BeiGene and SpringWorks Announce Presentation of Preclinical Data Combining RAF Dimer Inhibitor Lifirafenib with MEK Inhibitor Mirdametinib and Provide Update on Ongoing Phase 1b/2 Clinical Trial
Preclinical data presented at the American Association for Cancer Research 2020 Virtual Annual Meeting II
Ongoing Phase 1b/2 clinical trial on track to commence dose expansion cohorts in KRAS mutant solid tumors by the end of 2020
CAMBRIDGE, Mass. and BEIJING and STAMFORD, Conn., June 22, 2020 (GLOBE NEWSWIRE) -- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative molecularly-targeted and immuno-oncology drugs for the treatment of cancer, and SpringWorks Therapeutics, Inc. (NASDAQ: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, today announced the presentation of preclinical data and provided a program update on their ongoing Phase 1b/2 study evaluating the combination of BeiGene’s investigational RAF dimer inhibitor, lifirafenib, with SpringWorks’ investigational MEK inhibitor, mirdametinib, in patients with advanced or refractory solid tumors harboring mutations in the MAPK pathway, including those with RAS mutations.
The preclinical data were presented today in a poster at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting II by researchers from BeiGene, SpringWorks, and Memorial Sloan Kettering Cancer Center. Among the findings presented, lifirafenib and mirdametinib demonstrated potent and synergistic activity in vitro and in vivo across a panel of RAS-mutated cancer models harboring a variety of mutations using clinically relevant concentrations of the compounds. Furthermore, in KRAS Q61K and KRAS G12C xenograft models, the combination demonstrated synergy as validated by pharmacodynamic pathway inhibition and tumor regressions. These preclinical findings provided further support for the ongoing Phase 1b/2 combination study of lifirafenib and mirdametinib, which is evaluating this “vertical inhibition” strategy for treating patients whose cancers harbor RAS mutations and other MAPK pathway aberrations.
Based on the progress of the program and the clinical data observed to date, the companies reiterated their previous guidance to complete the dose escalation portion of the trial by the end of 2020 and to commence dose expansion cohorts in tumor types of interest thereafter, including KRAS-mutated non-small cell lung cancer and KRAS-mutated endometrial cancer. Initial clinical data from the trial is expected to be presented at a medical conference in 2021.
“We have been pleased with the progress of the lifirafenib and mirdametinib combination therapy trial to date, and we look forward to commencing dose expansion cohorts in the coming months,” said Ben Solomon, M.B.B.S., Ph.D., Senior Faculty Member and Medical Oncologist in the Lung and Head & Neck Service at the Peter MacCallum Cancer Centre, who is the principal investigator of the study. “There remains a significant unmet need for the nearly one-third of solid tumor patients whose cancers are driven by RAS mutations, RAF mutations, and other MAPK pathway aberrations, and this combination therapy represents a novel targeted approach for these tumors.”
More information about the ongoing trial of lifirafenib and mirdametinib may be found by searching clinical trial identifier NCT03905148 at https://clinicaltrials.gov.
Details for the AACR 2020 Virtual Meeting II presentation are as follows:
Title: RAF dimer inhibitor lifirafenib enhances the antitumor activity of MEK inhibitor mirdametinib in RAS mutant tumors
Authors: Xi Yuan, Xinwen Zhang, Rong Du, Shing-Hu Cheung, Xikun Wu, Beibei Jiang, Zhiyu Tang, Min Wei, Changyou Zhou, Lai Wang, Todd Shearer, Badreddin Edris, L. Mary Smith, Claire N. Thant, Zhan Yao, Neal Rosen, Lusong Luo
Poster #: 6415
Session: Novel Therapeutic Approaches
Date and Time: June 22, 2020; 9:00 a.m. ET
Lifirafenib was discovered in BeiGene’s research facilities in Beijing, China, and is an investigational small molecule kinase inhibitor with RAF monomer and dimer inhibition activities. Lifirafenib has shown antitumor activities in preclinical models and in cancer patients with tumors harboring BRAF V600E mutations, non-V600E BRAF mutations, non-small cell lung cancer and endometrial cancer harboring KRAS mutations. To date, lifirafenib has been dosed in more than 150 patients globally.
Mirdametinib is an investigational, selective, orally bioavailable small molecule inhibitor of MEK1 and MEK2, proteins that play key roles in the MAPK pathway. The MAPK pathway is critical for cell survival and proliferation, and overactivation of this pathway has been shown to help enable tumor growth. By blocking activity of the MAPK pathway, mirdametinib may help arrest uncontrolled cellular growth associated with many types of tumors.
Mirdametinib has been tested in several Phase 1 and Phase 2 clinical trials, and approximately 260 subjects have been exposed to treatment. SpringWorks is evaluating mirdametinib as a monotherapy for the treatment of patients with neurofibromatosis type 1-associated plexiform neurofibromas (the ReNeu trial) and is also pursuing mirdametinib in combination with other rational anti-cancer agents across a range of solid tumors.
BeiGene is a global, commercial-stage biotechnology company focused on discovering, developing, manufacturing, and commercializing innovative medicines to improve treatment outcomes and access for patients worldwide. Our 3,800+ employees in China, the United States, Australia, and Europe are committed to expediting the development of a diverse pipeline of novel therapeutics for cancer. We currently market two internally-discovered oncology products: BTK inhibitor BRUKINSA® (zanubrutinib) in the United States and China and anti-PD-1 antibody tislelizumab in China. We also market or plan to market in China additional oncology products licensed from Amgen Inc., Celgene Logistics Sàrl, a Bristol Myers Squibb (BMS) company, and EUSA Pharma. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneUSA.
About SpringWorks Therapeutics
SpringWorks is a clinical-stage biopharmaceutical company applying a precision medicine approach to acquiring, developing and commercializing life-changing medicines for underserved patient populations suffering from devastating rare diseases and cancer. SpringWorks has a differentiated portfolio of small molecule targeted oncology product candidates and is advancing two potentially registrational clinical trials in rare tumor types, as well as several other programs addressing highly prevalent, genetically defined cancers. SpringWorks’ strategic approach and operational excellence in clinical development have enabled it to rapidly advance its two lead product candidates into late-stage clinical trials while simultaneously entering into multiple shared-value partnerships with industry leaders to expand its portfolio. For more information, please visit www.springworkstx.com.
BeiGene Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the encouraging pre-clinical data for the combination of lifirafenib and mirdametinib, planned milestones for the Phase 1b/2 clinical trial and presentation of data, and the potential for the combination to be a novel targeted approach to treat solid tumor patients whose cancers are driven by RAS mutations, RAF mutations, and other MAPK pathway aberrations. Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed products and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its technology and drugs; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited operating history and BeiGene's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates; the impact of the COVID-19 pandemic on the Company’s clinical development, commercial and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.
SpringWorks Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding SpringWorks’ clinical trials and its strategy, business plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those related to SpringWorks’ financial results, the timing for completion of SpringWorks’ clinical trials of its product candidates, whether and when, if at all, SpringWorks’ product candidates will receive approval from the U.S. Food and Drug Administration, or FDA, or other foreign regulatory authorities, uncertainties and assumptions regarding the impact of the COVID-19 pandemic on SpringWorks’ business, operations, clinical trials, supply chain, strategy, goals and anticipated timelines, competition from other biopharmaceutical companies, and other risks identified in the section entitled “Risk Factors” in Item 1A of Part II of SpringWorks’ Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings with the Securities and Exchange Commission. SpringWorks cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. SpringWorks disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent SpringWorks’ views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date.
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SpringWorks Investor and Media Contact