Gonadal Tissue Neoplasms

– Achieved $40.2 million in OGSIVEO® (nirogacestat) net product revenue in the second quarter – – Completed submission of NDA to the FDA for mirdametinib for the treatment of children and adults with NF1-PN – – Presented Phase 2b ReNeu trial results and additional analyses from Phase 3 DeFi trial at the 2024 ASCO Annual Meeting – – Initiated Phase 1a trial of SW-682 in patients with Hippo mutant solid tumors – STAMFORD, Conn., Aug. 07, 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 second quarter of 2024 and provided an update on recent company developments. "We are very pleased with the continued strong momentum of our U.S. launch of OGSIVEO for adults with desmoid tumors. In the second quarter, we also completed the submission of our NDA for mirdametinib in NF1-PN, which positions us to potentially have our second medicine available for patients in 2025," said Saqib Islam, Chief Executive Officer of SpringWorks. "Our focus for the second half of 2024 will be to drive broader adoption of OGSIVEO, to advance our commercial preparations for the launch of mirdametinib for children and adults with NF1-PN, to continue advancing OGSIVEO and mirdametinib through the European regulatory process, and to progress our emerging portfolio for patient populations with high unmet needs." Recent Business Highlights and Upcoming Milestones OGSIVEO® (Nirogacestat) Strong commercial execution of the OGSIVEO launch, with net product revenue of $40.2 million in the second quarter of 2024.In May 2024, SpringWorks introduced OGSIVEO 150 mg and 100 mg tablets in blister packaging, which was developed to enhance patient convenience with OGSIVEO.A Marketing Authorization Application (MAA) for nirogacestat for the treatment of adult patients with desmoid tumors is under review with the European Medicines Agency (EMA).Additional data from the Phase 3 DeFi trial of nirogacestat in adults with desmoid tumors highlighting consistent safety and efficacy across subgroups of high-risk patient populations and updated ovarian toxicity resolution data supporting the transience of ovarian toxicity were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.SpringWorks expects to present long-term follow-up data from the Phase 3 DeFi trial at a medical conference in the second half of 2024.SpringWorks expects 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.SpringWorks is 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 SpringWorks completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for mirdametinib for the treatment of children and adults with NF1-PN.The Company expects to complete the submission of an MAA for mirdametinib for the treatment of children and adults with NF1-PN in the European Union in the second half of 2024.Data from the pediatric and adult cohorts of the Phase 2b ReNeu trial were presented in an oral presentation at the 2024 ASCO Annual Meeting and were also featured at the 2024 Global NF Conference and at the International Symposium on Pediatric Neuro-Oncology (ISPNO) 2024 meeting. Results showed robust objective response rates confirmed by blinded independent central review, deep responses, significant reductions in pain, improvement in other quality of life measures, and a manageable and tolerable safety profile were achieved across both the pediatric and adult cohorts. SpringWorks expects to publish the ReNeu trial results in a peer-reviewed journal in the second half of 2024.A poster evaluating the dispersible tablet of mirdametinib in children with NF1-PN in the ReNeu trial was presented at the ISPNO 2024 meeting. Patients and caregivers reported high acceptability scores for ease of swallowing and willingness to take the dispersible tablet formulation, indicating that this formulation provides an acceptable option for children or adults with swallowing difficulties.Initial data from the Phase 1/2 trial evaluating mirdametinib in patients with pediatric low-grade gliomas (pLGG) were presented at the ISPNO 2024 meeting. Results from 23 patients enrolled in the Phase 1 portion of the study suggested that mirdametinib, which has high blood brain barrier penetration, has encouraging clinical activity in patients with recurrent/progressive pLGG across a variety of MAPK pathway aberrations. The Phase 2 portion of the study is ongoing and recruiting patients. Emerging Pipeline A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion of the study is expected to be presented in the first half of 2025. 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 several combination therapy oncology programs: a Phase 1/2a study of brimarafenib and mirdametinib in MAPK mutant solid tumors, a Phase 1b trial of brimarafenib and Amgen’s EGFR inhibitor, panitumumab, in colorectal and pancreatic cancer patients with known MAPK pathway mutations, and a Phase 1b trial of mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with NRAS mutant solid tumors.SpringWorks initiated a Phase 1a trial of SW-682, an investigational novel, oral, potent, and selective pan-TEAD inhibitor, in Hippo-mutant solid tumors in the second quarter of 2024. General Corporate In July, SpringWorks appointed Martin Mackay, Ph.D. to the Company’s Board of Directors. Dr. Mackay is a highly accomplished R&D executive with more than 30 years of pharmaceutical and biotech R&D experience, including leadership roles at Pfizer, AstraZeneca and Alexion. Second Quarter 2024 Financial Results Product Revenue: OGSIVEO net product revenue was $40.2 million in the second quarter of 2024.Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $57.8 million for the second quarter of 2024, compared to $47.0 million for the comparable period of 2023. The increase in SG&A expense was primarily attributable to commercial activities supporting the U.S. launch of OGSIVEO, as well as commercial readiness activities to support the U.S. launch of mirdametinib, if approved.Research and Development (R&D) Expenses: R&D expenses were $44.4 million for the second quarter of 2024, compared to $35.9 million for the comparable period of 2023. The increase in R&D expenses was primarily attributable to an increase in costs related to drug manufacturing, clinical trials, other research, consulting and professional services, and an increase in employee costs associated with headcount growth.Net Loss Attributable to Common Stockholders: SpringWorks reported a net loss of $39.9 million, or $0.54 per share, for the second quarter of 2024. This compares to a net loss of $77.9 million, or $1.25 per share, for the comparable period of 2023.Cash, Cash Equivalents, and Marketable Securities: Cash, cash equivalents and marketable securities were $521.9 million as of June 30, 2024. Conference Call Information SpringWorks will host a conference call and webcast today, Wednesday, August 7, at 8:30 a.m. ET to review its second quarter 2024 financial results and discuss recent business updates. 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 by clicking 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 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 the adequacy of the data contained in the nirogacestat 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 approval of the mirdametinib NDA or an MAA submission for mirdametinib in the second 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, our plans to present additional data from the Phase 3 DeFi trial of nirogacestat at upcoming conferences, 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 expectations and the timing of the Phase 1a trial of SW-682, 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 and the timing of the Phase 1b dose expansion phase of brimarafenib, our expectations regarding the timing of enrollment in our combination therapy oncology programs, 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 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 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 II of SpringWorks’ Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, 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) ​Three Months Ended June 30, Six Months Ended June 30,(in thousands, except share and per-share data) 2024 2023 2024 2023 Revenue: Product revenue, net$40,186 $— $61,192 $— Other revenue (1) 19,547 — 19,547 — Total revenue 59,733 — 80,739 — Operating costs and expenses: Cost of product revenue 2,453 — 3,655 — Selling, general and administrative 57,839 46,994 117,952 91,169 Research and development 44,362 35,858 97,984 69,382 Total operating costs and expenses 104,654 82,852 219,591 160,551 ​ Loss from operations (44,921) (82,852) (138,852) (160,551)Interest and other income: Interest and other income, net 6,778 5,828 14,349 11,385 Total interest and other income 6,778 5,828 14,349 11,385 Equity method investment loss (1,776) (901) (2,801) (2,179)Net loss$(39,919) $(77,925) $(127,304) $(151,345)​ Net loss per share, basic and diluted$(0.54) $(1.25) $(1.72) $(2.43)Weighted average common shares outstanding, basic and diluted 74,121,014 62,464,081 73,944,809 62,360,651 (1) Related to recognition of all previously deferred revenue associated with the GSK License Agreement following notice of termination of the agreement received from GSK, as announced in June 2024. SpringWorks Therapeutics, Inc.Selected Balance Sheet Data(Unaudited) June 30, 2024 December 31, 2023(in thousands) Cash, cash equivalents and marketable securities$521,933 $662,588 Working Capital (1) 376,824 422,742 Total assets 617,331 725,788 Total liabilities 60,601 99,569 Accumulated deficit (1,022,338) (895,034)Total stockholders’ equity 556,730 626,219 (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

– Results from pivotal Phase 2b ReNeu trialof mirdametinib in patients with NF1-PN to be presented in an oral presentation – – Additional data and analyses from Phase 3 DeFi trial of OGSIVEO® (nirogacestat) highlighting consistent safety and efficacy across subgroups of adults with desmoid tumors also being presented in oral and poster sessions – STAMFORD, Conn., May 23, 2024 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, today announced that four abstracts from the company's portfolio will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting being held May 31 to June 4, 2024. Data from the pivotal Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in adults and children with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) will be presented in an oral presentation. ReNeu is the largest multicenter trial conducted to date in patients with NF1-PN, a condition in which tumors can grow aggressively along peripheral nerves and lead to pain, disfigurement and other morbidities. In the ReNeu trial, mirdametinib treatment demonstrated deep and sustained tumor volume reductions, and improvement in pain and health-related quality of life across both the adult and pediatric cohorts. In addition, three new data sets from the pivotal Phase 3 DeFi trial of nirogacestat in adults with desmoid tumors will be presented at ASCO. Monitoring ovarian function in oncology studies and the onset and resolution of ovarian toxicity for desmoid tumor patients treated with nirogacestat in the DeFi trial will be discussed in an oral presentation. Investigators will also present two posters that include post hoc analyses from the DeFi trial in high-risk patient populations, which reinforce the efficacy and safety of nirogacestat in adults with desmoid tumors across various clinical characteristics. “We are very pleased to present important data at this year’s ASCO annual meeting, including positive results from our pivotal Phase 2b ReNeu trial of mirdametinib in NF1-PN, which showed significant objective response rates confirmed by blinded independent central review, deep responses, as well as a manageable and tolerable safety pro both adult and pediatric patients. These data are the foundation of our NDA, which we are on track to submit to the FDA by the end of the second quarter, and we believe provide compelling evidence of differentiation and potentially transformative benefit for patients with this devastating disease,” said Jim Cassidy, M.D., Ph.D., Chief Medical Officer of SpringWorks. “In addition, new data and analyses from our Phase 3 DeFi trial further reinforce the robust efficacy and manageable safety pro OGSIVEO across subgroups of adults with desmoid tumors who require systemic treatment.” Rapid Oral Presentations at the 2024 ASCO Annual Meeting ReNeu: A pivotal phase 2b trial of mirdametinib in children and adults with neurofibromatosis type 1 (NF1)-associated symptomatic inoperable plexiform neurofibroma (PN) Abstract #: 3016 Date and Time: June 3, 8:00 - 9:30 a.m. CDT (9:00 – 10:30 a.m. EDT) As previously reported, results from the pivotal Phase 2b ReNeu trial (NCT03962543) demonstrated a statistically significant confirmed objective response rate (ORR), the primary endpoint of the study, as well as deep and sustained reduction in tumor volume and significant improvement in key secondary patient-reported outcome measures in both adults and children with NF1-PN. The data being presented at ASCO include: As of the data cutoff of September 20, 2023, mirdametinib treatment resulted in a confirmed ORR of 41% (24/58; P<0.001) in adults and 52% (29/56; P<0.001) in children, as assessed by blinded independent central review (BICR). Two additional adult patients and one additional pediatric patient had a confirmed partial response in the long-term follow-up phase. Tumor volume reductions were deep and durable over the course of the study. Median (range) best change in tumor volume from baseline was -41% (-90% to 13%) in adults and -42% (-91% to 48%) in children. Among study participants with a confirmed objective response on mirdametinib, 62% of adults and 52% of children achieved a >50% reduction in tumor volume. The median treatment duration for both adults and children was 22 months; the median (range) time to onset of response was 7.8 months (4 to 19 months) in adult patients and 7.9 months (4 to 19 months) in pediatric patients; the median duration of response was not reached in either group. Both adult and pediatric patients experienced improvement in patient-reported pain and patient-reported (adult) or patient- or parent proxy-reported (children) health-related quality of life (HRQoL) at the pre-specified Cycle 13 assessment. Least square (LS) mean change from baseline at Cycle 13 in worst tumor pain (assessed by Numeric Rating Scale-11) was -1.3 (P<0.001) in adults and -0.8 (P=0.003) in children. LS mean change from baseline at Cycle 13 in HRQoL was 3.9 in adults (P=0.018) and 4.0 (P=0.096) as self-reported in children; parent-proxy reported LS mean change in HRQoL in children was 5.6 (P=0.005). Mirdametinib was generally well tolerated in the ReNeu trial, with most adverse events (AEs) being Grade 1 or 2. Among all study participants, 21% of adults and 9% of children discontinued the study due to treatment-related adverse events (TRAEs), and dose reductions due to TRAEs were 17% in adults and 12% in children. The most frequently reported TRAEs affecting >20% of adult participants were dermatitis acneiform, diarrhea, nausea, vomiting, and fatigue. The most frequently reported TRAEs affecting ≥20% of pediatric participants were dermatitis acneiform, diarrhea, paronychia (infection of the tissue adjacent to a fingernail or toenail), nausea, decrease in ejection fraction (asymptomatic), and increase in blood creatinine phosphokinase (asymptomatic). “ReNeu is the largest multicenter NF1-PN trial conducted to date and prospectively used blinded independent central review to confirm target tumor response in NF1-PN patients,” said Christopher L. Moertel, M.D., Medical Director of the Pediatric Neuro-Oncology and Neurofibromatosis Program and Kenneth and Betty Jayne Dahlberg Professor of Pediatrics at the University of Minnesota School of Medicine and lead investigator of the ReNeu trial. “The potentially unprecedented depth of response and significant reduction in pain and other quality of life measures across the pediatric and adult cohorts in the ReNeu study, coupled with the manageable safety profile, support the potential for mirdametinib to become an important and much needed treatment for patients with NF1-PN, particularly adults who currently do not have an approved treatment option.” Monitoring ovarian function in oncology trials: Results and insights from the DeFi phase 3 trial of nirogacestat in desmoid tumor Abstract #: 11520 Date and Time: May 31, 2:45 - 4:15 p.m. CDT (3:45 – 5:15 p.m. EDT) Results and insights from the DeFi trial (NCT03785964) on monitoring ovarian function in oncology studies will be presented at ASCO. In the DeFi trial, ovarian toxicity (OT) was reported in 75% (27 of 36) of females of reproductive potential (FORP) receiving nirogacestat and 0% (0 of 37) of FORP patients receiving placebo. In a post hoc analysis, resolution of OT was reported by investigators in 78% (21 of 27) of FORP patients, assessed by reproductive hormone values (FSH, LH, AMH, progesterone and estradiol) or perimenopausal symptoms (e.g., menstrual irregularity) or both. Investigators reported OT resolution among all patients (11/11) who were off treatment for any reason, with a median time to resolution of 76 days. Among patients who remained on nirogacestat, 71% (10/14) of patients experienced resolution of OT according to investigators, with a median time to resolution of 171 days. “Historically, ovarian toxicity has rarely been systematically assessed in cancer clinical trials. And when collected, data have not always been gathered with the goal of counseling future patients clearly in mind. The DeFi trial developed one of the most comprehensive assessments of ovarian function in an oncology clinical trial to date. This timely and important ASCO presentation will review best practices for evaluating a drug’s effect on ovarian function for future cancer trials, using the DeFi trial as an example,” said Elizabeth Loggers, M.D., Ph.D., Associate Professor, Clinical Research Division, sarcoma expert and Medical Director, Supportive and Palliative Care, Fred Hutchinson Cancer Center, and Associate Clinical Professor of Medicine, University of Washington. “In this case, our ability to confirm resolution of ovarian toxicity in most DeFi participants, including all who discontinued nirogacestat for any reason, is possible because DeFi observed ASCO’s recommendations to assess ovarian function through both clinical measures and biomarkers, even beyond the end of a trial, if necessary, to better characterize the temporality and nature of resolution.” Poster Presentations at the 2024 ASCO Annual Meeting Efficacy of nirogacestat in patients with poor prognostic factors for desmoid tumors: Analyses from the randomized phase 3 DeFi trial Abstract #: 11556 Date and Time: June 1, 1:30 - 4:30 p.m. CDT (2:30 – 5:30 p.m. EDT) A post hoc analysis of the DeFi trial was conducted to assess the effect of nirogacestat in subgroups of patients with desmoid tumors who have risk factors associated with poor prognosis (i.e., larger tumor size, younger age, CTNNB1 gene mutation, and presence of pain at baseline). Nirogacestat demonstrated consistent improvements in progression-free survival (PFS) and ORR versus placebo in patients with these poor prognostic factors. These results were consistent with the overall DeFi patient population and suggest that nirogacestat can provide clinically meaningful benefit in patients with characteristics that have been historically associated with poor prognosis. Efficacy and safety of nirogacestat in patients with desmoid tumor and adenomatous polyposis coli (APC) mutation: phase 3 DeFi analyses Abstract #: 11558 Date and Time: June 1, 1:30 - 4:30 p.m. CDT (2:30 – 5:30 p.m. EDT) A post hoc analysis of the DeFi trial was conducted to assess the effects of nirogacestat in desmoid tumor patients with APC mutations, which are associated with more aggressive desmoid tumor behavior and poor prognosis. Of the 142 patients in the DeFi trial intent-to-treat population, 29 had identified APC mutations (nirogacestat, N=13; placebo, N=16). Results of the analysis demonstrated improvements in PFS, ORR and patient-reported outcomes, including pain, desmoid tumor-specific symptom burden, role and physical functioning, and overall quality of life in this subgroup of patients. Reductions in tumor size, volume, and T2 hyperintensity were also observed with nirogacestat compared with placebo in desmoid tumor patients with identified APC mutations. These efficacy results, as well as the safety results in this subgroup, were consistent with the overall DeFi trial population, and suggest that nirogacestat can provide clinically meaningful benefits in the challenging population of patients with progressing desmoid tumors and APC mutations. 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 was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint 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 to Cycle 13. 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.6 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.8,9 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.10 MEK inhibitors have emerged as a validated class of treatment for NF1-PN.11 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 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 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 and Rare Pediatric Disease designation for the treatment of NF1. SpringWorks expects to complete the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for mirdametinib in children and adults with NF1-PN in the second quarter of 2024. The Company also plans to Marketing Authorization Application (MAA) with the European Medicines Agency (EMA) for mirdametinib for the treatment of children and adults with NF1-PN in the second half of 2024. About the DeFi Trial DeFi (NCT03785964) is a global, randomized (1:1), double-blind, placebo-controlled Phase 3 trial evaluating the efficacy, safety and tolerability of nirogacestat in adult patients with progressing desmoid tumors. The double-blind phase of the study randomized 142 patients (nirogacestat, n=70; placebo n=72) to receive 150 mg of nirogacestat or placebo twice daily. Key eligibility criteria included tumor progression by ≥20% as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to screening. The primary endpoint was progression-free survival, as assessed by blinded independent central review, or death by any cause. Secondary and exploratory endpoints include safety and tolerability measures, objective response rate (ORR), duration of response, changes in tumor volume assessed by magnetic resonance imaging (MRI), and changes in patient-reported outcomes (PROs). DeFi includes an open-label extension phase, which is ongoing. 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.12,13 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.14,15 It is estimated that there are 1,000-1,650 new cases diagnosed per year in the United States.15,18,19 Although they do not metastasize, desmoid tumors are associated with recurrence rates of up to 77% after surgical resection.14,16,17 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.17 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, sometimes severe, can occur in patients treated with OGSIVEO. Diarrhea occurred in 84% of patients treated with OGSIVEO, and included Grade 3 events in 16% of patients. Median time to first diarrhea event was 9 days (range: 2 to 434 days). 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 of OGSIVEO 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: OGSIVEO can cause fetal harm when administered to pregnant women. Oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicity and death 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 (84%), ovarian toxicity (75% in the 36 females of reproductive potential), rash (68%), nausea (54%), fatigue (54%), stomatitis (39%), headache (30%), abdominal pain (22%), cough (20%), alopecia (19%), upper respiratory tract infection (17%), and dyspnea (16%). Serious adverse reactions occurred in 20% of patients who received OGSIVEO. 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. USE IN SPECIFIC POPULATIONS Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with OGSIVEO and for 1 week after the last dose. 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 potential for mirdametinib to become an important new treatment for pediatric and adult patients with NF1-PN, the potential for the results of the Phase 2b ReNeu clinical trial to support an NDA submission, the timing of our planned NDA submission for mirdametinib, our plans for seeking regulatory approval for and making mirdametinib available to NF1-PN patients, if approved, 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 mirdametinib for patients with NF1-PN, (ii) estimates regarding the global birth incidence of NF1-PN and the number of patients living with NF1-PN in the United States and the potential market for mirdametinib, (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 II of SpringWorks’ Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, 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 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. 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. 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. 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. 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. 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. 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. 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. Orphanet Report Series: Rare Diseases collection. Prevalence and incidence of rare diseases: bibliographic data. Number 1, January 2022. Accessed November 24, 2023. U.S. Department of Commerce. News Blog. U.S. population estimated at 332,403,650 on Jan. 1, 2022. Accessed November 24, 2023.

▲5月30-31日 第八届广州生物医药创新者峰会 扫码立即报名 注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。罕见肿瘤新药获批，获NCCN指南1类推荐药融云数据www.pharnexcloud.com显示，2023年11月27日，美国FDA正式批准Ogsiveo（Nirogacestat）片剂用于治疗需要全身治疗的进展性硬纤维瘤成人患者。该药是FDA批准的首个也是唯一一个硬纤维瘤治疗药物，也是FDA批准的首个罕见非癌性肿瘤治疗药物。截图自FDA官网硬纤维瘤（DT）又称为侵袭性纤维瘤病，是一种罕见的软组织肉瘤亚型，是非癌性的，但可具有局部侵袭性。虽然硬纤维瘤并非癌症，但会像癌症一样生长到附近的结构和器官中，因此，硬纤维瘤患者通常由癌症医生负责治疗。该病的特征是非癌性软组织生长，通常导致严重的疼痛、影响运动能力、生活质量降低以及毁容。虽然手术切除历来是该病的首选治疗方案，但肿瘤复发风险（高达77%）或其他健康风险依然很高。Ogsiveo（Nirogacestat）的有效性已在一项国际、多中心、随机、双盲、安慰剂对照的临床试验中进行了评估，该研究包括了142例不适合手术的进行性硬纤维瘤患者。结果表明，与安慰剂相比，Ogsiveo在无进展生存期方面提供了具有临床意义和统计学意义的改善，疾病进展风险降低了71%。同时，Ogsiveo组的客观缓解率为41%，安慰剂组为8%，具有统计学差异。Ogsiveo组患者报告的疼痛评估也支持了无进展生存期的改善。药融云数据www.pharnexcloud.com显示，Ogsiveo（Nirogacestat）此前被FDA授予优先审评资格、突破性疗法认定、快速通道资格，以及孤儿药资格认定，用于治疗硬纤维瘤（侵袭性纤维瘤病）。截图自药融云数据库Ogsiveo（Nirogacestat）是一种新型口服选择性小分子γ分泌酶抑制剂，γ分泌酶是一种蛋白酶复合物，可切割多种跨膜蛋白，包括Notch蛋白，而Notch蛋白被认为能够激活导致硬纤维瘤生长的信号通路。据了解，Nirogacestat入围了Drug Hunter 2023年度十大小分子药物榜单。来源：Drug Hunter在Ogsiveo（Nirogacestat）获批两周之内，2023年12月，美国NCCN肿瘤临床实践指南更新，Nirogacestat获NCCN指南1类推荐，作为硬纤维瘤的首选治疗方案。除了在美国推出以外，2024年2月，欧洲药品管理局（EMA）验证了Nirogacestat的上市许可申请（MAA），并开始了集中审查程序。从辉瑞分离的公司，新药“身世曲折”Ogsiveo（Nirogacestat）是美国制药公司SpringWorks Therapeutics(NASDAQ:SWTX)的第一个商业化产品，最初SpringWorks是辉瑞设想的一家独立公司，该公司设立的目标是在患者迫切需要的治疗领域推进有前景的研究性治疗药物。据报道，Nirogacestat（PF-03084014）一开始是辉瑞为阿尔兹海默症开发的药物，2006年启动1期临床，但在2009年停止阿尔兹海默症临床研究。而在肿瘤领域，Nirogacestat最先也是针对乳腺癌开发，但当时在美国国家癌症研究所（National Cancer Institute）领导早期临床试验开发的Shivaani Kummar博士从1期篮式实体瘤试验中看到了该药物在硬纤维瘤患者中的阳性反应。Shivaani Kummar博士2014年，Kummar博士领导了一项在进展性硬纤维瘤成人患者中开展的开放标签2期试验，并受到了硬纤维瘤肿瘤研究基金会的帮助，在不到6个月的时间里招募了17名患者。2017年9月，SpringWorks正式推出，获得了来自贝恩资本生命科学、Bain Capital Double Impact、奥博资本、辉瑞、LifeArc（原英国MRC Technology）的1.03亿美元的A轮融资，并从辉瑞引进了包括Nirogacestat在内的共4种临床阶段项目资产。融资历程 截图自药融云数据库辉瑞制药将SpringWorks Therapeutics视为一种开创性的合作新模式，旨在通过与各种利益相关者（包括科学家、生物制药合作伙伴、患者团体、资助者和慈善家）的合作，提供社会和财务回报。当时辉瑞的全球研发战略和产品组合解决方案副总裁Lara Sullivan博士是SpringWorks的创始人兼总裁，前辉瑞执行副总裁兼首席医学官Freda Lewis-Hall博士加入SpringWorks的董事会。在SpringWorks Therapeutics的首款产品Ogsiveo（Nirogacestat）获批之后，四周之内，该药卖出了540万美元。同时，SpringWorks还推出了CareConnections™患者支持计划，为符合条件的患者提供全面的个性化服务。研发进展SpringWorks Therapeutics目前拥有差异化、靶向肿瘤的小分子资产组合，研发管线主要聚焦于罕见肿瘤类型和高度流行的、基因驱动的肿瘤。除了全资项目外，SpringWorks还与工业界和学术界的创新者进行合作，以释放产品潜力。更新截至2024年2月·γ分泌酶抑制剂Nirogacestat：潜在BCMA靶向药物增强剂Ogsiveo（Nirogacestat）获批治疗进展性硬纤维瘤成人患者的同时，小儿适应症的研究也在进行。目前，Nirogacestat用于治疗小儿硬纤维瘤的研究处于2期临床阶段。作为一种新型口服选择性小分子γ分泌酶抑制剂，Nirogacestat有治疗多种疾病的潜力。除了硬纤维瘤，Nirogacestat针对卵巢颗粒细胞瘤正在开展一项2期试验，2023年5月完成患者入组，预计将在2024年下半年报告该研究的初步数据。由于γ分泌酶能够直接切割细胞膜上的BCMA（B细胞成熟抗原），而BCMA是经临床验证的多发性骨髓瘤治疗靶点（包括ADC药物、CAR-T疗法、单克隆抗体、双特异性药物）。因此γ分泌酶的抑制剂已被证明能够增加多发性骨髓瘤细胞上BCMA的表达，从而有望在临床上增强BCMA靶向治疗的效果，提高应答率、延长临床获益的持续时间或通过低剂量给药减少副作用。SpringWorks正与多个合作伙伴共同研究Nirogacestat与BCMA靶向药物联用治疗多发性骨髓瘤的潜力，包括葛兰素史克（与BCMA靶向ADC药物Belamaf联用）、再生元（与靶向BCMA/CD3双抗Linvoseltamab联用）、强生（与靶向BCMA/CD3双抗Teclistamab联用）、辉瑞（与靶向BCMA/CD3双抗Elranatamab联用）、Seagen（与靶向BCMA单抗SEA-BCMA联用）、艾伯维（与靶向BCMA/CD3双抗ABBV-383联用）。·MEK抑制剂Mirdametinib：潜在best in class罕见肿瘤药物Mirdametinib（PD-0325901，也是来自辉瑞）是一种口服变构MEK1/2（丝裂原活化的细胞外信号调节激酶1和2）小分子抑制剂。MEK蛋白在MAPK（丝裂原活化蛋白激酶）通路中占据着关键位置，MAPK通路是调节细胞生长和存活的关键信号网络，在多种肿瘤和罕见疾病中起着核心作用。SpringWorks正在研究将Mirdametinib用于治疗1型神经纤维瘤相关丛状神经纤维瘤（NF1-PN）。NF1-PN是一种罕见的疾病，由NF1基因的突变引起，其特征是MAPK通路畸变，引起周围神经鞘肿瘤的生长，从而导致明显的疼痛、毁容，极少数情况下是致命的。目前尚无药物获批治疗NF1-PN。药融云数据www.pharnexcloud.com显示，Mirdametinib此前已获得孤儿药资格认定、快速通道资格，以及罕见儿科疾病用药资格认定，用于治疗NF1-PN。截图自药融云数据库2023年11月16日，SpringWorks宣布了Mirdametinib在成人和儿童NF1-PN患者中关键2b期ReNeu试验的阳性结果。结果显示，儿童患者的确认客观缓解率为52%，成人患者的确认客观缓解率为41%；在儿童与成人患者队列中，靶肿瘤体积相对于基线的最佳百分比变化中位数分别为-42%和-41%。通过多个患者报告结果（PRO）工具的评估，在ReNeu试验中，儿童和成人患者在疼痛、生活质量和身体功能方面也经历了统计学上的显著改善。基于这些结果，SpringWorks认为Mirdametinib有望成为治疗儿童和成人NF1-PN的潜在best in class治疗方案。2024年3月4日，SpringWorks宣布已向美国FDA滚动递交Mirdametinib的NDA申请，用于治疗NF1-PN儿童和成人患者。此外，SpringWorks正在评估Mirdametinib单药治疗或采用联合疗法，用于治疗MAPK信号通路基因相关实体肿瘤。例如，该公司正与百济神州合作研究Mirdametinib与RAF二聚体抑制剂Lifirafenib（BGB-283）联用治疗携带NRAS突变的晚期或难治性实体肿瘤患者（双方在2018年8月建立合作）；Mirdametinib治疗儿童和青年成人低级别胶质瘤患者的研究正在由圣犹大儿童研究医院进行1/2期临床试验。·RAF抑制剂：来自百济神州合资公司2019年，SpringWorks与百济神州成立合资企业MapKure，以开发一种由百济神州科学家发现的在研高选择性新一代口服小分子RAF激酶抑制剂Brimarafenib（BGB-3245）。MapKure正在推进Brimarafenib用于BRAF驱动突变和BRAF融合的实体瘤，这些患者在临床前研究中被观察到对该化合物敏感。MapKure、百济神州与SpringWorks正在开展一项1期临床研究，评估Brimarafenib在MAPK通路畸变的晚期或难治性实体瘤患者中的疗效，预计将在2024年下半年分享最新的数据。2023年2月，SpringWorks在一项1/2a期开放标签、剂量递增和扩展试验中完成首例患者给药，该试验旨在评估Brimarafenib（BGB-3245）联合MEK1/2抑制剂Mirdametinib治疗携带MAPK激活突变的晚期实体肿瘤患者的潜力，目前正在美国和澳大利亚招募患者。2023年8月，MapKure递交了Brimarafenib与靶向EGFR的单克隆抗体帕尼单抗联用，治疗已知MAPK通路畸变的结肠直肠和胰腺癌患者的IND申请，MapKure预计将在2024年第一季度启动1b期试验。·TEAD抑制剂早期研究项目SW-682是一种口服小分子TEAD（转录增强缔合域）抑制剂，由SpringWorks于2021年从鲁汶大学和弗兰德斯生物技术研究所获得全球独家许可，目前正在评估用于治疗Hippo河马信号通路突变的实体瘤。2024年第一季度，FDA批准了SW-682的临床试验申请，公司预计在2024年上半年启动1a期临床试验。·EGFR抑制剂项目2021年10月，SpringWorks宣布与达纳-法伯癌症研究所签订全球独家许可协议，据此引进了一种新型小分子EGFR抑制剂，用于治疗EGFR突变肺癌。与此同时，SpringWorks与斯坦福医学院签订了一项为期多年的研究赞助协议，以资助斯坦福医学实验室以及达纳-法伯合作实验室的研究和开发工作。该项目中的领先资产最快已进入先导化合物优化阶段，针对C797S耐药突变。·两度转手的FAAH抑制剂，现终止研发2020年10月，爵士制药以3500万美元预付款从SpringWorks引进了一款脂肪酸酰胺水解酶（FAAH）抑制剂PF-04457845（后称JZP150），用于治疗创伤后应激障碍（PTSD）及相关症状。该产品由辉瑞于2017年许可给SpringWorks。2023年12月，爵士制药宣布了其JZP150治疗PTSD的2期临床试验的初步结果。该试验没有达到其主要或次要终点。爵士制药预计将不再推进JZP150用于PTSD的进一步研究。（相关阅读：收购医药大麻第一品牌，爵士制药肿瘤与CNS双管齐下）截图自药融云数据库财务状况自2017年成立以来，SpringWorks将资源投入于候选产品研发、执行业务发展战略、建立知识产权组合、组织和配备公司、建设商业化能力、商业规划、筹集资金和提供销售，以及一般和行政支持。截至2023年底，SpringWorks拥有现金、现金等价物和有价证券共6.626亿美元。成立至今公司累计赤字为8.95亿美元。2024年12月，SpringWorks Therapeutics的首款产品Ogsiveo（Nirogacestat）在美国正式开始销售，为2024财年贡献了544.7万美元业绩收入。2023全年，SpringWorks公司研发费用为1.505亿美元，与上年同期相比持平；全年销售、一般和行政费用为1.976亿美元，同比增长47%，主要归因于支持美国市场推出Ogsiveo（Nirogacestat）的商业准备活动；年度净亏损为3.251亿美元，或每股亏损5.15美元。具体项目研发支出：截至2024年5月8日，SpringWorks Therapeutics（NASDAQ:SWTX）总市值为31.31亿美元。此文仅用于向医疗卫生专业人士提供科学信息，不代表平台立场，不作任何用药推荐参考：NMPA/CDE；药融云数据www.pharnexcloud.com；FDA/EMA/PMDA；相关公司公开披露（正文图片均来自企业官方，除非另有说明）；https://springworkstx.com/pipeline/；https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-rare-type-non-cancerous-tumors；https://drughunter.com/molecule/nirogacestat/；https://www.fiercepharma.com/pharma/fda-approves-pfizer-spinout-springworks-ogsiveo-first-treatment-disfiguring-rare-tumor-type；https://www.prnasia.com/story/221878-1.shtml；https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-provides-update-phase-2-trial；等等 活动推荐  5月 • 第八届大湾区生物医药创新者峰会  关键词：  小分子，XDC，多肽及GLP-1热点话题，80+行业专家（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。