Different dosing enlivens Enliven’s share price

Investors were apparently premature to write off Enliven Therapeutics a month ago. Updated numbers from the Enable trial of the group’s BCR-ABL inhibitor ELVN-001, zeroing in on different doses, have made this project’s efficacy look a lot more like that of Terns’ rival TERN-701, and pushed Enliven shares to close up 50% on Thursday.

However, the debate over which molecule will win out in the initial setting in question, heavily refractory chronic myelogenous leukaemia, is far from over. If only high doses of TERN-701 are considered the Terns project still appears better on a cross-trial basis, and it’s not entirely clear why Enliven’s data look better than before, given that they actually include a lower dose.

Specifically, the ELVN-001 update, press released on Thursday, concerns 60mg and 120mg daily doses, and the headline number for these is a 69% major molecular response (MMR) overall, including patients who were already in MMR at baseline; looking only at patients who weren’t already in MMR the number is 53%.

This looks notably better than the numbers Enliven put out at the European Hematology Association conference last year, respectively 47% and 32%, concerning a wider range of doses. They also look much more like the figures Terns cited at ASH for TERN-701: 74% MMR rate overall, and 64% in patients not already in MMR at baseline.

So far so good, but one problem for Enliven is that even at ASH Terns was already zeroing in on its preferred TERN-701 dosing, namely 320mg/kg or higher. And this produced numbers that apparently enable the Terns molecule to stay ahead of ELVN-001 – all still on a cross-trial basis, of course.

Cross-trial comparison of selected doses of Enliven and Terns’ BCR-ABL inhibitors

Note: MMR=major molecular response. Source: OncologyPipeline.

A further complication is that Enliven has appeared to put ELVN-001’s relatively poor previous showing down to the 80mg dose, where its press release cites overall and achieved MMR responses of 47% and 38% respectively.

But the company only presents the new 60/120mg result as a joint dataset, not splitting out the 60mg from the 120mg dose. It would be logical for 120mg to push up the efficacy of ELVN-001, but Enliven says only that there was “no clear evidence of dose response within this range”.

This suggests that 60mg is contributing to the MMR results improving versus the 80mg dose. Such a perverse result would raise at least some questions over the robustness of the data, though admittedly only a relatively small number of patients is involved. Notwithstanding the nuance, Terns fell 6% on Thursday, though at $4.1bn its valuation is still three times higher than Enliven’s.

Mizuho’s Salim Syed, who covers Enliven, wrote in a note to investors that the ELVN-001 data looked strong considering that patients in Terns’ study were not as heavily pretreated. He also claimed that the numbers “should effectively settle the recent debate” over whether ELVN-001, an active-site inhibitor, is competitive versus TERN-701, an allosteric molecule. 

Enliven last month replaced its founding chief executive, Sam Kintz, with Rick Fair, the former head of the now defunct cell therapy company Bellicum. Enliven promises further data from Enable in mid-2026, and hopes to start the pivotal Enable-2 study in the second half, pending talks with the FDA.