Mezigdomide in New Combos: Early Results for Relapsed/Refractory Myeloma

So I'm Luciano Costa, my local physician at the University of Alabama at Birmingham, and I'm here at the ASH meeting in San Diego to 2024. We have the opportunity to present data on MEZI, we call novel-novel combination. So as many of you know, MEZIGdomide is the most potent cell mod, and I think for the patients, think of cell mod as being two generations up from Revlimid and Pomelis. So this is an oral drug, very active, very potent, taking very much like Revlimid and Pomelis, so one pill a day, three weeks out of four. And the prior experience with this drug in combination with dexamethasone that has now been presented and published, you know, gave responses in a little bit over a third of the patients, close to 40% of the patients. Most of those patients have received all the other conventional agents. So this trial that we're presenting here took the premise that there are some oncogenic pathways that become more relevant as the cancer becomes more resistant, okay? For example, the ARC map kinase pathway, the EZH2 pathway, as well as amplification 1Q downstream consequences. Some of those pathways are druggable. So we have drugs approved in other cancers or drug in development that could synergize with MEZIGdomide and try to overcome that intrinsic mechanism of resistance and lead to better activity. So what we have here is 56 patients treated in three different cohorts. One cohort was MEZIGdomide, dexamethasone, and Tasmetostat, which is an EZH2 inhibitor. Another cohort was MEZIGdomide, dexamethasone, and a drug that we're calling for short 158, which is a BAT inhibitor. And the third cohort is MEZIGdomide, dexamethasone, and Trametinib, which is a MAC inhibitor that is approved in melanoma, for example. And what we found is this is a very tough population. I think it's perhaps one of the first trials where the majority of the patients have seen a prior T cell redirecting therapy. Close to 40% of patients had had a prior CAR T cell therapy. More than a quarter of the patients had received and had become resistant to a bispecific T cell engager. So very tough population. And despite that, we saw that the treatments where it's all oral, all those are oral drugs, was well tolerated. The toxicity profile that we saw was very similar to what we have seen before with MEZIGdomide and dexamethasone, which is mostly reversible neutropenia that you can treat with growth factor. Some of those responses, and the responses are actually quite frequent. Remember the baseline here is MEZID-X give about 40% response in the last heavily treated population. Now here we saw a 50% response with EZH2 inhibitor. We saw about 35% response with the BAT inhibitor. But we saw 75% response rate with the MAC inhibitor. So that's really formidable. You have a combination that's all oral. That can be really a lifeline for those patients who have received all the three main classes of therapy, but the 87% are triple class refractory. Many of those have received CAR T cell or T cell engager, and these two are able to induce 70, 75% response with an oral agent. So this is, I think, very encouraging results. This program is going forward. And we anticipate it might perform even better and be even safer when we test that in earlier populations. Thank you.