MEK1

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.

Treatment options for the disease include some off-label medications to support symptoms, but AstraZeneca’s Alexion unit provides the only FDA-approved medication for the underlying condition with Koselugo. Patients with neurofibromatosis type 1 have an option for treatment: AstraZeneca’s Koselugo. But it’s “a difficult drug to take,” according to SpringWorks Therapeutics CMO Jim Cassidy, M.D. That’s where his biotech is hoping to make its move, and a batch of mid-stage data seems to support the case. SpringWorks reported that its mirdametinib achieved a 52% response rate in pediatric patients with NF1 who have plexiform neurofibromas in the phase 2b ReNeu trial, according to a Thursday press release. Adults in the study achieved a 41% response rate. The therapy also led to “deep and durable responses” on key secondary endpoints, including pain and quality of life. NF1 is a rare genetic disorder caused by mutations to the NF1 gene, which encodes for a key suppressor of the MAPK pathway called neurofibromin. The disease is characterized by abnormal skin pigmentation, skeletal deformities and tumor growth, as well as neurological complications or cognitive impairment. Patients with NF1 also have a high risk of developing plexiform neurofibromas, or PN—tumors that grow along the peripheral nerve sheath and can cause disfigurement, pain and functional impairment. The disease can even be fatal in rare cases. NF1 typically grows more rapidly during childhood and is typically diagnosed in the first two decades of life. Some of the tumors can be removed surgically, but not always, leaving a need for therapeutic options. Treatments for the disease include some off-label medications to address symptoms, but AstraZeneca’s Alexion unit provides the only FDA-approved medication for the underlying condition with Koselugo. But, according to SpringWorks, there are major gaps left in care for NF1 patients: That therapy led to a 66% complete or partial response rate in a phase 2 trial, according to an investigator assessment. For a more apples-to-apples comparison, SpringWorks pointed to a Blinded Independent Central Review, which was what the biotech used in the ReNeu trial, where Koseluga scored a 44% response.   Koselugo has a sub-optimal response profile and challenging tolerability, which prevents patients from staying on it long term, SpringWorks CEO Saqib Islam said on a Thursday conference call (PDF). Since NF1 Is a long-term disease, an option that patients can stay with is important. Mirdametinib is an oral small-molecule MEK inhibitor that is designed to inhibit MEK1 and MEK2 in the MAPK pathway. This key signaling network regulates cell growth and survival and plays a role in oncology and rare diseases such as NF1 when it's genetically altered. Chief Medical Officer Jim Cassidy, M.D., Ph.D., said mirdametinib demonstrated a best-in-class response in the pediatric population and a first-in-class response among adults. The median duration of treatment in the pediatric group was 22 months, with median time to first response at 7.9 months. But more than 40% of patients had a response by four months. Twenty-eight patients in the pediatric group remain on treatment at the time of data cutoff and 85% of patients opted to continue. “The number of patients rolling into the long-term follow-up phase is indicative of the enduring clinical benefit that these patients experienced, as well as the tolerability profile, and highlights their desire to remain on mirdametinib,” Cassidy said. Despite the executive optimism, SpringWorks did not see a bounce in its share price. The company was trading down 10% Thursday morning at $19.83, compared to a previous close of $22.07.  While SpringWorks executives took a shot at Koselugo’s safety profile, mirdametinib wasn’t without its adverse events either. The main treatment-emergent adverse events reported were rash, a known side effect of the MEK inhibitor class, Cassidy noted. But rashes led to more discontinuations in the adult arm of the trial, which had 13 patients stop treatment, compared to five in the pediatric group. SpringWorks implemented a protocol amendment with supportive care after the initial cases of rash were seen, which later cut down on the number of discontinuations in the adult group. “I should point out that in isolation, we think the adult tolerability is quite good … What we did learn anecdotally in the context of this study is that with less parental discretion on decision-making, adults were more likely to discontinue therapy for less severe side effects,” Cassidy said. “We saw this in the beginning of the trial, where we initially did not have preventive measures in place to manage rash and a number of adult patients stopped treatment for rather low-grade events.” Other adverse events were fairly consistent across the two patient populations. Cassidy called the pediatric safety profile “really exceptional.” Other reported events were diarrhea, acne, vomiting and headache. There were 22 grade 3 or higher adverse events in the pediatric cohort, including four cases of increased blood creatine phosphokinase, which can indicate muscle tissue damage. SpringWorks did not report any cases of that adverse event in the adult group. There were 21 grade 3 or higher events, however, including six rashes and five cases of acne. With the topline mid-phase data in hand, SpringWorks now plans to file a new drug application with the FDA in the first half of 2024, after a first-quarter meeting with the agency. The therapy has an orphan drug designation in the U.S. and Europe, as well as fast-track designation in the U.S. Further data will be published from the ReNeu trial at a future medical meeting and in a peer-reviewed journal.   Koselugo notched $208 million in sales for AstraZeneca for 2022. Analysts were keen to hear how SpringWorks might break into that market with mirdametinib. Chief Operating Officer Badreddin Edris, Ph.D, said there are 100,000 NF1 patients in the U.S. right now, and 40,000 have NF1-PN. “This is a lifelong disease. Many patients require active treatment at some point during their treatment journey,” Edris said. Patients with NF1-PN typically are not candidates for surgical removal of their tumors, so they require systemic therapy. “What this does is it places a premium on effective systemic options that have tolerability profiles that are suitable for long-term use, especially because patients are known to progress when they stop treatment.” SpringWorks believes that the benefit-risk profile presented today will help lift mirdametinib over Koselugo. While it’s unclear exactly how many people are taking Alexion’s medicine today, Edris said that other off-label therapies are still taking up a share of the market. Edris also noted that the biotech was able to rapidly enroll the ReNeu trial despite Koselugo being on the market, which supports the claim that there is an unaddressed patient population. “The fact that [Koselugo] is on market, we do not believe is going to be a meaningful barrier to entry for mirdametinib, especially with the strength of the data that we shared today,” Edris said. “Koselugo’s very encouraging revenue run rates set a nice backdrop for us for to come in and have an agent that could really improve the treatment paradigm.”

– Confirmed objective response rate of 52% in pediatric patients and 41% in adult patients, as assessed by Blinded Independent Central Review – – Mirdametinib treatment resulted in deep and durable responses and significant improvements in key secondary patient-reported outcome measures – – Mirdametinib was generally well tolerated with low rates of Grade 3+ adverse events – – Additional data expected to be presented at medical conference and NDA submission to the U.S. FDA planned in the first half of 2024 – – Company to host conference call today at 8:30 a.m. Eastern Time – STAMFORD, Conn., Nov. 16, 2023 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, today announced positive topline results from the pivotal Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in pediatric and adult patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN). The ReNeu trial enrolled 114 patients in two cohorts (pediatric and adult) across 50 sites in the U.S. 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, 52% (29/56) of pediatric patients and 41% (24/58) of adult patients had BICR confirmed objective responses within the 24-cycle treatment period (cycle length: 28 days). An additional pediatric patient and two additional adult patients achieved confirmed objective responses after Cycle 24 in the long-term follow up phase of the trial, where patients continue to receive mirdametinib treatment. Median best percent change from baseline in target tumor volume was -42% and -41% in the pediatric and adult cohort, respectively. As of the data cut-off, the median duration of treatment was 22 months in both the pediatric and adult cohorts. Median duration of response was not reached in either cohort. Pediatric and adult patients in the ReNeu trial also 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 ReNeu 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. Twenty-five percent of pediatric patients and 16% of adult patients experienced a Grade 3 or higher treatment-related AE. 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. “Plexiform neurofibromas can grow aggressively along peripheral nerves and lead to extreme pain, disfigurement and other morbidities that have a significant impact on the lives of patients and their families,” said Saqib Islam, Chief Executive Officer of SpringWorks. “We are extremely pleased that the results of our ReNeu trial demonstrate a compelling clinical profile across measures of both safety and efficacy. Our data indicates that mirdametinib has the potential to be the best-in-class therapy for children and the first approved treatment for adults with NF1-PN and we are working with urgency to bring this differentiated medicine to patients.” The U.S. Food and Drug Administration (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, FDA 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. SpringWorks plans to submit a New Drug Application (NDA) for mirdametinib to the FDA in the first half 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 blinded independent central review. 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 3,000 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.3,4,6 Patients with NF1 can also experience additional manifestations, including neurocognitive deficits and developmental delays.4 NF1-PNs are most often diagnosed in the first two decades of life.3 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.7,8 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.9 MEK inhibitors have emerged as a validated class of treatment for NF1-PN.4 About Mirdametinib 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 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. Conference Call and Webcast Information SpringWorks will host a conference call and webcast to discuss the ReNeu topline data today, November 16, at 8:30 a.m. ET. To join the live webcast and view the corresponding slides, please click here. To access the live call by phone, please pre-register for the call here. Once registration is complete, participants will be provided with a dial-in number and conference code to access the call. A replay of the webcast will be available for a limited time following the event on the Investors and Media section of the Company’s website at https://ir.springworkstx.com. 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, visit www.springworkstx.com and follow @SpringWorksTx on Twitter and LinkedIn. 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, the potential for the results of the Phase 2b ReNeu clinical trial to support an NDA submission for mirdametinib, 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, the potential for SpringWorks to receive a priority review voucher following an FDA approval of mirdametinib, 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) our expectations regarding the potential clinical benefit of mirdametinib for patients with NF1-PN, (iii) 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, (iv) the success and timing of our collaboration partners’ ongoing and planned clinical trials, (vi) the timing of our planned regulatory submissions and interactions, including our planned NDA submission for mirdametinib in the first half of 2024, and the timing and outcome of decisions made by the FDA, the European Medicines Agency (EMA) and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; (vi) 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, (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 enter into collaborations for the development of new product candidates and our ability to realize the benefits expected from such collaborations, (x) our ability to maintain adequate patent protection and successfully enforce patent claims against third parties (xi) our ability to establish and maintain manufacturing capabilities, and our and our collaboration partners’ abilities to manufacture our products and product candidates and scale production, and (xii) 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 II of SpringWorks’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings. Contacts:Kim DiamondVice President, Communications and Investor RelationsPhone: 203-561-1646 Email: kdiamond@springworkstx.com Samantha Hilson SandlerSenior Director, Investor RelationsPhone: 203-461-5501Email: samantha.sandler@springworkstx.com 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.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.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.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.Hirbe A, Gutmann D. Neurofibromatosis type 1: a multidisciplinary approach to care. The Lancet Neurology. 2014;13(8):834-843. doi:10.1016/s1474-4422(14)70063-8.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.