Avid Bioservices Inc (CDMO)

[golfho]

FOCUS ON 2016 (FINAL)

My first few posts this year started with the header:
FOCUS ON 2016
FOCUS ON 2016 Part 2
FOCUS ON 2016 Part 3
Well we are nearly there…

It’s been a long and frustrating 3+ years since 9/2012 but I believe that we are now in sight of the finish line.

The recently announced planned trials with AZ will commence soon. Sunrise will finish enrolling. The melanoma trial is fully enrolled and I hope that we will be able to present some data on this trial at the next NYAS meeting in February…though at this moment we are not presenting. Perhaps ASCO...?

http://www.nyas.org/Events/Default.aspx


Monday, February 29, 2016 | 9:00 AM - 5:00 PM

Emerging Approaches to Cancer Immunotherapy
Keynote Speakers: Renier Brentjens (Memorial Sloan Kettering Cancer Center), Jedd Wolchok (Memorial Sloan Kettering Cancer Center)
Speakers: Jane Gross (Emergent Biosolutions, Inc), John Hunter (Compugen Ltd), Jane S. Lebkowski (Asterias Biotherapeutics), Jens-Peter Marschner (Affimed AG), Charles Nicolette (Argos Therapeutics, Inc), Charles L. Sentman (Dartmouth Geisel School of Medicine), Roland Walter (Fred Hutchinson Cancer Research Center)
Emerging strategies for Cancer Immunotherapy are changing the face of cancer treatment. This symposium will bring together experts in immunotherapy and immunology to discuss emerging approaches, challenges, and opportunities in this evolving field

In the interim I’ve been keeping myself busy playing with numbers…It’s a pastime.

For nearly two years I’ve maintained and modified projections on the Sunrise trial. I’ve traded notes with several posters during that time. My latest version narrows down the enrollment rate to a range one patient enrolled every 4.0 to 4.75 months (121.6 to 144.6 days)
That is represented in three scenarios noted below. On of which will go away in 5 days.

I will now ramble on…

For the average of one patient every 4.0 to 4.25 months which represents 4 months and a week (121.6 days to 128.6 days) enrollment will complete around the beginning of November and that didn’t happen.

For the average of one patient every 4.25 to 4.5 months (129.6 to 136.6 days) enrollment will complete around the end of November to the beginning of December.

For the average of one patient every 4.5 to 4.75 months (137.6 to 144.6 days) enrollment will complete around the end of January to the beginning of February.

This will be the first reality check. Did we complete enrollment by the end of 2015 or not. We did not complete enrollment early (November) so the first scenario is looking poorly. If we complete enrollment on time (December) then the second scenario is in play. If we complete enrollment late (January-February) then the third scenario is in play.

We will know this within the next ~35+ days.

The next issue for me is when the two scheduled look-ins will occur.
We have been told that the look-ins will occur at the 33% & 50% point of a predetermined number of events…And we don’t know the number.

The only guidance the company provided was at the last CC when SK was repeatedly asked about the companies anticipated look-in time frame and finally deviated from his standard answer of “We are not prepared/able to provide any guidance at this time” to…Within the first half of 2016 for the first look-in and around mid year for the second.

Here are my assumptions on number of events and most recent updates.
Assumption #1 is, assume that 80% of total enrolled patients (80% X 582 = 466) 33% of 466 is 154 and 50% is 233

Assumption #2 is, assume a fixed number of patients enrolled I chose 500. 33% of 582 is 164 and 50% is 250

For MOS I chose a subset of possibilities 7, 10, 12, 15, 18 & 20 months. I then selected several combinations of the above subset that might represent some possible outcomes. i.e. (10:7) or (15:10) etc.

What has my three scenarios indicate to date?

Scenario #1 In general for some of the very low MOS numbers the event trigger would have already occurred. For some of the very long MOS numbers the event trigger for first look-in will not occur until the February to March time frame and for the second look-in around the March to May time frame.

For scenario #2 (Enrollment complete at the end of December) the very low MOS numbers the event trigger would have already occurred. For some of the very long MOS numbers the event triggers remain fundamentally the same as the first scenario.

For scenario #3 (Enrollment complete at the end of January or beginning of February) the very low MOS numbers the event trigger will occur between now and December. For some of the very long MOS numbers the event trigger for first look-in will not occur until the February to April time frame and for the second look-in around the March to end of June time frame.

So what can I conclude now with only the above information?

The pattern appears to me to indicate that the MOS numbers must be on the high side. Once we have a date for complete enrollment the average rate of enrollment will be known and the rate of events will be constrained to a narrower number of possibilities. My goal is not to predict the MOS numbers. My goal is to determine the time frame for the two most important SUNRISE milestones, first and second look-ins AND more importantly predict the outcome for these events.

From a previous post…

Now for my interpretation of certain words:
Possibility: I use this term to define things that can occur regardless of the odds.
Probability: I use this term to define things that can more likely occur and generally I try to attach a percentage of probability (Odds) of it occurring.

This is the interesting part…IF the MOS numbers are tracking towards a ratio of 15 months for the Bavituximab combo vs. 10 months for placebo combo then my predicted number of events for first look-in indicate:
Bavituximab combo = 30 to 40 events
placebo combo = 120 to 130 events

What are the odds (probability)?
28%...A little better than 1 in 4
That implies that there is, in my view a 28% probability that the trial could be stopped at the first look-in.
Not likely…But possible with a 28% probability.

SECOND LOOK-IN:
Bavituximab combo = 70 to 80 events
placebo combo = 150 to 165 events

WELL NOW…
What are the odds (probability)?
47.6%...Nearly a 50-50 proposition…!!!
Slightly less likely then likely by only 2.4%

Some other thoughts…

IF full enrollment is achieved by 12/2015 and the treatment cycle takes about 4 months then all patients will have been treated by the end of April 2016. If the first look-in occurs as management predicts in the first half of 2016 then HOW AND WHY WOULD OR COULD THE IDMC STOP THE TRIAL FOR SAFETY…??? Almost everyone would have received the full course of treatment. What are they going to do…??? Suck the treatment out of them?

Here’s another thought…
There has been some discussion on the board on the topic of the IDMC recommending stopping the trial at the first or second look-in and the impact of that stopping. Here’s my take; if the IDMC recommends that the trial be stopped in either look-in it will have ZERO impact on the results of the trial…ALL patients will have had their full course of treatment, the only thing left is continuing the data collection that would be on the sponsors nickel. Do you really think that PPHM would not spend the extra money to get the full data set? The money is in the plan already. If the IDMC recommends stopping the trial it is implied to me that that means that they think that there is enough evidence to recommend seeking marketing approval from the FDA before the complete data set is achieved. Implied is that the interim data at one of the look-ins is overwhelming. Does anyone really think that all of the patients would be lost to further follow-up?

Regards
golfho