Avid Bioservices Inc (CDMO)

[Protector]

Carboat let me rely to your 3 posts to me at ones because they are related to a same topic.

They likely let bavi go to PIII based on safety.No risk to patients. Too bad for shareholders there ever was this PIII.

Yes and No.

- No because at the time this PIII SUNRISE was the only logical path. Again, the sudden rise of I-O behind the ASCO 2013 initial hype has been missed by most BPs. Only a handful, those driving ASCO 2013 I-O where at the forefront (BMY, Merck who clearly won round one I-O Mono therapies and to a lesser extend Roche, AstraZeneca).

- Yes with hindsight. The STOP is never nice, look at what it did to the PPS, and it is my opinion that SUNRISE approval was a disruptive thread to many I-O investments of previously mentioned companies but also to others that work on competitive approaches.

So you wish they never got PIII approval?

Approval would have been a fast path to revenue with a SOC statute. It would have generated cash during a number of years and would probably have driven PPHM into MORE CHEMO. That is a short term vision were it not that PPHM at the SAME TIME was/is clearly doing effort to drive I-O combo's with Memorial Sloan Kettering and the NCCN and AstraZeneca.

One could say: What is the problem then to have both...sounds good! Well yes it sounds good and for the PPS would have been better in the short term BUT SUNRISE in parallel with I-O would have remained a disruptive threat. In the slide I posted yesterday it shows that the PII performance of the 3mg/Kg arm (that was NOT tempered with) had %-wise double of ECOG 2 patients then the combined arms. So in a PIII with a normal stage/ecog distribution over the two arms Bavituximab could have set a SOC record that might be beatable with CHEMO+Bavi+Durva but that would be hard to beat with Durva+Bavi (and any other PD-1/PD-L1, CTLA-4) in a sufficient way to move the SOC up. Just as Bavituximab beating the Pancreatic SOC by two weeks was not sufficient, beating a NSCLC SOC won't either for the FDA. And BP doesn't want chemo because of the generics available. There is no more real money in it for them.

So SUNRISE approval would cost the main I-O BP's BILLIONS PER YEAR in loss of sales and new attempts to make combo's to beat the SOC. Those combo's will have 3 or more components and there starts the trouble. Higher cost and if you don't own them, as said the Novartis CEO on CNBC, you will have to share the profit leverage and let that be the very last thing BP wants to do.

Oh I see the BLA will not be approved on the failed PIII results but the botched PII results. That makes sense now.

You may have misunderstood that. An approval, based on a BLA, is NOT based on a clinical trial. One approves the drug for usage under well defined conditions based on a STUDY including pre-clinical, PI, PII and PIII results. A PIII like SUNRISE is not a must, you can have confirmational trials, etc. But in the end you file a BLA and EVERYTHING must be in it (also data that works AGAINST your drug). You may withhold NOTHING from the FDA.

Based on that data the FDA either approves or not. The FDA does not ask whether you do this based on a REGISTRATIONAL TRIAL as PII or PIII, whether it stopped earlier or not, etc. The FDA only needs to approve your trial design and they monitor safety and they make sure a sponsor does the follow-up of patients that started treatment and not let them hand in the middle of the trial. Besides that the FDA may grant things such as the Fast Tract that we got. But in the end they approve based on a BLA that either tells them this drug can be safely given to the public and has the need efficacy.

So in answer to your question: No, they would NOT approve on the PII trial data, they would get the salvaged trial data and they would get a comparable dataset but LARGER with 2 arms of 77 patients each (compared to 41+40 vs 40 in PII) that has ALSO be acquired in a REGISTRATIONAL format (Double Blinded, Placebo controlled).

Now at first one would say they CANNOT get approved on that because the 77 Bavi arm patients in SUNRISE did NOT beat the 77 CTRL arm patients by 2 months as was defined in the end-points. And without any other provisions that would be a 100% correct statement. However here is what is different in the PPHM case:

1) All patients were enrolled and PPHM said more then required by the FDA for unblinding (=mainly safety related). Very often this is NOT the case when trials are stopped early and hence FDA safety concerns exists, but not here.

2) The Bavituximab arm performed as expected. We don't even have to know how many months and how much margin PPHM added for the control arm expectations because as expected means "expected per trial design approved by the FDA and hence within FDA satisfactory scope"

3) 1st ln NSCLC ctrl arm, Pancreatic Stage/ECOG distribution, 2nd ln NSCLC dose switching (whether intentional or not) and now again in SUNRISE a control arm outperforming (while Opdivo last year had an underperforming one at 9.4 months which artificially increases their results) will motivate the FDA to look at what happened here because all these events to a same company/drug is ALSO statistically abnormal.

4) Now, point 4 above become more important because we have TWO PPHM sources that said some guarantees where given by the FDA as to effects on SUNRISE by the approval of drugs since it started (which show that the FDA must have had some appreciation for the delays the PII dose switching caused/would cause because otherwise such guarantees would be VERY UNLIKELY. We can prove that with PPHM's Yervoy+Bavi melanoma PI which was stopped because the SOC for melanoma changed and no such guarantees where present. Opdivo and Keytruda where the main two drugs that could and did approve before Bavituximab unblinding and constitute 3rd ln treatements.


Conclusion
If PPHM enters a BLA for 2nd ln NSCLC it will contain the pre-clinical and all PI, PII, ¨PIII data, it will have the SALVAGED PII data which was NOT available at the End Of PII meeting with the FDA, they'll have the data explaining why the control arm outperformed drastically and based on those results if it is due to 3rd ln treatments that where NOT available BEFORE SUNRISE started they have PRE-DEFINED rules for HOW TO DEAL with that and try to make the FDA look PAST the dramatical out-performance of the control arm based on FDA pre-agreed upon rules and guarantees related to that. We had a post last week (or the week before) from another company that stopped the trial and claimed they would start dialogue with the FDA never the less.

And for those claiming that filing a BLA for 2nd ln NSCLC after ALL communications by PPHM since the SUNRISE STOP would lead to class actions...well you can never avoid class actions, it is becoming a sport, but they must be justified and enforceable and PPHM didn't communicate ANYTHING that keeps them from filing a BLA that would lead to a justified and enforceable class action. But again all that IF, and only IF, PPHM files for a BLA in 2nd ln NSCLC Doce+Bavi which I kind of hope they don't.