Actuate Reports Preclinical Synergy for Elraglusib With RAS Inhibitors in Pancreatic Cancer

Key Points

• Actuate Therapeutics reported preclinical data showing that elraglusib enhanced the activity of two investigational RAS-targeted therapies in pancreatic cancer models.
• The studies tested elraglusib with zoldonrasib, a KRAS G12D-selective inhibitor, and daraxonrasib, a multi-selective RAS(ON) inhibitor.
• Combination treatment showed greater reductions in pancreatic cancer-cell growth and viability than either drug alone across murine and human models.
• The combination also showed enhanced activity in pancreatic cancer models resistant to FOLFIRINOX chemotherapy.
• The findings are preclinical and do not establish safety or effectiveness in patients.

Actuate Therapeutics (NASDAQ: ACTU) reported new laboratory data suggesting that its investigational drug elraglusib may enhance the anticancer activity of RAS inhibitors in pancreatic ductal adenocarcinoma, or PDAC.

The studies were conducted with researchers at Northwestern University and the Mayo Clinic. They evaluated elraglusib with zoldonrasib, also known as RMC-9805, and daraxonrasib, also known as RMC-6236, in mouse and human pancreatic cancer models.

Combination Treatment Reduced Pancreatic Cancer Cell Growth

Across mouse KPC pancreatic cancer cell lines, adding elraglusib to zoldonrasib resulted in greater inhibition of tumor-cell growth than zoldonrasib alone.

Researchers also observed combination activity in human patient-derived xenograft, or PDX, pancreatic cancer cell lines. These models are developed from patient tumor tissue and are commonly used to study cancer biology and possible drug activity.

Actuate said the results across both mouse and human models suggest that the combination effect was not limited to a single pancreatic cancer model.

Elraglusib Also Enhanced Activity of Daraxonrasib

The company also tested elraglusib with daraxonrasib, a multi-selective RAS(ON) inhibitor.

According to Actuate, the combination showed greater anticancer activity in multiple mouse and human pancreatic cancer models than either treatment alone.

The results with both zoldonrasib and daraxonrasib support the company’s view that elraglusib may have combination potential with more than one type of RAS-targeted therapy.

FOLFIRINOX-Resistant Models Showed Added Activity

Actuate also studied elraglusib plus zoldonrasib in pancreatic cancer models resistant to FOLFIRINOX, a chemotherapy regimen often used in pancreatic cancer.

In both mouse and human FOLFIRINOX-resistant models, the combination resulted in greater reductions in tumor-cell viability than either drug by itself.

The company said the findings support further study of the combination for patients whose pancreatic cancer progresses after FOLFIRINOX treatment. However, these findings came from laboratory models and cannot predict clinical benefit in people.

Next Studies Will Explore Clinical Combination Potential

Elraglusib targets GSK-3β, while zoldonrasib and daraxonrasib target RAS-driven cancer signaling through different approaches.

Actuate believes the different mechanisms may create a complementary treatment strategy for pancreatic cancer and potentially other RAS-driven cancers.

The company said additional studies are underway and results will be presented at upcoming medical conferences. The announcement did not disclose a specific clinical-trial timeline, patient-enrollment plan, or regulatory pathway for an elraglusib-RAS inhibitor combination.

Elraglusib, zoldonrasib, and daraxonrasib remain investigational based on the supplied information. The preclinical data are an early research finding, and clinical studies will be needed to evaluate the safety, dosing, and potential effectiveness of these combinations in patients.