CLINICAL AND REGULATORY

Alkermes presented two posters related to its nemvaleukin during ASCO

ARTISTRY-6 is evaluating nemvaleukin as a monotherapy in patients with advanced cutaneous melanoma or advanced mucosal melanoma. ARTISTRY-7 is evaluating nemvaleukin as a monotherapy and in combination with pembrolizumab in comparison to investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer. Enrollment in both ARTISTRY-6 and ARTISTRY-7 is underway and we are excited to continue to accumulate data from these studies which we believe have potential to support registration in two difficult-to-treat tumor types.

Anaveon presented trial in progress data for OMNIA-1 and OMNIA-2 trials at ASCO

Anaveon evaluates its ANV419, a fusion protein of IL-2 and anti-IL-2 monoclonal antibody ANV419 in patients with melanoma and multiple myeloma. The molecule is designed to selectively activate cytotoxic T cells and NK cells and avoid a suppressive tumor response while minimizing toxicities. ANV419 preferentially stimulates cytotoxic CD8+ T and NK cells over immunosuppressive regulatory T cells, with a significantly longer half-life than that of conventional IL-2. Safety and tolerability data from this study confirmed the ability of ANV419 to deliver high molar equivalents of IL-2 in a tolerable way.

Actym Therapeutics is engineering microbes to enable safe systemic delivery

Actym’s platform, dubbed STACT, is a Salmonella typhimurium bacterium genetically engineered for tumor-specific payload delivery. Bacterial vectors are typically limited to an intra-tumoral route of administration because delivering them systemically would be too toxic. Actym took Salmonella and removed the inflammatory and immunogenic surface components that make the bacterium toxic.

The bacterium was also modified to become dependent on synthesis of metabolites that exist at elevated levels in the tumor microenvironment and not in healthy tissue. The modifications resulted in tumor-specific delivery and internalization by phagocytic cells and reduced the systemic inflammatory cytokine signature in mice. Actym performed a large, multiplex screen across innate agonists, checkpoints, cytokines and co-stimulatory receptors and measured attributes such as potency, expression level, efficacy, synergy and safety to determine an optimal payload combination.

Its lead candidate, ACTM-838, encodes an IL-15 plus IL-15RA fusion protein and an engineered, constitutively active STING variant. The combination reprograms the immunosuppressive tumor microenvironment. ATM-838 increased T, B and NK cell infiltration; macrophage and dendritic cell activity; cytokines and an IFN response signature.

In a refractory, metastatic breast cancer mouse model, ACTM-838 reduced tumor volume and protected the mice against tumor rechallenge. It produced a synergistic effect when combined with anti-PD-1 therapy. ACTM-838 also reduced tumor volume in a colon cancer mouse model, while decreasing the percentage of exhausted T cells and regulatory T cells.