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 ...

company presentation LEAP THERAPEUTICS Sirexatamab (DKN-01) Clinical Development DeFianCe Study Preliminary Results March 26, 2025 Forward looking statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, clinical trials, collaborations and partnerships, future financial position, future revenues, p ...

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].

Leap to host a conference call to present updated CRC clinical data today, March 26, 2025, at 8:00 a.m. ETCAMBRIDGE, Mass., March 26, 2025 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today reported financial results for the fourth quarter and year ended December 31, 2024.Leap Highlights: Reported positive updated data from Part B of the Phase 2 DeFianCe study of sirexatamab (DKN-01) in second-line patients wi ...

Core Insights - Leap Therapeutics has presented updated data from the DeFianCe study, indicating that sirexatamab in combination with bevacizumab and chemotherapy shows statistically significant improvements in overall response rate (ORR) and progression-free survival (PFS) for colorectal cancer (CRC) patients with high DKK1 levels and those who have not received prior anti-VEGF therapy [1][2][3] Study Results - In patients with high DKK1 levels (n=44), the sirexatamab Experimental Arm demonstrated a 32% higher ORR (48.0% vs. 15.8%) and a median PFS of 9.36 months compared to 5.88 months in the Control Arm [3][4] - For patients without prior anti-VEGF therapy (n=95), the sirexatamab Experimental Arm showed a 22% higher ORR (55.1% vs. 32.6%) and a median PFS of 10.94 months compared to 8.34 months in the Control Arm [4][3] - Across the intent-to-treat population (n=188), the sirexatamab Experimental Arm had an ORR of 36.2% compared to 25.5% in the Control Arm, with median PFS still maturing [4][3] Market Opportunity - The combination therapy has a significant market opportunity, targeting approximately 30,000 second-line treated CRC patients in the US and 160,000 in the next seven largest markets, particularly among the 25-50% of patients with high DKK1 levels and the 50% who have not received prior anti-VEGF therapy [7] - There is potential to expand into first-line CRC treatment, with an estimated 45,000 patients in the US and 265,000 in the next seven largest markets [7] Future Plans - Leap Therapeutics is considering a registrational Phase 3 clinical trial to further evaluate the efficacy of sirexatamab in the identified patient populations [7][2] - The company has engaged a leading financial advisor to explore business development opportunities to advance the development of sirexatamab [7]

Group 1 - Leap Therapeutics is a precision medicine developer focusing on novel targets for managing solid tumors [1] - The company's main drug is currently undergoing multiple mid-stage clinical tests as an add-on to approved therapies [1] Group 2 - The author has a PhD in biochemistry and extensive experience analyzing clinical trials and biotech companies [1] - The mission is to educate investors on the science behind biotech businesses to aid in due diligence [1]

CAMBRIDGE, Mass., Nov. 26, 2024 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced that Douglas E. Onsi, President and Chief Executive Officer, will participate in a fireside chat at the Piper Sandler 36th Annual Healthcare Conference in New York, NY.Leap Presentation Details:Piper Sandler 36th Annual Healthcare ConferenceDate: Wednesday, December 4, 2024Time: 4:00 p.m. Eastern TimeA live webcast of ...

Exhibit 99.1 Leap Therapeutics Reports Third Quarter 2024 Financial Results Cambridge, MA – November 13, 2024 – Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today reported financial results for the third quarter ended September 30, 2024. Leap Highlights: · Completed enrollment in the expanded randomized controlled Part B of the Phase 2 DeFianCe study evaluating DKN-01, Leap's anti-DKK1 monoclonal antibody, in combination with ...