Scholar Rock to Develop Cancer Immunotherapy Product Candidate, SRK-181, a Selective Inhibitor of TGFβ1 Activation, to Overc...
13 March 2019 - 7:30AM
Selective inhibition of TGFβ1 activation enables immune cell
entry into the tumor microenvironment in preclinical models,
demonstrating potential for overcoming a key mechanism of primary
resistance to cancer immunotherapies
Scholar Rock Holding Corporation (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 that it has selected SRK‑181, a highly
specific inhibitor of TGFβ1 activation, as the first product
candidate in its TGFβ1 cancer immunotherapy program based on the
strength of its preclinical data and human translational insights.
Scholar Rock has initiated manufacturing and is progressing
preclinical development efforts with plans to initiate a Phase 1
trial in patients with solid tumors in mid- 2020.
“Given that a majority of cancer patients fail to respond to
checkpoint blockade therapies, we are eager to advance the next
product candidate from our pipeline of growth factor modulators to
potentially address a key mechanism of pre-existing resistance,”
said Nagesh Mahanthappa, Ph.D., President and CEO of Scholar Rock.
“A growing body of evidence strongly implicates elevated
TGFβ1 activity as a cause of immunotherapy failure, and we see
tremendous potential for SRK-181 to expand the number of patients
who could benefit from checkpoint blockade therapies by potently
and selectively inhibiting the activation of TGFβ1.”
SRK-181 is a fully human antibody designed to bind to, and
prevent the activation of, latent TGFβ1 with high affinity and high
selectivity, as evidenced by minimal or no binding to latent TGFβ2
and latent TGFβ3 isoforms. Several important factors led to
the decision to advance SRK-181 as a clinical development product
candidate for the treatment of tumors resistant to checkpoint
blockade therapies (CBTs), such as anti-PD1 antibodies. These
factors include:
- TGFβ signaling has been implicated as a culprit in primary
resistance to CBTs in multiple peer-reviewed studies.
- Translational data analyses by Scholar Rock highlight the
prominent expression of TGFβ1 in many human tumor types, such as
bladder cancer, non-small cell lung cancer and melanoma, for which
CBTs have either been approved or demonstrated clinical activity in
trials.
- Clinical correlation and preclinical model data suggest that
TGFβ1 excludes effector cell entry into the tumor, thereby limiting
immune system access to tumor cells.
- Preclinical studies in syngeneic mouse tumor models resistant
to CBT show SRK-181-mIgG1 (the murine version of SRK-181), when
combined with anti-PD1 antibodies, permitted effector T cell
infiltration and expansion into the tumor microenvironment and led
to tumor regression or control as well as significant survival
benefit.
- A 28-day pilot toxicology study of SRK-181 in adult rats showed
no observed drug-related toxicity up to a weekly dose of 100 mg/kg
for 4 weeks.
Detailed preclinical results for SRK-181-mIgG1 (formerly
referred to as SRTβ1-Ab3) were presented at the Society for
Immunotherapy of Cancer (SITC) 33rd Annual Meeting in November
2018. The poster presented at SITC can be accessed by
visiting the Scholar Rock website at
http://www.scholarrock.com/platform/publications/. Additional
preclinical data for SRK-181-mIgG1 will be presented at the 2019
American Association for Cancer Research Annual Meeting scheduled
to take place March 29 to April 3, 2019 in Atlanta, GA.
About SRK-181SRK-181 is a highly specific
inhibitor of TGFβ1 activation being developed to overcome primary
resistance to checkpoint blockade therapies (CBTs). 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 CBT, TGFβ1 is implicated as a key contributor to
exclude immune cell entry into the tumor microenvironment, thereby
preventing normal immune function. By overcoming this immune
cell exclusion, SRK-181 has the potential to induce tumor
regression when administered in conjunction with CBT.
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 newly elucidated
understanding of 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 StatementsThis 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,
Scholar Rock’s expectations regarding the potential of SRK-181 in
cancer immunotherapy and the timeline for and progress in
developing SRK-181. 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 testing of SRK-181 may not be predictive of the results or
success of clinical trials, the development of SRK-181 will take
longer and/or cost more than planned, SRK-181 will not receive
regulatory approval and those risks more fully discussed in the
section entitled "Risk Factors" in Scholar Rock’s Quarterly Report
on Form 10-Q for the quarter ended September 30, 2018, 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.
Scholar Rock Contact:
Investors/Media
Catherine Hu
chu@scholarrock.com
917-601-1649
Media Contact:
The Yates Network
Kathryn Morris
kathryn@theyatesnetwork.com
914-204-6412
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