Actuate Pivots to Oral Cancer Drug, Eyes RAS Combination Therapy

CHICAGO and FORT WORTH, Texas – May 11, 2026 – Actuate Therapeutics has announced a significant strategic shift for its lead cancer drug, elraglusib, securing Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for a new oral tablet formulation. This move away from its original intravenous (IV) version paves the way for a new Phase 1/2 clinical trial slated to begin in the second half of 2026, targeting some of the most difficult-to-treat solid tumors, including pancreatic cancer, metastatic melanoma, and non-small cell lung cancer (NSCLC).

The decision represents a pivotal moment for the clinical-stage biopharmaceutical company, reflecting both a broader industry trend toward more patient-friendly treatments and a specific data-driven strategy to maximize the drug's potential efficacy.

The Patient-Centric Pivot: From IV to Oral

Actuate is prioritizing the development of an oral tablet for elraglusib, a move intended to dramatically enhance patient convenience and broaden the drug's clinical utility. The transition from hospital-based infusions to a pill that can be taken at home is a profound change that can improve quality of life, reduce healthcare system burdens, and potentially increase treatment adherence.

However, this strategic pivot is rooted in more than just convenience. It is backed by a key finding from the company's prior Phase 2 study of IV elraglusib in metastatic pancreatic ductal adenocarcinoma (mPDAC). An analysis of that data, the results of which were published in the prestigious journal Nature Medicine, revealed a positive correlation between higher drug exposure and improved clinical outcomes, including a meaningful increase in overall survival. This suggests that getting more of the drug to the tumor, and maintaining its presence over time, is critical to its success.

“Advancing the elraglusib oral tablet is an important element to the success of our overall development strategy,” said Daniel Schmitt, President & Chief Executive Officer of Actuate, in a statement. “Transitioning from an IV to an oral formulation of elraglusib... is supported by an analysis of the completed Phase 2 data of elraglusib in mPDAC, showing higher exposures are associated with improved clinical activity.”

While oral drugs face challenges like bioavailability and first-pass metabolism—where a drug is partially broken down by the liver before reaching the bloodstream—Actuate’s upcoming Phase 1/2 study is designed specifically to demonstrate that the new oral formulation can achieve higher, more sustained drug exposure compared to the IV version. The trial will first establish a safe and effective dose before expanding into patient groups with advanced solid tumors.

A Two-Pronged Attack on Difficult Cancers

The company's updated strategy for elraglusib is a two-pronged attack. The first prong is optimizing the drug as a monotherapy through the new oral formulation. The second, and potentially more impactful, is exploring its power in combination with other cutting-edge cancer therapies.

Actuate is actively investigating elraglusib’s potential to be paired with RAS inhibitors. RAS genes are the most frequently mutated oncogenes in human cancer, driving tumor growth in approximately 30% of all cancers and being particularly prevalent in pancreatic (around 90%), colorectal (around 45%), and lung (around 30%) cancers. For decades, RAS was considered an “undruggable” target.

While recent breakthroughs have led to the approval of RAS inhibitors like sotorasib and adagrasib, tumors often develop resistance. Actuate believes elraglusib, a novel GSK-3β inhibitor, can counteract these resistance mechanisms. By targeting key survival pathways that cancer cells use to evade treatment, elraglusib could enhance the effectiveness of RAS inhibitors, potentially positioning it as a foundational “backbone agent” in combination regimens.

“In parallel, we are actively exploring elraglusib’s combination potential in RAS-driven cancers, where early preclinical data show potential for synergy with RAS inhibitors,” Schmitt continued. “We look forward to further maturing this data, with additional updates expected in mid-2026.”

Bolstering Leadership Amidst High Stakes

To navigate this critical phase of development, Actuate has strengthened its leadership by appointing industry veteran Martin Huber, MD, to its Board of Directors. Dr. Huber brings a wealth of experience in oncology drug development, having previously served as President and CEO of Mersana Therapeutics and currently sitting on the board of Syndax Pharmaceuticals. His track record of guiding clinical-stage companies through the complexities of oncology trials and corporate strategy is a significant asset.

“I am excited to join a team that has successfully demonstrated improved survival in patients with pancreatic cancer who were treated with elraglusib,” said Dr. Huber. “I look forward to helping the Actuate team advance the new oral formulation in the evolving pancreatic treatment landscape and potentially bring elraglusib to more patients.”

Dr. Huber's appointment comes at a crucial time. Like many clinical-stage biopharmaceutical firms, Actuate operates in a high-risk, high-reward environment where success is contingent on both scientific progress and financial stability. The company's own public filings note the inherent risks and the need to secure additional capital to fund operations beyond mid-2026. The addition of a seasoned leader like Dr. Huber is a strategic move to build investor confidence and provide expert guidance as the company advances its ambitious and capital-intensive clinical plans.

A Groundbreaking Mechanism with a Competitive Edge

At the heart of Actuate's strategy is elraglusib's unique mechanism of action as a GSK-3β inhibitor. This enzyme is involved in multiple cellular pathways that promote tumor growth and resistance to treatment. By inhibiting GSK-3β, elraglusib is believed to disrupt cancer cell survival, DNA damage repair, and also modulate the immune system to help fight the tumor.

This scientific foundation is not just theoretical. The previously mentioned Phase 2 study in pancreatic cancer demonstrated that adding IV elraglusib to standard-of-care chemotherapy resulted in a statistically significant improvement in overall survival—a landmark achievement in a disease known for its dismal prognosis.

As Actuate prepares to launch its new trial, it enters crowded and competitive fields in melanoma, lung, and colorectal cancer, where immunotherapies and other targeted agents have become standard. However, a significant unmet need remains for patients whose cancers become resistant to these therapies. With its distinct mechanism and promising early data in refractory melanoma and pancreatic cancer, elraglusib may be able to carve out a crucial niche. For Actuate, the path forward involves not just demonstrating the superiority of its new oral formulation, but also proving that its unique scientific approach can deliver on the promise of becoming a cornerstone therapy in some of oncology’s most challenging fields.