The DeFianCe study ( NCT05480306 ) is a Phase 2, open-label, global study of sirexatamab in combination with bevacizumab and chemotherapy in patients with advanced microsatellite stable (MSS) CRC who have received one prior systemic therapy for advanced disease. Part B of the study is a 188 patient randomized controlled trial, with the primary objective being progression-free survival (PFS) in patients with left-sided cancers and in all patients. Key secondary and exploratory objectives include objective response rate ( ORR ), duration of response, and overall survival across tumor, treatment, and biomarker subgroups.

The strong signal in CRC from the DeFianCe study supports Leap moving forward to plan a registrational Phase 3 clinical trial to evaluate sirexatamab plus bevacizumab and chemotherapy in second-line MSS CRC patients with high unmet need, subject to regulatory discussions. Potential Phase 3 patient populations include: DKK1 biomarker-selected, anti-VEGF naïve, anti-EGFR experienced, or RAS-wt patients. While the data matures, Leap intends to conduct global commercial and regulatory strategic analysis to select the optimal population.

Key Findings from Part C of the DisTinGuish study:

Leap also reported data from Part C of the DisTinGuish study evaluating sirexatamab in combination with tislelizumab, BeiGene's anti-PD-1 antibody, and chemotherapy in first-line patients with advanced GEJ and gastric cancer. While demonstrating activity in biomarker populations, the study did not generate a clear positive signal and will be negative on the primary PFS endpoints when the study completes, resulting in the decision not to move forward with Phase 3 studies in gastric cancer.

"Sirexatamab plus tislelizumab and chemotherapy demonstrated improved confirmed response rates compared to the control arm in the ITT, DKK1 -high, and PD-L1 negative patients by Blinded Independent Central Review (BICR). However, gastric cancer is a difficult tumor to assess radiologically, and unfortunately, there was a high level of discordance between investigator assessment (IA) and BICR," said Dr. Sirard. "Therefore, we have decided to focus our internal effort and resources on advancing sirexatamab in CRC and will explore strategic partnership opportunities to advance sirexatamab plus anti-PD-1 antibodies in gastric cancer and other indications where there is high DKK1 expression."

Part C of the DisTinGuish study ( NCT0436380 ) is a Phase 2, randomized, open-label, multicenter study of sirexatamab in combination with tislelizumab and chemotherapy in first-line patients with advanced GEJ and gastric cancer. Part C enrolled 170 first-line, HER2-negative patients. Patients were randomized 1:1 to evaluate sirexatamab in combination with tislelizumab and chemotherapy, compared to tislelizumab and chemotherapy alone. The primary objective is PFS by IA in all patients and in DKK1 TPS > 20 ( DKK1 -high) patients. Secondary objectives include ORR , duration of response, and overall survival as measured by BICR and IA in all patients and in DKK1 -high patients.

Conference Call:
Leap's management team will host a conference call today, January 28, 2025 at 8:00 a.m. Eastern Time to further discuss the data. The conference call will be broadcast live in listen-only mode and can be accessed via the webcast URL: https://edge.media-server.com/mmc/p/t93pn2ke . A replay of the event will be available for a limited time on the Investors page of the Company's website at https://investors.leaptx.com/ .

About Leap Therapeutics
Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, sirexatamab (DKN-01), is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. Sirexatamab is being studied in patients with colorectal, esophagogastric, and gynecological cancers. Leap's pipeline also includes FL-501, a humanized monoclonal antibody targeting the growth and differentiation factor 15 (GDF-15) protein, in preclinical development. For more information about Leap Therapeutics, visit http://www.leaptx.com or view our public filings with the SEC that are available via EDGAR at http://www.sec.gov or via https://investors.leaptx.com/ .

FORWARD-LOOKING STATEMENTS
This press release contains forward-looking statements within the meaning of the federal securities laws. Such statements are based upon current plans, estimates and expectations of the management of Leap that are subject to various risks and uncertainties that could cause actual results to differ materially from such statements. The inclusion of forward-looking statements should not be regarded as a representation that such plans, estimates and expectations will be achieved. Words such as "anticipate," "expect," "project," "intend," "believe," "may," "will," "should," "plan," "could," "continue," "target," "contemplate," "estimate," "forecast," "guidance," "predict," "possible," "potential," "pursue," "likely," and words and terms of similar substance used in connection with any discussion of future plans, actions or events identify forward-looking statements.

All statements, other than historical facts, including statements regarding the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates; the anticipated timing for initiation or completion of clinical trials and release of clinical trial data and the expectations surrounding the outcomes thereof; Leap's future clinical or preclinical product development plans for any of Leap's product candidates; Leap's estimations of projected cash runway; and any assumptions underlying any of the foregoing, are forward-looking statements. Important factors that could cause actual results to differ materially from Leap's plans, estimates or expectations could include, but are not limited to: (i) the results of Leap's clinical trials and pre-clinical studies, including whether the final data from Part B of the DeFianCe study or Part C of the DisTinGuish study are the same as the initial data reported, (ii) Leap's ability to successfully finance or enter into new strategic partnerships for sirexatamab or any of its other programs; (iii) any regulatory feedback that Leap may receive from U.S. Food and Drug Administration (FDA) or equivalent foreign regulatory agency with respect to the registrational Phase III clinical trials that Leap proposes to conduct using sirexatamab for the treatment of patients with second-line CRC or with respect to any other pre-clinical or clinical development activities that Leap will be required to conduct in order to obtain regulatory approval of sirexatamab for the treatment of second-line CRC; (iv) whether any Leap products will receive approval from the FDA or equivalent foreign regulatory agencies; and (v) exposure to inflation and interest rate fluctuations, as well as fluctuations in the market price of Leap's traded securities. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Leap may not actually achieve the forecasts disclosed in such forward-looking statements, and you should not place undue reliance on such forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Leap's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in its subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither Leap, nor any of its affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing Leap's views as of any date subsequent to the date hereof.

CONTACT:
Douglas E. Onsi
President & Chief Executive Officer
Leap Therapeutics, Inc.
617-714-0360
[email protected]

Matthew DeYoung
Investor Relations
Argot Partners
212-600-1902
[email protected]

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SOURCE Leap Therapeutics, Inc.