Springworks Therapeutics, Inc.

March 04, 2024 -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, announced today that the Company has initiated a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for mirdametinib, an investigational MEK inhibitor, in pediatric and adult patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN). “There is tremendous potential for mirdametinib to address the substantial needs that exist for children and adults with NF1-PN, and the initiation of our rolling NDA submission brings us one step closer toward our goal of providing these patients with a best-in-class therapy that could make a significant impact on their lives,” said Saqib Islam, Chief Executive Officer of SpringWorks. “We are excited to advance the regulatory filing for our second product and look forward to working closely with the FDA on their review of our application.” The NDA submission includes data from the Phase 2b ReNeu trial, a multi-center, open-label study that opened across 50 sites in the U.S. and enrolled 114 patients across two cohorts (pediatric and adult). The primary endpoint was confirmed objective response rate (ORR), defined as ≥ 20% reduction in target tumor volume as measured by MRI and assessed by Blinded Independent Central Review (BICR). As of the data cutoff date of September 20, 2023, the BICR-confirmed objective response rate was 52% in pediatric patients and 41% in adult patients. Mirdametinib treatment showed deep and durable responses and demonstrated significant improvements in key secondary patient-reported outcome measures. Pediatric and adult patients in the ReNeu trial experienced statistically significant improvements from baseline in pain, quality of life, and physical function, as assessed across multiple patient-reported outcome tools. Mirdametinib was generally well tolerated in the trial, with the majority of adverse events (AEs) being Grade 1 or Grade 2. The most frequently reported AEs were rash, diarrhea, and vomiting in the pediatric cohort and rash, diarrhea, and nausea in the adult cohort. The FDA and the European Commission have granted Orphan Drug designation for mirdametinib for the treatment of NF1. The FDA has also granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity. In July 2023, the FDA granted mirdametinib Rare Pediatric Disease designation for the treatment of NF1, which provides eligibility for a priority review voucher upon FDA approval. SpringWorks expects to complete the NDA submission in the second quarter of 2024. About the ReNeu Trial ReNeu (NCT03962543) is an ongoing, multi-center, open-label Phase 2b trial evaluating the efficacy, safety, and tolerability of mirdametinib in patients two years of age and older with an inoperable NF1-associated PN causing significant morbidity. The study enrolled 114 patients to receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food. Mirdametinib is administered orally in a 3-week on, 1-week off dosing schedule and has a pediatric formulation (dispersible tablet) for patients who cannot swallow a pill. The primary endpoint of the ReNeu trial is confirmed objective response rate defined as ≥ 20% reduction in target tumor volume as measured by MRI and assessed by BICR. Secondary endpoints include safety and tolerability, duration of response, and changes from baseline in patient reported outcomes. About NF1-PN Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.1,2 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals, and approximately 100,000 patients living with NF1 in the United States.3,4 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.5 Patients with NF1 have an eight to 15-year mean reduction in their life expectancy compared to the general population.2 NF1 patients have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.6,7 Patients with NF1-PN can also experience additional manifestations, including neurocognitive deficits and developmental delays. NF1-PNs are most often diagnosed in the first two decades of life.9 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.10,11 Surgical removal of these tumors is challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.12 MEK inhibitors have emerged as a validated class of treatment for NF1-PN.13 Mirdametinib is a potent, oral, allosteric small molecule MEK inhibitor in development as a monotherapy treatment for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) and low-grade glioma (LGG), and as a combination therapy for the treatment of several subsets of biomarker-defined metastatic solid tumors. Mirdametinib is an investigational drug for which safety and efficacy have not been established. Mirdametinib is designed to inhibit MEK1 and MEK2, which occupy pivotal positions in the MAPK pathway. The MAPK pathway is a key signaling network that regulates cell growth and survival and that plays a central role in multiple oncology and rare disease indications when genetically altered. The U.S. Food and Drug Administration (FDA) and the European Commission granted Orphan Drug designation for mirdametinib for the treatment of NF1, and the FDA granted Fast Track designation for the treatment of patients ≥ 2 years of age with NF1-PN that are progressing or causing significant morbidity. SpringWorks is a commercial-stage biopharmaceutical company applying a precision medicine approach to developing and delivering life-changing medicines for people with severe rare diseases and cancer. OGSIVEO™ (nirogacestat), approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, is the Company’s first FDA-approved therapy. SpringWorks also has a diversified targeted therapy pipeline spanning solid tumors and hematological cancers, with programs ranging from preclinical development through advanced clinical trials. In addition to its wholly owned programs, SpringWorks has also entered into multiple collaborations with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients in need. References Yap YS, McPherson JR, Ong CK, et al. The NF1 gene revisited - from bench to bedside. Oncotarget. 2014;5(15):5873-5892. doi:10.18632/oncotarget.2194. Rasmussen S, Friedman J. NF1 Gene and Neurofibromatosis 1. Am J Epidemiol. 2000;151(1):33-40. doi:10.1093/oxfordjournals.aje.a010118. CTF: Children’s Tumor Foundation. New and Improved: The way to talk about NF. Press release. May 9, 2023. Accessed February 2, 2024. Lee: Lee TJ, et al. Incidence and prevalence of neurofibromatosis type 1 and 2: a systematic review and meta-analysis. Orphanet J Rare Dis. 2023;18(1):292. Published 2023 Sep 14. doi:10.1186/s13023-023-02911-2) 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. Prada: Prada CE, Rangwala FA, Martin LJ, et al. Pediatric plexiform neurofibromas: impact on morbidity and mortality in neurofibromatosis type 1. J Pediatr. 2012;160(3):461-467. Miller: Miller DT, et al. Health Supervision for Children With Neurofibromatosis Type 1. Pediatrics. 2019;143(5):e20190660. Ferner R. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. The Lancet Neurology. 2007;6(4):340-351. doi:10.1016/s1474-4422(07)70075-3. Prada C, Rangwala F, Martin L, et al. Pediatric Plexiform Neurofibromas: Impact on Morbidity and Mortality in Neurofibromatosis Type 1. J Pediatr. 2012;160(3):461-467. doi:10.1016/j.jpeds.2011.08.051. Gross A, Singh G, Akshintala S, et al. Association of plexiform neurofibroma volume changes and development of clinical morbidities in neurofibromatosis 1. Neuro Oncol. 2018;20(12):1643-1651. doi:10.1093/neuonc/noy067. Nguyen R, Dombi E, Widemann B, et al. Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1. Orphanet J Rare Dis. 2012;7(1):75. doi:10.1186/1750-1172-7-75. Needle M, Cnaan A, Dattilo J, et al. Prognostic signs in the surgical management of plexiform neurofibroma: The Children’s Hospital of Philadelphia experience, 1974-1994. J Pediatr. 1997;131(5):678-682. doi:10.1016/s0022-3476(97)70092-1. Ferner R. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. The Lancet Neurology. 2007;6(4):340-351. doi:10.1016/s1474-4422(07)70075-3. The content above comes from the network. if any infringement, please contact us to modify.

STAMFORD, Conn., Feb. 29, 2024 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, announced today that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for nirogacestat, an oral gamma secretase inhibitor, for the treatment of adults with desmoid tumors. If approved, nirogacestat will be the first therapy to receive marketing authorization in the European Union (EU) for the treatment of desmoid tumors. Nirogacestat previously received Orphan Drug designation from the European Commission for the treatment of soft tissue sarcoma. “The validation of our marketing authorization application is an important step towards bringing nirogacestat to patients with desmoid tumors in the European Union who currently do not have an approved therapy,” said Saqib Islam, Chief Executive Officer of SpringWorks. “We look forward to working with the EMA on this important submission.” The MAA submission is based on results from the Phase 3 DeFi trial. In DeFi, nirogacestat met the primary endpoint of improving progression-free survival (PFS), demonstrating a statistically significant improvement over placebo with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p< 0.001). Median PFS was not reached in the nirogacestat arm and was 15.1 months in the placebo arm. Confirmed objective response rate (ORR) based on blinded independent central review of Response Evaluation Criteria in Solid Tumors v1.1 was 41% with nirogacestat versus 8% with placebo (p<0.001); the complete response rate was 7% in the nirogacestat arm and 0% in the placebo arm. Nirogacestat also demonstrated early and sustained improvements in patient-reported outcomes (PROs) measured as of the cycle 10 assessment, including pain (p<0.001), desmoid tumor-specific symptoms (p<0.001), physical/role functioning (p<0.001), and overall health-related quality of life (p≤0.01). Nirogacestat exhibited a manageable safety and tolerability profile. The most common adverse events (>15%) reported in patients receiving nirogacestat were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. The DeFi trial results were published in the March 9, 2023 edition of the New England Journal of Medicine and presented during a Presidential Symposium at the European Society for Medical Oncology Congress 2022.1, 2 “Desmoid tumors can have a significant impact on patients’ lives and there is a pressing need for a new treatment for patients in Europe,” said Bernd Kasper, M.D., Ph.D., University of Heidelberg, Mannheim Cancer Center, Mannheim, Germany and Principal Investigator of the DeFi trial. “In the DeFi trial, nirogacestat demonstrated significant improvements across progression-free survival, objective response rate, and patient-reported outcomes, and had a safety pro supports long-term dosing. These results support that nirogacestat will be a practice-changing therapy if approved by the EMA.” In November 2023, the U.S. Food and Drug Administration approved OGSIVEO™ (nirogacestat) for the treatment of adults with progressing desmoid tumors who require systemic treatment. The U.S. prescribing information includes the following Warnings & Precautions: diarrhea, ovarian toxicity, hepatotoxicity, non-melanoma skin cancers, electrolyte abnormalities, and embryo-fetal toxicity. Please see below for additional Important Safety Information. About Desmoid Tumors Desmoid tumors (sometimes referred to as aggressive fibromatosis, or desmoid fibromatosis) are rare, aggressive, locally invasive tumors of the soft tissues that can be serious, debilitating, and, in rare cases when vital structures are impacted, life-threatening.3,4 Desmoid tumors are most commonly diagnosed in patients between the ages of 20 and 44 years, with a two-to-three times higher prevalence in females. 5,6 In the European Union, the incidence of desmoid tumors is estimated to be approximately 3-5 cases per million per year.7 Although they do not metastasize, desmoid tumors are associated with recurrence rates of up to 77% after surgical resection.5,8,9 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.9 About OGSIVEO™ (nirogacestat) OGSIVEO (nirogacestat) is an oral, selective, small molecule gamma secretase inhibitor approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. OGSIVEO is not approved for the treatment of any other indication in the United States, or for any indication in any other jurisdiction by any other health authority. SpringWorks is also evaluating nirogacestat as a potential treatment for patients with ovarian granulosa cell tumors and for patients with multiple myeloma as part of several B-cell maturation agent (BCMA) combination therapy regimens in collaboration with leaders in industry and academia. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Diarrhea: Diarrhea occurred in 84% of patients treated with OGSIVEO. Grade 3 events occurred in 16% of patients. Monitor patients and manage using antidiarrheal medications. Modify dose as recommended. Ovarian Toxicity: Female reproductive function and fertility may be impaired in patients treated with OGSIVEO. Impact on fertility may depend on factors like duration of therapy and state of gonadal function at time of treatment. Long-term effects on fertility have not been established. Advise patients on the potential risks for ovarian toxicity before initiating treatment. Monitor patients for changes in menstrual cycle regularity or the development of symptoms of estrogen deficiency, including hot flashes, night sweats, and vaginal dryness. Hepatotoxicity: ALT or AST elevations occurred in 30% and 33% of patients, respectively. Grade 3 ALT or AST elevations (>5 × ULN) occurred in 6% and 2.9% of patients. Monitor liver function tests regularly and modify dose as recommended. Non-Melanoma Skin Cancers: New cutaneous squamous cell carcinoma and basal cell carcinoma occurred in 2.9% and 1.4% of patients, respectively. Perform dermatologic evaluations prior to initiation of OGSIVEO and routinely during treatment. Electrolyte Abnormalities: Decreased phosphate (65%) and potassium (22%) occurred in OGSIVEO-treated patients. Phosphate <2 mg/dL occurred in 20% of patients. Grade 3 decreased potassium occurred in 1.4% of patients. Monitor phosphate and potassium levels regularly and supplement as necessary. Modify dose as recommended. Embryo-Fetal Toxicity: Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity at maternal exposures below human exposure at the recommended dose of 150 mg twice daily. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose. ADVERSE REACTIONS The most common (≥15%) adverse reactions were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. Serious adverse reactions occurring in ≥2% of patients were ovarian toxicity (4%). The most common laboratory abnormalities (≥15%) were decreased phosphate, increased urine glucose, increased urine protein, increased AST, increased ALT, and decreased potassium. DRUG INTERACTIONS CYP3A Inhibitors and Inducers: Avoid concomitant use with strong or moderate CYP3A inhibitors (including grapefruit products, Seville oranges, and starfruit) and strong or moderate CYP3A inducers. Gastric Acid Reducing Agents: Avoid concomitant use with proton pump inhibitors and H2 blockers. If concomitant use cannot be avoided, OGSIVEO can be staggered with antacids (e.g., administer OGSIVEO 2 hours before or 2 hours after antacid use). Consult the full Prescribing Information prior to and during treatment for important drug interactions. To report suspected adverse reactions, contact SpringWorks Therapeutics at 1-888-400-SWTX (1-888-400-7989) or FDA at 1-800-FDA-1088 or Please see full U.S. Prescribing Information for OGSIVEO for more information. About SpringWorks Therapeutics SpringWorks is a commercial-stage biopharmaceutical company applying a precision medicine approach to developing and delivering life-changing medicines for people with severe rare diseases and cancer. OGSIVEO™ (nirogacestat), approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, is the Company’s first FDA-approved therapy. SpringWorks also has a diversified targeted therapy pipeline spanning solid tumors and hematological cancers, with programs ranging from preclinical development through advanced clinical trials. In addition to its wholly owned programs, SpringWorks has also entered into multiple collaborations with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients in need. For more information, visit and follow @SpringWorksTx on X (formerly Twitter), LinkedIn, and YouTube. 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 and commercialization plans, our preclinical and clinical results, the market potential of OGSIVEO for adult patients with desmoid tumors, expectations regarding timing and results of the EMA’s review of the MAA for nirogacestat, including the adequacy of the data contained in the MAA to serve as the basis for marketing approval of nirogacestat for the treatment of desmoid tumors in the European Union, 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 presentation 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 presentation, including, without limitation, risks relating to: (i) our expectations regarding the potential clinical benefit of nirogacestat for patients with desmoid tumors, (ii) estimates regarding the number of adult patients who are diagnosed with desmoid tumors annually per year in Europe and the potential market for nirogacestat, (iii) the fact that topline or interim data from clinical studies may not be predictive of the final or more detailed results of such study or the results of other ongoing or future studies, (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), European Medicines Agency (EMA), and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, (v) whether FDA, EMA, or other regulatory authorities will require additional information or further studies, or may fail or refuse to approve or may delay approval of our product candidates, including nirogacestat and mirdametinib, (vi) our ability to obtain regulatory approval of any of our product candidates or maintain regulatory approvals granted for our products, (vii) our ability to maintain adequate patent protection and successfully enforce patent claims against third parties, and (viii) our ability to meet any specific milestones set forth herein. 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, 2023, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings. Contacts Kim Diamond Vice President, Communications and Investor Relations Phone: 203-561-1646 Email: kdiamond@springworkstx.com Samantha Hilson Sandler Senior Director, Investor Relations Phone: 203-461-5501 Email: samantha.sandler@springworkstx.com References 1 Gounder M, Ratan R, Alcindor T, et al. Nirogacestat, a Gamma-Secretase Inhibitor for Desmoid Tumors. N Engl J Med. 2023;388:898-912. doi:10.1056/NEJMoa2210140. 2 Kasper B, Ratan R, Alcindor T, et al. DeFi: A phase III, randomized controlled trial of nirogacestat versus placebo for progressing desmoid tumors (DT). Ann Oncol. 2022;33(suppl_7): S808-S869. 3 Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives. Pathologica. 2021;113(2):70-84. doi:10.32074/1591-951X-213. 4 Penel N, Chibon F, Salas S. Adult desmoid tumors: biology, management and ongoing trials. Curr Opin Oncol. 2017;29(4):268-274. doi:10.1097/CCO.0000000000000374. 5 Skubitz KM. Biology and treatment of aggressive fibromatosis or desmoid tumor. Mayo Clin Proc. 2017;92(6):947-964. doi:10.1016/j.mayocp.2017.02.012. 6 van Broekhoven DLM, Grünhagen DJ, den Bakker MA, van Dalen T, Verhoef C. Time trends in the incidence and treatment of extra-abdominal and abdominal aggressive fibromatosis: a population-based study. Ann Surg Oncol. 2015;22(9):2817-2823. doi:10.1245/s10434-015-4632-y. 7 Orphanet Report Series: Rare Diseases collection. Prevalence and incidence of rare diseases: bibliographic data. January 2019. . 8 Easter DW, Halasz NA. Recent trends in the management of desmoid tumors. Summary of 19 cases and review of the literature. Ann Surg. 1989;210(6):765-769. doi:10.1097/00000658-198912000-00012. 9 Gronchi A, Kasper B, et al. Desmoid Tumor Working Group. The management of desmoid tumours: a joint global consensus-based guideline approach for adult and paediatric patients. Eur J Cancer. 2020;127:96-107. doi:10.1016/j.ejca.2019.11.013.

– Reported OGSIVEO™ (nirogacestat) net product revenue of $5.4 million in first partial quarter of launch following FDA approval on November 27, 2023 – – Submitted Marketing Authorization Application to the European Medicines Agency for nirogacestat for the treatment of desmoid tumors – – Presented positive topline data from Phase 2b ReNeu trial of mirdametinib in patients with NF1-PN; on track to submit New Drug Application in first half of 2024 – – Submitted IND for SW-682 and received FDA clearance to proceed with Phase 1a trial – – Ended 2023 with $662.6 Million in Cash, Cash Equivalents and Marketable Securities – STAMFORD, Conn., Feb. 27, 2024 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, today reported financial results for the fourth quarter and full year periods ended December 31, 2023 and provided an update on recent company developments. “In 2023, OGSIVEO became the first FDA-approved therapy for adults with desmoid tumors with our approval in November and we are very pleased with the initial progress of our launch. We are also very excited by our opportunity in NF1-PN based on the positive topline data from our pivotal Phase 2b ReNeu trial, which demonstrated mirdametinib's best-in-class potential for both children and adults with these devastating tumors. In addition, we made strong progress across our broader pipeline and continued to strengthen our financial position and our intellectual property protection for our lead assets,” said Saqib Islam, Chief Executive Officer of SpringWorks. “Our focus for 2024 is to continue delivering a successful U.S. launch for OGSIVEO in desmoid tumors, to file our NDA for mirdametinib with the goal of having our second approval by 2025, to make progress towards expanding the reach of OGSIVEO into additional geographies outside of the U.S., and to unlock additional opportunities across our emerging portfolio.” Recent Business Highlights and Upcoming Milestones OGSIVEO™ (Nirogacestat) Received U.S. Food and Drug Administration (FDA) approval for OGSIVEO, an oral gamma secretase inhibitor, for the treatment of adult patients with progressing desmoid tumors who require systemic treatment on November 27, 2023.Launched OGSIVEO in the U.S. and achieved net product revenue of $5.4 million in the first partial quarter of the launch. To date, OGSIVEO has been reimbursed by payers representing over 98% of commercial lives, as well as by Medicare and Medicaid, with coverage aligned to the FDA-approved label.Highlighted the update of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) in December 2023 which recommend nirogacestat as an NCCN Category 1, Preferred treatment option for desmoid tumors.Submitted a Marketing Authorization Application (MAA) for nirogacestat for the treatment of adult patients with desmoid tumors to the European Medicines Agency (EMA) in February 2024.Presented additional patient-reported outcome data from the Phase 3 DeFi trial at the 2023 Connective Tissue Oncology Society Annual Meeting.On track to report initial data from the Phase 2 trial evaluating nirogacestat as a monotherapy in patients with recurrent ovarian granulosa cell tumors in the second half of 2024.Continuing to support several industry and academic collaborator studies evaluating nirogacestat as part of B-cell maturation antigen (BCMA) combination therapy regimens across treatment lines in patients with multiple myeloma. Mirdametinib Presented positive topline data from the pediatric and adult cohorts of the Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in NF1-associated plexiform neurofibromas (NF1-PN) in November 2023. The confirmed objective response rate was 52% in pediatric patients and 41% in adult patients, as assessed by Blinded Independent Central Review, which was the primary endpoint of the study. Mirdametinib treatment also showed deep and durable responses and demonstrated significant improvements in key secondary patient-reported outcome measures. Mirdametinib was generally well tolerated in the trial, with the majority of adverse events (AEs) being Grade 1 or Grade 2. The most frequently reported AEs were rash, diarrhea, and vomiting in the pediatric cohort and rash, diarrhea, and nausea in the adult cohort.On track to submit an New Drug Application (NDA) to the FDA for mirdametinib for the treatment of children and adults with NF1-PN in the first half of 2024.Expect to present data from the pediatric and adult cohorts of the ReNeu trial at a medical congress in the first half of 2024 and to submit the trial results for publication in a peer-reviewed journal in 2024. Emerging Pipeline On track to present additional data from the dose expansion portion of the Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors in the second half of 2024. Brimarafenib is an investigational, selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene, Ltd.Patients continue to be enrolled in the dose escalation phase of the SpringWorks-sponsored Phase 1/2a combination study of brimarafenib and mirdametinib.The FDA cleared the Investigational New Drug (IND) application submitted by MapKure 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.Dose expansion cohort is ongoing in the BeiGene-sponsored Phase 1b/2 trial evaluating mirdametinib in combination with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with NRAS mutant solid tumors.The FDA cleared the IND application for SW-682, a novel, oral, potent, and selective TEA Domain inhibitor designed to treat tumors driven by Hippo pathway mutations. SpringWorks plans to initiate a Phase 1a trial of SW-682 in Hippo mutant solid tumors in the first half of 2024. General Corporate Strengthened balance sheet with upsized public offering in December 2023; gross proceeds from the offering, before deducting underwriting discounts and commissions and offering expenses, were approximately $316.2 million.The United States Patent and Trademark Office has recently issued four new patents for OGSIVEO and one new patent for mirdametinib, extending protection for both products into 2043. The U.S. patent portfolio for OGSIVEO includes 16 Orange Book listed patents; the U.S. patent portfolio for mirdametinib includes 10 patents that are expected to be Orange Book listed. Fourth Quarter and Full Year 2023 Financial Results Revenues: OGSIVEO net product revenues were $5.4 million in the fourth quarter of 2023, the first partial quarter of the U.S. launch.Research and Development (R&D) Expenses: R&D expenses were $43.7 million and $150.5 million for the fourth quarter and full year 2023, respectively, compared to $37.9 million and $146.1 million for the comparable periods of 2022. The increase in R&D expense for the fourth quarter and year ended 2023 was primarily attributable to an increase in employee costs associated with head count growth, partially offset by a decrease in costs related to drug manufacturing, clinical trials and other research.Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $59.8 million and $197.6 million for the fourth quarter and full year 2023, respectively, compared to $40.5 million and $134.6 million for the comparable periods of 2022. The increase in SG&A expense for the fourth quarter and the full year 2023 were largely attributable to commercial readiness activities to support the U.S. launch of OGSIVEO.Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $94.3 million, or $1.44 per share, for the fourth quarter of 2023 and a net loss of $325.1 million, or $5.15 loss per share, for the year ended December 31, 2023. This compares to a net loss of $74.2 million, or $1.19 per share, for the fourth quarter of 2022 and a net loss of $277.4 million, or $5.21 per share for the year ended December 31, 2022.Cash Position: Cash, cash equivalents and marketable securities were $662.6 million as of December 31, 2023. About SpringWorks Therapeutics SpringWorks is a commercial-stage biopharmaceutical company applying a precision medicine approach to developing and delivering life-changing medicines for people with severe rare diseases and cancer. OGSIVEO™ (nirogacestat), approved in the United States for the treatment of adult patients with progressing desmoid tumors who require systemic treatment, is the Company’s first FDA-approved therapy. SpringWorks also has a diversified targeted therapy pipeline spanning solid tumors and hematological cancers, with programs ranging from preclinical development through advanced clinical trials. In addition to its wholly owned programs, SpringWorks has also entered into multiple collaborations with innovators in industry and academia to unlock the full potential for its portfolio and create more solutions for patients in need. For more information, visit www.springworkstx.com and follow @SpringWorksTx on X (formerly Twitter), LinkedIn, and YouTube. SpringWorks uses its website as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD. Such disclosures will be included on SpringWorks' website in the Investors & Media section. Accordingly, investors should monitor such portions of the SpringWorks website, in addition to following press releases, SEC filings and public conference calls and webcasts. 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 and commercialization plans, our preclinical and clinical results, the market potential of OGSIVEO for adult patients with desmoid tumors, expectations regarding timing and results of the EMA’s review of the MAA for nirogacestat, including its ongoing validation of our submission package, and the adequacy of the data contained in the MAA to serve as the basis for marketing approval of nirogacestat for the treatment of desmoid tumors in the European Union, the potential for the results of the Phase 2b ReNeu clinical trial to support an NDA submission for mirdametinib in first half of 2024, our plans to report additional data from the Phase 2b ReNeu clinical trial at an upcoming medical conference and submit for publication data from such clinical trial in a peer-reviewed medical journal in 2024, the potential for mirdametinib to become an important new treatment for patients with NF1-PN, our plans for seeking regulatory approval for and making mirdametinib available for NF1-PN patients, if approved, expectations regarding the timing and initial data from the Phase 2 trial evaluating nirogacestat in patients with recurrent ovarian granulosa cell tumors, our plans to initiate a Phase 1a trial of SW-682 in Hippo mutant solid tumors in the first half of 2024, our plans to report additional clinical data of nirogacestat in combination with BCMA-directed therapies and initiate additional planned Phase 1 collaborator studies, our expectations regarding the potential for the Phase 1b dose expansion phase of brimarafenib, our plans to present additional data for brimarafenib monotherapy in MAPK-mutant solid tumors in second half of 2024, our plans to support MapKure’s initiation of a Phase 1b trial of brimarafenib with panitumumab in CRC and pancreatic cancer patients in first quarter of 2024, expectations about whether our patents for our lead assets will adequately protect SpringWorks against competition, 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 presentation 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 presentation, including, without limitation, risks relating to: (i) the success of our commercialization efforts with respect to OGSIVEO, (ii) our limited experience as a commercial company, (iii) our ability to obtain or maintain adequate coverage and reimbursement for OGSIVEO, (iv) the success and timing of our product development activities, including the initiation and completion of our clinical trials, (v) our expectations regarding the potential clinical benefit of OGSIVEO for adult patients with desmoid tumors who require systemic treatment, (vi) the potential for OGSIVEO to become the new standard of care for adult patients with desmoid tumors, (vii) estimates regarding the number of adult patients who are diagnosed with desmoid tumors annually per year in the U.S. and the potential market for OGSIVEO, (viii) the fact that topline or interim data from clinical studies may not be predictive of the final or more detailed results of such study or the results of other ongoing or future studies, (ix) the success and timing of our collaboration partners’ ongoing and planned clinical trials, (x) the timing of our planned regulatory submissions and interactions, including the timing and outcome of decisions made by the FDA, EMA, and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, (xi) whether FDA, EMA, or other regulatory authorities will require additional information or further studies, or may fail or refuse to approve or may delay approval of our product candidates, including nirogacestat and mirdametinib, (xii) our ability to obtain regulatory approval of any of our product candidates or maintain regulatory approvals granted for our products, (xiii) our plans to research, discover and develop additional product candidates, (xiv) our ability to enter into collaborations for the development of new product candidates and our ability to realize the benefits expected from such collaborations, (xv) our ability to maintain adequate patent protection and successfully enforce patent claims against third parties, (xvi) the adequacy of our cash position to fund our operations through any time period indicated herein, (xvii) our ability to establish manufacturing capabilities, and our and our collaboration partners’ abilities to manufacture our product candidates and scale production, and (xviii) our ability to meet any specific milestones set forth herein. 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, 2023, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings. SpringWorks Therapeutics, Inc.Condensed Consolidated Statements of Operations(Unaudited) ​Year Ended December 31,(in thousands, except share and per-share data)2023 2022 2021Revenue: Product revenue, net$5,447 $— $— Total revenue 5,447 — — Operating expenses: Cost of product revenue 422 — — Research and development 150,487 146,122 101,676 Selling, general and administrative 197,551 134,552 71,792 Total operating expenses 348,460 280,674 173,468 Loss from operations (343,013) (280,674) (173,468)Interest and other income: Interest and other income, net 22,947 6,147 546 Total interest and other income 22,947 6,147 546 Equity method investment loss (5,038) (2,890) (988)Net loss$(325,104) $(277,417) $(173,910) Net loss per share, basic and diluted$(5.15) $(5.21) $(3.59)Weighted average common shares outstanding, basic and diluted 63,123,936 53,290,528 48,497,790 SpringWorks Therapeutics, Inc.Selected Balance Sheet Data(Unaudited) As of December 31, 2023 2022(in thousands) Cash, cash equivalents and marketable securities$662,588 $597,006 Working Capital (1) 422,742 548,711 Total assets 725,788 630,242 Total liabilities 99,569 72,050 Accumulated deficit (895,034) (569,930)Total stockholders’ equity 626,219 558,192 (1) We define Working Capital as current assets less current liabilities. Contacts:Kim DiamondVice President, Communications and Investor RelationsPhone: 203-561-1646Email: kdiamond@springworkstx.com Samantha Hilson SandlerSenior Director, Investor RelationsPhone: 203-461-5501Email: samantha.sandler@springworkstx.com