SpringWorks Therapeutics Announces Initiation of Phase 1b Clinical Trial of MEK Inhibitor PD-0325901 in Combination with BeiGene’s RAF Dimer Inhibitor Lifirafenib in Advanced or Refractory Solid Tumors

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 first patient
has been dosed in a Phase 1b study to evaluate the combination of
SpringWorks Therapeutics’ investigational MEK inhibitor, PD-0325901, and
BeiGene, Ltd.’s (Nasdaq: BGNE; HKEX: 06160) investigational RAF dimer
inhibitor, lifirafenib (BGB-283), in patients with advanced or
refractory solid tumors.

The Phase 1b clinical trial, being conducted by BeiGene, is an
open-label, dose-escalation and expansion study to investigate the
safety, pharmacokinetics (PK) and antitumor activity of PD-0325901 in
combination with lifirafenib in patients with advanced or refractory
solid tumors that harbor RAS mutations, RAF mutations and other MAPK
pathway aberrations. The trial is designed to define the dose and
tolerability of the combination as well as to capture early efficacy
signals to allow for rapid cohort expansion.

“We are excited to explore this combination therapy approach in
collaboration with BeiGene, as it could address the approximately
one-fourth of solid tumor patients whose cancers are driven by RAS
mutations, as well as those with RAF mutations and other MAPK pathway
aberrations, which occur in many of the most devastating tumor types,”
said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics.
“Despite decades of research, no anti-RAS therapies have been approved
to-date. This trial has the potential to meet a critical need for
patients and is an important evolution for SpringWorks as it provides
the opportunity to study our MEK inhibitor in patients with more
commonly occurring tumors.”

The rationale for the Phase 1b study is supported by data presented by
BeiGene at the 2015 Annual Meeting of the American Association for
Cancer Research (AACR)¹, which demonstrated that the
combination of PD-0325901 and lifirafenib led to antitumor activity in
preclinical models of RAS-mutated cancers. Vertical inhibition of the
MAPK pathway, enabled by the combination of a MEK inhibitor with a RAF
dimer inhibitor, has been further validated preclinically by multiple
academic and industry investigators, and has the potential to overcome
the drug resistance mechanisms that have impeded previous attempts to
develop therapies for tumors with MAPK mutations and aberrations.

In addition to this Phase 1b study, SpringWorks Therapeutics is
preparing to initiate a Phase 2b single-arm, open-label study of
PD-0325901 as a monotherapy in patients with neurofibromatosis type
1-associated plexiform neurofibromas (NF1-associated PN). NF1-associated
PN is a rare genetic disorder characterized by the growth of painful,
disfiguring and debilitating tumors along peripheral nerves throughout
the body.

About the Phase 1b Trial in Advanced or Refractory Solid Tumors

The Phase 1b trial is a multicenter, open label, dose-escalation trial
of PD-0325901 in combination with lifirafenib in adult patients with
advanced or metastatic, unresectable tumors harboring K-RAS/N-RAS or
B-RAF mutations, or any other MAPK pathway aberration. The study will
enroll patients who have experienced disease progression during or after
at least one line of systemic therapy or for which treatment is not
available, not tolerated or refused.

The trial is designed in two parts; the first part will consist of a
dose-escalation and dose-finding study to assess the safety and
tolerability of combining PD-0325901 and lifirafenib, and to determine
the maximum tolerated dose and/or the recommended Phase 2 dose for the
combination. The second part is a multiple-group, noncomparative,
indication expansion study to assess the preliminary antitumor activity
of the combination in patients with selected tumor types, in addition to
further assessing the safety, tolerability and PK of the combination.

The trial is being conducted under a global clinical collaboration
agreement between SpringWorks Therapeutics and BeiGene, which was
entered into in September 2018. Under the terms of the agreement,
BeiGene is responsible for administering the Phase 1b clinical trial,
with all costs of the clinical studies and governance responsibilities
to be shared equally among both parties. More information about the
study is available at www.clinicaltrials.gov
under the identifier NCT03905148.

About PD-0325901

PD-0325901 is an investigational, selective, orally bioavailable small
molecule inhibitor of MEK1 and MEK2, proteins that play key roles in the
MAPK pathway. The MAPK pathway is critical for cell survival and
proliferation, and overactivation of this pathway has been shown to help
enable tumor growth. By blocking activity of the MAPK pathway,
PD-0325901 may help arrest uncontrolled cellular growth associated with
many types of tumors.

PD-0325901 has been tested in several Phase 1 and Phase 2 clinical
trials, and approximately 260 subjects have been exposed to treatment.
SpringWorks is evaluating PD-0325901 as a monotherapy for the treatment
of patients with neurofibromatosis type 1-associated plexiform
neurofibromas and is also pursuing PD-0325901 in combination with other
rational anti-cancer agents across a range of solid tumors.

About Lifirafenib

Lifirafenib was discovered in BeiGene’s research facilities in Beijing,
China, and is an investigational small molecule kinase inhibitor with
RAF monomer and dimer inhibition activities. Lifirafenib has shown
antitumor activities in preclinical models and in cancer patients with
tumors harboring BRAF V600E mutations, non-V600E BRAF mutations,
non-small cell lung cancer and endometrial cancer harboring KRAS
mutations. To date, lifirafenib has been dosed in more than 150 patients
globally.

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. Two of our therapies will
be entering potentially pivotal studies this year: nirogacestat, a gamma
secretase inhibitor for the treatment of desmoid tumors, and PD-0325901,
a MEK 1/2 inhibitor for neurofibromatosis type 1 patients with plexiform
neurofibromas. 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 Yuan, X., Tang, Z., Du, R., et al. BGB-283 Effectively
Enhances MEK Inhibitor Induced Tumor Suppression in RAS Mutant Cancers.
Poster (Abstract 669) presented at the American Association for Cancer
Research Annual Meeting 2015.

Contacts

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