- Dosing of patients with locally advanced or
metastatic solid tumors has commenced in the DRAGON Phase 1
clinical trial of SRK-181, a highly specific inhibitor of latent
TGFβ1 activation
- Update on dose escalation is expected in the
fourth quarter of 2020; clinical response and safety data
anticipated in 2021
Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical
company focused on the treatment of serious diseases in which
protein growth factors play a fundamental role, today announced the
initiation of patient dosing in the DRAGON Phase 1 dose escalation
and dose expansion clinical trial of SRK-181 in patients with
locally advanced or metastatic solid tumors. SRK-181 is a potent
and highly selective inhibitor of latent TGFβ1 activation and is
being developed to increase responses to immunotherapy by
overcoming primary resistance to anti-PD-1 or anti-PD-L1 antibody
therapy.
“Based on emerging evidence in the field from human and
preclinical data implicating TGFβ1 as a key culprit in primary
resistance to anti-PD-(L)1 therapy, we are excited to be
investigating a rational approach to combination immunotherapy,”
said Yung Chyung, M.D., Chief Medical Officer of Scholar Rock. “Our
team’s focus and determination to advance SRK-181 and this Phase 1
trial, particularly as the evolving COVID-19 pandemic has resulted
in various challenges, has been truly impressive. We remain
committed to our mission of developing important therapies for
patients and the initiation of dosing in this proof-of-concept
trial represents an important milestone for us and our TGFβ1
platform.”
DRAGON Phase 1 Proof-of-Concept
Trial
The DRAGON Phase 1 open-label, dose escalation and dose
expansion clinical trial is evaluating the safety, tolerability,
pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of
SRK-181 in adult patients with locally advanced or metastatic solid
tumors enrolled across multiple sites in the U.S. The two-part
trial consists of a dose escalation portion (Part A) for SRK-181 as
both a single agent and in combination with approved anti-PD-(L)1
therapy, followed by a dose expansion portion (Part B) evaluating
SRK-181 in combination with approved anti-PD-(L)1 therapy in
multiple tumor-specific cohorts. Intravenous (IV) SRK-181 is
administered every 3 weeks (Q3W) and additional dosing regimens may
be explored.
Due to the COVID-19 pandemic and the anticipated pace of
enrollment, Scholar Rock now plans to provide an update on dose
escalation of SRK-181 as a single agent as well as in combination
with anti-PD-(L)1 therapy in the fourth quarter of 2020. Clinical
response and safety data are anticipated in 2021. Timing of data
read-outs may be further impacted by COVID-19-related
disruptions.
Part A Dose Escalation: Part A of the Phase 1 trial
assesses SRK-181 both as a single agent and in combination with
approved anti-PD-(L)1 therapy and will be conducted in a staggered
fashion. The safety, PK, and activity of SRK-181 will be evaluated,
including effects upon biomarkers, such as CD8 T cell infiltration,
based on biopsies before and after treatment.
Part A1 evaluates SRK-181 as a single agent in patients with
locally advanced or metastatic solid tumors. The dose escalation
will follow a modified 3+3 design and assess doses starting at 80
mg up to 2400 mg (based on an average body weight of approximately
80 kg).
Part A2 evaluates SRK-181 in combination with anti-PD-(L)1
therapy in patients with locally advanced or metastatic solid
tumors that exhibit primary resistance to anti-PD-(L)1 antibodies.
Lack of response is characterized as either stable disease or
progressive disease following at least three cycles of treatment
with an approved anti-PD(L)1 therapy, either alone or in
combination with chemotherapy. Patients must have received their
most recent dose of anti-PD-(L)1 therapy within six months of
enrollment. In combination with SRK-181, patients will be treated
with the same anti-PD-(L)1 therapy that they had previously tried
and did not experience a response. The dose escalation will follow
a 3+3 design and assess doses up to 2400 mg.
Part B Dose Expansion: Part B of the trial consists of
multiple parallel cohorts to evaluate the anti-tumor activity of
SRK-181 in combination with anti-PD-(L)1 therapy. The target
indications are expected to include non-small cell lung cancer,
urothelial carcinoma, and cutaneous melanoma, amongst other solid
tumor types.
Each cohort will enroll up to 40 patients with locally advanced
or metastatic solid tumors for which anti-PD-(L)1 therapy is
approved and have demonstrated primary resistance, characterized as
a lack of response (stable or progressive disease) following at
least three cycles of treatment. Patients must have received their
most recent dose of anti-PD-(L)1 therapy within six months of
enrollment. Similar to Part A2, patients will be treated with
SRK-181 in combination with the same anti-PD-(L)1 therapy that they
had previously tried and did not experience a response.
About SRK-181
SRK-181 is a potent and highly selective inhibitor of TGFβ1
activation and is an investigational product candidate being
developed to overcome primary resistance to checkpoint inhibitor
therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant
TGFβ isoform expressed in many human tumors, particularly for those
tumors where checkpoint therapies are currently approved. Based on
analyses of human tumors that are resistant to anti-PD-(L)1
therapy, data suggests TGFβ1 is a key contributor to excluding
immune cell entry into the tumor microenvironment, thereby
preventing normal immune function. By overcoming this immune cell
exclusion, Scholar Rock believes SRK-181 has the potential to
induce tumor regression when administered in combination with
anti-PD-(L)1 therapy. A Phase 1 proof-of-concept clinical trial in
patients with locally advanced or metastatic solid tumors is
ongoing. The effectiveness and safety of SRK-181 have not been
established and SRK-181 has not been approved for any use by the
FDA or any other regulatory agency.
About Scholar Rock
Scholar Rock is a clinical-stage biopharmaceutical company
focused on the discovery and development of innovative medicines
for the treatment of serious diseases in which signaling by protein
growth factors plays a fundamental role. Scholar Rock is creating a
pipeline of novel product candidates with the potential to
transform the lives of patients suffering from a wide range of
serious diseases, including neuromuscular disorders, cancer,
fibrosis and anemia. The Company’s two lead product candidates
include SRK-015, a selective inhibitor of the activation of
myostatin, for the treatment of patients with Spinal Muscular
Atrophy and SRK-181, an isoform-selective inhibitor of TGFβ1
activation as a cancer immunotherapy in combination with
anti-PD(L)1 therapies. Scholar Rock’s approach to targeting the
molecular mechanisms of growth factor activation enabled it to
develop a proprietary platform for the discovery and development of
monoclonal antibodies that locally and selectively target these
signaling proteins at the cellular level. By developing product
candidates that act in the disease microenvironment, the Company
intends to avoid the historical challenges associated with
inhibiting growth factors for therapeutic effect. Scholar Rock
believes its focus on biologically validated growth factors may
facilitate a more efficient development path.
For more information, please visit www.ScholarRock.com or follow
Scholar Rock on Twitter @ScholarRock and LinkedIn.
Scholar Rock® is a registered trademark of Scholar Rock,
Inc.
Forward-Looking Statement
This press release contains "forward-looking statements" within
the meaning of the Private Securities Litigation Reform Act of
1995, including, but not limited to, statements regarding Scholar
Rock’s future expectations, plans and prospects, including without
limitation, expectations regarding the potential of Scholar Rock’s
platform, TGFβ programs and molecules and progress, timing and
design of its clinical trials, and the impact of COVID-19 on its
clinical trials and its business and operations in general. The use
of words such as “may,” “might,” “will,” “should,” “expect,”
“plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,”
“future,” “potential,” or “continue,” and other similar expressions
are intended to identify such forward-looking statements. All such
forward-looking statements are based on management's current
expectations of future events and are subject to a number of risks
and uncertainties that could cause actual results to differ
materially and adversely from those set forth in or implied by such
forward-looking statements. These risks and uncertainties include
the risks that preclinical data and results may not be predictive
of clinical results or the success of Scholar Rock’s platform and
those risks more fully discussed in the section entitled "Risk
Factors" in Scholar Rock’s Annual Report on Form 10-K for the year
ended December 31, 2019, as well as discussions of potential risks,
uncertainties, and other important factors in Scholar Rock’s
subsequent filings with the Securities and Exchange Commission. Any
forward-looking statements represent Scholar Rock’s views only as
of today and should not be relied upon as representing its views as
of any subsequent date. All information in this press release is as
of the date of the release, and Scholar Rock undertakes no duty to
update this information unless required by law.
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