Granulosa Cell Tumor of the Ovary

iStock, Anton Vierietin The transaction, which sources say could be agreed upon as soon as Monday, would price SpringWorks at $47 per share, totaling approximately $3.5 billion for the acquisition. Germany’s Merck KGaA is in advanced talks with SpringWorks Therapeutics for an acquisition that could be valued at about $3.5 billion, according to several media reports on Thursday. Confirming the news to The Wall Street Journal , Merck KGgA revealed that while no formal, legally binding arrangement has yet been reached, the companies are considering a purchase price of around $47 per share of SpringWorks. If all goes smoothly from here, the parties could reach an agreement as soon as Monday, according to sources familiar with the negotiations. SpringWorks share prices jumped 9% Thursday after the news reports. Rumors of the courtship between Merck KGaA and SpringWorks first broke in February, with anonymous sources telling Reuters at the time that the parties could reach an agreement in weeks’ time. Merck KGaA confirmed the talks, sending SpringWorks’ stocks surging some 30% in reaction, even as the German pharma insisted that “there is no certainty that any transaction will materialize.” But when a deal didn’t materialize, investor interest in SpringWorks waned. Earlier this month, the cancer-focused biotech had dropped roughly 40% from its high in February. Since the first buyout rumors swirled, SpringWorks has become a more valuable prospect for potential buyers, winning FDA approval for Gomekli, its oral drug for neurofibromatosis type 1 with symptomatic plexiform neurofibromas. If the acquisition deal pushes through, Merck KGaA will inherit SpringWorks’ Ogsiveo, indicated for adults with progressing desmoid tumors. Last year, Ogsiveo pulled in $172 million for the company in the U.S alone. SpringWorks is also studying Ogsiveo in other rare cancers, including ovarian granulosa cell tumors and relapsed/refractory multiple myeloma. The SpringWorks deal could help Merck KGaA rebound after a series of clinical setbacks. In April 2023, its BTK blocker evobrutinib was hit with a partial clinical hold from the FDA after the regulator detected cases of liver injury in a Phase III trial. Later that year, in December, Merck KGaA announced that evobrutinib had failed two Phase III studies in relapsing multiple sclerosis, unable to significantly reduce yearly relapse rates versus Sanofi’s Aubagio. Merck KGaA was forced to terminate evobrutinib’s multiple sclerosis run in March 2024. Then, in June 2024, the company also axed a couple of trials of xevinapant after the drug candidate failed to significantly improve survival in patients with locally advanced head and neck cancer. Amid these failures, Merck in April 2024 attempted to buttress its cancer pipeline with a potential $1.4 billion discovery and development deal with Texas biotech Caris Life Sciences, focused on antibody-drug conjugates for oncology targets.

– Achieved $61.5 million and $172.0 million in preliminary fourth quarter and full year 2024 OGSIVEO® (nirogacestat) U.S. net product revenues, respectively – – Ended 2024 with approximately $462 million in cash, cash equivalents, and marketable securities – – Additional updates across Company’s commercial portfolio and investigational pipeline to be provided during J.P. Morgan Healthcare conference presentation today at 11:15 a.m. PT – STAMFORD, Conn., Jan. 13, 2025 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, today announced its preliminary fourth quarter and full year 2024 U.S. net product revenue for OGSIVEO® (nirogacestat) and provided additional company updates ahead of its presentation at the 43rd Annual J.P. Morgan Healthcare conference. Preliminary Fourth Quarter and Full Year 2024 Financial Results* and Recent Business Highlights Preliminary fourth quarter and full-year 2024 U.S. net product revenue for OGSIVEO were $61.5 million and $172.0 million, respectively.As of December 31, 2024, total preliminary cash, cash equivalents, and marketable securities was $461.9 million. SpringWorks expects its cash position to fund operations through profitability, which the Company anticipates achieving in the first half of 2026.Presented long-term follow-up data from the Phase 3 DeFi trial of nirogacestat in adults with progressing desmoid tumors in the fourth quarter of 2024. These results showed that longer-term treatment with nirogacestat (median duration of treatment: 34 months) was associated with further reductions in tumor size, increase in objective response rate with additional partial responses and complete responses, sustained improvements in desmoid tumor symptoms including pain, and a consistent safety profile.Obtained an exclusive, global license from Rappta Therapeutics Oy for a first-in-class molecular glue of specific Protein Phosphatase 2A (PP2A) complexes. PP2A mutations represent a class of targetable oncogenic drivers in molecularly defined subsets of uterine cancer patients with high unmet need. In preclinical models of PP2A mutant uterine cancer, SW-3431 (formerly RPT04402) showed rapid, deep and durable tumor regressions as a monotherapy. In exchange for the license, Rappta received a $13 million upfront payment and is eligible to receive further clinical, regulatory and commercial milestone payments, and tiered single digit royalties on net sales. * The preliminary fourth quarter and full year 2024 financial results are unaudited and do not present all information necessary for an understanding of the Company’s results of operations and financial position for the fourth quarter and full year 2024. Such financial results are subject to adjustment and could differ from the Company’s announcement of complete financial results in February 2025. 2025 Priorities and Anticipated Milestones OGSIVEO (nirogacestat) Continue strong commercial execution of the OGSIVEO launch in the U.S.Secure regulatory approval for OGSIVEO in the European Union (EU) and launch OGSIVEO following reimbursement authorization in individual EU countries, beginning with Germany in mid-2025.Publish long-term follow-up data from the Phase 3 DeFi trial of nirogacestat in adults with desmoid tumors in a peer-reviewed journal by the end of 2025.Report initial data from the Phase 2 trial evaluating nirogacestat as a monotherapy in patients with ovarian granulosa cell tumors in the first half of 2025.Continue 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 (NF1-PN) Secure FDA approval in adults and children with NF1-associated plexiform neurofibromas, or NF1-PN (PDUFA: February 28, 2025), and launch in the U.S.Obtain regulatory approval in the EU for mirdametinib for the treatment of adults and children with NF1-PN and begin initial launch in 2025. Emerging Pipeline SpringWorks expects additional data to be presented by MapKure from the brimarafenib monotherapy trial in the second half of 2025.Continue enrolling patients in Phase 1 trial of SW-682 in Hippo-mutant solid tumors.File an Investigational New Drug (IND) application for SW-3431 by the end of 2025. “2025 is set up to be another transformative year for SpringWorks. With the potential launch of our second medicine and global expansion to serve patients with two devastating diseases, we are energized by the opportunity to continue delivering on the commitments we have made to the patient communities we are dedicated to serving,” said Saqib Islam, Chief Executive Officer of SpringWorks. “In parallel with our commercial launches, we are advancing our pipeline of oncology programs for heavily underserved patient populations and are confident that our strong foundation will drive our long-term growth and success.” Presentation at the 43rd Annual J.P. Morgan Healthcare Conference SpringWorks will webcast its presentation from the 43rd Annual J.P. Morgan Healthcare Conference today, Monday, January 13, 2025 at 11:15 a.m. PT (2:15 p.m. ET). To access the live webcast, please visit the Events & Presentations page within the Investors & Media section of the company’s website at https://ir.springworkstx.com. A replay of the webcast will be available on SpringWorks’ website for a limited time following the conference. 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. 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 our preliminary financial results for the fourth quarter and full year 2024, current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our development and commercialization plans, the timing of and results from our preclinical studies and clinical trials, the potential for mirdametinib to become an important new treatment for adult and pediatric NF1-PN patients, expectations regarding the timing and results of the reviews by the FDA and the EMA, as applicable, of each of the NDA and the MAA for mirdametinib for the treatment of adult and pediatric NF1-PN patients, including the FDA's PDUFA target action date for the NDA, expectations regarding the timing and results of the MAA for OGSIVEO and our plans to make OGSIVEO commercially available in individual countries in the European Union following required approvals beginning in mid-2025, our plans to present additional data from the Phase 3 DeFi trial of nirogacestat at upcoming conferences, 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 timing for additional data for brimarafenib in the second half of 2025, our expectations and the timing of the Phase 1 trial of SW-682, our plans to file an IND for SW-3431 by the end of 2025, 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) 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, (vii) 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, (viii) the success and timing of our collaboration partners’ ongoing and planned clinical trials, (ix) 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, (x) 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, (xi) our ability to obtain regulatory approval of any of our product candidates or maintain regulatory approvals granted for our products, (xii) our plans to research, discover and develop additional product candidates, (xiii) our ability to enter into collaborations for the development of new product candidates and our ability to realize the benefits expected from such collaborations, (xiv) our ability to maintain adequate patent protection and successfully enforce patent claims against third parties, (xv) the adequacy of our cash position to fund our operations through any time period indicated herein, (xvi) our ability to establish manufacturing capabilities, and our and our collaboration partners’ abilities to manufacture our product candidates and scale production, and (xvii) 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, 2024, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings. Contacts Investors investors@springworkstx.com Media media@springworkstx.com

– Long-term follow-up data highlight further reductions in tumor size, increase in ORR with additional CRs, sustained improvement in desmoid tumor symptoms, and consistent safety profile, now with a median duration of therapy of approximately 3 years – Nov. 07, 2024 -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, today announced that long-term efficacy and safety data from the Phase 3 DeFi trial of nirogacestat in adults with progressing desmoid tumors will be presented as a late-breaking oral presentation at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting, being held November 13-16, 2024, in San Diego, CA. These results, utilizing an August 2024 data cutoff date, showed that longer-term treatment with nirogacestat was associated with further reductions in tumor size, increase in objective response rate (ORR) with additional partial responses (PRs) and complete responses (CRs), sustained improvements in desmoid tumor symptoms including pain, and a consistent safety profile compared to the April 2022 data cut utilized for the primary results of the trial. “Our findings demonstrate that longer-term nirogacestat treatment was associated with durable tumor size reductions, evidence of deepening responses, and sustained benefits in pain, physical functioning and other desmoid tumor symptoms,” said Ravin Ratan, M.D., M.Ed., Associate Professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, and DeFi study investigator presenting the data at CTOS. “Given the oftentimes persistent and debilitating nature of desmoid tumors, these results are meaningful for patients and clinicians as they provide valuable insights on the longer-term use of this medicine.” “We are pleased that the growing body of evidence from the DeFi trial continues to support the significant benefits that OGSIVEO is providing for patients with desmoid tumors,” said Jim Cassidy, M.D., Ph.D., Chief Medical Officer of SpringWorks Therapeutics. “It is also gratifying that feedback from the real-world setting is consistent with our clinical trial experience, with patients reporting rapid, sustained and continued symptomatic relief, which is contributing to their overall improved quality of life.” Additional DeFi data to be presented at CTOS include an oral presentation of a post-hoc analysis assessing the effect of nirogacestat in subgroups of patients with desmoid tumors who have risk factors associated with poor prognosis and a poster on patients with CTNNB1 and APC mutations. Oral Presentations at the CTOS 2024 Annual Meeting Nirogacestat treatment in adult patients with desmoid tumors: Long-term efficacy and safety from the Phase 3 DeFi trial Date and Time: November 16, 3:30-4:30 p.m. PT (6:30-7:30 p.m. ET) As previously reported, 70 patients were randomized to nirogacestat in the double-blind (DB) portion of the Phase 3 DeFi trial (NCT03785964); these patients achieved statistically and clinically significant improvement in progression-free survival (PFS) and ORR, as well as rapid and sustained improvement in pain, physical functioning, role functioning and overall quality of life, as compared to those randomized to placebo. At the primary analysis data cut-off date (April 2022), the median (range) duration of nirogacestat treatment was 20.6 (0.3-33.6) months. Following the DB portion of the study, patients could continue to receive nirogacestat as part of the open-label extension (OLE). As of this long-term follow-up analysis (August 2024 data cut-off date), the median (range) duration of nirogacestat treatment in these patients was 33.6 (0.3 to 60) months. The data being presented at CTOS evaluated the overall efficacy and safety of continuous nirogacestat treatment in patients initially randomized to nirogacestat in DeFi and further explored safety and efficacy analyses at milestones of one, two, three, and four years on treatment. Results demonstrated that: Three new PRs and three new CRs were reported using the August 2024 versus the April 2022 data cut-off date, resulting in an ORR of 45.7% (34.3% PR, 11.4% CR) (N=70). The median best percent reduction from baseline in target tumor size by RECIST 1.1 with continuous nirogacestat treatment was −32.3% at year one (n=46) and −75.8% for patients completing at least four years (n=15) of treatment. Improvement in patient reported outcomes (PROs) of pain, desmoid tumor-specific symptom severity, and desmoid tumor-specific physical functioning, which occurred early (at Cycle 2, the first post-treatment timepoint evaluated as disclosed at the primary analysis) and were sustained with up to 45 months of treatment with nirogacestat. The most frequently reported treatment emergent adverse events (TEAEs) that occurred in >20% of patients receiving nirogacestat over the entire treatment period were diarrhea, nausea, fatigue, hypophosphatemia, and headache, and were generally consistent between the April 2022 and August 2024 data cutoffs. Most events were Grade 1 or 2, with first onset occurring in the first year of treatment for most patients. Overall, the incidence and severity of frequently reported TEAEs decreased through years two, three and four of treatment. Efficacy of nirogacestat in patients with poor prognostic factors for desmoid tumors: patient-reported outcomes, progression-free survival, and objective response in the phase 3 DeFi trial Date and Time: November 16, 3:30-4:30 p.m. PT (6:30-7:30 p.m. ET) A post hoc analysis of the DeFi trial was conducted to assess the effect of nirogacestat on PFS, ORR and PROs in subgroups of patients with desmoid tumors who have risk factors associated with a poor prognosis: larger tumor size (>10 cm), younger age (≤30 years), specific types of CTNNB1 gene mutations, and presence of pain at baseline. Results include: Treatment with nirogacestat led to consistent improvements in PFS, ORR and PROs versus placebo regardless of the patient subgroups. The ORR risk difference between nirogacestat and placebo ranged from 18.1% to 56.0%, favoring nirogacestat. Compared with placebo, patients treated with nirogacestat generally reported greater improvement from baseline at cycle 10 in PROs (pain, desmoid tumor-specific symptom burden, physical and role functioning, and overall quality of life) across subgroups of patient-related and tumor-related poor prognostic factors. The authors concluded that nirogacestat demonstrates uniform efficacy and consistent improvement in PROs across the desmoid tumor population. Poster Presentations at the CTOS 2024 Annual Meeting Descriptive evaluation of patients with desmoid tumor and co-occurring somatic mutations of CTNNB1 and APC in the Phase 3 DeFi trial Date and Time: November 14, 5:45-6:45 p.m. PT (8:45-9:45 p.m. ET) This analysis identified three patients with desmoid tumors enrolled in the DeFi trial who had co-occurring somatic mutations of CTNNB1 and APC, including two treated with nirogacestat. Both patients achieved a best overall response of partial response (with time to response of 6.0 and 13.8 months). Although the small number of patients limited a formal analysis, descriptive results suggest that patients with this mutational profile benefit from nirogacestat treatment in a manner that is generally consistent with the overall DeFi study population but may take longer to experience a treatment response. DeFi (NCT03785964) is a global, randomized (1:1), multicenter, double-blind, placebo-controlled pivotal 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 (PFS), 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. 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.1,2 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.3,4 It is estimated that there are 1,000-1,650 new cases diagnosed per year in the United States.4,5,6 Although they do not metastasize, desmoid tumors are associated with recurrence rates of up to 77% after surgical resection.3,7.8 Desmoid tumor experts and treatment guidelines now recommend systemic therapies as first-line intervention instead of surgery for most tumor locations requiring treatment.8 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. 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 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. Orphanet Report Series: Rare Diseases collection. Prevalence and incidence of rare diseases: bibliographic data. Number 1, January 2022. Accessed November 5, 2024. https://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf. U.S. Department of Commerce. News Blog. U.S. population estimated at 332,403,650 on Jan. 1, 2022. Accessed November 5, 2024. https://www.commerce.gov/news/blog/2022/01/us-population-estimated-332403650-jan-1-2022. 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. The content above comes from the network. if any infringement, please contact us to modify.