Core Insights - Leap Therapeutics reported financial results for Q1 2025, highlighting the progress of its lead candidate, sirexatamab, in clinical trials for colorectal cancer (CRC) [1][3] Financial Performance - The net loss for Q1 2025 was $15.4 million, an increase from $13.8 million in Q1 2024, primarily due to higher research and development expenses [8] - Research and development expenses rose to $12.9 million in Q1 2025 from $11.3 million in the same period in 2024, driven by increased clinical trial costs [9] - General and administrative expenses decreased to $3.0 million in Q1 2025 from $3.5 million in Q1 2024 [10] - Cash and cash equivalents totaled $32.7 million as of March 31, 2025, down from $47.2 million at the end of 2024 [10] Clinical Development Updates - Sirexatamab demonstrated statistically significant higher overall response rates (ORR) and longer progression-free survival (PFS) in DKK1-high and VEGF-naïve second-line CRC patients [3][6] - In the DeFianCe study, the Sirexatamab arm showed a 32% higher ORR and 3.5 months longer PFS in patients with high DKK1 levels compared to the control arm [7] - The company is advancing FL-501, a novel GDF-15 neutralizing antibody, in preclinical development, with promising preclinical data presented at the AACR 2025 Annual Meeting [6][7] Strategic Initiatives - Leap Therapeutics announced a strategic restructuring to focus on the clinical development of sirexatamab and FL-501, resulting in a workforce reduction of approximately 50% [6][14] - The company engaged a financial advisor to explore business development opportunities to further the development of sirexatamab, indicating a focus on expanding its market potential [14]

Table of Contents LEAP THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware State or other jurisdiction of incorporation or organization UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2025 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period ...

Core Insights - Leap Therapeutics, Inc. announced preclinical data for FL-501, a monoclonal antibody targeting GDF-15, at the AACR Annual Meeting, highlighting its potential in treating cancer cachexia [1][2][3] Group 1: Product Development - FL-501 is engineered for higher affinity to GDF-15 and has a longer plasma half-life compared to competing therapies [5][7] - In preclinical models, FL-501 fully restored body composition, showing effectiveness comparable or superior to clinical-stage antibodies like visugromab and ponsegromab [7] - The company plans to advance FL-501 into clinical trials in 2026 [3] Group 2: Disease Context - Cancer cachexia is a severe condition leading to significant weight loss and reduced quality of life, contributing to cancer-related mortality [3] - High levels of GDF-15 are associated with cancer cachexia symptoms such as loss of appetite and weight loss [5] Group 3: Presentation Details - The poster presentation for FL-501 will take place on April 29, 2025, at the AACR Annual Meeting, under the session category of Experimental and Molecular Therapeutics [5]

Core Viewpoint - Leap Therapeutics is hosting a virtual KOL event to discuss the potential of sirexatamab (DKN-01) in treating advanced microsatellite stable colorectal cancer, highlighting its clinical data and unmet medical needs [1][2][3] Company Overview - Leap Therapeutics, Inc. is a biotechnology company focused on developing targeted and immuno-oncology therapeutics, with its most advanced clinical candidate being sirexatamab, a humanized monoclonal antibody targeting the DKK1 protein [5] - The company is also developing FL-501, another humanized monoclonal antibody targeting GDF-15, which is currently in preclinical development [5] Event Details - The virtual KOL event will feature Dr. Zev A. Wainberg from UCLA, who will discuss the unmet needs in treating advanced MSS colorectal cancer and the potential improvements offered by sirexatamab [1][2] - The event will review positive data from Part B of the Phase 2 DeFianCe study, focusing on second-line patients with advanced MSS CRC [3] - A live Q&A session will follow the discussion, and a replay will be available on the company's investor page [3] Research and Development - Dr. Wainberg's research includes clinical trials for various gastrointestinal cancers, and he is currently focused on targeting cancer stem cells and molecular classification of gastrointestinal cancers [4] - Sirexatamab is being studied specifically for its efficacy in patients with colorectal cancer, addressing a significant unmet need in the treatment landscape [2][5]

Leap Therapeutics (NASDAQ:LPTX) Conference Call to discuss Updated Data from Part B of the DeFianCe Study March 26, 2025 8:00 AM ET Company Participants Douglas Onsi - President and CEO Cyndi Sirard - Chief Medical Officer Jason Baum - Chief Scientific Officer Good morning. Welcome to the Leap Therapeutics Conference Call to discuss Updated Data from Part B of the DeFianCe Study. At this time, all participants are on a listen-only mode. After the speakers' presentation, there will be a question-answer sessi ...

DeFianCe Study Preliminary Results - In the DKK1-high subgroup (upper quartile), sirexatamab showed a 32% higher response rate by Investigator Assessment (48% vs 16%) [11, 12, 14, 15] - In the DKK1-high subgroup (upper quartile), sirexatamab showed a 35% higher response rate by BICR (40% vs 5%) [16, 17] - In the DKK1-high subgroup (upper quartile), sirexatamab resulted in a 3.5-month longer Progression-Free Survival (PFS) with a median of 9.36 months vs 5.88 months (HR 0.46, p = 0.0248) [18, 20] - In the DKK1-high subgroup (upper quartile), sirexatamab significantly improved Overall Survival (OS) with a median not yet reached vs 9.49 months (HR 0.09, p = 0.0018) [21, 23] VEGF-Naive Population - In the no prior anti-VEGF subgroup, sirexatamab improved ORR by 22% (55% vs 33%) by Investigator Assessment (p=0.0116) [27, 28, 29, 30] - In the no prior anti-VEGF subgroup, sirexatamab doubled ORR (45% vs 22%) as assessed by BICR (p=0.0066) [31, 32] - In the no prior anti-VEGF subgroup, sirexatamab resulted in a 2.6-month longer Progression-Free Survival (PFS) with a median of 10.94 months vs 8.34 months (HR 0.59, p = 0.0386) [33, 35] Intent-to-Treat (ITT) Population - In the Intent-to-Treat (ITT) population, sirexatamab improved ORR by 10% (36% vs 26%) by Investigator Assessment (p = 0.0536) [41, 42, 43] - In the Intent-to-Treat (ITT) population, sirexatamab improved ORR by 17% (33% vs 16%) as assessed by BICR (p = 0.0023) [45, 46] Market Opportunity - DKK1 biomarker high represents approximately 25%-50% of the global second-line colorectal cancer (2L CRC) market [57, 60] - VEGF-naïve patients are expected to represent approximately 50% of the global 2L market [57, 60]

Leap Therapeutics, Inc. LPTX presented updated preliminary data on Wednesday from Part B of the DeFianCe Phase 2 trial of sirexatamab (DKN-01) in combination with bevacizumab and chemotherapy (Experimental Arm) compared to bevacizumab and chemotherapy (Control Arm).The trial enrolled patients with advanced microsatellite stable (MSS) colorectal cancer (CRC) who have received one prior systemic therapy for advanced disease.The updated analysis shared on Wednesday includes the overall response rate (ORR), an ...

Clinical Development - The lead clinical stage drug candidate is sirexatamab (DKN-01), currently studied in a clinical trial for colorectal cancer[22]. - In the DeFianCe study, the overall response rate (ORR) for 27 response-evaluable patients was 33%, with a disease control rate (DCR) of 93%[37]. - For patients with high circulating DKK1 plasma levels, the experimental arm of sirexatamab showed an ORR of 48.0% compared to 15.8% in the control arm, with a p-value of 0.0067[38]. - Median progression-free survival (PFS) for the experimental arm was 9.36 months, while the control arm had a median PFS of 5.88 months, with a hazard ratio (HR) of 0.46[38]. - The relevant DKK1-high population is estimated to be 25% of second-line colorectal cancer patients[27]. - Sirexatamab has shown additive activity with 5-fluorouracil (5-FU) chemotherapy, including in models resistant to 5-FU therapy[35]. - In patients with high circulating DKK1 plasma levels, the sirexatamab experimental arm achieved an Overall Response Rate (ORR) of 40.0% compared to 23.7% in the control arm, with a p-value of 0.0476[39]. - In patients who had not received prior anti-VEGF therapy, the sirexatamab experimental arm had an ORR of 55.1% versus 32.6% in the control arm, with a p-value of 0.0116[39]. - Across the intent-to-treat population with second-line MSS CRC, the sirexatamab experimental arm had an ORR of 36.2% compared to 25.5% in the control arm, with a p-value of 0.0536[39]. - In the DisTinGuish study, the experimental arm had a confirmed ORR of 52% by both IA and BICR, while the control arm had an ORR of 56% by IA and 42% by BICR[42]. - The preliminary median Progression-Free Survival (PFS) in the experimental arm was 9.72 months by BICR compared to 11.99 months in the control arm[42]. - The company is currently conducting clinical trials for product candidates sirexatamab and FL-501, with ongoing studies required for registration[143]. - The clinical-stage product candidate sirexatamab is currently in Phase II randomized, controlled clinical trials, with no products having gained regulatory approval yet[173]. - The company announced results from the DisTinGuish Part C study for sirexatamab, which did not generate a clear positive signal and was negative on primary progression-free survival endpoints[168]. Market Potential - The company estimates that there were approximately 45,000 first-line treated patients and 265,000 second-line treated patients for advanced colorectal cancer in the U.S. and top 7 non-U.S. markets, respectively[27]. - The market for colorectal cancer is projected to see over 2 million new cases globally by 2025, with nearly 1 million deaths[25]. - The company has redirected its development focus primarily toward the colorectal cancer program based on data from the DeFianCe study[169]. Financial Performance - Total research and development expenses were $57.2 million and $73.2 million for the years ended December 31, 2024 and 2023, respectively[125]. - For the year ended December 31, 2024, the company reported a net loss of $67.6 million and had an accumulated deficit of $467.4 million[132]. - The company has not generated any product revenues and has no commercial products[134]. - The company anticipates continued significant expenses and operating losses as it develops sirexatamab and FL-501[133]. - The company believes its cash and cash equivalents will fund planned operating expenses for at least the next 12 months[137]. - The company has incurred significant losses since its inception in 2011 and expects to continue incurring losses in the future[131]. - The company may require additional capital to fund operations, which may not be available on acceptable terms[136]. Intellectual Property and Licensing - The company has exclusive rights under 25 issued patents and 2 pending patent applications related to sirexatamab, with a base term expiring in 2030[50]. - The company plans to pursue in-licensing opportunities to strengthen its proprietary position in the field[49]. - The company entered into a license agreement with Eli Lilly, granting exclusive rights for certain intellectual property related to cancer treatment[58]. - The company expects to apply for patent term extensions for its products upon receiving FDA approval[57]. - The Lilly Agreement involves granting 65,761 shares of common stock and a royalty in the low single digits of net sales for a specific product, with no royalties paid yet[59]. - The royalty term begins on the first commercial sale of the product and lasts until the later of the tenth anniversary of the first sale, expiration of the last patent, or expiration of any data exclusivity period[60]. - The Adimab Agreement, initiated on August 10, 2020, allows Adimab to develop monoclonal antibodies, with the company having the option to acquire exclusive rights upon payment of an option fee[66]. - Under the Adimab Agreement, the company will pay milestones upon completion of clinical development and regulatory milestones, along with a royalty in the low single digits of net sales[66]. - The royalty term for products under the Adimab Agreement starts on the first commercial sale and lasts until the expiration of the last patent or the twelfth anniversary of the first sale[67]. Regulatory Environment - The FDA regulates the company's products under the FDCA and PHSA, requiring substantial time and financial resources for the approval process[81]. - The clinical trial process involves multiple steps, including preclinical studies, IND submission, and approval by an Institutional Review Board[84]. - The FDA may require the temporary or permanent discontinuation of clinical trials if they do not comply with FDA requirements or pose unacceptable risks to patients[85]. - Human clinical trials for BLA approval typically consist of three phases, with Phase 3 requiring two adequate and well-controlled trials for product approval[89][90]. - The FDA has a review goal of completing 90% of BLA applications within ten months from the initial filing date under the Prescription Drug User Fee Act (PDUFA)[100]. - A reference biologic is granted 12 years of exclusivity from the time of first licensure, and no biosimilar application can be submitted for four years from that date[108]. - The Orphan Drug Act provides incentives for developing products for rare diseases, including financial incentives and seven years of exclusivity upon FDA approval[109]. - The FDA may require a risk evaluation and mitigation strategy (REMS) to ensure that the benefits of a biologic outweigh the risks[96]. - Companies may request a Special Protocol Assessment (SPA) to agree on Phase 3 clinical trial protocols with the FDA, which can influence product approval[93]. - The FDA may refer certain applications to an advisory committee for recommendations, although it is not bound by these recommendations[101]. - The approval process can be lengthy, and the FDA may refuse to approve a BLA if regulatory criteria are not met or if additional data is required[103]. - The FDA may impose conditions on approved products, including post-approval studies and distribution restrictions, which can affect market potential[105]. Competition and Risks - The company faces significant competition from major pharmaceutical and biotechnology companies, which may have greater financial resources and expertise[75]. - The company faces substantial competition from larger competitors, including Novartis, Merck, Pfizer, and Amgen, which may hinder its ability to develop and commercialize products[174]. - The company may need to raise additional capital through various means, which could dilute existing stockholders and affect operational rights[141]. - The company may face challenges in demonstrating that product candidates provide advantages over existing therapies, impacting approval chances[151]. - Enrollment in clinical trials may be affected by competition and other factors, potentially leading to increased development costs and delays[160][162]. - The company relies on third-party contractors for regulatory compliance and clinical trial support, which poses risks if they fail to meet obligations[155]. - Changes in regulatory policies or requirements during clinical development could necessitate additional studies or amendments to trial protocols[148][152]. - Preliminary data from clinical trials may change as more data becomes available, which could materially affect the company's business outlook[161][164]. Operational Challenges - The company has not yet established a sales, marketing, or distribution infrastructure as lead candidates are still in clinical development[78]. - The company relies on third-party contract manufacturers for clinical trial material production, with ThermoFisher Scientific producing the bulk drug substance[76]. - The company does not have long-term commitments from CMOs for clinical trial material, which could delay development or commercialization[183]. - The company’s ability to generate revenues from product sales is contingent upon successful development and commercialization of its product candidates, which is subject to various risks[172]. - Compliance with current Good Manufacturing Practices (cGMP) is mandatory for all CMOs, and failure to meet these standards could result in costly remedial measures or delays in clinical trials and commercialization[187]. - The company has limited control over its CMOs' adherence to regulatory requirements, which could jeopardize the ability to develop and market product candidates if manufacturing facilities are not approved by the FDA[188]. - Any failure to supply sufficient quantities of product candidates from CMOs could delay clinical development and commercialization efforts, potentially leading to significant costs[189]. - The company is increasingly dependent on information technology systems, and any significant disruption could adversely affect business operations and lead to data breaches[191]. - The company faces substantial penalties if it fails to comply with federal and state healthcare laws, which could adversely affect its financial condition and operational results[193]. Employee Relations - The company has 52 full-time employees, including 41 in research and development[126]. - The company has not experienced a work stoppage and considers its relations with employees to be good[126]. Cybersecurity - The company maintains a comprehensive cybersecurity program integrated into its overall risk management systems[211]. - There have been no cybersecurity threats that have materially affected the company's business or financial condition as of the report date[213]. - The company has engaged third-party experts for various security implementation and maintenance activities related to its cybersecurity program[212]. Stock and Compliance - The company’s common stock has been publicly traded on the Nasdaq Capital Market under the symbol "LPTX" since January 24, 2017[220]. - The company qualifies as a "smaller reporting company," which may make its common stock less attractive to investors and could affect its ability to raise additional capital[205]. - The company does not anticipate paying cash dividends in the foreseeable future, meaning capital appreciation will be the sole source of gain for investors[208]. - The company received a letter from Nasdaq on March 12, 2025, indicating non-compliance with the Closing Bid Price Rule due to the stock price being below $1.00 for 30 consecutive business days[209]. - The company has until September 8, 2025, to regain compliance, with the possibility of an additional 180-day grace period if necessary[209]. - As of March 20, 2025, there were approximately 41 holders of record of the company's common stock[221]. - The company has never declared or paid cash dividends on its common stock and does not expect to do so in the foreseeable future[222]. - The principal office is leased in Cambridge, Massachusetts, covering approximately 7,667 square feet, with the lease extended through July 31, 2025[216].

Financial Performance - Leap Therapeutics reported a net loss of $67.6 million for the year ended December 31, 2024, a decrease from a net loss of $81.4 million in 2023, primarily due to reduced research and development expenses[12]. - Leap's net loss per share for the year ended December 31, 2024, was $1.81, compared to $3.98 for the previous year[21]. - Total stockholders' equity fell from $60,141 million in 2023 to $35,048 million in 2024, a decline of around 41.8%[23]. - Accumulated deficit widened from $(399,582) million in 2023 to $(467,371) million in 2024[23]. Research and Development - Research and development expenses for the full year 2024 were $57.2 million, down from $73.2 million in 2023, with Q4 2024 expenses at $13.1 million compared to $11.7 million in Q4 2023[13]. - The updated data from the Phase 2 DeFianCe study showed a statistically significant 32% higher overall response rate (ORR) and a 3.5-month longer progression-free survival (PFS) for patients with high DKK1 levels[6]. - For patients who had not received prior anti-VEGF therapy, the study indicated a statistically significant 22% higher ORR and a 2.6-month longer PFS[6]. - The company plans to present preclinical data for FL-501 at the 2025 American Association for Cancer Research (AACR) Annual Meeting, with clinical trials expected to begin in 2026[10]. Market Opportunity - Approximately 30,000 second-line treated colorectal cancer (CRC) patients in the US and 160,000 in the next seven largest markets represent a significant market opportunity for sirexatamab[8]. - Leap has engaged a leading financial advisor to explore business development opportunities for the advancement of sirexatamab[9]. Cash and Assets - Cash and cash equivalents totaled $47.2 million as of December 31, 2024[15]. - Cash and cash equivalents dropped from $70,643 million in 2023 to $47,249 million in 2024, representing a decrease of about 33.2%[23]. - Cash used in operating activities increased from $43,753 million in 2023 to $60,299 million in 2024, an increase of approximately 37.7%[25]. - Total assets decreased from $72,825 million in 2023 to $49,124 million in 2024, a decline of approximately 32.5%[23]. - Cash provided by financing activities rose significantly from $(30) million in 2023 to $37,184 million in 2024[25]. - Net decrease in cash and cash equivalents for the year was $23,394 million, compared to a net increase of $5,143 million in 2023[25]. - Current liabilities increased from $12,684 million in 2023 to $14,076 million in 2024, an increase of approximately 10.9%[23]. - Research and development incentive receivable slightly decreased from $771 million in 2023 to $704 million in 2024[23]. - Total current assets decreased from $71,597 million in 2023 to $48,039 million in 2024, a decline of about 32.9%[23].

Core Insights - Leap Therapeutics reported financial results for Q4 and the full year 2024, highlighting advancements in their lead product, sirexatamab, and a decrease in net loss compared to 2023 [1][9]. Product Development - The company advanced sirexatamab through Phase 2 clinical trials, showing promising data in patients with high DKK1 levels and those without prior anti-VEGF therapy, which represent significant portions of the second-line colorectal cancer (CRC) market [2][4][12]. - A registrational Phase 3 clinical trial is planned to evaluate sirexatamab in combination with bevacizumab and chemotherapy for second-line MSS CRC patients [4]. - The potential market opportunity for sirexatamab includes approximately 30,000 second-line treated CRC patients in the US and 160,000 in the next seven largest markets, with a focus on patients with high DKK1 levels and those who have not received prior anti-VEGF therapy [5]. Financial Performance - Leap Therapeutics reported a net loss of $67.6 million for the year ended December 31, 2024, a decrease from $81.4 million in 2023, primarily due to reduced research and development expenses [9][10]. - Research and development expenses for 2024 were $57.2 million, down from $73.2 million in 2023, with Q4 expenses at $13.1 million compared to $11.7 million in the same period of 2023 [10]. - General and administrative expenses decreased to $12.8 million for the full year 2024 from $13.8 million in 2023, with Q4 expenses at $3.0 million [11]. Cash Position - As of December 31, 2024, the company had cash and cash equivalents totaling $47.2 million, down from $70.6 million at the end of 2023 [11][18]. Upcoming Events - Leap Therapeutics will present preclinical data for FL-501 at the 2025 American Association for Cancer Research (AACR) Annual Meeting, with plans to begin clinical trials in 2026 [7].