ASH 2023 preview – the first cell therapy winners

Cell therapy doesn’t play as big a role at the annual ASH conference as it used to in the early days of Car-T mania, but it still generates winners. A case in point is Arcellx, which climbed 19% yesterday on the unveiling of the ASH abstract for its Gilead-partnered anti-BCMA Car-T project CART-ddBCMA.

The meeting also features cell therapies from Bristol Myers Squibb, Autolus and Vor Biopharma, though these and other biological approaches are largely playing second fiddle to real-world and post-marketing trials of established players like Yescarta, Carvykti and Tecartus. And the most important recent departure for Car-T therapy is not even oncology but autoimmune disease.

Multiple myeloma

In oncology it’s Arcellx that has taken the early ASH prize, with CART-ddBCMA yielding a landmark 12-month PFS of 74%. This is highly significant as it’s in line with the 75% rate seen in two-year follow-up of the registrational Cartitude-1 study of the market leader, Johnson & Johnson/Legend’s Carvykti.

The CART-ddBCMA abstract shows the same 38 patients as at its last update, with a slight improvement in the CR rate. All the ASH abstracts went live yesterday except for the late-breakers, of which there are usually only six, and which will be unveiled on 21 November; as ever, many abstracts feature relatively old cutoffs, so investors have to wait for ASH for the most up-to-date results.

Other multiple myeloma presentations featuring Car-T therapies include Gracell’s fast-manufactured GC012F, similarly to last year featuring in an early-line setting, and Autolus’s AUTO8, the latter alone or combined with an anti-CD19 Car. Both of these constructs are anti-CD19 x BCMA bispecifics.

There’s also an update on Bristol Myers Squibb’s GPRC5D-directed BMS-986393, with an ORR of 86% now in 64 patients, versus the 19 discussed at ASH 2022. Outside multiple myeloma, Vor Biopharma’s CD33CART has impressed in an academic AML trial, albeit in just five patients, and Cellular Biomedicine Group will present data on C-CAR039, a CD19 x CD20 Car licensed to J&J in May.

Selected oral ASH presentations on cell therapies & other biologicals

Note: excludes posters and late-breaking abstracts.

For Car-T therapy the other focus so far is autoimmune disease, with an ASH press briefing highlighting the work of Professor Georg Schett, whose trial of a CD19-directed Car-T therapy has put all eight treated lupus patients into complete remission. Novartis, among others, has signalled its intentions to take Car-T into lupus, and Schett is on the scientific advisory board of Cabaletta Bio.

Biologicals

There are several oral ASH presentations of note on biological approaches, including that covering Novartis’s anti-Tim-3 MAb sabatolimab, which will also be of interest to followers of GSK and AstraZeneca.

The long-running saga of Innate Pharma’s anti-KIR3DL2 MAb lacutamab has now seen two clinical holds, the latest coming in October on the death of a patient from hemophagocytic lymphohistiocytosis. The abstract on lacutamab’s Tellomak trial makes no mention of this, likely because it comes from a 1 May data cutoff, so investors will have to wait for the conference for more information.

And some will also bemoan the absence of Allogene, Caribou and Adicet, which do not appear in ASH's oral sessions.

The ASH conference takes place in San Diego on 9-12 December.