The Link: Changing the Nature of the Game
Sitting Down With… Robert Pierce
(from an interview given by The Pathologist in 2014)
What was the story of PD-1?
The PD-1 program came to DNAX when we acquired Organon, who had planned to move forward in human development without “companion” mouse studies. This was a bold approach. Although it was clear from the literature that anti-PD-1 was a strong candidate molecule for immuno-oncology, Schering-Plough were more conservative and tasked us with building the mouse surrogate program. When Merck and Schering-Plough merged,the PD-1 program was "deprioritized" until Bristol-Myers Squibb published their candidate’s Phase I data.
Then it was like Lazarus – raised from the dead! It’s amazing that Merck still got first approval in the US. I think they benefited from going after ipilimumab-refractory melanoma patients as their main indication; that triggered the breakthrough therapy designation. It’s exciting that we have such a good idea of who responds to anti-PD-1 and who doesn’t. That’s critical to why PD-1 development is going so fast – in large part, we understand the mechanism of action.
My first ah-ha! moment came when I saw tumors IHC-stained with PD-1 and PDL1. Patients who respond to anti-PD-1 have cytotoxic T cells in their tumors; you only need immunology 101 to say, “Wow! The T cell coming in is generating a cytokine which upregulates PD-L1 to shut off the T cells.” It’s a homeostatic mechanism we evolved – every immune reaction contains its own brakes, and tumors hijack them. It took a long time to convince the scientific community that immunotherapy would work – over 100 years of chasing Dr Coley’s vision of harnessing immune responses to treat tumors. If you think about where we are with anti-PD-1 today, where might we be if this transformation had happened earlier? What new treatment strategies hold most potential?
