Private biotechs and novel targets head for human trials

Two private US biotechs, Pheast Therapeutics and Auron Therapeutics, are putting venture capital to use, recently revealing plans to start first-in-human studies of their lead projects.

These have emerged in recent updates to listings on clinicaltrials.gov, which also include studies of a fifth immtac from Immunocore, and a new project from Cero Therapeutics, which last year gained a public listing via Spac. The Pheast and Auron assets are the anti-CD24 MAb PHST001 and KAT2A/B degrader AUTX-703 respectively, notable for having rather limited industry competition.

OncologyPipeline reveals no other projects acting on KAT2A or KAT2B, using any modality, not just target degradation. Auron says the lysine acetyltransferases KAT2A/B are key drivers of disease, and claims to have validated the targets preclinically in AML, SCLC and neuroendocrine prostate cancer.

Venture capital

Last month Auron said an IND had been cleared for trials in haematological malignancies, and the first-in-human study concerns AML and myelodysplastic syndromes.

The company presented a preclinical poster on AUTX-703 at last year's ASH conference, and has raised $75m in series A and B financing rounds. For its part Pheast closed a $76m series A round in 2022, and had preclinical data for PHST001 at last year's SITC meeting.

Pheast says CD24 is a macrophage checkpoint inhibitor, and its approach perhaps feeds into recent interest in targeting myeloid cells. OncologyPipeline shows phase 1 projects targeting CD24 from Chengdu Kanghong (KH801), Antengene (ATG-031) and ImmuneOnco (IMM47).

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 19 Feb and 3 Mar 2025.

Immunocore has made its name with immtacs, which are T-cell engagers that use a soluble form of the T-cell receptor, as a result of which they are restricted to patients with a specific HLA type. The most advanced immtac, Kimmtrak, targets gp100 and was approved in 2022, since when the company has turned its hand to PRAME with brenetafusp and IMC-P115C, and to NY-ESO-1/LAGE-1a with GSK3537142.

Now a fifth immtac comes into play, with the listing of a first-in-human study of the anti-PWIL1 project IMC-R117C. Curiously, the company announced dosing of the first patient in this trial in December, but the clinicaltrials.gov entry, first posted late last month, states that the study had been due to begin in January 2024.

Elsewhere, gaining a Nasdaq listing by reversing into a special-purpose acquisition company (Spac) rather than by IPO has proved controversial, but was thrown back into the limelight this month by the planned listing of BridgeBio's cancer spinout BridgeBio Oncology.

Another Spac, Cero Therapeutics, is now being put to the test with the planned start of a phase 1 study of this company's Car-T therapy CER-1236. This is an autologous T-cell therapy comprising the external domain of the phagocytic receptor TIM-4 with intracellular signalling domains from T and other cells, and uses a lentiviral vector for gene delivery.

However, despite Cero's enthusiasm for this approach, the programme's short life so far has already had one stumble, with its IND being put on clinical hold last year. This hold having been lifted, the phase 1 trial is to begin next month.