Leap Therapeutics is laying off half of its staff as the company narrows the focus of its lead cancer drug against the backdrop of a challenging environment for biotechs.

The Massachusetts-based company’s retooled strategy for its sole clinical-stage asset, an anti-DKK1 antibody called sirexatamab, will now be focused exclusively on colorectal cancer (CRC). Subgroup data from a phase 2 study in this indication, unveiled in March, showed 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.

The company pointed to the “strong signal” from the study as supporting the need for a phase 3 trial to evaluate the combo treatment in patients with second-line microsatellite stable CRC who have high DKK1 levels or in patients who have not received prior anti-VEGF therapy.

Back in January, Leap decided to scrap development of sirexatamab in combination with BeiGene’s anti-PD-1 antibody tislelizumab as a treatment for gastric cancer on the basis of an initial readout from the same phase 2 study. It was the unimpressive results from the other arm of that trial, evaluating sirexatamab as a first-line treatment for CRC, that persuaded the biotech to focus on the drug as second-line treatment. That readout saw Leap’s stock plunge below the $1 line, from which it has yet to recover.

Today’s announcement means previous clinical work to explore sirexatamab in combination with Merck & Co.’s Keytruda to treat endometrial cancer has also now been deprioritized.

Leap reaffirmed this morning that it has engaged a financial advisor to “explore business development opportunities to further the development of sirexatamab.”

The other centerpiece of Leap’s refocused portfolio is FL-50, a GDF-15 neutralizing antibody in preclinical development for targeting cachexia pathway, a wasting syndrome that can lead to poor outcomes in cancer patients.

In order to keep these programs running, Leap—which ended March with $32.7 million on hand—announced this morning a strategic restructuring to “realign its resources.” This involves reducing the company’s workforce by around 50%.

Leap entered 2025 with 52 full-time staff, of which 41 were employed in research and development roles.

“In this difficult market environment, we focused our resources to position Leap to advance sirexatamab in CRC and FL-501 preclinically in order to provide the greatest value for our shareholders,” Leap CEO Douglas Onsi said in a statement. “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.”