Crispr cans a next-gen project

Two years ago, Crispr Therapeutics shifted from first-gen to next-gen allogeneic Car-Ts – and now it’s abandoned one of those next-gen projects. The company slipped the discontinuation of CTX131, a CD70-targeting contender, into its third-quarter earnings release on Monday saying that, while phase 1 data were “encouraging”, it now plans to focus on “other programmes with the greatest potential for long-term value creation”.

One of these programmes might be the CD19-targeting Car-T CTX112, which is in a phase 1/2 trial in refractory B-cell malignancies, as well as being in development for autoimmune diseases. A “broad update” on this asset is due by year end, a delay from the previous timeline of mid-2025.

At last year’s ASH meeting, CTX112 produced an overall response rate of 67% among 12 patients with various B-cell malignancies given different doses of the project. On the face of it this looks a little lower, on a cross-trial basis, than response rates with autologous CD19 Car-Ts like Gilead’s Yescarta, Bristol Myers Squibb’s Breyanzi, and even allogeneic rivals like Caribou’s vispacabtagene regedleucel.

Patients in Crispr’s trial were heavily pretreated, but CTX112 will likely need to show something better to justify further development.

CTX112 isn’t listed among this year’s ASH abstracts, although the late-breakers are yet to be announced.

Any better?

Both CTX112 and CTX131 were supposed to represent an improvement over Crispr’s first-gen contenders, CTX110 and CTX130, by virtue of including extra edits: namely of Regnase-1 and TGF-β receptor type 2, with the aim of enhancing potency and reducing T-cell exhaustion.

However, in the case of CTX131 this clearly hasn’t led to enough extra activity to get Crispr excited. The project was being studied in phase 1/2 trials in both solid tumours and blood cancers, but no data have yet been reported.

Other CD70 Car-T contenders include Allogene, which at ASCO saw a 31% confirmed ORR in CD70 ≥50% expressing renal cancer with its allogeneic contender, ALLO-316.

However, allogeneic Car-T has been falling out of favour, with in vivo Car-T now the hot area for development, most recently attracting Bristol Myers Squibb to the deal table.

Crispr also said in its third-quarter release that it’s developing an in vivo Car-T programme for both oncology and autoimmune indications, although it didn’t give any more details. With the group’s in vivo editing work in other areas, the real surprise here is that it’s taken so long.

Crispr Therapeutics’ oncology pipeline

Source: OncologyPipeline & company presentations.