ASH 2024 – CellCentric's myeloma first

After a somewhat low-key existence over several years, but now fortified with a $25m investment from Pfizer and $35m from RA Capital, the private UK biotech CellCentric has reported its most significant clinical dataset so far.

The results, just unveiled at ASH, concern the p300/CBP inhibitor inobrodib, given as part of a combo with Pomalyst and dexamethasone to 40 late-line multiple myeloma patients, a third of whom had progressed on an anti-BCMA T-cell engager. Given this patient population a 51% response rate, including 67% in the nine patients given the highest dose, seems respectable.

It might not be apparent given CellCentric's low profile until now, but the company says it's dosed over 400 patients with inobrodib across several indications, including prostate cancer. But it's multiple myeloma that it now sees as offering the clearest way to make a clinical and commercial impact, especially given that inobrodib is an oral small molecule.

In the phase 1/2 trial presented at ASH 35 patients were efficacy evaluable at a 4 November cutoff, and 18 of these responded, including two with complete remissions. CellCentric highlighted one penta-refractory, post-BCMA responder, and said said among eight Pomalyst-refractory patients the ORR was 50%. How other BCMA therapy-relapsed patients did wasn't spelled out, however.

As for safety, the most common anticipated overlapping toxicity was thrombocytopenia, seen at grade 3 or higher in 33% of patients, but was said to be manageable. There was one death due to myocardial infarction, but this was deemed unrelated to inobrodib, and 13% of patients discontinued owing to treatment-emergent adverse events. 

Though the highest inobrodib dose, 35mg twice daily for four days on/three days off, seems optimal at this point, the phase 1/2 trial is continuing to evaluate several doses. 

Multiple myeloma

CellCentric is effectively a one-project company, having been founded 21 years ago specifically to investigate applications of p300/CBP inhibition. At last year's ASH it presented the first case reports with inobrodib in multiple myeloma, but the latest update comprises the biggest dataset so far.

p300 and CBP are closely related transcriptional coactivators, and their displacement is thought to trigger an epigenetic mechanism whereby expression of the oncogenic drivers IRF4 and MYC is downregulated.

More recently the profile of p300/CBP has increased, with several companies in play, according to OncologyPipeline. An early preclinical poster CellCentric presented was at ASCO in 2017, involving prostate cancer, but the group now describes subsequent clinical results are merely "OK", telling ApexOnco that multiple myeloma is where data really stand out.

Given this view it's surprising that just one other company is involved clinically in this setting: the private Swiss group Opna Bio took its p300/CBP inhibitor OPN-6602 into a first-in-human trial in fourth-line or later multiple myeloma in August.

The p300/CBP inhibitor pipeline

Source: OncologyPipeline.