8-K: Leap Therapeutics Announces Positive Data from Sirexatamab Colorectal Cancer Study and Reports Year-End Financial Results

Leap Therapeutics reports positive updated data from its Sirexatamab colorectal cancer study, showing statistically significant improvements in ORR and PFS in specific patient subgroups, and announces its fourth quarter and full year 2024 financial results.

Summary

• Leap Therapeutics announced its financial results for the fourth quarter and year ended December 31, 2024.
• The company reported positive updated data from Part B of the Phase 2 DeFianCe study of sirexatamab (DKN-01) in second-line patients with advanced microsatellite stable (MSS) colorectal cancer (CRC).
• The updated data confirmed a statistically significant 32% higher overall response rate (ORR) and a 3.5-month longer progression-free survival (PFS) in patients with high DKK1 levels.
• Patients who had not received prior anti-VEGF therapy showed a statistically significant 22% higher ORR and a 2.6-month longer PFS.
• Leap has engaged a leading financial advisor to explore business development opportunities to further the development of sirexatamab.
• The company's pipeline also includes FL-501, with preclinical data to be presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting, with the goal of beginning a clinical trial in 2026.
• Net loss for the year ended December 31, 2024, was $67.6 million, compared to $81.4 million for the year ended December 31, 2023.
• Research and development expenses were $57.2 million for the full year 2024, compared to $73.2 million for the same period in 2023.
• Cash and cash equivalents totaled $47.2 million at December 31, 2024.

Sentiment

Score: 8

Explanation: The document presents positive clinical data and financial results, indicating a favorable outlook for the company. The sentiment is high due to the potential for a Phase 3 trial and the advancement of FL-501.

Positives

• The DeFianCe study results support a registrational Phase 3 clinical trial for sirexatamab in second-line MSS CRC patients.
• Sirexatamab has a large market opportunity in the 25-50% of second-line CRC patients with high DKK1 levels or the approximately 50% who did not receive prior anti-VEGF therapy.
• The outcomes in patients with no prior anti-VEGF therapy provides an opportunity to move into treating first-line CRC patients.
• The company's net loss decreased from $81.4 million in 2023 to $67.6 million in 2024.

Negatives

• The company reported a net loss of $67.6 million for the year ended December 31, 2024.
• The company's cash and cash equivalents decreased from $70.643 million at the end of 2023 to $47.249 million at the end of 2024.

Risks

• The actual size of the potential addressable market for sirexatamab may be smaller than estimated.
• Leap's ability to successfully finance or enter into new strategic partnerships for sirexatamab or any of its other programs is uncertain.
• Regulatory feedback from the FDA or equivalent foreign regulatory agency could impact the registrational Phase III clinical trials for sirexatamab.
• Exposure to inflation and interest rate fluctuations, as well as fluctuations in the market price of Leap's traded securities, could impact the company's financial performance.

Future Outlook

Leap plans to move forward with a registrational Phase 3 clinical trial for sirexatamab in patients with CRC and to advance FL-501 towards clinical trials, with the goal of beginning a clinical trial in 2026.

Management Comments

• Douglas E. Onsi, President and Chief Executive Officer of Leap, stated that the updated data from Part B of the DeFianCe study demonstrated significantly higher ORR and longer PFS for sirexatamab in patients with high levels of DKK1 or who have not had prior anti-VEGF therapy.
• Cynthia Sirard, MD, Chief Medical Officer of Leap, stated that the updated data from Part B of the DeFianCe study confirms that sirexatamab can generate significantly higher ORR and longer PFS in CRC patients who have high levels of DKK1 or who have not had prior anti-VEGF therapy.

Industry Context

The announcement highlights Leap Therapeutics' progress in the competitive oncology market, particularly in colorectal cancer treatment, where new options are needed for heterogeneous patient populations. The focus on biomarker-driven therapies aligns with the industry trend towards personalized medicine.

Comparison to Industry Standards

• The bevacizumab benchmark studies (ML18147, E3200, SLAVE) demonstrate the need for new options for today's heterogeneous second-line patient population, with ORR ranging from 5.4% to 25.7% when combined with chemotherapy.
• The DeFianCe study results show a 32% higher ORR in DKK1-high patients and a 22% higher ORR in VEGF-naive patients, suggesting a potential improvement over existing treatments.
• The company is targeting a Phase 3 trial with BICR assessed Objective Response Rate as the primary endpoint, similar to other accelerated approval pathways in oncology.

Stakeholder Impact

• Shareholders may benefit from the positive clinical data and potential for a Phase 3 trial.
• Patients with CRC may have a new treatment option if sirexatamab is approved.
• Employees may benefit from the company's progress and potential growth.

Next Steps

• Leap plans to move forward with a registrational Phase 3 clinical trial to evaluate sirexatamab plus bevacizumab and chemotherapy in second-line MSS CRC patients with high DKK1 levels or in patients who have not received prior anti-VEGF therapy.
• The company will present preclinical FL-501 data at the 2025 American Association for Cancer Research (AACR) Annual Meeting.
• Leap aims to begin a clinical trial for FL-501 in 2026.

Key Dates

Keywords

sirexatamab, colorectal cancer, DKK1, anti-VEGF therapy, FL-501, clinical trial, oncology, biotechnology, financial results