Leap Therapeutics Announces Major Restructuring and Strategic Refocus

Leap Therapeutics, a Massachusetts-based biotech company, has unveiled a significant restructuring plan and a strategic shift in its drug development focus. The company, facing what CEO Douglas Onsi described as a "difficult market environment," is taking decisive action to streamline operations and concentrate on its most promising assets.

Workforce Reduction and Portfolio Narrowing

In a move to realign its resources, Leap Therapeutics announced a 50% reduction in its workforce. The company, which started 2025 with 52 full-time employees, including 41 in research and development roles, will see its headcount halved as part of this strategic restructuring.

The restructuring extends beyond personnel changes, with Leap narrowing its clinical pipeline to focus exclusively on colorectal cancer (CRC) for its lead asset, sirexatamab. This anti-DKK1 antibody has shown promise in recent clinical trials, particularly in combination with other therapies.

Promising Results in Colorectal Cancer

Leap's decision to focus on CRC stems from encouraging subgroup data in a phase 2 study. The trial demonstrated that a combination of sirexatamab, Roche's Avastin, and chemotherapy resulted in a statistically significant 32% higher overall response rate in patients with high DKK1 levels compared to Avastin and chemotherapy alone.

These results have bolstered the company's confidence in pursuing a phase 3 trial to evaluate the combination treatment in second-line microsatellite stable CRC patients with high DKK1 levels or in patients who have not received prior anti-VEGF therapy.

Deprioritization of Other Indications

As part of its strategic refocus, Leap has decided to deprioritize several other clinical programs. The company has scrapped the development of sirexatamab in combination with BeiGene's anti-PD-1 antibody tislelizumab for gastric cancer, following unimpressive results from a phase 2 study. Additionally, previous work exploring sirexatamab in combination with Merck & Co.'s Keytruda for endometrial cancer has also been sidelined.

Despite these setbacks, Leap remains committed to exploring business development opportunities to further the development of sirexatamab. The company has engaged a financial advisor to assist in this process.

Financial Position and Future Outlook

As of March, Leap Therapeutics reported having $32.7 million in cash on hand. The company's restructuring efforts are aimed at extending its financial runway and focusing resources on its most promising programs.

In addition to sirexatamab, Leap is also advancing FL-50, a GDF-15 neutralizing antibody in preclinical development. This asset targets the cachexia pathway, a wasting syndrome that can lead to poor outcomes in cancer patients.

CEO Douglas Onsi emphasized the company's commitment to creating value for shareholders while acknowledging the difficult decisions made: "I would like to personally thank all of our colleagues who have been impacted by this decision and express my appreciation for their contributions and dedication to provide meaningful new treatment options to cancer patients."