So BCL-2 inhibition has really been demonstrated to be one of the more effective treatments for hematological malignancies that has emerged over the last decade. The challenge with the current BCL-2 inhibitor that we have, venetoclax, is that many patients either don’t respond or respond initially and then relapse. There is a need for better BCL-2 inhibitors that do the job, but overcome some of the problems that we see with venetoclax...
So BCL-2 inhibition has really been demonstrated to be one of the more effective treatments for hematological malignancies that has emerged over the last decade. The challenge with the current BCL-2 inhibitor that we have, venetoclax, is that many patients either don’t respond or respond initially and then relapse. There is a need for better BCL-2 inhibitors that do the job, but overcome some of the problems that we see with venetoclax. And there are a number of emerging BCL-2 inhibitors. There are inhibitors of BCL-2 alone, and then there are inhibitors of both BCL-2 and BCLxL. When we’re thinking about this class of drugs, we want drugs that work for more diseases than venetoclax does, but have less toxicity, that do not cause tumor lysis syndrome, that can be given as an oral tablet, can be given without the palaver of venetoclax dose escalation, and are easy for patients to take- so one tablet a day. We have, in the emerging BCL-2 selective inhibitors, drugs such as lisaftoclax, which has demonstrated some early efficacy in a number of hematological malignancies, as well as sonrotoclax, which is made by Beigene. There are a number of others that are earlier in their development. In the BCLxL/BCL-2 co-inhibiting agents, we have drugs such as navitoclax, which is an earlier BCL-2 inhibitor that has been resurrected. That drug is complicated by on-target thrombocytopenia, and so dosing needs to be done with care. And also a drug called AZD0466, which is given as an IV agent once a week. So there are a number of emerging drugs, they all have pros and cons, how they compare to venetoclax really is yet to be seen.
