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Wednesday, 03/16/2011 10:31:26 AM

Wednesday, March 16, 2011 10:31:26 AM

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Excerpts+Slides from SK's 3-14-11 ROTH Talk (DanaPT CA), including his comments on Drs. Garnick & Menander, progress & plans for Cotara/GBM, Bavi as a potential replacement for Inteferon in HCV/combo regimens, and Bavi’s potential in the Imaging area. After the Roth Slides/Excerpts, I’ve added some background info. on Cotara/GBM Plans and Bavi Imaging.

3-14-11 CEO Steve King, Roth 23rd Annual OC Growth Stock Conf. (DanaPT CA)
Full Webcast replay: http://www.wsw.com/webcast/roth24/pphm
http://www.roth.com/main/Page.aspx?PageID=7236

Peregrine Pharmaceuticals, Inc.
PS-Targeting Antibodies
Broad Therapeutic Potential in Cancer and& Viral Infections

Roth Capital Partners
23rd Annual OC Growth Stock Conference (DanaPT CA)
March 14, 2011




SK/3-14-11/Roth/Slide3(1:54): “…From a strategic standpoint, even more importantly, Avid allows us to control our own manufacturing. And, again, as we move into later-stage clinical trials, the ability to manufacture our own products becomes a more & more valuable asset as we look at potentially commercializing the products down the road. In addition, we have a mgt. team experienced in commercializing biologics. One of the key members of the team is Robert Garnick [10-19-09: http://tinyurl.com/yga7z4x ], who is the former Head of Regulatory at Genentech – was there for 24 yrs., oversaw the development of really what are the household names in targeted therapies in oncology, Avastin, Herceptin, Rituxan – in addition, played a key role in the dev. of Lucentis in eye disease. So, again, really broad experience in not only just moving products forward, but actually successfully commercializing those products and building franchises around them. In addition, we recently added on a new member to the clinical team, Kerstin Menander [3-9-11: http://tinyurl.com/4cjlbzn ], who played a role in the approval of 15 products in the U.S. as well as Europe – again, broadening the expertise within the mgt. team as we move into later-stage clinical trials which we think can really be value-drivers moving forward.”






SK/3-14-11/Roth/Slide7/5:45 (Cotara/GBM): “…obviously a high unmet medical need; we have both Orphan Drug Status as well as Fast-Track designation for GBM. What’s really made Cotara stick out over time has been the number of long-term survivors; in fact, we’ve had long-term survivors in every trial we’ve run so far. Some of the very 1st patients that received this drug are alive over 10 yrs later, again, with confirmed GBM at the time of treatment. If you look at the historical expectations in this patient population, it’s about a 24 wk. MST with the drugs that have been available. In an earlier Ph.2 trial, a small trial where we were looking at a number of diff. dose levels as well as catheter placements, we had a 38-wk. MST. Based on this data, we zeroed in on a targeted dose of 2.5mCi/cc of tumor as well as 2 catheter placements to deliver the drug because of the nature & shape of these tumors being irregular – 2 catheters gives us very good opportunity for covering the entire tumor with the radiation. This led to this 40-patient Ph.2 study; in that study we completed enrollment in Dec.2010. The lead enroller in that study [ Dr. Deepak Gupta] had treated 14 patients, and last fall began to go out into the scientific circuit and talk about his experience [ 10-18-10: Interim Ph.2 update (n=14) at CNS’10, http://tinyurl.com/349kvca ]. In fact, in his 14 patients, he had a MST of 86 weeks, which is a pretty phenomenal number in this very difficult to treat patient population.”


SK/3-14-11/Roth/Slide8/7:18 (Cotara/GBM): “As I said earlier, we expect data from the full 40 patients towards the middle of this year. While the overall numbers may not be 86 weeks, we certainly expect them to be a very positive number that will propel us then into some meaningful discussions with the FDA. Again, enrollment completed in Dec.2010; expect top-line by the middle of this year. We’ve already begun preparing for an FDA meeting in the 2nd-half of this year, in which the goal is to get a SPA approved [ie, “Special Protocol Assessment”. Per David Miller, “the idea is if you sign an SPA with the FDA and conduct the trial as agreed, good results from the trial will be sufficient for marketing approval.” – see http://www.minyanville.com/businessmarkets/articles/5/11/2004/id/4441 ], which will set a very clear regulatory pathway for the rest of the development. At that point, I think the drug is highly partnerable – we have a number of discussions going on around the compound already. Or, it gives us unique opportunities for our own development pgm, depending on what the overall landscape of our product portfolio looks like at that time.”












SK/3-14-11/Roth/Slide14(18:25): “[New BaviRiba/HCV Ph.2 trial] Bavi is an immunotherapy, so we view it as the kind of heart of the immunotherapy-side of the HCV treatment regimen. In this trial we’re going to be testing Bavi+Ribavirin, the currently-approved direct-antiviral, vs. Ribavirin+Interferon in a head-to-head study, with the goal being Bavi could be a potential replacement for Interferon in that std. treatment. In fact, if you look at HCV dev. as we go forward, clearly new drugs are going to start to come to market, primarily on the direct antiviral side. What is also needed are new-gen. immunotherapies with a better safety profile, because Interferon is certainly a very caustic of the current SOC… In addition [to HCV], we still have a lot of potential for the platform in the infection disease area. We’re studying this for many diff. virus indications under various grants. We have potential in Herpes virus infection, various biodefense indications. So, this is really a technology platform that we think has a lot of potential not just as a naked antibody therapy, but also we know this is really a great marker of infected cells. In fact, in our hands, and all of our collaborators hands, this is a target that’s on all types of infected cells that we’ve ever looked at. One of the ways we can take advantage of that, from not just from a direct-targeting standpoint, but from a payload-delivery standpoint. So, we’re really excited about those potentials as we move forward. And, that can be future data generation and news flow for the company as we move into the rest of 2011 and into 2012.”






SK/3-14-11/Roth/Slide18(22:58): “PS represents a great immobile target of solid tumors which has not just implications in the therapy area, but also imaging diagnostics, and we’ll some data coming out on that at AACR’11 as well. This certainly creates new opportunities for the company on multiple fronts, ranging anywhere from just validating the proof-of-principle; secondly, the potential for companion diagnostics, and then just in the Imaging Diagnostics area in and of itself.”




*end*

= = = = = = = = = = = = = = = = = = =COTARA/GBM PLANS:
More on Peregrine’s Goal to secure from the FDA in the 2nd-half of 2011 an “SPA” (Special Protocol Assessment) for a Cotara/GBM Phase III trial which would set a “very clear regulatory pathway” for ultimate approval, following data-collection from the ongoing 40-pt Ph.2 India/USA trial…

CEO STEVE KING SAID THIS RE: COTARA/GBM SLIDES 7&8 OF HIS 3-14-11 ROTH PRESENTATION (see above):
“(Cotara/GBM)…obviously a high unmet medical need; we have both Orphan Drug Status as well as Fast-Track designation for GBM. What’s really made Cotara stick out over time has been the number of long-term survivors. . . In an earlier Ph.2 trial, a small trial where we were looking at a number of diff. dose levels as well as catheter placements, we had a 38-wk. MST. Based on this data, we zeroed in on a targeted dose of 2.5mCi/cc of tumor as well as 2 catheter placements. . . This led to this 40-patient Ph.2 [India/US] study; in that study we completed enrollment in Dec.2010 [12-20-10 http://tinyurl.com/2844wrq ]. The lead enroller in that study [ Dr. Deepak Gupta] had treated 14 patients, and last fall began to go out into the scientific circuit and talk about his experience - in his 14 patients, he had a MST of 86 weeks, which is a pretty phenomenal number in this very difficult to treat patient population. . . we expect data from the full 40 patients towards the middle of this year. While the overall numbers may not be 86 weeks, we certainly expect them to be a very positive number that will propel us then into some meaningful discussions with the FDA. . . We’ve already begun preparing for an FDA meeting in the 2nd-half of this year, in which the goal is to get a SPA approved, which will set a very clear regulatory pathway for the rest of the development. At that point, I think the drug is highly partnerable – we have a number of discussions going on around the compound already. . .”
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=60968164

==> I admit that I did not know what an “SPA” is, but a quick Google yielded:
SPA = “Special Protocol Assessment”
Per David Miller in his 5-11-2004 article, “Age of the Special Protocol Assessment”:
• An SPA should eliminate most of the ability of FDA statisticians to nitpick about the design of the trial. In many FDA briefing documents, we see long rationalizations by FDA staffers as to why a particular clinical trial did not measure what it was supposed to measure. Under an SPA, the FDA enters into a written, binding agreement that the design of the trial is sufficient to demonstrate an agreed-upon set of clinical endpoints.
• In general, the idea is if you sign an SPA with the FDA and conduct the trial as agreed, good results from the trial will be sufficient for marketing approval. This makes securing an SPA especially valuable to both the company and its investors
• In sum, an SPA is about as binding of a deal as you can get with a gov’t agency.
• I’ll go out on a limb here: If a biotech company starts a new Phase III pivotal trial and does not have an SPA for that trial, investors in that company should be concerned. The FDA is not being shy about handing out SPAs and the extra 2-5 months it takes to get one of these things negotiated and signed is well worth the time spent.
Any biotech company who has secured an SPA for their Phase III pivotal trial should receive a higher valuation – all things equal – than a company that has no SPA.
http://www.minyanville.com/businessmarkets/articles/5/11/2004/id/4441

And this Q&A discussion in the 3-11-11 Qtly Conf. Call (Transcript http://tinyurl.com/4p4hqr5 ) about the 2H’11 FDA meeting planned to get an SPA approved for a “highly partnerable” Phase III Cotra/GBM trial:
Q&A 3-11-11, MLV’s George Zavoico: With regard to Cotara and the registrational pathway that you mentioned, you're going to have the discussion with the FDA starting next half of this year. You really have a considerable amount of data with Cotara, you've got some pretty durable responses. Why wait? Why not start the discussions earlier?
S.KING: “Well, I think part of this time is needed to really put together an overall strategy, because this is not just clinical data-driven, but also we want to look at the marketplace, where we see Cotara fitting into that marketplace, design a Phase III trial that we think will end up with a clinical indication or labeling that will be successful in the marketplace, but also that can enroll the study in a reasonable amount of time. And so we're really thinking through this; we want to test these trial designs out, the potential outcome of those. Also, on the manufacturing side, this is a drug that does require addl. processing after we make the antibody here in our own mfg. facility, so that means working with 3rd-party vendors for the labeling process. Obviously, we're as anxious to get to that meeting and really work through this with them as we can. But, we also recognize you only get one shot at this, and so when we do this, we really want to put our best foot forward. Because our goal is to get this into decisive trial that can enroll in a roughly short period of timing and give us a quick clinical readout. And so, we're anxious to get there, but again, we want to make sure that when we get there, we are successful and give ourselves the best chance of doing that.”
GZ: So there's a lot of research that you still have to do before you get to the point where you can actually propose and write a protocol to propose to the FDA?
S.KING: “Yes, I think it's kind of an ebb & flow, because you come up with the ideas and you start to test them out and then you get more feedback and you feed that into the system. And so it requires a lot of modification, because then you've got to overlay all of the things that you'd like to do with how does your actual clinical data support that pathway forward. So yes, it's definitely a process, but again, I think we have a great bunch of people working on this on the clinical side, obviously, on the regulatory side. And so, I'm letting them guide the ship here as far as when we go there, let's give ourselves the best chance of being successful, because ultimately the outcome of that meeting is extremely important for the program.”

= = = = = = = = = = = = = = = = = = =BAVI IMAGING:
Also, in the 3-11-11 Qtly. Conf.Call (Transcript http://tinyurl.com/4p4hqr5 ), Dr. Philip Thorpe discussed Bavi’s as a potential IMAGING AGENT (see SK's Slide18 3-14-11 Roth comments above)…
Q&A, MLV’s George Zavoico: …And #2, one of your posters at AACR talks [ AACR’11, Apr3-6’11 - see http://tinyurl.com/4aofbso ] about PS-targeting as an Imaging Agent. This, of course, is very, very important when people are studying any sort of anti-cancer drugs, to see what's happening to the tumor. Does this suggest perhaps you're going to move into the diagnostics area with this and start a diagnostics division?
Dr. Thorpe (3-11-11): Certainly, the quality of the images is quite extraordinary. The antibody homes to tumor blood vessels beautifully in all tumors that we've seen with really very, very little of a staining seen in other tissues, and that's just what you'd like to see in a diagnostic - we are looking at that very seriously. And also, that binding is correlated to response, both with radiotherapy & chemotherapy. So again, we have the possibility of making a diagnostic that would be predictive of response. We are evaluating that possibility at this time.
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6-14-2011: Dr. Philip Thorpe, UTSW Research Presentation, Dallas http://tinyurl.com/2d3nn7o
…9am: “SAIRP: Imaging Tumor Vasculature” (UTSW's Advanced Imaging Res.Ctr)
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AACR’11 Abstract #4880
Title: ”Monitoring Tumor Response to Chemotherapy by In Vivo Real-Time Imaging of Phosphatidylserine Targeting Antibodies”
Jian Gong, Linda Him, Christopher Hughes, Bruce Freimark [Peregrine’s Dir./ProdDEV]
Wednesday, April 6, 2011, 8:00am -12:00pm ET (Poster)
ABSTRACT:
Phosphatidylserine (PS) is a phospholipid normally residing in the inner leaflet of the plasma membrane that becomes exposed on tumor vascular endothelial cells and tumor cells in response to chemotherapy, irradiation and oxidative stresses in the tumor microenvironment. Binding of antibodies targeting PS on the tumor endothelial cells recruit immune cells and engage the immune system to destroy tumor vasculature. The antibodies also enhance anti-tumor immunity by blocking the immunosuppressive action of PS. A chimeric anti-PS antibody, bavituximab, is being used in combination with chemotherapy to treat patients with solid tumors in randomized Phase IIb clinical trials. In the present study, we demonstrate in vivo tumor imaging of PS expression using real-time, near infrared fluorescence imaging of antibodies that specifically target PS. Human prostate PC-3 tumors expressing luciferase were orthotopically transplanted in SCID mice and tumor growth was monitored by bioluminescence. Targeting antibodies used in this study bind PS through the interaction of beta-2-glycoprotein 1 (B2GP1) in the same manner as bavituximab binding to B2GP1 in humans. Specific localization of fluorescence-labeled PS targeting antibodies after a single dose was observed in tumors compared to an isotype control antibody. Persistence of antibody localization was prolonged using intact IgG compared to F(ab’)2 fragment. Chemotherapy was shown to enhance the binding of PS targeting antibodies to tumors. These data provide a rationale to image PS expression to localize tumors or metastases and to monitor chemotherapy-induced PS expression during the course of bavituximab therapy.
AACR 2011 (Apr2-6/Orlando) Home: http://www.aacr.org/home/scientists/meetings--workshops/aacr-102nd-annual-meeting-2011.aspx
ABSTRACT SEARCH: http://www.abstractsonline.com/plan/start.aspx
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9-7-10 PS Patents Granted: 7790860/Imaging 7790159/Antiviral http://tinyurl.com/27zlc8a
6-24-09 U.S. Patent #7,550,141 granted: Anti-PS for Tumor Imaging: http://tinyurl.com/ln9ub8
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3-3-08: Thorpe/Mason C.C.R. (AACR) article on Arsenic-labeled Bavi for Imaging Tumors: http://tinyurl.com/32jbfl
…3-5-08 Chemistry World followup article on CCR Bavi+Arsenic/IMAGING: http://tinyurl.com/4m4lbse
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