ASH 2024 preview – CD19 back on the agenda

Merck & Co's $700m acquisition of Curon's anti-CD19 T-cell engager CN201 in August put this mechanism on investors' agendas, and the upcoming ASH conference will show how at least one competitor, AstraZeneca's AZD0486, is performing.

The meeting will also feature numerous other CD19-directed therapies, most notably in Car-T cell format, in which Novartis and Galapagos's fast-manufactured competitors will do battle. Among non-cell therapies another possible rival to CN201, Roche's englumafusp alfa, also has ASH data, though it uses a modality that has so far disappointed.

These feature among the most advanced presentations concerning clinical trial results to be discussed at ASH. Most of the meeting's regular abstracts have now been unveiled – the caveat is that many will merely be placeholders, with up-to-date results only being presented at the conference itself. Plenary presentations remain under wraps, and late-breakers go live on 25 November.

Astra vs Merck

For Merck's CN201, which put up a 100% ORR in indolent lymphomas at ASCO, the most relevant comparator will be an update on Astra's AZD0486 trial in follicular lymphoma, where an ASH abstract claims a 96% ORR among 27 patients; a phase 3 AZD0486 follicular lymphoma study is already under way.

A separate ASH abstract on AZD0486 notes a 43% ORR in the more aggressive DLBCL setting; no data on CN201 in DLBCL have been revealed. Astra acquired AZD0486, then coded TNB-486, in 2022 for $100m up front from Teneotwo, a division on the heavy chain-only antibody player Teneobio, and notes that in its DLBCL trial 61% of patients had previously received Car-T therapy.

Meanwhile, Roche's englumafusp alfa is an "antibody-like fusion protein" targeting CD19 and 4-1BB, an example of co-stimulation that hasn't yet yielded strongly positive results. A 68% ORR in aggressive non-Hodgkin's lymphoma cited in the ASH abstract seems impressive, but this trial doses patients first with Gazyva, then with step-up Columvi, and only then with englumafusp alfa, so it's hard to attribute benefit purely to the investigational molecule.

Fast Car-T

In Car-T therapy three companies – Novartis, Bristol Myers Squibb and Gracell (now part of AstraZeneca) – have been prominent developers of autologous projects that cut manufacturing time from weeks to days. However, Bristol stepped back from this in oncology, while Novartis discontinued two projects, most recently the anti-BCMA therapy durcabtagene autoleucel.

The fast-manufacturing brigade has been joined by Gilead's Kite division and Galapagos, and the latter will have ASH data on one of its contenders, GLPG5101. Meanwhile, Novartis will update on rapcabtagene autoleucel; these two anti-CD19 rivals are showing response rates of 88% in lymphoma, according to their ASH abstracts.

Anti-CD19 players have also worked on other cell types, and Takeda was one to try its luck with a Car-NK cell approach, namely TAK-007. However, this year the Japanese group first scaled back its work on autologous cell therapies, and then pivoted TAK-007, an anti-CD19 therapy that also encodes IL-15, away from oncology and towards autoimmune disease.

An ASH abstract notes a 50% ORR in large B-cell lymphoma patients given a high dose of TAK-007.

Selected oral presentations at ASH 2024 on CD19-directed therapies

ASH will take place on 7-10 December in San Diego.