The main first wave I-O players for PPHM to talk to
I-O Scene for bavituximab
CTLA-4
ipilimumab/Yervoy BMY Approved Melanoma
tremelimumab AZ PIII NSCLC, others
AGEN-1884 Agenus PI
PD-1
nivolumab/Opdivo BMY Approved Melanoma, NSCLC, kidney, others
pembrolizumab/KeyTruda MERCK Approved Melanoma, NSCLC, others
REGN2810/SAR439684 Regeneron/Sanofi PI
MEDI-0680 AZ PI
SHR1210 Incyte/Jiangsu PI
PD-L1
atezolizumab/TECENTRIQ ROCHE PIII NSCLC, bladder, others
durvalumab AZ PIII NSCLC, melanoma, others
avelumab PFE PIII NSCLC, stomach, others
BMS-936559/MDX-1105 BMY/Medarex PI withdrawn before enrolment
PPHM has quite some more parties it can talk to then just the big 4 when it comes to I-O combo's with the first wave I-O products PD-1/PD-L1 and CTLA-4.
However, I think CTLA-4 will disappear out of the picture although BMY showed that Yervoy combined with Opdivo gets very good results, were it not for an even smaller footprint of responders then both alone and at a very high price.
After Medarex, BMY abandoned the PD-L1 and focuses on PD-1 and CTLA-4 were it currently is undisputed market leader. The trial is marked withdrawn on clinicaltrials.com
AZ wasn't very successful with it's CTLA-4 program but claimed to plan its own CTLA-4/PD-L1 combination. If PD-L1 is a better target then PD-1 that could be a good move against Opdivo+Yervoy. Then add some bavi in the cocktail to increase responders.
But now that Roche has made the claim that anti-PD-L1 is the better target and that ROCHE, AstraZeneca and PFE are moving to the end of their PIII's in anti-PD-L1, I think the battle will take place there. In the PD-1 arena everyone staged at PI and only BMY and MRK continued the road to approval. That has placed them in the position that they are in today #1 and #2 because the others changed course towards PD-L1. BMY did the opposite and has given PD-L1 up, probably due to the Medarex story. That could become a regrettable decision in the future.
With Durvalumab PPHM will have a good combination for Bavituximab/TALCEPTRX. Both target the ligand and not the receptor. Also atezolizumab/TECENTRIQ from ROCHE would be a good candidate as would be avelumab. Roche is loosing its world leader position in oncology and must add some speed. AZ wants away from the #4 position in I-O according its CEO and PFE, who actually was more in the shadow, wants in. If PD-L1 is the right choice then they'll be on track if avelumab would be approved.
For PPHM having 3 BP's with a PD-L1 all 3 in PIII and all 3 with a pressing goal is a good thing. As posted before the difference will be made by the combination partners and they want to own them. And AstraZeneca has an advance for the moment, PFE has the pocket depth to solve things outside the lab and Roche is actually putting full steam on atezolizumab/TECENTRIQ and might suddenly surface on the PPHM scene.
So I wonder if the Merck KeyTruda+bavituximab in Liver trial is some kind of contingency in case PD-L1 wouldn't be the good choice.
