Leap Therapeutics(LPTX)2025-03-26 11:15Clinical 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 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 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].