On March 16, 2021 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a platform-driven, clinical-stage biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported the first patients have been dosed in its global Phase 1 clinical trial of ADG126 for the treatment of various advanced solid tumors (Press release, Adagene, MAR 16, 2021, View Source [SID1234576701]). ADG126 is a fully-human, antagonistic monoclonal antibody (mAb) targeting a novel epitope of CTLA-4 and is Adagene’s lead SAFEbody product candidate.
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"Dosing the first patients in our Phase 1 clinical trial of ADG126 is an exciting milestone for the development of our SAFEbody technology platform," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "SAFEbody technology is designed to mask antibody binding sites, which will be activated specifically within the tumor microenvironment (TME), to provide favorable safety and efficacy with significantly enhanced therapeutic windows. Our most advanced SAFEbody candidate, ADG126 targets a conserved epitope of CTLA-4 with broad species cross-reactivity for potent Treg depletion via strong antibody-dependent cellular cytotoxicity (ADCC) in TME versus peripheral tissue. Our preclinical studies provide proof-of-concept for the potential of ADG126 in leveraging our SAFEbody platform to overcome standing issues associated with existing anti-CTLA-4 therapies by limiting on-target off-tumor toxicities in normal tissues."
"Existing cancer therapies that target CTLA-4 are associated with safety concerns, creating an unmet need for new anti-CTLA-4 therapies that are both safe and potent," said Anthony W. Tolcher, M.D., FRCPC, FACP, medical oncologist, co-founder of NEXT Oncology , Adagene advisor and study investigator. "ADG126 demonstrated an impressive safety margin while maintaining its potent antitumor efficacy in pre-clinical studies, and I look forward to its evaluation in patients with advanced solid tumors."
The global Phase 1 open-label, dose-escalation clinical trial is investigating the tolerability and anti-tumor activity of ADG126 in patients with advanced/metastatic tumors in multiple clinical sites in Australia. Adagene has also received approval from the FDA to initiate the Phase 1 clinical trial of ADG126 in the United States. The dose escalation trial will test five doses at 0.1, 0.3, 1.0, 3.0 and 10 mg/kg, with dose-limiting toxicities (DLT) evaluation for 3 weeks. Additional information about this clinical trial is available at ClinicalTrials.gov using the identifier: NCT04645069.
About ADG126
ADG126 is a fully human antagonistic mAb targeting a novel epitope of CTLA-4 and has been shown to specifically deplete regulatory T-cells in tumors. ADG126 is Adagene’s lead SAFEbody product candidate. The SAFEbody technology, developed using Adagene’s AI-powered platform, enables binding of an antibody to a specific target only after conditional activation of the antibody in target tissues.
In preclinical studies, ADG126 was well tolerated in cynomolgus monkeys in a four-week repeat-dose GLP toxicology study at doses up to 200 mg/kg, and demonstrated an encouraging antitumor response in multiple immune-competent mouse tumor models in a dose-dependent manner both as a single agent and in combination with anti-PD1 and other therapies.
Unlike anti-PD1/PD-L1 check point inhibitors, anti-CTLA-4 is known for its dose-dependent clinical response in single and combination therapies, which is severely limited by the narrow therapeutic window available to current anti-CTLA-4 therapies. The large safety margin shown by ADG126 GLP toxicology studies of up to 200 mg/kg in targeting CTLA-4 will make it possible to dose patients for their optimal clinical benefits in single and combination therapies.