SpringWorks Therapeutics Announces Initiation of Phase 1/2

STAMFORD, Conn., June 16, 2021 (GLOBE NEWSWIRE) — SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing drugs for patients with severe rare diseases and cancer, today reported the initiation of a Phase 1/2 clinical trial evaluating mirdametinib, an investigational MEK inhibitor for the treatment of children, adolescents and young adults with low-grade glioma (LGG). The study is sponsored by St. Jude Children’s Research Hospital. More information about the study can be found at www.clinicaltrials.gov under the identification code NCT04923126.

Pediatric LGG may contain genetic changes that upregulate the MAPK pathway and promote tumor growth. Previous studies of therapeutic agents targeting the MAPK pathway have shown promising results in patients with childhood LGG.1 Mirdametinib is an oral, allosteric, brain-penetrating small molecule designed to inhibit MEK1 and MEK2, proteins that occupy critical positions in the MAPK. path. To date, more than 250 subjects have been exposed to mirdametinib treatment in clinical trials, with preliminary evidence of antitumor clinical activity driven by overactivated MAPK signaling.2

“Children with LGG who fail to achieve a cure after surgery may face years of increasingly aggressive chemotherapy, which can have lasting negative effects on learning, cognition, and quality of life,” says L. Mary Smith, Ph.D., SpringWorks Chief Development Officer. “It has recently been recognized that most cases of pediatric LGG have genetic changes that upregulate the MAPK pathway. Given its brain-penetrating properties, we look forward to studying mirdametinib to evaluate whether our MEK inhibitor can provide meaningful antitumor activity and clinical benefit in patients with LGG.”

This trial is being conducted under a research agreement SpringWorks has entered into with St. Jude Children’s Research Hospital, with St. Jude sponsoring the trial and SpringWorks providing partial funding, investigational drug and other non-financial support.

About the Phase 1/2 LGG Study

The open-label, multicenter Phase 1/2 study will evaluate the safety, tolerability and pharmacokinetics of mirdametinib in children, adolescents and young adults with LGG. The study plans to enroll up to 130 patients, ages 2 to 24. Patients will receive mirdametinib twice daily on a continuous schedule for up to two years.

The primary objective of the phase 1 portion of the study will be to evaluate the safety, tolerability and pharmacokinetics of mirdametinib. The phase 2 portion of the study is designed to measure the objective response rate and duration of response to mirdametinib. Patients in the phase 2 portion will be stratified into one of three treatment cohorts based on tumor status and history of MEK inhibitor exposure: Cohort 1: patients with newly diagnosed LGG; Cohort 2: Patients with progressive or recurrent LGG without previous exposure to a MEK inhibitor; Cohort 3: Patients with progressive or recurrent LGG with previous exposure to a MEK inhibitor.

About low-grade glioma

Pediatric LGG is a type of tumor that affects the brain and spinal cord. LGG is the most common childhood central nervous system (CNS) tumor and accounts for approximately 30% of all childhood CNS tumors.3 LGG can arise in several areas of the CNS, including the cerebellum, the cerebrum brainstem, hypothalamus, visual pathway, optic nerve, and spinal cord.3 Low-grade gliomas are associated with significant morbidity, including seizures and cognitive decline, and recurrent gliomas often undergo malignant transformation.4

Optimal management of LGG remains uncertain.3 While most children with LGG survive their cancer, children with progressive residual disease after surgery and children who are not amenable to surgery can often face years of increasingly aggressive cytotoxic therapies that can have lasting effects on learning, cognition and quality of life.3 There are no FDA-approved therapies for pediatric LGG and current treatments used off-label may be associated with significant acute and lifelong side effects.3 As a result, the unmet medical need remains great for these patients.

About Mirdametinib

Mirdametinib is an experimental, oral, potent, allosteric, small molecule MEK1/2 inhibitor with clinical validation and over 250 subjects exposed to date. It is designed to inhibit MEK1 and MEK2. MEK proteins occupy a critical position in the MAPK pathway, an important signaling network that regulates cell growth and survival and plays a central role in multiple indications for oncology and rare diseases. Mirdametinib is being evaluated in a Phase 2b study in pediatric and adult patients with NF1-associated plexiform neurofibromas (NF1-PN), which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath.

In addition to the monotherapy studies in NF1-PN and LGG, and given the critical role that the MAPK pathway plays in the growth and proliferation of a wide range of tumor types, SpringWorks also promotes mirdametinib in combination with other rational anticancer agents across a range of solid tumors.

About SpringWorks Therapeutics

SpringWorks is a clinical-stage biopharmaceutical company that applies a precision medicine approach to acquiring, developing and commercializing life-changing medicines for patients with serious rare diseases and cancer. SpringWorks has a differentiated, targeted oncology portfolio of small molecule product candidates and is advancing two potential registration clinical trials in rare tumor types, as well as eight programs addressing common, genetically defined cancers. SpringWorks’ strategic approach and operational excellence in clinical development has enabled it to rapidly advance its two key product candidates into late-stage clinical trials while forging multiple shared value partnerships with innovators in industry and academia to expand its portfolio and create more solutions for patients with cancer. For more information, visit www.springworkstx.com and follow @SpringWorksTx on Twitter and LinkedIn.

Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding 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 and other future circumstances. Words such as, but not limited to, “look forward to,” “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “should,” “should,” and “could” , ” and similar expressions or words, identify forward-looking statements. New risks and uncertainties may arise from time to time, and it is not possible to predict all risks and uncertainties. All forward-looking statements in this press release are based on current expectations and beliefs of management and are subject to a number of risks, uncertainties and important factors that could cause actual events or results to differ materially from those expressed or implied by any forward-looking statements in this press release, including but not limited to risks related to: (i) the success and timing of our product development activities, including the initiation and completion of S .’s clinical studies pringWorks, (ii) the fact that interim data from a clinical trial may not be predictive of the final results of such trial or the results of other ongoing or future studies, (iii) the success and timing of ongoing and planned clinical trials studies of our collaboration partners, (iv) our ability to obtain and maintain regulatory approval from one of our product candidates, (v) our plans to research, discover and develop additional product candidates, (vi) our ability to efforts to develop new product candidates, (vii) our ability to establish manufacturing capabilities, and the ability of us and our collaborative partners to manufacture our product candidates and scale production, (viii) our ability to implement specifics set forth herein achieve milestones, and (ix) uncertainties and assumptions regarding the impact of the COV ID-19 pandemic on SpringWorks operations, operations, clinical trials, supply chain, strategy, goals, and projected timelines. Except as required by applicable law, we do not intend to publicly update or revise any forward-looking statements in this document, whether as a result of new information, future events, changed circumstances or otherwise. While we believe that the expectations expressed in such forward-looking statements are reasonable, we cannot guarantee that such expectations will prove correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. For more information about the risks, uncertainties and other factors that could cause differences between SpringWorks’ expectations and actual results, please refer to the “Risk Factors” in Item 1A of Part I of SpringWorks’ Quarterly Report on Form 10-Q for the quarterly. ended March 31, 2021, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings.

SpringWorks Media/Investor Contact:
Kim Diamond
Vice President, Communications and Investor Relations
203-561-1646
kdiamond@springworkstx.com

References

1 de Blank P, Bandopadhayay P, Haas-Kogan D, Fouladi M, Fangusaro J. Management of pediatric low-grade glioma. Curr Opin Pediatr. 2019;31(1):21-27. doi:10.1097/MOP.0000000000000717.

2 Weiss BD, Wolters PL, Plotkin SR, et al. NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults with NF1-related Plexiform Neurofibromas. Journal of Clinical Oncology. 2021;JCO.20.02220. doi.org/10. 1200/JCO.20.02220.

3 Ryall S, Tabori U, Hawkins C. Pediatric low-grade glioma in the age of molecular diagnostics. Acta Neuropathy Commun. 2020;8(1):30. doi.org/10.1186/s40478-020-00902-z.

4 Schiff D. Low grade gliomas. Continuum (Minneap Minn). 2017;23(6):1564-1579. doi:10.1212/con.0000000000000537.

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