Asco 2022 – great expectations for Adicet, Arcellx and PMV

It might just be that the dire state of the biotech markets has given companies a low base from which to start, but yesterday’s Asco abstract drop has sent up the share prices of several, most notably Adicet, Arcellx, PMV Pharmaceuticals and Mereo.

On the flip side, Springworks’s disastrous week continued after Tuesday’s admittedly positive data release, while Mirati fell in the latest battle against its Kras rival Amgen. It is positive that some data are being rewarded with share price gains; but many of the abstracts are typically short on detail, and investors will be keen for full data presentations at Asco itself not to fall short of expectations.

Adicet is a case in point. It had soared last December when reporting that three of four lymphoma patients treated with ADI-001 had gone into remission, providing the first clinical backing for a gamma-delta Car-T cell therapy. The stock climbed 10% this morning after the Asco abstract added two more subjects – plus another remission.

For Adicet whether these remissions are durable remains an especially pertinent issue given the relapses that have derailed the allogeneic Car-T players Allogene, Precision and Crispr. Adicet promises data from a May 31 cutoff at Asco, including more on durability, and all eyes will be on any evidence of host-versus-graft elimination of the ADI-001 cells.

More BCMA

Arcellx pulled off an IPO in February, when biotech sentiment was dismal, and Asco shows its anti-BCMA Car-T therapy yielding a 100% remission rate in 24 multiple myeloma subjects. This is impressive, but the boat for such projects might already have sailed, given industry competition and the dominant position of Johnson & Johnson/Legend’s Carvykti, whose label cites a 95% ORR.

The same issue affects Gracell’s CD19/BCMA-directed Car-T therapy GC012F. This does boast a two-day manufacturing process, but the practical benefit of such an advance, given that it still takes weeks to book a patient’s slot for the procedure, remains unproven.

And another biotech with much to prove is PVM, whose PC14586 has yielded five partial remissions in 21 evaluable subjects with the highly intractable Y220C p53 mutation. This is a promising start, but three of the responses are unconfirmed, and nothing is known about durability.

Far worse news greeted Mirati investors yesterday with this group’s Asco abstract on the Krystal-1 study of the Kras G12C inhibitor adagrasib. Not only are the data broadly in line with Amgen’s marketed Lumakras, Mirati now faces the prospect of trying to seek an accelerated approval just at the time that Lumakras yields confirmatory phase 3 data.

There was more pain for Springworks, whose nirogacestat did score in the tiny niche of desmoid tumours this week, but whose potentially bigger opportunity is in combination with BCMA blockade in multiple myeloma. An Asco poster suggests that the gamma secretase inhibitor does not, in fact, add a huge amount of efficacy to GSK’s Blenrep, whose label cites a 31% ORR; and this ignores the problem of nirogacestat’s short patent life.

And formally the worst-performing Asco stock was probably Iovance, though strictly speaking its 63% collapse today was not down to the data it is presenting at Asco.

Late-breakers

It is also worth noting which abstracts investors still do not know about: yesterday’s reveal concerned only standard presentations, and not the late-breakers, which remain under wraps until the day they are presented at Asco.

Among these the Destiny-Breast04 trial of Enhertu stands out as having the potential to upset Seagen’s Tukysa, Gilead’s Trodelvy, and Her2-targeting projects. Investors nervously await the Asco late-breaker on Trodelvy’s ostensibly positive Tropics-02 trial, which Gilead has not gone out of its way to claim as clinically meaningful.

And the failed Skyscraper-02 SCLC study of Roche’s tiragolumab, in a late-breaker being presented on June 5, has taken on major significance given the Tigit blocker’s subsequent failure in NSCLC. Keenly awaited will be details on any numerical benefit seen and on biomarkers that might suggest reasons for the SCLC failure.

The data will surely also have an effect on other Tigit players, including Compugen, Iteos, Arcus and Mereo. The last of those traded up this morning on a hardly impressive Asco poster covering etigilimab.

Evaluate Vantage will report from Asco, which takes place in Chicago on June 3-7.

After this story was published Springworks pointed out that it is clinically studying nirogacestat's polymorphc form, which has composition patent coverage until 2039.