Avid Bioservices Inc (CDMO)

[BioBS2012]

Thanks, CP. Better articulated then my own effort if I may say so. Re-posting, as it never hurts.

7) The Opdivo trial for NSCLC being stopped lowers competition for patients to enrol. Those patients that could have qualified for BOTH trials between now and DEC 2015 would have less choice. SUNRISE could enrol faster because of it since Opdivo cannot be prescribed the coming 4-6 months, point at which SUNRISE should be fully enrolled in the US because PPHM for sure had some margin in DEC 2015. As you said for the rest of the World no Opdivo. 38 US centres opened in Q1-2/2014 vs 120 non affected World-wide centres.

8) As explained in the CC Q&A it doesn't matter whether Optivo becomes SOC over Docetaxel or not (even non-squamous). The FDA signed off on a trial design Bavi+Doce versus Doce alone and if the survival scores better then Doce alone (PPHM goes for 7.5 months or 50% improvement) then it will get approved. Whether that combination becomes then the new SOC will depend on how well Opdivo did on its own.

9) All anti-XYZ have small response foot prints which EXCLUDES a lot of patients from being treated with them. Bavi can solve that. FDA will not make a drug the SOC for all NSCLC if it only works for 10% of the population. And we all know anti-XYZ do very poor in the area.

10) All anti-XYZ have a big SIDE EFFECT problem (see lawsuits Yervoy in UK). Bavituximab milds that. Also side effects will come in play, should Opdivo work for everyone, for the FDA to decide whether it can become SOC.

11) If Bavi is approved with Doce it can be prescribed off-label in the US. But Bavi+Doce could prove more potent and better then Opdivo alone. SUNRISE has a potential outlook on 110-130% improvement. So I wonder what Opdivo did because BMY is relatively quite about that. Remember, as the director of the FDA Oncology Dept said, the industry is used to see 5-8% improvements as GOOD. So Opdivo could be candidate SOC off vs DOCETAXEL alone compared to Bavi+Docetaxel in no time because SUNRISE will not be stopped. But it can become SOC back on if combined with Opdivo. Same incentive for BMY to combine with it as for Yervoy?

12) And no matter how we turn this around or upside down, Opdivo will have competition form other BP's and when against each other the one combining with Bavituximab as first will steel the SOC because the second one must then outperform the new SOC set by that combination (while also only able to add just Bavi).

There was a time that being first was VERY important because every next one needed to beat you to take the SOC away. So a valuable 15% improvement could miss the SOC because 3 months earlier another trial increased it already by 16% as trials took many years. However, for bavituximab that doesn't play because it is a combo drug that can combine with whatever is the SOC and moved the score and whatever BP that comes from. But for BPs it does matter. Here is an example:

Docetaxel alone say 5.6 months (PII plus historical correct)
Opdivo alone 7.5 months (Assumption they went at least for 50%)
Docetaxel+Bavituximab say 11.4 months (PII 1mg, 3mg was 13+ months)

In this EXAMPLE for Bavi it doesn't matter whether it beats Doce and Opdivo in the same process. It becomes SOC, even if for a short time Opdivo has been SOC. However for Sanofi and BMY it is important. Because only beating 5.6 is more easy then beating 11.4, and beating 7.5 is also more easy then beating 11.4. But if Bavi+Doce scores 13+ months then that may become problematic for BMY because it would require 80% improvement on his just established 7.5 months to JUST match the SOC. And the only way TODAY to do that is very probably combining Opdivo with bavituximab and hope it has a better overall result.

But let's assume for a moment Opdivo puts down a super result like 11 months or even 13 months. Still then adding bavituximab will improve it but the monkey sits then on the shoulder of Sanofi, and actually also on all anti-XYZ players shoulder such as Merck.

For Opdivo Bavi will still mild side effects because it interacts with the MDSC's as well and it is very probable (PROBABLE not SURE) that as with Yervoy it increases the response foot-print and hence the SOC. Preclinical let believe so.

And I think that is why we currently all are in PPHM because Bavituximab's scoop of application is so large and it is so safe (in many combinations now) that it always has a place as the differentiator when 2 or more BP's compete. Bavituximab is the common denominator in ALL treatments of this kind and it is normal because it is an UPSTREAM not a DOWNSTREAM drug.

So let the downstream guys compete amongst them with there chemo's, radio's onco-immuno drugs and let PPHM/Bavituximab be the neutral provider of the BOOSTER additive that they will all need to stay in SOC position. I think Brekken's 200%-300% is applicable in 100%-200% range for combo's in oncology.