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ASH 2023 preview – the first cell therapy winners

Arcellx climbs 19%, but the most significant Car-T presentation at ASH might not even be in oncology.

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

ProjectMechanismCompanySummaryASH abstractTrial
CART-ddBCMABCMA Car-TArcellx/Gilead75% 12mth PFS in 38 multiple myeloma pts1023NCT04155749
AUTO8BCMA x CD19 Car-TAutolus+/- CAT19 cells, 100% ORR in 8 multiple myeloma pts350McCarty
GC012FBCMA x CD19 Car-TGracell100% ORR in 22 multiple myeloma pts, 1L maintenance1022NCT04935580
BMS-986393GPRC5D Car-TBristol Myers Squibb86% ORR in 64 multiple myeloma pts, incl 75% in those after prior BCMA219NCT04674813
PMB-CT01BAFF-R Car-TPeproMene Bio100% CR rate in 3 multiple myeloma pts221NCT05370430
HPN217BCMA trispecific TCEHarpoon55% ORR in 40 multiple myeloma pts1012NCT04184050
C-CAR-39CD20 x CD19 Car-TCBMG/J&J92% ORR in 47 NHL pts1025Unclear
CD33CARTCD33 Car-TVor Biopharma40% CR in 5 AML pts, 17% ICANS & ≥gr3 CRS771NCT03971799
SabatolimabAnti-Tim-3 MAbNovartis33% CR rate in 21 AML pts (Apr cutoff)59Stimulus-AML2
LacutamabAnti-KIR3DL2 MAbInnate Pharma38% ORR in 56 Sézary syndrome pts, no mention of gr5 event (May cutoff)185Tellomak
OdronextamabAnti-CD20 TCERegeneronJan cutoff, focus will be on safety in DLBCL436Elm-2
KER-050Activin receptor type IIA ligand trapKeros51% ORR in 37 low-risk MDS pts196NCT04419649
NVG-111Anti-Ror1 TCENovaGenFIH Imbruvica combo, 55% ORR in Ror1+ve pts329NCT04763083
IMM01SIRPa-Fc fusion proteinImmuneOnco+ tislelizumab, 64% ORR in 14 in post-CPI Hodgkin’s pts609IMM01-04
AFM13CD30/CD16A bispecificAffimed93% ORR in CD30+ve lymphomas774AFM13-104

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.