Adlai Nortye Begins Global Phase 1 Trial of AN4035 After U.S. FDA IND Clearance

Key Points

• Adlai Nortye dosed the first patient in Australia in a global Phase 1 trial of AN4035.
• The U.S. FDA cleared the company’s IND application and issued a “Study-May-Proceed” letter, allowing the trial to expand into the United States.
• AN4035 is an investigational antibody-drug conjugate, or ADC, designed to deliver a pan-RAS(ON) inhibitor to CEACAM5-enriched solid tumors.
• The Phase 1 trial will evaluate AN4035 alone and in combination with cetuximab.
• Adlai Nortye expects to report full Phase 1a data in the second half of 2027.

Adlai Nortye (NASDAQ: ANL) has dosed the first patient in Australia in its global Phase 1 clinical trial of AN4035, an investigational antibody-drug conjugate designed for patients with CEACAM5-enriched, RAS-addicted solid tumors.

The company also received a “Study-May-Proceed” letter from the U.S. Food and Drug Administration after filing an Investigational New Drug application. The FDA clearance allows Adlai Nortye to expand the AN4035 trial into the United States.

AN4035 Combines Tumor Targeting With Pan-RAS Inhibition

AN4035 is the first clinical proof-of-concept candidate from Adlai Nortye’s RAS Inhibitor Conjugated Antibody, or RASiCA™, platform.

The therapy combines a CEACAM5-targeting antibody with a pan-RAS(ON) inhibitor payload. The design aims to deliver the drug directly to tumor cells that express high levels of CEACAM5 while limiting exposure in normal tissue.

RAS proteins are involved in cell-growth signaling. RAS mutations are common in several solid tumor types, but systemic pan-RAS(ON) inhibitors can cause side effects because normal cells also rely on the same pathway.

Adlai Nortye said AN4035 is designed to address that challenge by using the CEACAM5-targeting antibody to concentrate the RAS inhibitor payload in tumors. The company specifically cited potential reductions in on-target, off-tumor toxicity in the skin and gastrointestinal tract. 

Trial Includes Patients With Colorectal, Pancreatic, and Lung Cancers

The global Phase 1 trial will evaluate AN4035 in patients with CEACAM5-enriched solid tumors that depend on RAS signaling.

CEACAM5 is highly expressed in colorectal, pancreatic, and lung cancers, which can also frequently carry RAS mutations.

The study will assess AN4035 as a monotherapy and in combination with cetuximab, another cancer treatment. Researchers will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and early signs of antitumor activity.

First Patient Dosed in Australia as U.S. Expansion Begins

Adlai Nortye received regulatory clearance to begin the study in Australia last month and has now dosed the first patient.

The FDA’s IND clearance allows the company to add U.S. clinical sites to the global study. Adlai Nortye is also preparing an IND submission to China’s National Medical Products Administration, which could support trial expansion into China if cleared.

The company said it remains on track to report full Phase 1a data in the second half of 2027.

Early-Stage Program Faces Standard Clinical Risks

The first-patient-dosed milestone begins human testing of AN4035 but does not provide clinical safety or efficacy data.

The Phase 1 trial will determine whether the proposed tumor-targeting approach can safely deliver a pan-RAS(ON) inhibitor and show early evidence of activity in patients. Results may differ from preclinical expectations, and Adlai Nortye will need to demonstrate an acceptable safety profile, drug exposure, and antitumor benefit before the candidate can advance into later-stage development.