Actuate Therapeutics has announced promising clinical data for elraglusib, a potential treatment for metastatic pancreatic cancer, a disease that continues to have limited therapeutic options. Five years after television host Alex Trebek publicly revealed his stage IV pancreatic cancer diagnosis, the market for pancreatic cancer therapies is projected to grow significantly, from $2.92 billion last year to $5.84 billion by 2030, according to Grand View Research. The five-year survival rate for pancreatic cancer remains critically low at 13% for all stages, and only 3% for advanced cases.
Actuate’s elraglusib is being evaluated in Phase II trials, including the Actuate-1801 trial (NCT03678883), which assesses its efficacy in combination with the chemotherapy regimen of gemcitabine/nab-paclitaxel (GnP) in patients with first-line metastatic pancreatic ductal adenocarcinoma (mPDAC). The trial recently presented data at the American Society of Clinical Oncology annual meeting, indicating a median overall survival (mOS) increase of 10.1 months for patients receiving elraglusib compared to 7.2 months for those on GnP alone. This data comes from a cohort of 155 patients, demonstrating a 37% reduction in the risk of death.
Among 29 efficacy evaluable patients in a larger intent-to-treat population, elraglusib exhibited a median overall survival of 15.3 months, with complete responses in two patients and partial responses in nine others. Notably, when combined with data from a separate single-arm trial, elraglusib has achieved four complete responses among over 200 patients.
Actuate’s president and CEO, Daniel M. Schmitt, emphasized the significance of these findings, noting that they compare favorably to the mOS of 8.5 months reported in the 2013 MPACT trial and 11.1 months in the 2020-21 NAPOLI 3 trial. Schmitt stated, “Everything points at this drug [elraglusib] being highly active and meeting the endpoint the FDA is most interested in, which is an increase in overall survival.”
The Actuate-1801 trial has enrolled 286 patients with no prior systemic treatment for metastatic pancreatic disease, randomizing them to receive either the elraglusib/GnP combination or GnP alone. As of September, 22 patients in the elraglusib arm were still in active treatment or follow-up, showcasing a much longer duration on study compared to just three patients in the GnP arm.
Actuate is also advancing multiple trials to explore elraglusib’s potential in combination with other chemotherapy drugs. A Phase II trial led by researchers from Harvard Medical School and Massachusetts General Hospital is currently underway, while Actuate is collaborating with UPMC Hillman Cancer Center and Incyte on a Phase I trial examining elraglusib with a modified version of Folfirinox and Incyte’s PD-1-blocking antibody, Zynyz®.
Schmitt described elraglusib as a potential “backbone” therapy for pancreatic cancer, highlighting its unique ability to enhance patient outcomes. He remarked, “It’s a very unique situation with elraglusib…the safety profile is exceptional, and the drug is very active.”
Current standard treatments for pancreatic cancer vary according to the disease stage. While early-stage tumors are often surgically removed, advanced cases typically require chemotherapy. The past year has seen some advancements, including FDA approvals for two new therapies: Bizengri® and Cabometyx®, aimed at specific subsets of pancreatic cancer patients.
Elraglusib operates as a selective small-molecule inhibitor of glycogen synthase kinase-3 beta (GSK-3β), an enzyme implicated in tumor progression. Developed by Actuate, which was established in 2015 as a spin-out from the University of Illinois Chicago and Northwestern University, the drug aims to disrupt molecular pathways that facilitate tumor growth and resistance to conventional treatments.
Beyond pancreatic cancer, Actuate is exploring elraglusib’s effectiveness against several other cancers, including colorectal cancer and melanoma, with plans for additional clinical trials. The company anticipates advancing its research into Ewing sarcoma, a rare form of cancer, with a Phase II study slated for 2026, contingent on funding.
In terms of financial health, Actuate reported a net loss of $5.407 million for the third quarter of 2025, showing improvement from a loss of $5.971 million in the same period the previous year. The company has raised significant capital over the past year, ending the third quarter with cash and equivalents of $16.925 million.
Actuate has acknowledged that its current financial resources may not be sufficient to meet operational needs beyond the second quarter of 2026, prompting discussions about potential mergers or acquisitions while also considering organic growth through expansion.
“We’re going to run a two-prong approach here,” Schmitt said, indicating a dual strategy of building internal capabilities while engaging with larger pharmaceutical companies. “If you think about the number of opportunities set for this drug and the breadth of the potential, you’d want to get that going as quickly as possible.”
