Avid Bioservices Inc (CDMO)

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SUNRISE, what are the chances?

SUNRISE is PPHM's 2nd ln NSCLC (Lung Cancer) PIII clinical trial that is currently running in 141 treatement centres world wide (and counting). It will enrol 582 patients at the last in DEC 2015 according PPHMs conservative estimates and projects and end of trial in DEC 2016 with a goal to achieve a 50% statistical significant improvement over SOC (Docetaxel alone, in this trial Docetaxel+Placebo) with Docetaxel plus a 3mg/kg body weight Bavituximab dosing in 4 cycles of 21 days.

What are the chances that this clinical trials reaches it's goals and that the cocktail Docetaxel+Bavituximab (or Docetaxel generic+Bavituximab) could become a SOC-grade prescription for 2nd ln NSCLC?

For staters one must keep in mind that it is not uncommon for PIII CT's to fail. Certainly if the PII results were not exceptional that risk is bigger then otherwise.

Secondly, what must we look at to make an estimation of chance? Well certainly not CT's on Prescription #4 :). We must look at two things:

- For the SOC we have the historical data that gives a clear view on how Docetaxel alone or Docetaxel+Placebo performs.

- For Bavituximab we have the past clinical trials were it was combined with Docetaxel (that is this 2nd ln NSCLC PII and our 2nd ln Breast Cancer PII CT's). The other Bavi-combination are worthless to compare with because our PIII clinical trial is not with Paclitaxel, Sorafenib, etc, etc, etc but with Docetaxel.

What is our plankton to reason with

1) Bavituximab did VERY WELL with Docetaxel in Breast HER 2 PII CT
2) Bavituximab did EXTREMELY WELL with Docetaxel in 2nd ln NSCLC PII CT
3) PPHM has stated (SK) that there seems to be a synergy with Doce/Bavi.
4) The PII 2nd ln NSCLC was sabotaged in Bavi's disadvantage
- the results of 113% (133% cj) SOC improvement must be BETTER
- the PII was stat.sig both arms combined
- in the PIII the Ctrl arm patients will NOT receive Bavituximab
- in the PIII the Bavi arm will NOT receive placebo
5) The PIII has a much higher 'n' value for both arms
6) Even the first look-in will already have better 'n' values
7) Higher 'n' is good for achieving better 'p' values and stat. sig.
8) Bavituximab is safe (proven on about 500 patients)
9) PPHM aims for 50% SOC improvement (while Bavi showed 100+% in PII)

The reasoning

The first thing that differentiates this 2nd ln NSCLC CT from many others are the extremely good results it achieved in PII, knowing that it even achieved them under the sabotage that was NOT in favour of Bavituximab. Even better it was ALREADY stat.sig and without the sabotage the FDA would probably have agreed with a PIII confirmational CT rather then one with 582 patients. But OK, things are what they are and at least thanks to the whole debacle we got rid of AbbVie and breadcrumb propositions.

Secondly we aim only for 50% improvement on SOC and that is LESS THEN 50% of the 113/133% improvement Bavi performed in PII and stat.sig.

Third, since this trial will be/is watch closely, PPHM is aware of sabotage risk, the Ctrl arm and Bavi Arm will separate even better as all patients will receive the treatment as planned and no Bavi for the Ctrl arm will lower the MOS of the control arm (below 5.6) and the other way around for the Bavi arm (unless randomizing gives us pancreatic alike sick patients in the Bavi arm vs healthy patients in the Ctrl arm).

It is BEFORE ALL the lowering of the Ctrl arm median that will define what 50% over SOC means in months in this trial, while it is the expected increase in the Bavi arm where everyone will have received the duly deserved amount of Bavi this time that will help reaching it faster because those patients will now have more chances to see their results added to the right of the median.

But, you know, we are talking about 'chances' here, the PII being stat.sig is actually the best way to say: It was not BY CHANCE because that is EXACTLY what stat.sig means. And Dr. Garnick has made it clear that, in his long career of approving some of the most popular drugs for Roche/Genetech, he did not often see a PII to be stat.sig and that he was IMPRESSED with Bavi's results.

But also the statement of SK that there is a kind of synergy between Docetaxel and Bavituximab (reason the more we do not compare with Liver or Pancreatic or whatever results because PPHM never claimed there was any synergy with Paclitaxel or any other chemo treatment -yet- for that matter) is very important. We should remember that Bavituximab already proved BEFORE that it works well with Docetaxel in our Breast Cancer clinical trials. And since we are talking about chance, TWO good PIIs reduce the chance that it was by change also.

But read this (source PPHM web-site)

Second-line breast cancer: In August 2011, we reported promising 20.3 month median OS from a trial evaluating bavituximab in combination with docetaxel. This compares favorably to 11.4 month median OS from a separate historical control trial in a similar patient population using docetaxel alone. Median OS is consistent with earlier encouraging data presented at ASCO 2010, including ORR of 61%, versus historical control data of 41% ORR using docetaxel alone.

There is something about that data that we NEVER compared to the 2nd ln NSCLC results (probably because we were majorly blinded and occupied by all the dose switching stuff). That Breast Cancer result is about 90% improvement over SOC.

So there seems to be more about this synergy and both product combined seem to augment efficacy on average about 100% over SOC (say 89+113/2), not just 5 or 10 or even 20 or 50%, but 100%. And that is quite exceptional, not unique but certainly much higher then what is needed.

Conclusion
Although certainty never exists it is my personal opinion that chances for success of SUNRISE are near 100% when it comes to achieving the 50% SOC improvement in a statistical significant way and 100% when it comes to safety because in that area all doubts are gone Bavi has no meaningful side effects of its own.

Why didn't I say 95% (because stat.sig on our p-value allows for a few percentage of risk - the FDA has chosen the 0.02 on that basis). Well very simple because we have 2 Bavi+Docetaxel super results, we don't need to achieve 100%, just 50%, and the PIII will not be sabotaged.

Hence I translate my overall chance on success to 99.75%. That is my full disclosed data and reasoning educated guess, not just my one-liner in which I try to play peoples ignorance to make them see things my way.

Timing
I never have hidden behind chairs or desk that I don't believe that PPHM will have to run this clinical trial till the full end. I firmly believe in an early stop, if not by the data monitoring committee then at one of the look-ins.

This is my educated guess for 1st and 2nd look-ins while here is some more on patients enrolment for the 2nd ln NSCLC CT and on the effect all this might have on the PPHM PPS appreciation in time.

Enjoy.