ACTM-838 / Actym Therap - LARVOL DELTA

Bulk and single-cell analysis of tumor microenvironment (TME) reprogramming induced via ACTM-838, a systemically administered microbial-based clinical-stage immunotherapy (SITC 2024) - "IV-delivered ACTM-838 is currently being evaluated in a phase 1 clinical trial. Ethics Approval All animals were used according to protocols approved by an Institutional Animal Care and Use Committee and maintained in specific pathogen-free conditions in a AAALAC accredited barrier facility."

Biomarker • Clinical • IO biomarker • Tumor microenvironment • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL15 • IL1B • IL6 • STING • TGFB1 • TNFA

Bulk and single-cell analysis of tumor microenvironment (TME) reprogramming induced via ACTM-838, a systemically administered microbial-based clinical-stage immunotherapy (SITC 2024) - "IV-delivered ACTM-838 is currently being evaluated in a phase 1 clinical trial. Ethics Approval All animals were used according to protocols approved by an Institutional Animal Care and Use Committee and maintained in specific pathogen-free conditions in a AAALAC accredited barrier facility."

Biomarker • Clinical • IO biomarker • Tumor microenvironment • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL15 • IL1B • IL6 • STING • TGFB1 • TNFA

ACTM-838-01: A Phase 1a/1b Study of ACTM-838 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=35 | Recruiting | Sponsor: Actym Therapeutics, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

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

IND • Oncology • Solid Tumor

ACTM-838 safely and comprehensively re-activates the immunosuppressive TME by exploiting myeloid biology intrinsic in many cancers (AACR 2024) - "To further understand the spatial heterogeneity in the TME across tumors, we performed multiplex immunofluorescence on patient tumor microarrays to validate tumor types with a high prevalence of myeloid populations coupled with an active adenosine pathway, which will help guide future clinical study design.In summary, we demonstrate that ACTM-838 modulates the TME and is stable and safe in animal models. Additionally, our studies recommend the prioritization of certain tumor indications for treatment with ACTM-838 in the clinic."

Oncology

A Phase 1a/1b Study of ACTM-838 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=35 | Not yet recruiting | Sponsor: Actym Therapeutics, Inc.

Metastases • New P1 trial • Oncology • Solid Tumor

PK/PD biomarker analysis to assess tumor-specific enrichment and payload delivery of ACTM-838, a microbial-based immunotherapy (SITC 2023) - "Conclusions ACTM-838 is a novel immunotherapy delivering IL-15plex + eSTING payloads to phagocytic APCs, inducing a durable anti-tumor immune response, after IV dosing. IV-delivered ACTM-838 possesses a compelling safety profile in mice and primates and is currently entering clinical trials in cancer patients in Australia."

Biomarker • IO biomarker • PK/PD data • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • IFNA1 • IL15 • STING

Actym to Present Preclinical Data on Clinical Candidate ACTM-838 at 38th SITC Annual Meeting (PRNewswire) - "Actym Therapeutics...announced today that it will present preclinical data of its lead asset, ACTM-838, in a poster presentation at the 2023 38th Society for Immunotherapy of Cancer (SITC) Annual Meeting in San Diego, California...Actym will also show that treatment with ACTM-838 induces tumor-antigen-specific cytolytic T cells and effector T cells. Furthermore, Actym will show that in healthy human donor cells, ACTM-838 treatment results in significantly lowered inflammatory cytokines than a control strain lacking ACTM-838's genetic modifications....In addition to demonstrating compelling efficacy characteristics, intravenously administered ACTM-838 exhibits a strong safety profile in mice and non-human primates with a first-in-human clinical trial planned in Australian cancer patients in early 2024."

New trial • Preclinical • Oncology • Solid Tumor

Actym Closes $59.5 Million Series A with New $25.5 Million Extension (PRNewswire) - "Actym Therapeutics...announced today it has extended its Series A financing round with an additional close of $25.5 million, bringing the total Series A amount raised to $59.5 million....Actym's lead candidate, ACTM-838, safely introduces optimized IL-15 and STING, two highly potent and synergistic payloads, directly into the TME....The Series A extension will support the company's entry into a Phase 1 clinical trial. This trial is designed to achieve proof of mechanism for ACTM-838, demonstrating its ability to selectively enrich in tumors, deliver payload combinations there, and positively re-activate the immuno-compromised TME. In addition, the trial is designed to assess the dose selection, safety, efficacy and pharmacokinetics of ACTM-838."

Financing • New P1 trial • Oncology • Solid Tumor

ACTM-838, a novel immunotherapy that enriches in solid tumors after IV dosing and comprehensively reverses the immunosuppressive TME to promote durable anti-tumor immunity (AACR 2023) - "Analyses of public RNAseq datasets from patients with primary or metastatic disease revealed cancer types with high levels of myeloid infiltration and adenosine enrichment, suggesting that ACTM-838 efficacy could provide benefit in these indications.ACTM-838 is a novel immunotherapy delivering IL-15plex + eSTING payloads to phagocytic APCs, inducing a durable anti-tumor immune response, after IV dosing. It possesses a compelling safety profile, and is currently in IND-enabling, preclinical development."

IO biomarker • Oncology • Solid Tumor • CD8 • IL15 • LAG3 • STING

ACTM-838, a microbial-based immunotherapy that enriches in solid tumors after IV dosing, reverses the immunosuppressive TME to promote durable anti-tumor immunity, alone and in combination with anti-PD1 in mice (SITC 2022) - "IV-delivered ACTM-838 possesses a compelling safety profile in mice and primates, and is currently in IND-enabling, preclinical development. Ethics Approval All animals were used according to protocols approved by an Institutional Animal Care and Use Committee and maintained in specific pathogen-free conditions in a AAALAC accredited barrier facility."

Combination therapy • IO biomarker • Preclinical • Colon Cancer • Oncology • Solid Tumor • CD8 • IL15 • STING

Actym Therapeutics Reports Preclinical Data Demonstrating ACTM-838's Ability to Generate Anti-Tumor Immunity (PRNewswire) - "'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."

Preclinical • Oncology • Solid Tumor

Actym Therapeutics and Wacker Biotech Sign Manufacturing Contract for Actym's Lead Candidate for the Treatment of Solid Tumors (PRNewswire) - "Actym Therapeutics...and Wacker Biotech announced today that they have signed a contract for the manufacturing of Actym's lead clinical candidate, ACTM-838, for the treatment of solid tumors. Under the terms of the agreement, Wacker Biotech will initiate GMP (Good Manufacturing Practice) production of Phase 1 clinical material of Actym's therapeutic candidate at its site in Amsterdam using its LIBATEC® technology. Both companies announced today that they are already working closely together on technology transfer and initiation of scale-up production of ACTM-838."

Licensing / partnership • Oncology • Solid Tumor

ACTM-838: A microbial-based immunotherapy that delivers combination IL-15 + engineered STING to tumor-resident APCs After IV dosing in T-cell excluded solid tumors (SITC 2021) - "In preclinical studies, ACTM-838 promotes CD8+ T-cell mediated tumor clearance in T-cell excluded tumors and elicits durable anti-tumor immunity, and is well tolerated in primates. Based on these data, ACTM-838 was nominated for clinical development and has entered cGMP manufacturing and IND-enabling studies."

Breast Cancer • Oncology • Solid Tumor • CD8 • IL15 • STING • TGFB1

Actym Therapeutics Announces Lead Candidate for Clinical Development, Presentation at SITC (PRNewswire) - "Actym Therapeutics today announced that ACTM-838 has been selected as a lead clinical development candidate for the treatment of solid tumors. ACTM-838 is based on the company's immunotherapy platform called STACT (S. Typhimurium-Attenuated Cancer Therapy), which delivers multiplexed immuno-modulatory payloads directly to tumor-resident immune cells....n preclinical studies, the IL-15plex + eSTING payload combination delivered by STACT resulted in primary human and mouse M2 macrophage production of type I interferon, and repolarization into a novel hybrid M1/M2 phenotype capable of tumor cell phagocytosis and priming of CD8+ T-cells."

Pipeline update • Preclinical • Breast Cancer • Oncology • Solid Tumor