SOHO 2026 | Phase I ENABLE trial of ELVN-001, a selective ATP-competitive inhibitor of BCR::ABL1, in R/R CML

So this is the ENABLE trial. It’s a Phase I study that evaluated this compound ELVN-001, which is an oral ATP competitor, ABL1 inhibitor, for the patients with relapsed/refractory CML. So in this study, we treated patients who had failed at least one prior drug. Either they had resistance or they had side effects to prior therapies. And then they went on to receive the ELVN-001 at different dose levels. Of course, this is a Phase I study. And I think what is really characterizing this compound, as I said, it is a direct ABL1 kinase inhibitor, ATP competitive inhibitor. But I think the biggest characteristic that differentiates this compound from other ATP inhibitors is the fact that it doesn’t have off-target effects and it’s very potent and very selective in the inhibition of ABL1. And that’s why we are seeing better tolerability and less side effects with this compound compared to the other FDA-approved ATP competitors. In this study, we have treated so far at the last cut-off that we presented today at SOHO, 161 patients. The results look very promising. So far, almost 80% of the patients still continue therapy. Those patients are heavily pretreated. They have received anywhere from one to up to seven lines of therapy. More than 70% of the patients had received three or more previous treatments, including ponatinib, including asciminib. So really heavily pretreated patient population. Most of them, 61%, had failed prior drugs because of lack of efficacy or resistance. And when we looked at the outcomes of these patients, almost 60% or more did achieve a major molecular response after six months of therapy, primarily at the optimal biologic dose, which was determined to be 80 milligrams once per day. This drug is very well tolerated, it is very safe, the grade three or higher side effects range between one to five percent, so not really much less than 10%, discontinuation rate, in fact, we had only six percent of the patients stopping ELVN-001 because of side effects, so very effective drug, very, very safe drug. And also importantly, in patients who had, I would say, asciminib failure or prior asciminib exposure, the rate of MMR was between 60 to 70%. So this drug had shown promising efficacy among patients who received multiple drugs before, including the newest drugs such as ponatinib or asciminib. So in summary, I think this drug is very safe. It is very effective in patients with CML and chronic phase who have failed multiple lines of therapy. And now before the end of 2026, the pivotal trial in ENABLE-2 will be open for accrual of patients across multiple centers.

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