SpringWorks Therapeutics Stock

SpringWorks Therapeutics, Inc. operates as a commercial-stage biopharmaceutical company. The company is applying a precision medicine approach to developing and commercializing life-changing medicines for underserved patient populations suffering from devastating rare diseases and cancer. The company has a differentiated portfolio of small molecule targeted oncology assets, including one approved product and several clinical candidates, and are advancing programs in both rare tumor types, as well as highly prevalent, genetically defined cancers.

OGSIVEO (nirogacestat) is the company's first commercial product. OGSIVEO was approved by the United States Food and Drug Administration, or FDA, on November 27, 2023. OGSIVEO is a novel, oral, selective gamma secretase inhibitor that is the first and only FDA-approved therapy for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. Nirogacestat is also in clinical development as a monotherapy for the treatment of ovarian granulosa cell tumors, or GCT, a subtype of ovarian cancer; the company is also evaluating novel combination regimens of nirogacestat alongside B-cell maturation antigen, or BCMA, directed therapies for the treatment of multiple myeloma.

Mirdametinib is an investigational oral, small molecule MEK inhibitor that is in late-stage development for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas, or NF1-PN. On November 16, 2023, the company announced positive topline results from its potentially registrational Phase 2b ReNeu trial of mirdametinib in adult and pediatric patients with NF1-PN. The company expects these positive data to support submission of a New Drug Application, or NDA, to the FDA in the first half of 2024 for mirdametinib for the treatment of NF1-PN. Further, the company is evaluating mirdametinib for the treatment of solid tumors harboring mitogen activated protein kinase, or MAPK, pathway aberrations in both monotherapy and combination approaches.

Brimarafenib is an investigational oral, small molecule, next-generation RAF dimer inhibitor that the company is also advancing in the clinic in a distinct set of genetically defined BRAF mutated tumors via MapKure, LLC, an entity jointly owned by it and BeiGene, Ltd.

SW-682 is an investigational oral, small molecule TEA Domain, or TEAD, inhibitor that the company is evaluating in Hippo-mutant solid tumors. In the first quarter of 2024, the FDA cleared the company's investigational New Drug Application, or IND, for SW-682 for clinical evaluation, and it anticipates commencing its Phase 1a trial in the first half of 2024.

The company has additional discovery programs that represent potentially first-in-class and best-in-class product candidates designed to address tumors where no or limited treatment options exist. The company continues to invest in its R&D infrastructure in a focused manner in order to support both its drug discovery capabilities and its translational medicine activities for development programs. The company also plans to continue entering into shared-value partnerships to maximize the potential of its therapies to transform the lives of oncology patients.

Strategy

The key elements of the company's strategy are to successfully commercialize OGSIVEO in the United States, and seek regulatory approval for OGSIVEO in other jurisdictions to further serve the global desmoid tumor patient community; efficiently advance mirdametinib towards marketing approval for the treatment of adults and children with NF1-PN based upon the positive topline data from its potentially registrational Phase 2b ReNeu trial that was disclosed on November 16, 2023; expand the opportunity for nirogacestat and mirdametinib to serve patients in rare oncology indications and more prevalent, genetically defined cancers, either alone or in partnership with others; deliver new medicines to underserved patient populations using a focused and efficient approach including through the continued development of earlier stage product candidates, such as brimarafenib, SW-682, and its preclinical portfolio; and maximize the potential of its portfolio through strategic partnerships and continue to deploy its value-driven approach to discovering, acquiring and developing new medicines to further expand its pipeline.

Product and Product Candidates

The company's product portfolio consists of OGSIVEO, its first approved product, and several clinical-stage candidates under investigation for additional underserved patient populations.

OGSIVEO (nirogacestat)

OGSIVEO is a commercially available, novel, oral, selective gamma secretase inhibitor that has received FDA approval in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment.

OGSIVEO approval and launch

On November 27, 2023, the FDA approved OGSIVEO (nirogacestat) for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. The FDA previously granted Fast Track and Breakthrough Therapy designations to nirogacestat for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis; nirogacestat also received Orphan Drug Designation from the FDA for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma.

OGSIVEO is the first and only FDA-approved treatment indicated specifically for desmoid tumors. In December 2023, the NCCN Clinical Practice Guidelines in Oncology, or NCCN Guidelines, were updated to recommend nirogacestat as an NCCN Category 1, Preferred treatment option for desmoid tumors.

The company is advancing a targeted launch strategy focused on positioning OGSIVEO as the potential standard of care for adult desmoid tumor patients. To support commercialization of OGSIVEO, the company has assembled a U.S. commercial field organization of 35 territory business managers plus regional business directors.

The company is also seeking to expand the reach of OGSIVEO to additional geographies and submitted a Marketing Authorisation Application, or MAA, to the European Medicines Agency, or EMA, in February 2024. Beyond the United States and Europe, the company continues to evaluate additional territories in which to potentially commercialize OGSIVEO.

Ongoing Development

The company is also developing nirogacestat for the potential treatment of ovarian GCT and, in combination with agents that target BCMA, multiple myeloma, where significant unmet medical need exists despite currently available therapies.

Nirogacestat for the Treatment of Ovarian Granulosa Cell Tumors

The company is evaluating nirogacestat's potential as a treatment for patients with ovarian GCT. In September 2022, the company announced that the first patient had been dosed in a Phase 2 trial evaluating nirogacestat as a monotherapy in adult patients with recurrent ovarian GCT, and in May 2023, the company announced full enrollment of the trial. The company expects to report initial data from the trial in the second half of 2024.

Nirogacestat in Combination with BCMA-Targeted Agents

The company is evaluating this novel combination therapy approach through clinical collaborations with several industry partners. In June 2019, the company entered a clinical collaboration with GlaxoSmithKline, or GSK, or the GSK Collaboration Agreement, to explore the combination of nirogacestat with their BCMA-targeted ADC, belantamab mafodotin, or belamaf, in patients with relapsed or refractory multiple myeloma, or RRMM. In September 2022, the company expanded the GSK Collaboration Agreement to include the potential for continued development and commercialization of the combination of belamaf and nirogacestat in earlier lines of treatment, including in newly diagnosed MM patients.

The company has entered into other separate non-exclusive clinical collaborations with several industry partners, each of whom is developing one or more BCMA-targeted therapies. Each partner is responsible for the conduct and expenses of a clinical trial to evaluate the combination of nirogacestat with its respective BCMA agent in RRMM.

In September 2023, Regeneron initiated a Phase 1b study arm evaluating nirogacestat in combination with linvoseltamab, a bispecific antibody targeting BCMA and CD3. In July 2023, the Hellenic Society of Haematology, through a co-supported collaborative study agreement with GSK and SpringWorks, initiated a Phase 1/2 study evaluating low-dose belamaf and nirogacestat in combination with lenalidomide and dexamethasone in transplant-ineligible newly diagnosed MM patients.

In June 2023, updated clinical data from the GSK-sponsored Phase 1/2 trial of nirogacestat in combination with low-dose belamaf and initial clinical data from the Janssen Research and Development, LLC, or Janssen, -sponsored Phase 1b clinical trial evaluating nirogacestat in combination with teclistamab, a bispecific antibody targeting BCMA and CD3, were presented at the European Hematology Association 2023 Congress. The updated clinical data from the GSK-sponsored trial, as of the December 9, 2022 data cut-off date, continued to support that combining nirogacestat with a low dose of belamaf may result in comparable efficacy to a higher monotherapy belamaf dose, while substantially reducing the frequency of high-grade ocular adverse events. The initial clinical data from the Janssen-sponsored trial, as of the December 16, 2022, data cut-off date, represented the first clinical data set of nirogacestat in combination with a BCMA bispecific agent, with the results demonstrating high and deep response rates for the nirogacestat plus teclistamab combination across all dose levels assessed and an optimized safety profile with delayed administration of lower-dose nirogacestat.

Mirdametinib

The company is initially investigating mirdametinib as a monotherapy for the potential treatment of patients with NF1-PN, a rare disorder characterized by mutations in the MAPK pathway that lead to the growth of peripheral nerve sheath tumors, which cause significant pain, disfigurement and morbidity. In October 2018 and July 2019, the FDA and European Commission, respectively, granted mirdametinib Orphan Drug Designation for the treatment of NF1, and in May 2019, the FDA granted mirdametinib Fast Track Designation for the treatment of NF1-PN. In July 2023, the FDA also granted mirdametinib Rare Pediatric Disease Designation for the treatment of NF1, and as such, if approved, mirdametinib will be eligible to receive a priority review voucher. On November 16, 2023, the company announced positive topline results from its potentially registrational Phase 2b ReNeu trial.

In addition to its monotherapy program in NF1-PN, mirdametinib holds promise as part of targeted combination therapies in oncology and for the treatment of other genetically defined tumors, with multiple regimens in clinical development.

Phase 2b ReNeu trial in NF1-PN

In the fourth quarter of 2019, the company initiated the potentially registrational ReNeu clinical trial. The ReNeu trial is a Phase 2b, longitudinal, open-label clinical trial designed to evaluate the efficacy, safety and tolerability of mirdametinib in patients at least two years of age with an inoperable NF1-PN that is causing significant morbidity or major deformity. Mirdametinib was administered orally at a 2 mg/m2 BID dose with a maximum dose of 4 mg BID (without regard to food). The company plans to submit an NDA for mirdametinib to the FDA in the first half of 2024. Additional data are expected to be presented at an upcoming medical conference in the first half of 2024 and to be submitted for publication in a peer-reviewed journal.

Ongoing Development

The company's first effort is evaluating mirdametinib in combination with BeiGene's RAF dimer inhibitor, lifirafenib (BGB-283). A Phase 1b/2 clinical trial being conducted by BeiGene was initiated in May 2019, enrolling patients in the United States and Australia with advanced or refractory solid tumors harboring relevant genetic mutations in the MAPK pathway.

In February 2023, the company also dosed the first patient in a Phase 1/2a open-label, dose escalation and expansion trial evaluating mirdametinib in combination with brimarafenib (BGB-3245) in patients with advanced solid tumors harboring MAPK-activating mutations. This trial is enrolling patients in the United States and Australia.

The company is also evaluating mirdametinib for the treatment of solid tumors harboring other MAPK aberrations, in both monotherapy and combination approaches, including for the treatment of pediatric and young adult patients with low-grade gliomas, in an ongoing Phase 1/2 clinical trial being conducted by St. Jude Children's Research Hospital.

Brimarafenib (BGB-3245)

In June 2019, the company announced the formation of MapKure, which is jointly owned by it and BeiGene. BeiGene licensed to MapKure exclusive rights to brimarafenib, a novel, investigational oral, selective small molecule inhibitor of monomeric and dimeric forms of activating BRAF mutations, including V600 BRAF mutations, non-V600 BRAF mutations and RAF fusions. MapKure is advancing brimarafenib through clinical development for solid tumor patients harboring BRAF driver mutations and BRAF fusions that were observed to be sensitive to the compound in preclinical studies.

In February 2020, MapKure, BeiGene and the company announced the initiation of a Phase 1 dose-escalation and expansion clinical trial evaluating brimarafenib in adult patients with advanced or refractory solid tumors harboring specific genetic mutations that based on preclinical results are predicted to be sensitive to treatment with brimarafenib. The company presented clinical data from the ongoing Phase 1a/1b trial evaluating brimarafenib in patients with advanced or refractory solid tumors harboring MAPK pathway aberrations at the AACR Annual Meeting in April 2023. Dose expansion studies are ongoing and the company anticipates sharing updated data in the second half of 2024.

In August 2023, MapKure submitted an IND application for a combination study of brimarafenib with panitumumab, a monoclonal antibody targeting EGFR, in colorectal and pancreatic cancer patients with known MAPK pathway mutations; MapKure expects to initiate a Phase 1b trial in the first quarter of 2024.

In addition to its significant, but non-controlling equity ownership in MapKure, the company has one seat on each of MapKure's joint steering committee and its board of directors. The company is also contributing to the clinical development of brimarafenib and other operational activities through a service agreement with MapKure.

Other Pipeline Programs

The company's early-stage pipeline includes SW-682, an investigational oral, small molecule TEA Domain, or TEAD, inhibitor that it in-licensed from Katholieke Universiteit Leuven and the Flanders Institute for Biotechnology in 2021 and are evaluating in Hippo-mutant solid tumors. TEAD inhibition represents an emerging approach for addressing multiple biomarker- defined cancers characterized by aberrant Hippo pathway signaling, which is genetically altered in up to 10% of cancers. In the fourth quarter of 2023, the company filed an IND for SW-682, which was cleared by the FDA in the first quarter of 2024. The company plans to initiate a Phase 1 trial of SW-682 in Hippo mutant solid tumors in the first half of 2024. Additionally, the company is pursuing development of discovery programs that represent potentially first-in-class and best-in-class product candidates designed to address tumors where no or limited treatment options exist.

License and Collaboration Agreements

Pfizer license agreements

Nirogacestat License Agreement

In 2017, the company entered into a license agreement, or the Nirogacestat License Agreement, with Pfizer, pursuant to which it acquired exclusive (including as to Pfizer) worldwide sublicensable rights to research, develop and manufacture nirogacestat for the treatment, diagnosis and prevention of all diseases and commercialize nirogacestat for the treatment, diagnosis and prevention of all diseases other than Alzheimer's disease, breast cancer and prostate cancer. Additionally, Pfizer agreed that, for ten years, it would not conduct a clinical trial of a gamma secretase inhibitor for desmoid tumors. Pfizer retained rights to commercialize nirogacestat for the treatment of Alzheimer's disease, breast cancer and prostate cancer. The company subsequently amended the Nirogacestat License Agreement in July 2019 with regard to certain provisions relating to intellectual property.

In 2017, the company entered into a license agreement, or the Mirdametinib License Agreement, with Pfizer, collectively with the Nirogacestat License Agreement referred to as the Pfizer License Agreements, pursuant to which it acquired exclusive worldwide rights to mirdametinib. The company subsequently amended the Mirdametinib License Agreement in August 2019 with regard to certain provisions relating to intellectual property.

Mirdametinib License Agreement

In 2017, the company entered into a license agreement, or the Mirdametinib License Agreement with Pfizer pursuant to which it acquired exclusive (including as to Pfizer) worldwide sublicensable rights to research, develop, manufacture and commercialize mirdametinib for the treatment of all diseases. Additionally, Pfizer agreed, that for ten years, it will not conduct a clinical trial with a MEK inhibitor for NF1, but excluding a MEK inhibitor owned or controlled by a third party that acquires, or is acquired by, Pfizer. The company subsequently amended the Mirdametinib License Agreement in August 2019 with regard to certain provisions relating to intellectual property.

BeiGene Clinical Collaboration Agreement

In 2018, the cp,[amu entered into a clinical collaboration agreement with BeiGene, or the BeiGene Collaboration Agreement, to evaluate the safety, tolerability and preliminary efficacy of combining BeiGene's investigational RAF dimer inhibitor, lifirafenib (BGB-283), and mirdametinib, in a Phase 1b clinical trial for patients with advanced or refractory solid tumors.

GlaxoSmithKline Clinical Collaboration Agreement and Amendment

In 2019, the company entered into a clinical trial collaboration and supply agreement with GSK, or the GSK Collaboration Agreement, to evaluate nirogacestat in combination with belantamab mafodotin (belamaf), GSK's BCMA ADC, in an adaptive Phase 1b clinical trial in patients with RRMM.

In 2021, the company amended the GSK Collaboration Agreement to add additional dosing regimens to the ongoing clinical trial evaluating the combination of nirogacestat and belamaf and to collaborate on additional trials evaluating the combination with other pharmaceutical agents for relapsed and refractory MM. With this amendment, the company announced the initiation of an expanded Phase 2 cohort from the first combination dose level that evaluated 0.95 mg/kg Q3W belamaf plus nirogacestat based on encouraging preliminary data observed in the Phase 1 cohort. The expanded Phase 2 cohort is further exploring the safety and efficacy profile compared to a 2.5 mg/kg Q3W belamaf monotherapy control arm, which is the same as the FDA-approved monotherapy dose and schedule of belamaf. The company also announced the addition of two new sub-studies that will explore belamaf plus nirogacestat in combination with pomalidomide and dexamethasone and in combination with lenalidomide plus dexamethasone in patients with RRMM.

In September 2022, the company expanded the GSK Collaboration Agreement to include the potential for continued development and commercialization of the combination of belamaf and nirogacestat in earlier lines of treatment, including in newly diagnosed MM patients. Under the expanded agreement, the company continues to retain full commercial rights to nirogacestat.

Other Clinical Collaboration Agreements Related to Nirogacestat and BCMA-Directed Therapy Combination Development

In addition to the GSK Collaboration Agreement, the company has entered into several other clinical trial collaboration and supply agreements with industry partners to evaluate nirogacestat in combination with BCMA-directed therapies of various modalities, including CAR T-cell therapies, bispecific antibodies and monoclonal antibodies, in patients with RRMM.

Jazz Pharmaceuticals Asset Purchase and Exclusive License Agreement

In 2020, the company announced an asset purchase and exclusive license agreement with Jazz Pharmaceuticals Ireland Limited, or Jazz, the Jazz Agreement, pursuant to which Jazz acquired its fatty acid amide hydrolase, or FAAH, inhibitor program including PF-04457845.

Pursuant to the Jazz Agreement, Jazz is obligated to use commercially reasonable efforts to develop and seek regulatory approval for at least one product in the United States and if regulatory approval is obtained, to commercialize such product in the United States.

Pursuant to the development plan under the Jazz Agreement, Jazz initially studied PF-04457845, known as JZP150, as a treatment for post-traumatic stress disorder, or PTSD. On December 21, 2023, Jazz announced topline results from its Phase 2 trial of JZP150 in PTSD. The trial did not meet its primary or secondary endpoints.

TEAD Inhibitor Portfolio License Agreement

In May 2021, the company announced an exclusive worldwide license agreement with Katholieke Universiteit Leuven, or KU Leuven, and the Flanders Institute for Biotechnology, or VIB, pursuant to which it in-licensed a portfolio of novel small molecule inhibitors of the TEA Domain, or TEAD, family of transcription factors, designed for the potential treatment of biomarker-defined solid tumors driven by aberrant Hippo pathway signaling.

EGFR Inhibitor Portfolio License Agreement and Sponsored Research Agreement

In 2021, the company announced an exclusive worldwide license agreement with Dana-Farber Cancer Institute, or Dana-Farber, pursuant to which it in-licensed a portfolio of novel small molecule inhibitors of Epidermal Growth Factor Receptor, or EGFR, designed for the treatment of EGFR-mutant lung cancers.

Concurrent with this license agreement, the company entered a multi-year sponsored research agreement with Stanford Medicine to fund continued research and development in a laboratory at Stanford Medicine, as well as collaborating laboratories at Dana-Farber. This sponsored research agreement is intended to support lead optimization and translational biology efforts as the EGFR inhibitor portfolio advances towards development candidate nomination.

Intellectual property

Patents

The company has license agreements with Pfizer for its lead product candidates, pursuant to which it acquired exclusive worldwide rights under Pfizer patents and know-how to develop, manufacture and commercialize its lead product candidates.

The company has exclusive licenses under the Nirogacestat License Agreement to patent rights in the United States and numerous foreign jurisdictions relating to nirogacestat. The patent rights in-licensed under the Nirogacestat License Agreement include patents granted in the United States and foreign jurisdictions, including Australia, Canada, China, France, Germany, Spain, the United Kingdom and Japan. U.S. patents covering nirogacestat as a composition of matter have a statutory expiration date in 2025, U.S. patents that cover the drug substance and drug product, including polymorphic forms of nirogacestat, expire in 2039, U.S. patents that cover pharmaceutical compositions expire in 2042, and a U.S. patent that covers methods of treating desmoid tumors expires in 2043, in each case, not including patent term adjustment or any regulatory extensions, with foreign counterparts pending. Orphan drug exclusivity has been granted by the FDA and will provide seven years of marketing exclusivity in the United States until October 27, 2030.

The company has exclusive licenses under the Mirdametinib License Agreement to patent rights in the United States and numerous foreign jurisdictions relating to mirdametinib. The patent rights in-licensed under the Mirdametinib License Agreement include granted patents based on work conducted by the company and Pfizer and include U.S. patents that cover polymorphic forms of mirdametinib, including the form that is in clinical development, that expire in 2041, a U.S. patent that covers pharmaceutical compositions that expires in 2041, and U.S. patents directed to methods of treatment that expire in 2041 and 2043, in each case not including any regulatory extensions, with foreign counterparts pending.

Manufacturing

The company requires all of its contract manufacturing organizations (CMOs) to conduct manufacturing activities in compliance with current good manufacturing practice, or cGMP, requirements. The company relies on these CMOs for scale-up and process development work and to produce sufficient quantities of its product candidates for use in preclinical studies, clinical trials and commercial distribution requirements.

Customers

The company is approved to sell OGSIVEO for the treatment of desmoid tumors in adult patients who require systemic treatment in the U.S. market. The company distributes OGSIVEO principally through third party specialty drug distributors and specialty pharmacies.

Competition

OGSIVEO is the first and only FDA-approved therapy for desmoid tumors, with approval received on November 27, 2023. The company is aware that other companies are, or may be, developing products for this indication, including but not limited to, Ayala Pharmaceuticals, Inc., who announced the sale of their gamma secretase inhibitor AL102, in a Phase 3 clinical trial for the treatment of desmoid tumors to Immunome, Inc. on February 6, 2024, Bayer Corporation, Eisai Co., LTD. and Iterion Therapeutics, Inc.

The company is aware that other companies are, or may be, developing products for this indication, including but not limited to, Array BioPharma Inc. (a subsidiary of Pfizer), Chia Tai Tianqing Pharmaceutical Group Co., LTD, Infixion Bioscience, Inc., NFlection Therapeutics, Inc., Novartis International AG, Pasithea Therapeutics Corp. and Shanghai Fosun Pharmaceutical (Group) Co., Ltd.

The company is aware of efforts by others to combine a GSI and a BCMA-directed agent to treat RRMM. Celgene, a subsidiary of Bristol-Myers Squibb Company, is evaluating a BCMA-directed ADC, CC-99712, in combination with crenigacestat, a GSI licensed from Eli Lilly and Company in December 2017; this combination is in Phase 1 clinical testing. Celgene is also evaluating crenigacestat in combination with its approved autologous BCMA-directed CAR T-cell therapy, ABECMA (ide-cel), in an ongoing Phase 1/2 clinical trial.

For its biomarker-defined solid tumor portfolio, the company is aware that other companies are or may be developing products for the treatment of solid tumors with specific mutations or aberrations that are being targeted by its programs. Multiple products are in development targeting RAS mutations, RAF mutations and other MAPK aberrations, including but not limited to, those from Amgen Inc., AstraZeneca PLC, Black Diamond Therapeutics, Inc., Boehringer Ingelheim International GmbH, BridgeBio Inc., Chugai Pharmaceutical Co Ltd, Day One Biopharmaceuticals, Inc., Eli Lilly and Company, Erasca, Inc., F. Hoffmann-La Roche Ltd., Fore Biotherapeutics Inc., Hanmi Pharmaceutical Co., Ltd., Kinnate Biopharma Inc., Merck & Co., Inc., Mirati Therapeutics, Inc., Moderna Inc., Novartis International AG, Pfizer and Revolution Medicines, Inc.

The company is aware of other TEAD palmitoylation inhibitors in early-stage development, including but not limited to, product candidates from Ikena Oncology, Inc., Inventiva S.A., Genentech, Inc. and Vivace Therapeutics, Inc.

Research and Development Expenses

The company's research and development expense included $150.5 million for the year ended December 31, 2023.

History

SpringWorks Therapeutics, Inc. was founded in 2017. The company was incorporated in Delaware in 2019.