Pancreatic cancer remains one of the most challenging cancers to treat, with a five-year survival rate of just 13% across all stages. This statistic resonates particularly following the public battle of television icon Alex Trebek, who disclosed his stage IV metastatic pancreatic cancer diagnosis five years ago. The prognosis is even more dire for those with distant metastatic disease, where the survival rate drops to a mere 3%.
Despite these grim statistics, innovative approaches are emerging. Actuate Therapeutics has made significant strides with its lead compound, elraglusib, which has demonstrated promising results in clinical trials targeting metastatic pancreatic ductal adenocarcinoma (mPDAC). This form of cancer accounts for approximately 80-85% of pancreatic cancer cases, with a treatment market anticipated to expand from $2.92 billion in 2022 to $5.84 billion by 2030, according to Grand View Research.
At the recent American Society of Clinical Oncology (ASCO) Annual Meeting, Actuate unveiled positive topline results from its Phase II Actuate-1801 Part 3β trial (NCT03678883). The trial evaluated elraglusib in combination with the chemotherapy regimen of gemcitabine/nab-paclitaxel (GnP). Findings indicated a median overall survival increase of 10.1 months for patients treated with the elraglusib/GnP combination, compared to a median of 7.2 months for those receiving GnP alone.
Among the 29 patients deemed evaluable for efficacy, the median overall survival with elraglusib reached 15.3 months, with two patients achieving complete responses and nine others showing partial responses. These results are particularly noteworthy when compared to historical data, such as the 2013 MPACT trial, which reported a median overall survival of 8.5 months, and the 2020 NAPOLI 3 trial, which indicated a median overall survival of 11.1 months.
Actuate’s president and CEO, Daniel M. Schmitt, emphasized the significance of elraglusib’s clinical data, 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.” He further noted that no meaningful advancements in pancreatic cancer treatment have emerged in over a decade, making elraglusib’s potential groundbreaking.
The Actuate-1801 trial involved 286 patients with mPDAC, who had not received prior systemic treatment. Participants were randomized in a 2:1 ratio to receive elraglusib combined with GnP, or GnP alone, with the primary endpoint being median overall survival. As of September, 22 patients in the elraglusib plus GnP arm were either undergoing treatment or in follow-up, with treatment durations ranging from 20 to 42 months.
Actuate is also progressing with additional trials evaluating elraglusib in combination with other chemotherapy agents. A Phase II trial led by researchers from Harvard Medical School and Massachusetts General Hospital is investigating elraglusib alongside Folfirinox and losartan for mPDAC patients. Meanwhile, Actuate has partnered with UPMC Hillman Cancer Center and Incyte on the Phase I RiLEY trial, which explores elraglusib combined with a modified version of Folfirinox and Incyte’s PD-1-blocking antibody Zynyz® (retifanlimab-dlwr).
Looking ahead, Actuate is preparing for regulatory submissions to both the FDA and the European Medicines Agency (EMA) by the end of 2025. The company is also seeking Breakthrough Therapy designation from the FDA, which would require elraglusib to demonstrate substantial improvement over existing therapies for mPDAC.
Despite these positive developments, Actuate faces financial pressures. According to its recent Form 10-Q report, the company recorded a net loss of $5.407 million in the third quarter of 2025, although this was an improvement from $5.971 million a year earlier. Actuate ended the quarter with cash and cash equivalents totaling $16.925 million, bolstered by a series of capital-raising events, including a public offering that generated net proceeds of $15.574 million.
Actuate’s management has acknowledged that its current cash reserves may not be sufficient to sustain operations beyond the second quarter of 2026 without additional funding. Schmitt outlined two potential paths for the company: pursuing organic growth or exploring merger and acquisition opportunities. The future of Actuate’s workforce, currently around 12 employees plus various consultants, will largely depend on feedback from the FDA regarding elraglusib.
As the company navigates this critical period, the impact of elraglusib on the treatment landscape for pancreatic cancer could represent a significant breakthrough, offering hope to patients battling this aggressive disease.
