Another first-in-human mystery from Merck

With Genmab recently starting and then canning a clinical trial of a project with an undisclosed mechanism of action, and Merck & Co already in the clinic with a secret ADC coded MK-2750, the entry into human trials of another mystery Merck molecule suggests growing confidentiality surrounding certain pharmacological targets being pursued by biopharma.

The latest project, Merck's MK-8294, appears in new listings on the clinicaltrials.gov registry, but its entry gives nothing away as to possible targets. No such secrecy from PharmaEssentia and Shine-On Biomedical, which are starting trials of MAbs hitting PD-(L)1, or Tcelltech, which is advancing a Car-T therapy against another popular target, B7-H3.

The entry for the phase 1 solid tumour study of MK-8294 says the molecule will be delivered by IV infusion, so it's likely to be an antibody or other type of protein, but the only other clue is that the project is also coded DAB014236. This suggests that it might have come through a collaboration, though the DAB prefix doesn't suggest any obvious partners.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 22 Jun & 9 Jul 2025. 

For PharmaEssentia, a Taiwan-listed company, the start of a phase 1 study of the anti-PD-1 MAb P-1801 looks like an effort to secure an in-house combo for its lead project, ropeginterferon alfa-2b. The latter is to be studied with P-1801 in the new trial, having already been trialled in a phase 2 liver cancer test in combination with Opdivo.

PD-L1 is one of the targets of Shine-On's T-cell engager SOA101. This molecule is a trispecific, additionally hitting HLA-G, a molecule said to be overexpressed by tumour cells to evade immune surveillance, as well as the T-cell anchoring protein CD3. Shine-On is separately developing an exosome approach to targeting HLA-G.

Private biotechs

Two private US biotechs also feature in the new first-in-human starts. One is Tasca Therapeutics, with another mechanistic secrecy, CP-383. Tasca says it has a proprietary auto-palmitoylation technology, but describes CP-383 only as "first-in-class inhibitor for multi-cancer indications".

Meanwhile, Atavistik Bio in January tied up with Pfizer in a discovery alliance to use its know-how to identify novel allosteric binders against two Pfizer-designated targets. Now it's moving the AKT1 inhibitor ATV-1601 into a first-in-human trial in cancers with AKT1 E17K mutations.

Biopharma has worked on numerous AKT inhibitors, with AstraZeneca's Truqap being notable, but OncologyPipeline reveals only four clinical assets specifically against AKT1. Atavistik is being precise in targeting the AKT1 E17K mutation, which it says might be a resistance mechanism to PI3Kα inhibitors; ATV-1601 had a preclinical poster at last year's EORTC-NCI-AACR symposium.

Elsewhere, the anti-B7-H3 pipeline is also crowded, especially with ADC approaches like Daiichi Sankyo/Merck's ifinatamab deruxtecan, GSK/Hansoh's GSK5764227 and BioNTech/DualityBio's BNT324. Tcelltech is taking a different tack, however: its DIT309 is a Car-T therapy.