Venture-backed biotechs push into the clinic

Where Nkarta recently failed with a Car-NK therapy the private US biotech D2M Therapeutics is pressing on with an antibody approach. DM919, a MAb targeting the NKG2D ligands MICA/B and D2M’s lead pipeline asset, entered its first clinical trial this month.

The study appears among the latest first-in-human initiations, according to the clinicaltrials.gov registry. These do include another Car-NK therapy, from Senti Bio, though this has a different target; also featuring are the first clinical asset from the private US group Nested Therapeutics, and a project that will be of relevance to another venture-backed biotech, Volastra Therapeutics.

The D2M trial combines DM919 with Keytruda in solid tumours. Numerous companies have tried and failed to target NKG2D ligands, but few of these have attempted this with a MAb. Nkarta ditched NKX101, its lead project, earlier this month, while its rival Fate Therapeutics discontinued its MICA/B-targeting Car-NK project FT536 just over a year ago.

Still focusing on Car-NK cells is Senti Biosciences, a group that went public via a SPAC in June 2022, but which in common with many other such entities has seen its valuation crash subsequently.

With a market capitalisation whittled down to just $20m Senti recently cut costs and restructured to focus primarily on SENTI-202, a Car-NK derived from two licenses from the US NCI. This asset targets CD33 and FLT3 in an either/or fashion, and is to enter its first human trial in June; Senti promises first efficacy data in AML by the year end, followed by initial durability data in 2025.

Private companies

FLT3 is also one of the targets of the small molecule ETN101 that has entered a phase 1 liver cancer trial sponsored by the private South Korea group Etnova Therapeutics. However, this has additional targets beyond FLT3, so its side-effect profile will have to be monitored closely.

Meanwhile, also in the small-molecule arena, Nested Therapeutics this month became a clinical-stage biotech after taking NST-628 into a first-in-human solid tumour trial.

Not much has been revealed about NST-628’s precise mechanism of action, but Nested describes it as a CNS-penetrant MAPK pathway “non-degrading molecular glue” that inhibits RAS/RAF-driven cancers. The molecule featured in a poster at last year’s Triple (EORTC-NCI-AACR) meeting, after Nested was launched through a $125m venture financing round in October 2022.

And Genhouse Bio, a company with a presence in the once-hot area of Hippo signalling, has taken into the clinic its third pipeline asset, the KIF18A inhibitor GH2616. This is a rare mechanism, and OncologyPipeline reveals only two other clinical stage projects with this activity – sovilnesib and VLS-1488 – both owned by Volastra Therapeutics.

Volastra licensed the first of these from Amgen in return for undisclosed cash and equity, at the same time as closing a $60m series A funding round.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 20 and 25 Mar 2024.