AACR 2025 preview – distressed biotechs seek redemption

The struggling biotechs Ikena, Senti Bio and ALX Oncology might be hoping to attract some renewed investor love based on clinical data due to be presented at next month's AACR conference. 

Clinical trial presentations, for which abstract titles were unveiled on Tuesday but whose data details remain under wraps, include data on IK-595, the asset to which Ikena pivoted after its setback with the Hippo mechanism, and Senti's Car-NK project for which the first case reports were trumpeted in December. Meanwhile, interest in ALX could come courtesy of a separate asset, CSPC Pharmaceutical's SYS6010.

That last project is one of five active clinical-stage ADCs targeting EGFR, according to OncologyPipeline. Though EGFR represents a very popular industry target for MAbs, and the mutated kinase is a mainstay of small-molecule inhibitors, work on ADC approaches is considerably more limited, perhaps as a result of the discontinuations of no fewer than three AbbVie assets.

This is relevant for ALX, since that company this month pivoted to the preclinical anti-EGFR ADC ALX2004, a possible distraction from its troubles in CD47 inhibition. SYS6010, whose first-in-human trial features at AACR, uses a topoisomerase 1 inhibitor payload, a feature it shares with ALX2004.

Another pivot

Ikena, meanwhile, had persevered against the odds with its Tead1 inhibitor IK-930, a leading exponent of the Hippo/Yap/Tead pathway, before finally throwing in the towel last May.

That discontinuation was accompanied by a pivot to IK-595, a project described as a MEK-RAF “molecular glue” that was in phase 1 in RAS and RAF-mutated cancers. Now this first-in-human study is to yield results at an AACR minisymposium on 29 April.

ApexOnco separately covered AACR's clinical trial plenaries, which naturally have a higher profile.

Selected clinical trial presentations at AACR

Senti Bio, a company notable for coming to market via a Spac (special-purpose acquisition company) rather than IPO, is way off its peak, currently trading at a valuation of just $17m.

Its shares got a boost in December when the group claimed two MRD-negative complete remissions among the first three AML patients given its "or-gated" anti-CD33/FLT3 Car-NK therapy, SENTI-202. Now the pressure is on to back up the hype with real data from this AML study, due to be presented at AACR.

Also under pressure is Coherus, whose Surface Oncology-derived anti-CCR8 MAb CHS-114 uses an approach in which there's been significant interest, including from big pharma. However, the first data from a Coherus-sponsored study, at last year's ASCO, found zero responses among 19 patients given monotherapy.

AACR will bring an update to these results, with a poster that could detail the efficacy of combining CHS-114 with toripalimab. This could be a key test since the promise of CCR8 blockade lies in downregulating T regulatory cells, and thus boosting the activity of PD-(L)1 blockers, but the lack of monotherapy activity isn't a great sign.

Coherus remains out of favour with investors, as does Repare, whose most recent setback came in December when the Mythic study of lunresertib plus camonsertib yielded ORRs of 26% in endometrial and 38% in ovarian cancers, with many responses unconfirmed. Repare then switched to RP-1664 (PLK4 inhibitor) and RP-3467 (Polθ inhibitor), and put lunresertib and camonsertib up for licensing. 

The hope is that presentation of Mythic data at AACR could generate partnering interest, though the omens aren't great.

AACR takes place in Chicago on 25-30 April.