Slides
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Saqib Islam, Chief Executive Officer January 13, 2025 43rd Annual J.P. Morgan Healthcare Conference
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2 Note: Unless otherwise indicated, the information presented herein is as of January 2025 and made publicly available on January 13, 2025. This presentation 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, unaudited 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 of our preclinical studies and clinical trials, the market potential of OGSIVEO for adult patients with desmoid tumors, 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 report additional clinical data of nirogacestat in combination with BCMA-directed therapies and initiate additional planned Phase 1 collaborator studies, our plans to file an IND for SW-3431 by the end of 2025, 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, expectations about when we will be profitable, 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) estimates regarding the number of adult and pediatric NF1-PN patients and the potential market for mirdametinib, if approved, (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 approveor 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 September 30, 2024, as well as discussions of potential risks, uncertainties and other important factors in SpringWorks’ subsequent filings. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While SpringWorks believes these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. Forward-Looking Statements
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3 SpringWorks Therapeutics Is a Commercial-Stage Targeted Oncology Company Delivering New Advances for Patients OGSIVEO is the first and only FDA-approved therapy for desmoid tumors and is established as the systemic standard of care NDA for mirdametinib in NF1-PN granted Priority Review, representing opportunity for a second FDA approval in early 2025 Geographic expansion for lead assets and diversified pipeline of emerging targeted oncology programs broaden opportunity set Strong financial position with profitability expected in 1H 2026 and durable IP protection for lead programs NDA: New Drug Application; NF1-PN: Neurofibromatosis Type 1-Associated Plexiform Neurofibromas; IP: Intellectual Property.
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4 • First and only approved therapy for adult patients with desmoid tumors, an aggressive and highly debilitating soft tissue tumor • Rapidly established as systemic standard of care for adults • Real-world experience supports transformative benefits for patients, including significant reductions in pain • Evolving treatment dynamics, physician preferences, and long-term data support increased and sustained use of OGSIVEO OGSIVEO Gamma Secretase Inhibitor • Highly fragmented treatment landscape for NF1-PN, a disfiguring and highly morbid tumor that forms along peripheral nerves • No approved options for adult patients; challenges with approved therapy for pediatric patients • Pivotal data support mirdametinib’s potential as first-in-class therapy for adults and best-in-class option for children • NDA under Priority Review with February 28 PDUFA date Delivering on Our Promise to Patients With Second Approved Medicine Expected This Year Note: NF1-PN: Neurofibromatosis Type 1-Associated Plexiform Neurofibromas; NDA: New Drug Application; PDUFA: Prescription Drug U ser Fee Act. Mirdametinib Investigational MEK Inhibitor CHRISTINA LIVING WITH A DESMOID TUMOR ANTWAN LIVING WITH NF1-PN
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OGSIVEO for Desmoid Tumors
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6 Desmoid Tumors Are Highly Morbid and Patients Had No Approved Treatments Before OGSIVEO (1) Desmoid tumor-specific ICD-10 codes were introduced in October 2023. Data through October 2024 represents latest available. Note: QOL: Quality of Life; ICD-10: International Classification of Diseases, Tenth Edition. Aggressive, invasive, and highly debilitating soft tissue tumors Can cause severe and chronic pain, loss of physical function, disfigurement, and anxiety with significant QOL impact ~11,000 patients with desmoid tumor ICD-10 claims between October 2023 and October 2024(1) I was devastated when a small lump in my right arm found during a routine physical was diagnosed as a desmoid tumor. Within 6 months, it doubled in size and became so painful that even holding a coffee mug and cutting a sandwich was difficult. - Carol, desmoid tumor patient OGSIVEO changed the outlook for patients who were previously underserved with surgery and off-label systemic therapies
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7 Strong Launch of OGSIVEO Generated $172M of Net Revenue in First Full Year on Market $5.4 $21.0 $40.2 $49.3 $61.5 Q4 2023 Q1 2024 Q2 2024 Q3 2024 Q4 2024 Key Commercial HighlightsOGSIVEO Net Revenue Since Launch ($M) (1) OGSIVEO was approved on November 27, 2023 for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. (2) Q4 and FY 2024 revenue information shown is unaudited and preliminary, and does not present all information necessary for an understanding of the Company's results of operations for the quarter and fi scal year ended December 31, 2024. (2) Over $177M in net product revenue since launch(2) Rapidly established as systemic standard of care Sustained quarterly growth in revenue and patients on therapy Enthusiastic prescriber base with strong preference for OGSIVEO (1)
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8 Factors Underpinning Confidence in OGSIVEO’s Commercial Opportunity Addressable Patient Population Growing OGSIVEO Utilization Evolving Treatment Dynamics ✓ Large and growing number of addressable patients ✓ National and regional thought leader advocacy ✓ Geographic expansion outside the U.S. ✓ Robust adoption across CoEs and community ✓ Strong physician preference for OGSIVEO ✓ Long-term data supporting benefit of extended treatment durations ✓ Systemic-first treatment guidelines ✓ Clinically-driven urgency to treat ✓ Physician behavior aligned with label Note: CoE: Center of Excellence.
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9 Europe Preparing to Bring OGSIVEO to Patients Outside of the U.S. This Year Note: MAA: Marketing Authorization Application; KOL: Key Opinion Leader; NPP: Named Patient Program; EAP: Expanded Access Pro gram; AP1: Early Access Authorization. (1) SpringWorks market research; survey of 214 oncologists treating desmoid tumor patients in Germany, France, and the UK, July 2 024. Germany: Launch anticipated mid-2025 United Kingdom: MAA submission mid-2025 France: AP1 program acceptance Italy: EAP activated Japan • Single-arm ethno-bridging study initiating in 2025 that, together with DeFi, is expected to form the basis for a Japanese NDA filing Named Patient Program • NPP active with initial requests approved and shipped • MAA review ongoing with anticipated approval in mid-2025 • Significant and tractable commercial opportunity • Positive KOL experiences with OGSIVEO through DeFi trial • Physician enthusiasm for OGSIVEO’s profile expected to translate into prescribing(1) • >250 European patients enrolled in compassionate use program • European HQ established and key personnel onboarded
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Mirdametinib for NF1-PN
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11 NF1-PN Is a Debilitating Nerve Sheath Tumor With Multi-Faceted Impact on Patients Significant impact on patient and caregiver quality of life with physical, emotional, and psychological burden Pain is very common and often limits mobility and range of physical activities PNs can transform into malignant peripheral nerve sheath tumors, an aggressive and nearly always fatal disease I was diagnosed with NF1 as a baby. I’ve had 18 surgeries. 24 hospital stays and have been on a ventilator since 2013. I was told that my life expectancy would be short, but even so, I went to college, I have a good job, and I continue to fight NF. - Antwan, NF1-PN patient Disfiguring and highly morbid growth along nerves, often found in the head or neck, extremities, and trunk Note: NF1-PN: Neurofibromatosis Type 1-Associated Plexiform Neurofibroma; PN: Plexiform Neurofibroma.
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12 ~100,000 People with an NF1 diagnosis in the U.S.(1) ~40,000 Patients living with NF1-PN in the U.S.(2,3) ~30,000 Adult NF1-PN patients with no approved treatment option ~10,000 Pediatric NF1-PN patients with significant unmet need Note: NF1-PN: Neurofibromatosis Type 1-Associated Plexiform Neurofibroma; SoC: Standard of Care. Sources: (1) Lammert et al., Arch Dermat, 2005. U.S. Census Data; (2) Fisher et al., Neuro -Oncology, 2022. (3) SpringWorks market research. Surgery is difficult due to infiltrative growth along nerves and is viewed as an inadequate long-term solution for most patients Highly fragmented treatment landscape with significant use of off-label systemic options No approved options for adult patients, who represent majority of NF1-PN population One approved option for pediatric patients, but challenges with administration and tolerability limit use Mirdametinib Has the Potential to Address Substantial Unmet Needs for NF1-PN Patients U.S. NF1-PN Patient Population
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13 ReNeu Data Support Mirdametinib’s Potential Best-in-Class Profile in Adults and Children Note: ORR: Objective Response Rate; BICR: Blinded Independent Central Review; NDA: New Drug Application; MAA: Marketing Autho rization Application; PDUFA: Prescription Drug User Fee Act. Sources: Moertel C, Hirbe A, Shuhaiber H, et al. for the ReNeu Study Group. ASCO 2024; Babovic-Vuksanovic D, Hirbe A, Moertel C, et al. Global NF Conference 2024; Klesse LJ, Bornhorst M, Meade J, et al. ISPNO 2024. Meaningful Antitumor Activity Manageable Safety Profile Enhanced Quality Of Life Significant Patient Convenience • Oral tablet that dissolves easily in water provides convenience and facilitates compliance in children and patients with swallowing problems • Intermittent dosing schedule with built-in drug holiday • Robust ORRs confirmed by BICR • Deep and durable responses, with majority of responders experiencing tumor volume reduction over 50% • Low rates of Grade 3+ toxicities and dose interruptions • Extended treatment durations • Statistically significant improvements in patient-reported outcomes • Early, sustained, and clinically meaningful benefits in worst tumor pain and pain interference NDA accepted with Priority Review and PDUFA date of February 28, 2025 | MAA validated by EMA and review ongoing
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14 Market Research Supports Physician Belief in Mirdametinib’s Potential Differentiation in NF1-PN Note: NF1-PN: Neurofibromatosis Type 1-Associated Plexiform Neurofibroma; PN: Plexiform Neurofibroma. Source: (1) SpringWorks primary market research, December 2023 (N=100 physicians). (2) SpringWorks primary market research, F ebruary 2024 (N=170 physicians). Respondents in both studies answered questions based on review of blinded profiles derived from FDA labeling (selumetinib) and ReNeu topline data (mirdametinib). No head-to-head studies have been conducted between mirdametinib and selumetinib. High Unmet Need(1) Differentiated Profile(1) Likelihood to Prescribe(2) 89% found clinical profile to be more compelling than selumetinib’s on efficacy found clinical profile to be more compelling than selumetinib’s on safety 89% are likely to prescribe mirdametinib 91% believe mirdametinib will become a standard part of their NF1-PN treatment within 12 months 92% agreed there is an unmet need for pediatric NF1-PN patients 98% agreed there is an unmet need for adult NF1-PN patients 81% The efficacy and tolerability is superior to my current treatments with a much easier dosing regimen and lower rate of discontinuation. - Medical Oncologist [Mirdametinib] does look better in its overall response rate, and median PN reduction rate looks much better. - Neuro-Oncologist
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15 GOMEKLITM U.S. Pre-Launch Activities Underway Note: NFCN: Neurofibromatosis Clinical Network. Mirdametinib not yet approved, currently under FDA priority review with PDUFA target action date of February 28, 2025. 35 territory business managers onboarded, with deep oncology and rare disease experience Preliminary physician profiling underway with initial focus on ~70 NFCN centers and other key sites in the U.S. Robust patient service offerings designed to support the treatment experience and facilitate rapid access Disease state education campaign launched with high engagement from physicians and patients
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Looking Ahead
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17 Compound Indication Development Approach Preclinical Phase 1 Phase 2 Phase 3 Regulatory Submission Approved Collaborator(s) Nirogacestat Gamma Secretase Inhibitor Desmoid Tumors* Monotherapy (adult) Monotherapy (pediatric) Ovarian Granulosa Cell Tumors Monotherapy Multiple Myeloma + BCMA-Targeting Agents Several(2) Mirdametinib MEK Inhibitor NF1-Associated Plexiform Neurofibromas† Monotherapy Pediatric Low-Grade Gliomas Monotherapy NRAS Mutant Solid Tumors + Lifirafenib (Pan-RAF inhibitor) Brimarafenib RAF Fusion & Dimer Inhibitor MAPK Mutant Solid Tumors Monotherapy + Mirdametinib + Panitumumab SW-682 TEAD Inhibitor Hippo Mutant Tumors Monotherapy SW-3431 PP2A Activator Rare Uterine Cancers Monotherapy * Received Orphan Drug designation. † Received Orphan Drug, Fast Track, and Rare Pediatric Disease designations. NDA for NF1 -PN granted Priority Review with PDUFA date of February 28, 2025. (1) Indicated for adult patients with progressing desmoid tumors who require systemic treatment. (2) Includes preclinical, Phase 1, and Phase 2 studies planned or ongoing with GSK, Ja nssen, Pfizer, Regeneron, and AbbVie. On June 6, 2024, GSK notified SpringWorks that it is terminating the collaboration agreement and winding down the study; no further enrollment is expected, though the study will continue for the patients enro lled at the time of termination notice. (3) Being developed by MapKure, LLC, jointly owned by SpringWorks and BeiGene. (3) OGSIVEO (1) (U.S.) Diversified Targeted Oncology Pipeline Spanning Solid Tumors and Hematological Cancers
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18 Anticipated 2025 Milestones 2025 Priorities Across Our Pipeline • Secure EU regulatory approval and launch OGSIVEO in Europe, beginning with Germany in mid-2025 • Publish long-term follow-up data for desmoid tumors in a peer-reviewed journal by YE 2025 • Continue to expand opportunity set across indications, with initial Phase 2 OvGCT data in 1H 2025 • Support additional data disclosures by partners for ongoing BCMA collaborations and advance development of nirogacestat combination across lines of multiple myeloma treatment Nirogacestat (Gamma Secretase Inhibitor) • Secure FDA approval in adults and children with NF1-PN (NDA under Priority Review with February 28 PDUFA date) and launch in U.S., with potential to receive priority review voucher following approval • Obtain EU regulatory approval under Orphan Drug designation and launch mirdametinib in Europe in 2025 Mirdametinib (MEK Inhibitor) • Present additional data for brimarafenib(1) monotherapy in MAPK-mutant solid tumors in 2H 2025 • Continue enrolling patients in Phase 1 trial of SW-682 in Hippo-mutant solid tumors • Advance SW-3431 to IND filing by YE 2025, with initial development in uterine serous carcinoma (USC) and uterine carcinosarcoma (UCS) Emerging Pipeline (1) Being developed by MapKure, a joint venture owned by SpringWorks and BeiGene. Note: OvGCT: Ovarian Granulosa Cell Tumors; NF1-PN: Neurofibromatosis Type 1-Associated Plexiform Neurofibromas; NDA: New Drug Application; PDUFA: Prescription Drug User Fee Act; IND: Investigational New Drug Application.
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19 Strong Foundation in Place With Multiple Drivers for Continued Growth (1) This information is unaudited and preliminary, and does not present all information necessary for an understanding of the Company's results of operations for the quarter and fi scal year ended December 31, 2024. Cash refers to cash, cash equivalents, and marketable securities. Note: NF1-PN: Neurofibromatosis Type 1-Associated Plexiform Neurofibromas. MIRDAMETINIBOGSIVEO GLOBAL EXPANSION PIPELINE CAPITAL • OGSIVEO established as systemic standard of care • Real-world evidence of significant patient benefit • $172M in 2024 net product revenue(1) driven by patient demand • Mirdametinib PDUFA date set for February 28, 2025 • Differentiated clinical data and product profile in NF1-PN • Potential first-in-class option for adult patients • Strong balance sheet with $462M in cash(1) • Fully funded through expected profitability in 1H 2026 • Able to support disciplined portfolio expansion with capital efficient approach • Deep pipeline of late- and early-stage programs • Robust platform of discovery, clinical, and regulatory capabilities • Focus on underserved patient populations • MAA reviews for nirogacestat and mirdametinib ongoing • Potential approvals for both programs in 2025 • European launch readiness is on track Several Levers for Achieving Scale Over TimeMulti-Product Base Business Serves as Commercial Foundation
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20 THANK YOU