AI
Monday, July 07, 2014 11:46:00 AM
Here are all of Dr. Robert Garnick’s public comments regarding his association as Head of Regulatory with Peregrine, from 10/19/2009 – 3-7-2014.
http://www.peregrineinc.com/about-us/management-team.html
Oldest-to-Newest…
I. Oct 19, 2009: Peregrine announced that Dr. Robert Garnick has joined the company as the Head of Regulatory Affairs. Dr. Garnick was formerly the Senior VP of Regulatory, Quality & Compliance at Genentech…
• During his 24-year career at http://clinicaltrials.gov/ct2/show/NCT01138163 Genentech, he was responsible for 17 new product approvals including most of the company's top selling monoclonal antibody therapeutics such as Rituxan, Herceptin, Avastin, and Lucentis… In this role, Dr. Garnick was responsible for all the regulated aspects of Genentech's business including drug development, commercial production and promotional and labeling compliance.
• Dr. Garnick will be responsible for overseeing Peregrine's interactions with the U.S. FDA and regulatory agencies around the world, and will lead the development of the company's regulatory strategies for advancing its novel monoclonal antibody-based treatments for cancer and infectious diseases.
SAID DR. GARNICK:
• "Peregrine's bavituximab & Cotara products represent the kind of innovation that made my drug development work so exciting and fulfilling at Genentech.”
• “Peregrine's PS-targeting antibodies such as bavituximab represent an entirely new mechanism that has already shown considerable promise for the treatment of cancer and infectious diseases, while Cotara has shown promising survival benefits in patients suffering from the worst form of brain cancer. I welcome the opportunity to work with the Peregrine team to help advance these promising candidates through the clinical & regulatory process."
http://tinyurl.com/yga7z4x
II. 12-10-09 CC: ( http://tinyurl.com/y9tr3q3 )
DR. ROBERT GARNICK (HEAD OF REGULATORY AFFAIRS):
”Thank you, Steve, and thank you everyone for joining this call. I am really very pleased to be here with you today, since I’ve been working with Peregrine for only a few months. In this call, I’d like to focus on sharing with some general observations that I have made on Peregrine and its product pipeline.
Let me start by telling a little bit about myself. I’ve spent all of my professional career working in the area of drug development, focusing on the rigorous scientific, clinical, and regulatory assessments that must be completed before any potential new product or medical device can be marketed. As you know, this is typically a very long complex and challenging process. However, the rewards for both drug developers, investors, and most importantly the patients who so desperately need these new products, can be quite substantial. In my own career, I’ve had the good fortune to spend over 32 years in the pharmaceutical industry, 24 years of which were at Genentech, where I was part of the birth of the biotechnology industry. I joined Genentech in 1984, and had the unique opportunity to literally grow up with the company, and played a significant role in the development of its products. At Genentech, I was deeply involved in obtaining marketing approval for 17 drug products and 3 manufacturing facilities, including such anticancer blockbusters as Rituxan for non-Hodgkin Lymphoma, Herceptin for breast cancer, Avastin for colorectal cancer and non-small cell lung cancer, and Lucentis for age-related macular degeneration. After heading up Genentech’s formal regulatory efforts for 15 years and growing my own department to over 1,300 people, in 2008 I decided it was time to retire from the corporate life of a large company and form the biotechnology specialty consulting company through which I was very fortunate to meet the excellent folks here at Peregrine.
After carefully studying the company’s Phosphatidylserine-Targeting Antibody platform and its lead product candidate bavituximab, I became extremely excited and agreed to work with Steve and his team to help guide the drug’s development, focusing specifically on how we might accelerate its progress towards marketing approval.
I’d like to say that bavituximab reminds me a great deal of a similar and very important monoclonal antibody, Rituxan, because of the biological elegance of its mechanism of action. Because of the similarity, the regulatory approach I’m recommending to Peregrine for bavituximab is very consistent with the approach we took at Genentech for obtaining the approval of Rituxan. I’m extremely optimistic that bavituximab may represent a unique and valuable new approach to the treatment of advanced refractory cancer in combination with chemotherapy or radiation, and based on its mechanism of action may potentially be useful in anti-viral and other indications as well. In addition to my personal scientific interest in the potential Peregrine’s technology, I’ve also been very impressed with the Peregrine team and the mix of professionalism, enthusiasm and commitment that are so reminiscent of my early days of Genentech.
As Steve mentioned, this is a very exciting time for Peregrine’s drug development programs. We have recently completed patient enrollment in 3 signal seeking bavituximab Phase II cancer trails, as well as an earlier-stage bavituximab cancer & Cotara brain cancer studies, and we eagerly anticipate having data starting to come in from these studies in the next few months. This sets the stage for planning our next set of bavituximab cancer trials and we are actively embarking on that progress. Our goal is to implement a clinical and regulatory strategy, that will maximize our chances of getting that bavituximab approved and to do so in the shortest feasible timeframe.
We’re in the process of designing a randomized blinded and placebo controlled Phase II clinical study for bavituximab in 2nd-line NSCLC. This type of study is typically the gold standard in the U.S. for drug development and this study is intended to play a major role in our future approval strategy for this product. Just a week ago, we had a very successful meeting with FDA to discuss a number of clinical questions in order to help us design the Phase II program in NSCLC, and the team and I are very pleased with how well it went. It’s not appropriate to reveal the details of this meeting, but suffice it to say that we were encouraged by the FDA’s positive response and by the fact that we have received such excellent advice as to what the Phase II trials, which I just described, should look like. I should say that, while NSCLC is our lead indication, we are actively exploring other clinical trials in other refractory solid tumor cancers, for which bavituximab may hold particular promise. We look forward to sharing more about our emerging bavituximab cancer, clinical, and regulatory strategy with you in the coming months.
I’m just getting to know, the Cotara program and so I’ll hold my comments for now. However, it is noteworthy that I feel that this drug holds considerable promise for the treatment of such lethal diseases as glioblastoma multiforme [GBM], which unfortunately have so few current treatment options. In view of its sizable long-term patient safety database and the promising efficacy results observed in some patients, we’ll be exploring ways in which Cotara might be advanced towards market approval more rapidly and cost effectively.
The growing body of scientific evidence that phosphatidylserine-targeting antibodies may have application in anti-viral and other anti-infective indications and Peregrine’s success in attracting the support of the biodefense establishment and multiple collaborators to further explore their anti-viral potential is encouraging. I look forward to getting more involved in this program in the appropriate time. In summary, I think this is a very exciting time to be at Peregrine, as it moves ahead its programs to the next critical stage of development, and I very much look forward to working with the Peregrine team to advance these promising drug candidates. Back to you, Steve.”
12-10-09 CC/Q&A:
Question by R.Adams: “…if the results in the 3 Bavi Ph.2 trails recently completed, especially tumor shrinkage, were achieved in the 1st half of the definitive trials you’re now planning for lung cancer, would you be well positioned to apply for accelerated approval?”
Dr. Rob Garnick: “As you know, I’ve actually done accelerated approvals in the past and certainly, as Steve said, we want to be positioned such that if the data is striking and very compelling that we would be in a position to apply for that and that as you know takes a lot of coordination in across the company, not just in the clinical & regulatory side, but in the manufacturing & quality operations. We are actually making sure that should such an opportunity occur, that we would be in an excellent position in order to take advantage of that. Nevertheless, the real goal though is to obtain definitive data and develop our programs based on having really good solid clinical data in which to continue to develop the product.”
III. 7-14-10 CC: ( http://tinyurl.com/3a4p66c )
DR. ROBERT GARNICK (Head/Regulatory Affairs):
Thanks, Steve. Since I joined Peregrine last year, I’ve worked closely with the team here to develop a comprehensive clinical, regulatory, and manufacturing strategy for bavituximab, similar to what I used successfully for Avastin while I was at Genentech. And as you know, Avastin was the first broad-spectrum anti-cancer agent, and in my mind bavituximab could be potentially very similar to Avastin because of the broad presence of bavituximab phosphatidylserine target in numerous cancers.
We designed this comprehensive regulatory strategy to take advantage of the previous signal-seeking Phase II trials completed by Peregrine in order to design a regulatory strategy for bavituximab that could lead to a rapid regulatory approval. This strategy, which I again used successfully at Genentech for Avastin and Rituxan, targets a first approval in the Refractory Disease setting, followed by an approval in the Frontline setting, which as you all know is much more difficult.
In addition, we are initiating a number of investigator sponsored signal-seeking trials, or ISTs, to further develop bavituximab as a broad spectrum agent similar to Avastin. In order to execute this strategy, we initiated a Phase IIb Refractory NSCLC trial in June of this year [NSCLC: http://clinicaltrials.gov/ct2/show/NCT01138163 ], and today announced a Phase IIb trial in Frontline NSCLC cancer [NSCLC: http://clinicaltrials.gov/ct2/show/NCT01160601 ].
As I described previously, our first approach for approval for bavituximab is a proof of concept refractory NSCLC trial. We are pursuing the refractory disease setting as it is a high unmet medical need, and potentially the fastest route for FDA approval. An excellent recent example of this strategy is that last week Genentech submitted a BLA for Herceptin DM1. This application was based on a single-arm Phase II trial in 110 patients with HER2+ breast cancer with failed previous therapies. Genentech trial measured an objective response rate as the primary endpoint.
Clearly, there is a regulatory pathway for bavituximab if the data from our refractory Phase IIb trial are exceptional. In drug development, well-designed trials have the potential to generate exceptional data, and we need to be prepared to file for Accelerated Approval if we hit the home run scenario. I should point out that if the data from this trial aren’t a home run, but still positive, which is the more likely outcome, we would plan to conduct an addl. Phase III trial to pursue the refractory NSCLC indication for bavituximab.
A third critical aspect of our clinical, regulatory and mfg. strategy is that Peregrine has the major advantage of having its own clinical product manufacturing capability in Avid. While simultaneously developing the regulatory & clinical strategy I just outlined, we also over the last 9 mos. have put significant effort into increasing our manufacturing capability for bavituximab. This capability is now sufficient to support an early approval if we’re lucky enough to be in that situation. I’m very excited about the opportunity to execute this comprehensive strategy and feel fortunate to have the opportunity to work on a 2nd broad-spectrum agent such as bavituximab.
At this point, I would like to just turn your attention for a moment to our 2nd anti-cancer drug, Cotara. As you know, we’re currently completing the Phase II trial of this product in recurrent glioblastoma multiforme (GBM), and expect to have an end of Phase II meeting with the FDA early next year as soon as these data are available, and then be able to effectively plan our Phase III approval strategy.
I’d like to end by again saying how optimistic I am about bavituximab’s potential. The growing body of research points to bavituximab potentially providing a unique & valuable new approach for the treatment of cancer. The clinical results we have to date support moving forward with our regulatory strategy to advance this novel antibody. I will now turn the call over to Joe Shan for an update on our clinical programs designed to support the comprehensive strategy I have just outlined.
7-14-10 Q&A #1: Joe Pantginis (Roth Capital Partners) – Question about IST Pgm:
ROBERT GARNICK: Yes, good question. I think our interactions have really been exceptional, frankly. We’ve really had 2 meetings with the FDA, Type C meetings, so far in moving into our randomized controlled Phase II trial, and both on the CMC side [”Chemistry, Manufacturing and Controls”] and on the clinical side, and I would characterize the interactions at the agency has been extremely encouraging - frankly, more so than I’ve seen in many other experiences that I have had with them. I was frankly pleased and surprised. You know, one of the goals we have is to really have a very collegial respectful, and close relationship with the agency so that our drug development programs go as smoothly as possible. And that’s always been my goal in working with the agency and it has been very successful so far.
[NOTE:
• A TYPE A MEETING is immediately necessary for an otherwise stalled drug dev. program (critical path). Usually, it is reserved for dispute resolution, discussing clinical holds, and special protocol assessment after receipt of FDA’s assessment letter. Type A meetings are scheduled by FDA within 30 days of receipt of request from a sponsor or applicant.
• TYPE B MEETINGS are: Pre-IND meetings; End of Phase I meeting; End of Phase II/pre-Phase III meeting; and Pre-NDA/ BLA meeting. Pre-IND meetings and end of Phase I meetings are granted by FDA when the product is intended to treat life-threatening diseases or severely debilitating illnesses. A Type B meeting is scheduled by FDA within 60 days of receipt of request from a sponsor/applicant.
• TYPE C MEETING: Any meeting regarding the dev. and review of a drug product in humans between sponsor/applicant and FDA other than a Type A or B is classified as a Type C meeting (e.g., scientific meetings). FDA schedules a Type C meeting within 75 days of receipt of the request from the sponsor/applicant. ]
7-14-10 Q&A #4: Ian Somaiya (Piper Jaffray) – Question about Interactions with FDA:
ROB GARNICK: I think the approach we’ve taken with the FDA has been basically I think a very standard one. We’ve provided very detailed data packages, we’ve provided well thought-thru questions, and we have actually gotten, I would say, a lot of reaction from very senior people within the agency, certainly in the oncology area, both on the clinical side and on the CMC side. They really – I think they really appreciated the types and depth of the data that we provided them, and the fact that frankly the company has in the signal-seeking Phase II trials that Peregrine conducted, there is a substantial amount of safety data which we provided from all those trials to the agency, which really answered a lot of their questions having to do with the phosphatidylserine target. And once they became very comfortable that we had that information, and that it was on a reasonably large patient population, I think their interactions with us have really been consistent with that. I mean, generally with the FDA, the more open and sharing you are with information, the more open and willing they are to entertain different options and thought processes with the company, and I personally found the interactions to be extremely positive and productive. And out of those conversations came the trial design for the randomized controlled Phase II that Joe described, and other interactions we have had on the phone, for example, show that the agency is working with us in a very productive, professional and collegial manner. This is what I would expect and what I like to see in interactions with the company. So, you know, I would say our interactions are A+.
IV. 6-29-11 B.CHASE/MINYANVILLE ARTICLE, ”Peregrine Pharma's Secret Weapon [Robert Garnick]”
…Peregrine CEO Steven King credits Garnick, now Head of Regulatory Affairs for the small company, with guiding strategy for testing experimental drugs for brain, lung, and other types of cancer. Garnick has a deep understanding of the FDA process, particularly for approval of biotech treatments, King says. The CEO considers his company fortunate to have someone with Garnick’s long history with the agency. “Rob is the ringmaster,” King says. . .
Dr. Garnick: “I know how the system works -- I know what mistakes you shouldn’t make, and I make sure you don’t make those mistakes. My view is the FDA is my friend. I am not an adversary.”
Case in point: Bavituximab, Peregrine’s leading drug candidate, is being tested for multiple types of cancer, including lung, pancreatic, liver, and breast. But Garnick, after consultation with the FDA, advised the company to pursue approval of the drug as a secondary treatment for lung cancer.
Dr. Garnick: There’s a big unmet need and the drug in early testing appeared to be effective, Garnick says. . . Garnick admits to being a risk taker. As a young man, he drag raced and he still drives race cars. However, he sees promise in both bavituximab and Peregrine’s other drug candidate, Cotara for brain cancer. . . A number of biotech blockbuster products treat multiple conditions. That was the case with Genentech’s Avastin. . .
Dr. Garnick: While it’s a long way from being considered the next Avastin or Rituxan, bavituximab holds promise, Garnick says. He insists he would advise the company to kill the program if he didn’t think it had strong potential. “What I know is how to develop a drug, and I also know how to kill it.”
iHub: http://tinyurl.com/3lgoras
Direct: http://www.minyanville.com/businessmarkets/articles/peregrine-pharmaceuticals-bavituximab-robert-garnick-steven/6/29/2011/id/35458
V. 9-9-11 CC: ( http://tinyurl.com/3bx8eat )
DR. ROBERT GARNICK (Head/Regulatory Affairs):
Thanks, Steve. I'd like to review our overall regulatory strategy before discussing our specific plans for Cotara. We believe both bavituximab & Cotara are active drugs, and we have developed a regulatory strategy to increase the probability of successfully making it through the development and regulatory process. Our strategy is really focused on addressing indications representing high unmet medical needs, which offer a fast path to regulatory approval.
Bavituximab is an antibody that has broad therapeutic potential. We are focusing on 2nd-line NSCLC as a first potentially approvable indication. Our ongoing Phase II trial is a randomized double-blinded placebo-controlled trial in 120 patients. It was designed to have all of the hallmarks of a small registrational study that could be part of a registrational package if our data support Phase III development. We're also conducting a front-line NSCLC trial, which is designed to replicate and confirm the promising data from our prior Phase II single-arm trial. In addition to confirming the prior data in a randomized trial setting, the purpose of this open label trial is to use the interim data to help determine our investments, which we would need to make shortly in preparing for future Phase III development. And if the interim data are consistent with our prior positive data, we will certainly move ahead with Phase III trials and preparations.
As we saw over the last couple of weeks, the most recently approved therapy for NSCLC drugs can in fact receive Accelerated Approval based on objective response rate [ORR] data generated from single-arm studies, and we're very eager to assess bavituximab's potential in our ongoing trials.
[ Dr. Garnick is referring to Pfizer’s crizotinib (Xalkori), which received Acc. Approval on 8-26-11 “for the treatment of patients with locally adv. or metastatic NSCLC that is ALK-positive”. The approval was based on 2 single-arm trials, A:n=136(ORR=50%) & B:n=119(ORR=61%). See http://www.ons.org/news.aspx?id=150 ]
Switching to Cotara, we are making progress preparing for an end of Phase II meeting with the FDA in Q4 of this year. A novel, single-administration approach to treating deadly recurrent GBM, which has shown a promising 8.8-mo. MOS, really helps the stage for what we expect will be a productive meeting with the FDA. Our goal remains to determine the optimum registration path to support registration of Cotara. What do we intend to walk away with following this meeting? First, we need to negotiate a reasonably-sized trial that we, or with a potential partner, are able to enroll within a 24-mo. period. We expect the trial will be multicenter and international, with sites in both the U.S., Europe, and India. Following this FDA meeting, we expect that this information will form our development path and we will communicate this information as it transpires.
I'd like to discuss the progress that has been made in on the Cotara program and then to hit my perspectives on today's data announcement on bavituximab. Regarding the Cotara program, over the last several months, as you know, we have continued our dialogue with FDA with specific emphasis on the next development steps that we need to be taking for this novel approach to treating recurrent glioblastoma multiforme, or GBM. Recently, FDA has provided specific feedback to us regarding our proposed trial design and we, in turn, have submitted our responses back to the agency. This is part of a process that continues and we're looking to develop a study for Phase III that has criteria of enrolling a reasonable number of patients, and a study that can be completed in a 2-year time frame or less in this orphan indication. We believe that having an FDA-reviewed protocol for Phase III is critical to advancing our partnering discussions and/or initiating a pivotal trial on our own. From our perspective, these discussions with FDA, to date, had been extremely positive, with the FDA being quite responsive and very helpful. Overall, the process is progressing very well in my opinion, and I believe a properly designed pivotal trial can be agreed upon and that we will be able to continue moving Cotara closer towards regulatory approval.
At this time, I'd like to provide my personal perspective on the [bavituximab] data that was announced (Front-Line NSCLC trial, Topline ORR/PFS data - abnormally high Ctl-Arm results - http://tinyurl.com/7m9r6ya ] . As I'd like to explain, these data in no way impact our enthusiasm for developing bavituximab as a novel anti-cancer agent or the clinical path that we have established. We have been clear that we do not know fully what to make of these results, given the unusually high control arm results. As Joe mentioned, and I will repeat, bavituximab arm data from this trial was in line with our expectations and consistent with the previous data that we've seen in earlier development programs. But what also adds to the confusion surrounding this data is that discrepancy between the 2 types of analysis, which when taken all together really says that we need to wait for the Overall Survival data, the ultimate endpoint that matters in front-line NSCLC.
VI. 3-9-12 CC: (http://tinyurl.com/7t2xsks )
DR. ROBERT GARNICK (Head/Regulatory Affairs):
• Q&A#3 (Edward Nash – Cowen & Co. – re: First-Line NSCLC trial, OS vs. ORR/PFS):
ROB GARNICK: And just to add another point, in terms of the response rate, I mean, there are a lots that, Iressa for example, was approved, which had actually pretty impressive overall response rates, and it was given the Accelerated Approval based on that, and then when the actual pivotal trials were done in Iressa, it showed no overall survival benefit and FDA recommended pulling it off the market. So I've seen this go both ways. And again, you would like to see, what you'd love to see is a direct linear coloration between response rate & PFS and MOS, but most of the time doesn't work out that way. And that's why FDA really believes that Overall Survival is the most appropriate endpoint for judging the value and benefit of these products we would provide to the patients. So there are a lot of horror stories, I could go to a 100 of horror stories of drugs that had early development issues. A good example was Avastin failed as a monotherapy and I think everyone questioned why would this drug ever work if it didn't work as a monotherapy agent, given the moa that Avastin was designed and expected to have. And yet when it was combined with chemotherapy, it showed really stunning results in colorectal cancer. So again, drug development is all about designing your studies properly and giving the product the best opportunities and seeing where the data actually takes you. So it's kind of the perspective that I have and, hopefully, it provides some value to you.
• Q&A#5 (Stephen Dunn/LifeTech - re: Avastin vs. Bavituximab):
ROB GARNICK: I think it [Bavi] is somewhat similar to Avastin and it's certainly the kind of broad spectrum mechanism of action with respect to, in case of Avastin, anti-VEGF or seeking to combine with VEGF as a neo-vascularization preventative agent vs. being able to bind phosphatidylserine in any number of cancer cells. So, both of them have a lot of kind of broad-spectrum similarities. And I agree with Steve & Joe, that what we really want to do is find where bavituximab has the greatest benefit. And that may not be in a place where Avastin is currently approved. Given that the drug has potentially a good safety profile and it certainly seems to be very active, so it's really a question of finding the right indication through the studies that we're doing, and then to move aggressively & definitively towards an approval in that indication. So I think that's really the kind of drug-dev. program that we're envisioning.
VII. 7-16-12 CC: ( http://tinyurl.com/cs7spbz )
DR. ROBERT GARNICK (Head/Regulatory Affairs):
[PHONE PROBLEM, JOE SHAN READS ROB GARNICK’S PREPARED REMARKS: ]
We've been working very hard and very actively on the next steps in our bavituximab 2nd-Line NSCLC program, 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. What we'd like to see in a Phase III design is something that we can basically replicate from this Phase II that we just completed, but in a larger scale. Now with regard to Cotara, we're continuing our dialogue with the FDA with specific emphasis on the next steps for developing this novel approach to treating recurrent GBM brain cancer. The agency has been very responsive and certainly recognizes the potential importance of this novel drug candidate, and we remain positive that a mutually agreeable design can be reached. At this point, I believe that a solution can be met and if it were not able to be met, it would've been clear to all parties by now. But, having said that, these discussions do take time. And while we've come a long way, the agency knows and recognizes the unmet medical need and the potential of this novel drug candidate. And so, we remain very optimistic that we can come to a final resolution in the coming months. And now I'll turn the call over to Paul.
• Q&A#3 (Charles Duncan/JMP Securities - re: 2nd-Line NSCLC EOP2 FDA Mgt):
To Steve's point, I think we have more than enough data right now to initiate a meeting with FDA. I think as the data matures and the longer it runs out, we'll even have potentially better information. But, with respect to an EOP2 meeting to plan for a Phase III, I think we're really in a very excellent spot right now. And I think we know exactly what we're going to recommend for a trial design for Phase III. And of course, as Steve said, having a partner on board, because this is undoubtedly will be a global trial, we would like to have a partner's input into that information in order to provide that. But 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 Phase II & Phase III data, and this is as compelling Phase II data as I've ever seen. So, I'm very comfortable proposing a meeting with the agency for the 4th quarter of this year. Back over to you, Steve.
VIII. 9-10-12 CC: ( http://tinyurl.com/8nkwrml )
...Dr. Robert Garnick (Head/Reg.): "As you have just heard from Joe, the data we announced last week [9-7-12/Gerber/Chicago] 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. We took an extraordinary amount of care in developing this Phase II trial design and conferred with clinical experts & regulatory agencies, including the FDA, in the design of this rigorous clinical trial. Peregrine chose to conduct this trial to definitively establish the proof of concept to bavituximab and now plans to potentially include this data as part of a registrational package. Having personally been involved in the evaluation of over 30 Phase II trials over my career, none of which ever achieved statistical significance, including many of today's blockbuster biotech products, I am personally extremely pleased with the quality of this data and the clarity with respect to advancing bavituximab in Phase III trials which it provides. Our next steps are to present the data you saw last week to global regulatory authorities as part of the formal End of Phase II [EOP2] meetings from which we anticipate gaining concurrence into the planning & execution of a pivotal trial program. Normally, it takes approx. 60 days to arrange such EOP2 meetings, and following these meetings to submit IND amendments for the Phase III and initiate the trial by mid-2013.
Touching on Cotara for a moment, Peregrine and the FDA are continuing to have positive discussions about the design & execution of a pivotal trial in GBM. We appreciate your patience as we just strive to gain the most advantageous strategy for both parties for this novel and potentially important drug candidate."
• Q&A#1 (Joe Pantginis – Roth Capital Partners)
RG: I think the regulators will be very excited. Certainly, the FDA had a lot of input into our trial design, and I think they gave us some a very wise counsel and I think this is exactly the kind of study that they would like to see. And certainly it provides for us the clarity, which you rarely have in Phase II trials, to decide to go clearly into a Phase III study and to actually really focus on replicating what we've just done. And I think that de-risks the program enormously, and really gives us a lot of confidence in how to go forward.
• Q&A#2 (Charles Duncan - JMP Securities):
RG: Just a quick follow-on to what Joe said, I think the std. for approval for a drug in 2nd-Line NSCLC will be another trial that would replicate this one, and as Steve said, as closely as possible. I'm not sure what else we would do different other than increase the “N” of the patients. And once we have that data, the combination of information between this trial and the next one, the pivotal Phase III - the plan would be that, that would be the data that we'll need to achieve an approval. I think if we achieve anywhere near the degree of clarity that we just obtained, I think this will be a pretty straightforward approval process. I'm sure the FDA would agree with me; the FDA as well as other global regulatory authorities would agree, that this is a pretty straightforward design and we really just need to obtain concurrence on it and then to begin our execution by mid-2013.
• Q&A#3 (George Zavoico - MLV):
RG: Following on to what Steve said, one of the things that's always attracted me to bavituximab is the fact that it does have such a potential plethora of possible indications. And as you pointed out, we really went into NSCLC based on the signal-seeking data that we had originally gotten in early Phase I & II studies. I think that was a very wise way to go forward. Just like Avastin, as you'll remember, Avastin was first developed in colorectal cancer and then, having a broad anti-angiogenesis moa, we then were able to develop that drug into multiple other cancers where, theoretically, its moa would still apply. And of course, Avastin has gone on to become an extremely profitable and valuable drug in the oncology arena. So, we're thinking about a very, very similar strategy for bavituximab - basically, using these ISTs to guide you in terms of where you're most likely to succeed and in what combination of drugs to combine with bavituximab. I think, luckily, we're seeing very good safety signals with the drug, and that's really an important aspect that helps us to decide how broad the drug action can be applied. So using the ISTs and then potentially other signal-seeking Phase IIs, we plan to really maximize the benefit of this particular product. And I think we've got a broad potential and a bright future.
IX. 12-10-12 CC: ( http://tinyurl.com/a954bmw )
...Dr. Robert Garnick (Head/Reg.): "I'm pleased to report that as we announced last week, Peregrine has reached an agreement with the FDA on the clinical design aspects of a single registration trial for Cotara patients with recurrent glioblastoma multiforme, or GBM. As such, this represents a major step towards proceeding with our proposed randomized trial design, which compares 2 dose levels of Cotara in up to 300 patients. The trial design allows for interim analysis, with the potential to stop patient accrual based on predicted success or futility. This in turn could result in an improved development time line. With this news in having been granted orphan drug status and Fast Track designation for the treatment of GBM by the U.S. FDA and orphan drug designation by the EMA, Cotara has a much clearer path towards a pivotal Phase III trial.”
• Q&A#2 (George Zavoico - MLV):
RG: As Steve alluded, the efforts in conducting a global trial means that we not only have to have agreement on the trial design from FDA but, as well, from EMA, which has a very different process than the FDA does and as well as potentially other sovereign entities around the world. And the key to conducting this trial, given its size, is to have enough sites enrolled with enough patients so you can do this in a shorter time frame as possible. So we're pivoting right now and following the discussions with the FDA to discuss the same trial design plan with the European agency and as well as potentially other global regulatory authorities. So, it's going to take a lot of effort and a lot of time, but we're very confident that we're going to be able to come up with one unified trial that will accomplish all of our goals.
X. 2-19-13 PR: [Topline Data Update from 2nd-Line NSCLC Trial after data discrepancies review - 60% improvement in MOS: 3mg=11.7mos. vs. 7.3mos. for CTL-arm(combined 1mg & Doxy+placebo arms), HR=.73, p=.217 http://tinyurl.com/ansqcea ]
...Dr. Robert Garnick (Head/Reg.): “From a regulatory standpoint, this trial achieved its three main goals in preparing for a Phase III trial by identifying a dose, augmenting the existing set of favorable bavituximab safety data, and demonstrating good signs of survival effect in patients. With these data in hand, we are now preparing for additional discussions with regulatory bodies including an end-of-Phase II meeting with the FDA by mid-year with an overall goal of being in a position to initiate a pivotal trial near year-end."
XI. 3-12-13 CC: ( http://tinyurl.com/c48osut )
...Dr. Robert Garnick (Head/Reg.): "The Clinical & Regulatory Affairs group has had a really busy quarter, and as you have heard, the next quarter will certainly be no different. With respect to our lead indication, bavituximab, in 2nd-Line NSCLC, we are in the midst of planning for a meeting with the FDA some time during Q2/2013 to discuss the size & design of our proposed Phase III trial. What I can tell you is given the reanalysis of the Phase II data that both Steve & Joe have alluded to, we anticipate that this trial will be in the 600-pt. range and could involve an interim analysis. Our goal is to initiate a Phase III trial by the end of the year. I would like to point out that our bavituximab Phase II trial accomplished what it was designed to do, in that it achieved the determination of the intended dose for Phase III, expanded our understanding of the favorable safety profile of bavituximab, and produced a clear signal of clinical efficacy. Having accomplished these 3 critical things, we feel confident in moving the bavituximab 3mg dose into Phase III, that this dose has a favorable safety profile, and has demonstrated promising signs of clinical activity. With this data in hand, we feel that we have a strong package of information ready for discussion with the FDA and are confident that this program should move forward into late-stage development.”
• Q&A#1 (Joe Pantginis – Roth Capital Partners)
RG: We have quite a whole plethora of regulatory things that we're dealing with right now to get ready for the EOP2 meeting with FDA. And that meeting, as you know, really encompasses all of the information we have on the drug. We're tying up all the bows right now on the Chemistry, Manufacturing & Controls section of the IND and actually ready to make a submission to FDA shortly to cover that section of Phase II, of which there is no surprises and which has gone extremely well. So, we can certainly make the material; we can make it reliably; we can make it at an economical level. And then, of course, we have to deal with all the issues on the clinical side. And as Steve said, the 3 things you really need to know for EOP2 with FDA is that you need, and the actual purpose of Phase II, is to determine the dose that you're going to take forward into Phase III, and we certainly have done that with the 3mg dose. The next is the summary of all the safety data, and we’ve really integrated all the safety information from our Phase I and previous Phase II trials, as well as the randomized controlled 2nd-Line trial. And we'll be presenting that entire summary and safety profile of the drug, which is also extremely good and actually better than we anticipated. And the 3rd piece, which is important, is the efficacy piece, and as I point out to many people, there are very few and far between Phase II trials that ever show statistical significance in efficacy - that's an absolutely unbelievable hurdle for a Phase II product. And, what you're really looking for is an ability to describe that you do have clinical efficacy, and as Joe has said, showing 11.7 mos. for the 3mg arm and a difference in the pooled dataset for the product of 7.3 mos. when you combine the control & the placebo, definitely gives you the indication that in overall survival, we have a potentially highly efficacious product. So, I think the 3 critical things have been identified. And again, we're going to discuss the entire situation of the investigation with the agency, as well as all the data I just described, and we feel pretty confident that we have enough data to move the product effectively into Phase III.
XII. 5-20-13 PR: [ FDA Approves Bavituximab Ph.III Design for 2L/NSCLC; 600-pt trial to begin by y/e’13 http://tinyurl.com/n3dxtm6 ]
RG: "We are very pleased with the outcome from this highly collaborative effort with the FDA which allows us to proceed with our proposed Phase III clinical trial. We believe this trial, when combined with bavituximab's supporting data to date, could be sufficient to support a future BLA submission."
XIII. 7-11-13 CC: ( http://tinyurl.com/khpokw6 )
...Dr. Robert Garnick (Head/Reg.): “From a regulatory standpoint, I'm very pleased with the progress made during this quarter as we achieved 2 major goals in our most advanced program. First, the positive data that emerged from our 2nd-Line NSCLC trial provided additional safety, as well as clinically meaningful efficacy data needed to advance the program. Second, the reaching of an agreement with the FDA on our proposed clinical trial design was the result of a very successful and highly collaborative effort with the agency, which allowed us to proceed. Since our last quarterly conference call, we have had very positive interactions with FDA concerning our production processes and capability to manufacture Phase III material, and ultimately, bavituximab for the market, as a prelude to the EOP2 meeting, which was, by design, focused on our Phase III clinical plans. We believe this Phase III trial, along with the large amount of supporting data to date, could be sufficient to support a future biologics license application (BLA) submission. The next steps from a regulatory perspective are to initiate discussions with ex-U.S. regulatory agencies, such as the EMA, in order to facilitate the start of the global Phase III by year's end.”
Q&A/Roy Buchanan/Piper Jaffray re: “EOP2 FDA Meeting”…
RG: “…It was quite benign. They liked the plan we proposed. They thought it was well thought through, and there were absolutely no sticky issues whatsoever.”
XIV. 12-10-13 CC: ( http://tinyurl.com/mw776mk )
...Dr. Robert Garnick (Head/Reg.): “As you have just heard from Joe, the SUNRISE global Phase III trial is close to the beginning of its enrollment. This is an exciting time for this program, a point that we achieved following the execution of a great number of activities that relied on close collaboration with many worldwide regulatory agencies. From a regulatory perspective, this global trial was set to roll out first in the United States, followed by sites throughout Europe and the Asia Pacific region. Our interaction with these countries and regions has been a major focus for our regulatory department for the past several months. These discussions, including those with the FDA and various European regulatory agencies have been extremely positive, and I am pleased to say that the process of globally filing our Phase III study protocols is moving ahead very smoothly. We are also looking forward to further meetings with these regulatory authorities throughout the course of the trial. I'm very pleased with how these tasks have been executed to date, and believe that we have the necessary people and qualified third parties in place to support the SUNRISE trial.”
XV. 1-6-14 PR: [Peregrine Receives FDA Fast Track Designation for Its Immunotherapy Bavituximab for 2nd-Line NSCLC http://tinyurl.com/l799ukk ]
RG: "The Fast Track Designation is a milestone for the SUNRISE trial program and represents a step closer to bringing bavituximab to the market. We are very pleased that the FDA has recognized the potential of this novel therapy as a treatment for this serious and devastating type of cancer and look forward to working closely with them to ensure the most efficient review process."
XVI. 3-10-14 CC: ( http://tinyurl.com/kh9cnrg )
Q&A, Graig Suvannavejh/MLV – re: “competitive landscape”…
RG: “…Bavituximab really represents a unique opportunity, and I don't think you can draw any conclusions from failed Phase III trials from other companies' products because basically, a lot of drugs were taken into Phase III, basically, on much less compelling data than we were able to achieve with bavituximab. So, I think we're actually very well-poised, based on our data, to see potentially a very successful Phase III trial. And again, I wouldn't draw any conclusions on other people's trials. We're really in a very good position because based on our data - we've just recently achieved global regulatory approvals for going into Phase III based on the strength of the data - the total data package that we presented. So, I think that's quite a testimony to the data package that we've been able to achieve so far. And of course, we'll see how everything progresses during the SUNRISE trial, which now is ready to go.”
= = = = = = = = = = = = = = =
BusinessWeek EXECUTIVE PROFILE
Robert Garnick Ph.D.
Head of Regulatory Affairs, Peregrine Pharmaceuticals Inc.
Age: 60 --
BACKGROUND
Robert L. Garnick, Rob, Ph.D., has been Head of Regulatory Affairs at Peregrine Pharmaceuticals Inc., since October 19, 2009. Dr. Garnick is responsible for overseeing Peregrine's interactions with the U.S. FDA and regulatory agencies around the world, and leads the development of the Peregrine Pharmaceuticals's regulatory strategies for advancing its novel monoclonal antibody-based treatments for cancer and infectious diseases. Dr. Garnick has over 30 years of experience in drug and biologic pharmaceutical development, including 24 years at Genentech helping to build the biotechnology industry. He served as Senior Vice President of Regulatory, Quality & Compliance at Genentech Inc. since February 2001. During his 24-year career at Genentech, he was responsible for 17 new product approvals including most of the Genentech's top selling monoclonal antibody therapeutics such as Rituxan, Herceptin, Avastin and Lucentis. Previously, Dr. Garnick served as VP/Regulatory Affairs from Feb.1998 to Feb.2001, VP/Quality from Apr.1994 to Feb.1998, Senior Director, Quality Control from 1990-1994 and Director, Quality Control from 1988-1990. He joined Genentech in Aug.1984 from Armour Pharmaceutical, where he held various positions. After leaving Genentech in 2008, Dr. Garnick founded Lone Mountain Biotechnology and Medical Devices, Inc. [ http://lonemountainbiotechnology.com ], a successful company specializing in drug and device consulting where he remains as President and CEO. Dr. Garnick has also been extensively involved with the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). He has extensive experience in analytical methodology, process validation, and the regulatory review process in the U.S. and Europe. Dr. Garnick has authored numerous scientific papers and is a frequent keynote speaker at pharmaceutical Industry conferences and events.
= = = = = =
Genentech 10-K iss. 2-23-2007:
Robert L. Garnick, Ph.D. was appointed Senior Vice President, Regulatory, Quality and Compliance of Genentech in Feb.2001. Previously, he served as Vice President, Regulatory Affairs from Feb.1998 to Feb.2001, Vice President, Quality from Apr.1994 to Feb.1998, Senior Director, Quality Control from 1990-1994 and Director, Quality Control from 1988-1990. He joined Genentech in Aug.1984 from Armour Pharmaceuticals, where he held various positions.
http://www.gene.com/gene/ir/downloadDoc.do?id=3461
= = = = = = = = =FULL MINYANVILLE ARTICLE:
6-29-11/Minyanville: ”Peregrine Pharma's Secret Weapon [Robert Garnick]”
By Brett Chase [Bio: http://www.minyanville.com/gazette/bios.htm?bio=361 ]
• Robert Garnick, a veteran of Genentech, is steering the biotech company through FDA waters. Can he repeat his past success at the small cancer drug company?
http://www.minyanville.com/businessmarkets/articles/peregrine-pharmaceuticals-bavituximab-robert-garnick-steven/6/29/2011/id/35458
Peregrine Pharmaceuticals (PPHM) is an early-stage company working toward approval of its first product, a cancer drug. Navigating the regulatory waters alone can be daunting for a small company. But Peregrine has a seasoned skipper for the important job: Robert Garnick, a 24-year veteran of Genentech. In his 2 decades at the biotech company (now part of Roche), Garnick oversaw 17 product approvals, including for top-selling drugs Rituxan, Herceptin, Avastin, and Lucentis.
Peregrine CEO Steven King credits Garnick, now Head of Regulatory Affairs for the small company, with guiding strategy for testing experimental drugs for brain, lung, and other types of cancer. Garnick has a deep understanding of the FDA process, particularly for approval of biotech treatments, King says. The CEO considers his company fortunate to have someone with Garnick’s long history with the agency.
“Rob is the ringmaster,” King says.
To be sure, drugs have to work and they have to clearly demonstrate their safety and effectiveness in years of studies, but Garnick say sometimes companies have promising medicines that get scrapped for the wrong reasons. The 61-year-old biotech pioneer says companies need to figure out early on if a drug is approvable before moving forward. Taking cues from the FDA can help that process. A change in strategy may be needed to win an initial approval for a new treatment.
“I know how the system works -- I know what mistakes you shouldn’t make, and I make sure you don’t make those mistakes,” Garnick says. “My view is the FDA is my friend. I am not an adversary.”
Case in point: Bavituximab, Peregrine’s leading drug candidate, is being tested for multiple types of cancer, including lung, pancreatic, liver, and breast. But Garnick, after consultation with the FDA, advised the company to pursue approval of the drug as a secondary treatment for lung cancer. There’s a big unmet need and the drug in early testing appeared to be effective, Garnick says. The company is studying the drug in the 2nd of 3 phases of human testing usually needed for a drug’s approval.
Investors are not yet on board with this early-stage company. The shares are down 19% this year, trading at $1.86 midday Wednesday. The stock is down 94% since its public offering in 1996.
Garnick admits to being a risk taker. As a young man, he drag raced and he still drives race cars. However, he sees promise in both bavituximab and Peregrine’s other drug candidate, Cotara for brain cancer. Cotara is being studied for the treatment of gliboblastoma multiforme, or GBM. The drug is infused in a patient’s head and has been studied in 2 phases of human trials. The company hopes to meet with the FDA later this year about design of a so-called Phase III trial. But Cotara is designed for treatment of one disease, while bavituximab is being tested for multiple conditions. In addition to the various types of cancer treatment being researched, the drug is being studied for hepatitis C.
A number of biotech blockbuster products treat multiple conditions. That was the case with Genentech’s Avastin, a drug that has potential to treat multiple types of cancer by attacking tumors. Avastin is approved to treat colon, lung, brain, and kidney cancers. It’s also approved to treat advanced breast cancer but the FDA proposed rescinding that approval and the drug is the subject of a 2-day hearing in Washington this week.
While it’s a long way from being considered the next Avastin or Rituxan (a treatment for multiple cancers and rheumatoid arthritis), bavituximab holds promise, Garnick says. He insists he would advise the company to kill the program if he didn’t think it had strong potential. “What I know is how to develop a drug, and I also know how to kill it,” Garnick says.
*end*
Copyright 2011, Minyanville Media, Inc.
= = = = = = = A COUPLE OF EXAMPLES OF WHAT ROB GARNICK IS GOOD AT:
2-26-04 - ATTACHMENT D – AVASTIN APPROVAL LETTER
From: FDA, To: Dr. Robert Garnick
FOLLOWED BY AVASTIN EXPANSION APPROVAL AS 2ND-LINE VS. MET. COLORECTAL CANCER:
6-20-06: From: FDA
Dear Dr. Garnick:
http://www.peregrineinc.com/about-us/management-team.html
Oldest-to-Newest…
I. Oct 19, 2009: Peregrine announced that Dr. Robert Garnick has joined the company as the Head of Regulatory Affairs. Dr. Garnick was formerly the Senior VP of Regulatory, Quality & Compliance at Genentech…
• During his 24-year career at http://clinicaltrials.gov/ct2/show/NCT01138163 Genentech, he was responsible for 17 new product approvals including most of the company's top selling monoclonal antibody therapeutics such as Rituxan, Herceptin, Avastin, and Lucentis… In this role, Dr. Garnick was responsible for all the regulated aspects of Genentech's business including drug development, commercial production and promotional and labeling compliance.
• Dr. Garnick will be responsible for overseeing Peregrine's interactions with the U.S. FDA and regulatory agencies around the world, and will lead the development of the company's regulatory strategies for advancing its novel monoclonal antibody-based treatments for cancer and infectious diseases.
SAID DR. GARNICK:
• "Peregrine's bavituximab & Cotara products represent the kind of innovation that made my drug development work so exciting and fulfilling at Genentech.”
• “Peregrine's PS-targeting antibodies such as bavituximab represent an entirely new mechanism that has already shown considerable promise for the treatment of cancer and infectious diseases, while Cotara has shown promising survival benefits in patients suffering from the worst form of brain cancer. I welcome the opportunity to work with the Peregrine team to help advance these promising candidates through the clinical & regulatory process."
http://tinyurl.com/yga7z4x
II. 12-10-09 CC: ( http://tinyurl.com/y9tr3q3 )
DR. ROBERT GARNICK (HEAD OF REGULATORY AFFAIRS):
”Thank you, Steve, and thank you everyone for joining this call. I am really very pleased to be here with you today, since I’ve been working with Peregrine for only a few months. In this call, I’d like to focus on sharing with some general observations that I have made on Peregrine and its product pipeline.
Let me start by telling a little bit about myself. I’ve spent all of my professional career working in the area of drug development, focusing on the rigorous scientific, clinical, and regulatory assessments that must be completed before any potential new product or medical device can be marketed. As you know, this is typically a very long complex and challenging process. However, the rewards for both drug developers, investors, and most importantly the patients who so desperately need these new products, can be quite substantial. In my own career, I’ve had the good fortune to spend over 32 years in the pharmaceutical industry, 24 years of which were at Genentech, where I was part of the birth of the biotechnology industry. I joined Genentech in 1984, and had the unique opportunity to literally grow up with the company, and played a significant role in the development of its products. At Genentech, I was deeply involved in obtaining marketing approval for 17 drug products and 3 manufacturing facilities, including such anticancer blockbusters as Rituxan for non-Hodgkin Lymphoma, Herceptin for breast cancer, Avastin for colorectal cancer and non-small cell lung cancer, and Lucentis for age-related macular degeneration. After heading up Genentech’s formal regulatory efforts for 15 years and growing my own department to over 1,300 people, in 2008 I decided it was time to retire from the corporate life of a large company and form the biotechnology specialty consulting company through which I was very fortunate to meet the excellent folks here at Peregrine.
After carefully studying the company’s Phosphatidylserine-Targeting Antibody platform and its lead product candidate bavituximab, I became extremely excited and agreed to work with Steve and his team to help guide the drug’s development, focusing specifically on how we might accelerate its progress towards marketing approval.
I’d like to say that bavituximab reminds me a great deal of a similar and very important monoclonal antibody, Rituxan, because of the biological elegance of its mechanism of action. Because of the similarity, the regulatory approach I’m recommending to Peregrine for bavituximab is very consistent with the approach we took at Genentech for obtaining the approval of Rituxan. I’m extremely optimistic that bavituximab may represent a unique and valuable new approach to the treatment of advanced refractory cancer in combination with chemotherapy or radiation, and based on its mechanism of action may potentially be useful in anti-viral and other indications as well. In addition to my personal scientific interest in the potential Peregrine’s technology, I’ve also been very impressed with the Peregrine team and the mix of professionalism, enthusiasm and commitment that are so reminiscent of my early days of Genentech.
As Steve mentioned, this is a very exciting time for Peregrine’s drug development programs. We have recently completed patient enrollment in 3 signal seeking bavituximab Phase II cancer trails, as well as an earlier-stage bavituximab cancer & Cotara brain cancer studies, and we eagerly anticipate having data starting to come in from these studies in the next few months. This sets the stage for planning our next set of bavituximab cancer trials and we are actively embarking on that progress. Our goal is to implement a clinical and regulatory strategy, that will maximize our chances of getting that bavituximab approved and to do so in the shortest feasible timeframe.
We’re in the process of designing a randomized blinded and placebo controlled Phase II clinical study for bavituximab in 2nd-line NSCLC. This type of study is typically the gold standard in the U.S. for drug development and this study is intended to play a major role in our future approval strategy for this product. Just a week ago, we had a very successful meeting with FDA to discuss a number of clinical questions in order to help us design the Phase II program in NSCLC, and the team and I are very pleased with how well it went. It’s not appropriate to reveal the details of this meeting, but suffice it to say that we were encouraged by the FDA’s positive response and by the fact that we have received such excellent advice as to what the Phase II trials, which I just described, should look like. I should say that, while NSCLC is our lead indication, we are actively exploring other clinical trials in other refractory solid tumor cancers, for which bavituximab may hold particular promise. We look forward to sharing more about our emerging bavituximab cancer, clinical, and regulatory strategy with you in the coming months.
I’m just getting to know, the Cotara program and so I’ll hold my comments for now. However, it is noteworthy that I feel that this drug holds considerable promise for the treatment of such lethal diseases as glioblastoma multiforme [GBM], which unfortunately have so few current treatment options. In view of its sizable long-term patient safety database and the promising efficacy results observed in some patients, we’ll be exploring ways in which Cotara might be advanced towards market approval more rapidly and cost effectively.
The growing body of scientific evidence that phosphatidylserine-targeting antibodies may have application in anti-viral and other anti-infective indications and Peregrine’s success in attracting the support of the biodefense establishment and multiple collaborators to further explore their anti-viral potential is encouraging. I look forward to getting more involved in this program in the appropriate time. In summary, I think this is a very exciting time to be at Peregrine, as it moves ahead its programs to the next critical stage of development, and I very much look forward to working with the Peregrine team to advance these promising drug candidates. Back to you, Steve.”
12-10-09 CC/Q&A:
Question by R.Adams: “…if the results in the 3 Bavi Ph.2 trails recently completed, especially tumor shrinkage, were achieved in the 1st half of the definitive trials you’re now planning for lung cancer, would you be well positioned to apply for accelerated approval?”
Dr. Rob Garnick: “As you know, I’ve actually done accelerated approvals in the past and certainly, as Steve said, we want to be positioned such that if the data is striking and very compelling that we would be in a position to apply for that and that as you know takes a lot of coordination in across the company, not just in the clinical & regulatory side, but in the manufacturing & quality operations. We are actually making sure that should such an opportunity occur, that we would be in an excellent position in order to take advantage of that. Nevertheless, the real goal though is to obtain definitive data and develop our programs based on having really good solid clinical data in which to continue to develop the product.”
III. 7-14-10 CC: ( http://tinyurl.com/3a4p66c )
DR. ROBERT GARNICK (Head/Regulatory Affairs):
Thanks, Steve. Since I joined Peregrine last year, I’ve worked closely with the team here to develop a comprehensive clinical, regulatory, and manufacturing strategy for bavituximab, similar to what I used successfully for Avastin while I was at Genentech. And as you know, Avastin was the first broad-spectrum anti-cancer agent, and in my mind bavituximab could be potentially very similar to Avastin because of the broad presence of bavituximab phosphatidylserine target in numerous cancers.
We designed this comprehensive regulatory strategy to take advantage of the previous signal-seeking Phase II trials completed by Peregrine in order to design a regulatory strategy for bavituximab that could lead to a rapid regulatory approval. This strategy, which I again used successfully at Genentech for Avastin and Rituxan, targets a first approval in the Refractory Disease setting, followed by an approval in the Frontline setting, which as you all know is much more difficult.
In addition, we are initiating a number of investigator sponsored signal-seeking trials, or ISTs, to further develop bavituximab as a broad spectrum agent similar to Avastin. In order to execute this strategy, we initiated a Phase IIb Refractory NSCLC trial in June of this year [NSCLC: http://clinicaltrials.gov/ct2/show/NCT01138163 ], and today announced a Phase IIb trial in Frontline NSCLC cancer [NSCLC: http://clinicaltrials.gov/ct2/show/NCT01160601 ].
As I described previously, our first approach for approval for bavituximab is a proof of concept refractory NSCLC trial. We are pursuing the refractory disease setting as it is a high unmet medical need, and potentially the fastest route for FDA approval. An excellent recent example of this strategy is that last week Genentech submitted a BLA for Herceptin DM1. This application was based on a single-arm Phase II trial in 110 patients with HER2+ breast cancer with failed previous therapies. Genentech trial measured an objective response rate as the primary endpoint.
Clearly, there is a regulatory pathway for bavituximab if the data from our refractory Phase IIb trial are exceptional. In drug development, well-designed trials have the potential to generate exceptional data, and we need to be prepared to file for Accelerated Approval if we hit the home run scenario. I should point out that if the data from this trial aren’t a home run, but still positive, which is the more likely outcome, we would plan to conduct an addl. Phase III trial to pursue the refractory NSCLC indication for bavituximab.
A third critical aspect of our clinical, regulatory and mfg. strategy is that Peregrine has the major advantage of having its own clinical product manufacturing capability in Avid. While simultaneously developing the regulatory & clinical strategy I just outlined, we also over the last 9 mos. have put significant effort into increasing our manufacturing capability for bavituximab. This capability is now sufficient to support an early approval if we’re lucky enough to be in that situation. I’m very excited about the opportunity to execute this comprehensive strategy and feel fortunate to have the opportunity to work on a 2nd broad-spectrum agent such as bavituximab.
At this point, I would like to just turn your attention for a moment to our 2nd anti-cancer drug, Cotara. As you know, we’re currently completing the Phase II trial of this product in recurrent glioblastoma multiforme (GBM), and expect to have an end of Phase II meeting with the FDA early next year as soon as these data are available, and then be able to effectively plan our Phase III approval strategy.
I’d like to end by again saying how optimistic I am about bavituximab’s potential. The growing body of research points to bavituximab potentially providing a unique & valuable new approach for the treatment of cancer. The clinical results we have to date support moving forward with our regulatory strategy to advance this novel antibody. I will now turn the call over to Joe Shan for an update on our clinical programs designed to support the comprehensive strategy I have just outlined.
7-14-10 Q&A #1: Joe Pantginis (Roth Capital Partners) – Question about IST Pgm:
ROBERT GARNICK: Yes, good question. I think our interactions have really been exceptional, frankly. We’ve really had 2 meetings with the FDA, Type C meetings, so far in moving into our randomized controlled Phase II trial, and both on the CMC side [”Chemistry, Manufacturing and Controls”] and on the clinical side, and I would characterize the interactions at the agency has been extremely encouraging - frankly, more so than I’ve seen in many other experiences that I have had with them. I was frankly pleased and surprised. You know, one of the goals we have is to really have a very collegial respectful, and close relationship with the agency so that our drug development programs go as smoothly as possible. And that’s always been my goal in working with the agency and it has been very successful so far.
[NOTE:
• A TYPE A MEETING is immediately necessary for an otherwise stalled drug dev. program (critical path). Usually, it is reserved for dispute resolution, discussing clinical holds, and special protocol assessment after receipt of FDA’s assessment letter. Type A meetings are scheduled by FDA within 30 days of receipt of request from a sponsor or applicant.
• TYPE B MEETINGS are: Pre-IND meetings; End of Phase I meeting; End of Phase II/pre-Phase III meeting; and Pre-NDA/ BLA meeting. Pre-IND meetings and end of Phase I meetings are granted by FDA when the product is intended to treat life-threatening diseases or severely debilitating illnesses. A Type B meeting is scheduled by FDA within 60 days of receipt of request from a sponsor/applicant.
• TYPE C MEETING: Any meeting regarding the dev. and review of a drug product in humans between sponsor/applicant and FDA other than a Type A or B is classified as a Type C meeting (e.g., scientific meetings). FDA schedules a Type C meeting within 75 days of receipt of the request from the sponsor/applicant. ]
7-14-10 Q&A #4: Ian Somaiya (Piper Jaffray) – Question about Interactions with FDA:
ROB GARNICK: I think the approach we’ve taken with the FDA has been basically I think a very standard one. We’ve provided very detailed data packages, we’ve provided well thought-thru questions, and we have actually gotten, I would say, a lot of reaction from very senior people within the agency, certainly in the oncology area, both on the clinical side and on the CMC side. They really – I think they really appreciated the types and depth of the data that we provided them, and the fact that frankly the company has in the signal-seeking Phase II trials that Peregrine conducted, there is a substantial amount of safety data which we provided from all those trials to the agency, which really answered a lot of their questions having to do with the phosphatidylserine target. And once they became very comfortable that we had that information, and that it was on a reasonably large patient population, I think their interactions with us have really been consistent with that. I mean, generally with the FDA, the more open and sharing you are with information, the more open and willing they are to entertain different options and thought processes with the company, and I personally found the interactions to be extremely positive and productive. And out of those conversations came the trial design for the randomized controlled Phase II that Joe described, and other interactions we have had on the phone, for example, show that the agency is working with us in a very productive, professional and collegial manner. This is what I would expect and what I like to see in interactions with the company. So, you know, I would say our interactions are A+.
IV. 6-29-11 B.CHASE/MINYANVILLE ARTICLE, ”Peregrine Pharma's Secret Weapon [Robert Garnick]”
…Peregrine CEO Steven King credits Garnick, now Head of Regulatory Affairs for the small company, with guiding strategy for testing experimental drugs for brain, lung, and other types of cancer. Garnick has a deep understanding of the FDA process, particularly for approval of biotech treatments, King says. The CEO considers his company fortunate to have someone with Garnick’s long history with the agency. “Rob is the ringmaster,” King says. . .
Dr. Garnick: “I know how the system works -- I know what mistakes you shouldn’t make, and I make sure you don’t make those mistakes. My view is the FDA is my friend. I am not an adversary.”
Case in point: Bavituximab, Peregrine’s leading drug candidate, is being tested for multiple types of cancer, including lung, pancreatic, liver, and breast. But Garnick, after consultation with the FDA, advised the company to pursue approval of the drug as a secondary treatment for lung cancer.
Dr. Garnick: There’s a big unmet need and the drug in early testing appeared to be effective, Garnick says. . . Garnick admits to being a risk taker. As a young man, he drag raced and he still drives race cars. However, he sees promise in both bavituximab and Peregrine’s other drug candidate, Cotara for brain cancer. . . A number of biotech blockbuster products treat multiple conditions. That was the case with Genentech’s Avastin. . .
Dr. Garnick: While it’s a long way from being considered the next Avastin or Rituxan, bavituximab holds promise, Garnick says. He insists he would advise the company to kill the program if he didn’t think it had strong potential. “What I know is how to develop a drug, and I also know how to kill it.”
iHub: http://tinyurl.com/3lgoras
Direct: http://www.minyanville.com/businessmarkets/articles/peregrine-pharmaceuticals-bavituximab-robert-garnick-steven/6/29/2011/id/35458
V. 9-9-11 CC: ( http://tinyurl.com/3bx8eat )
DR. ROBERT GARNICK (Head/Regulatory Affairs):
Thanks, Steve. I'd like to review our overall regulatory strategy before discussing our specific plans for Cotara. We believe both bavituximab & Cotara are active drugs, and we have developed a regulatory strategy to increase the probability of successfully making it through the development and regulatory process. Our strategy is really focused on addressing indications representing high unmet medical needs, which offer a fast path to regulatory approval.
Bavituximab is an antibody that has broad therapeutic potential. We are focusing on 2nd-line NSCLC as a first potentially approvable indication. Our ongoing Phase II trial is a randomized double-blinded placebo-controlled trial in 120 patients. It was designed to have all of the hallmarks of a small registrational study that could be part of a registrational package if our data support Phase III development. We're also conducting a front-line NSCLC trial, which is designed to replicate and confirm the promising data from our prior Phase II single-arm trial. In addition to confirming the prior data in a randomized trial setting, the purpose of this open label trial is to use the interim data to help determine our investments, which we would need to make shortly in preparing for future Phase III development. And if the interim data are consistent with our prior positive data, we will certainly move ahead with Phase III trials and preparations.
As we saw over the last couple of weeks, the most recently approved therapy for NSCLC drugs can in fact receive Accelerated Approval based on objective response rate [ORR] data generated from single-arm studies, and we're very eager to assess bavituximab's potential in our ongoing trials.
[ Dr. Garnick is referring to Pfizer’s crizotinib (Xalkori), which received Acc. Approval on 8-26-11 “for the treatment of patients with locally adv. or metastatic NSCLC that is ALK-positive”. The approval was based on 2 single-arm trials, A:n=136(ORR=50%) & B:n=119(ORR=61%). See http://www.ons.org/news.aspx?id=150 ]
Switching to Cotara, we are making progress preparing for an end of Phase II meeting with the FDA in Q4 of this year. A novel, single-administration approach to treating deadly recurrent GBM, which has shown a promising 8.8-mo. MOS, really helps the stage for what we expect will be a productive meeting with the FDA. Our goal remains to determine the optimum registration path to support registration of Cotara. What do we intend to walk away with following this meeting? First, we need to negotiate a reasonably-sized trial that we, or with a potential partner, are able to enroll within a 24-mo. period. We expect the trial will be multicenter and international, with sites in both the U.S., Europe, and India. Following this FDA meeting, we expect that this information will form our development path and we will communicate this information as it transpires.
I'd like to discuss the progress that has been made in on the Cotara program and then to hit my perspectives on today's data announcement on bavituximab. Regarding the Cotara program, over the last several months, as you know, we have continued our dialogue with FDA with specific emphasis on the next development steps that we need to be taking for this novel approach to treating recurrent glioblastoma multiforme, or GBM. Recently, FDA has provided specific feedback to us regarding our proposed trial design and we, in turn, have submitted our responses back to the agency. This is part of a process that continues and we're looking to develop a study for Phase III that has criteria of enrolling a reasonable number of patients, and a study that can be completed in a 2-year time frame or less in this orphan indication. We believe that having an FDA-reviewed protocol for Phase III is critical to advancing our partnering discussions and/or initiating a pivotal trial on our own. From our perspective, these discussions with FDA, to date, had been extremely positive, with the FDA being quite responsive and very helpful. Overall, the process is progressing very well in my opinion, and I believe a properly designed pivotal trial can be agreed upon and that we will be able to continue moving Cotara closer towards regulatory approval.
At this time, I'd like to provide my personal perspective on the [bavituximab] data that was announced (Front-Line NSCLC trial, Topline ORR/PFS data - abnormally high Ctl-Arm results - http://tinyurl.com/7m9r6ya ] . As I'd like to explain, these data in no way impact our enthusiasm for developing bavituximab as a novel anti-cancer agent or the clinical path that we have established. We have been clear that we do not know fully what to make of these results, given the unusually high control arm results. As Joe mentioned, and I will repeat, bavituximab arm data from this trial was in line with our expectations and consistent with the previous data that we've seen in earlier development programs. But what also adds to the confusion surrounding this data is that discrepancy between the 2 types of analysis, which when taken all together really says that we need to wait for the Overall Survival data, the ultimate endpoint that matters in front-line NSCLC.
VI. 3-9-12 CC: (http://tinyurl.com/7t2xsks )
DR. ROBERT GARNICK (Head/Regulatory Affairs):
• Q&A#3 (Edward Nash – Cowen & Co. – re: First-Line NSCLC trial, OS vs. ORR/PFS):
ROB GARNICK: And just to add another point, in terms of the response rate, I mean, there are a lots that, Iressa for example, was approved, which had actually pretty impressive overall response rates, and it was given the Accelerated Approval based on that, and then when the actual pivotal trials were done in Iressa, it showed no overall survival benefit and FDA recommended pulling it off the market. So I've seen this go both ways. And again, you would like to see, what you'd love to see is a direct linear coloration between response rate & PFS and MOS, but most of the time doesn't work out that way. And that's why FDA really believes that Overall Survival is the most appropriate endpoint for judging the value and benefit of these products we would provide to the patients. So there are a lot of horror stories, I could go to a 100 of horror stories of drugs that had early development issues. A good example was Avastin failed as a monotherapy and I think everyone questioned why would this drug ever work if it didn't work as a monotherapy agent, given the moa that Avastin was designed and expected to have. And yet when it was combined with chemotherapy, it showed really stunning results in colorectal cancer. So again, drug development is all about designing your studies properly and giving the product the best opportunities and seeing where the data actually takes you. So it's kind of the perspective that I have and, hopefully, it provides some value to you.
• Q&A#5 (Stephen Dunn/LifeTech - re: Avastin vs. Bavituximab):
ROB GARNICK: I think it [Bavi] is somewhat similar to Avastin and it's certainly the kind of broad spectrum mechanism of action with respect to, in case of Avastin, anti-VEGF or seeking to combine with VEGF as a neo-vascularization preventative agent vs. being able to bind phosphatidylserine in any number of cancer cells. So, both of them have a lot of kind of broad-spectrum similarities. And I agree with Steve & Joe, that what we really want to do is find where bavituximab has the greatest benefit. And that may not be in a place where Avastin is currently approved. Given that the drug has potentially a good safety profile and it certainly seems to be very active, so it's really a question of finding the right indication through the studies that we're doing, and then to move aggressively & definitively towards an approval in that indication. So I think that's really the kind of drug-dev. program that we're envisioning.
VII. 7-16-12 CC: ( http://tinyurl.com/cs7spbz )
DR. ROBERT GARNICK (Head/Regulatory Affairs):
[PHONE PROBLEM, JOE SHAN READS ROB GARNICK’S PREPARED REMARKS: ]
We've been working very hard and very actively on the next steps in our bavituximab 2nd-Line NSCLC program, 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. What we'd like to see in a Phase III design is something that we can basically replicate from this Phase II that we just completed, but in a larger scale. Now with regard to Cotara, we're continuing our dialogue with the FDA with specific emphasis on the next steps for developing this novel approach to treating recurrent GBM brain cancer. The agency has been very responsive and certainly recognizes the potential importance of this novel drug candidate, and we remain positive that a mutually agreeable design can be reached. At this point, I believe that a solution can be met and if it were not able to be met, it would've been clear to all parties by now. But, having said that, these discussions do take time. And while we've come a long way, the agency knows and recognizes the unmet medical need and the potential of this novel drug candidate. And so, we remain very optimistic that we can come to a final resolution in the coming months. And now I'll turn the call over to Paul.
• Q&A#3 (Charles Duncan/JMP Securities - re: 2nd-Line NSCLC EOP2 FDA Mgt):
To Steve's point, I think we have more than enough data right now to initiate a meeting with FDA. I think as the data matures and the longer it runs out, we'll even have potentially better information. But, with respect to an EOP2 meeting to plan for a Phase III, I think we're really in a very excellent spot right now. And I think we know exactly what we're going to recommend for a trial design for Phase III. And of course, as Steve said, having a partner on board, because this is undoubtedly will be a global trial, we would like to have a partner's input into that information in order to provide that. But 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 Phase II & Phase III data, and this is as compelling Phase II data as I've ever seen. So, I'm very comfortable proposing a meeting with the agency for the 4th quarter of this year. Back over to you, Steve.
VIII. 9-10-12 CC: ( http://tinyurl.com/8nkwrml )
...Dr. Robert Garnick (Head/Reg.): "As you have just heard from Joe, the data we announced last week [9-7-12/Gerber/Chicago] 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. We took an extraordinary amount of care in developing this Phase II trial design and conferred with clinical experts & regulatory agencies, including the FDA, in the design of this rigorous clinical trial. Peregrine chose to conduct this trial to definitively establish the proof of concept to bavituximab and now plans to potentially include this data as part of a registrational package. Having personally been involved in the evaluation of over 30 Phase II trials over my career, none of which ever achieved statistical significance, including many of today's blockbuster biotech products, I am personally extremely pleased with the quality of this data and the clarity with respect to advancing bavituximab in Phase III trials which it provides. Our next steps are to present the data you saw last week to global regulatory authorities as part of the formal End of Phase II [EOP2] meetings from which we anticipate gaining concurrence into the planning & execution of a pivotal trial program. Normally, it takes approx. 60 days to arrange such EOP2 meetings, and following these meetings to submit IND amendments for the Phase III and initiate the trial by mid-2013.
Touching on Cotara for a moment, Peregrine and the FDA are continuing to have positive discussions about the design & execution of a pivotal trial in GBM. We appreciate your patience as we just strive to gain the most advantageous strategy for both parties for this novel and potentially important drug candidate."
• Q&A#1 (Joe Pantginis – Roth Capital Partners)
RG: I think the regulators will be very excited. Certainly, the FDA had a lot of input into our trial design, and I think they gave us some a very wise counsel and I think this is exactly the kind of study that they would like to see. And certainly it provides for us the clarity, which you rarely have in Phase II trials, to decide to go clearly into a Phase III study and to actually really focus on replicating what we've just done. And I think that de-risks the program enormously, and really gives us a lot of confidence in how to go forward.
• Q&A#2 (Charles Duncan - JMP Securities):
RG: Just a quick follow-on to what Joe said, I think the std. for approval for a drug in 2nd-Line NSCLC will be another trial that would replicate this one, and as Steve said, as closely as possible. I'm not sure what else we would do different other than increase the “N” of the patients. And once we have that data, the combination of information between this trial and the next one, the pivotal Phase III - the plan would be that, that would be the data that we'll need to achieve an approval. I think if we achieve anywhere near the degree of clarity that we just obtained, I think this will be a pretty straightforward approval process. I'm sure the FDA would agree with me; the FDA as well as other global regulatory authorities would agree, that this is a pretty straightforward design and we really just need to obtain concurrence on it and then to begin our execution by mid-2013.
• Q&A#3 (George Zavoico - MLV):
RG: Following on to what Steve said, one of the things that's always attracted me to bavituximab is the fact that it does have such a potential plethora of possible indications. And as you pointed out, we really went into NSCLC based on the signal-seeking data that we had originally gotten in early Phase I & II studies. I think that was a very wise way to go forward. Just like Avastin, as you'll remember, Avastin was first developed in colorectal cancer and then, having a broad anti-angiogenesis moa, we then were able to develop that drug into multiple other cancers where, theoretically, its moa would still apply. And of course, Avastin has gone on to become an extremely profitable and valuable drug in the oncology arena. So, we're thinking about a very, very similar strategy for bavituximab - basically, using these ISTs to guide you in terms of where you're most likely to succeed and in what combination of drugs to combine with bavituximab. I think, luckily, we're seeing very good safety signals with the drug, and that's really an important aspect that helps us to decide how broad the drug action can be applied. So using the ISTs and then potentially other signal-seeking Phase IIs, we plan to really maximize the benefit of this particular product. And I think we've got a broad potential and a bright future.
IX. 12-10-12 CC: ( http://tinyurl.com/a954bmw )
...Dr. Robert Garnick (Head/Reg.): "I'm pleased to report that as we announced last week, Peregrine has reached an agreement with the FDA on the clinical design aspects of a single registration trial for Cotara patients with recurrent glioblastoma multiforme, or GBM. As such, this represents a major step towards proceeding with our proposed randomized trial design, which compares 2 dose levels of Cotara in up to 300 patients. The trial design allows for interim analysis, with the potential to stop patient accrual based on predicted success or futility. This in turn could result in an improved development time line. With this news in having been granted orphan drug status and Fast Track designation for the treatment of GBM by the U.S. FDA and orphan drug designation by the EMA, Cotara has a much clearer path towards a pivotal Phase III trial.”
• Q&A#2 (George Zavoico - MLV):
RG: As Steve alluded, the efforts in conducting a global trial means that we not only have to have agreement on the trial design from FDA but, as well, from EMA, which has a very different process than the FDA does and as well as potentially other sovereign entities around the world. And the key to conducting this trial, given its size, is to have enough sites enrolled with enough patients so you can do this in a shorter time frame as possible. So we're pivoting right now and following the discussions with the FDA to discuss the same trial design plan with the European agency and as well as potentially other global regulatory authorities. So, it's going to take a lot of effort and a lot of time, but we're very confident that we're going to be able to come up with one unified trial that will accomplish all of our goals.
X. 2-19-13 PR: [Topline Data Update from 2nd-Line NSCLC Trial after data discrepancies review - 60% improvement in MOS: 3mg=11.7mos. vs. 7.3mos. for CTL-arm(combined 1mg & Doxy+placebo arms), HR=.73, p=.217 http://tinyurl.com/ansqcea ]
...Dr. Robert Garnick (Head/Reg.): “From a regulatory standpoint, this trial achieved its three main goals in preparing for a Phase III trial by identifying a dose, augmenting the existing set of favorable bavituximab safety data, and demonstrating good signs of survival effect in patients. With these data in hand, we are now preparing for additional discussions with regulatory bodies including an end-of-Phase II meeting with the FDA by mid-year with an overall goal of being in a position to initiate a pivotal trial near year-end."
XI. 3-12-13 CC: ( http://tinyurl.com/c48osut )
...Dr. Robert Garnick (Head/Reg.): "The Clinical & Regulatory Affairs group has had a really busy quarter, and as you have heard, the next quarter will certainly be no different. With respect to our lead indication, bavituximab, in 2nd-Line NSCLC, we are in the midst of planning for a meeting with the FDA some time during Q2/2013 to discuss the size & design of our proposed Phase III trial. What I can tell you is given the reanalysis of the Phase II data that both Steve & Joe have alluded to, we anticipate that this trial will be in the 600-pt. range and could involve an interim analysis. Our goal is to initiate a Phase III trial by the end of the year. I would like to point out that our bavituximab Phase II trial accomplished what it was designed to do, in that it achieved the determination of the intended dose for Phase III, expanded our understanding of the favorable safety profile of bavituximab, and produced a clear signal of clinical efficacy. Having accomplished these 3 critical things, we feel confident in moving the bavituximab 3mg dose into Phase III, that this dose has a favorable safety profile, and has demonstrated promising signs of clinical activity. With this data in hand, we feel that we have a strong package of information ready for discussion with the FDA and are confident that this program should move forward into late-stage development.”
• Q&A#1 (Joe Pantginis – Roth Capital Partners)
RG: We have quite a whole plethora of regulatory things that we're dealing with right now to get ready for the EOP2 meeting with FDA. And that meeting, as you know, really encompasses all of the information we have on the drug. We're tying up all the bows right now on the Chemistry, Manufacturing & Controls section of the IND and actually ready to make a submission to FDA shortly to cover that section of Phase II, of which there is no surprises and which has gone extremely well. So, we can certainly make the material; we can make it reliably; we can make it at an economical level. And then, of course, we have to deal with all the issues on the clinical side. And as Steve said, the 3 things you really need to know for EOP2 with FDA is that you need, and the actual purpose of Phase II, is to determine the dose that you're going to take forward into Phase III, and we certainly have done that with the 3mg dose. The next is the summary of all the safety data, and we’ve really integrated all the safety information from our Phase I and previous Phase II trials, as well as the randomized controlled 2nd-Line trial. And we'll be presenting that entire summary and safety profile of the drug, which is also extremely good and actually better than we anticipated. And the 3rd piece, which is important, is the efficacy piece, and as I point out to many people, there are very few and far between Phase II trials that ever show statistical significance in efficacy - that's an absolutely unbelievable hurdle for a Phase II product. And, what you're really looking for is an ability to describe that you do have clinical efficacy, and as Joe has said, showing 11.7 mos. for the 3mg arm and a difference in the pooled dataset for the product of 7.3 mos. when you combine the control & the placebo, definitely gives you the indication that in overall survival, we have a potentially highly efficacious product. So, I think the 3 critical things have been identified. And again, we're going to discuss the entire situation of the investigation with the agency, as well as all the data I just described, and we feel pretty confident that we have enough data to move the product effectively into Phase III.
XII. 5-20-13 PR: [ FDA Approves Bavituximab Ph.III Design for 2L/NSCLC; 600-pt trial to begin by y/e’13 http://tinyurl.com/n3dxtm6 ]
RG: "We are very pleased with the outcome from this highly collaborative effort with the FDA which allows us to proceed with our proposed Phase III clinical trial. We believe this trial, when combined with bavituximab's supporting data to date, could be sufficient to support a future BLA submission."
XIII. 7-11-13 CC: ( http://tinyurl.com/khpokw6 )
...Dr. Robert Garnick (Head/Reg.): “From a regulatory standpoint, I'm very pleased with the progress made during this quarter as we achieved 2 major goals in our most advanced program. First, the positive data that emerged from our 2nd-Line NSCLC trial provided additional safety, as well as clinically meaningful efficacy data needed to advance the program. Second, the reaching of an agreement with the FDA on our proposed clinical trial design was the result of a very successful and highly collaborative effort with the agency, which allowed us to proceed. Since our last quarterly conference call, we have had very positive interactions with FDA concerning our production processes and capability to manufacture Phase III material, and ultimately, bavituximab for the market, as a prelude to the EOP2 meeting, which was, by design, focused on our Phase III clinical plans. We believe this Phase III trial, along with the large amount of supporting data to date, could be sufficient to support a future biologics license application (BLA) submission. The next steps from a regulatory perspective are to initiate discussions with ex-U.S. regulatory agencies, such as the EMA, in order to facilitate the start of the global Phase III by year's end.”
Q&A/Roy Buchanan/Piper Jaffray re: “EOP2 FDA Meeting”…
RG: “…It was quite benign. They liked the plan we proposed. They thought it was well thought through, and there were absolutely no sticky issues whatsoever.”
XIV. 12-10-13 CC: ( http://tinyurl.com/mw776mk )
...Dr. Robert Garnick (Head/Reg.): “As you have just heard from Joe, the SUNRISE global Phase III trial is close to the beginning of its enrollment. This is an exciting time for this program, a point that we achieved following the execution of a great number of activities that relied on close collaboration with many worldwide regulatory agencies. From a regulatory perspective, this global trial was set to roll out first in the United States, followed by sites throughout Europe and the Asia Pacific region. Our interaction with these countries and regions has been a major focus for our regulatory department for the past several months. These discussions, including those with the FDA and various European regulatory agencies have been extremely positive, and I am pleased to say that the process of globally filing our Phase III study protocols is moving ahead very smoothly. We are also looking forward to further meetings with these regulatory authorities throughout the course of the trial. I'm very pleased with how these tasks have been executed to date, and believe that we have the necessary people and qualified third parties in place to support the SUNRISE trial.”
XV. 1-6-14 PR: [Peregrine Receives FDA Fast Track Designation for Its Immunotherapy Bavituximab for 2nd-Line NSCLC http://tinyurl.com/l799ukk ]
RG: "The Fast Track Designation is a milestone for the SUNRISE trial program and represents a step closer to bringing bavituximab to the market. We are very pleased that the FDA has recognized the potential of this novel therapy as a treatment for this serious and devastating type of cancer and look forward to working closely with them to ensure the most efficient review process."
XVI. 3-10-14 CC: ( http://tinyurl.com/kh9cnrg )
Q&A, Graig Suvannavejh/MLV – re: “competitive landscape”…
RG: “…Bavituximab really represents a unique opportunity, and I don't think you can draw any conclusions from failed Phase III trials from other companies' products because basically, a lot of drugs were taken into Phase III, basically, on much less compelling data than we were able to achieve with bavituximab. So, I think we're actually very well-poised, based on our data, to see potentially a very successful Phase III trial. And again, I wouldn't draw any conclusions on other people's trials. We're really in a very good position because based on our data - we've just recently achieved global regulatory approvals for going into Phase III based on the strength of the data - the total data package that we presented. So, I think that's quite a testimony to the data package that we've been able to achieve so far. And of course, we'll see how everything progresses during the SUNRISE trial, which now is ready to go.”
= = = = = = = = = = = = = = =
BusinessWeek EXECUTIVE PROFILE
Robert Garnick Ph.D.
Head of Regulatory Affairs, Peregrine Pharmaceuticals Inc.
Age: 60 --
BACKGROUND
Robert L. Garnick, Rob, Ph.D., has been Head of Regulatory Affairs at Peregrine Pharmaceuticals Inc., since October 19, 2009. Dr. Garnick is responsible for overseeing Peregrine's interactions with the U.S. FDA and regulatory agencies around the world, and leads the development of the Peregrine Pharmaceuticals's regulatory strategies for advancing its novel monoclonal antibody-based treatments for cancer and infectious diseases. Dr. Garnick has over 30 years of experience in drug and biologic pharmaceutical development, including 24 years at Genentech helping to build the biotechnology industry. He served as Senior Vice President of Regulatory, Quality & Compliance at Genentech Inc. since February 2001. During his 24-year career at Genentech, he was responsible for 17 new product approvals including most of the Genentech's top selling monoclonal antibody therapeutics such as Rituxan, Herceptin, Avastin and Lucentis. Previously, Dr. Garnick served as VP/Regulatory Affairs from Feb.1998 to Feb.2001, VP/Quality from Apr.1994 to Feb.1998, Senior Director, Quality Control from 1990-1994 and Director, Quality Control from 1988-1990. He joined Genentech in Aug.1984 from Armour Pharmaceutical, where he held various positions. After leaving Genentech in 2008, Dr. Garnick founded Lone Mountain Biotechnology and Medical Devices, Inc. [ http://lonemountainbiotechnology.com ], a successful company specializing in drug and device consulting where he remains as President and CEO. Dr. Garnick has also been extensively involved with the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). He has extensive experience in analytical methodology, process validation, and the regulatory review process in the U.S. and Europe. Dr. Garnick has authored numerous scientific papers and is a frequent keynote speaker at pharmaceutical Industry conferences and events.
= = = = = =
Genentech 10-K iss. 2-23-2007:
Robert L. Garnick, Ph.D. was appointed Senior Vice President, Regulatory, Quality and Compliance of Genentech in Feb.2001. Previously, he served as Vice President, Regulatory Affairs from Feb.1998 to Feb.2001, Vice President, Quality from Apr.1994 to Feb.1998, Senior Director, Quality Control from 1990-1994 and Director, Quality Control from 1988-1990. He joined Genentech in Aug.1984 from Armour Pharmaceuticals, where he held various positions.
http://www.gene.com/gene/ir/downloadDoc.do?id=3461
= = = = = = = = =FULL MINYANVILLE ARTICLE:
6-29-11/Minyanville: ”Peregrine Pharma's Secret Weapon [Robert Garnick]”
By Brett Chase [Bio: http://www.minyanville.com/gazette/bios.htm?bio=361 ]
• Robert Garnick, a veteran of Genentech, is steering the biotech company through FDA waters. Can he repeat his past success at the small cancer drug company?
http://www.minyanville.com/businessmarkets/articles/peregrine-pharmaceuticals-bavituximab-robert-garnick-steven/6/29/2011/id/35458
Peregrine Pharmaceuticals (PPHM) is an early-stage company working toward approval of its first product, a cancer drug. Navigating the regulatory waters alone can be daunting for a small company. But Peregrine has a seasoned skipper for the important job: Robert Garnick, a 24-year veteran of Genentech. In his 2 decades at the biotech company (now part of Roche), Garnick oversaw 17 product approvals, including for top-selling drugs Rituxan, Herceptin, Avastin, and Lucentis.
Peregrine CEO Steven King credits Garnick, now Head of Regulatory Affairs for the small company, with guiding strategy for testing experimental drugs for brain, lung, and other types of cancer. Garnick has a deep understanding of the FDA process, particularly for approval of biotech treatments, King says. The CEO considers his company fortunate to have someone with Garnick’s long history with the agency.
“Rob is the ringmaster,” King says.
To be sure, drugs have to work and they have to clearly demonstrate their safety and effectiveness in years of studies, but Garnick say sometimes companies have promising medicines that get scrapped for the wrong reasons. The 61-year-old biotech pioneer says companies need to figure out early on if a drug is approvable before moving forward. Taking cues from the FDA can help that process. A change in strategy may be needed to win an initial approval for a new treatment.
“I know how the system works -- I know what mistakes you shouldn’t make, and I make sure you don’t make those mistakes,” Garnick says. “My view is the FDA is my friend. I am not an adversary.”
Case in point: Bavituximab, Peregrine’s leading drug candidate, is being tested for multiple types of cancer, including lung, pancreatic, liver, and breast. But Garnick, after consultation with the FDA, advised the company to pursue approval of the drug as a secondary treatment for lung cancer. There’s a big unmet need and the drug in early testing appeared to be effective, Garnick says. The company is studying the drug in the 2nd of 3 phases of human testing usually needed for a drug’s approval.
Investors are not yet on board with this early-stage company. The shares are down 19% this year, trading at $1.86 midday Wednesday. The stock is down 94% since its public offering in 1996.
Garnick admits to being a risk taker. As a young man, he drag raced and he still drives race cars. However, he sees promise in both bavituximab and Peregrine’s other drug candidate, Cotara for brain cancer. Cotara is being studied for the treatment of gliboblastoma multiforme, or GBM. The drug is infused in a patient’s head and has been studied in 2 phases of human trials. The company hopes to meet with the FDA later this year about design of a so-called Phase III trial. But Cotara is designed for treatment of one disease, while bavituximab is being tested for multiple conditions. In addition to the various types of cancer treatment being researched, the drug is being studied for hepatitis C.
A number of biotech blockbuster products treat multiple conditions. That was the case with Genentech’s Avastin, a drug that has potential to treat multiple types of cancer by attacking tumors. Avastin is approved to treat colon, lung, brain, and kidney cancers. It’s also approved to treat advanced breast cancer but the FDA proposed rescinding that approval and the drug is the subject of a 2-day hearing in Washington this week.
While it’s a long way from being considered the next Avastin or Rituxan (a treatment for multiple cancers and rheumatoid arthritis), bavituximab holds promise, Garnick says. He insists he would advise the company to kill the program if he didn’t think it had strong potential. “What I know is how to develop a drug, and I also know how to kill it,” Garnick says.
*end*
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= = = = = = = A COUPLE OF EXAMPLES OF WHAT ROB GARNICK IS GOOD AT:
2-26-04 - ATTACHMENT D – AVASTIN APPROVAL LETTER
From: FDA, To: Dr. Robert Garnick
FOLLOWED BY AVASTIN EXPANSION APPROVAL AS 2ND-LINE VS. MET. COLORECTAL CANCER:
6-20-06: From: FDA
Dear Dr. Garnick:
