Actuate Publishes Scientific Report on Elraglusib's New Immunomodulatory Mechanism as GSK-3β Inhibitor

Actuate Therapeutics, Inc. has unveiled new mechanistic data highlighting the potential of its investigational drug, elraglusib, in modulating the immune system for the treatment of neuroblastoma. This data, recently published in Scientific Reports, provides strong evidence of the drug's ability to enhance immune activation against tumor cells, potentially offering new immunotherapeutic strategies.

Daniel Schmitt, President and CEO of Actuate, emphasized the significance of these findings. He noted that elraglusib improves antigen presentation and boosts CD8+ cytotoxic T cell activation. This could lead to more effective treatments, particularly when combined with checkpoint inhibitors. Neuroblastoma, typically resistant to such inhibitors, served as the model for these findings, which suggest that elraglusib could activate the immune system even in cancers previously unresponsive to checkpoint inhibitors.

The key mechanistic findings include:
1. Elraglusib significantly increases MHC-I molecule surface expression on neuroblastoma cells, enhancing their recognition by cytotoxic T lymphocytes (CTLs).
2. The drug disrupts NF-κB signaling, which is crucial for tumor cell survival, thereby promoting cancer cell apoptosis and reducing treatment resistance.
3. Elraglusib also enhances IFNγ signaling through the JAK/STAT pathway, particularly via STAT1, further supporting improved antigen presentation and immune response.
4. When used in conjunction with anti-PD-1 treatment, elraglusib amplifies CD8+ T cell proliferation and activation by neuroblastoma cells, indicating potential for further development in enhancing tumor immune response.

Dr. Andrew Mazar, Actuate’s Scientific Co-founder and Chief Operating Officer, highlighted the broader implications of these findings. He remarked that while checkpoint inhibitors have shown clinical benefits in many advanced cancers, most patients do not respond to such treatments. Enhancing tumor immunogenicity in neuroblastoma, which is typically unrecognized by the immune system, offers therapeutic promise. This approach could potentially be applied to other tumors that are similarly resistant to immune recognition.

Elraglusib is currently the subject of clinical evaluation in a Phase 2 trial for metastatic pancreatic cancer (NCT03678883) and a Phase 1/2 trial for Ewing Sarcoma and related sarcomas (NCT04239092).

Actuate Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing therapies for high-impact, difficult-to-treat cancers. Their lead investigational product, elraglusib, targets key molecular pathways in cancer that promote tumor growth and resistance to conventional treatments like chemotherapy. Elraglusib also modulates anti-tumor immunity by inhibiting NF-κB in immune cells and regulating multiple immune checkpoints and cell functions.

In conclusion, the novel mechanistic insights into elraglusib underscore its potential as an innovative immune modulator in cancer treatment. The data suggests that elraglusib could enhance immune system activation in tumors that are typically resistant to current treatments, paving the way for new therapeutic strategies in the fight against challenging cancers.