Adlai Nortye doses first patient in weekly arm of AN9025 Phase 1
Adlai Nortye has dosed the first patient in the United States in the intermittent weekly dosing arm of its ongoing Phase 1 trial of AN9025, an oral pan-RAS(ON) inhibitor. The milestone opens a second dosing schedule alongside the existing daily dosing cohort, with both arms now in active dose escalation.
The Phase 1 study is a first-in-human, multicentre, open-label trial assessing the safety, tolerability, pharmacokinetics, and anti-tumour activity of AN9025 in patients with advanced or metastatic solid tumours carrying RAS mutations. It is structured as a multi-regional clinical trial conducted jointly with Chinese partner Jiangsu Aosaikang Pharmaceutical, which holds rights in mainland China, Hong Kong, and Macao, while Adlai Nortye retains all ex-China rights to the asset.
The clinical rationale
The decision to add an intermittent weekly schedule reflects a hypothesis the company has built from preclinical data: that pausing dosing between cycles may allow normal tissue to recover while RAS-signalling inhibition is maintained within the tumour. Archie Tse, President and Head of Research and Development at Adlai Nortye, said the approach "could widen the therapeutic window, enabling higher dosing and/or improving tolerability and combinability by giving normal tissue a break." He added that the company plans to share initial Phase 1 dose-escalation data from the daily dosing arm in the first half of 2027, with a potential early look at weekly dosing data at the same point.
The therapeutic window argument is clinically meaningful. A number of RAS-targeted small molecules have faced tolerability challenges at doses required for sustained target engagement, making schedule optimisation a recognised lever in the field. Whether intermittent dosing delivers on this promise for AN9025 will depend on pharmacokinetic and pharmacodynamic data that have not yet been released.
Market context
The pan-RAS inhibitor space has attracted considerable industry attention since the clinical validation of KRAS-specific inhibitors demonstrated that previously "undruggable" RAS proteins are tractable targets. Pan-RAS approaches, which aim to cover a broader set of oncogenic RAS variants including KRAS, NRAS, and HRAS mutations, represent the next wave of development. Several programmes from large and mid-cap oncology-focused companies are at various stages of preclinical and early clinical development, making differentiation on tolerability, depth of mutation coverage, and combinability increasingly important.
Adlai Nortye describes AN9025 as having best-in-class potential, citing preclinical results across pancreatic, lung, and colorectal adenocarcinomas. The company says performance was comparable or superior to a benchmark agent of the same class in preclinical models, though it has not named the comparator. These characterisations should be read as company-issued claims ahead of any clinical validation.
Beyond AN9025, Adlai Nortye's pipeline includes an antibody-drug conjugate targeting CEACAM5, a multi-functional fusion protein modulating the PD-1/L1 pathway, and an oral PD-L1 inhibitor. The breadth of the pipeline adds context to the company's ex-China positioning and may attract partnership interest as clinical data emerge across programmes.
The key near-term catalyst remains the 1H 2027 data readout from the daily dosing arm, which will give investors and clinicians the first human pharmacokinetic and safety data on AN9025. That dataset will also set expectations for what the weekly arm might achieve on tolerability.