Adagene Announces Clinical Trial Collaboration with Roche to Evaluate Anti-CTLA-4 SAFEbody® ADG126 in Combination with Roche's Standard-of-Care Regimen for First-Line Treatment of Advanced Liver Cancer

Suzhou, China and San Diego, USA, December 16, 2022 — Adagene Inc. (“Adagene” or the “Company”) (NASDAQ: ADAG), dedicated to discovering and developing novel cancer immunotherapies based on original antibodies, today announced a collaboration with Roche to conduct a randomized, multinational, multicenter clinical trial to evaluate Adagene’s anti-CTLA-4 SAFEbody®^®Efficacy of ADG126 in combination with Roche’s atezolizumab (an anti-PD-L1 monoclonal antibody) and bevacizumab (an anti-VEGF monoclonal antibody) as a triple-immunotherapy regimen for first-line treatment of advanced hepatocellular carcinoma (HCC). This collaboration will leverage Roche’s MORPHEUS-LIVER platform to enable rapid and efficient co-development.

This collaboration will be funded by Roche, with an initial plan to conduct a randomized, multinational, multicenter Phase Ib/II trial in 60 patients with advanced hepatocellular carcinoma. The study aims to evaluate the efficacy, safety, and pharmacokinetics of ADG126 in combination with bevacizumab and atezolizumab versus the standard regimen of atezolizumab and bevacizumab. During the clinical trial, both companies will provide their respective anticancer drugs. Adagene will retain global development and commercialization rights for ADG126. Other financial details regarding this collaboration have not been disclosed.

This study expands Adagene’s global clinical development of ADG126 into first-line treatment for liver cancer, positioning it as a potential key component of first-line combination therapies for hepatocellular carcinoma (HCC). Currently, combination therapies involving anti-CTLA-4 and anti-PD-1/PD-L1 agents have demonstrated statistically significant clinical benefits. Ongoing Phase Ib/II clinical trial results have shown that ADG126 exhibits a highly differentiated safety profile, both when administered repeatedly at the highest monotherapy dose of 20 mg/kg and in combination with anti-PD-1 therapy at doses up to 10 mg/kg. Given its favorable safety profile after repeated dosing and positive antitumor activity, ADG126 is well-suited for combination with other therapeutics to further enhance treatment outcomes for cancer patients.

“Roche’s dual-drug combination therapy is the FDA-approved first-line standard of care for liver cancer. We are delighted to initiate this collaboration with Roche, focusing on first-line treatment for liver cancer and exploring the anti-CTLA-4 SAFEbody antibody beyond the current breakthrough dual-combination standard regimen.”^®“The tremendous potential of ADG126 in the triple-combination regimen,” said Dr. Peizhi Luo, Co-founder, CEO, and Chairman of Adagene. “For a long time, multi-drug combination regimens for liver cancer have faced safety challenges, while the SAFEbody antibody...”^®“ADG126 has demonstrated an unprecedented safety profile for anti-CTLA-4 therapy, and its incorporation into a triple immunotherapy combination represents a promising treatment strategy for liver cancer. We are highly optimistic about this approach.”

SAFEbody^®This technology can minimize the toxic side effects induced by targeting antigens expressed in healthy tissues, thereby addressing the safety and tolerability challenges faced by many antibody therapies. The safe antibody ADG126 applies precise masking technology to the parent anti-CTLA-4 antibody ADG116, enabling specific activation of ADG126 within the tumor microenvironment. This enhances the therapeutic index and resolves the safety issues associated with existing anti-CTLA-4 therapies.

The masked ADG126 binds to the same unique epitope of the CTLA-4 target as ADG116. By potently depleting regulatory T cells in the tumor microenvironment and exerting partial ligand-blocking effects, it steadily accumulates and prolongs drug exposure in tumor tissues, thereby enhancing its activity to improve safety and efficacy.