Actym Therapeutics Announces IND Clearance for Phase 1 Clinical Trial Investigating Lead Program ACTM-838 in Patients with Solid Tumors

• First-in-human trial will evaluate the safety, tolerability, payload delivery, and preliminary efficacy of ACTM-838 as a single agent in an open-label monotherapy dose escalation study

• Systemically administered ACTM-838 is designed to selectively accumulate in the tumor microenvironment to locally deliver two potent payloads, engineered versions of IL-15 and STING, to stimulate both innate and adaptive anti-tumor immunity
  

BERKELEY, CA — May 30, 2024

Actym Therapeutics, today announced that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application to start a Phase 1 clinical trial of its lead drug candidate, ACTM-838. The open-label monotherapy dose escalation study is designed to evaluate the safety, tolerability, payload delivery, and preliminary anti-tumor activity of escalating doses of ACTM-838, which represents the first drug candidate based on the company’s proprietary S. Typhimurium-Attenuated Cancer Therapy (STACT™) platform to reach the clinic. ACTM-838 delivers immunomodulatory payloads, engineered IL-15plex (IL-15/ IL-15R) and STING, specifically to tumor-resident phagocytic antigen-presenting cells (APCs) in the tumor microenvironment (TME).

“The immunosuppressive TME is a key challenge in the treatment of solid tumors, limiting the efficacy of many potentially effective anticancer drugs. Actym Therapeutics has developed an innovative technology to specifically deliver and express constitutively active STING in tumor-resident myeloid cells using a systemically administered therapy. IL-15plex expression adds complementary activity on B, T, and NK cells, achieving durable anti-tumor immunity,” said Jason J. Luke, MD, FACP, a leading international physician-scientist specializing in the clinical development of immunotherapies for solid tumors. “Actym’s approach to modulating the TME has a unique potential to overcome these immunological barriers. Their lead candidate, ACTM-838, was shown to be safe and effective in preclinical studies and is now ready to enter the clinic.”

“The IND clearance for ACTM-838 is a major milestone for Actym and potentially a significant step forward in harnessing the power of immunotherapy to treat patients with solid tumors more effectively,” said Tom Smart, CEO of Actym. “It is terrific to see the vision and impressive work pioneered by Actym’s founders translated into a promising clinical-stage asset. As we advance our lead clinical program, we also look forward to further expanding the potential applications of our STACT biological platform by developing new product candidates in-house and in collaboration with pharmaceutical companies.”

The Phase 1 (NCT06336148) open-label monotherapy dose escalation study with ACTM-838 will be conducted at clinical sites in the United States and Australia and will enroll patients with advanced solid tumors who have failed prior lines of therapy and have no clinically beneficial treatment options.

About STACT™ Biological Platform Actym Therapeutics has engineered a new drug modality, STACT™ (Salmonella Typhimurium-Attenuated Cancer Therapy), harnessing the power of a genetically modified bacterial vehicle that safely introduces therapeutic payloads to activate the immune response in the tumor microenvironment (TME). It is a modular multi-faceted platform enabling cell-, microenvironment-, and tissue-targeted delivery of large combinatorial multiplexed payloads via safe systemic administration with engineered auxotrophy allowing for tissue-specific localization and enrichment for oncology and non-oncology indications. Expression of payloads, including therapeutic DNA, RNA, protein, peptide, and gene editing effectors, can be enabled in either the bacterial vehicle or targeted human cells. Actym’s proprietary platform enables tumor-localized expression of payloads at levels that are not tolerated systemically, and the ensuing local engagement of both innate and adaptive anti-tumor immunity.

About ACTM-838 ACTM-838 is Actym’s first clinical asset utilizing the STACT™ Platform to deliver immune-modulatory payloads specifically to the tumor-resident, phagocytic antigen-presenting cells (APCs) in the TME. After a rigorous process to identify optimal payloads, the locally expressed IL-15 superagonist, IL-15plex (IL-15/ IL-15R), and the constitutively active engineered STING (eSTING) were selected. Separately, each payload has been clinically validated to mediate anti-tumor immunity when administered locally. Combined, Actym has shown these payloads have exceptional synergistic activity in preclinical models. When expressed in the TME by ACTM-838, their complementary mechanisms result in an effective durable anti-tumor immunotherapy that can be safely administered systemically.

Engineered to be auxotrophic for adenosine metabolites, ACTM-838 localizes to the TME where it survives and proliferates in the adenosine-rich tumor milieu. It is phagocytosed by APCs and delivers IL-15-plex and eSTING transgenes to these cells that subsequently express the proteins in the local TME. Phagocytosis of the accumulated STACT chassis in the TME initiates activation of innate immunity. Local expression of eSTING further stimulates the innate immune system by triggering type I interferon (IFN) pathways and other cytokines. This switches the immunosuppressive TME from a pro-tumor Th2/M2 TME to an anti-tumor Th1/M1 and activated NK immune phenotype, priming a new T cell response. Locally expressed IL-15-plex additionally supports the activation and viability of NK and B cells as well as existing and newly primed T cells. Through this multifaceted mechanism, ACTM-838 engages both innate and adaptive immunity to generate a comprehensive, robust, and durable anti-tumor immune response in the body. The Phase 1 clinical study of ACTM-838 is designed to establish safety, payload delivery, and proof-of-mechanism of the STACT biological platform and ACTM-838 in humans.

About Actym Therapeutics Actym Therapeutics is a clinical-stage biopharmaceutical company focused on transforming cancer treatment. The company has created a proprietary novel drug modality (STACT™ biological platform) that harnesses the power of a genetically modified bacterial vehicle designed to be safely systemically administered and deliver multiple therapeutic payloads that are amplified and produced locally at the disease site. To achieve targeted anti-tumor effects, STACT™ exploits intrinsic tumor microenvironment (TME)-specific metabolites, enabling selective enrichment of the bacterial vehicle and therapeutic payloads in tumors. Our flagship drug candidate, ACTM-838, uses STACT™ to deliver IL-15plex and eSTING to the TME. With the ability to tailor STACT™ to target specific cell and tissue types, and incorporate a broad range of payload combinations, we aim to achieve an unprecedented level of therapeutic impact for patients across multiple oncology and non-oncology indications. Based in Berkeley, California, Actym Therapeutics is funded by leading investors.

Contacts For Actym Therapeutics Tom Smart, CEO info@actymthera.com

Media Requests for Actym Dr. Alison Opalko or Sara Ortiz Trophic Communications +49 151 54041130 or +49 160 90816161 actym@trophic.eu