Business Overview
SpringWorks Therapeutics, Inc. (NASDAQ:SWTX) is a commercial-stage biopharmaceutical company at the forefront of developing and commercializing life-changing medicines for underserved patient populations suffering from devastating rare diseases and cancer. The company's differentiated portfolio of small molecule targeted oncology assets includes one approved product and several clinical candidates, positioning SpringWorks to make a significant impact across both rare tumor types and highly prevalent, genetically defined cancers.
SpringWorks was founded in 2017 with the mission of applying a precision medicine approach to address the unmet needs of patients with rare diseases and cancer. The company's lead product, OGSIVEO® (nirogacestat), was approved by the FDA in November 2023 for the treatment of adult patients with progressing desmoid tumors who require systemic treatment. OGSIVEO is the first and only FDA-approved therapy for this indication, representing a significant milestone for SpringWorks and the desmoid tumor community.
In addition to OGSIVEO, SpringWorks is advancing mirdametinib, an investigational oral MEK inhibitor, for the treatment of neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN), a rare and debilitating tumor of the peripheral nerve sheath. The company recently reported positive topline results from the potentially registrational Phase 2b RENEW trial, which demonstrated compelling antitumor activity and a favorable safety profile for mirdametinib in both pediatric and adult patients with NF1-PN. SpringWorks is now preparing to submit a New Drug Application (NDA) to the FDA for mirdametinib in the second quarter of 2024.
Beyond its lead programs, SpringWorks is evaluating nirogacestat in ovarian granulosa cell tumors, a rare and aggressive subtype of ovarian cancer, and is exploring novel combination regimens of nirogacestat with B-cell maturation antigen (BCMA)-directed therapies for the treatment of multiple myeloma. The company is also advancing a pipeline of earlier-stage assets, including the TEAD inhibitor SW-682, which is expected to enter the clinic in the second quarter of 2024 for the treatment of Hippo pathway-driven cancers.
Financial Performance
For the full year 2023, SpringWorks reported annual revenue of $5.4 million and a net loss of $325.1 million. The company's annual operating cash flow was -$222.8 million, and its annual free cash flow was -$230.2 million. These financial results reflect the company's continued investment in its pipeline and commercial launch activities.
In the first quarter of 2024, SpringWorks generated $21 million in net product revenue from the sales of OGSIVEO, its first commercial product. This strong performance in the initial months of the OGSIVEO launch underscores the high unmet need for patients with desmoid tumors and the transformative benefits of the therapy. The company's total operating expenses increased in the first quarter of 2024 compared to the same period in 2023, driven by the commercial activities to support the U.S. launch of OGSIVEO.
As of March 31, 2024, SpringWorks had $573 million in cash, cash equivalents, and marketable securities, providing the company with a strong financial position to execute on its strategic priorities.
OGSIVEO Launch Execution
The successful launch of OGSIVEO in the United States has been a top priority for SpringWorks. In the first full quarter of commercialization, the company reported $21 million in net product revenue, demonstrating robust adoption and high demand from both physicians and patients.
SpringWorks has been intensely focused on delivering OGSIVEO as the first and only FDA-approved therapy for adult patients with desmoid tumors and establishing it as the new standard of care. The company's field team has been actively engaging with physicians across treatment sites, including sarcoma centers of excellence and community practices, to drive awareness and adoption of OGSIVEO.
The strong early performance of OGSIVEO has been driven by several factors, including:
1. High unmet need: Desmoid tumors are a rare and debilitating condition, and prior to the approval of OGSIVEO, patients had limited treatment options, often relying on suboptimal off-label therapies.
2. Broad reimbursement: OGSIVEO has been broadly reimbursed by payers, representing 98% of commercially covered lives, as well as by Medicare and Medicaid, enabling efficient patient access.
3. Positive physician feedback: Surveys of oncologists who have prescribed OGSIVEO have shown overwhelmingly positive feedback, with 98% indicating they are likely to use the therapy as a frontline treatment.
4. Rapid symptom relief: Patients prescribed OGSIVEO have reported quick reductions in pain levels, a key driver of the therapy's value proposition.
SpringWorks is focused on executing a three-pronged strategy to drive sustained growth for OGSIVEO, which includes:
1. Continuing to deepen prescribing at centers of excellence and other high-volume treatment sites 2. Expanding the breadth of prescribing to academic and community centers 3. Maintaining strong access for patients and supporting appropriate utilization
The company believes it has reached only a small proportion of the estimated 5,500 to 7,000 actively managed desmoid tumor patients in the United States and sees a significant opportunity to serve this patient population with OGSIVEO.
Mirdametinib for NF1-PN
SpringWorks' second lead program, mirdametinib, is a potentially best-in-class treatment for both children and adults with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN). In the first quarter of 2024, the company initiated a rolling NDA submission for mirdametinib based on the positive topline results from the Phase 2b RENEW trial, which demonstrated compelling antitumor activity and a favorable safety profile.
The RENEW trial enrolled both pediatric and adult patients with NF1-PN, a rare and debilitating tumor of the peripheral nerve sheath that can cause significant pain, disfigurement, and functional impairment. In the trial, mirdametinib showed unprecedented depth of response, with 52% of pediatric patients and 41% of adult patients achieving confirmed objective responses. Importantly, patients also experienced statistically significant improvements in pain, quality of life, and physical function.
NF1-PN is a devastating and lifelong disease that typically requires chronic therapy. SpringWorks believes mirdametinib's optimized dosing regimen, which includes a built-in treatment holiday and a convenient pediatric-friendly formulation, has the potential to enhance the patient experience and improve long-term compliance.
With no approved treatments currently available for adult patients with NF1-PN, SpringWorks is poised to potentially bring the first-in-class therapy to this large patient population. The company expects to complete its NDA submission for mirdametinib in the second quarter of 2024 and plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the second half of 2024.
Expanding the Pipeline
In addition to its lead programs, SpringWorks is advancing a broader pipeline of targeted oncology assets, including:
1. Nirogacestat in ovarian granulosa cell tumors: The company's Phase 2 trial in this rare and aggressive subtype of ovarian cancer is fully enrolled, with initial data expected in the second half of 2024.
2. Nirogacestat in multiple myeloma: SpringWorks is evaluating novel combination regimens of nirogacestat with BCMA-directed therapies, building on the clinical validation of nirogacestat's ability to potentiate these agents.
3. Mirdametinib in MAPK-mutant solid tumors: The company is exploring the use of mirdametinib, both as a monotherapy and in combination with other agents, in genetically defined solid tumors harboring MAPK pathway aberrations.
4. SW-682, a TEAD inhibitor: This novel, oral, pan-TEAD inhibitor is expected to enter the clinic in the second quarter of 2024 for the treatment of Hippo pathway-driven cancers.
SpringWorks' pipeline reflects the company's commitment to addressing unmet needs across rare diseases and oncology, leveraging its expertise in targeted therapies and precision medicine approaches.
Intellectual Property and Financial Position
SpringWorks has a robust intellectual property portfolio, with 21 FDA Orange Book-listed patents providing protection for OGSIVEO into 2043. The company also maintains a strong financial position, with $573 million in cash, cash equivalents, and marketable securities as of March 31, 2024, which is expected to fund its operations through profitability.
Risks and Outlook
While SpringWorks has made significant progress in advancing its pipeline and executing on the OGSIVEO launch, the company faces several risks, including the potential for clinical trial failures, regulatory setbacks, competition from other therapies, and the inherent challenges of commercializing novel treatments in rare disease and oncology markets.
Despite these risks, SpringWorks remains well-positioned for continued success. The company's focus on precision medicine, its differentiated portfolio of targeted therapies, and its strong execution across research, development, and commercialization have positioned it as a leader in the rare disease and oncology landscapes. With the successful launch of OGSIVEO, the anticipated approval of mirdametinib, and a robust pipeline of promising candidates, SpringWorks is poised to transform the lives of patients suffering from devastating diseases and deliver long-term value for its shareholders.