- All doses were generally well tolerated, no
dose limiting toxicities observed including at the Part B dose of
1500 mg
- Biomarker data consistent with target
engagement
- Two confirmed partial responses observed in
patients with anti-PD-1 resistant clear cell renal cell
carcinoma
- Enrollment of DRAGON Part B continues to
progress
Scholar Rock (NASDAQ: SRRK), a Phase 3, clinical-stage
biopharmaceutical company focused on the treatment of serious
diseases in which protein growth factors play a fundamental role,
today announced early data from its Phase 1 DRAGON proof-of-concept
trial of SRK-181, a selective inhibitor of latent TGFβ1 activation
being developed with the aim of overcoming resistance to checkpoint
therapy in patients with advanced cancer. The data were shared in a
poster presentation during the Society for Immunotherapy of
Cancer's (SITC) 37th Annual Meeting & Pre-Conference being held
November 8-12 in Boston.
“Resistance to checkpoint inhibitor therapy remains a
significant challenge in the treatment of advanced cancer. The
DRAGON trial is investigating our novel TGFβ1 selective monoclonal
antibody, SRK-181, which was designed to address this challenge
based on the strong, scientific rationale that TGFβ1 is a driving
mechanism of resistance to checkpoint inhibitors. Our preclinical
work suggests that SRK-181 may overcome this resistance and avoid
the cardiotoxicities that have limited other non-selective
approaches,” said Jay Backstrom, M.D., M.P.H., President and Chief
Executive Officer of Scholar Rock. “These early DRAGON findings of
safety, target engagement and indications of efficacy support our
conviction around Scholar Rock’s differentiated approach and the
potential role that SRK-181 may play in addressing the existing
treatment hurdles. We are excited to continue advancing DRAGON and
look forward to sharing additional data next year.”
Data continue to show SRK-181 is generally well tolerated
Safety data from the dose escalation portion of the trial (Part A)
continue to show SRK-181 is generally well tolerated when used
alone or in combination with anti-PD-(L)1 checkpoint inhibitor
therapy. No dose-limiting toxicities were observed in patients
receiving SRK-181 as monotherapy (Part A1) when dosed up to 3000 mg
once every three weeks (q3w) or 2000 mg once every two weeks (q2w),
or in patients receiving SRK-181 in combination with checkpoint
inhibitor therapy (Part A2) when dosed up to 2400 mg q3w. All dose
levels were generally well tolerated, including the recommended
SRK-181 dose of 1500 mg q3w or 1000 mg q2w in combination with
anti‑PD-(L)1 for the dose expansion portion of the trial (Part
B).
No Grade 4 or 5 treatment-related AEs occurred.
Treatment-related Grade 3 adverse events were increased levels of
alanine aminotransferase (one patient in Part A1); pruritus (two
patients in Part A2), blister, immune-mediated lung disease, rash
and rash maculo-papular (one patient each in Part A2). A
treatment-related serious adverse event of elevated troponin I (one
patient) was observed in Part A1; blister, pruritus, and rash (all
in one patient) and immune-mediated lung disease (one patient) were
observed in Part A2.
Early indications of efficacy The response was assessed
by principal investigators based on RECIST 1.1. Partial response
(“PR”) is defined as at least a 30% tumor reduction. As of the data
cut-off date (August 29, 2022), 15 patients were enrolled in Part
A2 with the following results:
- One confirmed PR in a patient with anti-PD-1 resistant clear
cell renal cell carcinoma at 800mg in Part A2 of the trial who
remained in the study for 30 weeks.
- One ongoing patient in the 2400 mg dose group of Part A2 with
head and neck cancer experienced a 29.4% tumor reduction.
- Nine patients experienced a best response of stable disease.
This included six patients whose disease progressed prior to the
trial and were stable beyond the 16-week cutoff.
As of the data cut-off date, 14 patients were enrolled in Part
B. One ongoing patient with anti-PD-1 resistant clear cell renal
cell carcinoma had a confirmed PR.
Biomarker data from Part A consistent with target
engagement The biomarker strategy for DRAGON explores early
signs of SRK-181 activity, including target engagement and pathway
modulation. It includes measuring effects on both circulating and
tumor immune contexture, such as CD8+ T cell infiltration and
reductions in myeloid-derived suppressor cell (MDSC) populations,
as well as analysis of TGFβ-related pathway signaling.
Following treatment with SRK-181 in Part A, circulatory TGFβ1
levels increased in all dose groups. Given the small number of
participants in each dosing cohort, dose-dependent increases in
circulatory TGFβ1 levels were not apparent. These findings are
consistent with preclinical results from a mouse tumor model
(MBT-2) that suggest circulatory TGFβ1 may be a potential
pharmacodynamic biomarker of SRK-181. Combination treatment with
anti-PD-(L)1 therapy also appears to have similar circulatory TGFβ1
levels as monotherapy.
“At this early stage, the biomarker findings are consistent with
the circulating TGFβ1 levels observed in our preclinical studies.
We also saw target engagement accompanied by robust efficacy
measured through MDSC levels as PD biomarker and immune
infiltration into tumors and tumor regression in our preclinical
studies,” said Mo Qatanani, Senior Vice President, Research. “We
are excited to generate further biomarker analyses from DRAGON,
including MDSC levels to reflect PD activity and present them at
future scientific meetings.”
The poster will be made available in the Publications &
Posters section of Scholar Rock’s website following the
conference.
For conference information, visit
https://www.sitcancer.org/2022/home
About SRK-181 SRK-181 is a selective inhibitor of latent
TGFβ1 activation being developed to overcome primary resistance to
checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies, in
advanced cancer. TGFβ1 is the predominant TGFβ isoform expressed in
many human tumor types. Based on analyses of various human tumors
that are resistant to anti-PD-(L)1 therapy, data suggest TGFβ1 is a
key contributor to the immunosuppressive tumor microenvironment,
excluding and preventing entry of cytotoxic T cells into the tumor,
thereby inhibiting anti-tumor immunity. (1) Scholar Rock believes
SRK-181, which specifically targets the latent TGFβ1 isoform, has
the potential to overcome this immune cell exclusion and induce
tumor regression when administered in combination with anti-PD-(L)1
therapy while potentially avoiding toxicities associated with
non-selective TGFβ inhibition. The DRAGON Phase 1 proof-of-concept
clinical trial (NCT04291079) in patients with locally advanced or
metastatic solid tumors is ongoing. The trial is currently
enrolling and dosing patients in multiple proof of concept cohorts
conducted in parallel, including urothelial carcinoma (UC),
cutaneous melanoma (MEL), non-small cell lung cancer (NSCLC) and
clear cell renal cell carcinoma (ccRCC). SRK-181 is an
investigational product candidate and its efficacy and safety have
not been established. SRK-181 has not been approved for any use by
the FDA or any other regulatory agency.
(1) Martin et al., Sci. Transl. Med. 12: 25 March 2020
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, and fibrosis. 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/).
Availability of Other Information About Scholar Rock
Investors and others should note that we communicate with our
investors and the public using our company website
www.scholarrock.com, including, but not limited to, company
disclosures, investor presentations and FAQs, Securities and
Exchange Commission filings, press releases, public conference call
transcripts, and webcast transcripts, as well as on Twitter and
LinkedIn. The information that we post on our website or on Twitter
or LinkedIn could be deemed to be material information. As a
result, we encourage investors, the media and others interested to
review the information that we post there on a regular basis. The
contents of our website or social media shall not be deemed
incorporated by reference in any filing under the Securities Act of
1933, as amended.
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 Scholar Rock’s future
expectations, plans and prospects, including without limitation,
Scholar Rock’s expectations regarding its growth, strategy, and
progress and indication selection and development timing, the
ability of any product candidate to perform in humans in a manner
consistent with earlier nonclinical, preclinical or clinical trial
data, and the potential of its product candidates and proprietary
platform. The use of words such as “may,” “might,” “could,” “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, without limitation, Scholar Rock’s
ability to provide the financial support, resources and expertise
necessary to identify and develop product candidates on the
expected timeline, the data generated from Scholar Rock’s
nonclinical and preclinical studies and clinical trials, and
Scholar Rock’s ability to manage expenses and to obtain additional
funding when needed to support its business activities, as well as
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 June 30, 2022, 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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Scholar Rock: Investors Rushmie Nofsinger Scholar Rock
rnofsinger@scholarrock.com ir@scholarrock.com 857-259-5573 Media
Ariane Lovell Finn Partners ariane.lovell@finnpartners.com
media@scholarrock.com 917-565-2204
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