Adlai puts its faith in pan-RAS

Adlai Nortye, a micro-cap biotech trying to come back from the failure of buparlisib last year, has put in place another piece of its attempted recovery plan: a first-in-human study of the pan-RAS inhibitor AN9025 is to start in January, recently added listings to the clinicaltrials.gov registry reveal.

These also show the entry into phase 1 of a tetraspecific T-cell engager from Opko Health’s Modex subsidiary, and what could be the first ever clinical-stage inhibitor of ADAR1, Aspera’s rebecsinib. While Adlai can argue that RAS is a relatively more validated space, AN9025’s problem is the similarly acting industry projects it will be up against.

The lead of these is Revolution’s pan-RAS inhibitor daraxonrasib, which is in or about to enter five phase 3 trials, including the recently revealed Rasolute-304 study in adjuvant pancreatic cancer. Several other companies are developing pan-KRAS molecules, including Lilly with LY4066434, and BeOne with BGB-53038.

Adlai’s AN9025 is now set to be tested in a phase 1 trial in RAS-mutant solid tumours. The molecule is one of three key assets to which Adlai pivoted when buparlisib, a PI3K inhibitor, failed in the phase 3 Buran trial in head and neck squamous cell carcinoma last year.

Buparlisib was originated by Novartis, which gave up on it over toxicity concerns, licensing rights to Adlai in 2018. At the time Adlai was a Chinese biotech, but as of its 2023 IPO Adlai describes itself as Cayman Islands holding company with operations in China and the US.

Adlai also has AN8025, an anti-PD-L1 x LAG-3 x CD86 fusion protein, in phase 1, and AN4035, a CEACAM5-targeting ADC that uses a pan-RAS(on) inhibitor as its payload. The latter is still in preclinical development, with an IND filing planned in mid-2026. Adlai’s market cap stands at just $53m.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 14 and 26 Nov 2025.

Meanwhile, Modex’s MDX2003 is a multispecific T-cell engager that targets the tumour antigens CD19 and CD20, as well as the co-stimulatory protein CD28, and the T-cell molecule CD3 to which it anchors.

Modex was founded in 2020 as a private biotech with a focus on oncology and infectious disease, but two years later was acquired by Opko for about $300m in stock. Opko, which is better known as a diagnostics business, still uses the Modex Therapeutics name for its immunology R&D division.

And OncologyPipeline shows nine ADAR1 inhibitors in development at companies including Boehringer Ingelheim and Risen, but Aspera’s rebecsinib looks to be first into the clinic when its phase 1 study begins in April. ADAR1 is a double-stranded RNA-specific enzyme said to be associated with tumour progression, and rebecsinib is designed to inhibit its splicing-mediated activation.

The latest clinicaltrials.gov listings also show several phase 1 projects with undisclosed mechanisms, perhaps the most interesting of which is an ADC being developed by Adcytherix, a French biotech that closed a €105m series A round of financing in October.