ASH 2025 – Terns wins

In the battle of biotechs seeking to improve on Novartis’s BCR-ABL inhibitor Scemblix in chronic myelogenous leukaemia the markets have picked a winner: Terns Pharmaceuticals. Data at ASH on TERN-701 have propelled Terns to a $3.6bn valuation, also making it the clear winner of the conference, and marking a 600% share price climb since ASH abstracts went live in November.

That’s bad news for the rival biotech Enliven Therapeutics, whose own valuation until recently vastly overshadowed that of Terns. Both TERN-701 and Enliven’s ELVN-001 aim to improve on Scemblix, but the ASH presentation of Terns’ Cardinal study not only backed TERN-701’s market-leading activity, it also appeared to allay concerns that the companies’ datasets weren’t comparable.

At present the setting under consideration is heavily refractory CML, where patients have failed several BCR-ABL inhibitors including Glivec, Iclusig and/or Scemblix. With Scemblix now establishing itself in the front line, a therapy that can rescue a patient failing on it could secure a large slice of the CML pie to itself, so the thinking goes.

More data

Until now Terns had presented rather limited data on TERN-701, but that all changed at ASH, with results spanning 38 efficacy-evaluable CML patients at a 13 Sep 2025 cutoff.

10 of those patients were in major molecular response (MMR) at enrolment, and all 10 maintained this through treatment with TERN-701. More importantly, 18 of the remaining 28 patients achieved a new MMR within 24 weeks of starting the trial, resulting in what Terns called a cumulative MMR rate of 74%.

This concerned 160mg-500mg daily doses, and the good news was that TERN-701 showed a relatively clean safety profile, allowing Terns to decide to take 320mg and 500mg forward into the next stage of the trial. For doses of 320mg and above (30 patients) the cumulative MMR rate was 80%, while 75% of 24 subjects without MMR at baseline achieved MMR.

Cross-trial comparison with ELVN-001 data, presented at EHA earlier this year, doesn’t flatter the Enliven molecule: the 24-week MMR rate among 41 late-line CML patients not in MMR at baseline and treated with ELVN-001 was just 32%.

True, more patients in Enliven’s study (57%) had been on prior Scemblix than in Terns’ (38%), but both companies have broken out MMR rates specifically in this subgroup, and here too Terns comes out on top, albeit among just seven patients.

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

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

And another issue was the suggestion that the datasets weren’t comparable because in Enliven’s trial most post-Scemblix patients were resistant to the Novartis drug, whereas Terns’ ASH abstract suggested that about two thirds of those on TERN-701 were merely Scemblix intolerant.

However, this has apparently now been put to bed, with the full ASH data showing that three quarters of the post-Scemblix subjects treated with TERN-701 had actually discontinued Scemblix for lack of efficacy.

Just a few months ago Enliven’s $1bn market cap dwarfed that of Terns, but the tables have now turned: Enliven fell 6% on Monday, when the TERN-701 data were presented, and is nursing a 9% fall year to date.