Actym Gets IND Clearance for Phase 1 Trial of ACTM-838 in Solid Tumor Patients

Actym Therapeutics has received approval from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 clinical trial of its leading drug candidate, ACTM-838. The study aims to evaluate the safety, tolerability, payload delivery, and preliminary anti-tumor activity of escalating doses of ACTM-838. This marks the first clinical application of Actym's proprietary platform, Salmonella Typhimurium-Attenuated Cancer Therapy (STACT™).

ACTM-838 is designed to selectively accumulate in the tumor microenvironment (TME) delivering two potent immunomodulatory payloads: engineered versions of IL-15 and STING. These agents are aimed at stimulating both innate and adaptive anti-tumor immune responses. The trial will be an open-label monotherapy dose-escalation study, involving patients with advanced solid tumors who have exhausted other treatment options. The study will take place in the United States and Australia.

Jason J. Luke, MD, a prominent physician-scientist in immunotherapies for solid tumors, highlighted the significance of overcoming the immunosuppressive TME, which limits the efficacy of many anti-cancer therapies. ACTM-838 addresses this challenge by targeting tumor-resident myeloid cells with constitutively active STING, which enhances local immune responses. The IL-15 complex further supports the activation of B, T, and NK cells, contributing to durable anti-tumor immunity.

The approval of the IND application for ACTM-838 is a significant milestone for Actym Therapeutics. CEO Tom Smart emphasized the importance of this development in advancing their lead clinical program and exploring further applications of the STACT™ platform. The company is keen on developing new product candidates in collaboration with pharmaceutical companies.

The STACT™ platform is a novel cancer therapy modality that uses a genetically modified bacterial vehicle to deliver therapeutic payloads directly to the TME. This targeted delivery system leverages tumor-specific metabolites to localize and enrich the bacterial vehicle and its payloads in tumors. The platform enables the expression of various therapeutic agents, including DNA, RNA, proteins, peptides, and gene-editing effectors, either within the bacterial vehicle or in targeted human cells.

ACTM-838 utilizes the STACT™ platform to deliver IL-15plex and engineered STING (eSTING) to phagocytic antigen-presenting cells (APCs) within the TME. Once the bacterial vehicle accumulates in the TME, it is phagocytosed by APCs, which then express IL-15plex and eSTING proteins. This process activates innate immunity and shifts the TME from a pro-tumor phenotype to an anti-tumor phenotype. The locally expressed IL-15plex supports the activation and viability of NK and B cells as well as newly primed T cells. This comprehensive immune engagement results in a robust and durable anti-tumor response.

ACTM-838's Phase 1 clinical study (NCT06336148) aims to establish the safety, payload delivery, and proof-of-mechanism of the STACT™ platform in humans. The trial represents a critical step in demonstrating the potential of this innovative approach to cancer therapy.

Actym Therapeutics is a clinical-stage biopharmaceutical company based in Berkeley, California. The company focuses on transforming cancer treatment through its proprietary STACT™ platform, which is designed for the systemic delivery of multiple therapeutic payloads that are locally amplified at the disease site. Actym is committed to developing therapies with significant therapeutic impact for patients with various oncology and non-oncology conditions.