A flurry of first-in-human trial initiations

An unusually high number of first-in-human trial disclosures has seen four cell therapies and a radioconjugate, among others, set to enter the clinic for the first time. Venture financiers in particular will note that three of the new entrants come from private biotechs.

These are Affini-T, A2 Biotherapeutics and Alentis Therapeutics, companies that must nervously be eyeing the faltering financial markets. Still, it’s encouraging that four of the assets feature truly novel targets – important when the prevailing view is that too many companies are chasing the same old antigens.

One antigen that clearly isn’t novel is mesothelin, the target of A2’s Car-T therapy A2B694. However, the novelty of that project lies in its use of logic-gated activation, with one activating and one blocking receptor to spare non-cancer cells, and in recruiting patients who have permanently lost expression of the HLA-A*02 protein.

A2B694's phase 1/2 Everest-2 study won't actually start recruiting until March. A2’s first asset to use its approach, an anti-CEA Car coded A2B530, is already in phase 1/2, and a separate pre-screening study, Basecamp-1, aims to identify HLA-A*02-loss patients.

Another Car-T whose first study went up on clinicaltrials.gov in the past few days is Chimeric Therapeutics’ CHM 2101, targeting CDH17, the subject of just five other active projects, according to OncologyPipeline. Chimeric is already in the clinic with a lead Car-T called CHM 1101, against chlorotoxin, a peptide derived from deathstalker scorpion venom, and the CHM 2101 trial won't start until next year.

RAS cell therapies

The remaining two newly disclosed clinical-stage cell therapies are both engineered T-cell receptor projects that target RAS proteins: Affini-T’s AFNT-111 and Shanghai Genechem’s GB3010. Affini-T is notable for playing in the competitive area of KRAS G12D with a TCR coded AFNT-212, but AFNT-111 – its first clinical asset – hits KRAS G12V. GB3010 has actually been in phase 1 since 2021, its new clinicaltrials.gov entry states.

The novel targets continue with Bolt’s BDC-3042, a MAb that activates Dectin-2, an immune-activating receptor expressed by tumour-associated macrophages. The idea is that these macrophages can be repolarised, releasing the brake they have in establishing an immunosuppressive tumour microenvironment, as well as inducing expression of key antigen presentation machinery.

Meanwhile, Alentis Therapeutics, a private Swiss biotech, is putting into the clinic ALE.C04, a MAb against Claudin1. Indeed, Alentis, which closed a $105m series C raise last year, styles itself as “the Claudin1 company”, and work on this antigen is far less competitive than that in the hugely crowded Claudin18.2 space.

Finally, Bayer’s BAY 3546828 is another actinium-225 labelled anti-PSMA project, like Point’s PNT2001 and Convergent’s CONV 01-α, and its entry into phase 1 shows continuing interest in radiopharmaceutcials. 

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 21 and 26 September 2023.