CAR-T BMS-986354 | Luciano Costa, MD, PhD | ASH 2022

Hi, I'm Luciano Costa. I'm a myeloma physician at the University of Alabama at Birmingham. I'm here at the American Society of Hematology annual meeting in New Orleans. I want to share with you some of what I presented at this meeting. I had the privilege of presenting data on products called BMS 986354, which is a different type of CAR T cell therapy. As you might know, there are two CAR T cell therapy in the market. They both target BCMA. This one also targets BCMA with a fully human antibody based construct. The difference has been mostly on manufacturing, where you have some innovations that allows for more potent cells that are able to proliferate faster, produce more cytokines, which are the proteins that the cells use to orchestrate the response of the immune system. So as a result of that, we have products that can be manufactured faster. We can infuse one tenth of the number of cells than other CAR T products. And using this trial, we had 65 patients with very advanced disease, almost all patients with triple class refractory myeloma. And they still had an overall response rate of over 95%. But just as important as a very high rate of response was the safety that only one patient had a high grade of CRS and only one patient had a high grade of neurotoxicity. And in both cases, that was promptly reversed with therapy. So we think this is certainly an important stepping stone to developing better CAR T cell therapies that can be manufactured more quickly. Therefore, we can serve more patients, can deliver with high level of efficacy, but also with a very excellent safety profile. Also, at this meeting, my UAB colleague, Susan Ball, had an abstract that with another CAR T cell treatment, aim at GPRC5D. So as we talk about, BCMA has been the favorite target for CAR T up to this point. But GPRC5D is another protein on the surface of myeloma cells that has been targeted before effectively with the bispecific antibody, for example, toquetamab. But now there's a CAR T cell product that aims at the same target. So in this study, it's a phase one dose finding study. There's a little bit over 30 patients treated. The response rates were over 80%. But importantly, among the patients who had received other BCMA-directed therapy, mostly CAR T, you still had a very high chance of response, over 70%. And the patients who have not received other prior CAR T or other BCMA-directed therapy, their chance of response was 100%. Also, excellent safety profile with no high-grade neurotoxicity or CIS. So this gives us the hope that we're going to have development of not only more CAR T's that go after the same target, but also as we're going to have CAR T cell therapies that are safe, effective, they use an alternated target. And why is that important? Because we're going to discover more and more that as we use more of those immunotherapies, is expected at some point, we're going to start seeing progression or resistance that is driven by modifications on the target itself. You know, we're seeing very frequently, you know, mutations or losses of the target being described. So it's on everybody's benefit that we have more therapies that go after a different set of targets.