New phase 1 projects enter hot fields

As well as AstraZeneca entering the CDK2 inhibitor field, recent initiations of first-in-human studies include three novel Car-T therapies, a possible future challenger to Daiichi Sankyo/Merck & Co’s patritumab deruxtecan, and a FAP-targeting project in the hot space of radiopharmaceuticals.

Some of the other targets of this crop of phase 1 entrants, as gathered from the clinicaltrials.gov registry, will also ring bells, including Kanova’s anti-B7-H4 MAb XKH002 and Servier’s MAT2A inhibitor S95035. The apparent EX02 target of Zeno’s Car-T asset, work resulting from a joint venture with the German biotech Eximmium, remains a mystery, however. 

Zeno’s is one of three Cars newly into human trials. The others are Legend Bio’s LCAR-G08T, and a project targeting NKG2D ligands in development at Leucid Bio, a private UK company that’s been around for a while and which last year appointed a new chief executive, Filippo Petti.

Not only does LCAR-G08T target GCC (GUCY2C), a relatively unusual antigen among industry cell therapy work, it also includes a negative switch receptor that Legend claims can turn an immunosuppressive signal to the tumour microenvironment into an activatory one, with the aim of enhancing the Car’s potency.

Some of these trials have only just appeared on clinicaltrials.gov despite actually having been initiated some weeks ago. And Kanova’s study of XKH002, whose B7-H4 target has attracted GSK, Pfizer and others, already appeared on OncologyPipeline back in September.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 3 and 12 Jan 2024.

As for other targets that also face notable competition, Multitude Therapeutics’ AMT-562 hits HER3; the industry’s most advanced anti-HER3 asset, the ADC patritumab deruxtecan, is already awaiting US approval, with a 26 June PDUFA date.

Radiopharmaceuticals continue to generate significant deals, which have included the takeovers of Point Biopharma and RayzeBio, while Lantheus recently tied up with Perspective Therapeutics. China’s Sinotau claims to have a radiopharma focus in oncology, and is taking into phase 1 an asset that targets FAP and uses the beta-emitting lutetium-177 isotope.

Novartis’s FAP-2286 has the identical approach, while Lilly’s Point-derived anti-FAP asset PNT2004 uses the alpha emitter actinium-225. Last October Sinotau took into human trials an anti-PSMA radioconjugate that will seek to compete with Novartis’s Pluvicto and Lilly’s PNT2002.

Finally, Servier’s MAT2A inhibitor S95035 will be of interest to followers of synthetic lethality mechanisms. This approach’s most prominent exponent is probably Ideaya’s IDE397, which is being studied in combination with Amgen’s PRMT5 inhibitor AMG 193. However, GSK notably turned down an option over IDE397 in 2022.

In 2020 Servier acquired the oncology business of Agios, which included the phase 1 MAT2A inhibitor AG270/S095033, since discontinued. The first-in-human trial of S95035, which presumably is a follow-on, is due to begin in March.

This is an updated version of a story published earlier.