On August 2, 2023 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported second quarter financial results for the period ended June 30, 2023 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, AUG 2, 2023, View Source [SID1234633661]).

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"Our team continues to work with urgency and is ready to serve patients with desmoid tumors following the anticipated FDA approval of nirogacestat later this year," said Saqib Islam, Chief Executive Officer of SpringWorks. "We also believe that mirdametinib has the potential to be a best-in-class therapy for patients with NF1-PN and look forward to reporting topline data from our ReNeu trial in the fourth quarter while simultaneously advancing our portfolio of opportunities across our rare oncology, BCMA combinations in multiple myeloma, and biomarker-defined metastatic solid tumors programs."

Recent Business Highlights and Upcoming Milestones

Rare Oncology

In June 2023, SpringWorks announced that the U.S. Food and Drug Administration (FDA) has updated the Prescription Drug User Fee Act (PDUFA) action date for the New Drug Application (NDA) for nirogacestat for the treatment of adults with desmoid tumors to allow more time to review additional analyses of previously submitted data that had been provided by SpringWorks in response to the FDA’s information requests. No additional data or studies have been requested by the FDA at this time. The new PDUFA action date is November 27, 2023.
In June 2023, additional data from the Phase 3 DeFi trial assessing the impact of nirogacestat on pain, tumor volume, and T2 hypersensitivity in adults with desmoid tumors were presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Statistically significant and clinically meaningful reductions in pain were observed with nirogacestat compared with placebo at Cycle 10 across three prespecified pain assessment tools evaluated in DeFi. Reductions in pain were rapid, becoming evident as early as Cycle 2 (the first post-treatment timepoint evaluated), and these reductions were sustained through to the end of the double-blind phase of the trial. In addition, researchers presented data from the DeFi trial demonstrating that treatment with nirogacestat led to significantly improved median best change from baseline in MRI-assessed tumor volume of the largest target tumor compared with placebo. In addition, significant improvement in the median best percent change in T2 hyperintensity signal ratio of the largest target tumor compared with placebo was also observed with nirogacestat treatment.
In May 2023, SpringWorks announced full enrollment of the Phase 2 trial evaluating nirogacestat as a monotherapy in patients with recurrent ovarian granulosa cell tumors. SpringWorks expects to report initial data from the trial in 2024.
SpringWorks expects to present topline data from the pediatric and adult cohorts of the Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor, in NF1-associated plexiform neurofibromas (NF1-PN) in the fourth quarter of 2023. If these data are positive, SpringWorks plans to submit an NDA to the FDA for mirdametinib for the treatment of NF1-PN in the first half of 2024.
B-cell Maturation Antigen (BCMA) Combinations in Multiple Myeloma

SpringWorks continues to evaluate nirogacestat as part of several BCMA combination therapy regimens across treatment lines in collaboration with industry leaders.
In June 2023, updated clinical data from the Phase 1/2 study sponsored by GSK plc evaluating nirogacestat in combination with low-dose belamaf (belantamab mafodotin-blmf, GSK’s antibody-drug conjugate) in patients with relapsed or refractory multiple myeloma (RRMM) were presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Congress. These clinical data continue to support that combining nirogacestat with a low dose of belamaf may result in comparable efficacy to a higher monotherapy belamaf dose while simultaneously substantially reducing the frequency of high-grade ocular adverse events.
In June 2023, new data from the Phase 1b clinical trial sponsored by Janssen Research & Development, LLC (Janssen) evaluating nirogacestat in combination with teclistamab, Janssen’s bispecific antibody targeting BCMA and CD3, were presented at EHA (Free EHA Whitepaper), representing the first clinical data set of nirogacestat in combination with a BCMA bispecific agent. The results demonstrated that high and deep response rates were observed with the nirogacestat plus teclistamab combination across all dose levels assessed and the safety profile was optimized with delayed administration of lower-dose nirogacestat.
Biomarker-Defined Metastatic Solid Tumors

In April 2023, updated clinical data from the Phase 1b trial evaluating mirdametinib in combination with BeiGene’s investigational RAF dimer inhibitor, lifirafenib, in patients with advanced or refractory solid tumors with RAS mutations, RAF mutations and other MAPK pathway aberrations were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023. The combination showed antitumor activity in patients with various mutations across several solid tumor types and support the advancement of this combination into the dose-expansion portion of the study, which will evaluate the combination in patients with NRAS-mutated solid tumors. The expansion is expected to start in the second half of 2023.
In April 2023, updated clinical data from the Phase 1a/1b study of brimarafenib (BGB-3245), an investigational, selective RAF dimer inhibitor, in adult patients with advanced or refractory solid tumors harboring MAPK pathway aberrations were presented at AACR (Free AACR Whitepaper). Objective responders included patients with tumors harboring BRAF V600E that had progressed on prior BRAF/MEK inhibitors with or without checkpoint inhibitor treatment, BRAF Class II mutation, BRAF fusion, NRAS and KRAS mutations. These data supported the advancement of brimarafenib into the Phase 1b dose expansion portion of the study, which has been enrolling patients since October 2022 in defined cohorts.
Patients continue to be enrolled in the SpringWorks-sponsored Phase 1/2a combination study of brimarafenib and mirdametinib.
In April 2023, SpringWorks presented new preclinical data for SW-682, the Company’s TEAD inhibitor development candidate, at AACR (Free AACR Whitepaper). The data provide promising evidence of SW-682’s anti-tumor activity, a favorable pharmacokinetics profile and good tolerability in mice, and further support SpringWorks’ thesis that TEAD palmitoylation represents a rational point of intervention for Hippo-driven cancers. SpringWorks expects to file an Investigational New Drug Application for SW-682 in the fourth quarter of 2023.
Second Quarter 2023 Financial Results

Research and Development (R&D) Expenses: R&D expenses were $35.9 million for the second quarter, compared to $38.0 million for the comparable period of 2022. The decrease in R&D expenses was primarily attributable to a decrease in external costs related to drug manufacturing, clinical trials and other research, partially offset by an increase in internal costs driven by the growth in employee costs associated with increases in the number of personnel, including an increase in stock-based compensation expense.
General and Administrative (G&A) Expenses: G&A expenses were $47.0 million for the second quarter, compared to $31.0 million for the comparable period of 2022. The increase in G&A expenses was largely attributable to commercial readiness activities to support the U.S. launch of nirogacestat, if approved, for the treatment of adults with desmoid tumors. The increase in internal costs was attributable to the growth in employee costs associated with increases in the number of personnel, including an increase in stock-based compensation expense, driven by the growth of our commercial organization, which included establishing certain sales, marketing, and commercialization functions. The increase in consulting and professional services was also primarily attributable to commercial readiness activities as we expand the capabilities of the organization.
Net Loss Attributable to Common Stockholders: SpringWorks reported net loss of $77.9 million, or $1.25 per share, for the second quarter of 2023. This compares to a net loss of $69.1 million, or $1.41 per share, for the comparable period of 2022.
Cash Position: Cash, cash equivalents and marketable securities were $476.7 million as of June 30, 2023.