AI-Driven Analysis Optimizes Clinical Strategy for A28’s Liver Cancer Peptide Therapy
A28 Therapeutics, a clinical-stage biopharmaceutical company, and GATC Health Corp, a developer of AI-driven drug discovery tools, have announced the completion of an AI-based analysis of A28’s lead drug candidate, AT-101. This analysis was conducted to evaluate the drug’s efficacy, safety, and potential off-target effects, with the goal of supporting clinical trial optimization and minimizing development risks. The announcement was made during the J.P. Morgan Healthcare Conference.
Using GATC’s Multiomics Advanced Technology (MAT) AI platform, the analysis of AT-101 employed in-silico experiments to evaluate key factors such as pharmacokinetics, toxicology, bioaccumulation, adverse event risks, and immune responses. These findings aim to provide A28 with precise insights to inform its clinical strategy, potentially streamlining development timelines and optimizing resource allocation.
AT-101, A28’s lead compound, is built on the company’s targeted lytic peptide platform, leveraging a novel mechanism derived from host defense peptides (HDPs). These peptides, including A28’s CLYP-71, utilize cationic properties to selectively bind and kill negatively charged cancer cells without harming healthy tissue. The targeting domain of AT-101 binds to luteinizing hormone-releasing hormone (LHRH) receptors overexpressed on cancer cells, triggering an electrostatic interaction that results in membrane disruption and rapid immunogenic cell death. This mechanism releases tumor neoantigens, potentially enhancing the immune response.
Clinically, AT-101 has shown promising results, with Phase 1 and Phase 2 studies involving over 85 patients demonstrating favorable safety and efficacy profiles. In a Phase 2 trial, metastatic ovarian cancer patients with liver metastases achieved a 69% overall response rate (ORR) in combination with chemotherapy, compared to 17% ORR with chemotherapy alone, alongside a 61% increase in overall survival. Pharmacokinetic data indicates that AT-101 achieves biodistribution in the liver for up to 72 hours, with controllable exposure through infusion adjustments, supporting its use in hepatocellular carcinoma. Moreover, AT-101 has demonstrated synergy with multiple classes of cancer therapies, reverses multi-drug resistance, and is not associated with systemic side effects, off-target toxicity, or immune suppression.
Jayson Uffens, CTO of GATC Health, noted that the MAT platform, which evaluated AT-101, is capable of supporting other stages of drug development by reducing time and cost compared to traditional methods. The platform uses AI to simulate systems biology, processing 400 trillion genetic data points (2,500 whole exomes) in under eight minutes.
A28 Therapeutics is advancing its pipeline of targeted oncolytic peptides (TOPs) to address cancer through receptor-specific approaches. Besides the lead candidate, AT-101, AT-201 focuses on luteinizing hormone/chorionic gonadotropin (LH/CG) receptors, while AT-301 aims at follicle-stimulating hormone (FSH) receptors to address tumors and tumor neo-vasculature. Additionally, AT-401, an antibody-drug conjugate, targets CD20 and Her-2 to combat cancers linked to these markers.
Topics: AI & Digital
