Five years after television host Alex Trebek publicly announced his battle with stage IV metastatic pancreatic cancer, advances in treatment for this aggressive disease remain limited. Currently, metastatic pancreatic cancer accounts for approximately 80–85% of all pancreatic cancer diagnoses. The treatment market is projected to grow at a compound annual growth rate of 12.3%, from $2.92 billion in 2022 to $5.84 billion by 2030, according to Grand View Research. Despite these financial projections, the prognosis for patients remains grim; the American Cancer Society reports a five-year survival rate of just 13% for all stages, and a mere 3% for distant pancreatic cancer. Treatment costs can exceed $100,000 per patient.
In this challenging landscape, Actuate Therapeutics is making strides with its lead compound, elraglusib. The company is focused on developing treatments for pancreatic cancer, presenting positive clinical data at the recent American Society of Clinical Oncology (ASCO) Annual Meeting. Actuate shared results from the Phase II Actuate-1801 Part 3β trial (NCT03678883), which evaluated elraglusib in combination with the chemotherapy regimen gemcitabine/nab-paclitaxel (GnP) for patients with first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).
The trial involved 155 patients and demonstrated a median overall survival increase of 10.1 months compared to just 7.2 months for those receiving GnP alone. Among the 42 patients in the intent-to-treat population, elraglusib led to a median overall survival of 15.3 months, including two complete responses and nine partial responses. These findings position elraglusib favorably against previous trials, such as the MPACT trial and the NAPOLI 3 trial, which reported median overall survivals of 8.5 months and 11.1 months, respectively.
Daniel M. Schmitt, Actuate’s President and CEO, emphasized the significance of these results, stating, “Everything points at this drug being highly active and meeting the endpoint the FDA is most interested in, which is an increase in overall survival. There has been no meaningful advance in pancreatic cancer in the last 13 years. This would be the first one.”
Actuate has incorporated its promising data into an amended investigational new drug (IND) application. The company plans to submit regulatory applications to both the FDA and the European Medicines Agency (EMA) by the end of this year, with a continued push into early 2026. The FDA has indicated that elraglusib must show substantial improvement over existing standard therapies, including regimens containing irinotecan, to secure a Breakthrough Therapy designation.
The Actuate-1801 trial enrolled a total of 286 patients with mPDAC who had not received prior systemic treatment. Participants were randomly assigned to receive either the elraglusib/GnP combination or GnP alone. Actuate-1801 remains ongoing, and recent data from September indicated that 22 patients in the elraglusib plus GnP arm were still in active treatment or survival follow-up, with treatment durations ranging from 20 to 42 months.
Actuate is exploring elraglusib’s potential in combination with other chemotherapy agents in three ongoing trials. A Phase II study led by researchers from Harvard Medical School and Massachusetts General Hospital is examining elraglusib in conjunction with Folfirinox and losartan. Additionally, early data from a Phase I trial, known as the RiLEY trial, is evaluating elraglusib with a modified version of Folfirinox and Incyte’s PD-1-blocking antibody Zynyz®.
Schmitt highlighted the unique potential of elraglusib as a “backbone” therapy, stating, “I’ve never heard of putting another agent on top of chemo, and patients feeling better. It’s a very unique situation with elraglusib, a drug that has the potential to be the new backbone therapy in this highly aggressive and deadly disease.”
Current standard care for pancreatic cancer varies by stage, with early-stage tumors often treated through surgery, while advanced forms typically require chemotherapy. Promising developments are on the horizon, as Swiss-based Novocure anticipates approval for its Tumor Treating Fields (TTFields) wearable device in the second half of 2026, which is currently under FDA review.
In the past year, the FDA has approved two new therapies for pancreatic cancer: Bizengri®, a bispecific antibody approved in December 2024, and Cabometyx®, a kinase inhibitor approved in March 2025 for specific pancreatic neuroendocrine tumors.
Elraglusib, initially identified as a selective small-molecule inhibitor of glycogen synthase kinase-3 beta (GSK-3β), is designed to target pathways that promote tumor growth and chemotherapy resistance. This compound was developed by Actuate, which emerged from the University of Illinois Chicago and Northwestern University in 2015.
Beyond pancreatic cancer, Actuate is exploring elraglusib’s effectiveness against various cancers, including colorectal cancer and melanoma. The company plans to initiate a Phase I trial for a new oral tablet formulation in metastatic forms of these diseases. Additionally, the Phase I Actuate-1902 trial has identified Ewing sarcoma as a potential second indication for elraglusib, with plans to advance toward a Phase II study in 2026, contingent upon funding.
Financially, Actuate reported a net loss of $5.407 million in the third quarter of 2025, a slight improvement from a loss of $5.971 million in the same period the previous year. The company’s cash reserves stand at $16.925 million, bolstered by recent capital-raising efforts, including public offerings and private placements.
Actuate acknowledges that without additional funding, its financial resources may not support operations beyond the second quarter of 2026. Schmitt indicated that the company is evaluating two potential pathways: expanding organically or pursuing a merger-and-acquisition strategy. The future of Actuate’s workforce—currently comprising about 12 core team members—will depend on forthcoming FDA feedback regarding elraglusib.
In conclusion, Actuate’s elraglusib demonstrates significant potential for improving treatment outcomes in pancreatic cancer, a field that has seen limited advancements for over a decade. The company’s ongoing trials and regulatory efforts could pave the way for a new standard of care in the fight against this challenging disease.
