Adlai Nortye Announces First Patient Dosed in Phase Ia Clinical Trial of AN2025 and AN0025 in Combination with atezolizumab for Advanced Solid Tumors

NORTH BRUNSWICK, New Jersey and HANGZHOU, China, Sept. 8, 2021 /PRNewswire/ -- Adlai Nortye, a global biopharmaceutical company focused on developing innovative oncology drugs, today announced that the first patient has been dosed in the Phase Ia clinical trial in the U.S. to evaluate the triple combination of AN2025 (buparlisib, oral pan-PI3K inhibitor), AN0025 (oral EP4 antagonist) and atezolizumab (PD-L1 inhibitor) in patients with locally advanced/metastatic tumors.

This trial (AN2025S0101) is an open-label, multicenter, Phase Ia study to evaluate the safety, tolerability, pharmacokinetics ("PK") and preliminary efficacy of AN2025 and AN0025 in double or triple combination treatments with atezolizumab in patients with locally advanced/metastatic tumors. The study consists of three dose-limiting toxicity ("DLT") Observation Periods, Observation I, II and III. Observations I and II are double combination treatments, which will be conducted in parallel, whereas Observation III (the triple combination treatment) will be initiated only after a thorough review of the safety data from Observations I and II. Each Observation period will last 3 weeks. This study plans to recruit approximately 63 patients. The first patient was dosed at Florida Cancer Specialists - Lake Mary Cancer Center, while the study is also going to recruit patients from the University of Colorado Cancer Center, Rutgers Cancer Institute of New Jersey and Stephenson Cancer Center in Oklahoma.

AN2025 targets not only PI3K mediated tumorigenesis (e.g. via inhibition of PI3Kα/PIK3CA mutants) but also the immunosuppression of the tumor microenvironment (e.g. via inhibition of PI3Kδ and PI3Kγ). According to the Frost & Sullivan Report, PIK3CA alterations are found in approximately 13% of all solid tumors globally, including 25% to 40% of cervical cancer, 30% to 40% of breast cancer, 30% to 35% of endometrial cancer, 30% of ovarian cancer, 24% of urothelial cancer, 20% of colorectal cancer and 10% to 20% of head and neck squamous cell carcinoma ("HNSCC") globally. The global incidence of PIK3CA mutant solid tumors reached approximately 2.3 million in 2020 and is expected to reach approximately 2.9 million in 2030, indicating a substantial overall addressable market and significant commercial potential.

Adlai Nortye aspires to develop differentiated cancer immunotherapy medicines for global markets. The Company's Cocktail therapy strategy represents the third wave of immuno-oncology therapy, featuring the combination of an immune checkpoint inhibitor with two or more additional cancer therapies. The Company expects it to achieve significantly higher overall response rates than present combination therapies. The triple combination of AN2025 (targeted therapy), AN0025 (immuno-oncology therapy) and atezolizumab (immuno-oncology therapy) exemplifies the cocktail therapy strategy of Adlai Nortye.

"Results from preclinical studies of the triple combination of AN2025, AN0025 and an anti-PD1 antibody have demonstrated encouraging antitumor activity. We believe that this triple combination potentially could develop into a novel anti-cancer immune therapy by exquisitely and systemically targeting the suppressive tumor microenvironment and thus permitting enhanced host immune responses against the tumor." said Dr. Lars Birgerson, Chief Medical Officer of Adlai Nortye, "We expect to identify the recommended Phase II dose of this Phase I clinical trial in the second half of 2022 as a step in a planned development program to bring this therapy to patients worldwide. Adlai Nortye is strongly committed to improve the lives of patients and their families by continuously developing our pipeline in oncology through our cocktail therapy strategy."

About AN2025S0101

This is an open-label, multicenter, Phase Ia study to evaluate the safety, tolerability, PK and preliminary efficacy of AN2025 and AN0025 in double or triple combination treatments with atezolizumab in patients with locally advanced/metastatic tumors. This study consists of three DLT Observation Periods, Observation I, II and III. Observations I and II are double combination treatments, which will be conducted in parallel, whereas Observation III (the triple combination treatment) will be initiated only after a thorough review of the safety data from Observations I and II. Each Observation period will last 3 weeks.

About AN2025 (Buparlisib)

AN2025 (buparlisib) is an oral pan-PI3K inhibitor that targets all class I PI3K isoforms and is active in both hematologic malignancies and solid tumors. In the global randomized Phase II clinical trial for the treatment of recurrent or metastatic HNSCC with buparlisib in combination with paclitaxel, the median overall survival was as high as 10.4 months. Buparlisib was granted Fast-Track designation for this indication from the FDA. The ongoing study is the first global Phase III clinical trial conducted by Adlai Nortye.

About AN0025 (EP4 Antagonist)

AN0025 is a potentially first-in-class oral EP4 antagonist that blocks prostaglandin E2 from binding to its subtype 4 receptor (EP4) changing the immunosuppressive character of the tumor microenvironment. Based on preliminary results, it is well tolerated in patients with solid tumors in combination with radiotherapy/chemoradiotherapy ("RT/CRT"). A Phase Ib study of AN0025 in combination with the standard of care in a neoadjuvant setting for locally advanced rectal cancer showed excellent results, with 20% of patients achieving clinical complete remission and 16% achieving pathological complete remission in this study.

About Adlai Nortye

Adlai Nortye is a global biopharmaceutical company focused on developing innovative oncology drugs, with its R&D and clinical operation centers in both China and the United States. With a strategic emphasis on oncology, the Company has built a global pipeline through collaborations and internal discovery with more than 10 drug candidates in development. Currently, four of them are being investigated in clinical trials. With fast-track designation from the FDA, AN2025 (buparlisib), in combination with paclitaxel, is initially developed to be the drug of choice for 2L treatment of metastatic HNSCC after anti-PD-1 treatment (Phase III multi-center clinical trial). AN0025 is a clinical-stage, potential first-in-class EP4 antagonist designed to modulate tumor microenvironment. AN1004 (pelareorep), with fast-track designation from the FDA, is a registrational trial-stage, potential first-in-class intravenously delivered oncolytic virus for treating hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. AN4005, the Company's clinically most advanced drug candidate from in-house discovery, is a potential first-in-class, orally available, small-molecule PD-L1 inhibitor.

The Company has assembled an experienced management team, built its proprietary drug research and development platforms and partnered with multiple leading pharmaceutical companies to promote innovation. Adlai Nortye is committed to becoming an innovative biopharmaceutical company with global vision and strives to benefit patients worldwide. The mission of the Company is to transform deadly cancer into a chronic and eventually a curable disease. For more information, please visit: www.adlainortye.com.