ROUND TWO...MAYBE MORE ACCEPTABLE...
THERE IS ONLY ONE THING THAT KEEPS ME AWAKE AT NIGHT.
For those of you who have not read my early posts; the subject matter of my posts for the first few years consisted of calculating the Risk of this investment in PPHM vs. the Reward. In my risk assessment prior to the September 2012 disaster I considered the Risk to be on par with the historical statistical success rate for clinical trials going from a successful PII trial to a PIII trial (About 1 out of 3-4).
The one thing that I have not been able to assess was out and out sabotage by a BP or Hedge Fund. How does one factor that in? To what level will these (XXX) sink…After 50 years (STUFF HAPPENED...) BP’s are paying fines in the billions and now consider these fines just the cost of doing business and few…very few…go to jail.
As someone else already posted (Sorry I don’t remember) I’ll para-phrase…The sabotage is both bad & good. in that it was bad because of the delay to market & added cost but it was good in the sense that Bavituximab is a clear paradigm shifting threat to many PB’s…So much so that it is worthy of sabotage. So in my opinion the risk has risen significantly; but, I can’t quantify it.
For me it is the same as being in a high stakes no limit poker game and after you just pushed in all of your chips and declared “All in” you discover that the game is rigged. Huh…??? Excuse me…!!! Say what…???
No one knows, too what level these scum_bags will go. What was their purpose? Was it to slow down development of Bavituximab until they could catch up or bypass it? Hobble PPHM and then scoop it up as CP says…For breadcrumbs? Is there still more to come? Will they try to somehow subvert the SunRise trial? GOOD GRIEF…I have to stop thinking about this. But unlike a poker game, I can take my money off the table at any time. Everyone of you can. BUT I WON’T…
WHY…???
Because I am convinced beyond a doubt that Bavituximab works.
What if the nefarious forces succeed in destroying most of the current shareholders value?
Currently I am shifting between sitting in my darken bedroom and sucking my thumb and thinking very very dark thoughts.
At the end of the day…If things work out well, I’ll enjoy the remainder of my life. If the nefarious forces win…I may go postal.
NOW LOOKING FORWARD…
MY ASSESSMENT FOR THE NEXT 12 MONTHS:
Before I start I would like to thank Dia76ca again for starting this list of potentials. I have modified and grouped things in what I think might be the chronological order.
1 - SUNRISE TRIAL:
2 – IST’s, FUTURE TRIALS & COLLABORATIONS:
3 - FINANCE:
4 - LAWSUITS:
1 - SUNRISE TRIAL:
To my amazement the long hockey stick trial site opening has occurred. We now have a total of 143 trial site opened. FWIW 13 of those 143 sites are sites that were used in the PII trial. I have no idea when the first look-in will occur but, my estimate is aligned with Jbain, geo & several others. That is, we may hear something around the June to September 2015 time frame on the first look-in. Baring any shenanigans I believe that the results of the first look-in will produce results similar to the PII trial and that will prompt an early marketing approval from the FDA by the end of 2015 or the beginning of 2016.
2 – IST’s, FUTURE TRIALS & COLLABORATIONS:
Phase I/II Trial: IST of bavituximab in combination with sorafenib in patients with liver cancer
Like all of our IST’s there is a very long gestation period before the birth of data. We may hear about new tests that are surrogate indicators of active immune response in November. What about the trial data…? What’s with Dr. Yopp & Bayer…Inquiring mind want to know. More on that later…
Phase Ib Study: IST of bavituximab in combination with carboplatin and pemetrexed in patients with previously untreated Stage IV NSCLC
In the Overview section of PPHM’s Clinical Trials it states:
“Enrollment Complete” The clinicaltrials.gov site last updated in February 2014 states “This study is currently recruiting participants”
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
The above from clinicaltrials.gov tells the story…
Phase I Study: IST of bavituximab in combination with paclitaxel in patients with HER2-negative metastatic breast cancer
We are now waiting for the published paper from Dr. Alison Stopeck could be published by December...Hopefully.
Phase I Study: IST of bavituximab in combination with capecitabine and radiation therapy in patients with advanced rectal cancer
Still recruiting…
As of the May 2014 update:
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: August 2015
A Two-arm, Single Center Phase 1b Trial of Bavituximab Plus Ipilimumab in Advanced Melanoma Patients
This trial has been recruiting for 5 months now. They hope to complete the trial by 3/2016. Of importance here is the fact that Ipilimumab (Yervoy) is BMS’s already approved anti-CTLA-4. More on that later.
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Open-label, Single Arm, Tumor Imaging and Dosimetry Study of I-124 PGN650 in Advanced Solid Tumors
As of the last update in July this trial is still recruiting and has an estimated primary completion date of April 2015.
PRE-CLINICAL:
In August PPHM reported “Results show that the combination of a PS-targeting antibody equivalent to bavituximab administered with an anti-PD-1 antibody displayed statistically significant tumor growth suppression while also demonstrating a significant increase in tumor-fighting T-cells into the tumor microenvironment compared to anti-PD-1 antibody treatment alone in an immune competent animal model of breast cancer.”
AND:
“This presentation includes new data showing that animals treated with the PS-targeting antibody ch1N11, the preclinical equivalent to bavituximab, in combination with anti-PD-1 in an EMT-6 mouse breast tumor model, significantly delayed the treatments group median tumor growth compared to anti-PD-1 alone. Specifically, following once weekly treatments of ch1N11 plus anti-PD-1, tumor growth was inhibited by 78.7% (p= 0.0048 on day 23) compared anti-PD-1 alone. In addition, 50% of the tumors treated with the combination either regressed or did not progress compared to 0% for anti-PD-1 alone. Also, the once weekly combination treatment with ch1N11 and anti-PD-1 led to a 78% and 81% increase in intratumoral CD4+ and CD8+ T cells, two key indicators that show that tumor fighting immune cells are present in the local tumor environment, compared to the single agent anti-PD-1.”
What is interesting about this pre-clinical report is that PPHM DID NOT reveal whose anti-PD-1 it was. Roche…??? Merck…??? BMS…??? In my view for a reason. They most likely tested all of the PD-1 candidates. That implies the following. PPHM is in collaboration with:
(From cjgaddy’s super fine intro)
Examples of anti-PD-1 drugs in development: (PD1=”Programmed Cell Death Protein 1”)
1. Merck’s pembrolizumab (aka MK-3475, formerly=labrolizumab)
2. BMS’s nivolumab (aka BMS-936558)
3. Curetech’s pidilizumab (aka CT-011) Teva/partner term. 1-2013
4. AZ/MedImmune’s AMP-514 (aka MEDI0680)
5. GSK’s AMP-224 (collab. With Amplimmune)
No report yet on the following
Examples of anti-PD-L1 drugs in development: (PD-L1=”PD1 ligand”)
1. BMS’s BMS-936559
2. Roche/DNA’s MPDL3280A (aka RG7446)
3. AZ/Medimmune’s MEDI-4736
4. EMD/Serono’s MSB0010718C
And then from the IASCL poster we see a list of some downstream immunostimulatory treatments such as: Anti-TGF-b, Anti- IL-10, GM-CSF, IFN-a, IL-2 & Vaccines
We can stop at this point. Knowing that we are in collaboration with dozens of candidates implies that we are in collaboration with MANY of the major BP’s and probably with several second tier pharmaceuticals as well.
Now back to…”More on this later.”
We are in clinical trials with the following:
Bayer: Sorafenib + Bavituximab = Liver
Sanofi-Aventis: Docetaxel + Bavituximab = NSCLC
Bristol-Myers-Squibb: Paclitaxel + Bavituximab = with HER2-negative metastatic breast cancer
Bristol-Myers-Squibb & Eli Lilly: Carboplatin & Pemetrexed + Bavituximab = with Stage 4 NSCLC
And we have dozens of collaborations in pre-clinical. I was stuck on the word “collaborations” a while back. Partnerships, collaborations why bring in another term…? We all pondered this.
This is what I think is going on. We are collaborating with as many of the downstream immuno’s that we can. (Note: We cannot use anyone’s produce; that is not FDA approved without the sponsors’ approval.). I think that we are splitting the cost of these low cost pre-clinical trials. When all of the data is in we will select the most promising candidates and K & L Gates will negotiate as best they can regional partnerships. We don’t need a partner for the PIII NSCLC trial it will be paid for by us. I can’t see beyond this for now.
3 - FINANCE:
I think that management will try to maintain a cash reserve of ~$60M to $80M to fully finance the SUNRISE trial and continue to share the cost of the pre-clinical trials.
4 - LAWSUITS:
The frivolous CA lawsuit will go away some time. It is only an annoyance.
It appears that the CSM lawsuit will go on for some time to come.
OT observation:
Many of the longs are very frustrated, me included. But to lash out at management is miss-directed. They didn’t sabotage the trial and they had an agreement in principal for a partnership. Under the circumstances IMHO they are doing a commendable job. This was not an invitation to debate the subject. I’m just voicing my opinion and I respect everyone’s right to have a different one.
Regards
golfho
