SpringWorks Therapeutics Announces Presentation of Updated Interim Data from the Phase 2b ReNeu Trial at the 2021 Children’s Tumor Foundation NF Conference

SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, today announced that an update on the previously reported interim data from the first 20 adult patients enrolled in the ongoing Phase 2b ReNeu trial evaluating mirdametinib, an investigational MEK inhibitor being studied in adult and pediatric patients with NF1-associated plexiform neurofibromas (NF1-PN), was presented at the 2021 Children's Tumor Foundation NF Conference being held June 14-16, 2021. The data were presented by Christopher Moertel, M.D., Professor and Medical Director of the Pediatric Neuro-Oncology and Neurofibromatosis Programs at the University of Minnesota Medical School and Principal Investigator of the ReNeu trial.

In February 2021, SpringWorks reported results from the first 20 adult patients enrolled utilizing a January 22, 2021 data cutoff date and showed that 50% of these patients had achieved an objective response as assessed by blinded independent central review (BICR), that 80% remained on study, and that the median time on treatment for these patients was 10.1 cycles (approximately 10 months). The NF Conference presentation utilized a March 23, 2021 data cutoff date and showed durable efficacy in these same 20 patients, with the median time on treatment now having reached 13 cycles (approximately 12 months), the objective response rate remaining at 50%, and 80% of these patients still remain on study. Among these patients, there had been no further dose reductions as of the later data cutoff date and mirdametinib continued to be generally well tolerated, with the majority of treatment-related adverse events (TRAE) being Grade 1 or 2, with only one Grade 3 TRAE and no Grade 4 or 5 adverse events (AE) reported in these 20 patients.

"Plexiform neurofibromas are tumors that can cause serious disfigurement and significant pain," said Dr. Moertel. "These interim data from the ReNeu trial are promising for patients who are in need of new treatment options and the availability of a pediatric formulation of mirdametinib, along with a dosing schedule that does not require fasting, may also be meaningful for patients, many of whom are children and young adults that require long-term treatment in order to control tumor growth and its associated morbidities."

"We remain encouraged by these interim data, which reaffirm our belief that mirdametinib has the potential to be a best-in-class treatment for patients with NF1-PN," said Saqib Islam, Chief Executive Officer of SpringWorks. "The ReNeu trial is on track to complete enrollment in the second half of 2021 and we look forward to sharing additional updates as the trial progresses."

Interim Phase 2b Data from ReNeu Trial:

The interim Phase 2b ReNeu data set presented at the Children's Tumor Foundation NF Conference included the first 20 adult patients enrolled and utilized a March 23, 2021 data cutoff date. Objective responses were defined as a ≥ 20% reduction in target tumor volume measured by MRI and were assessed by BICR. Patients received mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose: 4mg twice daily) without regard to food on a 3 weeks-on, 1 week-off intermittent schedule, with patients being allowed to stay on therapy for up to 24 cycles (approximately two years). The median time on treatment for the 20 adult patients evaluated for this analysis was 13 cycles (approximately 12 months), with an initial efficacy assessment performed following cycle five and then every four cycles thereafter.

The preliminary efficacy and safety analysis presented showed:

• 10/20 (50%) of patients had achieved an objective response by BICR, seven of which have been confirmed at a subsequent scan.

• Responders had a median tumor volume reduction of 45%.

• 16/20 (80%) of these patients remained on study as of the data cutoff and only one patient required a dose reduction due to an AE. Reasons for discontinuation included one each of progressive disease, participant decision, AE (Grade 1 diarrhea), and a patient being unable to undergo required MRI imaging due to a titanium rod implant from non-treatment-related worsening of scoliosis.

• A generally well-tolerated safety profile. The majority of TRAEs were Grade 1 or 2; there was only one Grade 3 TRAE reported and no Grade 4 or 5 AEs reported in these 20 patients. The most common TRAEs were rash, nausea and diarrhea.

About the ReNeu Trial

The ReNeu trial is a multi-center, open-label Phase 2b trial evaluating the efficacy, safety, and tolerability of mirdametinib in patients two years of age and older with an inoperable NF1-associated PN causing significant morbidity. The study will enroll approximately 100 patients in the United States. Patients receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily, calculated based on body surface area) without regard to food. Mirdametinib is administered in a 3-week on, 1-week off dosing schedule.

The primary endpoint is objective response rate, defined as ≥ 20% reduction in target tumor volume as measured by MRI and assessed by BICR. Secondary endpoints include safety and tolerability measures, duration of response, and changes from baseline in patient reported outcomes.