On April 13, 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 updated preclinical data from its lead SAFEbody program, ADG126, are being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (Press release, Adagene, APR 13, 2021, View Source [SID1234577961]).

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"There is a critical unmet need for new anti-CTLA-4 therapies, and we are encouraged by the data generated to date, which demonstrate ADG126 has the potential to overcome the severe immune-mediated adverse reactions associated with the class," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "By leveraging our SAFEbody platform technology, designed to precisely and very efficiently mask the antibody binding interface and activate specifically within the tumor microenvironment, our preclinical data continues to highlight the opportunity to effectively deliver treatment; ADG126 has demonstrated superior systemic safety profile at efficacious dose levels with a significantly enlarged therapeutic index (TI). Our ongoing global Phase 1 trial is expected to provide clinical validation for our SAFEbody platform and our SAFEbody product candidate, ADG126. We have successfully finished DLT evaluation of 3 patients at 0.1 mg/kg of ADG126 and remain on track to report topline safety and efficacy data in the second half of 2021."

A copy of the poster presentation, entitled "A Novel Anti-CTLA-4 Checkpoint Inhibitor Prodrug to Address On-target Off-tumor Toxicity for Cancer Immunotherapy," is available on the AACR (Free AACR Whitepaper) website and is also available for download via our website (View Source).

The data presented show:

Notable Findings: ADG126 demonstrated an impressive safety margin while maintaining its potent antitumor activity.
Unique Epitope with Broad Species Cross-Reactivity: ADG126 targets a conserved epitope of CTLA-4 with broad species cross-reactivity and is an activatable prodrug for tumor suppression in multiple syngeneic mouse models in single and combination therapies.
Differentiated Mechanism of Action: Although the activated ADG126 is softer in blocking CTLA-4 binding with its ligands than ipilimumab, the activated ADG126 exhibited more potent antibody dependent cellular cytotoxicity (ADCC) in the tumor microenvironment.
Intra-Tumoral Treg Depletion: Treg cells in tumor tissues exhibited higher CTLA-4 expression than in peripheral tissues and were efficiently depleted upon treatment with ADG126 in the immune-competent mouse syngeneic colon tumor model.
Human T-Cell Activation in Vitro: Activated ADG126 potently enhanced T-cell activation, measured by IL-2 secretion, whereas the masked ADG126 did not.
In Vivo Monotherapy Antitumor Activity: ADG126 exhibited potent antitumor activity as a single agent in different immune-competent syngeneic mouse tumor models.
In Vivo Combination Antitumor Activity: ADG126 combined synergistically with other IO agents, such as anti-PD-1 antibody, to inhibit tumor growth in vivo. Combination therapy significantly slowed tumor growth and caused complete regression in 50% of Lewis lung cancer mouse models.
Safety and Tolerability: ADG126 was well tolerated in animals suggesting the potential for high therapeutic index. The highest non-severely toxic dose (HNSTD) was determined to be 200 mg/kg/dose, which is one of the highest reported HNSTD for anti-CTLA-4 antibodies.
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 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-PD-1 and other therapies.

Unlike anti-PD-1/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.