Scholar Rock Announces Publication of Preclinical Pharmacology, Pharmacokinetics, & Safety Profile of SRK-181 in the Internat...
March 22 2021 - 4:20PM
Business Wire
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
publication of preclinical development data for SRK-181 in the
peer-reviewed journal International Journal of Toxicology. SRK-181
is a product candidate that has been shown to be a potent and
highly specific inhibitor of latent growth factor-beta 1 (TGFβ1)
activation in preclinical studies. SRK-181 is being developed to
overcome primary resistance to checkpoint inhibitor therapy and is
currently being studied in the two-part DRAGON Phase 1 trial in
patients with locally advanced or metastatic solid tumors
exhibiting primary resistance to anti-PD-(L)1 therapy.
“This publication provides a comprehensive preclinical
assessment of the pharmacology, pharmacokinetics, and safety of
SRK-181, which support its evaluation in the DRAGON Phase 1 trial,”
said Gregory Carven, Ph.D., Chief Scientific Officer of Scholar
Rock. “The initial clinical response and safety data from the
DRAGON trial, which we anticipate by end of year, will provide an
early look into SRK-181’s safety and tolerability profile and the
potential for a specific inhibitor of latent TGFβ1 to overcome the
immune exclusion that we believe, for many patients, is responsible
for primary resistance to checkpoint inhibitor therapies.”
Targeting the TGFβ1 Pathway
Greater understanding of the role of TGFβ signaling in promoting
cancer progression has led to heightened interest in the
development of therapies that inhibit the TGFβ pathway. However,
most of the approaches to date have been non-selective and target
at least two of the three TGFβ isoforms, which may limit the
therapeutic window and potentially result in a lack of efficacy, an
unfavorable safety profile, or a combination of the two. Examples
of dose-limiting toxicities observed nonclinically for nonselective
anti-TGFβ therapies include cardiovascular abnormalities, skin
lesions, epithelial oral hyperplasia, and gingival bleeding.
Scholar Rock’s approach to targeting the TGFβ pathway is
fundamentally different. SRK-181 is a highly specific inhibitor of
the latent TGFβ1 isoform with minimal or no binding to latent
TGFβ2, latent TGFβ3, or any of the active TGFβ growth factors based
on in vitro studies. Based on preclinical evaluations of SRK-181’s
pharmacologic and safety profiles across multiple animal species,
SRK-181 may offer an improved safety profile and a wider
therapeutic window than non-selective TGFβ inhibitors.
About the Preclinical Data
The International Journal of Toxicology publication,
“Nonclinical Development of SRK-181: An Anti-latent TGFβ1
Monoclonal Antibody for the Treatment of Locally Advanced or
Metastatic Solid Tumors,” provides a comprehensive preclinical
assessment of the pharmacology, pharmacokinetics, and safety of
SRK-181. (Welsh et al., Int J. Tox, March 19, 2021). Key findings
include:
- Selective inhibition of latent TGFβ1 activation by SRK-181 was
shown to avoid dose-limiting toxicities associated with pan-TGFβ
inhibitors in preclinical pharmacology studies.
- In-vitro studies showed that SRK-181 had no effect on human
platelet aggregation, activation, or binding and that SRK-181 does
not trigger a proinflammatory cytokine response in peripheral blood
mononuclear cells (PBMC).
- Four-week toxicology study showed that weekly intravenous
administration of SRK-181 achieved sustained serum exposure and was
well-tolerated in rats and monkeys with no treatment-related
adverse findings.
- No observed adverse effect level (NOAEL) of 200 mg/kg and 300
mg/kg were achieved in rats and cynomolgus monkeys,
respectively.
- Preclinical pharmacologic and pharmacokinetics assessments
provided support for the dose-selection strategy for the ongoing
DRAGON Phase 1 trial in patients with solid tumors.
About SRK-181
SRK-181 is a 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 profiling 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. Scholar Rock believes SRK-181 has the potential to
overcome this immune cell exclusion and induce tumor regression
when administered in combination with anti-PD-(L)1 therapy. By
specifically targeting the latent TGFβ1 isoform, Scholar Rock
hypothesizes that SRK-181 can increase the therapeutic window by
potentially avoiding toxicities associated with non-selective TGFβ
inhibition. 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. 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
(https://www.linkedin.com/company/scholar-rock/).
Scholar Rock® is a registered trademark of Scholar Rock,
Inc.
Forward-Looking Statements
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 the
potential of SRK-181, Scholar Rock’s future expectations, plans and
prospects, including without limitation, Scholar Rock’s
expectations regarding its growth, strategy, progress and timing of
its clinical trials, the potential of its proprietary platform, and
its intellectual property protection. 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 possibility that data
from the DRAGON clinical trial will be inconsistent with the data
observed in preclinical studies, the data generated from Scholar
Rock’s nonclinical and preclinical studies and clinical trials,
competition from third parties that are developing products for
similar uses, Scholar Rock’s ability to obtain, maintain and
protect its intellectual property, Scholar Rock’s dependence on
third parties for development and manufacture of product candidates
including to supply any clinical trials, Scholar Rock’s ability to
manage expenses and to obtain additional funding when needed to
support its business activities and establish and maintain
strategic business alliances and new business initiatives, and the
impacts of public health pandemics such as COVID-19 on business
operations including its DRAGON clinical trial, as well as 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, 2020 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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version on businesswire.com: https://www.businesswire.com/news/home/20210322005778/en/
Scholar Rock Contacts: Investor Contact: Catherine
Hu chu@scholarrock.com Media Contact: Ariane Lovell Finn
Partners ariane.lovell@finnpartners.com 917-565-2204
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