Avid Bioservices Inc (CDMO)

[cjgaddy]

Bavi's_Goal: More anti-PD-1/L1 Responders AND Prolong The Attack. Bavi's effect (hopefully to be proven in human trials), when combined with an anti-PD-1 inhibitor like AZN's durvalumab(MEDI4736SK), is more than just to increase the # of patients who respond to PD-L1, but also to cause the responses to be more prolonged & robust. SK 10-15-15/ASM, “Get it started, and keep it going.”

10-15-15 PR(PPHM/AZN Collab. Expanded): “Preclinical data have demonstrated that combining the enhanced T-cell mediated anti-tumor activity of bavituximab with checkpoint inhibitors, like PD-L1 antibodies, prolong the ability of tumor-specific T-cells to continue attacking the tumor.” http://tinyurl.com/q79bkam

10-15-15/CEO S.King(ASM) 1:50: “Some of the most exciting data that we've seen to date is that, when you look at the immunotherapy revolution in the way cancer is being treated, what's really becoming clear is that the PD-1/PL-L1 inhibitors are very potent in patients who have an active immune response. So, what happens is, when you have an immune response, these markers, PD1/PD-L1, become expressed and basically shutdown the immune response. So, what those drugs are doing is basically stopping this inhibition that's caused by the PD-1/PD-L1 interaction. So, very simple – block the checkpoint and then now the immune system can keep mounting that immune response. But actually the majority of patients don't have that immune response going, and we really believe it's because they have this exposed PS which is knocking down that immune response from ever getting started. So what we see as a potential beautiful fit for bavituximab is, now we're able to block that PS signal, now the immune system gets started, and now we can keep it going with these PD-1/PD-L1 inhibitors. So, “get it started, and keep it going”, and now we believe, and we'll show this in data, that we can help more patients respond. Patients who are already responding are doing great, but it's the minority of patients, and now it's getting more & more patients to respond, and that's the whole goal of this combination therapy paradigm, which is really highlighted by today's announcement with AstraZeneca [10-15-15: http://tinyurl.com/q79bkam ] that we're expanding our collaboration into new areas to be able to look at those combinations.” 9:40: ”Now, immuno-oncology agents, as I mentioned earlier, are showing even by themselves very nice survival tails in a minority of patients, and this is typically 20-30% of patients who get such long-term benefits. So, the question is here, how do we make more & more patients able to enjoy that benefit of long-term survival, which means your body is really fighting the disease and helping the therapy, and when you look at our pre-clinical data, and obviously our goal next is to generate similar clinical data - when you at what happens when you're treating with an anti-PD-1 checkpoint inhibitor, you see some animals responding very well, but then you see these animals that just basically don't respond at all, or they have a very minimal response which then gives out over time. And this is exactly what you're seeing in patients, right? - the minority of patients are getting a long-term benefit, but most patients actually escaping treatment and relapsing. When you combine an anti-PD-1 with a bavituximab-equivalent for pre-clinical studies, what you see now is this wide variety of responses really beg ins to tighten up, so that most of these animals are now enjoying the benefit of a more-robust, combined anti-tumor effect caused by the immune system. Our goal thru our collaborations and with our clinical studies is to demonstrate this same effect in patients, so we're getting more & more patients with these long-term effects.”
**10-15-15/ASM Webcast Replay: http://edge.media-server.com/m/p/jghjvabo

= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
Opdivo works in only ~20-35% of NSCLC Patients, those that express PD-L1 > 10%. In BMY’s Checkmate-057 NSCLC trial, Opdivo DID NOT increase survival vs. DOCE in the 64% of All Pts that didn’t express PD-L1 > 10% (see BMY’s K-M Charts below). Thus, the window of opportunity for Bavi is essentially 2/3+ of the NSCLC market. Of course, the other 1/3 of the patients where Opdivo works well might live even longer if Bavi were added to the mix, or possibly Bavi will allow Opdivo at reduced dosages to cut back on its considerable side-effects…
- - - - - - - - -
PD-1/PD-L1 blockade therapies like Opdivo+Keytruda benefit 20-25% of patients. Peregrine’s objective with Bavi is to “increase the extent & amplitude” of such therapies…
“Although PD-1/PD-L1 blockade therapy [ex: Opdivo, Keytruda ] provides clinical benefits to approx. 20% of patients with advanced NSCLC, about 80% of patients still remain refractory to this treatment. Therefore, new molecules & combinations are urgently needed to address primary & secondary resistance to these new agents.”
From 3-2015 ClinCancerRes. article, “Immune Checkpoint Modulation for Non–Small Cell Lung Cancer”:
http://clincancerres.aacrjournals.org/content/21/10/2256.abstract
http://www.ncbi.nlm.nih.gov/pubmed/25979932
=> Bavi’s goal is to Extend The Range of patients that would benefit from the anti-PD1 mabs, in addition to helping the 20% that do benefit get Better Results.

= = = = = = = = = = = = = = = = =
BMY’s Ph3 Opdivo NSCLC trial – look at the KM-Curve and OS #’s for those pts that express < 10% PD-L1. The OS separation in the tail just collapses and Opdivo (nivolumab) dead standstill with Doce in MOS => That’s ~64% of ALL the pts in the n=582 trial!
http://investor.bms.com/files/doc_presentations/2015/ASCO-Investor-Presentation-June-1-FINAL_v001_p9iq7v.pdf (pg.25)









10-15-15: Peregrine & AstraZeneca Expand Collab. w/Ph2/2ndLine-NSCLC Trial
=> Bavi+durvalumab(MEDI4736), squamous or non-squamous… http://tinyurl.com/q79bkam

10-15-15: AstraZeneca and Peregrine Pharmaceuticals Expand Ongoing Immuno-Oncology Collaboration to Include Phase II Lung Cancer Combination Clinical Trial
Global, Randomized Phase II Trial to Evaluate Immunotherapy Combination of Peregrine's PS-Targeting Bavituximab and AstraZeneca's PD-L1 Inhibitor Durvalumab (MEDI4736) in Previously Treated NSCLC
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=936766