MapKure, BeiGene and SpringWorks Present Clinical Data on BGB-3245, a Selective Next-Generation B-RAF Inhibitor, in Adult Patients with Advanced or Refractory Solid Tumors at the American Association for Cancer Research Annual Meeting 2023

BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass. & SAN MATEO, Calif. & STAMFORD, Conn.--(BUSINESS WIRE)--MapKure, LLC, BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), and SpringWorks Therapeutics, Inc. (NASDAQ: SWTX), today announced that they will present updated clinical data from the Phase 1a/1b study of BGB-3245, an investigational, selective RAF dimer inhibitor, in adult patients with advanced or refractory solid tumors harboring MAPK pathway aberrations. The data are being presented today in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place in Orlando, Florida.

“The promising data we are sharing at AACR demonstrate the value of our next-generation RAF dimer inhibitor, BGB-3245, as a monotherapy in patients with MAPK pathway-altered cancers, especially its potential to address key primary and resistance gene alterations that are currently unaddressed by approved therapies,” said Lusong Luo, Ph.D., Acting CEO of MapKure and Senior Vice President, External Innovation at BeiGene. “We believe that our early clinical data supported the advancement into our selected expansion cohorts which are now underway.”

“SpringWorks is committed to developing genomically-targeted therapies for patients with cancer and our MAPK directed portfolio is a cornerstone of our efforts. In particular, we are encouraged by the promising activity BGB-3245 is showing in patients with MAPK pathway aberrations,” said Saqib Islam, CEO of SpringWorks. “We and our partners are excited by the advancement of this program and are eager to continue making strides to benefit patients in significant need of new therapeutic options.”

Oral Presentation at the 2023 AACR Annual Meeting:

A first-in-human, phase 1a/1b, open-label, dose-escalation and expansion study to investigate the safety, pharmacokinetics, and antitumor activity of the RAF dimer inhibitor BGB-3245 in patients with advanced or refractory tumors

Presenter: Alison M. Schram, M.D., Memorial Sloan Kettering Cancer Center in New York
Session Title: Mini-symposium Session CTMS02 - Targeting the KRAS Pathway in the Clinic
Abstract #: CT031
Session Date and Time: Monday, April 17, 2023, from 3:20-3:30 PM ET

This ongoing Phase 1a/1b trial (NCT04249843) is an open-label, dose escalation and expansion study of BGB-3245 in adult patients with advanced or refractory solid tumors harboring MAPK pathway alterations. Results from the Phase 1a dose-escalation and dose-finding study are being presented at AACR. This portion of the study was designed to evaluate the safety, pharmacokinetics, preliminary antitumor activity of BGB-3245, and to determine its maximum tolerated dose and/or recommended Phase 2 dose to be used in select expansion cohorts.

As of the data cut-off of September 1, 2022, 42 patients were treated across six dose levels (5-60 mg daily). Patients were heavily pre-treated, having received a median three prior lines of therapy (range 1-9), including standard of care immunotherapy and targeted therapy regimens. Results demonstrated that BGB-3245 had a manageable safety profile, with adverse event findings consistent with other MAPK pathway inhibitors. The most common treatment-related adverse events (>15%) were rash acneiform (33%), rash maculopapular (24%), and fever (17%). The 40 mg once daily dose was determined to be the maximum tolerated dose of BGB-3245. In addition, encouraging anti-tumor activity was observed in heavily pretreated patients, with an objective response rate of 18% (6 confirmed responses including one complete response in 33 efficacy evaluable patients). The disease control rate was 79% and clinical benefit rate was 42%. Objective responders include patients with tumors harboring BRAF V600E that had progressed on prior BRAF/MEK inhibitors with or without checkpoint inhibitor treatment, BRAF Class II mutation, BRAF fusion, NRAS and KRAS mutations. Median time on treatment was approximately 5 months (range: 1.9-23.6 months) and 9 patients remain on treatment. These data supported the advancement of BGB-3245 into the Phase 1b dose expansion portion of the study, which has been enrolling patients since October 2022 in defined cohorts.

“These data support the ongoing investigation of BGB-3245 in defined cohorts, including BRAF V600 tumors that have progressed after prior BRAF and/or MEK inhibitor treatment, solid tumors with BRAF class II mutations and BRAF fusions, and NRAS mutant melanoma,” said Alison M. Schram, M.D., Assistant Attending Physician at Memorial Sloan Kettering Cancer Center in New York. “These patients have very limited treatment options and I look forward to the further development of BGB-3245 as it continues to advance through the dose expansion cohorts.”

About BGB-3245

BGB-3245 is an investigational, oral, selective small molecule inhibitor of RAF monomer and dimer forms. Preclinical data demonstrate that BGB-3245 has activity in tumor models that have BRAF/MEK inhibitor-resistance mutations, suggesting BGB-3245 could provide a therapeutic option for patients who have progressed on prior BRAF and/or MEK inhibitions. In addition, BGB-3245 has shown activity in preclinical models that have BRAF class II/III mutations, fusions, and splice isoforms, for which approved BRAF inhibitors are ineffective. These mutations and fusions have been identified in several solid tumors to be drivers of cancer growth, including in melanoma, non-small cell lung cancer, colorectal cancer, thyroid cancer, and other cancers.

In addition to its development as a monotherapy in several genetically defined solid tumor types, a Phase 1/2a combination study of BGB-3245 and mirdametinib is ongoing (NCT05580770) and BGB-3245 also has the potential to be used in rational combination therapies in the future.

About MapKure

MapKure is a clinical-stage company created in 2019 to develop precision medicines for patients with life-threatening diseases, with an initial focus on cancer. By focusing on genetically defined disease drivers, MapKure is positioned to advance the development of transformative medicines to patients whose unmet medical needs are largely unaddressed. MapKure is jointly owned by BeiGene and SpringWorks and is currently developing BGB-3245 under an exclusive license from BeiGene in solid tumor patients harboring specific B-RAF driver mutations and RAF fusions, as well as in patients who have developed resistance to first-generation B-RAF inhibitors.

About BeiGene

BeiGene is a global biotechnology company that is developing and commercializing innovative and affordable oncology medicines to improve treatment outcomes and access for far more patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 9,000 colleagues spans five continents, with administrative offices in Basel, Beijing and Cambridge, Mass. To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.

About SpringWorks Therapeutics

SpringWorks is a clinical-stage biopharmaceutical company applying a precision medicine approach to acquiring, developing and commercializing life-changing medicines for patients living with severe rare diseases and cancer. SpringWorks has a differentiated targeted oncology pipeline spanning solid tumors and hematological cancers, including two late-stage clinical trials in rare tumor types as well as several 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 innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients with cancer. For more information, please visit www.springworkstx.com and follow @SpringWorksTx on Twitter and LinkedIn.

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 potential for BGB-3245 to address key primary and resistance gene alterations that are currently unaddressed by approved therapies; the future development and regulatory filing and approval of BGB-3245; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” 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 medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and the impact of the COVID-19 pandemic on BeiGene’s clinical development, regulatory, commercial, manufacturing, and other operations, as well as those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent annual report on Form 10-K, 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, relating to our business, operations, and financial conditions, including, but not limited to, current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development plans, our preclinical and clinical results, as well as relating to other future conditions. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “would,” “should” and “could,” and similar expressions or words, identify forward-looking statements. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. 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, risks relating to: (i) the success and timing of our product development activities, including the initiation and completion of SpringWorks’ clinical trials, (ii) the fact that topline or interim data from a clinical study may not be predictive of the final or more detailed results of such study, or the results of other ongoing or future studies, (iii) the success and timing of our collaboration partners’ ongoing and planned clinical trials, (iv) the timing of our planned regulatory submissions and interactions, including the timing and outcome of decisions made by the U.S. Food and Drug Administration (FDA) and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; (v) whether FDA or other regulatory authorities will require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, (vii) our ability to obtain and maintain regulatory approval of any of our product candidates, (viii) our plans to research, discover and develop additional product candidates, (ix) our ability to maintain adequate patent protection and successfully enforce patent claims against third parties, (x) our ability to enter into collaborations for the development of new product candidates, (xi) our ability to establish manufacturing capabilities, and our and our collaboration partners’ abilities to manufacture our product candidates and scale production, (xii) our ability to meet any specific milestones set forth herein, and (xiii) uncertainties and assumptions regarding the impact of the COVID-19 pandemic on SpringWorks’ business, operations, clinical trials, supply chain, strategy, goals and anticipated timelines.

Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements.

For further information regarding the risks, uncertainties and other factors that may cause differences between SpringWorks’ expectations and actual results, you should review the “Risk Factors” in Item 1A of Part I of SpringWorks’ Annual Report on Form 10-K for the year ended December 31, 2022, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings.

BeiGene Contacts:

Investors
Kevin Mannix
+1 857-302-5189
ir@beigene.com

Media
Kathleen Cuca
+1 551 222 6790
media@beigene.com

SpringWorks Contacts:

Kim Diamond
Vice President, Communications and Investor Relations
Phone: +1 203-561-1646
Email: kdiamond@springworkstx.com

Samantha Hilson Sandler
Senior Director, Investor Relations
Phone: +1 203-461-5501
Email: samantha.sandler@springworkstx.com