VIDEO: Role of targeting GPRC5D in multiple myeloma

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It's over-expressed on particularly malignant plasma cells and so we like that because, for example, when you target GPRC5D with bispecific antibody known as talquetamab, unlike BCMA bispecifics, we're not seeing that same infection signal. And I think part of that, it has to do with the dirtiness of the target. I think BCMA's probably more broadly expressed, not just on myeloma, but other B cells. When you try to repeatedly target that, yes, you kill myeloma, but you also really deplete the immune system and get profound hypogammaglobulinemia and a lot of serious infections despite myeloma control.

With GPRC5D, we don't see that immune paralysis and I'll give you an example of how this plays out: I was in New York in 2020 when the COVID pandemic was happening and obviously we were overwhelmed in New York City by COVID, and every day, a new floor of the hospital became COVID only. And we had a lot of patients on clinical trials at that point, and what was really unique is that the DCMA-targeted patients had a lot more complications. We saw more infections, serious infections, admissions, whereas GPRC5D-treated patients didn't seem to have that same profile. We didn't see as many COVID-related deaths. And we actually studied, when you look at vaccine responses, you could see good antibody production to COVID vaccines, even on patients on active therapy.

So that's why the target selection is so important. Of course, GPRC does come with other side effects, but that's the reason we wanna try to target an anagen that's uniquely expressed on, ideally, the malignant plasma cell, not even normal plasma cells, and let alone other tissues, so that's the reason for the target importance.