SpringWorks Therapeutics Announces FDA Fast Track Designation for PD-0325901 for the Treatment of a Severe Form of Neurofibromatosis Type 1

STAMFORD, Conn.–(BUSINESS WIRE)–SpringWorks Therapeutics, Inc., a clinical-stage biopharmaceutical
company focused on developing life-changing medicines for patients with
severe rare diseases and cancer, today announced that the U.S. Food and
Drug Administration (FDA) has granted Fast Track designation for
PD-0325901, an investigational, oral, small molecule inhibitor of MEK1
and MEK2, for the treatment of patients ≥ 2 years of age with
neurofibromatosis type 1-associated inoperable plexiform neurofibromas
that are progressing or causing significant morbidity.

Neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) is
a rare genetic disorder characterized by mutations in the MAPK pathway,
leading to the growth of peripheral nerve sheath tumors that cause
significant pain, disfigurement and morbidity. NF1-PNs are most often
diagnosed in the first two decades of life and are characterized by
aggressive tumor growth, which is typically more rapid during childhood.^1-3
There are currently no therapies approved for the treatment of NF1-PN.

“The Fast Track designation recognizes that plexiform neurofibromas have
a substantial impact on the lives of patients, and that our MEK
inhibitor has the potential to address the significant needs faced by
this patient community who currently do not have an FDA-approved
treatment,” said Saqib Islam, Chief Executive Officer of SpringWorks
Therapeutics. “We look forward to continuing to work closely with the
FDA on our upcoming Phase 2b study, which will enroll pediatric and
adult NF1 patients with plexiform neurofibromas.”

The FDA’s Fast Track program is designed to expedite the development and
review of drugs with the potential to treat serious or life-threatening
conditions, and with nonclinical or clinical data that demonstrate the
potential to address unmet medical needs. Fast Track designation enables
a company to have frequent communication with the FDA throughout the
drug development and review process.⁴

In November 2018, the FDA granted Orphan Drug designation for PD-0325901
for the treatment of neurofibromatosis type 1. SpringWorks expects to
initiate a Phase 2b single-arm, open-label study of PD-0325901 in
pediatric and adult patients with NF1-PN in the third quarter of 2019.

About Neurofibromatosis Type 1
Neurofibromatosis type 1
(NF1) is a rare genetic disorder that is caused by mutations in the NF1
gene, and that affects both children and adults. Throughout their
lifetime, about 30 to 50 percent of NF1 patients progress to a more
severe form of the disease that results in the development of plexiform
neurofibromas (PN), which are progressive peripheral nerve sheath tumors
that cause severe pain, disfigurement, debilitating loss of range of
motion, and can significantly shorten lifespan.^1-3 The
clinical course of NF1-PN is heterogeneous with varying manifestations
and severity across patients.

It is estimated that NF1 affects 1 in 3,000 individuals worldwide, and
that there are approximately 100,000 patients in the United States
living with this disease.⁵ Most patients with NF1-PN are
treated with surgical removal of the tumors, sometimes requiring
amputation; however, surgery has variable success rates and a high rate
of recurrence has been observed because of the aggressive nature of
these tumors.⁶ There are no therapies currently approved for
the treatment of NF1-PN.

About PD-0325901

PD-0325901 is an oral small molecule inhibitor of MEK1 and MEK2. MEK
proteins occupy a pivotal position in the MAPK pathway, a key signaling
network that regulates cell growth and survival, and whose activity is
highly relevant in multiple oncology and rare disease indications.

PD-0325901 has been evaluated in several Phase 1 and Phase 2 clinical
trials, with over 200 subjects having been exposed to treatment. A Phase
2 trial conducted by the Neurofibromatosis Clinical Trial Consortium
evaluated PD-0325901 in 19 adolescent and adult patients with inoperable
and symptomatic or growing plexiform neurofibromas. Results demonstrated
an objective response in 42 percent of patients, prospectively defined
as having greater than or equal to 20 percent reduction in tumor volume
as measured by volumetric MRI. In the clinical trial, PD-0325901 given
at 2mg/m² on a 3-week on 1-week off schedule was generally
well-tolerated. The most commonly reported treatment-emergent grade 2 or
higher AEs were acneiform rash in 53% (10/19), fatigue in 26% (5/19) and
nausea in 21% (4/19) of patients.

SpringWorks is evaluating PD-0325901 as a monotherapy for the treatment
of patients with NF1-PN and is also pursuing PD-0325901 in combination
with other rational anti-cancer agents across a range of solid tumors.

About SpringWorks Therapeutics

At SpringWorks Therapeutics, a clinical-stage biopharmaceutical company,
we are driven to develop life-changing medicines for patients with
severe rare diseases and cancer. Since our launch in 2017, we have
worked to identify and advance promising science, beginning with our
licensed clinical therapies from Pfizer Inc. We pioneer efficient
pathways for drug development, leveraging shared-value partnerships with
patient advocacy groups, innovators in industry and academia, and
investors so that together, we can unlock the potential of science and
bring new therapies to underserved patients. Nirogacestat, our gamma
secretase inhibitor for the treatment of desmoid tumors is currently in
a Phase 3 clinical trial, and SpringWorks Therapeutics expects to
initiate a Phase 2b study of PD-0325901, our MEK 1/2 inhibitor for
neurofibromatosis type 1 patients with plexiform neurofibromas, in the
third quarter of 2019. PD-0325901 also holds promise as the backbone for
combination therapies to treat metastatic solid tumors. At SpringWorks
Therapeutics, we ignite the power of promising science to unleash new
possibilities for patients. For more information, please visit www.springworkstx.com.

References

¹ Plotkin, S. R., Bredella, M. A., Cai, W., Kassarjian, A.,
Harris, G. J., Esparza, S., Mautner, V. F. (2012). Quantitative
Assessment of Whole-Body Tumor Burden in Adult Patients with
Neurofibromatosis. PLoS ONE, 7(4). doi:10.1371/journal.pone.0035711.

² Rasmussen, S.A., & Friedman, J.M. (2000). NF1 Gene and
Neurofibromatosis 1. Am J Epidemiol. 2000 Jan 1;151(1):33-40.

³ Prada, C. E., Rangwala, F. A., Martin, L. J., Lovell, A.
M., Saal, H. M., Schorry, E. K., & Hopkin, R. J. (2012). Pediatric
Plexiform Neurofibromas: Impact on Morbidity and Mortality in
Neurofibromatosis Type 1. J Pediatr,160(3), 461-467.
doi:10.1016/j.jpeds.2011.08.051.

⁴ U.S. Food & Drug Administration. (2018). Fast Track.
Retrieved from https://www.fda.gov/ForPatients/Approvals/Fast/ucm405399.htm

⁵ Ferner, R.E. (2007). Neurofibromatosis 1 and
neurofibromatosis 2: a twenty first century perspective. Lancet Neurol:
6, 340-51. doi:10.1016/S1474-4422(07)70075-3.

⁶ Needle, M. N., Cnaan, A., Dattilo, J., Chatten, J.,
Phillips, P. C., Shochat, S., . . . Molloy, P. T. (1997). Prognostic
signs in the surgical management of plexiform neurofibroma: The
Children’s Hospital of Philadelphia experience, 1974-1994. J Pediatr,
131(5), 678-682. doi:10.1016/s0022-3476(97)70092-1.

Contacts

Kim Diamond
Vice President, Communications and Investor Relations
Phone:
646-661-1255
Email: [email protected]