Leap Therapeutics Stock Surges on Strong DeFianCe Phase 2 Results and 50% Workforce Cut

Introduction

Leap Therapeutics, Inc. (NASDAQ: LPTX) is a clinical-stage biotechnology company headquartered in Cambridge, Massachusetts. The firm specializes in developing targeted and immuno-oncology therapeutics. Its most advanced program, sirexatamab (DKN-01), is a humanized monoclonal antibody that targets Dickkopf-1 (DKK1) and is being evaluated in esophagogastric, gynecologic, and colorectal cancers. The company is also developing two additional antibody candidates: FL-301, which targets Claudin18.2 and is focused on gastric and pancreatic cancers, and FL-501, which targets GDF-15 and addresses cachexia in oncology indications.

Corporate Structure

Leap Therapeutics operates with a team of 11–50 employees. Douglas E. Onsi serves as the President and Chief Executive Officer. The board of directors includes Christopher Mirabelli, PhD (Chairman), as well as industry professionals such as James Cavanaugh, PhD, and William Li, MD. A scientific advisory board, chaired by David Tuveson, MD, PhD, provides guidance on research strategy and includes members from institutions such as Cold Spring Harbor Laboratory, Duke University, and Memorial Sloan Kettering.

Biotechnology by National Cancer Institute

Developments and News

On May 13, 2025, Leap reported its first-quarter 2025 results, highlighting findings from Part B of the Phase 2 DeFianCe trial (NCT05480306) in patients with microsatellite-stable colorectal cancer. In the upper-quartile DKK1 subgroup (n=44), the sirexatamab arm achieved a 32% higher overall response rate and a progression-free survival (PFS) advantage of 3.5 months compared to the control arm, which consisted of bevacizumab plus chemotherapy. Among VEGF-naïve patients (n=95), the response rate improved by 22% with a 2.6-month PFS advantage. With 25 patients remaining on the investigational arm versus 17 on the control arm, PFS data continue to develop favorably for sirexatamab. These results support the plan for a registrational Phase 3 clinical study in targeted colorectal cancer populations.

In the first quarter, Leap also hosted a virtual event featuring Zev A. Wainberg, MD, to discuss the findings from the DeFianCe study. During the American Association for Cancer Research annual meeting in April 2025, the company presented preclinical data on FL-501, highlighting its extended half-life, reduced clearance, and efficacy in restoring body composition in cachexia models. Concurrently, Leap announced a strategic restructuring resulting in a workforce reduction of approximately 50% to concentrate resources on the clinical development of sirexatamab and the preclinical advancement of FL-501.

Financial and Strategic Analysis

As of August 15, 2025, LPTX shares closed at $0.3203, representing a 31.49% increase with a trading volume of 1,368,371 shares on the Nasdaq. This stock movement corresponds with expectations for mid-2025 data updates from the DeFianCe trial and the planned submission of an investigational new drug application for FL-501. The workforce reduction indicates a strategy to conserve capital while focusing efforts on initiating Phase 3 studies for sirexatamab in high-DKK1 and VEGF-naïve colorectal cancer patient populations. With no approved products currently, ongoing clinical results will significantly influence the company’s valuation and future financing requirements.

Market Position and Industry Context

Leap operates within the competitive immuno-oncology sector, where monoclonal antibodies that target tumor microenvironment factors are increasingly significant. The inhibition of DKK1 by sirexatamab represents an emerging therapeutic mechanism in colorectal and gastrointestinal cancers. FL-301 (Claudin18.2) and FL-501 (GDF-15) provide additional avenues for addressing solid tumors and cancer-associated cachexia. Larger biotechnology and pharmaceutical companies are also advancing similar programs, positioning Leap among a cohort of smaller firms seeking to establish proof-of-concept in their respective Phase 2 and Phase 3 studies. Strategic scientific partnerships and a streamlined asset portfolio are essential for navigating regulatory processes and potential collaborations.

tl;dr

– On May 13, 2025, Leap reported findings from Part B of the DeFianCe Phase 2 trial, showing a 32% higher response rate and a 3.5-month PFS gain in DKK1-high colorectal cancer patients, along with a 22% response boost and 2.6-month PFS extension in VEGF-naïve patients.
– Preclinical results for FL-501 presented at the AACR 2025 support efforts toward an IND filing.
– Workforce reduced by approximately 50% to prioritize the initiation of Phase 3 studies for sirexatamab and further development of FL-501.
– Shares rose by 31.49% on August 15, 2025, amid expectations for forthcoming updates from the DeFianCe trial and a planned registrational study in second-line colorectal cancer.