s goal in partnering with these immuno-oncology leaders is to define the broader scope of utility for bavituximab. Through these collaborations, we are actively identifying a range of indications & treatments that will benefit from combination therapy with bavituximab. This will undoubtedly yields important findings in the near-term that will continue to build shareholder value. We continue our dialog with a number of other world leading pharmaceutical organizations and believe that bavituximab will continue to generate partnering interest. I will now turn the call over to Rob Garnick, Peregrine’s Head of Regulatory Affairs, who’ll discuss our drug mfg. & regulatory activities.
Rob Garnick (Head of Regulatory Affairs):
As we reported in our press release today, our new facility has just been commissioned for the initial phase of GMP manufacturing. I’d like to reiterate that this facility, currently named the Myford facility, is state-of-the-art and its construction was completed for a fraction of the cost of building of comparable facilities. This in and of itself is a major accomplishment and I am very proud of our team for their success in this achievement. Going forward, we expect this facility will be a highly valuable asset for Peregrine & Avid. Initial engineering runs, which will be initiated tomorrow, will be followed by GMP runs prior to process validation for products entering into the facility. GMP material produced in the new facility can be used either in clinical trials or for commercial sale once Peregrine or Avid’s business partners make the appropriate regulatory filings in the territories where they intend to use the product. This generally requires several runs and demonstrating that the product produced in the Myford facility is comparable to product produced in our Franklin facility or in other production facilities. With the Myford site now in the initial phase of GMP manufacturing, we have seen a significant increase in demand for production capacity. Although, we have just opened the doors at Myford, we are already contemplating our options to increase further mfg. capacity. Although no decisions have been made, we are pleased to have what appears to be a growing opportunity in this important area of our business.
On the regulatory side, we are busy to taking the steps necessary to initiate up the new clinical trials that Joe described. To this end, we successfully filed the new IND supporting expanding the bavituximab breast cancer program and subsequently received FDA clearance to commence the study. We have also taken important steps to de-risk our bavituximab/durvalumab combination trials by requesting and receiving critical guidelines from the FDA. It’s been a busy time for the regulatory affairs team, but our recent efforts have put us on track to grow our mfg. business and initiate our newest clinical programs. This concludes my comments and I will now turn the call over to CFO Paul Lytle, who will discuss the company’s financial performance and our Avid Bioservices business.
CFO Paul Lytle:
I’ll start with an overview of our contract mfg. business. The Avid Bioservices business continues to strengthen. During Q2, our wholly-owned subsidiary achieved record quarterly revenue of $9.5mm, a 52% increase over the same prior year qtr. Year-to-date, we recorded mfg. revenue of $18.9mm or a 61% increase compared to the same prior year period. Our outlook for this business remains very positive, with our customers continuing to book available production capacity. This has raised our current revenue backlog to approx. $49mm. Based on this increase in demand, we are raising our revenue guidance to $35-40mm for the full FY2016 compared to previous guidance of $30-35mm.
We also believe that business has more opportunity to grow, as our 2nd mfg. Facility [Myford Facility] has the capacity to generate approx. $40mm in new revenue. As Rob mentioned, the new facility is ready for the initial phase of GMP manufacturing to support both to manufacturing of bavituximab in addition to growing our revenue from 3rd-party customers. As I wrap up this discussion on Avid, I can’t emphasize enough the strategic importance of this business. Avid continues to generate non-dilutive income that in turn continues to offset the amount of capital we need to raise by other means, plus it’s important to note that preparing bavituximab for commercial production is a significant financial endeavor and this strategic asset saves us millions of dollars each year in mfg. costs.
Turning now to expenses, R&D expenses for Q2 increased, primarily due to increase expenses associated with our Phase III SUNRISE trial and our newly planned later stage company-sponsored trials in breast cancer & lung cancer. While G&A expenses remained relatively flat qtr-over-qtr. Lastly, during the quarter Peregrine closed a registered direct offering with a single institutional investor raising $20mm [10-30-15: Kenneth Dart (Eastern Capital) acquires 13.1% stake (30,106,945sh.) in PPHM http://tinyurl.com/24qctos ]. These funds will help support our ongoing Phase III SUNRISE trial as well as our newly planned later staged company-sponsored trials. In more detailed analysis of our statement of operations is included in our Form 10-Q that was filed today. [10Q: http://tinyurl.com/zdbo9rv ] This concludes my financial overview, I now turn the call back over to Steve to discuss some important upcoming milestones.
CEO STEVE KING – MILESTONES:
As you’ve just heard from the team, although our SUNRISE enrollment milestone has been reached, we have no intention of selling down, quite the opposite. We are aggressively moving to initiate the clinical trials that will allow us to build the most robust oncology business possible. By mid-2016, we will initiate 2 breast cancer studies, a Phase II/III trial in metastatic HER2- breast cancer and the Phase I trial in early-stage breast cancer, a new Phase II trial in lung cancer, and a Phase I/Ib trial for multiple solid tumors. These studies will set the stage for expected clinical data readouts from at least 3 trials by early 2017, our SUNRISE Phase III trial, the new Phase II NSCLC trial, as well as the Phase II breast cancer study. In addition, we have other potential data coming from ongoing ISTs, as well as the other studies that we will be initiating. With each of these studies our goal is the same - we are committed to identifying key indications, patient populations, and therapeutics that can benefit from combination treatment with bavituximab. From what we have seen to-date, the opportunity appears vast and we are hard at work converting the most promising prospects in the true value.
Q&A: [23:30 mark]
1. Thomas Yip (FBR & Co.): http://www.fbr.com
TY: ”….congrats on a good qtr, especially for Avid. Re: the timing of your Phase II trials in lung cancer & breast cancer, are there other advantages to follow SUNRISE so tightly than to speed up enrollment? Because, like you said, we are expecting SUNRISE unblinding in 2nd-half 2016, and then in early 2017 we’ll have 2 Ph2 readouts in lung cancer & breast cancer.”
Steve King: The goal of the new studies is to continue to build the value proposition for the overall portfolio. I think the key to success eventually commercially for bavituximab is to be able to be used in multiple lines of therapy. Clearly the SUNRISE trial represents the combination with docetaxel, a chemotherapy regiment which is going to continue to be used, and the new Phase II study will then expand that into a combination in the IO space with the combination with the PD-L1 inhibitor. Clearly, those types of drugs are going to be used as the lung cancer space continues to evolve over the coming years. And so, the more we can be a part of both those better off we are, and again it’s really a golden opportunity to enroll right from the SUNRISE trial, which is in a very similar patient population to the new trial. The new trial has some advantages in that it will actually include both squamous & non-squamous, so it increases the number of eligible patients. So, to keep those investigators engaged suddenly moving right from one SUNRISE study into another SUNRISE study is a huge advantage in building that relationship with these key investigators and KOLs in the area. The breast cancer study, this is an area we wanted to move forward in previously. We’ve had some great Phase II data, as Joe mentioned, along with the data in HER2- breast cancer patients, in which we saw a nice 85% tumor response rate. That represents as big or a bigger market potential as NSCLC. So, taken together, that really is going to add tremendous value to the program, give us multiple data readouts, and from a partnering perspective adds a lot of potential value to the program. And Steve maybe you want to expand on that a little bit from partnering perspective?
Stephen Worsley: I think the exposure that we’re seeing with these 2 collaborations [AZN & MSKCC] have significantly increased who we're talking to, but also the ability for bavituximab to act in a variety of different indications. This is obviously leading to further discussions with some of the leading oncology players worldwide.
TY: ”Will the Ph1 breast cancer trial be an IST or sponsored by Peregrine?”
Steve King: I think the Ph1 study will end up being a company-sponsored study. It will obviously be a much smaller study than the 2 Ph2's we’re talking about. But it will allow us to run at multiple institutions. There's actually a lot of interest from number of different institutions, that allows us to run a study that we think can add a lot of value, but also that we can move forward on a nice timeline that sets the stage for, within the breast cancer space, a very nice addition to the Ph2 study that we’ll be running in another big patient population represented in that trial.
TY: ”Re: your collaboration with AstraZeneca, it seems that the Ph2 cancer trial has now been accelerated ahead of the solid tumor trial. So can you remind us what the advantages of combining bavituximab w/durvalumab over your previous planned Ph2 trial combination with Opdivo?”
Steve King: The advantages are on several fronts. #1 is it really gives us the flexibility to run the study in the way we want to run the study & where we want to run it. Because otherwise, we’d have to source Nivo [Opdivo=nivolumab] or one of the other PD-1 inhibitors on a regional basis, in which the drug isn’t approved in lot of different regions where you may want to run the study. So just operationally, it gives us the freedom to more efficiently run a study and get it up & running much quicker than we otherwise would have able to. #2, it really gives us a great opportunity to potentially reduce the cost of what study otherwise would have been, because if we would have to go out and acquire the drug for a clinical study, it could as much as double the cost of the trial. So, it just all around allows us to run a much more efficient trial with the drug that’s in our discussions with the KOLs in the field, people with direct experience, they feel that the PD-L1 antibodies work at least as well as the anti-PD-1 antibodies. Our goal is to answer a key question, which is, “can bavituximab add to the activity of a PD-1/PD-L1 inhibitor?”, and this allows us doing on a timeframe. So, there are just a lot of huge advantages. I’ll end that with the fact that also we’re working with a what we think is a great partner [AstraZeneca]. They’ve been very interactive so far. They also have a lot of knowledge of PD-L1/PD-L1 status in the patients, which is one of the things we'll want to be looking at as part of both the Ph2 as well as in the other studies we run in NSCLC, as our ability to have a positive impact on potentially those PD-L1 negative tumors, which don’t typically response well the PD-1 therapy. That’s sort of one of those things that’s hard to put a numeric value to, but is a true advantage of working with a great partner.
TY: “Thanks - look forward to see you guys at JP Morgan.”
2. George Zavoico – Jones Trading http://jonestrading.com
GZ: ”Congrats on a good qtr, particularly with the Avid revenues… You mentioned the possibility of expanding Avid’s mfg. capacity further. #1, will that be without including fill & finish capability, because I think there is a probably pretty good business there as well. And #2, if you do expand, do you have space where you are now you have to expand to some other property?”
Steve King: The expansion really is driven by our existing & new clients that have come in, and so obviously primarily that’s driven in the bulk drug specimens area not necessarily the fill/finish area. So that'll probably be the primary focus; we have considered and eventually would like to move into the fill/finished business, it's just we’ve been so busy expanding our drug specimens business, we really haven’t had the option to do that. For the question of space, there’s space in the current buildings that we’re in, but we’re also looking at other opportunities nearby that fit the same model as we did for the Myford facility and allows us to most efficiently grow the business. At the end of the day it will be a business decision and we’ll take on space as needed to expand the business. Again, it’s all really right now supported by the client base, which has had an extremely positive response to the Myford facility and that’s really driving we think even beyond what we expected going into it.
GZ: ”Would you finance that further expansion as sort of debt against the revenue coming in or are you just keeping all your options open for that?”
Steve King: We’re keeping our options wide open. At this point, we’ll do what’s best for the business itself. It’s a nice growing backlog of future revenue, it’s really a change in the way the Avid business can be viewed, as more a long-term go-forward business. So, we just need to make the right business decision based on the cost of capital, whatever avenue that takes, and then we’ll make the right decision.
GZ: ”Re: SUNRISE, there have been a couple of interesting & unfortunate events with some other companies where OS in the placebo arm of a trial has been much longer than expected. What are you seeing in that regard, because SUNRISE has been going on now for about 2 years now. What kind of advances have you seen in the SOC that might either make us more confident, or maybe a little bit more worried, about the possibility of having a surprise like that?”
Steve King: I can start off and maybe Joe can add in, but when we designed the SUNRISE study we did take into account the variability that had been seen in the docetaxel studies that had been reported up to that point. I don’t think we’ve seen any really significant variations from that as over time as more readouts have come. So, that’s one thing that we did take into account, that we were toward the upper end of what have been previously reported for docetaxel. Secondly, when we powered the study, in the Ph2 study we saw about a 4mos. difference in median OS, and the SUNRISE study was designed to really show a statistical difference even at 2mos; we built in some powering assumptions we think will give us some opportunity there should be arms behave in a way that was little bit unexpected. So, we’ve tried to hedge against that going into the stage design and we think we’re in good shape and now it’s just a matter of getting the readouts - we’re little under 2yrs right now from when we started to study, so at this point there’s really nothing more we can learn from the ongoing operations of the SUNRISE trial itself.
Joe Shan: George, obviously it's a very dynamic field right now. As Steve mentioned, we tried to make the SUNRISE design in such a way that it's as homogenous as practical. We obviously have some stratification criteria built in and some preplanned, subgroup analyses that are going to be pre-specified. Probably the biggest change in the landscape since we started enrollment is the approval of checkpoint inhibitors in this space, and we probably have patients that have received checkpoint therapy, and if there's an imbalance between the 2 arms of the study the subgroup analysis should account for that. But, it’s something that’s really impossible to predict how the changing SOC is going to effect the results of the control arms - this is why we have to run double-blind. Probably one predictor would be if we reach the number of interim events necessary to trigger the interim analyses, and the general projections that can give us some a little bit of confidence that these aren't too different than what we have previously seen.
George Zavoico - JonesTrading Institutional Services LLC
GZ: ”Quick question about MSKCC, Memorial Sloan Kettering, are they a site in the SUNRISE trial?”
Joe Shan: They are not a site in the SUNRISE trial, but we are discussing opening some of the new trials there.
GZ: ”Re: AZ's durvalumab, in the NSCLC space, we already have the 2 other PD-1s approved. How are you thinking of positioning the durvalumab-bavi combination in the already approved Opdivo/Keytruda space? How are you going to differentiate it and do you ever anticipate head-to-head comparison study?”
Joe Shan: The reason why we think this is a great opportunity is that the anti-PD-L1 agents, which none of them are approved yet in lung cancer, so far clinically they're behaving very similarly to approved anti-PD-1 agents. So, monotherapy head-to-head, that’s not a trial we're interested in doing. The differentiator for us is, can bavi make durvalumab, a PD-L1, better? If so, we would, I guess, extrapolate that into a benefit for other PD-1 or PD-L1 inhibitors. So, that’s our strategy, by showing, like in the preclinical setting, that bavi can modulate focal immunity and activate T-Cells and drives PD-1 expression, which makes PD-1 access blockhead more effective.
GZ: ”So basically if some positive result durvalumab actually open source for you with the other players in the space?”
Joe Shan: We still have to run the studies...
GZ: ”Right, of course.”
Steve King: The key here is that, from an activity standpoint, all the PD-1/PD-L1 targeting agents are all more or less interchangeable, and I think that there is no clear signal right now that any of them is really outperforming the others. And, I agree that’s not really our job to show which one of those is best, but really to show how we can actually make them all better. That’s how we view the durvalumab study, the ability to show that bavituximab can potentially make targeting PD-1 or PD-L1 a better therapy and that we can get more patients to respond. This is a Ph.2 study; if we can improve the long-term responses to durvalumab, we think that really extrapolates to the other molecules and is still leaves the potential of a Ph.3 with any of the molecules, which sets the stage on the partnering front for lots of opportunities to work with the difference groups.
GZ: ”Great. Congratulations, sounds like next year is going to be really interesting one to watch. Thank you.”
3. Rahul Jasuja - Noble Life Science Partners http://noblelsp.com/research
RJ: ”In planning your combination studies going forward, we are looking at PD-L1 low tumors because they are likely to be non-responsive to anti-PD-1's, like in Keytruda & Opdivo. Is that the only the rational, or is it also likely that PD-L1 low tumors also more responsive to bavituximab?”
Steve King: That’s what we want to show out in some of these studies we’re starting. We’re not planning on selecting for PD-L1 neg. patients in the Phase II study or the initial combination of bavi with chemo & durvalumab, but rather taking all-comers and then doing subset analysis and determining which patient populations we’re having the biggest impact in. Because, based on our translational data that’s been presented this year at ESMO & SITC'15 [11-9-15/SITC: http://tinyurl.com/pbof95w ], we’ve shown that we can take PD-L1 neg. tumors and actually elicit an immune response in those tumors. That’s the reason that we think that we have the potential to turn those into better responders on a PD-1 or PD-L1 therapy. As I mentioned during the prepared remarks it’s basically, “use bavi to get the immune response going and then use durvalumab to keep it going.” That's the reason there is a great scientific rationale right now for why we may have the biggest impact in those patients who don’t do well, because the delta between how they would normally do and how they might do with bavituximab may be the largest. We’re going to have some great insight into that from the studies we’re planning on running and the ability to go in and do subset analysis. Joe, do you want to add any more to that?
Joe Shan: I was going to use the word delta, but you beat me to it. I think in the PD-L1 neg. patient you have more opportunities to demonstrate the delta.
RJ: ”One of the concepts that’s evolving pretty rapidly is that you’ve got the TILs- & TILs+, and TILs+ are responding to PD-1 checkpoint immunotherapy. So is it fair to say, or is it an extrapolation, that PD-L1 positive tumors are more likely the ones that are TILs+? And in your case are you also seeing that TILs- tumors are probably the ones that are going to respond to chemo combination therapy better than the other ones that are the non-responders in combination with PS you can make them responders.”
Steve King: That’s certainly what our evidence has shown so far. The general assumption is that TILs- or TILs/Low tumors the ones that have low levels of the need for PD-L1, right, that’s really meant to stop an ongoing immune response. I think that’s generally true. Now it gets a little bit more complex because you’ve got Tregs and all kinds of T-cells present inside the tumor, so it also depends on the particular makeup. What we know is that when you get bavituximab, we seem to see a nice change in the levels of MDSCs (Myeloid-Derived Suppressor Cells) who are really the cell type that’s responsible for controlling the immune response in the tumor. It's been shown that patients with high levels of MDSCs have very poor prognosis. So as much as probably getting new TILs into the tumors is important, it’s probably more important to change the makeup of those cells into a more productive immune response positive phenotype. That’s exactly what we see with when you get bavituximab treatment; when we take a look a look at our translational data it shows an increase in CD4+ T-Cells and an increase in CD8+ T-Cells along with the changes in the suppressive cells types and the expression of immuno-suppressor cytokines, in which both decrease after treatment. So, it’s a matter of getting everything moving in the right direction. Again this is the role we think PS plays, by blocking it and activating an immune response, we're able to turn that around.
RJ: ”That does make sense. I think you’re looking at patient selection as being helpful in defining the population as well as the data you showedat SITC'15 [11-9-15/Duke's Herbert K. Lyerly http://tinyurl.com/pbof95w ], where you talked about immuno-profiling and looking at response to bavituximab, those are very interesting datasets. The other question I have is, there are a couple of trials running that are ISTs [at UTSW] - one of them is bavi in combination with Yervoy(ipilimumab) in melanoma, and the other one is a rectal cancer IST. Any updates on those?”
Steve King: The Rectal adenocarcinoma, we expect to have some data coming up this year from that study. As in any IST, it’s always a bit difficult, we do whatever we can to encourage them. But we do expect data to be becoming out of that study in 2015, which I think will be a real positive because in that study we did have the opportunity to collect pre- and post-treatment biopsies - #1, so we can see what happens following bavituximab treatment, but also that was a combination with radiation which we expect to be a very strong inducer of tumor antigens, which can then be taking advantage of by bavituximab treatment to make CD8+ T-Cells or killer T-Cells. For the Melanoma study, obviously the since that investigator (UTSW) started this study the SOC has changed pretty substantially. So right now, we're trying to work with that investigator, as well as some others, to probably change the profile of that study or start a new multi-center study in which we can then look at little bit more closely at what is the current SOC and make sure it’s an attractive trial for patients. As the treatment options for patient’s change, you need to be able to change with it and luckily it's a small IST trial and we may have an opportunity here to run a trial that I think would be very attractive for patients and will allow us to answer some key questions, because that was really the point of that study was to answer some of the key questions of combining with Yervoy. In addition, we’re starting the combination of durvalumab [AZN collab.] in multiple solid tumor types after the beginning of the year, so one way or another we’ll have lots of information coming from those studies.
RJ: ”Any updates any more color or comments on the collaboration with Sloan Kettering and Jed Wolchok on combination approaches - any data coming that way in the next few months?”
Steve King: That's an ongoing process. We’re very actively working with them to study a new combinations, looking for potential and different indications as well as those different combinations. We fully expect that it will be a fruitful collaboration; there will be a lots of data coming from that that we’ll see a very scientific meetings coming up. We already see a lot of data coming out of all for other collaborators nad we’ve had examples of presentations in multiple conferences this year. It always takes a while for them to get started, but then once they are going you tend to have a lot of data that continuously comes through them because the all the systems are up and running.
RJ:”Great.Thank you and congratulations on the healthy revenues at Avid.”
MR. KING’S CLOSING COMMENTS:
I’d like to thank all of you for participating in today’s phone call. As always, I want to especially thank our stockholders for their continued support, our mfg. clients for their continued business, and as always our patients and their families that are participating in our bavituximab clinical trials. With that, we will now conclude the call.
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12-10-15 PR: ”Peregrine Pharmaceuticals Reports Financial Results for 2ndQuarter of FY2016 2016 and Recent Developments”
* Peregrine and AstraZeneca Expand Immuno-Oncology Collaboration and Plan Phase II NSCLC Trial
* Phase III SUNRISE Clinical Trial Expected to Complete Enrollment in Coming Weeks While New Clinical Trials Are Being Initiated
* Peregrine Closes $20mm Financing to Support Late-Stage Clinical Trials
* Biomanufacturing Business, Avid Bioservices, Posts Strong Quarter With a 52% Increase in Revenue
* New State-of-the-Art Production Facility Ready for Initial Phase of GMP Manufacturing
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=946616
TUSTIN, Dec. 10, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM, PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced financial results for the 2nd quarter of FY2016 ended October 31, 2015, and provided an update on its advancing clinical pipeline and other corporate developments.
Highlights Since July 31, 2015
"I am pleased to report that we are nearing completion of enrollment for our Phase III SUNRISE trial with over 90% of the intended number of patients enrolled. We have also made substantial progress toward initiating several new trials including a Phase II/III breast cancer study and a Phase II NSCLC trial in combination with AstraZeneca's anti-PD-L1 antibody, durvalumab," said Steven W. King, President and CEO of Peregrine. "Our goal is to transition our leading SUNRISE clinical sites into our new Phase II NSCLC trial which should significantly expedite study start-up activities. We are encouraged by the fact that a number of investigators from hospitals that participated in the SUNRISE trial have already enthusiastically agreed to participate in our upcoming NSCLC trial."
"As treatment paradigms shift to incorporate new drugs, it is clear that both chemotherapy and immuno-oncology agents will continue to be critical to patient care. Taken together, we believe our SUNRISE trial, as well as the newly planned breast and lung cancer trials will allow us to maximize the potential of bavituximab in both settings," said Joseph Shan, VP of Clinical & Regulatory Affairs of Peregrine. "We are committed to continuing to identify new potential indications, patient populations and therapies that can benefit from combination treatment with bavituximab. From what we have seen to date in our preclinical and translational studies, the opportunity appears vast, and we are hard at work converting the most promising prospects into true value."
Clinical Development Highlights
As of today, more than 90% of the planned number of patients have been enrolled in the Phase III SUNRISE trial, representing a sufficient number of patients required to trigger the two pre-planned interim analyses as well as the final analysis for trial unblinding. The company expects to reach the trial's estimated enrollment of 582 patients in the coming weeks.
Peregrine and AstraZeneca expanded their cancer immunotherapy clinical trial collaboration to evaluate bavituximab in combination with AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The companies are currently planning a global Phase II study in patients with previously treated squamous or non-squamous NSCLC, as well as a Phase I/Ib trial that will evaluate the safety and efficacy of bavituximab in combination with durvalumab and chemotherapy in multiple solid tumors. The company expects the Phase II study to be initiated in early 2016 with the Phase I/Ib study beginning later in 2016.
Peregrine continues to finalize plans for its Phase II/III trial to evaluate bavituximab with chemotherapy combinations in HER2-negative metastatic breast cancer. This trial is on track to be initiated by the end of calendar year 2015.
Supportive Research Highlights
Positive results were presented at the 2015 annual meeting of the Society for Immunotherapy of Cancer (SITC) [11-9-15: SITC'15 'New Bavi+Checkpoint Inhibitors preclin. data (UTSW/DUKE's Herbert K. Lyerly) http://tinyurl.com/pbof95w ] from multiple new preclinical studies demonstrating enhanced anti-tumor activity and immune activation for combinations of a preclinical bavituximab equivalent and checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 in preclinical models of breast cancer and melanoma. Additionally, the company announced preliminary results for a new clinical test specifically designed to illustrate how bavituximab modulates immune responses in the tumor microenvironment.
New data presented at the International Association for the Study of Lung Cancer's (IASLC's) World Conference on Lung Cancer (WCLC) [9-8-15: Scott Antonia/MoffittCC IASLC’15 Mini-Oral Presentation Slideshow http://tinyurl.com/p9eduac ] from a translational study of bavituximab demonstrated the ability of bavituximab, alone or in combination with docetaxel, to induce signs of immune activation in non-small cell lung cancer (NSCLC) patient-derived tumor samples, particularly when there was negative PD-L1 expression in the tumor sample. These data further support the potential mechanistic synergies for bavituximab with chemotherapy and checkpoint inhibitors targeting the PD-1/PD-L1 pathway.
Summary data presented at the Combination Immunotherapy Strategies session at the 10th Annual Immunotherapy and Vaccine Summit (ImVacS) [8-26-15: ImVacS'15 http://tinyurl.com/qz64pzg ], highlighted key findings from several recent bavituximab-focused studies including: the potential of bavituximab to shift the tumor microenvironment from immuno-suppressive in which tumors evade immune detection to a state of immune activation in which the immune system recognizes and fights the tumor; bavituximab's potential to increase the number of activated CD8+ cells in the tumor, which stimulates PD-1 expression, potentially increasing the number of patients able to respond to PD-1 and PD-L1 targeting immunotherapies; and, results from several clinical and preclinical studies in a range of tumor types showing that bavituximab and bavituximab-like antibodies, in combination with conventional therapy, have consistently demonstrated Kaplan-Meier graphs that follow the classic immunotherapy survival plateau.
Corporate Highlights
Peregrine closed a registered direct offering to a single institutional investor raising $20mm dollars [10-30-15: Kenneth Dart (Eastern Capital) acquires 13.1% stake (30,106,945sh.) in PPHM http://tinyurl.com/24qctos ]. The funds raised from this financing will support the ongoing Phase III SUNRISE trial, and newly planned later-stage company-sponsored trials in breast cancer and NSCLC.
Avid Bioservices Highlights
"Our contract manufacturing business continues to strengthen with a 52% current quarter increase in revenue compared to the prior year period and year-to-date growth of 61%," stated Paul Lytle, CFO of Peregrine. "Our new state-of-the-art manufacturing facility is now ready for the initial phase of GMP manufacturing and demand for Avid's capacity continues to grow with our current backlog now at $49mm. Given the revenue growth and committed backlog, we are increasing our contract manufacturing revenue guidance to a range of $35 to $40mm for the full-year 2016."
During the second quarter of FY 2016, Avid Bioservices achieved record-breaking revenues generating approximately $9.5mm dollars, a 52% increase in revenue compared to the same quarter in the prior year.
Avid's new manufacturing facility is now ready for the initial phase of GMP manufacturing. The state-of-the-art facility will accommodate single use bioreactors (SUBs) at up to 2,000 liter scale. Upcoming production runs will support late stage clinical development as well as process validation activities in anticipation of bavituximab and other client commercial product needs. The facility has the capacity to potentially generate approximately $40mm in new revenue annually.
Contract manufacturing committed backlog reached $49mm from existing customers covering services to be completed in FY 2016 and into FY 2017.
Financial Results
Total revenues for the second quarter of FY 2016 were $9,523,000, compared to $6,300,000 for the same quarter of the prior fiscal year. The increase was attributed to an increase in contract manufacturing revenue generated from Avid Bioservices.
Contract manufacturing revenue from Avid's clinical and commercial biomanufacturing services provided to its third-party clients for the second quarter FY 2016 were $9,523,000, compared to $6,263,000 for the same quarter of the prior fiscal year. Peregrine expects third-party contract manufacturing revenue for the entire fiscal year to be between $35mm and $40mm, compared to previous guidance of $30mm to $35mm during last quarter's earnings call. In addition to providing biomanufacturing services to its third-party clients, Avid will continue to support the clinical development and potential commercialization of bavituximab.
Total costs and expenses in the second quarter of FY 2016 were $23,347,000, compared to $18,437,000 in the second quarter of FY 2015. This increase was primarily attributable to current quarter increases in research and development expenses associated with the SUNRISE Phase III trial, newly planned later-stage company-sponsored trials in breast cancer and NSCLC, and an increase in the cost of contract manufacturing associated with higher reported revenue. For the second quarter of FY 2016, research and development expenses were $14,190,000, compared to $10,003,000 for the second quarter of FY 2015. For the second quarter of FY 2016, cost of contract manufacturing was $4,741,000, compared to $4,139,000 for the second quarter of FY 2015.
Peregrine's consolidated net loss attributable to common stockholders was $14,578,000, or $0.07 per share, for the second quarter of FY 2016, compared to a net loss attributable to common stockholders of $13,131,000, or $0.07 per share, for the same prior year quarter.
Peregrine reported $72,005,000 in cash and cash equivalents as of October 31, 2015 compared to $68,001,000 at fiscal year ended April 30, 2015.
More detailed financial information and analysis may be found in Peregrine's Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today. [ http://tinyurl.com/zdbo9rv ]
Conference Call
Peregrine will host a conference call and webcast this afternoon, December 10, 2015, at 4:30 PM ET (1:30 PM PT). To listen to the conference call, please dial (877) 312-5443 or (253) 237-1126 and request the Peregrine Pharmaceuticals conference call. To listen to the live webcast, or access the archived webcast, please visit: http://ir.peregrineinc.com/events.cfm .
About Peregrine Pharmaceuticals, Inc.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials focused on the treatment of cancer. The company's lead immunotherapy candidate, bavituximab, is in Phase III development for the treatment of previously treated non-small cell lung cancer (the "SUNRISE trial") along with several investigator-sponsored trials evaluating other treatment combinations and additional oncology indications. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. ( http://www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and third-party customers. For more information, please visit http://www.peregrineinc.com .
Safe Harbor *snip*
PEREGRINE PHARMACEUTICALS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (UNAUDITED)
(UNAUDITED)
THREE MONTHS ENDED
OCTOBER 31,
SIX MONTHS ENDED
OCTOBER 31,
2015 2014 2015 2014
REVENUES:
Contract manufacturing revenue $ 9,523,000 $ 6,263,000 $ 18,902,000 $ 11,759,000
License revenue - 37,000 292,000 37,000
Total revenues 9,523,000 6,300,000 19,194,000 11,796,000
COSTS AND EXPENSES:
Cost of contract manufacturing 4,741,000 4,139,000 9,349,000 7,722,000
Research and development 14,190,000 10,003,000 28,108,000 20,204,000
Selling, general and administrative 4,416,000 4,295,000 9,315,000 9,178,000
Total costs and expenses 23,347,000 18,437,000 46,772,000 37,104,000
LOSS FROM OPERATIONS (13,824,000 ) (12,137,000 ) (27,578,000 ) (25,308,000 )
Interest and other income 626,000 37,000 657,000 79,000
NET LOSS $ (13,198,000 ) $ (12,100,000 ) $ (26,921,000 ) $ (25,229,000 )
COMPREHENSIVE LOSS $ (13,198,000 ) $ (12,100,000 ) $ (26,921,000 ) $ (25,229,000 )
Series E preferred stock accumulated dividends (1,380,000 ) (1,031,000 ) (2,413,000 ) (1,802,000 )
Net loss attributable to common stockholders $ (14,578,000 ) $ (13,131,000 ) $ (29,334,000 ) $ (27,031,000 )
WEIGHTED AVERAGE COMMON SHARES OUTSTANDING:
Basic and Diluted 203,942,411 179,962,275 200,629,892 179,540,265
BASIC AND DILUTED LOSS PER COMMON SHARE $ (0.07 ) $ (0. 07 ) $ (0.15 ) $ (0.15 )
PEREGRINE PHARMACEUTICALS, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
OCTOBER 31,
2015 APRIL 30,
2015
Unaudited
ASSETS
CURRENT ASSETS:
Cash and cash equivalents $ 72,005,000 $ 68,001,000
Trade and other receivables, net 2,904,000 3,813,000
Inventories 12,554,000 7,354,000
Prepaid expenses and other current assets, net 1,995,000 1,355,000
Total current assets 89,458,000 80,523,000
Property and equipment, net 21,764,000 15,124,000
Other assets 1,435,000 1,817,000
TOTAL ASSETS $ 112,657,000 $ 97,464,000
LIABILITIES AND STOCKHOLDERS' EQUITY
CURRENT LIABILITIES:
Accounts payable $ 6,901,000 $ 10,385,000
Accrued clinical trial and related fees 6,138,000 3,910,000
Accrued payroll and related costs 4,130,000 4,606,000
Deferred revenue 9,688,000 6,630,000
Customer deposits 14,935,000 11,363,000
Other current liabilities 667,000 437,000
Total current liabilities 42,459,000 37,331,000
Deferred rent, less current portion 972,000 1,098,000
Commitments and contingencies
STOCKHOLDERS' EQUITY:
Preferred stock - $0.001 par value; authorized 5,000,000 shares; issued and outstanding - 1,577,440 and 1,574,764, respectively 2,000 2,000
Common stock - $0.001 par value; authorized 500,000,000 shares; outstanding – 225,824,551 and 193,346,627, respectively 226,000 193,000
Additional paid-in capital 549,543,000 512,464,000
Accumulated deficit (480,545,000 ) (453,624,000 )
Total stockholders' equity 69,226,000 59,035,000
TOTAL LIABILITIES AND STOCKHOLDERS' EQUITY $ 112,657,000 $ 97,464,000
• Jay Carlson Peregrine Pharmaceuticals, Inc. 800-987-8256 info@peregrineinc.com
• Stephanie Diaz (Investors) Vida Strategic Partners 415-675-7401 sdiaz@vidasp.com
• Tim Brons (Media) Vida Strategic Partners 415-675-7402 tbrons@vidasp.com
- - - - - - - - -
[ From 10-Q header: “As of Dec. 9, 2015, there were 229,701,808 shares outstanding.”
- - - - - - - - - - - - - - - - -
Latest 10K 4-30-15 iss. 7-14-15 http://tinyurl.com/ocrtkuj PR: http://tinyurl.com/nw2v5u6 (Cash 4-30-15=$68.0mm)
Latest 10Q 10-31-15 iss. 12-10-15 http://tinyurl.com/zdbo9rv PR: http://tinyurl.com/jkp885g (Cash 10-31-15=$72.0mm)
ALL SEC filings for PPHM: http://tinyurl.com/6d4jw8
.
= = = = = = = = = = = = = = = = = = = = = = = = = = = =
Updated PPHM REVS-BY-QTR TABLE, now thru FY16'Q2(qe 10-31-15), per the 10-31-15 10-Q ( http://tinyurl.com/ocrtkuj ) issued 12-10-15.
• Total Revs since May’06: ($148.1mm/Avid + $24.1mm/Govt + $2.4mm/Lic.) = $174.7mm
• Deferred-Revs at 10-31-15, going fwd into FY’16/Q3 (q/e 1-31-16), total $9.7mm, UP from the $8.3mm of Deferred-Revs at 7-31-15 that drove into FY’16/Q2.
• Cust.Deposits at 10-31-15 total $14.9mm, UP from $9.6mm at 7-31-15.
• Avid’s Gross-Profit over last 3 qtrs: $14.1mm on revs of $28.2mm (GP%=50%)
• Recall, Avid Rev$ from Gov’t DTRA Contract work (6/30/08 – 4/15/11, totaling $24.15mm), went into GOVT-REVS, not AVID-REVS, in the Financials.
Avid’s website: http://www.avidbio.com
AVID PROFITABILITY (GROSS*) BY QTR:
QTR Avid-Rev$ CostofMfg$ Gross-Profit$ GP%
FY13Q1 7-31-12 4,135,000 2,024,000 2,111,000 51%
FY13Q2 10-31-12 6,061,000 3,703,000 2,358,000 39%
FY13Q3 1-31-13 6,961,000 3,651,000 3,310,000 47%
FY13Q4 4-30-13 4,176,000 3,217,000 959,000 23%
FY13 TOTAL: 21,333,000 12,595,000 8,738,000 41%*
FY14Q1 7-31-13 4,581,000 2,670,000 1,911,000 42%
FY14Q2 10-31-13 7,354,000 4,195,000 3,159,000 43%
FY14Q3 1-31-14 3,885,000 2,416,000 1,469,000 38%
FY14Q4 4-30-14 6,474,000 3,829,000 2,645,000 41%
FY14 TOTAL: 22,294,000 13,110,000 9,184,000 41%*
FY15Q1 7-31-14 5,496,000 3,583,000 1,913,000 35%
FY15Q2 10-31-14 6,263,000 4,139,000 2,124,000 34%
FY15Q3 1-31-15 5,677,000 3,113,000 2,564,000 45%
FY15Q4 4-30-15 9,308,000 4,758,000 4,550,000 49%
FY15 TOTAL: 26,744,000 15,393,000 11,151,000 42%*
FY16Q1 7-31-15 9,379,000 4,608,000 4,771,000 51%
FY16Q2 10-31-15 9,523,000 4,741,000 4,782,000 50%
*Avid Net-Profit (ie, incl. Selling, G&A) not split out from PPHM-Corp. in the financials.
.
PPHM REVENUES (in thousands) DEFERRED
-------REVENUES------- REVENUES INVEN-
Quarter Avid Govt Lic. TOTAL Avid Govt TORIES
FY07Q1 7-31-06 398 0 23 421 317 0 971
FY07Q2 10-31-06 636 0 48 684 1388 0 1899
FY07Q3 1-31-07 347 0 16 363 2202 0 1325
FY07Q4 4-30-07 2111 0 129 2240 1060 0 1916
FY08Q1 7-31-07 1621 0 4 1625 1820 0 2363
FY08Q2 10-31-07 1863 0 29 1892 1338 0 3500
FY08Q3 1-31-08 1662 0 13 1675 1434 0 2394
FY08Q4 4-30-08 751 0 150 901 2196 0 2900
FY09Q1 7-31-08 1193 324 0 1517 4021 980 4628
FY09Q2 10-31-08 983 958 0 1941 6472 1701 6700
FY09Q3 1-31-09 5778 1048 0 6826 4805 3262 5547
FY09Q4 4-30-09 5009 2683 175 7867 3776 3871 4707
FY10Q1 7-31-09 2070 4671 9 6750 5755 2332 6177
FY10Q2 10-31-09 5308 1510 78 6896 4260 3989 5850
FY10Q3 1-31-10 2945 6854 78 9877 3052 76 3861
FY10Q4 4-30-10 2881 1461 78 4420 2406 78 3123
FY11Q1 7-31-10 983 2111 115 3209 3719 47 4692
FY11Q2 10-31-10 3627 966 78 4671 2447 35 3555
FY11Q3 1-31-11 1922 882 79 2883 4300 40 3915
FY11Q4 4-30-11 1970 681 78 2729 5617 0 5284
FY12Q1 7-31-11 5439 0 216 5655 4145 0 4481
FY12Q2 10-31-11 4154 0 78 4232 2012 0 3178
FY12Q3 1-31-12 3203 0 78 3281 2552 0 2722
FY12Q4 4-30-12 1987 0 78 2065 3651 0 3611
FY13Q1 7-31-12 4135 0 116 4251 6056 0 5744
FY13Q2 10-31-12 6061 0 78 6139 6221 0 5426
FY13Q3 1-31-13 6961 0 78 7039 5061 0 4635
FY13Q4 4-30-13 4176 0 78 4254 4171 0 4339
FY14Q1 7-31-13 4581 0 107 4688 4164 0 5679
FY14Q2 10-31-13 7354 0 0 7354 3468 0 4033
FY14Q3 1-31-14 3885 0 0 3885 4329 0 5224
FY14Q4 4-30-14 6474 0 0 6474 5241 0 5530
FY15Q1 7-31-14 5496 0 0 5496 4670 0 5998
FY15Q2 10-31-14 6263 0 37 6300 3612 0 5379
FY15Q3 1-31-15 5677 0 0 5677 5752 0 6148
FY15Q4 4-30-15 9308 0 0 9308 6630 0 6148
FY16Q1 7-31-15 9379 0 292 9671 8291 0 10457
FY16Q2 10-31-15 9523 0 0 9523 9688 0 12554
Totals: 148114 24149 2416 174679 <=since5/1/2006
.
TOTAL REV’s BY YEAR (Avid+Gov’t+Lic):
FY04 4-30-04 3,314 …Avid(CMO)= 3,039 (Avid-Revs don’t incl. Govt-SVCS)
FY05 4-30-05 4,959 …Avid(CMO)= 4,684
FY06 4-30-06 3,193 …Avid(CMO)= 3,005
FY07 4-30-07 3,708 …Avid(CMO)= 3,492
FY08 4-30-08 6,093 …Avid(CMO)= 5,897
FY09 4-30-09 18,151 …Avid(CMO)= 12,963
FY10 4-30-10 27,943 …Avid(CMO)= 13,204
FY11 4-30-11 13,492 …Avid(CMO)= 8,502
FY12 4-30-12 15,233 …Avid(CMO)= 14,783
FY13 4-30-13 21,683 …Avid(CMO)= 21,333
FY14 4-30-14 22,401 …Avid(CMO)= 22,294
FY15 4-30-15 26,781 …Avid(CMO)= 26,744
...Total Gov’t Revs from 7-2008 inception thru FY11Q1(Apr’11): $24.15mm
.
AVID “Total Services”:
AVID OUTPUT$ 3rd-PARTY + PEREGRINE = TOTAL-OUTPUT$
FY09 4-30-09 13mm 10mm $23mm #
FY10 4-30-10 13mm 17mm $30mm #
FY11 4-30-11 9mm 11mm $20mm @
FY12 4-30-12 15mm 11mm $26mm @
FY13 4-30-13 21mm ~10mm ~$31mm ^
LTM ended 1/2010 3rd/$15.3mm + Govt/$8.3mm + PPHM/$8.8mm = $32.4mm *
@SKing 3-18-2013 RothOC/DanaPT (Slide21) http://tinyurl.com/cebtwen
#SKing 7-12-2012 JMP/NYC Conf. (Slide27) http://tinyurl.com/csdclwb
*SKing 3-17-2010 RothOC/DanaPT Conf. (Slide18) http://tinyurl.com/ye9v7jq
^PLytle 7-11-2013 Qtly-CC “Avid did ~$10mm in equivalent services for Peregrine in FY13, which doesn’t get reflected into the fin. statements, it's eliminated in consolidation.”
.
PPHM’S QTLY. NET LOSS BY QTR:
FY08Q1 7-31-07 4,656,000
FY08Q2 10-31-07 6,207,000
FY08Q3 1-31-08 6,154,000
FY08Q4 4-30-08 6,159,000
FY09Q1 7-31-08 5,086,000
FY09Q2 10-31-08 4,497,000
FY09Q3 1-31-09 3,332,000
FY09Q4 4-30-09 3,609,000
FY10Q1 7-31-09 2,428,000
FY10Q2 10-31-09 2,787,000
FY10Q3 1-31-10 1,538,000
FY10Q4 4-30-10 7,741,000
FY11Q1 7-31-10 7,695,000
FY11Q2 10-31-10 7,513,000
FY11Q3 1-31-11 8,929,000
FY11Q4 4-30-11 10,014,000
FY12Q1 7-31-11 8,092,000
FY12Q2 10-31-11 12,055,000
FY12Q3 1-31-12 11,090,000
FY12Q4 4-30-12 10,882,000
FY13Q1 7-31-12 7,664,000
FY13Q2 10-31-12 8,753,000
FY13Q3 1-31-13 4,914,000
FY13Q4 4-30-13 8,449,000
FY14Q1 7-31-13 7,600,000
FY14Q2 10-31-13 7,790,000
FY14Q3 1-31-14 9,724,000
FY14Q4 4-30-14 10,248,000
FY15Q1 7-31-14 13,129,000
FY15Q2 10-31-14 12,100,000
FY15Q3 1-31-15 12,994,000
FY15Q4 4-30-15 12,135,000
FY16Q1 7-31-15 13,723,000
FY16Q2 10-31-15 13,198,000
= = = = = = = =
OPER. CASH BURNS* BY QTR(FROM THE 10-Q/K’S):
FY10Q1 7-31-09 2,024,000 (from 10Q pg.25)
FY10Q2 10-31-09 2,351,000 (Q1+Q2: 4,375,000 pg.28)
FY10Q3 1-31-10 1,158,000 (Q1+Q2+Q3: 5,533,000 pg.30)
FY10Q4 4-30-10 6,375,000 (FY’10: 11,908,000 10K pg.58)
FY11Q1 7-31-10 6,567,000 (from 10Q pg.24)
FY11Q2 10-31-10 6,167,000 (Q1+Q2: $12,734,000 pg.25)
FY11Q3 1-31-11 7,736,000 (Q1+Q2+Q3: $20,470,000 pg.26)
FY11Q4 4-30-11 8,961,000 (FY’11: 29,431,000 10K pg.54)
FY12Q1 7-31-11 6,984,000 (from 10Q pg.25)
FY12Q2 10-31-11 11,668,000 (Q1+Q2: 18,652,000 pg.25)
FY12Q3 1-31-12 8,490,000 (Q1+Q2+Q3: 27,142,000 pg.25)
FY12Q4 4-30-12 11,265,000 (FY’12: 38,407,000 10K pg.55)
FY13Q1 7-31-12 6,742,000 (from 10Q pg.21)
FY13Q2 10-31-12 6,162,000 (Q1+Q2: 12,904,000 pg.23)
FY13Q3 1-31-13 3,597,000 (Q1+Q2+Q3: 16,501,000 pg.23)
FY13Q4 4-30-13 7,053,000 (FY’13: 23,554,000 10K pg.60)
FY14Q1 7-31-13 5,750,000 (from 10Q pg.23)
FY14Q2 10-31-13 5,834,000 (Q1+Q2: 11,584,000 10Q pg.24)
FY14Q3 1-31-14 7,875,000 (Q1+Q2+Q3: 19,459,000 10Q pg.26)
FY14Q4 4-30-14 8,706,000 (FY’14: 28,165,000 10K pg.55)
FY15Q1 7-31-14 11,076,000 (from 10Q pg.23)
FY15Q2 10-31-14 9,947,000 (Q1+Q2: 21,023,000 10Q pg.25)
FY15Q3 1-31-15 11,116,000 (Q1+Q2+Q3: 32,139,000 10Q pg.26)
FY15Q4 4-30-15 10,474,000 (FY’15: 42,613,000 10K pg.54)
FY16Q1 7-31-15 12,306,000 (from 10Q pg.25)
FY16Q2 10-31-15 11,701,000 (Q1+Q2: 24,007,000 10Q pg.26)
FY’09 total Op-Burn: $14,715,000
FY’10 total Op-Burn: $11,908,000
FY’11 total Op-Burn: $29,431,000
FY’12 total Op-Burn: $38,407,000
FY’13 total Op-Burn: $23,554,000
FY’14 total Op-Burn: $28,165,000
FY’15 total Op-Burn: $42,613,000
ATM Sales Summary (3/2009–12/9/2015). Also, PPHM O/S Shares History Table (’06–curr.) at the bottom of this post…
At 12-9-2015, shares O/S = 229,701,808
ATM = “At-The-Market Sales Issuance”
I. WM-SMITH 3-2009:
• $7.5mm ATM/Wm.SMITH 3-26-09: $7,500,000gr. / 2,150,759sh. = $3.49/sh. (commiss: 3%)
• $25mm ATM/Wm.SMITH 7-14-09: $25,000,000gr. / 7,569,314sh. = $3.30/sh. (commiss: 3%/1st$15mm, then 2%)
*Total Raised via WmSmith ATM Sales thru 7-31-10:
. . . . $32,500,000gr. / 9,720,073sh. = $3.34/sh.
II. MLV 6-2010: http://www.mlvco.com
$15mm ATM/MLV 6-22-10 (commiss: 2%) Form424: http://tinyurl.com/24txkxb
• Sold 6/22/10–10/31/10: $6,840,000gr. / 4,031,018sh. = $1.70/sh.
• Sold 11/1/10–11/30/10: $7,407,000gr. / 4,711,611sh. = $1.57/sh.
• Sold 12/1/10–1/31/11: $753,000gr. / 471,744sh. = $1.60/sh.
*Total Raised via MLV June’10 ATM Sales thru 1-31-11:
. . . . $15,000,000gr. / 9,214,373 = $1.63/sh.
III. MLV 12-2010: “Dec’10 AMI Agreement” http://www.mlvco.com
$75mm ATM/MLV 12-29-10 (commiss: max=5%) Form8K: http://tinyurl.com/2a6w76g
(pursuant to $75mm S-3 Shelf Reg. filed 12-17-10: http://tinyurl.com/2469b2d )
• Sold 12/29/10-1/31/11: $6,460,000gr. / 2,385,862sh. = $2.71/sh.
• Sold 2/1/11-2/28/11: $2,358,000gr. / 998,142sh. = $2.36/sh.
• Sold 3/1/11-4/30/11: $4,470,000gr. / 1,840,487sh. = $2.43/sh.
• Sold 5/1/11-7/31/11: $3,713,000gr. / 1,912,576sh. = $1.94/sh.
• Sold 8/1/11-10/31/11: $5,582,000gr. / 4,727,840sh. = $1.18/sh.
• Sold 9-2-12 Roth Direct: $6,940,000gr./ 6,252,252sh. = $1.11/sh.
• Sold 11/1/11-1/31/12: $10,961,000gr. / 10,308,025sh. = $1.06/sh.
• Sold 2/1/12-2/29/12: $5,871,000gr. / 5,726,946sh. = $1.03/sh.
• Sold 3/1/12-4/30/12: $1,263,000gr. / 2,198,543sh. = $.57/sh.
• Sold 5/1/12-6/30/12: $1,496,000gr. / 2,752,691sh. = $.54/sh.
• Sold 7/1/12-9/26/12: none**
• Sold 9/27/12-10/31/12: $16,719,000gr./ 18,557,928 = $.90/sh.
• Sold 11/1/12-11/30/12: $7,296,000gr./ 9,220,313 = $.79
• Sold 12/1/12-1/31/13: $1,540,000gr./ 1,131,282 = $1.36
• Sold 2/1/13-3/12/13: $330,000gr./ 201,154 = $1.64
*Total Raised via MLV Dec’10 ATM Sales thru 3-12-2013:
. . . . $75,000,000gr. / 68,214,041 = $1.10sh.
IV. MLV 12-2012: “Dec’12 AMI Agreement” http://www.mlvco.com
$75mm ATM/MLV 12-29-12 (commiss: max=5%) Form8K: http://tinyurl.com/2a6w76g
(pursuant to $75mm S-3 Shelf Reg. filed 3-9-12: http://tinyurl.com/7dl7pjm )
• Sold 2/1/13-3/12/13: $4,475,000gr. / 3,132,402sh. = $1.43/sh.
• Sold 3/13/13-4/30/13: $8,897,000gr. / 6,188,273sh. = $1.44/sh.
• Sold 5/1/13-7/11/13: $12,729,000gr. / 7,927,016sh. = $1.61/sh.
• Sold 7/12/13-7/31/13: $2,468,000gr. / 1,690,864sh. = $1.46/sh.
• Sold 8/1/13-9/9/13: $4,372,000gr. / 3,057,431sh. = $1.43/sh.
• Sold 9/10/13-10/31/13: $4,708,000gr. / 3,262,958sh. = $1.44/sh.
• Sold 11/1/13-12/6/13: NONE – see 10Q note below.
• Sold 12/7/13-1/31/14: $28,130,000gr. / 16,045,717sh. = $1.75/sh.
• Sold 2/1/14-4/30/14: $3,017,000gr. / 1,543,383sh. = $1.95/sh.
• Sold 5/1/14-7/31/14: $425,000gr. / 226,700sh. = $1.92/sh.
• Sold 8/1/14-10/31/14: $3,891,000gr. / 2,494,835sh. = $1.56/sh.
• Sold 11/1/14-1/31/15: $1,878,000gr. / 1,261,825sh. = $1.49/sh.
*Total Raised via MLV Dec’12 ATM Sales thru 10-31-2014:
. . . . $75,000,000gr. / 46,831,404 = $1.60sh.
V. MLV 6-2014: “Jun’14 AMI Agreement – up to $25mm” http://www.mlvco.com
• Sold 11/1/14-1/31/15: $1,193,000gr. / 869,504sh. = $1.43/sh.
• Sold 2/1/15-3/12/15: $6,204,000gr. / 4,354,954sh. = $1.44/sh.
• Sold 3/13/15-4/30/15: $6,147,000gr. / 4,457,299sh. = $1.38/sh.
• Sold 5/1/15-7/14/15: $8,896,000gr. / 6,534,400sh. = $1.36/sh.
• Sold 7/15/15-7/31/15: $1,270,000gr. / 1,003,830sh. = $1.27/sh.
• Sold 8/1/15-9/9/15: $1,290,000gr. / 1,091,508sh. = $1.18/sh.
*Total Raised via MLV Jun’14 ATM Sales thru 9-9-2015:
. . . . $25,000,000gr. / 18,311,495 = $1.37/sh.
VI. MLV 8-2015: “Aug’15 AMI Agreement – up to $30mm” http://www.mlvco.com
• Sold 8/7/15-9/9/15: $892,000gr. / 1,091,000sh. = $1.18/sh.
• Sold 9/10/15-10/31/15: $4,294,000gr. / 4,059,478sh. = $1.06/sh.
• Sold 11/1/15-12/10/15: $2,261,000gr. / 1,939,413sh. = $1.17/sh.
. . . . $7,447,000gr. / 6,751,651 = $1.10/sh.
TOTAL ALL A-T-M SALES – INCEPTION (3-2009) THRU 9-9-2015:
==> $229,947,000gr. / 159,043,037sh. = $1.45/sh.
- - - - - - - - - -
10-31-11 10Q: “During the 6mos. 10-31-11, we sold 6,440,416 shares of our common stock at mkt-prices for gross proceeds of $9,295,000 under the Dec’10 AMI Agreement before deducting commissions and other issuance costs of $260,000”
1-31-12 10Q: “During the 9mos. ended 1-31-12, we sold 16,948,441 shares of our common stock at mkt-prices for gross proceeds of $20,256,000 under the Dec’10 AMI Agreement before deducting commissions and other issuance costs of $482,000. …During Feb.2012, we sold an addl. 5,726,946 shares of common stock at market prices under the Dec’10 AMI Agreement in exchange for aggregate gross proceeds of $5,871,000. As of 2-29-12, gross proceeds of $38,644,000 remained available under our 2 effective shelf registration statements.”
4-30-12 10K: “Under the Dec. 2010 AMI Agreement with MLV …for aggregate gross proceeds of up to $75,000,000… During FY’s 2011 (5’10-4’11) and 2012 (5’11-4’12), we sold 30,098,421 shares of common stock at market prices under the Dec.2010 AMI for aggregate gross proceeds of $40,678,000 before deducting commissions & other issuance costs of $917,000. As of April 30, 2012, aggregate gross proceeds of up to $27,382,000 remained available under the Dec.2010 AMI… Subsequent to April 30, 2012 and through June 30, 2012, we sold 2,752,691 shares of common stock at mkt prices under the Dec.2010 AMI for aggregate gross proceeds of $1,496,000… Under the registered direct public offering dated Sept. 2, 2011, we entered into separate subscription agreements with 3 institutional investors, pursuant to which we sold an aggregate of 6,252,252 shares of our common stock at a purchase price of $1.11/sh. for gross proceeds of $6,940,000 before deducting placement agent fees and other offering expenses of $525,000.”
10-31-12 10Q: “During the 6mos. 10-31-12, we sold 21,310,619 shares… at varying mkt-prices under the Dec’10 AMI Agreement for gross proceeds of $18,215,000 before deducting commissions and other issuance costs of $620,000. From 11-1-12 thru 11-30-12, we sold 9,220,313 shares gross of $7,296,000. As of 11-30-12, aggregate gross proceeds of up to $1,871,000 remained available under the Dec’10 AMI Agreement. As of 11-30-12, gross proceeds of $151,871,000 remained available under 2 effective shelf registration statements.”
1-31-13 10Q/pg.11: “DEC’10-AMI(max=$75mm): During the 9 mos. ended 1-31-13, we sold 31,662,214 shares at varying mkt-prices for gross proceeds of $27,051,000 before deducting commissions/other-costs of $885,000. As of 1-31-13, gross proceeds of up to $330,000 remained available. From 2-1-13 – 3-12-13, we sold 201,154 shares at mkt prices for gross $330,000. As of 3-12-13, we had raised the full amt of gross proceeds available… DEC’12-AMI(max=$75mm): As of 1-31-13, we had not sold any shares. From 2-1-13 - 3-12-13, we sold 3,132,402 shares at mkt prices for gross proceeds of $4,475,000. As of 3-12-13, gross proceeds of up to $70,525,000 remained available.”
4-30-13 10K/pg.F26: Dec’12-AMI(max=$75mm)Agreement – During FY’13, we sold 9,320,675 shares gross proceeds of $13,372,000 before deducting commissions and other issuance costs of $337,000. As of April 30, 2013, gross proceeds of up to $61,628,000 remained available under the Dec’12-AMI. From 5/1/13 – 7/11/13, we sold 7,927,016 shares for gross proceeds of $12,729,000. As of 7-11-13, gross proceeds of $48,899,000 remained available under the Dec’12-AMI. http://tinyurl.com/p58jcbw
7-31-13 10Q/pg.10: During the 3mos ended 7-31-13, we sold 9,617,880 shares at mkt prices under the Dec’12 AMI Agreement for gross proceeds of $15,197,000 before deducting commissions and other issuance costs of $491,000. As of July 31, 2013, gross proceeds of up to $46,431,000 remained available under the Dec’12-AMI. From 8-1-13 – 9-9-13, we sold 3,057,431 shares for gross proceeds of $4,372,000. As of 9-9-13, gross proceeds of $42,059,000 remained available under the Dec’12-AMI.
10-31-13 10Q/pg.10: During the 6mos ended 10-31-13, we sold 15,938,269 at mkt prices under the Dec’12 AMI for gross proceeds of $24,277,000 before deducting costs of $722,000. As of 10-31-13, aggregate gross proceeds of up to $37,351,000 remained available under the Dec’12 AMI.
***NOTE: There is no stmt in the 10-Q regarding AMI Sales subsequent to 10-31-13 (thru 12-6-13) as has been the case in the 10Q’s for years – the assumption being: NO AMI Sales made 11/1/13-12/6/13, a period where O/S shares only went up by 77,149.
1-31-14 10Q/pg.11: During the 9 mos. ended 1-31-14, we sold 31,983,986 shares under the Dec’12/AMI for gross $52,407,000 before deducting commissions & other iss. costs of $1,427,000. As of 1-31-14, gross proceeds of up to $9,221,000 remained available under the Dec’12/AMI. http://tinyurl.com/pxcjocw
4-30-14 10K pg.F25: “During FY14, we sold 33,527,369 shares under the Dec’12/AMI for gross proceeds of $55,424,000 before deducting commissions & other iss. costs of $1,504,000. As of April 30, 2014, aggregate gross proceeds of up to $6,204,000 remained available under the December 2012 AMI Agreement.” http://tinyurl.com/mhva3k3
7-31-14 10Q/Pg5: During the 3mos. ended 7-31-14, we raised $10,000,000 in aggregate gross proceeds from the sale of our 10.50% SeriesE Convertible Preferred Stock under an At Market Issuance Sales Agreement. Pg.11: During the 3mos. ended 7-31-14, we sold 226,700sh. under the Dec’12-2012 AMI Agreement for gross of $435,000 before deducting commissions & other costs of $14,000. As of 7-31-14, gross of up to $5,769,000 remained available under the Dec’12-2012/AMI. On 6-13-14, we entered into an At Market Issuance Sales Agreement (“June2014/AMI”), with MLV, pursuant to which we may sell shares of our common stock through MLV, for aggregate gross proceeds of up to $25,000,000, in registered transactions from our shelf registration statement on Form S-3. As of 7-31-14, we had not sold any shares of common stock under the June 2014 AMI Agreement. http://tinyurl.com/phw6dkp
10-31-14 10Q/Pg12: COMMON: During 6mos. ended 10-31-14, we sold 2,721,535 sh. at mkt prices under the Dec’12-AMI for gross proceeds of $4,326,000 before deducting commissions and other issuance costs of $113,000. As of 12-31-14, gross proceeds of up to $1,878,000 remained available under the Dec’12-AMI. PREFERRED: During 6mos. ended 10-31-14, we sold 402,858 sh. at mkt prices gross proceeds of $10,070,000 before deducting commission and other issuance costs of $552,000. As of 10-31-14, gross proceeds of up to $19,930,000 remained available under the Series E AMI Agreement. http://tinyurl.com/m6ldhg7
1-31-15 10Q/Pg12: COMMON: During the 9mos. ended 1-31-15, we sold 3,983,360 sh. at mkt prices under the Dec’12-AMI for gross proceeds of $6,204,000 before deducting commissions and other issuance costs of $162,000. As of 1-31-15, we had raised the full-amt of gross proceeds available to us under the Dec’12-AMI. PREFERRED:
Jun’14-AMI: On 6-13-14, we entered into an AMI with MLV…up to $25mm… ,000,000, in registered transactions from our shelf registration statement on Form S-3 (File No. 333-180028). During the 9mos. ended 1-31-15, we sold 869,504 sh. at mkt prices under the Jun’14-AMI for gross of $1,193,000 before deducting commissions and other issuance costs of $31,000. As of 1-31-15, gross proceeds of up to $23,807,000 remained available. Subsequent to 1-15-15 and thru 3-12-15, we sold 4,354,954 sh. of common at mkt prices under the Jun’14-AMI for gross of $6,204,000. As of 3-12-15, 2015, gross proceeds of $17,603,000 remained available under the Jun’14-AMI.
PREFERRED: During the 9mos. ended 1-31-15, we sold 405,004 sh. of our Series E Preferred Stock at mkt prices under the Series E AMI Agreement for gross proceeds of $10,121,000 before deducting commission and other issuance costs of $553,000. As of 1-31-15, 2015, gross proceeds of up to $19,879,000 remained available under the Series E AMI. http://tinyurl.com/mwedt8w
4-30-15 10K pg.F25: During FY’15 we sold 9,681,757sh. under the June’14/AMI for $13,544,000, before deducting costs of $352,000. As of 4-30-15, $11,456,000 remained available. Pg.F35: Subsequent to 4-30-15 & thru 7-14-15, we sold 6,534,400sh. for $8,896,000. A/o 7-14-15, $2,560,000 remain. http://tinyurl.com/ocrtkuj
7-31-15 10Q/Pg12+18: During the 3mos ended 7-31-15, we sold 7,538,230sh. Under the JUNE2014 AMI for gross of $10,166,000 before deducting commiss/iss-costs of $275,000. As of 7-31-15, gross of $1,290,000 remained available under the JUNE2014 AMI, as amended. JUNE2014 AMI: subsequent to 7-31-15 and thru 9-9-15, we sold 1,091,508sh. gross of $1,290,000. As of 9-9-15, 2015, we had raised the full amount available under the June2014 AMI. AUG2015 AMI: on 8-7-15, we entered into an At Market Issuance Sales Agreement with MLV, for gross proceeds of up to $30,000,000, 2.5% commission; as of 9-9-15, we sold 752,760sh. under the AUG2015 AMI for gross of $892,000. http://tinyurl.com/pemub47
10-31-15 10Q/Pg13+19: During 6mos ended 10-31-15, we sold 4,812,238sh at mkt prices under AUG2015 AMI for gross=$5,186,000 before deducting commiss/costs of $132,000. As of 10-31-15, gross proceeds of up to $24,814,000 remained available. Subsequent to 10-31-15, thru 12-10-15, we sold 1,939,413sh for gross=$2,261,000. As of 12-10-15, $22,553,000 remained.
On 10-30-15, we entered into a Common Stock Pur. Agreement with EASTERN CAPITAL Ltd: sold 18,518,518shs @1.08/sh for gross=$20,000,000 before deducting issuance costs of $1,000.
10Q: http://tinyurl.com/zdbo9rv
[10-30-15: Kenneth Dart (Eastern Capital) acquires 13.1% stake (30,106,945sh.) in PPHM http://tinyurl.com/24qctos ]
PREFERRED SHARES:
4-30-15 10K/p.F26: On 6-13-14, we entered into an At Market Issuance Sales Agreement with MLV, pursuant to which we may issue & sell shares of our Series E Preferred Stock through MLV, as agent, for gross proceeds of up to $30,000,000, in registered transactions from our Jan2014 Shelf. During FY’2015, we sold 799,764 shares of our Series E Preferred Stock at mkt prices for gross $19,205,000 before deducting commissions/costs of $1,002,000. As of 4-30-15, gross proceeds of up to $10,795,000 remained available under the Series E AMI Agreement.
NOTE: One of the holders of Preferred is KENNETH DART (EASTERN CAPITAL), who in a 2-13-15 SG14G ( http://tinyurl.com/k4nsfuu ) reported their 240,000sh. Preferred holdings as 2,000,000 common shares (SHARED VOTING POWER: 9,921,760,% OF CLASS REPRESENTED: 5.4%).
“which has a liquidation preference of $25.00/sh. and a conversion price of $3.00/sh.” 2,000,000 / 240,000 = 8.333
- - - - - - - - - - - - - - - - -
Latest 10K 4-30-15 iss. 7-14-15 http://tinyurl.com/ocrtkuj PR: http://tinyurl.com/nw2v5u6 (Cash 4-30-15=$68.0mm)
Latest 10Q 10-31-15 iss. 12-10-15 http://tinyurl.com/zdbo9rv PR: http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=946616 (Cash 10-31-15=$72.0mm)
ALL SEC filings for PPHM: http://tinyurl.com/6d4jw8
- - - - - - - - - - - - - - - - - -
PPHM’S ATM PHILOSOPHY, CFO PAUL LYTLE, 12-9-10 CC:
“Beyond these 2 sources of capital ([Avid & Gov’t], we have raised addl. capital through the equity markets and it’s important to note that over the past 3 years we have sold every share at market prices [“ATM”], without warrants, without discounts. We continue to be active in the investment community and we have had strong interest from institutional investors intrigued by our clinical data, by our multiple trials to evaluate Bavituximab’s broad therapeutic potential, and by the interim survival data we have seen from our novel brain cancer therapy Cotara. Our goal is to maintain a balanced financial approach with multiple sources of capital and to carefully manage our cash burn as we continue to advance these programs.” http://tinyurl.com/24xmcsn
= = = = = = = = = = = = = = = = = =
PPHM - O/S Shares History (’06–curr.)
4-30-06 35,876,438
1-31-07 39,222,440
4-30-07 39,222,440
7-6-07 45,233,123
7-31-07 45,242,123
10-31-07 45,242,123
1-31-08 45,242,123
4-30-08 45,242,123
7-31-08 45,242,123
10-31-08 45,242,123
1-31-09 45,242,123
4-30-09 45,537,711
7-10-09 47,392,883
7-31-09 47,393,783
10-31-09 48,869,563 +1,475,780
1-31-10 50,903,404 +2,033,841
4-30-10 53,094,894 +2,191,490
6-21-10 54,388,917 +1,294,023 (6-22-10 ATM/mlv Form424)
7-9-10 55,069,449 +475,987 (4-30-10 10K iss. 7-14-10)
7-31-10 55,784,955 +715,506
10-31-10 59,220,742 +3,435,787
11-30-10 63,932,353 +4,711,611 (10-31-10 10Q iss. 12-9-10)
12-15-10 64,404,097 +471,744 (12-17-10 S-3: $75M Shelf Reg.)
1-31-11 66,813,419 +2,409,322
2-28-11 67,885,811 +1,072,392 (1-31-11 10Q iss. 3-11-11)
4-30-11 69,837,142 +1,951,331
7-8-11 71,069,858 +1,232,716 (4-30-11 10K iss. 7-14-11)
8-22-11 72,704,647 +1,634,789 (Proxy iss. 8-26-11)
8-31-11 73,284,016 +579,369 (424B5 iss. 9-2-11)
9-8-11 79,536,268 +6,252,252 (Roth Sale to 3 Inst’s @ $1.11/sh.)
10-31-11 82,638,201 +3,101,933
12-9-11 86,788,817 +4,150,616 (10-31-11 10Q iss. 12-12-11)
1-31-12 93,146,226 +6,357,409
2-29-12 98,873,172 +5,726,946 (1-31-12 10Q iss. 3-9-12)
4-30-12 101,421,365 +2,548,193
7-13-12 104,174,056 +2,752,691 (4-30-12 10K iss. 7-16-12)
7-31-12 104,178,431 +4,375 (7-31-12 10Q iss. 9-10-12)
8-16-12 104,191,176 +12,745 (prelim. proxy 14A http://tinyurl.com/c48bvof )
9-7-12 104,191,176 nochg (7-31-12 10Q iss. 9-10-12)
10-31-12 123,310,188 +19,119,012
12-7-12 132,539,783 +9,229,595 (10-31-12 10Q iss. 12-10-12)
1-31-13 133,770,614 +1,230,831
3-12-13 137,110,758 +3,340,144 (1-31-13 10Q iss. 3-12-13)
4-30-13 143,768,946 +6,658,188 (4-30-13 10K iss. 7-11-13)
7-5-13 151,602,765 +7,833,819 (4-30-13 10K iss. 7-11-13)
7-31-13 153,506,811 +1,904,046
9-5-13 156,461,114 +2,954,303 (7-31-13 10K iss. 9-9-13)
10-31-13 160,248,742 +3,781,628
12-6-13 160,325,891 +77,149 (10-31-13 10K iss. 12-10-13)
1-31-14 176,453,261 +16,127,370
3-3-14 176,481,054 +27,793 (1-31-14 10Q iss. 3-7-14)
4-30-14: 178,871,164 +2,390,110
7-7-14: 179,209,458 +338,294 (4-30-14 10-K cover page, iss. 7-14-14)
7-31-14: 179,216,032 +6,574 (7-31-14 10Q iss. 9-9-14)
8-22-14: 179,226,424 +10,392 (8-28-14 Proxy/Def14A)
9-5-14: 179,505,424 +279,000 (7-31-14 10Q iss. 9-9-14)
10-31-14: 182,000,583 +2,495,159 (10-31-14 10Q iss. 12-10-14)
12-5-14: 182,081,234 +80,651 (10-31-14 10Q cover pg., iss. 12-10-14)
12-19-14: 182,081,234 -0- (12-23-14 S-3)
1-31-15: 184,244,698 +2,163,464 (1-31-15 10Q iss. 3-12-15)
3-12-15: 188,332,872 +4,088,174 (1-31-15 10Q iss. 3-12-15)
4-30-15: 193,346,627 +5,013,755 (4-30-15 10-K iss. 7-14-15)
7-10-15: 199,934,918 +6,588,291 (4-30-15 10-K/cover-pg, iss. 7-14-15)
7-31-15: 200,983,948 +1,049,030 (7-31-15 10Q iss. 9-9-15)
9-4-15: 202,124,031 +1,140,083 (7-31-15 10Q iss. 9-9-15)
10-31-15: 225,824,551 +23,700,520 (10-31-15 10Q iss. 12-10-15)<=Incl. 18.5mm sh. Dart/EastCAP
12-9-15: 229,701,808 +3,877,257 (10-31-15 10Q iss. 12-10-15)
O/S WARRANTS & STOCK-OPTIONS A/O 10-31-2015 (10-Q pg.15/16):
• WARRANTS: As of 10-31-2015, warrants to purchase 273,280 shares at an exercise price of $2.47 were outstanding and are exercisable through Aug30 2018. These warrants were issued in FY’13 in connection with the Aug.2012 [Oxford] loan agreement, which was paid in full during Sept.2012.
• STOCK OPTIONS OUSTANDING A/O 10-31-2015: 23,623,601 shares at a wgt.avg. exercise price of $1.50. (during 6mos. ended 10-31-15, 165,266sh. exercised at avg=.80)
= = = = = = = = = = =PREFERRED STOCK:
...2-5-14: PPHM Announces Public Offering of 10.5% Series E Convertible Preferred Stock http://tinyurl.com/lkxsna6
...2-11-14: PPHM Raises net $16.2mm selling 700k Preferred Shares with 10.5% div. at $25/sh, convertible to common at $3/sh http://tinyurl.com/jwmsnsk (8-K)
...6/14/14-7/14/13: PPHM Raises net $9.5mm selling 400k Preferred Shares with 10.5% div. at $25/sh, convertible to common at $3/sh http://tinyurl.com/mhva3k3 (4-30-14 10-K pg. F-34; $20mm gross remaining)
PVAC=“Feedback” (SA Error)… Still working on correcting all the errors before posting corrected transcript...
XXX: Based on PVAC so far we expect that the new study
S/b: Based on feedback so far, we expect that the new study
12-10-15/CC: CEO STEVE KING – OPENING COMMENTS:
Thanks as always to all of you who have dialed in, and to all of you who are participating via webcast today. I’ll start by saying that we are making great progress in our broad overall development strategy for bavituximab. The strategy is to establish the potential of bavituximab in combination with current & evolving standard of care drugs, with both chemotherapy and immuno-oncology combinations in multiple cancer indications. Our goal is to drive to meaningful clinical data points in each of these areas by early 2017. In accordance, today’s development discussions will focus on these efforts, including upcoming completion enrollment in the SUNRISE trial which is evaluating a chemotherapy combination, and, as SUNRISE wraps up, our plans for a smooth transition of the key SUNRISE clinical sites directly to the next Phase II lung cancer trial evaluating an IO combination. In addition, we are expanding our potential cancer indications through initiation of a Phase II/III metastatic breast cancer study. All of this while continuing to work through several other clinical trial concepts actively under development or initiation in the new year.
On the development front, I’m pleased to report today that we are nearing completion of enrollment in the cornerstone of our bavituximab development strategy, our Phase III SUNRISE trial. In fact, with over 90% of the expected enrollment complete, we currently have sufficient patient enrollment based on the assumptions of the study to allow the trial’s planned interim evaluations and final readout based on the primary endpoint of overall survival. Having said that, we do expect to complete enrollment of at least the pre-specified 582 patients over the coming weeks. At this point, the next big milestones really are the interim data analysis from the study, expected to take place during early & mid 2016, with trial unblinding expected toward the end of 2016. Joe will add little more color to the up coming milestones for the SUNRISE trial during his prepared remarks.
For me, what has now become the most important thing at this point in our broader strategy is to engage our best enrolling sites from the SUNRISE trial toward a smooth transition to the new Phase II study that will evaluate bavi in combination with AstraZeneca’s anti-PD-L1 antibody durvalumab. We have a golden opportunity here to maintain continuity for our lung cancer program by continuing almost seamlessly working with our high enrolling sites and key investigators in essentially the same, even in extended, patient population with the inclusion of squamous non-small cell lung cancer patients. I have personally had the opportunity to meet with key investigators all over the globe and there is a lot of enthusiasm for continuing to work with Peregrine and bavituximab in the new study. Based on feedback so far, we expect that the new study could enroll even more quickly than the SUNRISE trial and the best way to ensure that is to get off to a quick start, again keeping us on track for data from the new study by early 2017. This would give us two nice sets of data in NSCLC to work with.
Equally exciting is the Phase II/III metastatic HER2- breast cancer study that we are looking forward to starting by year-end. I say exciting because the new trial design has a solid clinical data basis, and our previously completed Phase I & II trials in a patient population in these new treatment options. While we don’t have the same benefit as we do for the lung cancer program of rolling right from one study into another, the team has been working diligently to get the study started by the year-end, giving us additional enrollment months, which again can put us on track for some meaningful clinical data from the study by early 2017.
The company is also working diligently on a number of other studies, including our other collaboration with AstraZeneca, evaluating a combination of bavi with chemotherapy and adding in again their durvalumab antibody in multiple solid tumor indications. So, conceptually, “get an immune response going with chemotherapy & Bavi, and then keep it going with durvalumab”.
In addition, we are working toward initiating an earlier stage breast cancer study, as well as a number of other concepts that are in development. So, stay tuned for future clinical developments. Taken together, these clinical efforts, along with the plethora of preclinical & translation collaborations evaluating new combinations, new potential indications, and further validating our immune mechanism of action has a potential to add substantial value over the coming year. We expect a steady flow of scientific & clinical presentations over the coming year as we continue to learn to more about the potential bavituximab.
Oh, and by the way, today we also announced another record revenue quarter from our biomanufacturing business, with our new Myford manufacturing facility just ready for GMP production, which can help spur even more future growth for the business, not the least of which is getting ready for bavi commercial production. Rob & Paul will add more detail and discuss the continued growth for our mfg. business shortly. To say that these are busy times at Peregrine is an understatement.
Updated PPHM REVS-BY-QTR TABLE, now thru FY16'Q2(qe10-31-15), per the 10-31-15 10-Q ( http://tinyurl.com/ocrtkuj ) issued 12-10-15.
• Total Revs since May’06: ($148.1mm/Avid + $24.1mm/Govt + $2.4mm/Lic.) = $174.7mm
• Deferred-Revs at 10-31-15, going fwd into FY’16/Q3 (q/e 1-31-16), total $9.7mm, UP from the $8.3mm of Deferred-Revs at 7-31-15 that drove into FY’16/Q2.
• Cust.Deposits at 10-31-15 total $14.9mm, UP from $9.6mm at 7-31-15.
• Avid’s Gross-Profit over last 3 qtrs: $14.1mm on revs of $28.2mm (GP%=50%)
• Recall, Avid Rev$ from Gov’t DTRA Contract work (6/30/08 – 4/15/11, totaling $24.15mm), went into GOVT-REVS, not AVID-REVS, in the Financials.
Avid’s website: http://www.avidbio.com
AVID PROFITABILITY (GROSS*) BY QTR:
QTR Avid-Rev$ CostofMfg$ Gross-Profit$ GP%
FY13Q1 7-31-12 4,135,000 2,024,000 2,111,000 51%
FY13Q2 10-31-12 6,061,000 3,703,000 2,358,000 39%
FY13Q3 1-31-13 6,961,000 3,651,000 3,310,000 47%
FY13Q4 4-30-13 4,176,000 3,217,000 959,000 23%
FY13 TOTAL: 21,333,000 12,595,000 8,738,000 41%*
FY14Q1 7-31-13 4,581,000 2,670,000 1,911,000 42%
FY14Q2 10-31-13 7,354,000 4,195,000 3,159,000 43%
FY14Q3 1-31-14 3,885,000 2,416,000 1,469,000 38%
FY14Q4 4-30-14 6,474,000 3,829,000 2,645,000 41%
FY14 TOTAL: 22,294,000 13,110,000 9,184,000 41%*
FY15Q1 7-31-14 5,496,000 3,583,000 1,913,000 35%
FY15Q2 10-31-14 6,263,000 4,139,000 2,124,000 34%
FY15Q3 1-31-15 5,677,000 3,113,000 2,564,000 45%
FY15Q4 4-30-15 9,308,000 4,758,000 4,550,000 49%
FY15 TOTAL: 26,744,000 15,393,000 11,151,000 42%*
FY16Q1 7-31-15 9,379,000 4,608,000 4,771,000 51%
FY16Q2 10-31-15 9,523,000 4,741,000 4,782,000 50%
*Avid Net-Profit (ie, incl. Selling, G&A) not split out from PPHM-Corp. in the financials.
.
PPHM REVENUES (in thousands) DEFERRED
-------REVENUES------- REVENUES INVEN-
Quarter Avid Govt Lic. TOTAL Avid Govt TORIES
FY07Q1 7-31-06 398 0 23 421 317 0 971
FY07Q2 10-31-06 636 0 48 684 1388 0 1899
FY07Q3 1-31-07 347 0 16 363 2202 0 1325
FY07Q4 4-30-07 2111 0 129 2240 1060 0 1916
FY08Q1 7-31-07 1621 0 4 1625 1820 0 2363
FY08Q2 10-31-07 1863 0 29 1892 1338 0 3500
FY08Q3 1-31-08 1662 0 13 1675 1434 0 2394
FY08Q4 4-30-08 751 0 150 901 2196 0 2900
FY09Q1 7-31-08 1193 324 0 1517 4021 980 4628
FY09Q2 10-31-08 983 958 0 1941 6472 1701 6700
FY09Q3 1-31-09 5778 1048 0 6826 4805 3262 5547
FY09Q4 4-30-09 5009 2683 175 7867 3776 3871 4707
FY10Q1 7-31-09 2070 4671 9 6750 5755 2332 6177
FY10Q2 10-31-09 5308 1510 78 6896 4260 3989 5850
FY10Q3 1-31-10 2945 6854 78 9877 3052 76 3861
FY10Q4 4-30-10 2881 1461 78 4420 2406 78 3123
FY11Q1 7-31-10 983 2111 115 3209 3719 47 4692
FY11Q2 10-31-10 3627 966 78 4671 2447 35 3555
FY11Q3 1-31-11 1922 882 79 2883 4300 40 3915
FY11Q4 4-30-11 1970 681 78 2729 5617 0 5284
FY12Q1 7-31-11 5439 0 216 5655 4145 0 4481
FY12Q2 10-31-11 4154 0 78 4232 2012 0 3178
FY12Q3 1-31-12 3203 0 78 3281 2552 0 2722
FY12Q4 4-30-12 1987 0 78 2065 3651 0 3611
FY13Q1 7-31-12 4135 0 116 4251 6056 0 5744
FY13Q2 10-31-12 6061 0 78 6139 6221 0 5426
FY13Q3 1-31-13 6961 0 78 7039 5061 0 4635
FY13Q4 4-30-13 4176 0 78 4254 4171 0 4339
FY14Q1 7-31-13 4581 0 107 4688 4164 0 5679
FY14Q2 10-31-13 7354 0 0 7354 3468 0 4033
FY14Q3 1-31-14 3885 0 0 3885 4329 0 5224
FY14Q4 4-30-14 6474 0 0 6474 5241 0 5530
FY15Q1 7-31-14 5496 0 0 5496 4670 0 5998
FY15Q2 10-31-14 6263 0 37 6300 3612 0 5379
FY15Q3 1-31-15 5677 0 0 5677 5752 0 6148
FY15Q4 4-30-15 9308 0 0 9308 6630 0 6148
FY16Q1 7-31-15 9379 0 292 9671 8291 0 10457
FY16Q2 10-31-15 9523 0 0 9523 9688 0 12554
Totals: 148114 24149 2416 174679 <=since5/1/2006
.
TOTAL REV’s BY YEAR (Avid+Gov’t+Lic):
FY04 4-30-04 3,314 …Avid(CMO)= 3,039 (Avid-Revs don’t incl. Govt-SVCS)
FY05 4-30-05 4,959 …Avid(CMO)= 4,684
FY06 4-30-06 3,193 …Avid(CMO)= 3,005
FY07 4-30-07 3,708 …Avid(CMO)= 3,492
FY08 4-30-08 6,093 …Avid(CMO)= 5,897
FY09 4-30-09 18,151 …Avid(CMO)= 12,963
FY10 4-30-10 27,943 …Avid(CMO)= 13,204
FY11 4-30-11 13,492 …Avid(CMO)= 8,502
FY12 4-30-12 15,233 …Avid(CMO)= 14,783
FY13 4-30-13 21,683 …Avid(CMO)= 21,333
FY14 4-30-14 22,401 …Avid(CMO)= 22,294
FY15 4-30-15 26,781 …Avid(CMO)= 26,744
...Total Gov’t Revs from 7-2008 inception thru FY11Q1(Apr’11): $24.15mm
.
AVID “Total Services”:
AVID OUTPUT$ 3rd-PARTY + PEREGRINE = TOTAL-OUTPUT$
FY09 4-30-09 13mm 10mm $23mm #
FY10 4-30-10 13mm 17mm $30mm #
FY11 4-30-11 9mm 11mm $20mm @
FY12 4-30-12 15mm 11mm $26mm @
FY13 4-30-13 21mm ~10mm ~$31mm ^
LTM ended 1/2010 3rd/$15.3mm + Govt/$8.3mm + PPHM/$8.8mm = $32.4mm *
@SKing 3-18-2013 RothOC/DanaPT (Slide21) http://tinyurl.com/cebtwen
#SKing 7-12-2012 JMP/NYC Conf. (Slide27) http://tinyurl.com/csdclwb
*SKing 3-17-2010 RothOC/DanaPT Conf. (Slide18) http://tinyurl.com/ye9v7jq
^PLytle 7-11-2013 Qtly-CC “Avid did ~$10mm in equivalent services for Peregrine in FY13, which doesn’t get reflected into the fin. statements, it's eliminated in consolidation.”
.
PPHM’S QTLY. NET LOSS BY QTR:
FY08Q1 7-31-07 4,656,000
FY08Q2 10-31-07 6,207,000
FY08Q3 1-31-08 6,154,000
FY08Q4 4-30-08 6,159,000
FY09Q1 7-31-08 5,086,000
FY09Q2 10-31-08 4,497,000
FY09Q3 1-31-09 3,332,000
FY09Q4 4-30-09 3,609,000
FY10Q1 7-31-09 2,428,000
FY10Q2 10-31-09 2,787,000
FY10Q3 1-31-10 1,538,000
FY10Q4 4-30-10 7,741,000
FY11Q1 7-31-10 7,695,000
FY11Q2 10-31-10 7,513,000
FY11Q3 1-31-11 8,929,000
FY11Q4 4-30-11 10,014,000
FY12Q1 7-31-11 8,092,000
FY12Q2 10-31-11 12,055,000
FY12Q3 1-31-12 11,090,000
FY12Q4 4-30-12 10,882,000
FY13Q1 7-31-12 7,664,000
FY13Q2 10-31-12 8,753,000
FY13Q3 1-31-13 4,914,000
FY13Q4 4-30-13 8,449,000
FY14Q1 7-31-13 7,600,000
FY14Q2 10-31-13 7,790,000
FY14Q3 1-31-14 9,724,000
FY14Q4 4-30-14 10,248,000
FY15Q1 7-31-14 13,129,000
FY15Q2 10-31-14 12,100,000
FY15Q3 1-31-15 12,994,000
FY15Q4 4-30-15 12,135,000
FY16Q1 7-31-15 13,723,000
FY16Q2 10-31-15 13,198,000
= = = = = = = =
OPER. CASH BURNS* BY QTR(FROM THE 10-Q/K’S):
FY10Q1 7-31-09 2,024,000 (from 10Q pg.25)
FY10Q2 10-31-09 2,351,000 (Q1+Q2: 4,375,000 pg.28)
FY10Q3 1-31-10 1,158,000 (Q1+Q2+Q3: 5,533,000 pg.30)
FY10Q4 4-30-10 6,375,000 (FY’10: 11,908,000 10K pg.58)
FY11Q1 7-31-10 6,567,000 (from 10Q pg.24)
FY11Q2 10-31-10 6,167,000 (Q1+Q2: $12,734,000 pg.25)
FY11Q3 1-31-11 7,736,000 (Q1+Q2+Q3: $20,470,000 pg.26)
FY11Q4 4-30-11 8,961,000 (FY’11: 29,431,000 10K pg.54)
FY12Q1 7-31-11 6,984,000 (from 10Q pg.25)
FY12Q2 10-31-11 11,668,000 (Q1+Q2: 18,652,000 pg.25)
FY12Q3 1-31-12 8,490,000 (Q1+Q2+Q3: 27,142,000 pg.25)
FY12Q4 4-30-12 11,265,000 (FY’12: 38,407,000 10K pg.55)
FY13Q1 7-31-12 6,742,000 (from 10Q pg.21)
FY13Q2 10-31-12 6,162,000 (Q1+Q2: 12,904,000 pg.23)
FY13Q3 1-31-13 3,597,000 (Q1+Q2+Q3: 16,501,000 pg.23)
FY13Q4 4-30-13 7,053,000 (FY’13: 23,554,000 10K pg.60)
FY14Q1 7-31-13 5,750,000 (from 10Q pg.23)
FY14Q2 10-31-13 5,834,000 (Q1+Q2: 11,584,000 10Q pg.24)
FY14Q3 1-31-14 7,875,000 (Q1+Q2+Q3: 19,459,000 10Q pg.26)
FY14Q4 4-30-14 8,706,000 (FY’14: 28,165,000 10K pg.55)
FY15Q1 7-31-14 11,076,000 (from 10Q pg.23)
FY15Q2 10-31-14 9,947,000 (Q1+Q2: 21,023,000 10Q pg.25)
FY15Q3 1-31-15 11,116,000 (Q1+Q2+Q3: 32,139,000 10Q pg.26)
FY15Q4 4-30-15 10,474,000 (FY’15: 42,613,000 10K pg.54)
FY16Q1 7-31-15 12,306,000 (from 10Q pg.25)
FY16Q2 10-31-15 11,701,000 (Q1+Q2: 24,007,000 10Q pg.26)
FY’09 total Op-Burn: $14,715,000
FY’10 total Op-Burn: $11,908,000
FY’11 total Op-Burn: $29,431,000
FY’12 total Op-Burn: $38,407,000
FY’13 total Op-Burn: $23,554,000
FY’14 total Op-Burn: $28,165,000
FY’15 total Op-Burn: $42,613,000
Avid Scientist Dr. David Briggs' 10-7-15 Lecture @SSB Upstream & Downstream Technology Forum in Foster City, Calif...
12-7-15/GEN: “Boosting Upstream & Downstream Output - Sartorius Stedim Biotech Forum Focuses On Next Level Bioprocess Operations”
By: K. John Morrow, PhD (CEO, Newport Biotech)
GEN = Genetic Engineering & Biotechnology News
At the recent Sartorius Stedim Biotech (SSB) Upstream & Downstream Technology Forum in Foster City, CA, (Oct6-7 2015 http://www.sartorius.com/en/upstream-downstream-forum ) speakers dealt with both sides of these technological challenges...
. . .SCALE UP & SCALE DOWN
With tangential flow filtration of protein solutions, researchers are able to concentrate and buffer exchange biotherapeutics to their proper dose and excipients, according to David Briggs, PhD, a research scientist in Mfg. Sciences & Technology at Avid Bioservices. “However, we recognize that at higher protein concentrations this may present a problem, and of course the future of the industry will focus on highly concentrated protein solutions,” he pointed out.
Dr. Briggs discussed his experiences in fine-tuning TFF (Tangential-Flow Filtration), which is also known as cross-flow filtration. The technology is based on running the field stream parallel to the filter device. Small molecules are eliminated, and the larger ones are concentrated in the retentate. While TFF can be employed anywhere in the protein purification process, in general it is only used in the final formulation step.
Dr. Briggs uses diafiltration (DF) in the purification process, by which new buffer is constantly introduced into the flow. With the dilution of the solutes the unwanted molecular species and residual starting buffer components are gradually removed. “During DF, keeping the retentate volume constant is necessary for efficiency and reproducibility,” he told the forum attendees.
A major feature of TFF is that it can be upscaled & downscaled to meet the demands of different protocols without adversely affecting the parameters of the process. The data establish that at large and small scale, flux rates were similar during concentration and that step yields and recovery rates during the entire TFF operation were similar. Finally, at both the manufacturing scale and at lab bench scale, conductivity decreases as a function of diavolumes were similar. . .
http://www.genengnews.com/insight-and-intelligence/boosting-upstream-and-downstream-output/77900575
10-7-15 11:15am Lecture 3
”Successful Scale-Up and Scale-Down of Ultrafiltration Processes in Clinical Manufacturing”
DAVID BRIGGS, PhD, Scientist, MSAT, Avid Bioservices, Inc.
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= = = = = = = = = = = = = = = =
For latest Qtr(7-31-15), Avid ran GP%=51 on Sales of $9.4mm; for last 3 qtrs, GP%=49/GP$=$11.9mm on Sales of $24.1mm. Avid's “committed backlog” = $42mm at 9/2015.
Updated PPHM REVS-BY-QTR TABLE, now thru FY16/Q1 (q/e 7-31-15), per the 7-31-15 10-Q (http://tinyurl.com/pemub47 ) issued 9-9-15.
• Total Revs since May’06: ($138.6mm/Avid + $24.1mm/Govt + $2.4mm/Lic.) = $165.2mm
• Deferred-Revs at 7-31-15, going fwd into FY’16/Q2 (q/e 10-31-15), total $8.3mm, UP from the $6.6mm of Deferred-Revs at 4-30-15 that drove into FY’16/Q1.
• Avid’s Gross-Profit over last 3 qtrs: $12.5mm on revs of $24.4mm (GP% = 49%)
• Recall, Avid Rev$ from Gov’t DTRA Contract work (6/30/08 – 4/15/11, totaling $24.15mm), went into GOVT-REVS, not AVID-REVS, in the Financials.
Avid’s website: http://www.avidbio.com
AVID PROFITABILITY (GROSS*) BY QTR:
QTR Avid-Rev$ CostofMfg$ Gross-Profit$ GP%
FY14Q1 7-31-13 4,581,000 2,670,000 1,911,000 42%
FY14Q2 10-31-13 7,354,000 4,195,000 3,159,000 43%
FY14Q3 1-31-14 3,885,000 2,416,000 1,469,000 38%
FY14Q4 4-30-14 6,474,000 3,829,000 2,645,000 41%
FY14 TOTAL: 22,294,000 13,110,000 9,184,000 41%*
FY15Q1 7-31-14 5,496,000 3,583,000 1,913,000 35%
FY15Q2 10-31-14 6,263,000 4,139,000 2,124,000 34%
FY15Q3 1-31-15 5,677,000 3,113,000 2,564,000 45%
FY15Q4 4-30-15 9,308,000 4,758,000 4,550,000 49%
FY15 TOTAL: 26,744,000 15,393,000 11,151,000 42%*
FY16Q1 7-31-15 9,379,000 4,608,000 4,771,000 51%
*Avid Net-Profit (ie, incl. Selling, G&A) not split out from PPHM-Corp. in the financials.
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9-10-15/OutsourcingPharma: “Avid Revs Likely to Grow Substantially”
9-10-15: “Peregrine Up on CMO Q1 Sales & Backlog, as New Plant Set to Go Online”
By Dan Stanton, Outsourcing-Pharma
http://www.outsourcing-pharma.com/Contract-Manufacturing/Peregrine-up-on-CMO-sales-and-backlog-as-new-plant-set-to-go-online
Manufacturing backlog at Avid Bioservices has reached $42mm as the firm books up space at a new facility currently undergoing its first internal pilot run. For Q1/FY2016, Peregrine Pharmaceuticals reported record revenue from its contact mfg. business Avid Bioservices of $9.4mm, up 71% year-on-year. But revenues are likely to grow substantially, the firm said, as there is a $42mm committed backlog from existing customers which will be carried-out in part once a new mammalian cell culture mfg. facility in Tustin, CA comes online.
“The new manufacturing suite is fully built and the first internal pilot run is currently underway to verify all systems and equipment are properly functioning,” Peregrine CFO Paul Lytle said during an investor call yesterday. ”Our strategic investment in the Avid Bioservices business is already starting to pay dividends. Our clients are reserving mfg. slots in the new facility which has increased our revenue backlog to approximately $42mm.”
A large proportion of the firm’s revenues come from its major client, Halozyme Therapeutics, servicing monoclonal antibody development projects with Roche & Baxter. While the company hopes the new facility will attract new customers, it is the current customer base showing the most interest.
“In the new facility, a lot of the interest comes from the existing client base, even as much as we've had new potential customers coming through,” said CEO Steven King. “It's exciting, it's a real nice showpiece and it's really showing in the interest that it's generated from again the existing client base.”
The site, first announced last year, more than doubles Avid’s mfg. capacity, though some of the space has been reserved to service its parent company’s lead product bavituximab, a chimeric mAb in Phase III trials for non-squamous NSCLC. END
6-17-15: Avid’s John Haney (ex-Genentech/Pfizer) speaking at BIO-INTL’5/Philly http://tinyurl.com/pnlquu3 & http://tinyurl.com/nl4vbgk
...”Designing & Implementing Avid’s New State-of-the-Art Single-Use Facility for Late Ph.3 & Commercial Prod.” - SK: "We've seen tremendous interest for production in the new facility, both from new & existing clients"
12-10-14: Avid to Double Mfg. Capacity (“expanding client roster; potential commercial launch of bavituximab”) http://tinyurl.com/mmc3qgy & http://tinyurl.com/kmdgq8t
3-24-15: Avid Receives CMO Leadership Awards for Its Commitment to Innovation & Reliability http://tinyurl.com/psep47f
3-12-13: Avid Q3'FY13 GP=$3.3mm; S.King 3-2012, ”We have a profitable CMO, Avid Bioservices" http://tinyurl.com/l97rzm8
Roth's 12-16-15 Immuno-Oncology Corp. Access Day (PPHM=1of12)
Dec16 2015: “Roth Capital Partners' Immuno-Oncology Corp. Access Day”, NYC http://tinyurl.com/p8ykuu7
...Peregrine will be 1 of 12 participating companies.
FLYER:
“ROTH Capital Partners Senior Biotechnology Research Analysts; Joe Pantginis, PhD, Elemer Piros, PhD, and Michael Higgins invite you to join us for our Immuno-Oncology Corporate Access Day taking place on Wednesday, Dec. 16, 2015 in NYC.
http://www.meetmax.com/upload/event_35023/ROTH_ImmunoOncology_2015.pdf
http://www.roth.com
Fri/12-11-15: Freimark/Hutchins Poster at Annual SanAntonio-Breast-Cancer-Symposium
Dec8-12 2015: 38th Annual San Antonio Breast Cancer Symposium
“...presented by the Cancer Therapy & Research Center at UT Health Science Center San Antonio, AACR, and Baylor College of Medicine. The driving force behind this collaboration is the shared mission of the organizations to advance progress against breast cancer. As exciting strides are made in the field of breast cancer research and treatment our program continues to present essential up-to-the minute information combined with engrossing discussion for basic, translational and clinical cancer research professionals.
At SABCS'14, there were 7,362 Symposium attendees + 206 Media + 345 Exhibitors, Non-Exhibiting Sponsors & their Support Staff = 7,913 total attendance. More than 53% came from 94 countries outside the USA”
http://www.sabcs.org
http://www.sabcs.org/Program/Poster-Sessions/Poster-Session-4
12-11-15 7:30–9:00am Poster Session
TRACK: Tumor Cell & Molecular Biology: Immunology & Preclinical Immunotherapy
#P4-04-03 “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Immune Checkpoint Inhibitor PD-1/PD-L1 Therapy in Murine Breast Tumors”
M.Gray, J.Gong, V.Nguyen, Jeff Hutchins, Bruce Freimark - Peregrine Pharmaceuticals
= = = = = = = = =KNOWN UPCOMINGS:
Dec7-10/Avid/Booth307: IBC's Antibody Eng. & Therapeutics, SanDiego http://www.ibclifesciences.com/AntibodyEng
Dec10 4:30pmET(1:30pmPT): FY'16Q2 (qe 10-31-15) Financials & Conf. Call http://ir.peregrineinc.com/events.cfm
Dec11 7:30-9am: 38th Annual San Antonio Breast Cancer Symposium http://tinyurl.com/hyl8sqx
...Poster #P4-04-03 Freimark/Hutchins: “Targeting of PS by Mabs Augments the Activity of Immune Checkpoint Inhibitor PD-1/PD-L1 Therapy in Murine Breast Tumors”
Dec16: Roth Capital Partners' Immuno-Oncology Corp. Access Day, NYC http://tinyurl.com/p8ykuu7 (PPHM = 1 of 16 participating companies)
Mar6-11 2016: CHI’s 23rd Molecular Med TRI-CON 2016, SanFran http://www.triconference.com (Speaker: Dr. Jeff Hutchins, VP/Preclin.Res.)
~Mar10: FY'16Q3 (qe 1-31-16) Financials & Conf. Call http://ir.peregrineinc.com/events.cfm
Mar15-17 2016: Immune Checkpoint Inhibitors Conf., Boston http://immune-checkpoint.com (Peregrine is 1 of 4 Corp. Sponsors)
My 1st-Cut Summary List of Peregrine Collabs & KOLs
PRECLIN:
UTSW/preclin: Dr. Philip Thorpe(Inventor/anti-PS/Bavi 1951-2013)=> Dr. Rolf Brekken http://www.utsouthwestern.edu/labs/brekken
Sloan-Kettering (Dr. Jedd Wolchok Lab): http://tinyurl.com/o3k9ux8
Duke (Dr. Herbert K. Lyerly): http://tinyurl.com/pbof95w
UC/Irvine (Dr. Christopher C.W. Hughes): http://tinyurl.com/omqj5m3
Providence CC/Opal 6-plex assay (Dr. Bernard A. Fox): http://tinyurl.com/ojrpvqy
Mayo/Ocular(Dr. Jose S. Pulido) http://tinyurl.com/qhdmsa5
Tulane/Ocular(Dr. Shusheng Wang) http://tinyurl.com/qhdmsa5
CLINICAL:
AstraZeneca (Dr. Robert Iannone Head/I-O, Maria Karasarides Sr.Dir/I-O): http://tinyurl.com/q79bkam
UTSW (Dr. David Gerber, Dr. Adam Yopp): http://tinyurl.com/nv4jloo & http://tinyurl.com/opkh5qy
Moffitt (Dr. Scott Antonia): http://tinyurl.com/p9eduac & http://tinyurl.com/qxu4w2x
IST's:
UTSW - Melanoma (Dr. Arthur Frankel): http://www.clinicaltrials.gov/ct2/show/NCT01984255
UTSW - Rectal (Dr. Jeffrey Meyer): http://www.clinicaltrials.gov/ct2/show/NCT01634685
UNC – NSCLC (Dr. Juneko Grilley-Olson): http://clinicaltrials.gov/ct2/show/NCT01323062
UNIV-ARIZ – Breast (Dr. Alison Stopeck) http://clinicaltrials.gov/ct2/show/NCT01288261
UTSW – Liver (Dr. Adam Yopp) http://www.clinicaltrials.gov/ct2/show/NCT01272791
SAB: http://www.peregrineinc.com/about-us/medical-and-scientific-advisors.html
Scott J. Antonia, M.D., Ph.D. - H. Lee Moffitt CC
Rolf Brekken, Ph.D. - UT Southwestern MC
David Carbone, M.D., Ph.D. - Ohio State Univ., President/IASLC
Bruce Chabner, M.D. - Mass. General Hosp., Harvard Medical School
Harold F. Dvorak, M.D. - Beth Israel Deaconess, Harvard Medical School
Dmitry I. Gabrilovich, M.D., Ph.D. - The Wistar Institute
Christopher C. W. Hughes, Ph.D. - Univ. of California/Irvine
Hakan Mellstedt, M.D., Ph.D. - Karolinska Institute, Sweden
Alan J. Schroit, Ph.D. - M.D. Anderson
SPEAKERS AT PPHM's 11-6-15 SITC'15 I-O Roundtable: http://tinyurl.com/pbof95w
(in addition to SAB'ers Dmitry Gabrilovich, Rolf Brekken, and AZN's Maria Karasarides)
Rutgers (Dr. Raymond Birge) http://birgelab.org
Emory (Dr. Douglas Graham) http://tinyurl.com/pugjnbt
SPEAKERS AT PPHM's 5-31-15 ASCO’15 I-O Roundtable: http://tinyurl.com/qxu4w2x
(in addition to SAB'ers Scott Antonia, Dmitry Gabrilovich, Rolf Brekken)
Loxo Oncology - BOD (Dr. Lori Kunkel) http://www.loxooncology.com
Indiana Univ. (Dr. Kathy D. Miller) http://www.bcrfcure.org/researchers/kathy-d-miller
Sloan-Kettering (Dr. Dmitriy Zamarin) https://www.mskcc.org/research-areas/labs/members/dmitriy-zamarin
Sloan-Kettering (Dr. Matthew D. Hellman) http://www.mskcc.org/cancer-care/doctors/matthew-hellmann
Sloan-Kettering (Dr. Alexander M. Lesokhin) http://www.mskcc.org/research-areas/labs/members/alexander-lesokhin-01
BETABODIES Patent: U.S./Granted=2-17-15; EUR./INTENT-TO-GRANT=11-8-15. Excellent find, Endo!
BETABODIES (ex: KL15), “potentially the next generation of PS-targeting cancer therapeutics” - generated by fusing domains of the PS-binding the plasma protein, B2-glycoprotein I (B2GPI), to the Fc region of mouse IgG2a. Such ‘betabodies’ potentially have the following advantages: they bind directly to PS and do not require a cofactor protein (B2GPI) for binding; they can be made fully human; they are smaller in size (100 vs. 250 KDa); and they have slower blood clearance rates (half-life of ~5days vs. Bavi’s ~1day).
…See 7-6-13, “Entdoc, here’s a bunch of stuff on Betabodies” http://investorshub.advfn.com/boards/read_msg.aspx?message_id=89680206http://tinyurl.com/khopa3d
- - - - - - - - - - - - - - - -U.S. Patent #8,956,616:
UTSW/PPHM’s BetaBodies patent AWARDED(GRANTED) 2-17-15, U.S. Patent #8,956,616
‘BETABODIES’ patent app #20060228299, filed 1-24-2006, pub 10-12-2006, AWARDED 2-17-2015…
"Constructs Binding to Phosphatidylserine and Their Use in Disease Treatment" ("Betabodies & Receptorbodies”)
Inventors: Philip E. Thorpe, Troy A. Luster, Steven W. King
Assignee1: BOARD OF REGENTS, UNIV. OF TEXAS SYSTEM, 201 W. 7TH ST, AUSTIN, TX
Assignee2: PEREGRINE PHARMACEUTICALS, INC., 14272 FRANKLIN AVE, TUSTIN, CA
USPTO Patent #8,956,616: http://tinyurl.com/nj4jpry (Granted 2-17-15)
ABSTRACT: “Disclosed are new phosphatidylserine binding constructs with surprising combinations of properties, and a range of diagnostic and therapeutic conjugates thereof. The new constructs effectively bind phosphatidylserine targets in disease and enhance their destruction, and can also specifically deliver attached imaging or therapeutic agents to the disease site. Also disclosed are methods of using the new construct compositions, therapeutic conjugates and combinations thereof in tumor vasculature targeting, cancer diagnosis and treatment, and for treating viral infections and other diseases.”
1. A construct comprising an antibody Fc region operatively attached to two .beta.2-glycoprotein I (.beta.2GPI) polypeptides, wherein said .beta.2GPI polypeptides each comprise at least an intact domain V of .beta.2GPI, wherein said intact domain V binds to phosphatidylserine, wherein said .beta.2GPI polypeptides form a dimer when attached to said antibody Fc region and wherein said construct retains the property of binding to phosphatidylserine.
[0015] ReceptorBodies & BetaBodies: The invention first provides a range of phosphatidylserine binding construct compositions, in which the constructs comprise at least a first phosphatidylserine binding protein, polypeptide or receptor operatively attached to at least a first antibody Fc region. Joining a phosphatidylserine binding protein, polypeptide or "receptor" to an "antibody" Fc region gives rise to the terms "receptorbody" and "receptorbodies", which are used herein to refer to the phosphatidylserine-binding Fc constructs of the invention.
- - - - - - - - - - - - - - - -EUROPE Patent #EP06719706:
[Corresponding EUR. PATENT: https://register.epo.org/application?lng=en&number=EP06719706
11-8-15/Eur.: “Communication of intention to grant the patent.”]
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• Betabodies (Clipped/Nicked B2GPI - ex: KL15, “2nd-gen. PS-Targeting”) - bind to PS directly, are smaller in size (100 vs. 250KDa) and have a longer serum half-life (~5days) than natural antibodies (Bavi=~1day) – see 7-6-13, “Entdoc, here’s a bunch of stuff on Betabodies:” http://investorshub.advfn.com/boards/read_msg.aspx?message_id=89680206
11-6-14 Edcpf/iHub#196158, “Such Betabodies potentially have advantages over bavituximab”: http://investorshub.advfn.com/boards/read_msg.aspx?message_id=107891618
From Peregrine’s IASCL’15 9-8-15 PR: http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=930479
”Peregrine's PS signaling pathway inhibitor candidates, including bavituximab, reverse the immunosuppressive environment that many tumors establish in order to proliferate, while also fighting cancer by activating macrophages and cytotoxic T cells in tumors.”
11-1-15/IOVS: “PS-Targeting Mabs [PGN635] Inhibit Choroidal Angiogenesis InVivo & ExVivo” [CNV/MacDegen]
IOVS (Investigative Ophthalmol Visual Sci.) pg.7137-45
UTSW/Mayo/Tulane/PR-China (Brekken/Huang etal)…
Li T1, Aredo B2, Zhang K3, Zhong X2, Pulido JS4, Wang S5, He YG2, Huang X6, Brekken RA7, Ufret-Vincenty RL2
http://www.ncbi.nlm.nih.gov/pubmed/26529048
FULL ARTICLE: http://iovs.arvojournals.org/article.aspx?articleid=2468863
“Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo”
PURPOSE:
Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV.
METHODS: Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts.
RESULTS: We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies [Fully-Human PGN635] led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis.
CONCLUSIONS: We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.
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OCULAR APPLICATIONS Of PS-TARGETING MABS:
11-1-15/IOVS UTSW/Mayo/Tulane/PRChina: “PS-Targeting Mabs [PGN635] Inhibit Choroidal Angiogenesis InVivo & ExVivo” [CNV/Macular Degen] http://iovs.arvojournals.org/article.aspx?articleid=2468863
5-2012: Two Anti-PS (PGN632 + PGN635) Ocular posters at ARVO'12 Annual Mtg./FtLaud http://tinyurl.com/cax9a4p
..5-6-12/Thorpe+Mayo, "Anti-PS (PGN632 & PGN635) as Potential New Therapy Against Choroidal Neovascularization (CNV) – AMD"
..5-10-12/PPHM+LSU, "Efficacious Clinical Outcome of an Ophthalmic Formulation of PS-binding mab (PGN632) in a Rabbit Model of Acute HSV-1 Keratitis"
11-9-15/PR/SITC'15: New Bavi PreclinData (add: Duke & Immunotherapist/Dr.Bernard.Fox)
11-9-15: New Preclinical Data Presented at SITC Annual Meeting Highlight Bavituximab's Enhanced Anti-Tumor Activity When Combined With Checkpoint Inhibitors in Breast Cancer and Melanoma
* Bavituximab in Combination with Anti-PD-1 in Breast Cancer Studies Showed a Statistically Significant Improvement in Overall Survival as Compared to Subjects Receiving Anti-PD-1 Therapy Alone
* New Custom-Designed Immuno-Profiling Clinical Test Provides Further Evidence of Bavituxmab's Immune Modulating Mechanism of Action in the Tumor Microenvironment
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=941520
TUSTIN, Nov. 9, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM, PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced results from multiple new preclinical studies demonstrating enhanced anti-tumor activity and immune activation for combinations of a preclinical bavituximab equivalent and checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 in preclinical models of breast cancer and melanoma. Additionally, the company announced preliminary results for a new clinical test specifically designed to illustrate how bavituximab, the company's investigational phosphatidylserine (PS)-signaling pathway inhibitor, modulates immune responses in the tumor microenvironment. Results from these studies were presented at the 2015 annual meeting of the Society for Immunotherapy of Cancer (SITC), which was held in National Harbor, MD, on November 4 - 8, 2015.
"The positive data presented at SITC with regard to combinations of bavituximab and checkpoint inhibitors further support our belief that bavituximab has the potential to be a critical component of innovative combination cancer immunotherapies," said Jeff T. Hutchins, VP of Preclinical Development of Peregrine. "Particularly exciting is the new data in animal models of breast cancer which showed that a significantly greater number of subjects demonstrated anti-tumor activity when treated with the combination of bavituximab and anti-PD-1 as compared to treatment with anti-PD-1 alone. Additionally, combination treatment led to prolonged protection for animals as evidenced by their lack of new tumor development when later re-challenged with the same tumors."
Bavituximab is an investigational immunotherapy designed to assist the body's immune system by targeting and modulating the activity of phosphatidylserine (PS), a highly immune-suppressive signaling molecule expressed broadly on the surface of cells in the tumor microenvironment. Peregrine's PS signaling pathway inhibitor candidates, including bavituximab, reverse the immunosuppressive environment that many tumors establish in order to proliferate, while also fighting cancer by activating immune cells that target and fight cancer. The preclinical equivalent of bavituximab, ch1N11, is used in animal model studies as a guide for clinical development.
BREAST CANCER
Researchers from Duke University and Peregrine evaluated the combination of ch1N11 (preclinical bavituximab equivalent) and anti-PD-1 therapy versus anti-PD-1 stand-alone therapy in well-characterized murine breast cancers, including the triple negative breast cancer (TNBC) model E0771. Study data showed that the combination therapy significantly enhanced overall survival (p=0.0016) and was capable of mediating complete tumor regressions in a greater number of subjects compared to single agent treatments (60% vs. 20%). Data also demonstrated that animals receiving combination treatment had significant increases in tumor associated indicators of immune system activation, including CD45+, CD8+ and CD3+ T-cells. Importantly, the combination treatment led to a prolonged anti-tumor immune response which protected the animals against a re-challenge with the same tumor. This sustained anti-tumor response suggests the potential of the combination therapy to trigger immune system memory and support adaptive immune responses against reemerging disease in breast cancers. All study animals experienced no signs of adverse effects following repeated doses of all therapeutic agents.
MELANOMA
In follow-on work, researchers from the University of Texas Southwestern and Peregrine evaluated combinations of ch1N11 and checkpoint inhibitors (anti-PD-1 or anti-CTLA-4) versus each agent as a stand-alone therapy in common models of melanoma (B16F10 and K1735). Data showed that the combinations of ch1N11 with either anti-PD-1 or anti-CTLA-4 led to significantly greater levels of tumor infiltrating CD8+ T cells than any of the three agents alone. Additionally, findings demonstrated that the combination therapies were more effective at shifting the tumor microenvironment from immunosuppressive to immune active than the single agents, as shown by greater increases in the ratio of T effector cells to T regulatory cells, reactivation of tumor infiltrating T cells and restoration of the effector function of the tumor infiltrating T cells. This activity was more pronounced for the ch1N11/anti-PD-1 combination than for the ch1N11/anti-CTLA-4 combination. Based on these data, study investigators concluded that ch1N11 synergizes with checkpoint inhibitors to induce strong tumor specific CD8 T cell immunity.
"There is an extensive and growing collection of data that demonstrates that phosphatidylserine directly triggers broad immunosuppression in the tumor microenvironment and contributes to resistance to checkpoint inhibitor therapy. By targeting and blocking PS, bavituximab appears able to shift the tumor environment from immunosuppressive to immune active and, in turn, enhance the anti-tumor activity of checkpoint inhibitors such as anti-PD-1 and anti-CTLA4," said Bruce Freimark, Ph.D., Director of Pre-Clinical Oncology of Peregrine. "This latest data in well validated models of multiple tumor types further support our belief that bavituximab may be able to play an essential role in combination immuno-oncology treatment regimens. With this in mind, we are committed to evaluating the agent's potential in combination with a range of cancer therapies against various cancer types."
IMMUNOPROFILING
Researchers presented preliminary results for a new custom assay designed to provide detailed profiles of immune activity in patient tumors. The Opal 6-plex quantitative immunofluorescence (IF) assay is specifically designed to measure the level and type of lymphocytes, myeloid and dendritic cell subsets found within the tumor microenvironment. This information is important as it can be used to correlate immune response parameters with bavituximab treatment outcome and patient survival.
Presented results demonstrated that the Opal assay could reliably detect, measure and phenotype lymphocytes and monocytes present in tumor tissues from rectal adenocarcinoma, hepatocellular carcinoma and advanced melanoma patients treated with bavituximab combination therapies. Importantly, the findings were able to show changes in key indicators of immune activation, including CD8+, CD4+ and regulatory T-cells, as well as myeloid and dendritic cells, in the tumor microenvironment following bavituximab treatment. The ability of this new assay to accurately measure specific immune responses is expected to provide important additional information to assist in Peregrine's ongoing development efforts for bavituximab. This will be particularly valuable as the company works to better elucidate the connection between the drug candidate's impact on immunomodulation and patient response to treatment.
"We are very pleased with the performance of the Opal assay, particularly its ability to compare the interaction of up to 6 phenotypic and functional markers on a single slide of tissue. The power and prognostic value of such immune activity assessments in the area of cancer was initially established by the Immunoscore [ http://www.immunoscore.org ], and we believe the Opal assay represents an important evolution of that work," said Bernard A. Fox, Ph.D., Harder Family Endowed Chair for Cancer Research, Member and Chief, Molecular and Tumor Immunology, Earle A. Chiles Research Institute, Providence Cancer Center; a world-renowned translational cancer immunotherapist; a founding member of the Immunoscore steering committee [ http://www.ohsu.edu/xd/education/schools/school-of-medicine/academic-programs/graduate-studies/faculty/grad-studies-faculty.cfm?facultyid=104 ]. "I am looking forward to continued collaboration with Peregrine to further optimize and validate this assay to improve our understanding of immune infiltrate in tumors thereby facilitating the rational design and use of bavituximab in combination with novel and standard therapies."
ABOUT BAVITUXIMAB: A TARGETED INVESTIGATIONAL IMMUNOTHERAPY
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. PS targeting antibodies have been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT PEREGRINE PHARMACEUTICALS, INC.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials focused on the treatment of cancer. The company's lead immunotherapy candidate, bavituximab, is in Phase III development for the treatment of second-line non-small lung cancer (the "SUNRISE trial") along with several investigator-sponsored trials evaluating other treatment combinations and additional oncology indications. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. ( http://www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and third-party customers. For more information, please visit http://www.peregrineinc.com .
Safe Harbor *snip*
iImmunoscore is a registered trademark of Institut National de la Santé et de la Recherche Médicale (INSERM)
Contacts:
Jay Carlson Peregrine Pharmaceuticals, Inc. (800) 987-8256 info@peregrineinc.com
Stephanie Diaz (Investors) Vida Strategic Partners 415-675-7401 sdiaz@vidasp.com
Tim Brons (Media) Vida Strategic Partners 415-675-7402 tbrons@vidasp.com
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Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
Pics of PPHM's SITC'15 Booth #121 (Nov4-8 2015) - directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by...
SITC'15 PPHM's Booth #121...
NOTE: Join us for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
...Brochure handout (not sure if exactly it): http://www.personalizedmedonc.com/article/phosphatidylserine-an-immune-modulating-checkpoint-ushers-in-the-next-wave-of-immuno-oncology-targets/
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SITC'15 Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim (Herbert K.) Lyerly** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC
**Dr. Herbert Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology, Duke Univ. MC)
The other 2 Duke co-author scientists:
* Dr. Takuya Osada (MD/PhD – Duke Cancer Inst. - Hematology, Oncology, Clinical Immunology http://www.researchgate.net/profile/Takuya_Osada2 )
* Dr. Zachary Hartman (PhD) – Duke MC, Section of Applied Therapeutics http://surgery.duke.edu/faculty/details/0281172 ”My group is also involved in strategies to modulate the immune response to tumors, which involves the use of novel immunotherapeutic strategies & dev. of vaccines to specific oncogenic targets.”
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P357.pdf
POSTER P357 IMAGE (PDF): http://www.peregrineinc.com/images/stories/pdfs/sitc_2015_breast_gray.pdf
ABSTRACT INTRO:
The phospholipid lipid phosphatidylserine (PS) normally resides in the inner plasma membrane leaflet in most mammalian cells, including tumor and tumor associated vascular cells. Inducers of cellular stress, such as hypoxia and oxygen radicals encountered in tumors, and treatments by cytotoxic therapies promote PS relocation to the outer leaf of the plasma membrane. In tumors this re-localization allows PS recognition by a number of receptors on myeloid and lymphoid cells in the microenvironment, promoting tumor growth and metastatic disease through the development of an immunosuppressive environment. Currently the PS-targeting antibody bavituximab is being used to treat patients with solid tumors in multiple late-stage clinical trials. Bavituximab’s anti-tumor properties are attributed in part through alleviating PS- receptor mediated immunosuppression and assisting in generating an Fc-FcR mediated pro-inflammatory response.
METHODS: Immune competent mice with E0771 induced tumors were administered either paclitaxel, or anti-PD-1/PD-L1 single agent therapy, or in triple combination with PS targeting antibody (ch1N11) to evaluate the efficacy of PS & PD-1/PD-L1 immune checkpoint inhibitors blockade in combination with cytotoxic chemotherapeutics. The levels of PS and PD-L1 expression were also evaluated on E0771 tumor cells following in vitro treatment via FACS analysis.
RESULTS: Preliminary results in multiple studies demonstrated differential sensitivity to either paclitaxel, or anti- PD-1/PD-L1 single agent therapy while inclusion of ch1N11 triple combination significantly enhanced anti-tumor efficacy over either single agent therapy. Also, FACs analysis demonstrated induction of PS & PD-L1 levels on E0771 cells following in vitro treatment with paclitaxel, suggesting that combining paclitaxel with PS and PD-1 targeting antibodies will have greater anti-tumor activity in triple combination treatments. No in vivo adverse effects were observed in animals given repeated doses of single or triple combinations.
CONCLUSION: These results support combination blockade of PS & PD-1/PD-L1 with paclitaxel to treat breast cancer.
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SITC'15 Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#2: Poster P358, “Targeting Phosphatidylserine Synergizes with Immune Checkpoint Blockade by Inducing De Novo Tumor Specific Immunity”
Presenting Author: Xianming Huang, PhD (UTSW-MC/Dallas)
Xianming Huang 1, Jian Gong 2, Dan Ye 1, Van Nguyen 2, Michael Gray 2, Steven King 2, Jeff Hutchins 2, Rolf Brekken 1, Bruce Freimark 2
...1 UTSW-MC/Dallas
...2 Peregrine Pharmaceuticals, Tustin CA
Direct Link: http://bit.ly/1LS4VYk
POSTER P358 IMAGE (PDF): http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P358.pdf
BACKGROUND: Extensive studies have demonstrated that the inside-out membrane phospholipid phosphatidylserine (PS) actively drives global immunosuppression in the tumor microenvironment and is a major contributor to tumor resistance to immune checkpoint blockade. We have shown that PS targeting antibodies can re-program the tumor microenvironment from immunosuppressive to immune potentiating by reducing the number of myeloid-derived suppressor cells (MDSCs), repolarizing tumor associated macrophages from M2 to M1 and by promoting the maturation of dendritic cells. We have found that PS targeting antibodies synergize with and significantly enhance the therapeutic efficacy of immune checkpoint blockade in multiple tumor models. In the present study, we examined the effect of combination of a PS targeting antibody and anti-PD-1 or anti-CTLA-4 on tumor-specific CD8 T cell immunity.
METHODS: B16 tumor-bearing mice were treated weekly i.p. at 5 mg/kg with each antibody or combination. Splenocytes were harvested after three treatments. The number of tumor-specific IFNg-producing splenocytes was evaluated by ELISPOT in the presence or absence of irradiated B16 tumor cells. Tumors were harvested and single cell suspensions were obtained and immune profiled by FACS.
RESULTS:
In the absence of B16 tumor cell stimulation, the combination of ch1N11 and anti-PD-1 resulted in the highest number of IFNg Elispots (109+/-25), significantly better than anti-CTLA-4 (29.4±4, p < 0.005), ch1N11 (16.6+/-3.2, p < 0.001), anti-PD-1 (41.6+/-5.5, p < 0.001), and ch1N11+anti-CTLA4 (73.6+/-13.9, p < 0.05); in addition, the combination of ch1N11 and anti-CTLA-4 was significantly better than anti-CTLA-4 alone (29.4+/-4.2, p < 0.01), indicating that there were significantly more functional T cells in the spleens of mice treated with combination therapy. Importantly, stimulation with irradiated B16 tumor cells resulted in robust induction of IFNg production from splenocytes harvested from mice treated with ch1N11 and anti-PD-1. Tumor cell stimulation resulted in a >2-fold increase in IFNg Elispots (198+/- 39 vs 70+/-5, p < 0.01), which was also 13-fold higher than that of control group (15+/-2.1, p < 0.001).
These data demonstrate that combination treatment induced significantly more tumor specific T cells. FACS analysis of tumor infiltrating lymphocytes (TILs) indicated that combination of antibody-mediated blockade of PS and PD1 significantly enhanced effector function of tumor infiltrating CD8+ T cells, as demonstrated by significant increases in TILs producing IFN-g, TNFa, IL-2, granzyme B, and Ki-67.
CONCLUSIONS:
PS targeting antibodies synergize with immune checkpoint blockade to induce strong tumor specific CD8 T cell immunity.
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11-6-15 7:30-9pm “Sci.Session” Detail:
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10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial, Bavi+durvalumab(MEDI4736), squamous or non-squamous… http://tinyurl.com/q79bkam
10-15-15: AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial
Global, Randomized Phase II Trial to Evaluate Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor Durvalumab (MEDI4736) in Previously Treated NSCLC
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=936766
TUSTIN, Oct. 15, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that it has expanded its ongoing cancer immunotherapy clinical collaboration with AstraZeneca to include a second, later-stage trial. The companies will now also evaluate the immunotherapy combination of Peregrine's phosphatidylserine (PS)-targeted immune-activator, bavituximab, and AstraZeneca's anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), in a global Phase II study in patients with previously treated squamous or non-squamous non-small cell lung cancer (NSCLC). The randomized Phase II trial will be conducted by Peregrine. . .
ABOUT BAVITUXIMAB: A TARGETED INVESTIGATIONAL IMMUNOTHERAPY
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT DURVALUMAB (MEDI4736)
Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor's immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
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8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors”…
Durvalumab=MEDI4736, an anti-PD-L1 immune checkpoint inhibitor.
AZN’s Head/I-O(Robert Iannone): “…Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
8-24-15: AstraZeneca and Peregrine Pharmaceuticals to Collaborate on Immuno-Oncology Combination Clinical Trial
• Collaboration to Focus on Cancer Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor MEDI4736
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=928488
TUSTIN, Aug. 24, 2015: AstraZeneca (NYSE:AZN) and Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that they have entered into a cancer immunotherapy clinical trial collaboration. The collaboration will evaluate Peregrine's investigational phosphatidylserine (PS)-signaling pathway inhibitor, bavituximab, in combination with AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The planned Phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors.
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By Aikifredicist 11-6-15 #241864: I'm just back from an excellent Peregrine sponsored seminar featuring Raymond Birge, Douglas Graham, Dmitry Gabrilovich and Rolf Brekken. Maria Karasarides of AZ had short comments during the discussion. Talked to Steve King, Carlton Johnson, Bruce Freimark and others from Peregrine. I'm sure North will have a summary soon. (I also spoke with North and his wife). The session was well attended and I was plied with free food! North caught Maria from AZ after the close and was having a good discussion with here when I left to head home for supper.
By North40000 11-7-15 #241915 & FU's: The better half and I will consult on respective memories and impressions of last evening. A preliminary warning: much of what we saw and heard was obviously aimed at attendees of SITC, not mere uneducated mortals like us. Specifics like numerous slides and speech were filled with jargon, words, letters, numbers, symbols, and were delivered in time limited span, mostly beyond the skim-reading capability, not to mention comprehension of others besides other experts. … At last count, 4 SHs managed to attend the Friday evening seminar program - 2 of us found the following 10-12pg. brochure, dated Sept.2015, at the PPHM SITC booth, a link to which had been difficult for me to find. As far as I know, it has not been posted here to date by others: http://www.personalizedmedonc.com/article/phosphatidylserine-an-immune-modulating-checkpoint-ushers-in-the-next-wave-of-immuno-oncology-targets ...I confirmed with Jay[IR] that the slide decks of the Friday evening "Scientific Session" presentations would not be made available via PPHM. What may be available via individual contacts with presenters is a question to which I know no answer. You will recall I had no success in receiving presenter slide decks from the AANS BMY sponsored evening seminar in May 2015 that my wife & I attended. BMY personnel had promised I would receive them. Without the slides and accompanying transcript from past Friday evening, I would have great difficulty describing with any degree of accuracy or completeness what was said or what was shown on slides. The presenters had relatively little time to present a great deal of information - each talked fast with insufficient use of microphone available to them, and the slides flipped by too quickly for me to assimilate. I mentioned that in my preliminary warning comment earlier yesterday. My wife, an MD with no particular immunology or immunotherapy education of recent vintage, told me she understood ~10% of the entirety of what was said & illustrated Friday evening. Dr. Gabrilovich was particularly challenging to hear and understand because of his Russian accent. In person, he looks far less "fierce" than his photo seems to suggest. I did mention to Dr. Birge [Irish name, I found] that each speaker "talked faster than I could hear" - he commented that was a good observation that he would try to keep in mind the next time. Under the time constraints imposed Friday evening, that will be difficult, IMO. I agree that Dr. Brekken was easiest to understand. AZN's Dr. Karasarides made no formal presentation, but was invited on stage later for the Q&A session of other presenters. I have little or nothing to add to aikfrecist's comments from yesterday.
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SITC 2014: 3 Peregrine posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal), and 1 poster by UTSW's Dr. Adam Yopp on the Bavi+Sorafenib/LIVER Ph2 IST: http://tinyurl.com/pchzr6h
Cancer/Bavi: UTSW SLOAN-KETTERING ASTRAZENECA DUKE (Moffitt Rutgers Emory Wistar UPENN UC/Irvine) – did I leave out any?
SITC'15, Poster=B357(Bavi+PD-L1/Breast), Senior-Author: Duke's Dr. Herbert K. Lyerly. The Lead(publishing) author is Peregrine's Dr. Michael Gray, but interesting that Dr. Lyerly is listed as the last author (typically the Senior Author), along with 2 other Duke researchers listed as co-authors. Clearly Duke is working with Peregrine on pre-clinical bavituximab cancer I-O combination studies.
...As Johnny Carson would say, “I did not know that.”
2 other Duke scientists are listed as co-authors:
* Dr. Takuya Osada (MD/PhD – Duke Cancer Inst. - Hematology, Oncology, Clinical Immunology http://www.researchgate.net/profile/Takuya_Osada2 )
* Dr. Zachary Hartman (PhD) – Duke MC, Section of Applied Therapeutics http://surgery.duke.edu/faculty/details/0281172 ”My group is also involved in strategies to modulate the immune response to tumors, which involves the use of novel immunotherapeutic strategies & dev. of vaccines to specific oncogenic targets.”
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SITC'15 Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#2: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim (Herbert K.) Lyerly** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC
**Dr. Herbert Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology, Duke Univ. MC)
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P357.pdf
INTRODUCTION:
The phospholipid lipid phosphatidylserine (PS) normally resides in the inner plasma membrane leaflet in most mammalian cells, including tumor and tumor associated vascular cells. Inducers of cellular stress, such as hypoxia and oxygen radicals encountered in tumors, and treatments by cytotoxic therapies promote PS relocation to the outer leaf of the plasma membrane. In tumors this re-localization allows PS recognition by a number of receptors on myeloid and lymphoid cells in the microenvironment, promoting tumor growth and metastatic disease through the development of an immunosuppressive environment. Currently the PS-targeting antibody bavituximab is being used to treat patients with solid tumors in multiple late-stage clinical trials. Bavituximab’s anti-tumor properties are attributed in part through alleviating PS- receptor mediated immunosuppression and assisting in generating an Fc-FcR mediated pro-inflammatory response.
METHODS: Immune competent mice with E0771 induced tumors were administered either paclitaxel, or anti-PD-1/PD-L1 single agent therapy, or in triple combination with PS targeting antibody (ch1N11) to evaluate the efficacy of PS & PD-1/PD-L1 immune checkpoint inhibitors blockade in combination with cytotoxic chemotherapeutics. The levels of PS & PD-L1 expression were also evaluated on E0771 tumor cells following in vitro treatment via FACS analysis.
RESULTS: Preliminary results in multiple studies demonstrated differential sensitivity to either paclitaxel, or anti- PD-1/PD-L1 single agent therapy while inclusion of ch1N11 triple combination significantly enhanced anti-tumor efficacy over either single agent therapy. Also, FACs analysis demonstrated induction of PS & PD-L1 levels on E0771 cells following in vitro treatment with paclitaxel, suggesting that combining paclitaxel with PS and PD-1 targeting antibodies will have greater anti-tumor activity in triple combination treatments. No in vivo adverse effects were observed in animals given repeated doses of single or triple combinations.
CONCLUSION: These results support combination blockade of PS & PD-1/PD-L1 with paclitaxel to treat breast cancer.
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Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
Pics of PPHM's SITC'15 Booth #121 (Nov4-8 2015) - directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by.: http://tinyurl.com/p32rqfn
SITC'15 PPHM's Booth #121...
NOTE: Join us for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
= = = =PPHM's 2nd Poster at SITC'15 (Nov 4-8 2015:)
PPHM#1: Poster P358, “Targeting Phosphatidylserine Synergizes with Immune Checkpoint Blockade by Inducing De Novo Tumor Specific Immunity”
Presenting Author: Xianming Huang, PhD (UTSW-MC/Dallas)
Xianming Huang 1, Jian Gong 2, Dan Ye 1, Van Nguyen 2, Michael Gray 2, Steven King 2, Jeff Hutchins 2, Rolf Brekken 1, Bruce Freimark 2
...1 UTSW-MC/Dallas
...2 Peregrine Pharmaceuticals, Tustin CA
Direct Link: http://bit.ly/1LS4VYk
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P358.pdf
N40K, this snapshot shows Peregrine's SITC'15 11-6-15 Sci.Session in more detail – you can clearly see the titles of 4 of the 5 presentations. AstraZeneca's Dr. Maria Karasarides' (Sr. Director, ImmunoOncology, Global Medicines Dev.) talk is not titled – wouldn't you love to hear that one?!!
SITC'15 PPHM's Booth #121...
NOTE: Join us for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
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Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
.
.
.
.
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10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial, Bavi+durvalumab(MEDI4736), squamous or non-squamous… http://tinyurl.com/q79bkam
10-15-15 Peregrine's ASM: ATTENDEE Reports & Link to SK's 18min/16slide webcast: http://tinyurl.com/o6z4bm4
9-9-15 Qtly. Conf. Call (King/Shan/Worsley/Lytle) Transcript http://tinyurl.com/ph22vdn
...CEO S.King: “The Memorial Sloan Kettering & AstraZeneca collaborations are an important part of our announced plans to expand our bavituximab clinical pgm.”
8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors” http://tinyurl.com/owlxpsf
...Durvalumab=MEDI4736(anti-PD-L1 immune checkpoint inhibitor).
AZN’s Head/I-O(Robert Iannone): “Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/qxu4w2x
N4K, when I enlarge that Sci.Session pic on my 'pute, there are clearly TITLES listed for each of the Scientists Talks (Birge, Graham, Gabrilovich, Brekken) - not for AstraZeneca's Maria Karasarides (Sr. Director, ImmunoOncology, Global Medicines Dev.).
SITC'15 PPHM's Booth #121...
NOTE: Join us for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
N40K, didn't call anybody; an attendee emailed the pics - didn't expect them, but very grateful. Otherwise, I'd have had no idea about the Fri/Nov6 Scientific Session they are holding with 4 nop-notch scientists & a Sr.Director/Immunology from AstraZeneca.
N40K, I pulled the info about Peregrine's 11-6-15 SITC'15 “Scientific Session” directly from one of the Booth #121 pics that an attendee sent me this afternoon. I can't quite read the titles of each talk, nor the paragraphs at the bottom. Good to see that AstraZeneca's Sr.Director/ImmunoOncology/GlobalMedicinesDev. is one of the speakers.
SITC'15 PPHM's Booth #121...
NOTE: Join us for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
.
.
.
Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
= = = = = = = = = = = = = =
10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial, Bavi+durvalumab(MEDI4736), squamous or non-squamous… http://tinyurl.com/q79bkam
10-15-15 Peregrine's ASM: ATTENDEE Reports & Link to SK's 18min/16slide webcast: http://tinyurl.com/o6z4bm4
9-9-15 Qtly. Conf. Call (King/Shan/Worsley/Lytle) Transcript http://tinyurl.com/ph22vdn
...CEO S.King: “The Memorial Sloan Kettering & AstraZeneca collaborations are an important part of our announced plans to expand our bavituximab clinical pgm.”
8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors” http://tinyurl.com/owlxpsf
...Durvalumab=MEDI4736(anti-PD-L1 immune checkpoint inhibitor).
AZN’s Head/I-O(Robert Iannone): “Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
5-29-15: Peregrine & Sloan Kettering Enter Collab. to “Investigate Novel PS-Targeting Immunotherapy Combos” http://tinyurl.com/qxu4w2x
Pics of PPHM's SITC'15 Booth #121 (Nov4-8 2015) - directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by...
Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
SITC'15 PPHM's Booth #121...
NOTE: Join us for a Scientific Session - FRI Nov6 2015 7:30-9:00pm
“The PS Signaling Pathway: A Promising
Therapeutic Target Exploited by
Tumors for Immune Evasion”
PGM:
* Raymond Birge (PhD, Rutgers) http://birgelab.org
* Douglas Graham (MD, PhD, Emory) http://choa.org/Childrens-Hospital-Services/Cancer-and-Blood-Disorders/Meet-the-Team/Physicians-and-Researchers/Douglas-Graham
* Dmitry Gabrilovich (MD, PhD, Wistar Inst.) http://www.wistar.org/our-science/scientists/dmitry-gabrilovich-md-phd
* Rolf Brekken (PhD, UTSW/Dallas) http://www.utsouthwestern.edu/labs/brekken
* Maria Karasarides (PhD, AstraZeneca - Sr. Director, ImmunoOncology, Global Medicines Dev.) http://www.linkedin.com/pub/maria-karasarides-ph-d/6/769/136
= = = = = = = = = = = = = = = = = =
SITC’15(Nov4-8): Peregrine-Exhibiting; 2 Posters(UTSW/DUKE/PPHM), “Optimizing Combination Immunotherapy” by UTSW's X.Huang/Rolf Brekken/etal, DUKE's Dr.Kim Lyerly/etal, PPHM Scientists…
[Note: Duke's Dr. Kim Lyerly is the senior author of Poster P357]
Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
- - - - - - - -
Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P358, “Targeting Phosphatidylserine Synergizes with Immune Checkpoint Blockade by Inducing De Novo Tumor Specific Immunity”
Presenting Author: Xianming Huang, PhD (UTSW-MC/Dallas)
Xianming Huang 1, Jian Gong 2, Dan Ye 1, Van Nguyen 2, Michael Gray 2, Steven King 2, Jeff Hutchins 2, Rolf Brekken 1, Bruce Freimark 2
...1 UTSW-MC/Dallas
...2 Peregrine Pharmaceuticals, Tustin CA
Direct Link: http://bit.ly/1LS4VYk
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P358.pdf
BACKGROUND: Extensive studies have demonstrated that the inside-out membrane phospholipid phosphatidylserine (PS) actively drives global immunosuppression in the tumor microenvironment and is a major contributor to tumor resistance to immune checkpoint blockade. We have shown that PS targeting antibodies can re-program the tumor microenvironment from immunosuppressive to immune potentiating by reducing the number of myeloid-derived suppressor cells (MDSCs), repolarizing tumor associated macrophages from M2 to M1 and by promoting the maturation of dendritic cells. We have found that PS targeting antibodies synergize with and significantly enhance the therapeutic efficacy of immune checkpoint blockade in multiple tumor models. In the present study, we examined the effect of combination of a PS targeting antibody and anti-PD-1 or anti-CTLA-4 on tumor-specific CD8 T cell immunity.
METHODS: B16 tumor-bearing mice were treated weekly i.p. at 5 mg/kg with each antibody or combination. Splenocytes were harvested after three treatments. The number of tumor-specific IFNg-producing splenocytes was evaluated by ELISPOT in the presence or absence of irradiated B16 tumor cells. Tumors were harvested and single cell suspensions were obtained and immune profiled by FACS.
RESULTS:
In the absence of B16 tumor cell stimulation, the combination of ch1N11 and anti-PD-1 resulted in the highest number of IFNg Elispots (109+/-25), significantly better than anti-CTLA-4 (29.4±4, p < 0.005), ch1N11 (16.6+/-3.2, p < 0.001), anti-PD-1 (41.6+/-5.5, p < 0.001), and ch1N11+anti-CTLA4 (73.6+/-13.9, p < 0.05); in addition, the combination of ch1N11 and anti-CTLA-4 was significantly better than anti-CTLA-4 alone (29.4+/-4.2, p < 0.01), indicating that there were significantly more functional T cells in the spleens of mice treated with combination therapy. Importantly, stimulation with irradiated B16 tumor cells resulted in robust induction of IFNg production from splenocytes harvested from mice treated with ch1N11 and anti-PD-1. Tumor cell stimulation resulted in a >2-fold increase in IFNg Elispots (198+/- 39 vs 70+/-5, p < 0.01), which was also 13-fold higher than that of control group (15+/-2.1, p < 0.001).
These data demonstrate that combination treatment induced significantly more tumor specific T cells. FACS analysis of tumor infiltrating lymphocytes (TILs) indicated that combination of antibody-mediated blockade of PS and PD1 significantly enhanced effector function of tumor infiltrating CD8+ T cells, as demonstrated by significant increases in TILs producing IFN-g, TNFa, IL-2, granzyme B, and Ki-67.
CONCLUSIONS:
PS targeting antibodies synergize with immune checkpoint blockade to induce strong tumor specific CD8 T cell immunity.
- - - - - - - -
Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#2: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim Lyerly** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC - **Dr. Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology)
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P357.pdf
INTRODUCTION: The phospholipid lipid phosphatidylserine (PS) normally resides in the inner plasma membrane leaflet in most mammalian cells, including tumor and tumor associated vascular cells. Inducers of cellular stress, such as hypoxia and oxygen radicals encountered in tumors, and treatments by cytotoxic therapies promote PS relocation to the outer leaf of the plasma membrane. In tumors this re-localization allows PS recognition by a number of receptors on myeloid and lymphoid cells in the microenvironment, promoting tumor growth and metastatic disease through the development of an immunosuppressive environment. Currently the PS-targeting antibody bavituximab is being used to treat patients with solid tumors in multiple late-stage clinical trials. Bavituximab’s anti-tumor properties are attributed in part through alleviating PS- receptor mediated immunosuppression and assisting in generating an Fc-FcR mediated pro-inflammatory response.
METHODS: Immune competent mice with E0771 induced tumors were administered either paclitaxel, or anti-PD-1/PD-L1 single agent therapy, or in triple combination with PS targeting antibody (ch1N11) to evaluate the efficacy of PS & PD-1/PD-L1 immune checkpoint inhibitors blockade in combination with cytotoxic chemotherapeutics. The levels of PS and PD-L1 expression were also evaluated on E0771 tumor cells following in vitro treatment via FACS analysis.
RESULTS: Preliminary results in multiple studies demonstrated differential sensitivity to either paclitaxel, or anti- PD-1/PD-L1 single agent therapy while inclusion of ch1N11 triple combination significantly enhanced anti-tumor efficacy over either single agent therapy. Also, FACs analysis demonstrated induction of PS & PD-L1 levels on E0771 cells following in vitro treatment with paclitaxel, suggesting that combining paclitaxel with PS and PD-1 targeting antibodies will have greater anti-tumor activity in triple combination treatments. No in vivo adverse effects were observed in animals given repeated doses of single or triple combinations.
CONCLUSION: These results support combination blockade of PS & PD-1/PD-L1 with paclitaxel to treat breast cancer.
= = = = = = = = = = = = = = = = = = = = = = = = = =
10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial, Bavi+durvalumab(MEDI4736), squamous or non-squamous… http://tinyurl.com/q79bkam
10-15-15: AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial
Global, Randomized Phase II Trial to Evaluate Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor Durvalumab (MEDI4736) in Previously Treated NSCLC
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=936766
TUSTIN, Oct. 15, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that it has expanded its ongoing cancer immunotherapy clinical collaboration with AstraZeneca to include a second, later-stage trial. The companies will now also evaluate the immunotherapy combination of Peregrine's phosphatidylserine (PS)-targeted immune-activator, bavituximab, and AstraZeneca's anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), in a global Phase II study in patients with previously treated squamous or non-squamous non-small cell lung cancer (NSCLC). The randomized Phase II trial will be conducted by Peregrine. . .
ABOUT BAVITUXIMAB: A TARGETED INVESTIGATIONAL IMMUNOTHERAPY
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT DURVALUMAB (MEDI4736)
Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor's immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
= = = = = = = = = = = = = = = = = = = = = =
8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors”…
Durvalumab=MEDI4736, an anti-PD-L1 immune checkpoint inhibitor.
AZN’s Head/I-O(Robert Iannone): “…Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
8-24-15: AstraZeneca and Peregrine Pharmaceuticals to Collaborate on Immuno-Oncology Combination Clinical Trial
• Collaboration to Focus on Cancer Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor MEDI4736
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=928488
TUSTIN, Aug. 24, 2015: AstraZeneca (NYSE:AZN) and Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that they have entered into a cancer immunotherapy clinical trial collaboration. The collaboration will evaluate Peregrine's investigational phosphatidylserine (PS)-signaling pathway inhibitor, bavituximab, in combination with AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The planned Phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors.
Pitter-Patter, SITC'15, Nov4-8 2015 – just having a little fun this morning before heading out…
SITC’15(Nov4-8): Peregrine-Exhibiting; 2 Posters(UTSW/DUKE/PPHM), “Optimizing Combination Immunotherapy” by UTSW's X.Huang/Rolf Brekken/etal, DUKE's Dr.Kim Lyerly/etal, PPHM Scientists…
[Note: Duke's Dr. Kim Lyerly is the senior author of Poster P357]
Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
- - - - - - - -
Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P358, “Targeting Phosphatidylserine Synergizes with Immune Checkpoint Blockade by Inducing De Novo Tumor Specific Immunity”
Presenting Author: Xianming Huang, PhD (UTSW-MC/Dallas)
Xianming Huang 1, Jian Gong 2, Dan Ye 1, Van Nguyen 2, Michael Gray 2, Steven King 2, Jeff Hutchins 2, Rolf Brekken 1, Bruce Freimark 2
...1 UTSW-MC/Dallas
...2 Peregrine Pharmaceuticals, Tustin CA
Direct Link: http://bit.ly/1LS4VYk
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P358.pdf
BACKGROUND: Extensive studies have demonstrated that the inside-out membrane phospholipid phosphatidylserine (PS) actively drives global immunosuppression in the tumor microenvironment and is a major contributor to tumor resistance to immune checkpoint blockade. We have shown that PS targeting antibodies can re-program the tumor microenvironment from immunosuppressive to immune potentiating by reducing the number of myeloid-derived suppressor cells (MDSCs), repolarizing tumor associated macrophages from M2 to M1 and by promoting the maturation of dendritic cells. We have found that PS targeting antibodies synergize with and significantly enhance the therapeutic efficacy of immune checkpoint blockade in multiple tumor models. In the present study, we examined the effect of combination of a PS targeting antibody and anti-PD-1 or anti-CTLA-4 on tumor-specific CD8 T cell immunity.
METHODS: B16 tumor-bearing mice were treated weekly i.p. at 5 mg/kg with each antibody or combination. Splenocytes were harvested after three treatments. The number of tumor-specific IFNg-producing splenocytes was evaluated by ELISPOT in the presence or absence of irradiated B16 tumor cells. Tumors were harvested and single cell suspensions were obtained and immune profiled by FACS.
RESULTS:
In the absence of B16 tumor cell stimulation, the combination of ch1N11 and anti-PD-1 resulted in the highest number of IFNg Elispots (109+/-25), significantly better than anti-CTLA-4 (29.4±4, p < 0.005), ch1N11 (16.6+/-3.2, p < 0.001), anti-PD-1 (41.6+/-5.5, p < 0.001), and ch1N11+anti-CTLA4 (73.6+/-13.9, p < 0.05); in addition, the combination of ch1N11 and anti-CTLA-4 was significantly better than anti-CTLA-4 alone (29.4+/-4.2, p < 0.01), indicating that there were significantly more functional T cells in the spleens of mice treated with combination therapy. Importantly, stimulation with irradiated B16 tumor cells resulted in robust induction of IFNg production from splenocytes harvested from mice treated with ch1N11 and anti-PD-1. Tumor cell stimulation resulted in a >2-fold increase in IFNg Elispots (198+/- 39 vs 70+/-5, p < 0.01), which was also 13-fold higher than that of control group (15+/-2.1, p < 0.001).
These data demonstrate that combination treatment induced significantly more tumor specific T cells. FACS analysis of tumor infiltrating lymphocytes (TILs) indicated that combination of antibody-mediated blockade of PS and PD1 significantly enhanced effector function of tumor infiltrating CD8+ T cells, as demonstrated by significant increases in TILs producing IFN-g, TNFa, IL-2, granzyme B, and Ki-67.
CONCLUSIONS:
PS targeting antibodies synergize with immune checkpoint blockade to induce strong tumor specific CD8 T cell immunity.
- - - - - - - -
Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#2: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim Lyerly** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC - **Dr. Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology)
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P357.pdf
INTRODUCTION: The phospholipid lipid phosphatidylserine (PS) normally resides in the inner plasma membrane leaflet in most mammalian cells, including tumor and tumor associated vascular cells. Inducers of cellular stress, such as hypoxia and oxygen radicals encountered in tumors, and treatments by cytotoxic therapies promote PS relocation to the outer leaf of the plasma membrane. In tumors this re-localization allows PS recognition by a number of receptors on myeloid and lymphoid cells in the microenvironment, promoting tumor growth and metastatic disease through the development of an immunosuppressive environment. Currently the PS-targeting antibody bavituximab is being used to treat patients with solid tumors in multiple late-stage clinical trials. Bavituximab’s anti-tumor properties are attributed in part through alleviating PS- receptor mediated immunosuppression and assisting in generating an Fc-FcR mediated pro-inflammatory response.
METHODS: Immune competent mice with E0771 induced tumors were administered either paclitaxel, or anti-PD-1/PD-L1 single agent therapy, or in triple combination with PS targeting antibody (ch1N11) to evaluate the efficacy of PS & PD-1/PD-L1 immune checkpoint inhibitors blockade in combination with cytotoxic chemotherapeutics. The levels of PS and PD-L1 expression were also evaluated on E0771 tumor cells following in vitro treatment via FACS analysis.
RESULTS: Preliminary results in multiple studies demonstrated differential sensitivity to either paclitaxel, or anti- PD-1/PD-L1 single agent therapy while inclusion of ch1N11 triple combination significantly enhanced anti-tumor efficacy over either single agent therapy. Also, FACs analysis demonstrated induction of PS & PD-L1 levels on E0771 cells following in vitro treatment with paclitaxel, suggesting that combining paclitaxel with PS and PD-1 targeting antibodies will have greater anti-tumor activity in triple combination treatments. No in vivo adverse effects were observed in animals given repeated doses of single or triple combinations.
CONCLUSION: These results support combination blockade of PS & PD-1/PD-L1 with paclitaxel to treat breast cancer.
= = = = = = = = = = = = = = = = = = = = = = = = = =
10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial, Bavi+durvalumab(MEDI4736), squamous or non-squamous… http://tinyurl.com/q79bkam
10-15-15: AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial
Global, Randomized Phase II Trial to Evaluate Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor Durvalumab (MEDI4736) in Previously Treated NSCLC
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=936766
TUSTIN, Oct. 15, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that it has expanded its ongoing cancer immunotherapy clinical collaboration with AstraZeneca to include a second, later-stage trial. The companies will now also evaluate the immunotherapy combination of Peregrine's phosphatidylserine (PS)-targeted immune-activator, bavituximab, and AstraZeneca's anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), in a global Phase II study in patients with previously treated squamous or non-squamous non-small cell lung cancer (NSCLC). The randomized Phase II trial will be conducted by Peregrine. . .
ABOUT BAVITUXIMAB: A TARGETED INVESTIGATIONAL IMMUNOTHERAPY
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT DURVALUMAB (MEDI4736)
Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor's immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
= = = = = = = = = = = = = = = = = = = = = =
8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors”…
Durvalumab=MEDI4736, an anti-PD-L1 immune checkpoint inhibitor.
AZN’s Head/I-O(Robert Iannone): “…Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
8-24-15: AstraZeneca and Peregrine Pharmaceuticals to Collaborate on Immuno-Oncology Combination Clinical Trial
• Collaboration to Focus on Cancer Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor MEDI4736
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=928488
TUSTIN, Aug. 24, 2015: AstraZeneca (NYSE:AZN) and Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that they have entered into a cancer immunotherapy clinical trial collaboration. The collaboration will evaluate Peregrine's investigational phosphatidylserine (PS)-signaling pathway inhibitor, bavituximab, in combination with AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The planned Phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors.
SITC’15(Nov4-8): Peregrine-Exhibiting; 2 Posters(UTSW/DUKE/PPHM), “Optimizing Combination Immunotherapy” by UTSW's X.Huang/Rolf Brekken/etal, DUKE's Dr.Kim Lyerly/etal, PPHM Scientists…
[Note: Duke's Dr. Kim Lyerly is the senior author of Poster P357]
Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
Abstract Embargo Lifted: 11-3-15; pub. in Journal for ImmunoTherapy of Cancer: 11-4-15
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
- - - - - - - -
Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#1: Poster P358, “Targeting Phosphatidylserine Synergizes with Immune Checkpoint Blockade by Inducing De Novo Tumor Specific Immunity”
Presenting Author: Xianming Huang, PhD (UTSW-MC/Dallas)
Xianming Huang 1, Jian Gong 2, Dan Ye 1, Van Nguyen 2, Michael Gray 2, Steven King 2, Jeff Hutchins 2, Rolf Brekken 1, Bruce Freimark 2
...1 UTSW-MC/Dallas
...2 Peregrine Pharmaceuticals, Tustin CA
Direct Link: http://bit.ly/1LS4VYk
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P358.pdf
BACKGROUND: Extensive studies have demonstrated that the inside-out membrane phospholipid phosphatidylserine (PS) actively drives global immunosuppression in the tumor microenvironment and is a major contributor to tumor resistance to immune checkpoint blockade. We have shown that PS targeting antibodies can re-program the tumor microenvironment from immunosuppressive to immune potentiating by reducing the number of myeloid-derived suppressor cells (MDSCs), repolarizing tumor associated macrophages from M2 to M1 and by promoting the maturation of dendritic cells. We have found that PS targeting antibodies synergize with and significantly enhance the therapeutic efficacy of immune checkpoint blockade in multiple tumor models. In the present study, we examined the effect of combination of a PS targeting antibody and anti-PD-1 or anti-CTLA-4 on tumor-specific CD8 T cell immunity.
METHODS: B16 tumor-bearing mice were treated weekly i.p. at 5 mg/kg with each antibody or combination. Splenocytes were harvested after three treatments. The number of tumor-specific IFNg-producing splenocytes was evaluated by ELISPOT in the presence or absence of irradiated B16 tumor cells. Tumors were harvested and single cell suspensions were obtained and immune profiled by FACS.
RESULTS:
In the absence of B16 tumor cell stimulation, the combination of ch1N11 and anti-PD-1 resulted in the highest number of IFNg Elispots (109+/-25), significantly better than anti-CTLA-4 (29.4±4, p < 0.005), ch1N11 (16.6+/-3.2, p < 0.001), anti-PD-1 (41.6+/-5.5, p < 0.001), and ch1N11+anti-CTLA4 (73.6+/-13.9, p < 0.05); in addition, the combination of ch1N11 and anti-CTLA-4 was significantly better than anti-CTLA-4 alone (29.4+/-4.2, p < 0.01), indicating that there were significantly more functional T cells in the spleens of mice treated with combination therapy. Importantly, stimulation with irradiated B16 tumor cells resulted in robust induction of IFNg production from splenocytes harvested from mice treated with ch1N11 and anti-PD-1. Tumor cell stimulation resulted in a >2-fold increase in IFNg Elispots (198+/- 39 vs 70+/-5, p < 0.01), which was also 13-fold higher than that of control group (15+/-2.1, p < 0.001).
These data demonstrate that combination treatment induced significantly more tumor specific T cells. FACS analysis of tumor infiltrating lymphocytes (TILs) indicated that combination of antibody-mediated blockade of PS and PD1 significantly enhanced effector function of tumor infiltrating CD8+ T cells, as demonstrated by significant increases in TILs producing IFN-g, TNFa, IL-2, granzyme B, and Ki-67.
CONCLUSIONS:
PS targeting antibodies synergize with immune checkpoint blockade to induce strong tumor specific CD8 T cell immunity.
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Track: “Optimizing Combination Immunotherapy”
11-7-15/Sat./12:45-2:00pm
PPHM#2: Poster P357, “Targeting of Phosphatidylserine by Monoclonal Antibodies Augments the Activity of Paclitaxel & anti-pd1/pd-L1 Therapy in the Murine Breast Model E0771”
Presenting Author: Michael Gray, PhD (Sr.Scientist, Peregrine Pharmaceuticals)
Michael Gray 1, Jian Gong 1, Van Nguyen 1, Takuya Osada 2, Zachary Hartman 2, Jeff Hutchins 1, Bruce Freimark 1, Kim Lyerly** 2
...1=Peregrine Pharmaceuticals, Tustin CA
...2=Duke University, Durham, NC - **Dr. Kim Lyerly: http://surgery.duke.edu/faculty/details/0117267 (Professor of Surgery, Assistant Professor in Immunology, Associate Professor of Pathology)
http://www.immunotherapyofcancer.org/content/pdf/2051-1426-3-S2-P357.pdf
INTRODUCTION: The phospholipid lipid phosphatidylserine (PS) normally resides in the inner plasma membrane leaflet in most mammalian cells, including tumor and tumor associated vascular cells. Inducers of cellular stress, such as hypoxia and oxygen radicals encountered in tumors, and treatments by cytotoxic therapies promote PS relocation to the outer leaf of the plasma membrane. In tumors this re-localization allows PS recognition by a number of receptors on myeloid and lymphoid cells in the microenvironment, promoting tumor growth and metastatic disease through the development of an immunosuppressive environment. Currently the PS-targeting antibody bavituximab is being used to treat patients with solid tumors in multiple late-stage clinical trials. Bavituximab’s anti-tumor properties are attributed in part through alleviating PS- receptor mediated immunosuppression and assisting in generating an Fc-FcR mediated pro-inflammatory response.
METHODS: Immune competent mice with E0771 induced tumors were administered either paclitaxel, or anti-PD-1/PD-L1 single agent therapy, or in triple combination with PS targeting antibody (ch1N11) to evaluate the efficacy of PS & PD-1/PD-L1 immune checkpoint inhibitors blockade in combination with cytotoxic chemotherapeutics. The levels of PS and PD-L1 expression were also evaluated on E0771 tumor cells following in vitro treatment via FACS analysis.
RESULTS: Preliminary results in multiple studies demonstrated differential sensitivity to either paclitaxel, or anti- PD-1/PD-L1 single agent therapy while inclusion of ch1N11 triple combination significantly enhanced anti-tumor efficacy over either single agent therapy. Also, FACs analysis demonstrated induction of PS & PD-L1 levels on E0771 cells following in vitro treatment with paclitaxel, suggesting that combining paclitaxel with PS and PD-1 targeting antibodies will have greater anti-tumor activity in triple combination treatments. No in vivo adverse effects were observed in animals given repeated doses of single or triple combinations.
CONCLUSION: These results support combination blockade of PS & PD-1/PD-L1 with paclitaxel to treat breast cancer.
- - - -
SITC 2014: 3 Peregrine posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal), and 1 poster by UTSW's Dr. Adam Yopp on the Bavi+Sorafenib/LIVER Ph2 IST: http://tinyurl.com/pchzr6h
SITC'15 Nov4-8: Short Stroll from PPHM-to-AZN's booths, with BMS able to keep a watch on the goings-on if they choose to...
Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
- - - - - - - -
11-7-15/Sat./12:45-2:00pm Track: “Optimizing Combination Immunotherapy”
Poster: “Targeting Phosphatidylserine Synergizes with Immune Checkpoint Blockade by Inducing De Novo Tumor Specific Immunity”
Presenting Author: Xianming Huang, PhD (UTSW-MC/Dallas)
Xianming Huang 1, Jian Gong 2, Dan Ye 1, Van Nguyen 2, Michael Gray 2, Steven King 2, Jeff Hutchins 2, Rolf Brekken 1, Bruce Freimark 2
...1 UTSW-MC/Dallas
...2 Peregrine Pharmaceuticals, Tustin CA
Direct Link: http://bit.ly/1LS4VYk
= = = = = = = = = = = = = = = = = = = = =
10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial, Bavi+durvalumab(MEDI4736), squamous or non-squamous… http://tinyurl.com/q79bkam
10-15-15: AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial
Global, Randomized Phase II Trial to Evaluate Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor Durvalumab (MEDI4736) in Previously Treated NSCLC
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=936766
TUSTIN, Oct. 15, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that it has expanded its ongoing cancer immunotherapy clinical collaboration with AstraZeneca to include a second, later-stage trial. The companies will now also evaluate the immunotherapy combination of Peregrine's phosphatidylserine (PS)-targeted immune-activator, bavituximab, and AstraZeneca's anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), in a global Phase II study in patients with previously treated squamous or non-squamous non-small cell lung cancer (NSCLC). The randomized Phase II trial will be conducted by Peregrine. . .
ABOUT BAVITUXIMAB: A TARGETED INVESTIGATIONAL IMMUNOTHERAPY
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT DURVALUMAB (MEDI4736)
Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor's immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
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8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors”…
Durvalumab=MEDI4736, an anti-PD-L1 immune checkpoint inhibitor.
AZN’s Head/I-O(Robert Iannone): “…Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
8-24-15: AstraZeneca and Peregrine Pharmaceuticals to Collaborate on Immuno-Oncology Combination Clinical Trial
• Collaboration to Focus on Cancer Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor MEDI4736
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=928488
TUSTIN, Aug. 24, 2015: AstraZeneca (NYSE:AZN) and Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that they have entered into a cancer immunotherapy clinical trial collaboration. The collaboration will evaluate Peregrine's investigational phosphatidylserine (PS)-signaling pathway inhibitor, bavituximab, in combination with AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The planned Phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors.
Thanks, Krakonos - PPHM doubled their orig. booth #119. Peregrine has moved from #119 to twice as big #121 recently - within the last couple of weeks I KNOW they showed at #119...
SITC'15 EXHIBITOR: Peregrine Pharm. - booth #121 (directly across from #120/ASCO & BMY/124; AstraZeneca/108 & DNA/113 are close by)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
ATTENDEE Reports from 10-15-2015 ASM (updated*/will delete+repost as more added - thanks for sharing, contributors!)… *HorseLover45/Djohn/Eb0783/followups
10-15-15/10amPT: Annual SHM, Irvine Marriott – Final Proxy: http://tinyurl.com/qan2qec Webcast Replay(SK's Presentation): http://edge.media-server.com/m/p/jghjvabo
By: djohn 10-15-15 6:49pm iHub #239179
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117754746
I attended the ASM this morning. My impression is very good. I am now very comfortable with my investment in PPHM. These are real good people doing a real difficult job to move Bavi forward. I don't have much time because I have to get to JW for a flight to SFO then the redeye to ORD. Sorry I did not get on earlier, but had business to attend to in OC. I will give more details tomorrow when I have time.
I don't have my notes but the 175mm share increase was approved - rough numbers: For/106.5mm, Against/44.5mm, Abstained/2mm (so, 40 some million didn't vote. Interesting!)
I voted all my shares for. Everything else passed.
I talked to everyone...
CJ is a very nice guy, southern guy went to Auburn. I felt he has the best interests for PPHM and shareholders. I have no problem with him being COB now. If and when we get in the big leagues I will maybe re-look. I liked him, real guy not a fake!
ES Good guy, genuinely concerned about pps and long time shareholders. Remember he holds a big stake of real shares not just options.
DP was there. Talked briefly. Came crossed as a good board member. Didn't talk very long.
My take away is these guys are doing a good job and ARE concerned about the shareholders. I am good with them being the independent directors.
Talked to SK,JH,JS briefly and others (don't have my notes) Gerber's presentation was great.
Got to go.
I said I was going to the ASM to see if I would continue my investment, buy more or bale.
At this point I will carefully buy more! -dj
FU/239180: Oh forgot: Garnick was there talked to him briefly. I like him, he likes big bullets. Maybe someday soon PPHM will be a big bullet.
FU/239327: EB, after talking to everyone it kind of all came together. These guys Have an excellent plan and are executing it well. When we were talking about the 175mm share increase and someone asked the question how they came up with the 175mm figure. PL kind of dropped the ball and SK came up and started talking, when he said, “we want to be able to react and respond to success”. First of all, at that point I thought SK displayed leadership and really looked like a CEO. It was funny, because when SK was talking on the webcast, he sounded like a scientist giving a canned presentation. But when the webcast was over and talking to him personally, he sounded like a CEO. We asked these guys to get Bavi FDA approved. They developed a plan and are exciting it. But I think there is a big bold plan if and when Bavi is approved. This is where shareholder value maximizes, IMO. If and when Bavi is approved, we won't be sitting around and waiting for a BP to come around and offer us a deal. We will be ready to go on our own (at least in the US), Not having to share revenues other than with the UTSW regents. Cash Cow comes to mind.
FU/239340[re: bringing Bavi to mkt]: It will not be worldwide just in US. We will partner in Europe & Asia. Sorry [carboat], but it will highly increase shareholder upside. Don't underestimate this mgt. team until you have talked to them.
FU/239343: N40, Dr Gerber's talk was more on Lung Cancer, the different types, and how PS-targeting & Bavi fit into the different types. Nothing earth-shattering at I can recall.
FU/239689[re: ”You were lied to.”]: It's funny, I had some of the same concerns you have before I talked to each Board Member and most of the Top Mgt. people at the Peregrine ASM. They all answered all my questions without hesitation and IMO truthfully. I suggest you attend next year's meeting, talk and ask all you want before you jump to your opinion. I did that and my opinion changed. I would value your opinion so much more should you do this.
FU/239694[re: 1) 3 other Penny Stocks BOD involved with; 2) PPS down over 80% yet why don't they don't buy on open-mkt?]: I did not hear anyone ask your 1st question. I think the people there asked questions related to their own concerns, and that did not concern me. Each and every person I talked to at the ASM was confident in their plan to get Bavi approved, and when approved move Bavi to commercialization. If Bavi is approved by the FDA, that plan will move quickly and shareholders will be rewarded. I formed that opinion from my conversations. IMO there is an excellent plan in place and once the first domino falls, things will move quickly.
FU/241327[re: carboat's ”Garnick is just a part-time consultant.”]: Try talking to Dr. Garnick face to face and ask the right questions and you will soon realize his the real deal! Have you ever had a face to face discussion with him???? It's easy speculate on a person's worth not knowing anything, but when you gather all the facts from the person, Well, that's the real deal!!!
By: eb0783 10-15-15 11:43pm iHub #239200
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117759249
Actually the sign at the door today specifically said no recordings, no photos, no videos.
Sorry you couldn't make it this year Green. It was refreshing as always. Looked to be slightly less than 50 attendees with about 20 -25 being shareholders.
FU/239201: Avid will not be operational/FDA-certified for another 4-5 weeks minimum. It is running test/pilot batches but (imo) like any new mfg. complex, it needs to be run through (and wrung out) to perfection.
FU/239203[re: possible Avid Expansion beyond the current expansion]: You did not misunderstand. They are thinking about it only. No plans yet. Besides the need to control the mabufacturing & delivery of their own drugs, they are under increasing demand from new and growing customers. They are the latest in new, high-tech, and leading-edge biologic manufacturing. They are in demand.
FU/239204: I fell quite vindicated. Eom [at voting Yes for Auth-Shares increase]
FU/239204: Proposal #2: For/144.5, Against/6.4, Abstain/2.2
Proposal #3: 106.5, 44.5, 2
Proposal #4: 43, 18, 0.8
Proposal #5: 35.5, 25.5, 1
Finally, I totally agree with djohn, and I'm glad he finally got to look into their eyes to find they are good people doing a pretty good job in shark infested waters. Good report djohn.
FU/239324[re: new ANZ Bavi+durvalumab NSCLC/Ph2=global/enrolls faster]: Keep in mind that although PPHM will “conduct” the trial, AZN will be involved and they have contacts, doctors that are familiar with them, and other ”networked” people/orgs especially in Europe. They will help. King said they have been very good to work with. King also said that he expects the new trial to be started/using the same locations and doctors (as SUNRISE), so there will be less relationship/training/process issues. Hence, faster, cheaper. AVID: Agree with what is said here. My take also is that Avid II is not as simple as an extension of an existing facility. It is absolutely the latest technology and most leading edge design out there today. Although they tried to duplicate the Avid existing equipment as such, even to using the same vendors & models, it is a few years later than the first Avid and some insignificant code and technical upgrades may have been made (like a different connector), and not made clear in specs, which has to be noted & documented or changed as they turn them up and make their trial runs. They do want their runs to be perfect and data perfectly “replicate-able.” VOTE: I’m not sure how much of the Q&A on the addl. shares that you heard on the webcast, but shareholders asked a number of questions and got decent, straight-forward answers. One answer (to a question that created days of wasted discussion & fud ammunition) was by CJ: The board was unanimous in proposal #3 [Auth.Addl.Shares].
FU/239328[re: were BOD vote results reported?]: I was ready with pen-in-hand and they did not. They just said that all 4 got the most votes and are hereby elected.
FU/239336: That reminds me of one point that Gerber made, I think during the Q&A. He was asked if there were any difference between PD-L drugs (which one is better). He said that as of now, Oct. 2015, he could not tell the difference about if one was better than another. I'm not sure if that was in his presentation, like if patients ask him that, or if it was later in discussion of the difference, if any, between Opdivo and the AZN drug [durvalumab=MEDI4736].
FU/239345[re: Sunrise enrollment completion timing]: Hayward, this is not a real answer to your question, but it might make others feel better about this full enrollment concern. King was asked if we were “on target for end of year” (or some term like that). He smiled and said, we are right where we have been saying. And he was asked then, or soon thereafter, if he thought it was important for us (or maybe it was additionally termed “for investors”) to PR when we hit the end. He said it was real important so that people would see Peregrine as a company that could complete trials and not just start them.
FU/241337[re: HorseLover's comments about Rob Garnick]: I was standing right beside you Horselover45, and that was part of a good conversation with Garnick. You are right, hearing him say it (and other things) was more confirmation of what we have here in Bavi! [Astronomical value]
By: Holotawoopas 10-16-15 11:42am iHub #239275
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117770870
Good morning everyone. The ASM was a pleasant experience for me this time as I got a better opinion of where my investment stands. Being invested in PPHM for 15 years and having attended many ASM's, I walked away feeling that the business side of PPHM outside of AVID is in progress and that the timeline for it to reflect in the share price did not make me concerned about the 175mm newly approved shares (which I voted no). I talked to SK, ES, and Dr. Garnick to get a better understanding of where we are, and I was satisfied with their answers/opinions. With all the generalization I just wrote, I am now in the camp that the first reflection of the value of bavi in the share price should be after the announcement of the completion of enrollment in the Sunrise trial.
By: Copper888 10-16-15 12:56pm iHub #239300
http://investorshub.advfn.com/boards/manage_msg.asp?message_id=117773742
Sorry for the delay, but I am snaking my way back up the coast to my home in Paso Robles, CA today. Have some good notes on my thoughts of the ASM for those interested. Great input from Dr.J and Eb. Did anyone mention that Dr. Gerber said that he is publishing an article this month about how Bavi is the only molecule they have worked with that binds directly to the tumor? He had a slide that showed a tumor "lit up" after Bavi exposure.
FU/239310[re: Dr.Gerber/Bavi-or-PGN650?]: I am 80% sure that it was Bavi, as he never talked about PGN650. He was going pretty fast and said it in the context that it was a bit of a surprise...thus the article to be published. I am not sure about the tumor being human or not.
FU/239316: Also, it was pretty clear to me that they are actively seeking to further expand to a 3rd Avid facility. This came up a few times subtly weaved into their answers on a range of topics. PL said they use an industry metric of 2-4 times sales for valuation.
He had a slide deck with his presentation. I am in my car with an iPad and have no idea whether the company plans on posting it or not. However I can tell you that the Bavi relevant info was contained on the last 2 slides. They were chock full of info and he sped through them in about 30 seconds.
FU/239322[re: Dr.Gerber's pres.]: He had a slide deck with his presentation. I am in my car with an iPad and have no idea whether the company plans on posting it or not. However, I can tell you that the Bavi relevant info was contained on the last 2 slides. They were chock full of info and he sped through them in about 30secs. I turned to my wife and said "did he just say that he is publishing an article later this month"? She said yes.
By: Copper888 10-17-15 3:44pm iHub #239501
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117793495
Observations from the ASM:
I apologize in advance for what may be redundant or deemed unimportant by some, but these are my observations, information and impressions from the ASM. Since I do not know what was cut off from the webcast, there might be some overlap.
* Attendance - Stockholders. there were definitely less than last year. Someone posted that they thought attendance was around 20 25 people…I think that is pretty close.
* During the pre-meeting chat session, I overheard CJ tell an attendee that "yes, but Cotara works, I was there when a doctor administered Cotara directly into a patients brain, and 3 days later that guy was out mowing his lawn."
* CJ - During the introduction by CJ when he was introducing PL, he commented that those attendees that are upset at the use of the ATM should "throw their darts" at him. But then praised him for a job well done. This led to an offhand comment by someone from PPPH (I couldn't see who) that CJ reads the "Chat Rooms" and that's where he gets the impression that people are pissed at the ATM usage. CJ said that in fact he does not read the Chat rooms, but some people do print certain posts for him to read which he sometimes reluctantly does.
* When talking about the new Avid Facilities, CJ thought that we would have the opportunity after the meeting to go and tour the facilities…this was quickly poopoo'd by the mgmt team, saying that there was too much activity going on there to have a tour that day.
* CJ also commented about the growth of the company and number of employees over the years. He said that there is no more room in the company parking lot and that employees are now forced to park in the streets which is not looked on favorably by the Tustin PD.
* As a strange side note, during CJ's preamble, PL was at times laughing so hard he was red in the face, lots of innuendo and inside jokes being tossed about between the 2…and PL was laughing so often and loud that my wife said it was "borderline unprofessional". IMO as I was sitting and having lost well over 100K on paper, I wasn't in as good a mood as they seemed to be.*
During the lead up to the votes, and in an unscheduled way, 2 of our stockholders (who should be commended by the way) wanted to know more about the 175M share increase and a discussion took place. PL did a decent job of explaining how they basically have calculated the cash needs over the short & long hauls and that they need to plan on a variety of scenarios to make sure they have everything they need. IMO he gave the company line, stock answer and did it well. However, he was asked then why can't you ask for 50M now and 50M later or some other smaller amt. than what we are now faced with. It was then that SK stepped up and took control of the meeting, he first said that he understood the concern, and said that we all want the same thing, BUT they now have to start planning for success - that there is a possibility that the trial is stopped early during the 2nd look-in (he mentioned this a few times during the meeting) and that they have to be prepared for commercialization, which is a very expensive process.
IMO, having listened and seen SK over the last few years, he has come a LOOONG way…he was very professional, and spoke frankly & confidently. He sounded like a CEO!
* Dr. Jeff Hutchins - Always a good speaker IMO but no new INFO to speak of.
* Dr. Gerber - I have posted on him prior. 100% on the intricacies of Lung Cancer, look for an article to be published on BAVI attaching directly to the tumor. Last 2 Slides were the BAVI focused slides. Blazed through them. (North - are you trying to get your hands on these?)
Q&A Period (the things that stood out to me; I have to paraphrase throughout this - but the other attendees PLEASE help me with any inaccuracies or if you heard things differently...
1. MSK Collaboration - Preclinical or Clinical? Answer: the collaboration will contain both preclinical & Clinical aspects on an on-going basis.
2. Are there cancers that don't respond well to I/O, how do they determine what studies to pursue? Answer: they are looking to start trials that why think will offer them the biggest differential between control and with BAVI arms. As an example, SK said that in Breast cancer patients/tumors with the highest mutations respond best (sorry for the non-scientific interpretation).
3. Addl. study readouts prior to Sunrise Unblinding…why is this important? Answer: they are trying to have as much data available as they can prior to Sunrise unblinding. SK said that they view this data as being "supportive from a regulatory standpoint" This played into the decision to go with AZ vs. Opdivo. He said that not only did the save substantial money with AZ, but the DATA gathering would be much faster. Shan confirmed this by saying that "time is money".
4. Is the IDMC able to ask for a look-in or can they view the data PRIOR to the scheduled look-ins for efficacy? Answer: No the only thing that they can do is stop the trial for a safety problem. they do not have access to data other than that is it may cause "operational bias". SK gave the impression that there was little to no chance that the trial would be stopped at 1st look-in as it is for futility only. (he did say offhandedly that maybe if ALL the BAVI patients were alive and therefore all of the events were the control arm that they might suggest stopping, but that is not going to happen). He stated again that the chance for an early stop could be the 2nd look-in, and at that time they would determine what to do. They have the option to keep going with the trial to garner further data and complete the study. IMO it sounded like that is what they are leaning towards…no stop even if they can. (my interpretation based on Shan, who was sitting right next to Garnick).
5. Why don't we seek a BTD on Breast? Don't you guys realize how that would effect the stock price?…we could sell our ATM shares at $2 or $3 vs. $1 today. Answer: Garnick stood up and said that in his opinion, BTD is meaningless. It was designed to ease the pressure off of the FDA, and that our Fast Track designation gives us everything that we want and could get from a BTD. The questioner then pushed that from a perception and PPS standpoint, a BTD could be huge. SK agreed that "who doesn't like the sound of a BTD?" and they are not ruling anything out, and if the opportunity would arise that would fit applying for one, that they would consider it.
6. The poison Pill is expiring this Spring, what are you going to do? Answer: we are aware and are meeting on the topic as we speak, we are determining what to do.
7. Why are the PR's written so vaguely? They are written in Scientific Jargon and the average investor does not get it and/or does not get excited about the company? Answer: SK - this is great feedback and we will look into writing our PR's in a more accessible way. IMO, here again, SK said that we all want the same thing here (PPS to go up).
8. I have to ask about getting a partnership to boost the PPS, is this a unicorn or is it a real possibility? Will the Full Enrollment PR be a big deal or is it meaningless? Throw us a bone please! Answer: SK thinks that the enrollment is a big deal, because not only does it prove that we can get the job done, BUT it starts a timer ticking. As each month goes by the pressure of 1st look-in, then 2nd look-in, is looming. This is the only time that Worsley spoke…he said that he is seeing the interest ramping up, and that as we get closer that he expects the pressure to make deals from potential suitors to pick up substantially.
FWIW - I came to the meeting a bit pissed but hopeful. I walked out feeling that they have it handled and they have a plan. No i was not drinking the Kool-Aid, it was Passion Tea…seriously. I apologize for the long rambling post but I wanted to get everything in - for those that attended, PLEASE Feel free to add, change or edit as you see fit. I truly hope this in some ways will help!
FU/239536[re: confidence level of mgt team?]: I would say they seemed very confident. SK really took control of the meeting this year...he was the clear leader. Last year CJ took more of the leader role presiding over the meeting. The room is Much better served with SK IMO.
By: JJ1223 10-16-15 4:37pm iHub #239382
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117782249
[re: results for BOD voting]: Paul Lytle went through every proposal and gave the total votes for/against and the number abstaining. After each proposal presented, he declared it approved by shareholders. Not sure how anyone could have heard anything else.
FU239386[re: SK's remarks on Sunrise enrollment]: He said in today’s environment, it was normal for companies to not finish a trial on time...for many reasons. I spoke with him directly and he remains confident on Bavi completing enrollment by EOY. He also mentioned it would be important to the share price because it would signal that the clinical data would be forth coming within a defined period of time. All the people I spoke with had glowing comments about the working relationship with AstraZeneca. I had many good & positive conversations, but the most excited guy in the room seemed to be Steve Worsley.
FU/239569[re: BTD option]: Garnick spoke only about BTD as it relates to speed-to-market, saying fast track gives Bavi the same advantages in terms of FDA meetings & priority review. SK did comment that if the opportunity presented, the company would make the application.
FU/239746: The company continues to make great strides in the IO space. The collaborations, MSK in particular, will pay great dividends in the not to distant future. IMO, the company has navigated some rough waters successfully and has put shareholders in a solid position to win. Not perfect, but the BOD deserves credit here. The next several months will be interesting. I was told (in a sidebar at the ASM meeting) that the company compared Bavi data against 67 other IO agents currently approved or in test...none had reported data results as strong or with a response as positive as those reported with Bavituximab. I am sure those comparisons are documented and being shared with many BP's and other interested companies.
FU/239791[re: maybe they said “6-to-7”?]: Very clearly 67, and the enthusiasm was very evident.
FU/239951: At the ASM, I was told that Peregrine has 2 full time employees working on Ebola. I have no other details.
By: HorseLover45 11-3-15 7:56am iHub #241312
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=118195423
Spoke to him [Rob Garnick] on Oct 15th at the meeting. Very positive about Bavi. Exact statement that he made to me was I am not here for the money have way more then I can ever spend. Of course, most of us know that but it was nice to personally hear it from him.
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10-15-15 PR(PPHM/AZN Collab. Expanded): “Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T-cells to continue attacking the tumor.” http://tinyurl.com/q79bkam
10-15-15/CEO S.King(ASM) 1:50: “Some of the most exciting data that we've seen to date is that, when you look at the immunotherapy revolution in the way cancer is being treated, what's really becoming clear is that the PD-1/PL-L1 inhibitors are very potent in patients who have an active immune response. So, what happens is, when you have an immune response, these markers, PD1/PD-L1, become expressed and basically shutdown the immune response. So, what those drugs are doing is basically stopping this inhibition that's caused by the PD-1/PD-L1 interaction. So, very simple – block the checkpoint and then now the immune system can keep mounting that immune response. But actually the majority of patients don't have that immune response going, and we really believe it's because they have this exposed PS which is knocking down that immune response from ever getting started. So what we see as a potential beautiful fit for bavituximab is, now we're able to block that PS signal, now the immune system gets started, and now we can keep it going with these PD-1/PD-L1 inhibitors. So, “get it started, and keep it going”, and now we believe, and we'll show this in data, that we can help more patients respond. Patients who are already responding are doing great, but it's the minority of patients, and now it's getting more & more patients to respond, and that's the whole goal of this combination therapy paradigm, which is really highlighted by today's announcement with AstraZeneca [10-15-15: http://tinyurl.com/q79bkam ] that we're expanding our collaboration into new areas to be able to look at those combinations.” 9:40: ”Now, immuno-oncology agents, as I mentioned earlier, are showing even by themselves very nice survival tails in a minority of patients, and this is typically 20-30% of patients who get such long-term benefits. So, the question is here, how do we make more & more patients able to enjoy that benefit of long-term survival, which means your body is really fighting the disease and helping the therapy, and when you look at our pre-clinical data, and obviously our goal next is to generate similar clinical data - when you at what happens when you're treating with an anti-PD-1 checkpoint inhibitor, you see some animals responding very well, but then you see these animals that just basically don't respond at all, or they have a very minimal response which then gives out over time. And this is exactly what you're seeing in patients, right? - the minority of patients are getting a long-term benefit, but most patients actually escaping treatment and relapsing. When you combine an anti-PD-1 with a bavituximab-equivalent for pre-clinical studies, what you see now is this wide variety of responses really begins to tighten up, so that most of these animals are now enjoying the benefit of a more-robust, combined anti-tumor effect caused by the immune system. Our goal thru our collaborations and with our clinical studies is to demonstrate this same effect in patients, so we're getting more & more patients with these long-term effects.”
**10-15-15/ASM Webcast Replay: http://edge.media-server.com/m/p/jghjvabo
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http://tinyurl.com/njtgpm3 ASM/10-15-15: PIPELINE & CLINICAL MILESTONES Slides...
PIPELINE 10-15-15/ASM:
CLINICAL MILESTONES 10-15-15/ASM:
iBox Upcoming Trials: (per 10-15-15 ASM http://tinyurl.com/njtgpm3 )
...Init 2H'15: Phase2/3, Bavi+Paclitaxel-or-Docetaxel(Dr’sChoice), Early-Stage Her2- Breast Cancer
...Init Early '16: Phase2, Bavi+durvalumab(AZN's MEDI4736 anti-PD-L1), 2ndLine NSCLC, squam+nonsquam (randomized, open-label)
...Init 2016: Phase1b, Bavi+durvalumab(AZN's MEDI4736 anti-PD-L1)+chemo, mult. Tumor types
...Init 2016: Phase1 Early Stage Her2- Breast Cancer
10-30-15: Kenneth Dart PPHM stake now 30,106,945 (13.1% of O/S)
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1-8-10: Kenneth Dart (Eastern Capital) acquires 7.1% stake (3,961,568) in PPHM http://tinyurl.com/24qctos
...2-14-12: Kenneth Dart adds 3,460,192, now 7,421,760 (8.55% a/o 12-9-11) http://tinyurl.com/7bb26j4 (13G)
...2-13-13: Kenneth Dart adds 500,000, now 7,921,760 (5.9% a/o 12-31-12) http://tinyurl.com/b25a93j (13G)
...2-13-15: Kenneth Dart PPHM stake now 9,921,760 (5.4% a/o 12-31-14) http://tinyurl.com/k4nsfuu (13G)
...10-30-15: Kenneth Dart PPHM stake now 30,106,945 (13.1% a/o 10-30-15) http://tinyurl.com/pexs62e & http://tinyurl.com/ns2s9p6 (13G & Form3)
“KENNETH B. DART (born 1955) is a United States-born Caymanian-Belizean-Irish businessman & billionaire. His wealth was estimated in 2013 at $6.6 billion. He is an heir of William F. Dart, who founded the Dart Container Corporation (originally the Dart Manufacturing Company) in Michigan in 1937.”
SITC’15 (Nov4-8): Peregrine Exhibiting; Abstracts Embargo'd till 11-3-15
Nov4-8 2015: “(SITC) Society for Immunotherapy of Cancer 30th Annual Meeting”, Natl-Harbor MD
”The premier destination for scientific exchange, education, and networking in the Cancer Immunotherapy Field”
SITC = The Society for Immunotherapy of Cancer http://www.sitcancer.org
SITC 2015 Meeting: http://www.sitcancer.org/2015
Abstract Embargo Lifted: 11-3-15 8am-Noon
Abstracts Published in Journal for ImmunoTherapy of Cancer: 11-4-15
EXHIBITOR: Peregrine Pharm. - booth #119 (directly across from #120/ASCO; AstraZeneca=#108)
...Floorplan: http://www.eventscribe.com/2015/sitc/exhibitors/index.asp
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SITC 2014: 3 Peregrine posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal), and 1 poster by UTSW's Dr. Adam Yopp on the Bavi+Sorafenib/LIVER Ph2 IST: http://tinyurl.com/pchzr6h
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Rutgers' Dr. Raymond Birge, 10-29-15 John-Hopkins/Seminar: “PS is a Global-Immune-Checkpoint In Cancer”
Oct29 2015: “John Hopkins MMI/ID Research Seminar”, Baltimore
MMI = Molecular Microbiology & Immunology
12-1:00pm: "Phosphatidylserine is a Global Immune Checkpoint In Cancer"
Raymond Birge, PhD, Vice Chair, Professor, Dept of Molecular, Biochemistry & Molecular Genetics, Rutgers Univ., Biomedical & Health Sciences, Newark, NJ
Loc: Bloomberg School of Public Health W1020
Contact: Maryann Smith (John Hopkins Univ. http://www.jhu.edu )
https://calendar.jhu.edu/EventList.aspx?fromdate=10/24/2015&todate=10/30/2015&display=Week&type=public&eventidn=60196&view=EventDetails&information_id=136317
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R.Birge Lab/Rutgers: http://birgelab.org
R.Birge Rutgers Profile: http://njms.rutgers.edu/resource_locator/find_people/profile.cfm?mbmid=birgera
“Avid with high-gross-profitability & sales-backlog” => For latest Qtr(7-31-15), Avid ran GP%=51 on Sales of $9.4mm; for last 3 qtrs, GP%=49/GP$=$11.9mm on Sales of $24.1mm. Avid's “committed backlog” = $42mm at 9/2015.
Updated PPHM REVS-BY-QTR TABLE, now thru FY16/Q1 (q/e 7-31-15), per the 7-31-15 10-Q (http://tinyurl.com/pemub47 ) issued 9-9-15.
• Total Revs since May’06: ($138.6mm/Avid + $24.1mm/Govt + $2.4mm/Lic.) = $165.2mm
• Deferred-Revs at 7-31-15, going fwd into FY’16/Q2 (q/e 10-31-15), total $8.3mm, UP from the $6.6mm of Deferred-Revs at 4-30-15 that drove into FY’16/Q1.
• Avid’s Gross-Profit over last 3 qtrs: $12.5mm on revs of $24.4mm (GP% = 49%)
• Recall, Avid Rev$ from Gov’t DTRA Contract work (6/30/08 – 4/15/11, totaling $24.15mm), went into GOVT-REVS, not AVID-REVS, in the Financials.
Avid’s website: http://www.avidbio.com
AVID PROFITABILITY (GROSS*) BY QTR:
QTR Avid-Rev$ CostofMfg$ Gross-Profit$ GP%
FY14Q1 7-31-13 4,581,000 2,670,000 1,911,000 42%
FY14Q2 10-31-13 7,354,000 4,195,000 3,159,000 43%
FY14Q3 1-31-14 3,885,000 2,416,000 1,469,000 38%
FY14Q4 4-30-14 6,474,000 3,829,000 2,645,000 41%
FY14 TOTAL: 22,294,000 13,110,000 9,184,000 41%*
FY15Q1 7-31-14 5,496,000 3,583,000 1,913,000 35%
FY15Q2 10-31-14 6,263,000 4,139,000 2,124,000 34%
FY15Q3 1-31-15 5,677,000 3,113,000 2,564,000 45%
FY15Q4 4-30-15 9,308,000 4,758,000 4,550,000 49%
FY15 TOTAL: 26,744,000 15,393,000 11,151,000 42%*
FY16Q1 7-31-15 9,379,000 4,608,000 4,771,000 51%
*Avid Net-Profit (ie, incl. Selling, G&A) not split out from PPHM-Corp. in the financials.
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9-10-15/OutsourcingPharma: “Avid Revs Likely to Grow Substantially”
9-10-15: “Peregrine Up on CMO Q1 Sales & Backlog, as New Plant Set to Go Online”
By Dan Stanton, Outsourcing-Pharma
http://www.outsourcing-pharma.com/Contract-Manufacturing/Peregrine-up-on-CMO-sales-and-backlog-as-new-plant-set-to-go-online
Manufacturing backlog at Avid Bioservices has reached $42mm as the firm books up space at a new facility currently undergoing its first internal pilot run. For Q1/FY2016, Peregrine Pharmaceuticals reported record revenue from its contact mfg. business Avid Bioservices of $9.4mm, up 71% year-on-year. But revenues are likely to grow substantially, the firm said, as there is a $42mm committed backlog from existing customers which will be carried-out in part once a new mammalian cell culture mfg. facility in Tustin, CA comes online.
“The new manufacturing suite is fully built and the first internal pilot run is currently underway to verify all systems and equipment are properly functioning,” Peregrine CFO Paul Lytle said during an investor call yesterday. ”Our strategic investment in the Avid Bioservices business is already starting to pay dividends. Our clients are reserving mfg. slots in the new facility which has increased our revenue backlog to approximately $42mm.”
A large proportion of the firm’s revenues come from its major client, Halozyme Therapeutics, servicing monoclonal antibody development projects with Roche & Baxter. While the company hopes the new facility will attract new customers, it is the current customer base showing the most interest.
“In the new facility, a lot of the interest comes from the existing client base, even as much as we've had new potential customers coming through,” said CEO Steven King. “It's exciting, it's a real nice showpiece and it's really showing in the interest that it's generated from again the existing client base.”
The site, first announced last year, more than doubles Avid’s mfg. capacity, though some of the space has been reserved to service its parent company’s lead product bavituximab, a chimeric mAb in Phase III trials for non-squamous NSCLC. END
6-17-15: Avid’s John Haney (ex-Genentech/Pfizer) speaking at BIO-INTL’5/Philly http://tinyurl.com/pnlquu3 & http://tinyurl.com/nl4vbgk
...”Designing & Implementing Avid’s New State-of-the-Art Single-Use Facility for Late Ph.3 & Commercial Prod.” - SK: "We've seen tremendous interest for production in the new facility, both from new & existing clients"
12-10-14: Avid to Double Mfg. Capacity (“expanding client roster; potential commercial launch of bavituximab”) http://tinyurl.com/mmc3qgy & http://tinyurl.com/kmdgq8t
3-24-15: Avid Receives CMO Leadership Awards for Its Commitment to Innovation & Reliability http://tinyurl.com/psep47f
3-12-13: Avid Q3'FY13 GP=$3.3mm; S.King 3-2012, "We have a profitable CMO, Avid Bioservices" http://tinyurl.com/l97rzm8
Rutgers' Dr. Raymond Birge, 10-29-15 John-Hopkins/Seminar: “PS is a Global-Immune-Checkpoint In Cancer”
Oct29 2015: “John Hopkins MMI/ID Research Seminar”, Baltimore
MMI = Molecular Microbiology & Immunology
12-1:00pm: "Phosphatidylserine is a Global Immune Checkpoint In Cancer"
Raymond Birge, PhD, Vice Chair, Professor, Dept of Molecular, Biochemistry & Molecular Genetics, Rutgers Univ., Biomedical & Health Sciences, Newark, NJ
Loc: Bloomberg School of Public Health W1020
Contact: Maryann Smith (John Hopkins Univ. http://www.jhu.edu )
https://calendar.jhu.edu/EventList.aspx?fromdate=10/24/2015&todate=10/30/2015&display=Week&type=public&eventidn=60196&view=EventDetails&information_id=136317
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R.Birge Lab/Rutgers: http://birgelab.org
R.Birge Rutgers Profile: http://njms.rutgers.edu/resource_locator/find_people/profile.cfm?mbmid=birgera
ATTENDEE Reports from 10-15-2015 ASM (updated*/will delete+repost as more added - thanks for sharing, contributors!)… *JJ1223/followup
10-15-15/10amPT: Annual SHM, Irvine Marriott – Final Proxy: http://tinyurl.com/qan2qec Webcast Replay(SK's Presentation): http://edge.media-server.com/m/p/jghjvabo
By: djohn 10-15-15 6:49pm iHub #239179
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117754746
I attended the ASM this morning. My impression is very good. I am now very comfortable with my investment in PPHM. These are real good people doing a real difficult job to move Bavi forward. I don't have much time because I have to get to JW for a flight to SFO then the redeye to ORD. Sorry I did not get on earlier, but had business to attend to in OC. I will give more details tomorrow when I have time.
I don't have my notes but the 175mm share increase was approved - rough numbers: For/106.5mm, Against/44.5mm, Abstained/2mm (so, 40 some million didn't vote. Interesting!)
I voted all my shares for. Everything else passed.
I talked to everyone...
CJ is a very nice guy, southern guy went to Auburn. I felt he has the best interests for PPHM and shareholders. I have no problem with him being COB now. If and when we get in the big leagues I will maybe re-look. I liked him, real guy not a fake!
ES Good guy, genuinely concerned about pps and long time shareholders. Remember he holds a big stake of real shares not just options.
DP was there. Talked briefly. Came crossed as a good board member. Didn't talk very long.
My take away is these guys are doing a good job and ARE concerned about the shareholders. I am good with them being the independent directors.
Talked to SK,JH,JS briefly and others (don't have my notes) Gerber's presentation was great.
Got to go.
I said I was going to the ASM to see if I would continue my investment, buy more or bale.
At this point I will carefully buy more! -dj
FU/239180: Oh forgot: Garnick was there talked to him briefly. I like him, he likes big bullets. Maybe someday soon PPHM will be a big bullet.
FU/239327: EB, after talking to everyone it kind of all came together. These guys Have an excellent plan and are executing it well. When we were talking about the 175mm share increase and someone asked the question how they came up with the 175mm figure. PL kind of dropped the ball and SK came up and started talking, when he said, “we want to be able to react and respond to success”. First of all, at that point I thought SK displayed leadership and really looked like a CEO. It was funny, because when SK was talking on the webcast, he sounded like a scientist giving a canned presentation. But when the webcast was over and talking to him personally, he sounded like a CEO. We asked these guys to get Bavi FDA approved. They developed a plan and are exciting it. But I think there is a big bold plan if and when Bavi is approved. This is where shareholder value maximizes, IMO. If and when Bavi is approved, we won't be sitting around and waiting for a BP to come around and offer us a deal. We will be ready to go on our own (at least in the US), Not having to share revenues other than with the UTSW regents. Cash Cow comes to mind.
FU/239340[re: bringing Bavi to mkt]: It will not be worldwide just in US. We will partner in Europe & Asia. Sorry [carboat], but it will highly increase shareholder upside. Don't underestimate this mgt. team until you have talked to them.
FU/239343: N40, Dr Gerber's talk was more on Lung Cancer, the different types, and how PS-targeting & Bavi fit into the different types. Nothing earth-shattering at I can recall.
FU/239689[re: ”You were lied to.”]: It's funny, I had some of the same concerns you have before I talked to each Board Member and most of the Top Mgt. people at the Peregrine ASM. They all answered all my questions without hesitation and IMO truthfully. I suggest you attend next year's meeting, talk and ask all you want before you jump to your opinion. I did that and my opinion changed. I would value your opinion so much more should you do this.
FU/239694[re: 1) 3 other Penny Stocks BOD involved with; 2) PPS down over 80% yet why don't they don't buy on open-mkt?]: I did not hear anyone ask your 1st question. I think the people there asked questions related to their own concerns, and that did not concern me. Each and every person I talked to at the ASM was confident in their plan to get Bavi approved, and when approved move Bavi to commercialization. If Bavi is approved by the FDA, that plan will move quickly and shareholders will be rewarded. I formed that opinion from my conversations. IMO there is an excellent plan in place and once the first domino falls, things will move quickly.
By: eb0783 10-15-15 11:43pm iHub #239200
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117759249
Actually the sign at the door today specifically said no recordings, no photos, no videos.
Sorry you couldn't make it this year Green. It was refreshing as always. Looked to be slightly less than 50 attendees with about 20 -25 being shareholders.
FU/239201: Avid will not be operational/FDA-certified for another 4-5 weeks minimum. It is running test/pilot batches but (imo) like any new mfg. complex, it needs to be run through (and wrung out) to perfection.
FU/239203[re: possible Avid Expansion beyond the current expansion]: You did not misunderstand. They are thinking about it only. No plans yet. Besides the need to control the mabufacturing & delivery of their own drugs, they are under increasing demand from new and growing customers. They are the latest in new, high-tech, and leading-edge biologic manufacturing. They are in demand.
FU/239204: I fell quite vindicated. Eom [at voting Yes for Auth-Shares increase]
FU/239204: Proposal #2: For/144.5, Against/6.4, Abstain/2.2
Proposal #3: 106.5, 44.5, 2
Proposal #4: 43, 18, 0.8
Proposal #5: 35.5, 25.5, 1
Finally, I totally agree with djohn, and I'm glad he finally got to look into their eyes to find they are good people doing a pretty good job in shark infested waters. Good report djohn.
FU/239324[re: new ANZ Bavi+durvalumab NSCLC/Ph2=global/enrolls faster]: Keep in mind that although PPHM will “conduct” the trial, AZN will be involved and they have contacts, doctors that are familiar with them, and other ”networked” people/orgs especially in Europe. They will help. King said they have been very good to work with. King also said that he expects the new trial to be started/using the same locations and doctors (as SUNRISE), so there will be less relationship/training/process issues. Hence, faster, cheaper. AVID: Agree with what is said here. My take also is that Avid II is not as simple as an extension of an existing facility. It is absolutely the latest technology and most leading edge design out there today. Although they tried to duplicate the Avid existing equipment as such, even to using the same vendors & models, it is a few years later than the first Avid and some insignificant code and technical upgrades may have been made (like a different connector), and not made clear in specs, which has to be noted & documented or changed as they turn them up and make their trial runs. They do want their runs to be perfect and data perfectly “replicate-able.” VOTE: I’m not sure how much of the Q&A on the addl. shares that you heard on the webcast, but shareholders asked a number of questions and got decent, straight-forward answers. One answer (to a question that created days of wasted discussion & fud ammunition) was by CJ: The board was unanimous in proposal #3 [Auth.Addl.Shares].
FU/239328[re: were BOD vote results reported?]: I was ready with pen-in-hand and they did not. They just said that all 4 got the most votes and are hereby elected.
FU/239336: That reminds me of one point that Gerber made, I think during the Q&A. He was asked if there were any difference between PD-L drugs (which one is better). He said that as of now, Oct. 2015, he could not tell the difference about if one was better than another. I'm not sure if that was in his presentation, like if patients ask him that, or if it was later in discussion of the difference, if any, between Opdivo and the AZN drug [durvalumab=MEDI4736].
FU/239345[re: Sunrise enrollment completion timing]: Hayward, this is not a real answer to your question, but it might make others feel better about this full enrollment concern. King was asked if we were “on target for end of year” (or some term like that). He smiled and said, we are right where we have been saying. And he was asked then, or soon thereafter, if he thought it was important for us (or maybe it was additionally termed “for investors”) to PR when we hit the end. He said it was real important so that people would see Peregrine as a company that could complete trials and not just start them.
By: Holotawoopas 10-16-15 11:42am iHub #239275
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117770870
Good morning everyone. The ASM was a pleasant experience for me this time as I got a better opinion of where my investment stands. Being invested in PPHM for 15 years and having attended many ASM's, I walked away feeling that the business side of PPHM outside of AVID is in progress and that the timeline for it to reflect in the share price did not make me concerned about the 175mm newly approved shares (which I voted no). I talked to SK, ES, and Dr. Garnick to get a better understanding of where we are, and I was satisfied with their answers/opinions. With all the generalization I just wrote, I am now in the camp that the first reflection of the value of bavi in the share price should be after the announcement of the completion of enrollment in the Sunrise trial.
By: Copper888 10-16-15 12:56pm iHub #239300
http://investorshub.advfn.com/boards/manage_msg.asp?message_id=117773742
Sorry for the delay, but I am snaking my way back up the coast to my home in Paso Robles, CA today. Have some good notes on my thoughts of the ASM for those interested. Great input from Dr.J and Eb. Did anyone mention that Dr. Gerber said that he is publishing an article this month about how Bavi is the only molecule they have worked with that binds directly to the tumor? He had a slide that showed a tumor "lit up" after Bavi exposure.
FU/239310[re: Dr.Gerber/Bavi-or-PGN650?]: I am 80% sure that it was Bavi, as he never talked about PGN650. He was going pretty fast and said it in the context that it was a bit of a surprise...thus the article to be published. I am not sure about the tumor being human or not.
FU/239316: Also, it was pretty clear to me that they are actively seeking to further expand to a 3rd Avid facility. This came up a few times subtly weaved into their answers on a range of topics. PL said they use an industry metric of 2-4 times sales for valuation.
He had a slide deck with his presentation. I am in my car with an iPad and have no idea whether the company plans on posting it or not. However I can tell you that the Bavi relevant info was contained on the last 2 slides. They were chock full of info and he sped through them in about 30 seconds.
FU/239322[re: Dr.Gerber's pres.]: He had a slide deck with his presentation. I am in my car with an iPad and have no idea whether the company plans on posting it or not. However, I can tell you that the Bavi relevant info was contained on the last 2 slides. They were chock full of info and he sped through them in about 30secs. I turned to my wife and said "did he just say that he is publishing an article later this month"? She said yes.
By: Copper888 10-17-15 3:44pm iHub #239501
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=117793495
Observations from the ASM:
I apologize in advance for what may be redundant or deemed unimportant by some, but these are my observations, information and impressions from the ASM. Since I do not know what was cut off from the webcast, there might be some overlap.
* Attendance - Stockholders. there were definitely less than last year. Someone posted that they thought attendance was around 20 25 people…I think that is pretty close.
* During the pre-meeting chat session, I overheard CJ tell an attendee that "yes, but Cotara works, I was there when a doctor administered Cotara directly into a patients brain, and 3 days later that guy was out mowing his lawn."
* CJ - During the introduction by CJ when he was introducing PL, he commented that those attendees that are upset at the use of the ATM should "throw their darts" at him. But then praised him for a job well done. This led to an offhand comment by someone from PPPH (I couldn't see who) that CJ reads the "Chat Rooms" and that's where he gets the impression that people are pissed at the ATM usage. CJ said that in fact he does not read the Chat rooms, but some people do print certain posts for him to read which he sometimes reluctantly does.
* When talking about the new Avid Facilities, CJ thought that we would have the opportunity after the meeting to go and tour the facilities…this was quickly poopoo'd by the mgmt team, saying that there was too much activity going on there to have a tour that day.
* CJ also commented about the growth of the company and number of employees over the years. He said that there is no more room in the company parking lot and that employees are now forced to park in the streets which is not looked on favorably by the Tustin PD.
* As a strange side note, during CJ's preamble, PL was at times laughing so hard he was red in the face, lots of innuendo and inside jokes being tossed about between the 2…and PL was laughing so often and loud that my wife said it was "borderline unprofessional". IMO as I was sitting and having lost well over 100K on paper, I wasn't in as good a mood as they seemed to be.*
During the lead up to the votes, and in an unscheduled way, 2 of our stockholders (who should be commended by the way) wanted to know more about the 175M share increase and a discussion took place. PL did a decent job of explaining how they basically have calculated the cash needs over the short & long hauls and that they need to plan on a variety of scenarios to make sure they have everything they need. IMO he gave the company line, stock answer and did it well. However, he was asked then why can't you ask for 50M now and 50M later or some other smaller amt. than what we are now faced with. It was then that SK stepped up and took control of the meeting, he first said that he understood the concern, and said that we all want the same thing, BUT they now have to start planning for success - that there is a possibility that the trial is stopped early during the 2nd look-in (he mentioned this a few times during the meeting) and that they have to be prepared for commercialization, which is a very expensive process.
IMO, having listened and seen SK over the last few years, he has come a LOOONG way…he was very professional, and spoke frankly & confidently. He sounded like a CEO!
* Dr. Jeff Hutchins - Always a good speaker IMO but no new INFO to speak of.
* Dr. Gerber - I have posted on him prior. 100% on the intricacies of Lung Cancer, look for an article to be published on BAVI attaching directly to the tumor. Last 2 Slides were the BAVI focused slides. Blazed through them. (North - are you trying to get your hands on these?)
Q&A Period (the things that stood out to me; I have to paraphrase throughout this - but the other attendees PLEASE help me with any inaccuracies or if you heard things differently...
1. MSK Collaboration - Preclinical or Clinical? Answer: the collaboration will contain both preclinical & Clinical aspects on an on-going basis.
2. Are there cancers that don't respond well to I/O, how do they determine what studies to pursue? Answer: they are looking to start trials that why think will offer them the biggest differential between control and with BAVI arms. As an example, SK said that in Breast cancer patients/tumors with the highest mutations respond best (sorry for the non-scientific interpretation).
3. Addl. study readouts prior to Sunrise Unblinding…why is this important? Answer: they are trying to have as much data available as they can prior to Sunrise unblinding. SK said that they view this data as being "supportive from a regulatory standpoint" This played into the decision to go with AZ vs. Opdivo. He said that not only did the save substantial money with AZ, but the DATA gathering would be much faster. Shan confirmed this by saying that "time is money".
4. Is the IDMC able to ask for a look-in or can they view the data PRIOR to the scheduled look-ins for efficacy? Answer: No the only thing that they can do is stop the trial for a safety problem. they do not have access to data other than that is it may cause "operational bias". SK gave the impression that there was little to no chance that the trial would be stopped at 1st look-in as it is for futility only. (he did say offhandedly that maybe if ALL the BAVI patients were alive and therefore all of the events were the control arm that they might suggest stopping, but that is not going to happen). He stated again that the chance for an early stop could be the 2nd look-in, and at that time they would determine what to do. They have the option to keep going with the trial to garner further data and complete the study. IMO it sounded like that is what they are leaning towards…no stop even if they can. (my interpretation based on Shan, who was sitting right next to Garnick).
5. Why don't we seek a BTD on Breast? Don't you guys realize how that would effect the stock price?…we could sell our ATM shares at $2 or $3 vs. $1 today. Answer: Garnick stood up and said that in his opinion, BTD is meaningless. It was designed to ease the pressure off of the FDA, and that our Fast Track designation gives us everything that we want and could get from a BTD. The questioner then pushed that from a perception and PPS standpoint, a BTD could be huge. SK agreed that "who doesn't like the sound of a BTD?" and they are not ruling anything out, and if the opportunity would arise that would fit applying for one, that they would consider it.
6. The poison Pill is expiring this Spring, what are you going to do? Answer: we are aware and are meeting on the topic as we speak, we are determining what to do.
7. Why are the PR's written so vaguely? They are written in Scientific Jargon and the average investor does not get it and/or does not get excited about the company? Answer: SK - this is great feedback and we will look into writing our PR's in a more accessible way. IMO, here again, SK said that we all want the same thing here (PPS to go up).
8. I have to ask about getting a partnership to boost the PPS, is this a unicorn or is it a real possibility? Will the Full Enrollment PR be a big deal or is it meaningless? Throw us a bone please! Answer: SK thinks that the enrollment is a big deal, because not only does it prove that we can get the job done, BUT it starts a timer ticking. As each month goes by the pressure of 1st look-in, then 2nd look-in, is looming. This is the only time that Worsley spoke…he said that he is seeing the interest ramping up, and that as we get closer that he expects the pressure to make deals from potential suitors to pick up substantially.
FWIW - I came to the meeting a bit pissed but hopeful. I walked out feeling that they have it handled and they have a plan. No i was not drinking the Kool-Aid, it was Passion Tea…seriously. I apologize for the long rambling post but I wanted to get everything in - for those that attended, PLEASE Feel free to add, change or edit as you see fit. I truly hope this in some ways will help!
FU/239536[re: confidence level of mgt team?]: I would say they seemed very confident. SK really took control of the meeting this year...he was the clear leader. Last year CJ took more of the leader role presiding over the meeting. The room is Much better served with SK IMO.
By: JJ1223 10-16-15 4:37pm iHub #239382
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[re: results for BOD voting]: Paul Lytle went through every proposal and gave the total votes for/against and the number abstaining. After each proposal presented, he declared it approved by shareholders. Not sure how anyone could have heard anything else.
FU239386[re: SK's remarks on Sunrise enrollment]: He said in today’s environment, it was normal for companies to not finish a trial on time...for many reasons. I spoke with him directly and he remains confident on Bavi completing enrollment by EOY. He also mentioned it would be important to the share price because it would signal that the clinical data would be forth coming within a defined period of time. All the people I spoke with had glowing comments about the working relationship with AstraZeneca. I had many good & positive conversations, but the most excited guy in the room seemed to be Steve Worsley.
FU/239569[re: BTD option]: Garnick spoke only about BTD as it relates to speed-to-market, saying fast track gives Bavi the same advantages in terms of FDA meetings & priority review. SK did comment that if the opportunity presented, the company would make the application.
FU/239746: The company continues to make great strides in the IO space. The collaborations, MSK in particular, will pay great dividends in the not to distant future. IMO, the company has navigated some rough waters successfully and has put shareholders in a solid position to win. Not perfect, but the BOD deserves credit here. The next several months will be interesting. I was told (in a sidebar at the ASM meeting) that the company compared Bavi data against 67 other IO agents currently approved or in test...none had reported data results as strong or with a response as positive as those reported with Bavituximab. I am sure those comparisons are documented and being shared with many BP's and other interested companies.
FU/239791[re: maybe they said “6-to-7”?]: Very clearly 67, and the enthusiasm was very evident.
FU/239951: At the ASM, I was told that Peregrine has 2 full time employees working on Ebola. I have no other details.
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10-15-15 PR(PPHM/AZN Collab. Expanded): “Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T-cells to continue attacking the tumor.” http://tinyurl.com/q79bkam
10-15-15/CEO S.King(ASM) 1:50: “Some of the most exciting data that we've seen to date is that, when you look at the immunotherapy revolution in the way cancer is being treated, what's really becoming clear is that the PD-1/PL-L1 inhibitors are very potent in patients who have an active immune response. So, what happens is, when you have an immune response, these markers, PD1/PD-L1, become expressed and basically shutdown the immune response. So, what those drugs are doing is basically stopping this inhibition that's caused by the PD-1/PD-L1 interaction. So, very simple – block the checkpoint and then now the immune system can keep mounting that immune response. But actually the majority of patients don't have that immune response going, and we really believe it's because they have this exposed PS which is knocking down that immune response from ever getting started. So what we see as a potential beautiful fit for bavituximab is, now we're able to block that PS signal, now the immune system gets started, and now we can keep it going with these PD-1/PD-L1 inhibitors. So, “get it started, and keep it going”, and now we believe, and we'll show this in data, that we can help more patients respond. Patients who are already responding are doing great, but it's the minority of patients, and now it's getting more & more patients to respond, and that's the whole goal of this combination therapy paradigm, which is really highlighted by today's announcement with AstraZeneca [10-15-15: http://tinyurl.com/q79bkam ] that we're expanding our collaboration into new areas to be able to look at those combinations.” 9:40: ”Now, immuno-oncology agents, as I mentioned earlier, are showing even by themselves very nice survival tails in a minority of patients, and this is typically 20-30% of patients who get such long-term benefits. So, the question is here, how do we make more & more patients able to enjoy that benefit of long-term survival, which means your body is really fighting the disease and helping the therapy, and when you look at our pre-clinical data, and obviously our goal next is to generate similar clinical data - when you at what happens when you're treating with an anti-PD-1 checkpoint inhibitor, you see some animals responding very well, but then you see these animals that just basically don't respond at all, or they have a very minimal response which then gives out over time. And this is exactly what you're seeing in patients, right? - the minority of patients are getting a long-term benefit, but most patients actually escaping treatment and relapsing. When you combine an anti-PD-1 with a bavituximab-equivalent for pre-clinical studies, what you see now is this wide variety of responses really begins to tighten up, so that most of these animals are now enjoying the benefit of a more-robust, combined anti-tumor effect caused by the immune system. Our goal thru our collaborations and with our clinical studies is to demonstrate this same effect in patients, so we're getting more & more patients with these long-term effects.”
**10-15-15/ASM Webcast Replay: http://edge.media-server.com/m/p/jghjvabo
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http://tinyurl.com/njtgpm3 ASM/10-15-15: PIPELINE & CLINICAL MILESTONES Slides...
PIPELINE 10-15-15/ASM:
CLINICAL MILESTONES 10-15-15/ASM:
iBox Upcoming Trials: (per 10-15-15 ASM http://tinyurl.com/njtgpm3 )
...Init 2H'15: Phase2/3, Bavi+Paclitaxel-or-Docetaxel(Dr’sChoice), Early-Stage Her2- Breast Cancer
...Init Early '16: Phase2, Bavi+durvalumab(AZN's MEDI4736 anti-PD-L1), 2ndLine NSCLC, squam+nonsquam (randomized, open-label)
...Init 2016: Phase1b, Bavi+durvalumab(AZN's MEDI4736 anti-PD-L1)+chemo, mult. Tumor types
...Init 2016: Phase1 Early Stage Her2- Breast Cancer
Baviman, I join all the others here that are praying for you. Please hang tough - advancements are being made rapidly!
JJ, re: "the company compared Bavi data against 67 other IO agents currently approved or in test"...How clear did you hear that? I'm wondering if "6 or 7" or "6 to 7" was heard as "67"??
Bavi's_Goal: More anti-PD-1/L1 Responders AND Prolong The Attack. Bavi's effect (hopefully to be proven in human trials), when combined with an anti-PD-1 inhibitor like AZN's durvalumab(MEDI4736SK), is more than just to increase the # of patients who respond to PD-L1, but also to cause the responses to be more prolonged & robust. SK 10-15-15/ASM, “Get it started, and keep it going.”
10-15-15 PR(PPHM/AZN Collab. Expanded): “Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T-cells to continue attacking the tumor.” http://tinyurl.com/q79bkam
10-15-15/CEO S.King(ASM) 1:50: “Some of the most exciting data that we've seen to date is that, when you look at the immunotherapy revolution in the way cancer is being treated, what's really becoming clear is that the PD-1/PL-L1 inhibitors are very potent in patients who have an active immune response. So, what happens is, when you have an immune response, these markers, PD1/PD-L1, become expressed and basically shutdown the immune response. So, what those drugs are doing is basically stopping this inhibition that's caused by the PD-1/PD-L1 interaction. So, very simple – block the checkpoint and then now the immune system can keep mounting that immune response. But actually the majority of patients don't have that immune response going, and we really believe it's because they have this exposed PS which is knocking down that immune response from ever getting started. So what we see as a potential beautiful fit for bavituximab is, now we're able to block that PS signal, now the immune system gets started, and now we can keep it going with these PD-1/PD-L1 inhibitors. So, “get it started, and keep it going”, and now we believe, and we'll show this in data, that we can help more patients respond. Patients who are already responding are doing great, but it's the minority of patients, and now it's getting more & more patients to respond, and that's the whole goal of this combination therapy paradigm, which is really highlighted by today's announcement with AstraZeneca [10-15-15: http://tinyurl.com/q79bkam ] that we're expanding our collaboration into new areas to be able to look at those combinations.” 9:40: ”Now, immuno-oncology agents, as I mentioned earlier, are showing even by themselves very nice survival tails in a minority of patients, and this is typically 20-30% of patients who get such long-term benefits. So, the question is here, how do we make more & more patients able to enjoy that benefit of long-term survival, which means your body is really fighting the disease and helping the therapy, and when you look at our pre-clinical data, and obviously our goal next is to generate similar clinical data - when you at what happens when you're treating with an anti-PD-1 checkpoint inhibitor, you see some animals responding very well, but then you see these animals that just basically don't respond at all, or they have a very minimal response which then gives out over time. And this is exactly what you're seeing in patients, right? - the minority of patients are getting a long-term benefit, but most patients actually escaping treatment and relapsing. When you combine an anti-PD-1 with a bavituximab-equivalent for pre-clinical studies, what you see now is this wide variety of responses really beg ins to tighten up, so that most of these animals are now enjoying the benefit of a more-robust, combined anti-tumor effect caused by the immune system. Our goal thru our collaborations and with our clinical studies is to demonstrate this same effect in patients, so we're getting more & more patients with these long-term effects.”
**10-15-15/ASM Webcast Replay: http://edge.media-server.com/m/p/jghjvabo
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Opdivo works in only ~20-35% of NSCLC Patients, those that express PD-L1 > 10%. In BMY’s Checkmate-057 NSCLC trial, Opdivo DID NOT increase survival vs. DOCE in the 64% of All Pts that didn’t express PD-L1 > 10% (see BMY’s K-M Charts below). Thus, the window of opportunity for Bavi is essentially 2/3+ of the NSCLC market. Of course, the other 1/3 of the patients where Opdivo works well might live even longer if Bavi were added to the mix, or possibly Bavi will allow Opdivo at reduced dosages to cut back on its considerable side-effects…
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PD-1/PD-L1 blockade therapies like Opdivo+Keytruda benefit 20-25% of patients. Peregrine’s objective with Bavi is to “increase the extent & amplitude” of such therapies…
“Although PD-1/PD-L1 blockade therapy [ex: Opdivo, Keytruda ] provides clinical benefits to approx. 20% of patients with advanced NSCLC, about 80% of patients still remain refractory to this treatment. Therefore, new molecules & combinations are urgently needed to address primary & secondary resistance to these new agents.”
From 3-2015 ClinCancerRes. article, “Immune Checkpoint Modulation for Non–Small Cell Lung Cancer”:
http://clincancerres.aacrjournals.org/content/21/10/2256.abstract
http://www.ncbi.nlm.nih.gov/pubmed/25979932
=> Bavi’s goal is to Extend The Range of patients that would benefit from the anti-PD1 mabs, in addition to helping the 20% that do benefit get Better Results.
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BMY’s Ph3 Opdivo NSCLC trial – look at the KM-Curve and OS #’s for those pts that express < 10% PD-L1. The OS separation in the tail just collapses and Opdivo (nivolumab) dead standstill with Doce in MOS => That’s ~64% of ALL the pts in the n=582 trial!
http://investor.bms.com/files/doc_presentations/2015/ASCO-Investor-Presentation-June-1-FINAL_v001_p9iq7v.pdf (pg.25)
10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial
=> Bavi+durvalumab(MEDI4736), squamous or non-squamous… http://tinyurl.com/q79bkam
10-15-15: AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial
Global, Randomized Phase II Trial to Evaluate Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor Durvalumab (MEDI4736) in Previously Treated NSCLC
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=936766
UC/Irvine: TUMOR IMAGING, MMan (may be more - I don't know)...
Note: Christopher C. W. Hughes (UC/Irvine), PhD, is a member of Peregrine's SRB:
http://www.peregrineinc.com/about-us/medical-and-scientific-advisors.html
AACR'13:
4-9-13/Tue Poster #2850: “Predicting Anti-Tumor Responses to Phosphatidylserine-Targeting Antibodies Using Tumor Imaging”
Jian Gong 1, Richard Archer 1, Van Nguyen 1, Christopher C.W. Hughes 2, Jeff Hutchins 1, Bruce Freimark 1
1 Peregrine Pharmaceuticals; 2 Univ. of California/ Irvine
Session: Immune Therapeutics & Monoclonal Antibodies 1
ABSTRACT:
Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane and becomes exposed on tumor vascular endothelial cells and tumor cells in response to chemotherapy, irradiation and oxidative stresses in the tumor microenvironment. Binding of antibodies targeting PS on the tumor endothelial cells and tumors induces the recruitment of immune cells and engages the immune system to destroy tumor vasculature. The antibodies also enhance anti-tumor immunity by blocking the immunosuppressive action of PS. A chimeric PS-targeting antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in Phase II trials. Fully human antibody PGN635 binds PS through the interaction of beta-2-glycoprotein 1 (B2GP1) in the same manner as bavituximab. Using human PC-3 prostate tumor xenografts in SCID mice, we demonstrate that targeting of PS in tumors by PGN635 is enhanced by chemotherapy. Combination of PGN635 with docetaxel inhibited tumor growth compared to the control IgG plus docetaxel group (p<0.05). Near-infrared optical imaging of PS in tumors with PGN650, an F(ab')2 antibody fragment of PGN635, showed tumor growth inhibition in mice treated with docetaxel correlates with PS expression levels in the tumors. Maximal uptake of the PS imaging was observed when chemotherapy was given 24 hours before the imaging probe.
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PPHM 4-10-13 PRESS RELEASE COMMENTS RE: #2850:
Data presented from imaging studies(2) demonstrate that the chemotherapeutic drug docetaxel, a commonly prescribed second-line treatment for patients with advanced NSCLC, increases the exposure of bavituximab's target molecule, phosphatidylserine (PS), on tumor blood vessel cells and tumor cells. Results also showed that PS exposure in tumors is correlated with tumor burden and response to docetaxel treatment, supporting exposed PS as a promising biomarker of cancer and response to therapy. Peregrine's PS-targeting imaging agent I-124-PGN650 is currently being evaluated in a clinical trial [ http://clinicaltrials.gov/ct2/show/NCT01632696 ] to assess its safety and potential to image multiple tumor types in patients with cancer.”
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=755519
PDF of AACR’13 Poster #2850:
http://www.peregrineinc.com/images/stories/pdfs/jian_2013.pdf
AACR'13: http://investorshub.advfn.com/boards/read_msg.aspx?message_id=86709291
Oct18-21 2015: “ASTRO's 57th Annual Meeting” San Antonio
“ASTRO's Annual Meeting is the premier radiation oncology scientific event in the world and draws more than 11,000 attendees each year.."
ASTRO = The American Society for Radiation Oncology https://www.astro.org
MTG: https://www.astro.org/Meetings-and-Events/2015-Annual-Meeting/Index.aspx
…CEO Steve King 7-14-15/CC: “We expect interim data from the going Ph1 Rectal adenocarcinoma IST (UTSW/Dr.JeffreyMeyer) evaluating bavituximab+capecitabine+radiation to be presented at the ASTRO Mtg. in October.” http://tinyurl.com/nw2v5u6
I thought the presentation was excellent, RevMonster - just shows how different you & I are.
ASM/10-15-15: PIPELINE & CLINICAL MILESTONES Slides
Oct15/10amPT: Annual SHM, Irvine Marriott – Final Proxy: http://tinyurl.com/qan2qec Webcast: http://edge.media-server.com/m/p/jghjvabo
10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial - Bavi+durvalumab(MEDI4736), squamous or non-squamous, global, randomized...
10-15-15: AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial
Global, Randomized Phase II Trial to Evaluate Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor Durvalumab (MEDI4736) in Previously Treated NSCLC
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=936766
TUSTIN, Oct. 15, 2015: Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that it has expanded its ongoing cancer immunotherapy clinical collaboration with AstraZeneca to include a second, later-stage trial. The companies will now also evaluate the immunotherapy combination of Peregrine's phosphatidylserine (PS)-targeted immune-activator, bavituximab, and AstraZeneca's anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736), in a global Phase II study in patients with previously treated squamous or non-squamous non-small cell lung cancer (NSCLC). The randomized Phase II trial will be conducted by Peregrine.
As part of the Phase II bavituximab and durvalumab combination trial, patients will be evaluated retrospectively for the correlation between their PD-L1 levels and clinical outcomes. This new study builds on the non-exclusive collaboration initiated between the companies in August 2015 [8-24-15: http://tinyurl.com/owlxpsf ] to conduct a Phase I/Ib basket clinical trial evaluating the combination of bavituximab and durvalumab with chemotherapy in multiple solid tumors.
Bavituximab and durvalumab are investigational immunotherapies with different mechanisms that assist the body's immune system in fighting cancer. Bavituximab targets and modulates the activity of phosphatidylserine, a highly immune-suppressive molecule expressed broadly on the surface of cells in the tumor microenvironment. In pre-clinical and translational clinical studies, the treatment increases activated T-cells in tumors and fights cancer by reversing the immunosuppressive environment that many tumors establish in order to proliferate. Durvalumab is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T-cells to continue attacking the tumor.
"In the short period of time that we have been working with AstraZeneca, we have been very impressed with the company's commitment to innovative translational efforts that will help us better understand the dynamics of tumor immunity and clinical response to durvalumab and bavituximab combination in a range of cancers," said Joseph Shan, MPH, VP, Clinical and Regulatory Affairs of Peregrine. "We expect this extension of our collaboration with AstraZeneca will allow us to run a much more cost-effective and time-efficient trial than would have been possible under our previously planned study using Opdivo as the combination drug in the same lung cancer population. This Phase II study offers several key advantages including a supply of durvalumab that will enable us to conduct a global trial that can enroll patients more rapidly. In addition, the expanded collaboration provides for a more cohesive clinical program utilizing the same PD-L1 and other biomarker analysis across both the new Phase II trial and the already planned Phase I/Ib study combining durvalumab and bavituximab in multiple indications."
ABOUT BAVITUXIMAB: A TARGETED INVESTIGATIONAL IMMUNOTHERAPY
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT DURVALUMAB (MEDI4736)
Durvalumab is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Durvalumab blocks these signals, countering the tumor's immune-evading tactics. Durvalumab is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
ABOUT PEREGRINE PHARMACEUTICALS, INC.
Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a pipeline of novel drug candidates in clinical trials focused on the treatment of cancer. The company's lead immunotherapy candidate, bavituximab, is in Phase III development for the treatment of second-line non-small lung cancer (the "SUNRISE trial") along with several investigator-sponsored trials evaluating other treatment combinations and additional oncology indications. Peregrine also has in-house cGMP manufacturing capabilities through its wholly-owned subsidiary Avid Bioservices, Inc. ( http://www.avidbio.com ), which provides development and biomanufacturing services for both Peregrine and third-party customers. For more information, please visit http://www.peregrineinc.com .
ABOUT ASTRAZENECA
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: http://www.astrazeneca.com .
Safe Harbor snip
Contacts:
Jay Carlson Peregrine Pharmaceuticals, Inc. (800) 987-8256 info@peregrineinc.com
Stephanie Diaz (Investors) Vida Strategic Partners 415-675-7401 sdiaz@vidasp.com
Tim Brons (Media) Vida Strategic Partners 415-675-7402 tbrons@vidasp.com
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8-24-15: AstraZeneca & Peregrine Collaborate on Bavi+Durvalumab Ph1/1B Trial for “multiple solid tumors”…
Durvalumab=MEDI4736, an anti-PD-L1 immune checkpoint inhibitor.
AZN’s Head/I-O(Robert Iannone): “…Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
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8-24-15: AstraZeneca and Peregrine Pharmaceuticals to Collaborate on Immuno-Oncology Combination Clinical Trial
• Collaboration to Focus on Cancer Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor MEDI4736
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=928488
TUSTIN, Aug. 24, 2015: AstraZeneca (NYSE:AZN) and Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM/PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body's immune system to fight cancer, today announced that they have entered into a cancer immunotherapy clinical trial collaboration. The collaboration will evaluate Peregrine's investigational phosphatidylserine (PS)-signaling pathway inhibitor, bavituximab, in combination with AstraZeneca's investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The planned Phase I/Ib trial will evaluate the safety and efficacy of bavituximab in combination with durvalumab in multiple solid tumors.
Peregrine and AstraZeneca will collaborate on a non-exclusive basis, to evaluate the combination of bavituximab and durvalumab with chemotherapy as a potential treatment in various solid tumors. The Phase I part of the trial is expected to establish a recommended dose regimen for the combination and the Phase Ib part of the trial will assess the safety and efficacy of the investigational combination. Under the terms of the agreement, the initial trial will be conducted by Peregrine.
Robert Iannone, Head of Immuno-Oncology, Global Medicines Development, at AstraZeneca said, "We believe that combination therapy in immuno-oncology has the potential to be a novel and highly effective approach to treating cancer. Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
Bavituximab and durvalumab are investigational immunotherapies with different mechanisms that assist the body's immune system in fighting cancer. Bavituximab targets and modulates the activity of phosphatidylserine, a highly immune-suppressive molecule expressed broadly on the surface of cells in the tumor microenvironment. The treatment increases activated T-cells in tumors and fights cancer by reversing the immunosuppressive environment that many tumors establish in order to proliferate. MEDI4736 is a monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T-cells to continue attacking the tumor.
”Data generated to date have shown significant potential for combining bavituximab with agents targeting the PD-1/PDL-1 pathway and we're excited to further explore this approach in studies with AstraZeneca's durvalumab," said Steven W. King, President and CEO of Peregrine. "AstraZeneca is a recognized leader in the immuno-oncology field and this collaboration will play a key role as we continue to fully explore the potential of bavituximab in combination immunotherapies for a variety of clinical applications."
ABOUT BAVITUXIMAB: A Targeted Investigational Immunotherapy
Bavituximab is an investigational chimeric monoclonal antibody that targets phosphatidylserine (PS). Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab, the lead compound in Peregrine's immuno-oncology development program, blocks PS to remove this immunosuppressive signal and sends an alternate immune activating signal. Targeting PS with bavituximab has been shown to shift the functions of immune cells in tumors, resulting in robust anti-tumor immune responses.
ABOUT DURVALUMAB (MEDI4736)
MEDI4736 is an investigational human monoclonal antibody directed against programmed cell death ligand 1 (PD-L1). Signals from PD-L1 help tumors avoid detection by the immune system. MEDI4736 blocks these signals, countering the tumor's immune-evading tactics. MEDI4736 is being developed, alongside other immunotherapies, to empower the patient's immune system and attack the cancer.
ABOUT PEREGRINE PHARMACEUTICALS, INC. *snip*
ABOUT ASTRAZENECA IN ONCOLOGY?
Oncology is a therapeutic area in which AstraZeneca has a deep-rooted heritage. It will be potentially transformational for the company's future, becoming the sixth growth platform. Our vision is to help patients by redefining the cancer treatment paradigm and one day eliminate cancer as a cause of death. By 2020, we are aiming to bring six new cancer medicines to patients.
Our broad pipeline of next-generation medicines is focused on four main disease areas - ovarian, lung, breast and haematological cancers. These are being targeted through four key platforms - immuno-oncology, the genetic drivers of cancer and resistance, DNA damage repair and antibody drug conjugates.
ABOUT ASTRAZENECA *snip*
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Durvalumab (MEDI4736, anti-PD-L1) has a Net Present Value of $6.5B.
AZN’s Head/I-O(Robert Iannone): “…Our partnership with Peregrine provides the opportunity to explore an exciting, novel combination that could deliver important clinical benefit to patients across a range of cancers."
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SCIENCE: "Evolution has favored pathogenesis that resembles apoptosis."
Dr. Judah Folkman: ”This [Thorpe’s VTA research] is very promising and very elegant work... The whole goal is really 2-part, reducing the harsh side effects of cancer treatment, and reducing the chance that some cancer cells will evade treatment. That would be a big step in the next decade, and anti-vascular therapy will play a major role." (’97 & ’02 http://tinyurl.com/k5qe96g & http://tinyurl.com/n6vh9hp )
Peregrine's Bavituximab Clinical Trials website: http://PeregrineTrials.com
BAVITUXIMAB MOA & CLINICAL DATA: http://www.peregrineinc.com/pipeline/bavituximab-oncology.html
...Bavi Publications: http://www.peregrineinc.com/publications/publications.html
...Bavi Posters & Presentations: http://www.peregrineinc.com/publications/posters-and-presentations.html
Bavi MOA: Video (3:34) added ~3-2014 http://vimeo.com/87116642 "Bavituximab: A Novel Immunotherapy Candidate Targeting an Upstream Immune Checkpoint to Fight Cancer"
Bavi MOA: Video (1:33) on Bavi’s Immunotherapeutic MOA added to Youtube on 3-27-14 https://www.youtube.com/watch?v=Esewl35JD8s
BAVI MOA 8-26-15: Jeff Hutchins(VP/PreClin-Res) ImVacS’15 Talk – 29pg. Slideshow http://tinyurl.com/qz64pzg
…“Expansion & Activation of T Cells via the Targeting of the Immunosuppressive Ligand PS: Combination Strategy with Conventional, Targeted, and Checkpoint Inhibitor Therapy”
5-31-15: ASCO’15 Roundtable (webcast), “Raising the Immuno-Oncology Bar” - 7 panel members, incl. 3 Sloan Kettering researchers http://tinyurl.com/qxu4w2x
BAVI MOA 3-25-15: PPHM/VP Dr. Jeff Hutchins’ presentation at "Immune Checkpoint Inhibitors Conf.", Boston - PDF(34 Slides): http://tinyurl.com/ooxkhq7
BAVI MOA 2-9-15: PPHM/VP Dr. Bruce Freimark’s presentation at KEYSTONE "Tumor Immunology Meeting", Banff/CN – PR & Slides: http://tinyurl.com/q6cx4w6
BAVI MOA 12-12-14 San Antomio Breast Cancer Symposium, Dr. Bruce Freimark, Bavi+anti-PD-1 vs. Breast Cancer http://tinyurl.com/p5ng6vs
BAVI MOA 11-2014 SITC’14: 3 posters on preclin. Bavi+aCTLA4/aPD1 combo data (Hutchins Freimark Brekken Huang etal) http://tinyurl.com/pchzr6h
BAVI MOA 8-28-14: Italy’s Dr. Federico Cappuzzo, Bavi/NSCLC profile article (DovePress OpenAccess, 7pgs) - http://tinyurl.com/n3oa7bc
BAVI MOA 8-11-14: PPHM/VP Dr. Jeff Hutchins’ presentation at ImVacS "Immunotherapies & Vaccine Summit", Boston - PR: http://tinyurl.com/lpjy3u7 ; PDF(31 Slides): http://tinyurl.com/oueldme
...MLV’s Dr. George Zavoico’s 8-27-14 report on Dr. Jeff Hutchins’ 8-11-14 ImVacS/Boston Bavi MOA presentation: http://tinyurl.com/l3tw63c
BAVI MOA 5-28-14: Dr. Rolf Brekken’s 47min CRI “Cancer Immunotherapy” webinar about Bavituximab as an Upstream/Global Immune Checkpoint Inhibitor – REPLAY: http://tinyurl.com/lxgftyx
. . .CRI=Cancer Research Institute (NYC – Supported by BMS): http://www.cancerresearch.org - Facebook: http://tinyurl.com/pbmhb2z , https://twitter.com/CancerResearch
. . .CRI launches “Answer to Cancer” (cancer immunotherapy) website http://www.theanswertocancer.org
. . .8-12-14: CRI adds Youtube links to the 5-28-14 CRI Immunotherapy webinar, incl. Dr. Brekken's talk "about Bavi and how it works against lung, liver, and other kinds of cancers" http://tinyurl.com/ps5h6h8
BAVI MOA 3-25-14: Dr. Rolf Brekken’s 40min talk at NYAS Lung Cancer Symposium http://tinyurl.com/lq9stnk (45 Slides)
. . .Dr.Brekken’s talk: “Antibody-mediated Inhibition of PS - A Novel Strategy for Immune Checkpoint Blockade” (the 5 speakers: Jessica Donington, Roy Herbst, Balazs Halmos, Suresh Ramalingam, Rolf Brekken)
12-10-13: With recent scientific insights highlighting bavi’s immunostimulatory moa, these additions to PPHM’s SAB: Dimitry Gabrilovich, Scott Antonia, David Carbone**, Hakan Mellstedt http://tinyurl.com/mw776mk
......**A/o 9-2014, Dr. David Carbone (PPHM SAB/KOL) is President-Elect of IASLC https://www.iaslc.org/about-us/board
BAVI MOA: 12-2013 Bavi’s Immunotherapeutic MOA overviewed by UTSW’s Brekken/Huang in Pan European Networks Jrnl. http://tinyurl.com/lnb46pq
BAVI MOA 11-9-13: Annual SITC (WashDC) – 2 posters about Bavi’s Immunostimulatory MOA http://tinyurl.com/mjaweu5
...“We are actively working towards initiating a clinical trial in the coming months to further investigate the potential synergistic effects of bavituximab and an approved [anti-CTLA-4] immunotherapy in patients with Melanoma."
10-28-13 IASLC/Sydney: “Immune Checkpoints in the Tumor Environment: Novel Targets & the Clinical Promise of Combined Immunotherapies” http://tinyurl.com/mjaweu5
…Symposium speakers: Scott J. Antonia/MD-PhD(H.Lee Moffitt CC), Dmitry I. Gabrilovich/MD-PhD(Wistar Inst), Rolf A. Brekken/PhD(UTSW), David E. Gerber/MD(UTSW)
BAVI MOA: 8-19-13 Data Supporting Bavituximab’s Immunotherapy MOA Published in “Cancer Immunology Research” (AACR) - http://tinyurl.com/mhjftka (PDF)
…“PS-Targeting Antibody Induces M1 Macrophage Polarization & Promotes Myeloid-Derived Suppressor Cell Differentiation” (Thorpe etal)
BAVI MOA: 8-13-13 PPHM/VP Dr. Jeff Hutchins’ Presentation on the Downstream Immunostimulatory Effects/Moa of PS-targeting antibodies (like Bavi) at CHI’s “Immunotherapies Congress”/Boston http://tinyurl.com/m6h2tvt
BAVI MOA: 10-12-12 NMB article on how Bavi "Induces Innate & Specific Anti-tumor Responses" http://tinyurl.com/cw9odb8
BAVI MOA: 5-1-12 Dr. Phil Thorpe's 46min talk at NYAS PS-Targeting Symposium http://tinyurl.com/9792gl5
. . .Symposium title: "Phosphatidylserine (PS) Asymmetry - Therapeutic Apps. in Cancer & Infectious Disease Symposium"
. . .Replays of 5 speakers: Alan Schroit, Chris Reutlingsperger, David Ucker, Ari Helenius, Philip Thorpe
Michael - I'm 99% sure it was Webcast last year (just Audio?) - not sure how many times before that. Haven't made one yet - hope to next year.