Adlai Nortye (NASDAQ:ANL) outlined the status of its oncology pipeline and upcoming development milestones during a presentation at the Jefferies Healthcare Global Conference, with a particular focus on two RAS-related programs: the oral pan-RAS inhibitor AN9025 and the antibody-drug conjugate AN4035.
Benjamin Graves, an investment banking representative at Jefferies, introduced the session, which featured Archie Sze, President and Head of R&D at Adlai Nortye, and Alex Ye. The company said its lead program, AN9025, is currently in a Phase 1 dose-escalation study and is being evaluated under a global protocol in the U.S. and China.
AN9025 Dose Escalation Expected to Continue Into 2027
The company is initially studying AN9025 using once-daily oral dosing. Ye said Adlai Nortye plans to begin an intermittent, once-weekly dosing track by mid-2026 while continuing daily dosing. Sze said the company expects to have some once-weekly data available when it reports data, which Ye indicated could occur in the first half of 2027.
Sze emphasized that Adlai Nortye is not claiming that a more potent drug is automatically a better drug. Instead, he said the company has benchmarked AN9025 against divarasib in preclinical studies and modeling to estimate therapeutic index. According to Sze, those estimates suggested AN9025 had a comparable or slightly better therapeutic index than divarasib across certain species and projected human modeling.
Company Sees Potential in Weekly Dosing Approach
Sze said Adlai Nortye’s interest in intermittent dosing is based on preclinical studies in which weekly dosing produced comparable efficacy to daily dosing when the total weekly dose was the same. He said the company also evaluated safety in rat dose-range-finding studies and observed a higher maximum tolerated weekly dose with once-weekly dosing than would have been expected from daily dosing.
“This is supporting the hypothesis that the intermittent dosing can further widen the therapeutic window,” Sze said.
He explained that normal tissue may recover more quickly from on-target toxicity during a drug holiday because it is less dependent on RAS signaling, while cancer cells may be more vulnerable to high-dose pathway inhibition. If the hypothesis translates clinically, Sze said Adlai Nortye could see either comparable efficacy with better safety, which may support combinations, or comparable safety at higher doses that could improve efficacy.
Sze also addressed questions about GTP hydrolysis, saying the company believes there may be more than one way to inhibit the RAS signaling pathway. He said AN9025 has slightly lower GTP hydrolysis than divarasib and sotorasib, but Adlai Nortye’s cell-line data suggested GTP hydrolysis may not be critical if a molecule is potent enough to inhibit the pathway stoichiometrically.
AN4035 ADC Program Positioned as Complementary
Adlai Nortye also discussed AN4035, its CEACAM5-targeting ADC that uses a pan-RAS inhibitor payload. Ye said the company expects to file an investigational new drug application around mid-2026 and enter human studies in the second half of 2026 across China, the U.S. and Australia. He said Adlai Nortye expects to report ADC data in the second half of 2027.
Sze said the company views AN9025 and AN4035 as complementary rather than competing programs. He said the oral small molecule program is more advanced and convenient to administer, while the ADC approach may address limitations of systemic pan-RAS inhibition by delivering the inhibitor more selectively to tumors.
According to Sze, that selectivity could help reduce skin and gastrointestinal toxicities and may make combinations more feasible, including potential combinations with EGFR-targeted therapies in colorectal cancer.
Sze said the ADC platform, which the company calls RASiCA, or RAS inhibitor conjugated antibody, is designed around potent RAS inhibitor payloads. He described preclinical findings showing sustained intracellular retention of free payload after ADC treatment and higher concentrations of payload in tumors compared with blood and other normal tissues in biodistribution studies.
Development Strategy and Cash Runway
During the question-and-answer portion, Amy Y. Qian, Equity Research Senior Associate at Jefferies, asked how dosing would differ between the oral pan-RAS inhibitor and the ADC. Sze said AN9025 is an oral drug being tested with once-daily and once-weekly schedules, while the ADC is intravenous and expected to be given once every two weeks.
Sze said the ADC’s initial focus is expected to be more “colon-centric,” with colorectal cancer as the primary indication, followed by pancreatic ductal adenocarcinoma and then lung cancer. He said the first-in-human ADC study is expected to include monotherapy dose escalation and, in a staggered manner, an EGFR combination arm.
Ye also said Adlai Nortye has approximately $290 million in cash following two PIPE financings completed earlier in the year. He said the company believes that cash position provides runway through the end of 2028, allowing it to execute its RAS development plan.
About Adlai Nortye (NASDAQ:ANL)
Adlai Nortye Inc (NASDAQ: ANL) is a specialty chemical manufacturer headquartered in China’s Jiangsu Province. The company focuses on the research, development, production and sale of fine chemicals, with a primary emphasis on amino acids and their derivatives.
Adlai Nortye’s product portfolio includes betaine compounds, a range of high-purity L-amino acids such as L-methionine, L-threonine and glycine, as well as various chemical intermediates. These offerings serve multiple end markets, including animal feed and nutrition, personal care and cosmetic formulations, pharmaceutical ingredients and industrial chemical processes.
The company operates multiple production facilities alongside an in-house research and development center dedicated to process innovation and quality control.
