Phase 1 Therapy PHE885 BCMA-Directed CAR-T Cell Therapy for RRMM | Adam Sperling, MD, PhD | ASCO 2023

I'm Adam Sperling. I'm a medical oncologist at the Dana-Farber Cancer Institute in Boston, and I specialize in treating patients with multiple myeloma. I presented at the ASCO annual meeting this week our updated clinical data from a phase one study of PHE 885, which is an anti-BCMA CAR T cell product for patients with relapsed and refractory multiple myeloma. So I think one of the most exciting developments in multiple myeloma therapy has been the development of cell therapies like CAR T cells, and this is a technology in which we remove a patient's own immune T cells and then engineer them in the lab to target the multiple myeloma cells. And we do that by targeting specific proteins on the myeloma cell surface, and the target that has been used most in multiple myeloma is a protein called BCMA. And so as you can imagine, this is a complex process, and so even though we've had two products that are very successful, IdaCell and CiltaCell, and have been approved by the FDA over the last couple of years, the problem is that for a lot of patients, you have to take the cells out, you have to engineer them. That can take weeks, often six to eight weeks to engineer the cells and get them back. And there are a lot of patients who have very aggressive disease who would certainly benefit from this treatment but just can't receive it because they can't wait for that lengthy period of time. And then the other issue is that even for patients who receive this therapy, they often relapse after months to years, depending on their response. And so we really need to develop CAR T cells that we can engineer faster to get them back to patients and where we've improved the product and potentially the characteristics of the T cells themselves such that they produce more durable and better clinical responses. And that was the goal here with this study. And it uses a novel manufacturing approach, which has been called the T-Charge approach. And that shortens the manufacturing period to under two days. And so that has a couple of advantages. One, you're manufacturing the cells much faster so they can get back to patients faster. And the other advantage is that because they're not grown outside the body in an artificial media for days to weeks, the cells can actually grow and expand mostly in the patient in a more natural environment after they're re-infused. And we think that that has the potential to improve the characteristics of the T cells to allow them to expand for or show much greater expansion, persist so they will stick around for longer and potentially have better function. And we've shown certainly in the lab that we can see some of these improved characteristics. But I think one thing we'll have to see is over the long term whether or not that translates to better outcomes for patients. So the study that I presented as a phase one study where we gave different doses to patients to see both the safety of the product as well as how well it works. And in the study we treated 50 patients at various dose levels ranging from 2.5 to 20 million cells. And we saw expansion of the cells in patients in basically all cases. And we saw a 98% response rate. So only one patient didn't have a response. So a very, very high response rate with very deep responses. So many patients who had minimal residual disease negativity. And the safety profile was very similar to other CAR T products. So overall we're very excited about this product and then we hope that it will shrink the manufacturing time to increase availability and may improve the actual product itself which we hope will produce better responses in patients and durability of the responses in patients.