Leap Therapeutics, Inc.

After previous rejections, Astellas reached a milestone to celebrate over the weekend when its new stomach cancer treatment, Vyloy (zolbetuximab), received its first approval from the U.S. Food and Drug Administration (FDA). On Friday, the FDA officially approved Vyloy as a first-line treatment for ClDN18.2-positive adult patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) negative gastric or gastroesophageal junction adenocarcinoma. This approval marks Vyloy as the first anti-ClDN18.2 (known as Claudin-18.2) drug approved in the United States, a transmembrane protein that has become a high-profile target in oncology. It has attracted the attention of several companies, including AstraZeneca, Leap Therapeutics, Legend and Moderna. The FDA approval specifically covers Vyloy in combination with fluoropyrimidine and platinum-containing chemotherapy agents. To ensure patient availability, the FDA has approved both Ventana Medical System and Roche's CLDN18.2-positive companion diagnostic test. In clinical studies, Vyloy has demonstrated significant efficacy. In the SPOTLIGHT study, which included 565 patients, the median progression-free survival (PFS) of patients in the Vyloy combined chemotherapy group was 10.6 months, which was significantly better than 8.7 months in the placebo combined chemotherapy group. At the same time, the median overall survival (OS) of patients in the Vyloy group was 18.2 months, which was also better than 15.5 months in the control group. Another GLOW study of 507 patients showed that Vyloy helped patients achieve a median PFS of 8.2 months, compared to 6.8 months in the placebo/chemotherapy group, and a median OS of 14.4 months and 12.2 months, respectively. It's worth noting that Vyloy's path to approval was not smooth. Despite being granted a priority review label by the FDA in July 2023, after receiving a full response letter in January, the FDA rejected the application for the drug due to unresolved deficiencies identified during pre-licensing inspections at third-party manufacturing facilities. However, Astellas responded quickly, announcing in late May that the FDA had accepted its resubmitted application. The approval of Vyloy is significant for Astellas. The company acquired its interest in Vyloy in 2016 when it acquired Ganymed Pharmaceuticals for $1.4 billion. Despite setbacks in the U.S. regulatory process, Vyloy has received several approvals overseas, including a successful listing in Japan. In addition, Vyloy has received regulatory approvals in Europe and the United Kingdom. While Astellas currently has a leading position in the anti-ClDN18.2 field, several other companies are also actively advancing clinical trials of related drug candidates. For example, Astrazeneca has invested tens of millions of dollars to acquire global rights to an antibody-drug conjugate that targets CLDN18.2. At the same time, while Merck has adjusted its business in this area, other companies such as Kellen are still showing positive research results and potential.

The FDA on Friday approved Astellas’ treatment for a type of gastric cancer, marketed as Vyloy (zolbetuximab). The approval came three weeks ahead of its scheduled PDUFA date of Nov. 9. Vyloy targets a protein called Claudin18.2 that is expressed on the surface of some gastric cancer cells. The drug is now approved in combination with chemotherapy for the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma. According to the company, Claudin18.2 is expressed by 38% of patients with advanced gastric cancer. The treatment previously won approval in Japan in March based on data from two Phase 3 clinical trials, with Astellas saying at the time ​​that it’s the first of its class to receive approval worldwide. The drug was also authorized in Europe in September and approved by the UK in August. Data from the Phase 3 SPOTLIGHT and GLOW trials showed statistically significant improvements in progression-free survival and overall survival compared to standard of care chemotherapy. But Vyloy had faced hurdles in the US, including a CRL in January a week before its original decision date, after the FDA found “unresolved deficiencies” at a third-party manufacturer. The FDA gave the drug priority review back in July 2023. Astellas did not immediately respond to a request for comment on the approval, pricing and launch details. Other companies are also in the Claudin18.2 space, though further behind: Leap Therapeutics bought out Flame Biosciences last year with a focus on an antibody called FL-301 and a preclinical anti-Claudin18.2/CD137 bispecific. Also in 2023 , AstraZeneca licensed the antibody-drug conjugate CMG901, which is in a Phase 1 trial in China for Claudin18.2-positive solid tumors, including gastric cancer.

CAMBRIDGE, Mass., Sept. 30, 2024 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced that enrollment of 188 patients has been completed in the randomized controlled Part B of the DeFianCe study evaluating DKN-01, Leap's anti-Dickkopf-1 (DKK1) antibody, in combination with standard of care bevacizumab and chemotherapy as a second-line treatment for patients with advanced colorectal cancer (CRC). "The completion of enrollment in Part B of the DeFianCe study marks a significant achievement and highlights the enthusiasm in the potential of DKN-01 from both patients and healthcare providers," said Cynthia Sirard, M.D., Chief Medical Officer of Leap. "The encouraging data from Part A of the study which showed clinically meaningful response rates and durable tumor reductions, as well as a favorable safety profile in advanced CRC patients, provides a strong foundation to the expanded Part B of the study. We look forward to sharing initial data from Part B, including the subpopulation of patients with left-sided CRC, in mid 2025." The DeFianCe study (NCT05480306) is a Phase 2, open-label, global study of DKN-01 in combination with standard of care bevacizumab and chemotherapy in patients with advanced CRC who have received one prior systemic therapy for advanced disease. Part B of the study expanded from a 130 to a 188-patient randomized controlled trial, with the primary endpoint being progression free survival (PFS). An additional primary endpoint will measure PFS in the subpopulation of patients with left-sided CRC. Secondary objectives include objective response rate, duration of response, and overall survival. About Leap Therapeutics Leap Therapeutics (Nasdaq: LPTX) is focused on developing targeted and immuno-oncology therapeutics. Leap's most advanced clinical candidate, DKN-01, is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein. DKN-01 is being developed in patients with esophagogastric, gynecologic, and colorectal cancers. For more information about Leap Therapeutics, visit or view our public filings with the SEC that are available via EDGAR at or via . 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 anticipated timing of the release of clinical data, and any outcomes of such trials; the interpretation or signficiance of, or any conclusions or suggestions that can or should be drawn from, the results of, and the clinical data generated from, any of our clinical trials; the potential safety, efficacy, and regulatory and clinical progress of Leap's product candidates; our future preclinical and clinical development plans in connection with our programs; the ability to enter into a strategic partnership for DKN-01 or any of Leap's other programs; 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) Leap's ability to successfully execute its clinical trials and the timing of enrollment in and cost of such clinical trials; (ii) the results of Leap's clinical trials and pre-clinical studies, including that subsequent or final results from Leap's clinical trials or pre-clinical studies may supersede, qualify, limit, or change the interpretation or significance of, preliminary or earlier results of Leap's clinical trials or pre-clinical studies; (iii) Leap's ability to successfully enter into new strategic partnerships for DKN-01 or any of its other programs; (iv) whether any Leap products will receive approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies; (v) exposure to inflation, currency rate and interest rate fluctuations, as well as fluctuations in the market price of Leap's traded securities; and (vi) that the initiation, conduct, and completion of clinical trials, laboratory operations, manufacturing campaigns, and other studies may be delayed, adversely affected, or impacted by global conflict or supply chain related issues. 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 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] SOURCE Leap Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED