Actym Therapeutics Reports Preclinical Data Demonstrating Ability to Generate Anti-Tumor Immunity

Actym Therapeutics recently announced an abstract highlighting detailed in vivo and in vitro preclinical data of its lead candidate, ACTM-838, was accepted for presentation at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting, to be held virtually and at the Boston Convention & Exhibition Center from November 8-12, 2022.  ACTM-838 is Actym’s lead candidate from its proprietary STACT platform and encodes an engineered IL-15 payload (IL-15plex) and engineered STING payload (eSTING). The data showed ACTM-838 to offer powerful efficacy as a single agent, including when used in checkpoint refractory tumors, and to work synergistically when used in combination with anti-PD1 therapies.

“The data we are presenting at SITC highlights the power of ACTM-838 to overcome the highly immunosuppressive tumor microenvironment and generate durable anti-tumor immunity in preclinical models,” said Christopher Thanos, PhD, Actym’s President, CEO, and Cofounder. “ACTM-838 is systemically delivered, with potent, tumor-specific effects. These preclinical data give us confidence in our approach to comprehensively and broadly re-program the tumor microenvironment as we prepare to enter the clinic in 2023.”

Research highlights include:

• Broad and comprehensive reprogramming of the immunosuppressive tumor microenvironment (TME) to an anti-tumor immunophenotype occurs after safe, intravenous dosing with ACTM-838.
• Profound immune infiltration and activation across T-cells, macrophages, dendritic cells, and B-cells, after treatment with ACTM-838.
• Potent ACTM-838 single agent efficacy and highly synergistic efficacy in combination with anti-PD1 therapies in checkpoint refractory breast and colon cancer tumor models, inducing complete responses in both regimens. As a monotherapy, ACTM-838 generated durable immunity upon re-challenge in cured animals.
• Increased T-cell infiltration and activation, and decreased T-regs after treatment with ACTM-838. Myeloid cell re-polarization to a preferred, dual M1/M2 phenotype was also observed.
• Overcoming a known immune evasion strategy for tumors (downregulation of MHC class I) and observing MHC class I upregulation in the TME, after ACTM-838 treatment.

“Our preclinical work has shown ACTM-838’s efficacy in transforming the tumor microenvironment both as a potent single agent and in synergy with anti-PD1 therapies,” said Chan Whiting, PhD, Actym’s Chief Development Officer and Head of Research and Development. “We look forward to entering the clinic next year with this new and potentially powerful therapeutic approach, and bringing hope to cancer patients with limited treatment options.”

Actym Therapeutics is a privately held, Berkeley-based biotechnology company focused on the discovery and development of transformational immunotherapies to treat cancer.  The company has developed an avirulent, programmable, live immunotherapeutic modality called STACT (S. Typhimurium-Attenuated Cancer Therapy). After IV dosing, STACT naturally and selectively expands in the extracellular milieu of the TME, an environment well-known to be hospitable for bacterial growth. Once there, it is naturally internalized by phagocytic, tumor-resident immune cells, facilitating combinatorial payload delivery to these cells. This approach enables the tumor-specific delivery of payloads (and combos) too toxic to be dosed systemically via conventional modalities, in a single therapeutic composition. Actym’s lead candidate, ACTM-838 leverages these capabilities and is being tested as a single agent and in combination with anti-PD1 therapy across multiple solid tumor types.  In April of 2020, Actym raised $34 million in a Series A financing, co-led by Boehringer-Ingelheim Venture Fund and Panacea Venture Healthcare, with participation from Illumina Ventures, Korea Investment Partners, and JLO Ventures.