6-3-13: Roth Ups Peregrine Price Target To $7, “the final data at ASCO and the FDA agreement & visibility should represent the final potential triggers to conclude a partnership deal.”…
6-3-13: ”Roth Ups Peregrine Price Target To $7” http://biotuesdays.com/2013/06/03/roth-ups-peregrine-price-target-to-7 Roth Capital Partners has raised its price target for “buy-rated” Peregrine Pharmaceuticals (NASDAQ:PPHM) to $7 from $4 after the company presented final survival data at ASCO from a Phase 2 study in 2nd-line lung cancer with bavituximab. The stock closed at $1.65 on Friday.
“Overall survival was an encouraging: 11.7 months in the 3 mg/kg arm (unaffected by the prior 3rd party coding errors) and 7.3 months for pooled 1 mg/kg and control arms,” writes analyst Joseph Pantginis. “We believe the final lung data puts the final piece in place for the planned bavituximab Phase III program starting by the end of the year,” he said, adding that the first key piece in place came recently with the announcement that the FDA has agreed to the Phase 3 design.
Mr. Pantginis said discussions with Peregrine shed further positive light on the recent interactions with the FDA. “In short, the interaction was very clean and timelines were kept very tight in the end. The company outlined their entire analysis of the study discrepancies and for the entire study and the FDA did not raise any question regarding the pooling of the 1 mg/kg & control arms. Based on the data and the size of the safety database, the design was cleared to move forward,” he added.
Mr. Pantginis said management has been in discussions with prospective partners and “we believe the final data at ASCO and the FDA agreement and visibility should represent the final potential triggers to conclude a deal.”
= = = = = = = = = = Roth Capital /Joe Pantginis - init. 7-15-10 Buy/PT=$10, CURR: Buy/$7.00 http://www.roth.com . . .Universe (click link bottom right): http://roth.bluematrix.com/docs/pdf/BLUE.pdf . . .6-3-13: Roth raises PPHM PT 4=>$7 ("ASCOdata+FDA_ph3 agreement & visibility should represent the final potential triggers to conclude a partnership deal.") http://tinyurl.com/kkvddt2 . . .1-14-13: Roth raises PPHM PT 2.70=>$4.00 ("partnering discussions have new found life") http://tinyurl.com/a9t29lb . . .1-7-13: Roth ups Neutral to BUY, PT 1.25=>$2.70 (after 2nd-Line NSCLC Review Upd) http://tinyurl.com/bfj7mva . . .12-11-12: Roth ups PT $.70=>$1.25 after Cotara Ph3 design approval & 12-10-12/10Q-CC. . . .9-24-12: Roth cuts PT $9=>$.70 after PPHM PR about 2nd-Line NSCLC trial data problems. . . .9-10-12: Roth ups PT $5=>$9 ("highly encouraged by 2ndLine NSCLC clinical data") http://tinyurl.com/9blrqk7 . . .8-15-12: Roth adds PPHM to focus list as a Top Biotech Pick: http://tinyurl.com/9rx5bps . . .5-21-12: Roth ups PT $3.30=>$5 ("impressed by the strong 2ndLine NSCLC clinical data") http://tinyurl.com/cnghzyv
Piper Jaffray/Charles Duncan, PhD - init. PPHM 3-5-13 OverWgt/PT=$2.50. There was a 4-10-13 AACR’13 update/commentary that I think we missed at the time – see below.
= = = = = = = = = = = = = 4-10-13 Piper Jaffray (Charles Duncan, PhD) comments on Peregrine’s AACR’13 presentations, sp. Betabodies, and the upcoming Ph.III 2nd-Line NSCLC trial: http://oncology.healthace.com/041113/oncology_report_041113_s8.pdf Peregrine: Pre-clinical Data at AACR Points to Broader Phosphatidylserine Platform [ie, “Betabodies”]; Regulatory Clarity for Bavituximab in NSCLC Could Emerge This Year Pre-clinical investigators recently presented data at AACR from studies of bavituximab (Bavi) and a novel phosphatidylserine targeting fusion-protein construct "betabodies”. Data generated with the KL15 betabody indicate a ~5x longer half-life vs. the mouse Bavi, and localization to tumor vasculature and inflammatory cells in mice. We believe this data represents the tip of the spear of what may be a new platform with potentially superior performance and broader lipid-targeting applicability. Other data presented provided further evidence for bavi's ability to enhance immune activity and target the tumor vasculature, two characteristics that underscore our conviction in the novel platform for cancer therapeutics. In terms of regulatory progress with bavi', we look forward to Peregrine's discussions with the FDA to forge a path forward to pivotal studies in NSCLC later this year. Betabodies a tested approach, applied to a novel target. The most impactful data presented at AACR, in our view, could be that describing the betabody fusion-protein. The betabody KL15 consists of a fusion of domains I & V from the phosphatidylserine (PS) binding protein beta2-glycoprotein 1 (B2GP1) with the CH2 & CH3 constant domains of a mouse IgG2a antibody. We note this is a somewhat similar approach to receptor-Fc fusions that can be used to bind soluble growth factors present in the blood stream, such Regeneron’s “trap” proteins that target molecules like VEGF and others. Due to the typical high-binding affinities between a receptor and its ligand, these constructs often possess high affinity as well as long durability due to the stability of the antibody domain. Regulatory clarity could emerge yet this quarter. We anticipate that Peregrine will soon conduct meetings with the FDA regarding the path forward for Bavi in NSCLC. Recall that the company recently reported positive top-line results in 2nd-line NSCLC but then discovered discrepancies in the conduct of the trial due to misconduct at a CRO. Peregrine believes it has effectively addressed the issues by pooling the data from the low-dose drug & placebo arms in order to adequately compare to the high-dose (3mg/kg) arm that is intended to be used in the pivotal studies. We look to outcomes from the FDA discussions and initiation of a pivotal study in 2nd-line NSCLC in 2H13 to enhance investor conviction in Peregrine’s PS-targeting platform. In addition, data from a Phase II study in 1st-line NSCLC may be presented at ASCO (May 31-June 4) and could further support pivotal studies of Bavi and investor sentiment, in our view.
= = = = = = = = = = = = = = = = = 3-6-13/Benzinga: “Piper Jaffray Initiates Peregrine Pharmaceuticals with Overweight on Attractive Risk-Reward Opportunities” By Dwight Einhorn, Benzinga Staff Writer In a report published Tuesday, Piper Jaffray initiated coverage on Peregrine Pharmaceuticals (PPHM) with an Overweight rating and $2.50 price target. Piper Jaffray noted: “Peregrine is advancing 2 novel cancer drug candidates that, combined with its hybrid business model, present attractive risk-reward opportunities in our view. Lead candidate bavituximab (bavi) has recently endured negative news flow, increasing skepticism from investors but creating a potential buying opportunity, in our view. Bavi has broad potential due to its novel mechanism of action, providing many shots on goal for potentially large oncology markets like non-small cell lung cancer (NSCLC, ~$10bn+ market) and pancreatic cancer (PC), with multiple data-driven & regulatory catalysts in 2013. A 2nd major therapeutic candidate, Cotara, is a high risk but potentially high-return targeted radiopharmaceutical for brain cancer that we believe Peregrine will partner prior to starting a Phase III trial late in ‘13.” PPHM closed on Tuesday at $1.31. http://www.benzinga.com/analyst-ratings/analyst-color/13/03/3394234/update-piper-jaffray-initiates-peregrine-pharmaceuticals => Per RRDog iHub 115066/83, PJ report also said, “Bavi Controversy unfairly weighing on shares in our view… In addition, we believe the size & fully-human nature may support PGN650’s utility as a 2nd-gen “bavi-better.” Phase I data for PGN650 is expected this year, and this may result in the company becoming an acquisition candidate, vs. simply a partnering candidate, based on broad applicability but also long run-way potential for the emerging PS-targeting franchise."
= = = = = = = = = = = = = By: Biopharm 3-20-13 iHub #117279 http://investorshub.advfn.com/boards/read_msg.aspx?message_id=85926750 Piper Jaffray's Charles Duncan recently initiated coverage at Peregrine. You may want to watch this video which showcases Charles Duncan talking about DNDN and what went right.. and more importantly what went wrong with DNDN. Sorry if posting this is of no interest to some... but Piper Jaffray's Charles Duncan is probably one of the more legit analysts that have brought Peregrine further into the spotlight. Bottom line is DNDN... went from about $2-3.. to $20 in a couple days or so... then took 1 year to go from $20 to $40 ..etc Peregrine is much more aligned with its pipeline to show (at least) similar pps movement... and Peregrine management does have the advantage of past decisions made by companies such as DNDN. If you have the time... its a 1 hour video and Charles Duncans has the first 11 min's ... introducing the Dendreon Story: You may have read Deep Capture... but this gives the view directly from Charles Duncan and the DNDN panelists:
Moderator: Charles Duncan (with JMP Securities at the time) Panelists: • Reiner Laus MD - Bavarian Nordic • David Sable MD - Special Situations Life Sciences Fund • James Gulley MD PhD - National Cancer Institute • Susan Slovin MD - Memorial Sloan-Kettering Cancer Center 25 min mark: talks of --time to progression... PFS..vs the more important stat of O.S. -- very interesting ... overall a good video
= = = = = = = = = = = = = = PJ Research: http://www.piperjaffray.com/3col.aspx?id=103 Charles Duncan, PhD Sr. Research Analyst – Universe “Emerging BioPharma” Charles Duncan, Ph.D., joined Piper Jaffray in 2012 as a managing director and senior research analyst focused on small- and mid-cap emerging growth biotechnology companies. Duncan brings more than 17 years of sell-side experience during which he has covered a broad range of biopharma companies, most recently serving as an analyst at JMP Securities since 2002. Previously, Duncan covered the sector at Dresdner Kleinwort Wasserstein, Vector Healthcare Group - Prudential Securities, Tucker Anthony Cleary Gull and Chatfield Dean & Co. Duncan has been recognized by industry sources, including the Financial Times and StarMine Analyst Awards, as being among the best analysts for his fundamental and timely analysis. Duncan began his career as a manager of clinical development at Global Drug Dev., Inc., a pharmaceutical development consulting firm, and he also launched InfusionVision Medical, a venture-backed start-up medical device company. He is a graduate of the Univ. of Wisconsin-Madison and holds a doctorate in pharmaceutical sciences with a concentration in neuropharmacology from the Univ. of Colorado. http://www.piperjaffray.com/2col.aspx?id=7&analystid=1275&title=Analyst%20Information%20for%20Charles%20Duncan,%20PhD
12-30-13: ”Peregrine Pharmaceuticals Initiates SUNRISE Pivotal Phase III Clinical Trial of Bavituximab in Second-Line Non-Small Cell Lung Cancer” • Company Launches http://www.SunriseTrial.com to Assist Patients and Physicians http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=816379 TUSTIN, 12/30/13: Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), today announced the opening to enrollment of its SUNRISE trial at leading oncology centers in the United States. SUNRISE is a pivotal Phase III clinical trial comparing the company's investigational immunotherapy bavituximab plus the chemotherapy docetaxel against placebo plus the chemotherapy docetaxel in patients with second-line non-small cell lung cancer (NSCLC). This trial will enroll approximately 600 patients from more than 100 medical centers worldwide.
"The design of the SUNRISE trial was based on the compelling Phase II data [6-3-13/ASCO’13: Final Data Ph.II 2L/NSCLC http://tinyurl.com/my8qxw7 ] demonstrating encouraging improvement in overall survival in patients with second-line NSCLC. Furthermore, peer-reviewed published data support that bavituximab and docetaxel share highly compatible mechanisms of action that we believe hold promise for improved patient outcomes," (1-6) said Joe Shan, MPH, VP of Clinical & Regulatory Affairs at Peregrine. "We believe harnessing the body's natural immune system to fight cancer will be an integral part to conquering this deadly disease. Multiple peer-reviewed published data support bavituximab's immunotherapy mechanism of action whereby the targeted monoclonal antibody blocks an immune checkpoint responsible for immune suppression at the local tumor environment, thereby allowing the immune system to recognize and fight this deadly disease."
"This is a significant milestone for the company as patients with advanced non-small cell lung cancer who have progressed on a prior treatment have few therapeutic options, and new approaches to managing their disease are in demand," said Steven King, CEO of Peregrine. "As part of our plan to provide patient and physicians with the necessary information regarding this trial, today we launched the http://SunriseTrial.com web portal to serve as a gateway for trial parameters and additional resources. We anticipate that in executing our global plan we can enroll the majority of patients in this trial from the United States and Western Europe."
SUNRISE ("Stimulating ImmUne RespoNse thRough BavItuximab in a PhaSE III Lung Cancer Study") is a Phase III, global, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety, tolerability and efficacy of bavituximab plus docetaxel in patients with second-line NSCLC. The trial will evaluate bavituximab plus docetaxel versus docetaxel plus placebo in approximately 600 patients at clinical sites worldwide. Patients with Stage IIIb/IV non-squamous, NSCLC who have progressed after standard front-line treatment are eligible for enrollment. Patients will be randomized into 1 of 2 treatment arms. All patients will receive up to six 21-day cycles of docetaxel (75 mg/m2) plus weekly infusions of either bavituximab (3mg/kg) or placebo until progression of toxicity. The primary endpoint of the trial will be overall survival. For additional information about the SUNRISE trial please visit http://www.SunriseTrial.com or ClinicalTrials.gov using Identifier NCT01999673. [ http://www.clinicaltrials.gov/ct2/show/NCT01999673 ]
About Peregrine Pharmaceuticals, Inc. Peregrine Pharmaceuticals, Inc. is a biopharmaceutical company with a portfolio of innovative monoclonal antibodies in clinical trials focused on the treatment and diagnosis of cancer. The company is pursuing multiple clinical programs in cancer with its lead immunotherapy candidate bavituximab while seeking a partner to further advance its novel brain cancer agent Cotara®. 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. Additional information about Peregrine can be found at http://www.peregrineinc.com . Safe Harbor *snip* REFERENCES [See: http://www.peregrineinc.com/pipeline/bavituximab-oncology.html & http://www.peregrineinc.com/technology/bavituximab-oncology.html ] 1. Yin et al. “Phosphatidylserine-Targeting Antibody Induces M1 Macrophage Polarization and Promotes Myeloid-Derived Suppressor Cell Differentiation”, Cancer Immunology Research. 2013 Oct 1 (4):256-68. 2. Fabbri et al. “Sequential events of apoptosis involving docetaxel, a microtubule-interfering agent: a cytometric study” BMC Cell Biol. 2006 Jan 26;7:6. 3. Gong et al. “Measuring response to therapy by near-infrared imaging of tumors using a phosphatidylserine-targeting antibody fragment” Mol Imaging. 2013 Jun 1;12(4):244-56. 4. Huang et al. “A monoclonal antibody that binds anionic phospholipids on tumor blood vessels enhances the antitumor effect of docetaxel on human breast tumors in mice” Cancer Res. 2005 May 15;65(10):4408-16. 5. Kodumudi et al. “A Novel Chemoimmunomodulating Property of Docetaxel: Suppression of Myeloid-Derived Suppressor Cells in Tumor Bearers” Clin Cancer Res 2010;16:4583-94. 6. Hodge et al. “Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death”. Int. J. Cancer: 2013; 133(3):624-36. CONTACT: Christopher Keenan or Jay Carlson - Peregrine Pharmaceuticals, (800) 987-8256, info@peregrineinc.com
= = = = = = = = = = = = = = BAVITUXIMAB PHASE III TRIAL: ( http://www.SunriseTrial.com ) A. Phase III Bavi+Doce vs. 2nd-Line NSCLC "SUNRISE" (randomized, double-blind, placebo-ctl'd, n=582) Protocol: http://www.clinicaltrials.gov/ct2/show/NCT01999673 (Start=Dec2013 Est PrimaryComp=Dec2016) 5-20-13: FDA Approves Bavituximab Ph.III Design for 2L/NSCLC; 600-pt trial to begin by y/e’13 http://tinyurl.com/n3dxtm6 ...S.King: “We will now focus on starting the Ph.III trial while continuing ongoing partnering discussions.” …R.Garnick: “This was a highly collaborative effort with the FDA; this trial, when combined with Bavi’s supporting data to date, could be sufficient to support a future BLA submission."
= = = = = = = = = = = = = = = = = = = = = = = = = PRIOR (2010-2011) PHASE II 2nd-LINE NSCLC BAVI+DOCE TRIAL (n=121): F. LEAD IND: Phase IIb Bavi+Doce vs. 2nd-Line NSCLC (randomized, double-blinded, placebo-ctl'd, n=120, 'registrational') Protocol: http://clinicaltrials.gov/ct2/show/NCT01138163 (24 U.S. + 15 India + 2 RepGA + 7 RussianFED + 5 Ukraine = 53 as of 8-12-11) Enrolled Oct2010 - Oct2011 at 40 global sites (per J.Shan 9-7-12 webcast ( http://tinyurl.com/8cn87la ) 8-2012: Compare Bavi+Doce's MOS=11.7mos (Bavi/3mg) to the 4 Curr-Approved 2Line/NSCLC Drugs http://tinyurl.com/cgnkvpa • Taxotere/docetaxel => MOS=6.3mos (meta-analysis of 5 trials, 865 pts) • Altima/pemetrexed => No diff. vs. Docetaxel (Ph.3 non-inferiority vs. Doce, 571 pts) • Tarceva/erlotinib => MOS=5.3mos (TITAN Ph.III n=424 trial - see http://tinyurl.com/8w8lo93 ) • Iressa/gefitinib => "Iressa does not improve OS" 6-3-13/ASCO’13: Final Data Ph.II 2L/NSCLC http://tinyurl.com/my8qxw7 …60% improvement in MOS: Bavi/3mg=11.7mos. vs. 7.3mos. for CTL-arm(combined Bavi/1mg + DoxyOnly arms), HR=.662, P=.113 5-20-13: FDA Approves Bavituximab Ph.III Design for 2L/NSCLC; 600-pt trial to begin by y/e’13 http://tinyurl.com/n3dxtm6 ...S.King: “We will now focus on starting the Ph.III trial while continuing ongoing partnering discussions.” …R.Garnick: “This was a highly collaborative effort with the FDA; this trial, when combined with Bavi’s supporting data to date, could be sufficient to support a future BLA submission." 2-19-13: Topline Data Update from 2nd-Line NSCLC Trial after data discrepancies review http://tinyurl.com/ansqcea …60% improvement in MOS: 3mg=11.7mos. vs. 7.3mos. for CTL-arm(combined 1mg & Doxy+placebo arms), HR=.73, p=.217 6-5-13: FTM's table of MOS data in 15 prior Doxy 2nd-Line NSCLC trials (Bavi's 60% MOS Improvement is Tops) http://tinyurl.com/m886ctb 1-25-13: MLV's George Zavoico recaps 2ndLine/NSCLC data errors & current status of PPHM's review http://tinyurl.com/b9u4pk8 ...GZ: "This means that patients randomized into the high dose arm were administered Bavi correctly, whereas some of the patients in the placebo arm were administered low dose Bavi and some in the low dose Bavi arm were administered placebo. More importantly, the findings suggested that the MOS of 13.1 mos. in the high dose arm was likely to be valid. Even by historical measures, this is a remarkable result, since docetaxel's product insert lists the MOS of NSCLC patients receiving this widely used drug as 2nd-Line therapy in 2 trials as 5.7 & 7.5 mos. In effect, adding Bavi doubled the MOS. In our view, this was an extraordinary stroke of luck. If the high dose arm had been affected by the coding discrepancy, Peregrine would have been in a completely different & unfortunate position… Moreover, Peregrine must determine how best to present its case to the FDA. Will the historical controls be sufficient to justify moving Bavi into a Phase III pivotal trial, or will Peregrine have to pool the results of the placebo & low-dose arms and use that as a comparator to argue for moving ahead? A simple average of the placebo & low-dose arms results in a new control MOS of about 8.4 mos., still several months less than that of the high dose arm. This quick analysis results in about a 5-mo. survival advantage, a substantial prolongation for patients with second-line NSCLC and likely to justify moving Bavi into a pivotal Phase III trial in 2013, in our view." 1-7-13 PPHM PR - Review Update: "discrepancies are isolated to the placebo and 1 mg/kg arms; no evidence of discrepancies in the 3 mg/kg arm… Peregrine is taking a very conservative approach toward analyzing the results by combining the placebo & 1mg/kg arms into one treatment arm (control arm), and comparing to the 3mg/kg arm. This analysis indicates that the 3 mg/kg arm continues to show favorable TRR's, PFS, and OS over the new combined control arm. Peregrine expects to announce more detailed results from the analysis in the near term when it is completed." http://tinyurl.com/asup54d 9-24-12: Major Discrepancies found in 2nd-Line NSCLC Ph.2B Treatment Group Coding by Indep. Third-Party Vendor http://tinyurl.com/8r9zcqy …"Investors should not rely on clinical data that the company disclosed on or before Sept. 7, 2012 from its Ph.2 Bavi trial in patients with 2nd-Line NSCLC or any presentations or other documents related to this Ph.2 trial." 9-24-12: Peregrine sues CSM Over Bavi Ph.2B 2nd-Line NSCLC Clinical Trial Mix-Up http://tinyurl.com/8fpgngu …CSM = Clinical Supplies Management Inc., Fargo ND http://www.csmondemand.com ...1-17-13: Peregrine's lawsuit against CSM for "breach of contract & negligence" SERVED http://tinyurl.com/a7zrgys …9-10-12 CEO Steve King, QtlyCC ( http://tinyurl.com/8nkwrml ) ……"These are truly remarkable results (statistically doubling MOS) that are not only great for the pgm… but also great news for the NSCLC patients in the trial…" …9-10-12 Robert Garnick (Head/Reg), QtlyCC ( http://tinyurl.com/8nkwrml ) ……"The NSCLC data we announced 9-7-12 has far exceeded our expectations, and I hope that you're as excited as I am with bavituximab's potential. I feel strongly that Peregrine should be recognized for having the corporate courage to conduct the rigorous, randomized placebo-controlled Phase II trial that provided these robust data and that provide the basis for us to plan for a pivotal Phase III program." ...9-7-12: PPHM Press Release about Dr. Gerber's plenary at ASTRO/Thoracic/Chicago: http://tinyurl.com/96wrrso …"The interim data showed a statistically significant improvement in OS (Hazard Ratio 0.524, p-value .0154) and a doubling of MOS (12.1/13.1mos. vs. 5.6mos.) in the Bavituximab-containing arms compared to the [Docetaxel] ctl-arm." ......VP Joe Shan's 15min. Webcast & Slideshow recapping Dr. David Gerber's 9-7-12 ASTRO/Chicago Plenary: http://tinyurl.com/96wrrso …8-15-12 CEO Steve King, Wedbush/NYC ( http://tinyurl.com/8mhrtld ) ......"As we're sitting here today, we have still not reached the # of events for MOS in either of the Bavituximab arms - and, in fact, we still have patients that are on treatments." Q&A: "it's going to be a very positive MOS result, it's just a matter now of magnitude." …7-16-12 CEO Steve King, QtlyCC ( http://tinyurl.com/cs7spbz ) ......"The strength of this 2nd-Line NSCLC data (esp. MOS trends) in this large area of high unmet medical need has also sparked a surge in partnering discussions that has included over 15 in-person partnering meetings since that time with major players in oncology, with all discussions ongoing and addl. parties showing interest. Our goal for the program is to position ourselves, along with a potential partner, to initiate Ph3 by mid-2013, which means an EOP2 meeting by yr-end'12. It would be ideal to have a partner on board to participate in the EOP2 meeting, and we have communicated this to interested parties and they agree." …7-16-12 Robert Garnick (Head/Reg), QtlyCC ( http://tinyurl.com/cs7spbz ) ……"We've been working very hard and very actively on the next steps in our Bavi 2nd-Line NSCLC pgm, given the favorable data that we've seen. As you can imagine, with data like this, there are many things that we need to consider. One consideration is that, should the data continue to trend the way it is, particularly in survival, this opens a door for potential discussions around a pathway for Accelerated Approval. At this point, all options are being considered, with Peregrine working towards the most efficient path forward from a regulatory standpoint." Q&A: "…all in all, I think the data is extremely compelling and I think it makes a really good case. Certainly, I think, I've seen a lot of Ph2 & Ph3 data, and this is as compelling Ph2 data as I've ever seen. So, I'm very comfortable proposing a meeting with the FDA for Q4'12." …7-12-12 CEO Steve King, JMP-Conf/NYC ( http://tinyurl.com/csdclwb ) ……"Re: 2nd-Line/NSCLC trial, the most thrilling thing is the fact that, even though we'd reached MOS for the ctl-arm(Doce) at end of Apr'12 of LESS THAN 6MOS, the majority of patients are still alive (today) in both Bavi arms, and we expect that to continue for some period of time still. Ph3 planning is underway already; our goal is to start this Ph3 by mid'13, meaning an EOP2 meeting with the FDA in Q4'12; our goal is to bring a partner on board, ideally in time for that EOP2 meeting, certainly before the beg. of the Ph3 trial." …5-21-12: TopLine data n=117 for Bavi/3mg+Doce arm: ORR=17.9%/PFS=4.5mos (vs. CTL 7.9%/3mos) http://tinyurl.com/73aeyxj ......Importantly, MOS for CTL-arm "< 6 mos", but not yet reached in both Bavi arms. ...10-6-11: Enrollment complete. http://tinyurl.com/3m9re39 ...7-14-11/CC: Enrollment was taking longer than expected; have amended protocol; expanding to ~45 sites, expect enroll. comp. "early in Q4/2011", data unblinding 1H'12. http://tinyurl.com/6k6y2as …3-17-10/Roth, CEO S.King: "We refer to this trial as a Registrational Phase II Study, because we believe that if we have results anywhere near approaching what we saw in the earlier [India] study, it could be a conduit for Accelerated Approval." ...6-4-10: Ph.2b randomized reg. trial Open for enrollment: http://tinyurl.com/25v22qk ……"up to 120 refractory patients at ~30 clinical sites; goal: fully-enroll by mid'11, topline data by y/e'11."
3-28-14: Peregrine files 1st Amended Complaint vs. CSM First, Images (courtesy Cheynew iHub #170371), followed by TEXT Version, courtesy InternetForumUser, iHub#170472)…
= = = = = = = = = = = = = = = = = = = = = TEXT (courtesy InternetForumUser, iHub#170472 – “please forgive any spelling errors or translations”) PPHM vs CSM (3-28-14 1st Amended Complaint) in Text Converted For Easier Reading:
For its First Amended Complaint herein. Plaintiff Peregrine Pharmaceuticals, Inc. ("Peregrine") alleges as follows:
PARTIES Peregrine is a Delaware corporation with principal place of business at 14272 Franklin Avenue, Tustin, California. Peregrine is informed and believes that Defendant Clinical Supplies Management, Inc. ("CSM") is a North Dakota corporation with principal place of business at 342 42nd Street South, Fargo, North Dakota. [ http://www.csmondemand.com/ ]
JURISDICTION AND VENUE This action is based on diversity of citizenship and the amount in controversy exceeds S75,000. As such, this Court has jurisdiction pursuant to 28 U.S.C. § 1332(a). Venue is proper in this Court pursuant to 28 U.S.C. § 1391(a) because a substantial part of the events or omissions giving rise to the claims occurred in this District and because the terms of the parties' written agreement at issue specify that California law governs the interpretation of the agreement.
GENERAL ALLEGATIONS Peregrine is a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment and diagnosis of cancer.
Bavituximab, Peregrine's lead drug candidate, is a first-in-class phosphatidylserine targeting monoclonal antibody that has demonstrated broad therapeutic potential across multiple oncology indications and represents a new approach to treating cancer. Bavituximab is being evaluated in a randomized Phase III clinical trial for second line non-small cell lung cancer and has been evaluated in multiple Phase 1 and Phase II clinical trials for multiple indications.
Among the trials was the subject trial at issue in this case, a randomized, double-blinded, placebo-controlled Phase II trial evaluating bavituximab in 121 patients in which bavituximab doses were combined with docetaxel (chemotherapy) in patients who had previously treated unsuccessfully for locally advanced or metastatic non-squamous non-small cell lung cancer ("NSCLC"). The goal of the trial was to demonstrate increased anti-tumor activity (shrinking of tumors, delay of disease progression or extension of life) through the addition of bavituximab as had been experienced in prior similar clinical trials.
As a double-blind study, the various patients, treating physicians, and the Contract Research Organizations ("CROs") were hired to collect and verify trial data and Peregrine itself would not know the dosage assignments given to the patients in order to avoid any potential bias in patient outcome. Peregrine designed the trial to contain three treatment arms. One group of patients, the control or "A" arm, would receive docetaxel plus placebo treatments to serve as a baseline to compare the responses of the other two arms. The second or "B" arm would receive 1 mg/kg doses of bavituximab plus docetaxel. The third or "C" arm patients would receive 3 mg/kg doses of bavituximab plus docetaxel. The trial evaluated patients randomized into the three treatment arms in 40 sites around the world. Patient enrollment was completed in October 2011.
Peregrine utilized an experienced clinical trial consultant to coordinate with experienced vendors to perform the necessary work Peregrine could not do or even oversee due to the double-blind nature of the trial. Based on the consultant's recommendations and experience, eight main clinical vendors were assembled to perform the trial. Perceptive Informatics ("Perceptive") was contacted to provide randomization services for assignment of patients to treatment groups through a detailed proprietary protocol called "Clinphone Compact" ("Clinphone Protocol"). The project specifications were set forth in detail in the Clinphone Protocol which allocated responsibilities to contractors.
In connection with the subject clinical trial. Peregrine entered into a written Master Services Agreement ("MSA") with Defendant CSM in March 2010.
Pursuant to the MSA, the parties executed a Work Order which became part of the Agreement Specifically, CSM was hired under the MSA and its Work Order to receive clinical trial product, to package and label vials with labeling agreed to by Peregrine, to distribute the vials as directed by Perceptive under the Clinphone Protocol, and to track their distribution. CSM there represented that it would follow the project specifications and comply with FDA regulations, good manufacturing practices, and good clinical practices.
On February 25-26, 2010, Peregrine hosted a kick-off meeting ("Kick-Off Meeting") for the trial in Doheny Beach for a day and a half for the vendors to discuss the role of each vendor and to make sure their efforts were properly coordinated. Importantly, although Peregrine was the "client" and the "Sponsor," its role was necessarily limited in light of the double-blind aspect of the trial, and so the Kick-Off Meeting was intended to hand off the coordinated clinical vendor efforts among the vendors.
As confirmed at the kick-off meeting, CSM was responsible for supply chain activity, ensuring proper labeling and distribution to sites, and product vial reconciliation to inventory. It then would receive shipments of placebo, 1 mg/kg bavituximab and 3 mg/kg bavituximab in separate lots from Avid Bioservices ultimately totaling approximately 8,000 vials. CSM was supposed to label the 8,000 vials as set forth and agreed to in the Clinphone Protocol using a form of label agreed to with Peregrine. CSM shared marketing slide charts at the Kick-Off Meeting confirming that it had the capability to perform these simple tasks. Moreover, CSM understood and knew the extent which its related responsibilities and duties under the MSA and Work Order were intended to affect Peregrine and the trial.
As explained and agreed to by CSM at the Kick-Off Meeting by Perceptive and in accordance with the project requirements. Perceptive would apply the Clinphone Protocol's patient randomization program and direct CSM to distribute properly labeled placebo, 1 mg/kg or 3 mg/kg doses accordingly to the trial sites, to thereafter be processed by pharmacists and distributed to physicians to administer to the patients in the study. Thereafter, CSM would keep track of the administration of the doses and which patients fell into which treatment arm until the study was unblinded.
In carrying out its tasks, CSM was also obligated as a Contract Research Organization ("CRO") to comply with good clinical practices established by the International Conference on Harmonization ("ICH") Guidelines and to comply with various FDA regulations including, without limitation, good manufacturing practiccs established by and set forth in 21 CFR Parts 210 (Current Good Manufacturing Practice in Manufacturing, Processing, Packaging, or Holding of Drugs, General), and 211 (Current Good Manufacturing Practice for Finished Pharmaceuticals). In this regard, CSM was required to comply with numerous subparts of 211, including, but not limited to, (i) 211.125 Labeling issuance, subparts (a-f); (ii) 211.130 Packaging and labeling operations, subparts (a-e);(iii) 211.142 Warehousing procedures, subparts (a-b); and (iv) 211.150 Distribution procedures, subparts (a-b).
Due to the blinded nature of the study. Peregrine, as well as many of the other blinded clinical vendors participating in the trial, was dependent on CSM to strictly follow the protocol developed by Perceptive as set forth in the Clinphone Protocol. Further, CSM was informed and understood the harm Peregrine could suffer as a result of any wrongful conduct by CSM in performing its duties and responsibilities in connection with the trial.
Following the Kick-Off Meeting, Perceptive emailed CSM's Project Manager to confirm that CSM was following the Clinphone Protocol (specifying the A, B and C arms as "placebo," 1 mg/kg and 3 mg/kg, respectively, as she was instructed to do in the Kick-Off Meeting and had agreed to do pursuant to the Clinphone Protocol).
On April 15, 2010, CSM's Project Manager confirmed again to Perceptive and to Plaintiff that CSM was following Pereeptive's instructions and Clinphone Protocol. However, CSM's Project Manager's confirmation was false because CSM already had secretly and unilaterally swapped the A and B arms so that those patientsthat were randomized to the A arm (control arm) and supposed to receive placebo treatments, were actually receiving 1 mg/kg bavituximab treatments and vice-versa.
Peregrine's investigation in Fall 2012, revealed that CSM committed other labeling and distribution errors affecting the A and B arms above and beyond the swap of the A and B arms noted above. Further, CSM did not inform any other clinical vendor and did not disclose that CSM had made any sort of Clinphone Protocol change at all. CSM's Project Manager did not even advise CSM's own Director of QA that CSM had changed the Clinphone Protocol.
Additionally, CSMs activities were heavily regulated by the FDA, including those contained in 21 CFR Parts 211.125,211.130, 211.142 and 211.150 referenced above. Even if CSM had been authorized by Perceptive to make such a change to the Clinphone Protocol, CSM would have needed to notify the clinical vendors, including Perceptive. Upon such a change. Perceptive would have needed to redo its validated Clinphone Protocol and the Project Requirements Specification, which would have taken a significant amount of time and money to revise, revalidate and obtain approval prior to the trial commencing. Moreover, CSM breached its own written "Standard Operating Procedures" (SOP) which provide for CSM to prepare a "Planned Deviation Form" to be signed by CSM's Project Manager and approved by its Quality Assurance in the event of any change in the Clinphone Protocol.
Top-line data from the trial announced in May 2012 showed a doubling of overall response rates, the primary endpoint, and an improvement in progression- free survival, a second endpoint, in patients treated in the bavituximab-containing arms when compared to the control arm. Interim data publicly announced on September 7, 2012, showed a statistically significant improvement in overall survival and a doubling of median overall survival in the bavituximab-containing arms compared to the control arm.
However, thereafter, CSM's actions above began to be revealed in the course of preparing for an end-of-Phase II meeting with the FDA about the study. On September 24, 2012, Peregrine publicly announced major discrepancies between some patient sample test results and patient treatment code assignments. CSM's conduct caused substantial harm to the study and caused Peregrine substantial
FIRST CLAIM FOR RELIEF (Breach of Contract) Peregrine repeats and realleges each and every allegation of the foregoing paragraplis as though fully set forth herein.
The MSA and its Work Order together form a valid and enforceable written contract. Peregrine performed all obligations under the contract and/or was legally excused from doing so.
CSM failed to perform its obligations under the MSA and its Work Order including as set forth above.
As a consequence of the foregoing breaches) of the MSA and its Work Order, Peregrine has incurred substantial time and expense analyzing and evaluating the ramifications of the breach(es) and has incurred substantial damages, in manner and amounts to be proven at trial. These include the cost of the study, increased future clinical trial costs, delay in bringing bavituximab to market, and impact to the value of the bavituximab platform, all in amounts to be proven at trial.
SECOND CLAIM FOR RELIEF (Negligence) Peregrine repeats and realleges each and every allegation of the foregoing paragraphs as though fully set forth herein in performing under the MSA and its Work Order, CSM owed Peregrine a duty of due care to conduct itself in accordance with relevant professional standards, applicable laws, rules and regulations, including but not limited to the Federal Food, Drug and Cosmetic Act, the regulations promulgated under the Act, other applicable laws and regulations and the applicable good manufacturing and clinical practice standards.
Peregrine did not reasonably discover until on or about September 20, 2012 that CSM negligently failed to fulfill those duties.
CSM's conduct in connection with the clinical trial lacked any care and/or was an extreme departure from what a careful person/entity would do in the same situation to prevent harm to itself and to others. CSMs conduct was also grossly negligent as CSM intentionally performed its clinical services so carelessly, unreasonably and dangerously that it knew and/or should have known there was a high probability the trial would be rendered ineffective or less effective while Peregrine was undertaking a huge investment of time, money and resources in the trial.
As a proximate result of CSM's negligence. Peregrine has and will suffer damages as set forth above, in manner and amounts to be proven at trial.
THIRD CLAIM (Negligence Per Se) Peregrine repeats and realleges each and every allegation of the foregoing paragraphs as though fully set forth herein.
CSM's conduct as set forth herein violated multiple federal regulations, according to proof.
CSM's foregoing violations constitute negligence per se.
Peregrine has been damaged in manner and amounts as set forth above, to be determined according to proof at trial.
FOURTH CLAIM FOR RELIEF (Negligent Misrepresentation/Concealment) Peregrine repeats and realleges each and every allegation of the foregoing paragraphs as though fully set forth herein.
Peregrine is informed and believes that CSM's Project Manager was an agent and/or employee of CSM, and in doing the things herein alleged was acting within the course and scope of such agency and employment and with the permission and consent of CSM.
CSM's Project Manager for the subject trial negligently and unreasonably represented to Peregrine and vendors that CSM was following the Clinphone Protocol and negligently concealed that she had secretly decided for herself to deviate from the Clinphone Protocol. Specifically, on April 15, 2010, CSM's Project Manager confirmed [in writing/by email] that CSM was following Perceptive's instructions in this regard. She further concealed from Peregrine that she was not honoring CSMs packaging and labeling obligations.
The true facts were that CSM had secretly and unilaterally swapped the A and B arms so that those patients that were randomized to the A arm (control arm) and supposed to reccive placebo treatments, were actually receiving 1 mg/kg bavituximab, and vice-versa. Additionally, CSM failed to inform or disclose that it had secretly and unilaterally changed the Clinphone Protocol.
When CSM made these representations of material fact, it had no reasonable ground for believing them to be true.
Further, CSM made these representations with the intention of inducing Peregrine to act in reliance on these representations, or with the expectation that Peregrine would so act by continuing to pay CSM for services and cany on with the trial.
Peregrine, at the time of these representations and non-disclosures by CSM, was ignorant of the falsity of CSM's representations and concealment and believed CSM's representations to be true.
In reliance on CSM's misrepresentations, Peregrine was induced to use, did use and continued to use CSM's clinical services in connection with the clinical trial and paid it accordingly. Had Peregrine known the actual facts, Peregrine would have removed CSM from the clinical trial and taken all appropriate actions to revise, revalidate and obtain approval for a redesigned trial years earlier.
Peregrine's reliance on CSM's representations was justified as CSM held itself out as an experienced and sophisticated clinical services company with properly credentialed and trustworthy employees that could competently follow the Clinphone Protocol as set forth in the Project Requirements Specification as well as the applicable laws, regulations and standards of good clinical and manufacturing practices.
As a proximate result of the conduct of CSM as herein alleged. Peregrine was injured as set forth above in a manner and amounts to be proven at trial.
FIFTH CLAIM FOR RELIEF (Constructive Fraud) Peregrine repeats and realleges each and every allegation of the foregoing paragraphs as though fully set forth herein.
Peregrine hired CSM to receive product, label the vials, distribute them as directed by another vendor, and to keep track of its efforts. However, CSM contends (erroneously) that it took on responsibility to make adjustments to the Clinphone Protocol without telling anyone. While Peregrine denies that CSM was authorized to do so. Peregrine alleges alternatively that in taking such steps, CSM thereby took on fiduciary, special and confidential relationship obligations to Peregrine in connection with the subject trial by causing great and unnecessary risk to the trial. Given the highly confidential nature of the bavituximab clinical trial, the human subjects participating in the trial who could be harmed, the double blind trial format, and applicable regulations, CSM'S alleged "initiative" in secretly deviating from the Clinphone Protocol necessarily required that it perform with utmost care, loyalty and responsibility toward Peregrine.
As a result of taking on this fiduciary, special and confidential relationship, CSM was obligated to disclose certain material facts to Peregrine including, but not limited to, whether CSM was actually following the Clinphone Protocol, abiding by the applicable FDA regulations, and conducting the clinical trial in accordance with the applicable standards of good clinical and manufacturing practices. Any error by CSM would become subject to close scrutiny by the FDA and would put the trial at great risk.
CSM failed to disclose to Peregrine that it was not following the Clinphone Protocol as set forth in the Project Requirements Specification. CSM failed to disclose to Peregrine that CSM had secretly and unilaterally swapped the A and B arms so that those patients that were randomized to the A arm (control arm) and supposed to receive placebo treatments, were actually receiving 1 mg/kg bavituximab, and vice-versa. Additionally, Peregrine is informed and believes that CSM failed to disclose to Peregrine that CSM had violated numerous FDA regulations and the applicable standards of good clinical and manufacturing practices in connection with the services being provided by CSM.
The failure to disclose and the suppression of these material facts by CSM was likely to mislead Peregrine and did in fact mislead Peregrine into carrying on with the trial at great expenditures of time, money and resources, unaware of the risk CSM created. Further, the failure to disclose and the suppression of these material facts by CSM was done with the intent to induce Peregrine to act in reliance thereon. And so Peregrine paid CSM substantial sums and incurred millions pursuing the trial through September 2012 even though CSMs unilateral actions beginning in June 2010 placed those expenditures at great risk.
By failing to disclose and suppressing these material facts to Peregrine, CSM breached the fiduciary, special and confidential relationship between CSM and Peregrine.
Peregrine, at the times of these failures to disclose and suppressions of material facts occurred, was ignorant of the existence of the facts that CSM suppressed and failed to disclose. If Peregrine had been aware of the existence of these material facts not disclosed by CSM, Peregrine would have removed CSM as a CRO in connection with the clinical study and taken all appropriate actions to revise, revalidate and obtain approval for a redesigned trial. Instead, CSM benefited and gained an advantage as a result of its failure to disclose and suppression of material facts by continuing to receive payment.
As a proximate result of the wrongful conduct of CSM as herein alleged. Peregrine was injured by reason of which Peregrine has been damaged as set forth above, in manner and amounts to be proven at trial.
PRAYER FOR RELIEF
WHEREFORE, Peregrine prays that this Court enter judgment in favor of Peregrine and against CSM awarding the following: Damages according to proof at trial; Prejudgment and post-judgment interest on the foregoing sums; Costs of suit herein; Attorneys' fees if and to the extent permitted by law; and Such other and further relief as this Court deems just and proper.
KIRBY NOONAN LANCE & HOGE LLP /s/ John K. Landay David J. Noonan Charles T.Hoge John K. Landay Attorneys for Plaintiff Peregrine Pharmaceuticals, Inc.
= = = = = = = = = = = = = = = = = = = = = = = = = = = = 3-28-14: Peregrine files 1st Amended Complaint vs. CSM (13pgs) http://tinyurl.com/lsgf5lz ...Pg6: ”[as of 4-15-10], CSM had already secretly & unilaterally swapped the A & B arms so that those patients that were randomized in the A arm (CTL) and supposed to receive placebo treatments, were actually receiving 1MG Bavi treatments, and vice-versa. Peregrine’s Fall’12 investigation revealed that CSM committed other labeling & distribution errors affecting the A & B arms above & beyond the swap of the A& B arms noted above.”
6-3-13/ASCO’13: Final Data Ph.II 2L/NSCLC http://tinyurl.com/my8qxw7 …60% improvement in MOS: Bavi/3mg=11.7mos. vs. 7.3mos. for CTL-arm(combined Bavi/1mg + DoxyOnly arms), HR=.662, P=.113
5-20-13: FDA Approves Bavituximab Ph.III Design for 2L/NSCLC; 600-pt trial to begin by y/e’13 http://tinyurl.com/n3dxtm6 ...S.King: “We will now focus on starting the Ph.III trial while continuing ongoing partnering discussions.” …R.Garnick: “This was a highly collaborative effort with the FDA; this trial, when combined with Bavi’s supporting data to date, could be sufficient to support a future BLA submission."
2-19-13: Topline Data Update from 2nd-Line NSCLC Trial after data discrepancies review http://tinyurl.com/ansqcea …60% improvement in MOS: 3mg=11.7mos. vs. 7.3mos. for CTL-arm(combined 1mg & Doxy+placebo arms), HR=.73, p=.217
1-7-13 PPHM PR - Review Update: "discrepancies are isolated to the placebo and 1 mg/kg arms; no evidence of discrepancies in the 3 mg/kg arm… Peregrine is taking a very conservative approach toward analyzing the results by combining the placebo & 1mg/kg arms into one treatment arm (control arm), and comparing to the 3mg/kg arm. This analysis indicates that the 3 mg/kg arm continues to show favorable TRR's, PFS, and OS over the new combined control arm. Peregrine expects to announce more detailed results from the analysis in the near term when it is completed."http://tinyurl.com/asup54d
9-24-12: Major Discrepancies found in 2nd-Line NSCLC Ph.2B Treatment Group Coding by Indep. Third-Party Vendor http://tinyurl.com/8r9zcqy …"Investors should not rely on clinical data that the company disclosed on or before Sept. 7, 2012 from its Ph.2 Bavi trial in patients with 2nd-Line NSCLC or any presentations or other documents related to this Ph.2 trial."
News 
Market Data 
Discover 
AI
