Avid Bioservices Inc (CDMO)

[Protector]

PPHM to Feet on Earth Control!

1st ln NSCLC results are expected the coming days according PPHM statements, slides and corporate fact sheet that all place them in H1/2013. Does that mean we will get the announcement in H1/2013, or will we only see clinicaltrials.gov be updated to indicated the termination of this clinical trial after which the processing of the results can start? In this later case we will not see the 1st ln NSCLC results before September.

I can imagine that PPHM is not going to announce any results lightly and that they leave no stone unturned before informing the investment community given their past experiences with 2nd ln NSCLC announcements.

Another option is another extension of the period. That would be even better news then getting results. Why! Well some will say, "no" because you posted several times that FTM made it clear it is the difference between control arm and Bavi arm MOS that is of importance and extending the period again doesn't change that.

That is not absolutely correct. PPHM cannot, is not allowed, to extend the clinical trial if all patients would be death. So if they would extend the trial again it means patients are still alive. But there comes a point at which control arm patients being alive on pure SOC treatment isn't inline anymore with historical SOC only treatment statistics because the SOC alone cannot keep them alive that long as was proven in historical trials.

Let me put it this way in a 2nd ln example. If the MOS of 2nd ln NSCLC was somewhere between about 5.4 and 8.3 then control arm patients living 9 months would/could be considered plausible. Between 8.3 and 9 the difference is not that big. However if MANY SOC patients would suddenly, against all statistical historical data, live 15 months that would be suspicious.

Before some exited minds think I am posting about possible sabotage of the control arm let me explicitly say I am not. I am just saying that as time evolves, under normal non tampered with clinical trail conditions, the control arm patients are no longer massively in the expected historical survivor period range to contribute much to the remaining 20% survivors!

And since we start from the assumption of a REGULAR NON TAMPERED WITH clinical trial, UNLESS someone wants to say otherwise, we must assume that every further extension of the 1st ln NSCLC clinical trial is due to that 80% deaths level not being reached. Only Bavi patients can be responsible for that in a REGULAR NON TAMPERED WITH clinical trial because from SOC we know for sure that it isn't able to keep patients alive that long to constitute the bulk of the remaining patients.


But let me take another approach to all this, just reasoning into it from a completely different angle and see where we end up.

We know Bavi has a certain latency. It needs a certain amount of time before it activates the immune system and then seems to perform great. This isn't proper to oncology (cancer) applications but we also saw it in viral.

Now lets bring that discovery in line comparing 1st and 2nd line NSCLC clinical trials.

What is needed, and pancreatic proved that again, is that you get the most early stage patients. In a second line treatment, by definition, all patients have already received a PREVIOUS treatment say with 1st ln SOC. That means valuable time has past between diagnosis and before those patients enter the 2nd ln Bavi trial and cell damage and previous side effects already affected the patients who had no help from their own immune system at the extend that Bavi can activate it.

But in our first line NSCLC we are in pole position. We are combined with 1st ln SOC and get patients that get a first treatment and therefor in general, not always, should be healthier then those that 2nd ln is/was presented with. That is a NET ADVANTAGE for Bavi applications. For these patients BAVI can work from the start and activate the immune system in a very early stage. Just think about the intermediate results of our small but telling Breast Cancer IST!

So as a general conclusion logic dictates that if Bavi has a latency and that it performs best with early stage patients and that in a 1st ln ct you get in general earlier stage patients compared to a 2nd ln ct, THEN since the 2nd ln NSCLC results where super, official 60% MOS improvement and corporate 100+% due to the now understanding that the dose switching worked at our DISADVANTAGE on our Sept 7th announcement, then 1st ln should, hands down, outperform the 100% MOS.

Now where can it go wrong! Well for one we know there was something completely unexpected with the control arm as communicated in the beginning of past year, outperforming historical SOC only results. But assuming that, as Shan said in the PR, this is/may be due to human interpretation and the issue should be of the table if that factor is removed from the equation in the end results, I think we'll be alright. However, if Shan is wrong and the patients really outperform the historical stats consistently then something may be wrong because SOC cannot achieve that on its own.


Which brings us to the SOC. The 1st ln and 2nd ln SOC are NOT the same! That introduces another factor. Although we know that Bavi only needs the SOC to damage the cancer cells resulting in PS being exposed so that Bavi can disable this immune system suppressor and allows the immune system to detect the cell damage and be activated, it could be that both SOC's do not do that equally well. So combining Bavi with both of them in a 1st ln and 2nd ln clinical trial does not by definition have to result in both extremely good results.

But here again logic dictated that Bavi should work EVEN BETTER with the 1st ln SOC then with the 2nd ln SOC. Why? Well very simple. Both SOCs where not just placed there arbitrarily. They had to pass the FDA approval just like any other drug to become SOC! That means that the 1st ln SOC is the BEST working with the type of stage patients that are entering the first line treatment, otherwise it wouldn't have been it's SOC. That means Bavi should have much more opportunity to manifest itself on PS and activate the immune system in a VERY EARLY STAGE! Why, well because SOC has been established monitoring progression and a better working drug slows down tumor progression, or achieves some tumor regression, and in chemo that response can only be because cancer cells are more successfully destroy. That means more PS is exposed. So from that angle the results should be good too.

Finally something about the side effects. If a chemo like 1st ln SOC is more successful in destroying cancer cells then it is equally successful in destroying healthy cells. As posted before chemo's delivering system has very poor targeting which is why many side effects such as hair loss surface. As we know Bavi tempers that just because the immune system is activate and not only clean-up but also repair is sped-up! This should result in lesser intensive or, if equally intensive, in lesser duration of the typical side effects that are associated with the application of a given SOC. So in this safety and side effect area we seem again to have the advantage in 1st ln over second line. We would, in this reasoning, have to measure more/higher fever as of the moment that Bavi achieved the immune system activation because as of then the body wide cell clean-up and repair should trigger systemic functions and try to conserve energy for this process by giving the patient fever and try to immobilize him into rest and sleep.


Now, let's not be carried away and stay with our feet on Earth. I prefer to expect good results, rather then extremely good results, and then be disappointed because we have good results. If we get 15/25% MOS improvement then we have good results. Everything above that will heavily weight on partnership and later acquisition price setting.

Remember, all the above is not a reasoning set-up by a scientific researcher with hands-on experience of Bavi but just by a poster on IHub. But I am sure you can follow the reasoning why clinical trial extensions, of the past and possible new ones, are in our favor in a regular non tampered with clinical trial and why Bavi should perform better on healthier 1st line patients and in combination with a more performent 1st ln SOC in comparison to 2nd ln where it scored extremely well nonetheless!