On August 4, 2022 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, 2022 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, AUG 4, 2022, View Source [SID1234617465]).
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"In the second quarter of 2022, we were very pleased to report positive data across each of our core focus areas of rare oncology, BCMA combinations in multiple myeloma, and biomarker-defined metastatic solid tumors, most notably the positive topline data from the Phase 3 DeFi trial as well as encouraging preliminary data from the study evaluating nirogacestat with low-dose belantamab mafodotin in patients with multiple myeloma," said Saqib Islam, Chief Executive Officer of SpringWorks. "The second half of 2022 will be focused on continued preparation for our first potential product launch, including submitting our NDA for nirogacestat in desmoid tumors and progressing the commercial preparations to serve patients with desmoid tumors while continuing to advance our diversified targeted oncology pipeline."
Recent Business Highlights and Upcoming Milestones
Rare Oncology
In May 2022, SpringWorks announced positive topline results from the Phase 3 DeFi trial evaluating nirogacestat in adult patients with progressing desmoid tumors. The DeFi trial met its primary endpoint of improving progression-free survival, or PFS, demonstrating a statistically significant improvement for nirogacestat over placebo, with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p < 0.001). In addition, the trial met all key secondary endpoints, with nirogacestat demonstrating statistically significant improvements as compared to placebo in objective response rate, and patient-reported outcomes. Nirogacestat was generally well tolerated with a manageable safety profile. Additional data are expected to be presented at a medical conference in the second half of 2022 and published in a peer-reviewed journal publication. In addition, SpringWorks plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second half of 2022, which will be reviewed under the FDA’s Real-Time Oncology Review (RTOR) program.
In June 2022, updated data from the National Cancer Institute, or NCI, sponsored Phase 2 study of nirogacestat in patients with progressing desmoid tumors were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Of the 16 evaluable patients, no disease progression has been observed for any patient while on study. The median time on treatment for all evaluable patients was 4.4 years (range 0.17-7.99 years) with 4/16 patients remaining on treatment over 7 years.
Dosing is ongoing in the Phase 2b ReNeu trial evaluating mirdametinib in adult and pediatric patients with NF1-associated plexiform neurofibromas (NF1-PN). As previously announced, this trial is fully enrolled.
Recruitment is ongoing in a Phase 1/2 clinical trial evaluating mirdametinib in children and young adults with low-grade glioma. Initial data from the first 11 patients treated across two initial dose levels during the Phase 1 dose escalation study were presented at the International Symposium on Pediatric Neuro-Oncology (ISPNO) 2022 meeting.
B-cell Maturation Antigen (BCMA) Combinations in Multiple Myeloma
SpringWorks continues to advance nirogacestat as a potential cornerstone of BCMA combination therapy across modalities in collaboration with eight industry leaders. Five studies are currently ongoing: nirogacestat + GSK’s belantamab mafodotin, nirogacestat + Allogene’s ALLO-715, nirogacestat + Janssen’s teclistamab, nirogacestat + Precision Biosciences’ PBCAR269A, and nirogacestat + Pfizer’s elranatamab; three additional studies are planned: nirogacestat + Seagen’s SEA-BCMA, nirogacestat + AbbVie’s ABBV-383, and nirogacestat + Regeneron’s REGN5458.
In June 2022, initial clinical data from the GSK-sponsored Phase 1/2 study evaluating nirogacestat in combination with low-dose belantamab mafodotin in patients with relapsed or refractory multiple myeloma were presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting. At the time of data cut-off, the objective response rate at low-dose (0.95 mg/kg) belantamab mafodotin plus nirogacestat across the dose escalation, or DE, and cohort expansion, or CE, arms was 38% in 24 patients, with 17% of patients achieving a very good partial response or better. An encouraging safety profile for the combination was observed, with Grade 3 ocular adverse events occurring in 1/14 (7%) patients in the CE cohort with the low-dose belantamab mafodotin plus nirogacestat combination compared to 7/14 patients (50%) in the belantamab mafodotin monotherapy arm, using the Keratopathy Visual Acuity, or KVA, ocular toxicity grading scale. The DE cohort utilized the CTCAE-5 ocular toxicity grading scale; the low-dose belantamab mafodotin plus nirogacestat combination demonstrated Grade 3 ocular adverse events in 2/10 (20%) patients. SpringWorks expects the next data cut from the randomized Phase 2 cohort expansion study to occur towards the end of 2022. In addition, new sub-studies will evaluate low-dose belantamab mafodotin and nirogacestat with lenalidomide/dexamethasone and pomalidomide/dexamethasone to support potential development in earlier lines of therapy.
In July 2022, SpringWorks entered into a co-supported collaborative study agreement with GSK and the Hellenic Society of Haematology to conduct a Phase 1/2 study to evaluate low-dose belantamab mafodotin and nirogacestat in combination with lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma patients. Evangelos Terpos, MD, PhD, Professor of Hematology in the Department of Clinical Therapeutics of the National & Kapodistrian University of Athens, School of Medicine, Athens, Greece will serve as the principal investigator of the study.
Biomarker-Defined Metastatic Solid Tumors
Initial clinical data from the BeiGene-sponsored Phase 1b/2 trial evaluating mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with RAS/RAF mutant and other MAPK pathway aberrant solid tumors were presented at a SpringWorks-sponsored R&D Day in June 2022. Clinical responses were observed across a range of MAPK-altered tumors during the dose escalation portion of the study and there was evidence of acceptable safety and tolerability with multiple patients exposed to the combination for more than two years. SpringWorks expects these data to be presented at a medical conference in the second half of 2022.
Initial clinical data from a Phase 1 trial evaluating BGB-3245, a selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene, in adult patients with RAF mutant solid tumors were presented at a SpringWorks-sponsored R&D Day in June 2022. Objective responses were seen in patients with BRAF, KRAS, and NRAS mutations, including in some patients who had exhausted standard of care therapeutic options, and the emerging safety profile of BGB-3245 is consistent with other MAPK pathway inhibitors. SpringWorks expects these data to be presented at a medical conference in the second half of 2022. BGB-3245 monotherapy is advancing into cohort expansion studies and SpringWorks expects to initiate a combination study of BGB-3245 and mirdametinib in the second half of 2022. To support the further advancement of BGB-3245, an additional equity financing in MapKure was completed in June 2022, which included participation from SpringWorks and BeiGene.
In July 2022, SpringWorks entered into a Cooperative Research and Development Agreement (CRADA) with the NCI Cancer Therapy Evaluation Program (CTEP) to collaborate on the non-clinical and clinical development of mirdametinib.
General Corporate
In July 2022, SpringWorks appointed Carlos Albán to its Board of Directors. Mr. Albán previously served as Vice Chairman and Chief Commercial Officer at AbbVie until his retirement last year and brings over 30 years of experience in global commercial strategy and operations.
Second Quarter 2022 Financial Results
Research and Development (R&D) Expenses: R&D expenses were $38.0 million for the second quarter, compared to $32.1 million for the comparable period of 2021. The increase in R&D expense was primarily attributable to 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, and an increase in external costs related to drug manufacturing, clinical trial and other research, partially offset by a decrease in licensing costs related to the nonrefundable upfront payment to KU Leuven and VIB for the in-licensing of the TEAD inhibitor program in May 2021.
General and Administrative (G&A) Expenses: G&A expenses were $31.0 million for the second quarter, compared to $14.9 million for the comparable period of 2021. The increase in G&A expense was primarily attributable to 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 as we continue to expand our operations to support the organization, and an increase in information technology costs and consulting and professional services, including legal, regulatory and compliance, as we continue to build new capabilities, including commercial.
Net Loss Attributable to Common Stockholders: SpringWorks reported net loss of $69.1 million, or $1.41 per share, for the second quarter of 2022. This compares to a net loss of $47.0 million, or $0.97 per share, for the comparable period of 2021.
Cash Position: Cash, cash equivalents and marketable securities were $334.5 million as of June 30, 2022.
COVID-19 Update
To date, the COVID-19 pandemic has had a relatively modest impact on SpringWorks’ business operations, in particular on SpringWorks’ clinical trial programs, and SpringWorks is undertaking considerable efforts to mitigate the various challenges presented by this crisis. For further details and descriptions of the risks associated with the COVID-19 pandemic, please see the Risk Factors in SpringWorks’ periodic filings with the Securities and Exchange Commission, or SEC, and refer to the Forward-Looking Statements section in this press release.