- Promising objective response rates (ORR) were observed in
multiple tumor types in anti-PD-(L)1 resistant patients
- Analysis of baseline biomarker data in clear cell renal cell
carcinoma (ccRCC) patients reveals a doubling of the ORR
highlighting a potential patient selection strategy
- SRK-181 combination with pembrolizumab was generally well
tolerated
- Company holding conference call to discuss data with Dr. Toni
Choueiri on Tuesday, June 4th at 7 a.m. CDT/8 a.m. EST
Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical
company focused on advancing innovative treatments for spinal
muscular atrophy (SMA), cardiometabolic disorders, and other
serious diseases where protein growth factors play a fundamental
role, today announced encouraging data from its Phase 1 DRAGON
proof-of-concept trial of SRK-181, a selective inhibitor of latent
TGFβ1 activation, in combination with pembrolizumab in patients
with advanced solid tumors. The results show encouraging responses
in heavily pretreated and anti-PD-(L)1 resistant patients across
multiple tumor types. Data were shared in an oral presentation
during the American Society of Clinical Oncology (ASCO) Annual
Meeting on June 3 in Chicago.
“These new data from our SRK-181 program show promising response
to treatment with SRK-181 across multiple tumor types and represent
further evidence of the value of our highly selective TGFβ
platform,” said Jay Backstrom, M.D., MPH, President and Chief
Executive Officer of Scholar Rock. “The anti-tumor activity we
observed in heavily pretreated cancer patients, most notably in
ccRCC and melanoma gives us confidence that SRK-181 could be part
of a treatment strategy to overcome immune checkpoint
inhibitor-associated resistance. In addition, our new finding that
baseline CD8+ infiltration status and elevated baseline regulatory
T-cell levels in ccRCC correspond with the twofold increase in
response rate has the potential to inform a patient selection
strategy. We are very encouraged by these new data and are
committed to engaging with the FDA in an end of Phase 1 meeting,
while also continuing to evaluate opportunities to partner this
important program.”
Safety data continued to show SRK-181 was generally well
tolerated Safety data from all cohorts in the dose expansion
phase (Part B; n=78 patients; 1500 mg q3w) continued to show
SRK-181 was generally well tolerated when used in combination with
pembrolizumab. One Grade 4 treatment-related adverse event (AE) of
generalized dermatitis exfoliative was observed in one patient. No
Grade 5 treatment-related AEs occurred. The only treatment-related
serious adverse event related to SRK-181 or pembrolizumab that
occurred in at least 2% of patients was pemphigoid. The most common
AEs were rash, pruritis, fatigue, and diarrhea.
Data presented continues to provide objective evidence of
anti-tumor activity Encouraging responses were observed in
multiple tumor types, continuing to support proof-of-concept for
SRK-181. The response was assessed by principal investigators based
on RECIST 1.1 for patients across five cohorts: clear cell renal
cell carcinoma (ccRCC), head and neck squamous cell carcinoma
(HNSCC), melanoma (MEL), urothelial carcinoma (UC), and non-small
cell lung cancer (NSCLC). A summary of anti-tumor activity is
presented in the table below; results for NSCLC (n=11) are not
included because no response was observed.
Summary of Response Rate in Multiple Tumor
Types
ccRCC (n=30)
HNSCC (n=11)
MEL (n=11)
UC (n=11)
Objective response rate (ORR)
7 (23.3%)
2 (18.2%)
3 (27.3%)
1 (9.1%)
Durability of response (DoR);
median (range), months
7.7+ (2.5+, 20.9+)
2.2+ (0.1, 4.3+)
4.9 (1.8, 7.1)
12.9 (12.9, 12.9)
Biomarker findings continue to support proof of mechanism
Tumor infiltration by CD8+ T-cells was measured in multiple tumor
types for which paired biopsy samples (i.e., samples before and
after treatment for individual patients) were available. The
analysis included patients with ccRCC, melanoma, non-small cell
lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC)
or urothelial carcinoma (UC). In 6 out of 9 paired biopsies
analyzed, the combination of SRK-181 and pembrolizumab was
associated with an enhanced proinflammatory microenvironment, with
activated CD8+ T-cells in responding patients across multiple
cohorts and the number of activated T-cells correlating with tumor
shrinkage.
New biomarker findings in ccRCC could inform patient
selection strategy Notably, the baseline immune contexture
unique to ccRCC amongst the cohorts examined has been identified,
predictive of clinical response.
An analysis in ccRCC patients showed a positive correlation
between baseline CD8+ infiltration status and response rate, with
an increase in ORR from 23.3 to 40%, and an improvement in median
durability of response (mDoR) from 7.7 to 9.3 months if enrollment
had been limited to patients whose tumors were infiltrated by CD8+
T-cells at baseline.
In addition, an independent analysis showed a positive
correlation between elevated regulatory T-cell (Treg) levels in
ccRCC patients pre-treatment and response rate, with an increase in
ORR from 23.3 to 50% and improvement in mDoR from 7.7 to 9.8 months
if enrollment had been limited to patients whose tumors had
elevated Treg levels at baseline. Together, these results suggest
that baseline CD8+ status and Treg levels should be further
investigated as a potential future patient selection strategy,
aimed to predict ccRCC patients who are likely to respond to
SRK-181 and anti-PD-(L)1 combination therapy.
The presentation is available in the Publications & Posters
section of Scholar Rock’s website.
For conference information, visit
https://conferences.asco.org/.
Conference Call Information Scholar Rock will host a
conference call on June 4 at 8 a.m. EST that can be accessed
from Events and Presentations page of Scholar Rock’s website.
Members of Scholar Rock’s executive management team will be joined
by Dr. Toni Choueiri, M.D., Director of the Lank Center for
Genitourinary (GU) Oncology at Dana-Farber Cancer Institute (DFCI).
The audio of the conference call can be accessed by registering in
advance at the following link:
https://register.vevent.com/register/BIca0060fe57734207b3fc21ce38d84a63
About SRK-181 SRK-181 is a selective inhibitor of 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 that TGFβ1
is a key contributor to the immunosuppressive tumor
microenvironment, excluding and preventing entry of cytotoxic T
cells into the tumor, as well as suppressing T cell activity,
thereby inhibiting anti-tumor immunity.
SRK-181 specifically targets the latent TGFβ1 isoform in a
context-independent manner, designed to enable complete inhibition
of TGFβ1 in all compartments within the tumor microenvironment.
Scholar Rock believes that SRK-181 has the potential to overcome
this immunosuppressive tumor microenvironment and induce tumor
regression when administered in combination with anti-PD-(L)1
therapy while potentially avoiding toxicities associated with
non-selective TGFβ inhibition. Enrollment of the DRAGON Phase 1
proof-of-concept clinical trial (NCT04291079) was completed in
December 2023, and patients who remain on the study continue to be
treated. The trial enrolled patients in multiple proof of concept
cohorts conducted in parallel, including urothelial carcinoma (UC),
cutaneous melanoma (MEL), non-small cell lung cancer (NSCLC), head
and neck squamous cell carcinoma (HNSCC), 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.
About Scholar Rock
Scholar Rock is a biopharmaceutical company that discovers,
develops, and delivers life-changing therapies for people with
serious diseases that have high unmet need. As a global leader in
the biology of the transforming growth factor beta (TGFβ)
superfamily of cell proteins and named for the visual resemblance
of a scholar rock to protein structures, the clinical-stage company
is focused on advancing innovative treatments where protein growth
factors are fundamental. Over the past decade, Scholar Rock has
created a pipeline with the potential to advance the standard of
care for neuromuscular disease, cardiometabolic disorders, cancer,
and other conditions where growth factor-targeted drugs can play a
transformational role.
Scholar Rock is the only company to show clinical proof of
concept for a muscle-targeted treatment in spinal muscular atrophy
(SMA). This commitment to unlocking fundamentally different
therapeutic approaches is powered by broad application of a
proprietary platform, which has developed novel monoclonal
antibodies to modulate protein growth factors with extraordinary
selectivity. By harnessing cutting-edge science in disease spaces
that are historically under-addressed through traditional
therapies, Scholar Rock works every day to create new possibilities
for patients. Learn more about our approach at ScholarRock.com and
follow @ScholarRock and on LinkedIn.
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,
progress and timing of its clinical trials for SRK-181, and
indication selection and development timing, including the
therapeutic potential, clinical benefits and safety thereof,
expectations regarding timing, success and data announcements of
current ongoing clinical trials, 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, that preclinical and clinical data, including
the results from the Phase 1 clinical trial of SRK-181, are not
predictive of, may be inconsistent with, or more favorable than,
data generated from future or ongoing clinical trials of the same
product candidates; 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; information provided or decisions made by
regulatory authorities; 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, without limitation, to supply any
clinical trials; and 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; 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 March 31, 2024,
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/20240603004778/en/
Scholar Rock:
Investors Rushmie Nofsinger Scholar Rock
rnofsinger@scholarrock.com ir@scholarrock.com 857-259-5573
Media Molly MacLeod Scholar Rock mmacleod@scholarrock.com
media@scholarrock.com 802-579-5995
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