ASH 2024 movers – moments of reckoning for menin and BTK

The 2024 edition of the American Society of Hematology conference will go down as a relatively quiet vintage that might be best remembered for marking a popping of the menin inhibitor bubble and a moment of reckoning over BTK inhibition.

Plenty of menin data were presented at ASH, but with no meaningful clinical disappointments perhaps the biggest blow has been the realisation of just how many players are now fighting for a slice of this small pie. An analysis of share prices reveals several other significant movements over the ASH weekend, but as ever funds shuffling their year-end portfolios played a part too.

This was surely why BeiGene, for instance, saw its stock drop 9%, a move that marked one of the biggest losses of market cap among companies with a significant ASH presence. In reality, that group has a leading position in covalent BTK inhibition, and is neck and neck with Nurix in BTK degradation, an area that might one day change the way CLL is treated.

Still, it's no secret that the impact of BTK-based approaches to treating CLL is shifting. Before BTK degraders become reality the sector is absorbing the impact of non-covalent BTK inhibitors, and at ASH this space was hit by the failure of Lilly's Jaypirca to show an overall survival benefit in its confirmatory Bruin CLL-321 trial.

That OS miss was brought about by a near-unprecedented level of crossover from control to active treatment, but nevertheless the withdrawal of Jaypirca's accelerated US approval now has to be seen as a risk, however remote it might be. 

ASH 2024 risers

In pure percentage terms, over the ASH weekend the best performing biotechs with a presence at the conference were Innate Pharma, Cogent and Beam Therapeutics. The first two were both losers of the 2023 edition of ASH, and had only incremental updates this time around.

Beam, meanwhile, reported the first clinical data with its base-edited sickle cell project BEAM-101, from seven patients in the phase 1/2 Beacon trial where fetal haemoglobin levels were increased as hoped, although there was one death, blamed on busulfan conditioning. Excitement might have also come from preclinical findings on Beam's Escape antibody-based preconditioning regimen.

Menin

In menin inhibition perhaps the biggest clinical impact at ASH came from the entry of Sumitomo into this race; though that company lags the competition, its molecule, enzomenib, impressed.

More important is that this small space now includes at least four players, with Johnson & Johnson also challenging the leaders Syndax and Kura. And Kura dealt the field the biggest recent blow when it signed a licensing deal for ziftomenib with Kyowa Kirin last month; Kyowa is a somewhat obscure company, and many investors had been hoping for an outright takeover.

As such both Syndax and Kura fell over the weekend. But the 5% decline in Kura stock doesn't tell the whole story: that company has actually lost 42% of its value since the ASH abstracts went live on 5 November, a period that includes the announcement of its Kyowa deal.

Another big theme of ASH was whether Arcellx/Gilead's BCMA-targeted Car-T therapy anitocabtagene autoleucel (anito-cel) could challenge J&J/Legend's Carvykti. Over the weekend the companies traded minor insults, with Arcellx scheduling an ASH press release to coincide with Legend's analyst meeting on Sunday evening, while Legend's chief executive appeared to dismiss anito-cel as a "me-too drug" during an interview.

In the final reckoning Legend appeared to come off worse, seeing its stock fall 9% while Arcellx was off a more restrained 3%. However, the latter company had seen its shares climb to above $106 in the wake of its ASH abstract release, and its stock is now trading 15% below that peak.

ASH 2024 fallers