Scholar Rock Reports Preliminary Pharmacokinetic and Pharmacodynamic Data from TOPAZ Phase 2 Trial of SRK-015 for the Treatme...
November 19 2019 - 6:30AM
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 preliminary pharmacokinetic (PK) and
pharmacodynamic (PD) results from the TOPAZ Phase 2
proof-of-concept trial of SRK-015 for the treatment of patients
with spinal muscular atrophy (SMA). The planned preliminary
PK/PD analysis, which includes data from 29 patients with SMA
across all three cohorts, showed dose-proportional drug
exposure and demonstrated target engagement, as evidenced by
dose-dependent increases of up to 100-fold in the serum levels of
latent myostatin following SRK-015 treatment (2 mg/kg and 20 mg/kg
doses). SRK-015 is a highly selective inhibitor of the
precursor, or latent form, of myostatin, and was specifically
designed to avoid interactions with related targets such as
activins, GDF-11, or BMPs, to potentially improve the therapeutic
profile compared to traditional non-selective inhibitors.
“We are pleased with the progress we have made to date towards
our goal of developing SRK-015 as a muscle-directed therapy to
address the functional deficits that remain a significant unmet
need for patients with SMA despite advancements with SMN
upregulators,” said Yung Chyung, M.D., Chief Medical Officer
of Scholar Rock. “These preliminary PK/PD results positively
address two important questions for the program by both confirming
the presence of latent myostatin in patients with SMA and further
corroborating the ability of SRK-015 to engage this drug target,
including in pediatric patients with SMA.”
“These results represent a key milestone for Scholar Rock by
showing that we can indeed bring together cutting-edge monoclonal
antibody technology with deep structural biology insights to target
latent forms of growth factors in the context of human disease,”
said Nagesh Mahanthappa, Ph.D., President and CEO of Scholar
Rock. “We look forward to building upon these insights as we
advance a growing portfolio of product candidates.”
TOPAZ Phase 2 Preliminary PK/PD ResultsThe
Phase 2 proof-of-concept trial is evaluating the safety and
efficacy of SRK-015 dosed intravenously every four weeks (Q4W) over
a 12-month treatment period. The trial is anticipated to
enroll approximately 55 patients with Type 2 or Type 3 SMA in the
U.S. and Europe across three distinct cohorts.
Patients in Cohorts 1 and 2 are being treated with 20 mg/kg of
SRK-015 Q4W and patients in Cohort 3 are randomized to either 20
mg/kg or 2 mg/kg Q4W. The primary objectives of the cohorts
are to assess safety and clinically meaningful motor functional
outcomes, such as the Revised Hammersmith Scale (RHS) and the
Hammersmith Functional Motor Scale Expanded (HFMSE). The
TOPAZ trial is ongoing and further details about the trial can be
found on clinicaltrials.gov.
The preliminary PK/PD analysis of the TOPAZ trial includes data
from 29 patients across the three cohorts; 12 patients in Cohort 1,
eight patients in Cohort 2, and nine patients in Cohort 3. These
patients had received one dose of SRK-015 and were evaluated for
four weeks as of the data cutoff. The preliminary results are as
follows:
- Dose-dependent increases of up to 100-fold in serum latent
myostatin levels following treatment with SRK-015 (2 mg/kg and 20
mg/kg doses) confirms the presence of latent myostatin in patients
with SMA and demonstrates robust target engagement.
- Fold-increases from baseline in serum latent myostatin levels
in the first four weeks following SRK-015 treatment were comparable
between SMA patients in the TOPAZ trial and healthy adult
volunteers in the Phase 1 trial.
- In patients with SMA, SRK-015 displayed a preliminary PK
profile exhibiting dose proportionality and low variability,
consistent with PK observations from the Phase 1 trial in healthy
adult volunteers.
- No clinically significant safety signals had been observed as
of the data cutoff for this preliminary PK/PD analysis.
An interim efficacy and safety analysis is planned, encompassing
a subset of patients with at least six months of treatment
exposure. The interim results are expected in the first half of
2020 with top-line results for the full 12-month treatment period
expected starting in the fourth quarter of 2020 and through the
first quarter of 2021.
About SRK-015 SRK-015 is a selective
inhibitor of the activation of myostatin and is an investigational
product candidate for the treatment of patients with spinal
muscular atrophy (SMA). Myostatin, a member of the TGFβ
superfamily of growth factors, is expressed primarily by skeletal
muscle cells and the absence of its gene is associated with an
increase in muscle mass and strength in multiple animal
species. Scholar Rock believes the inhibition of the
activation of myostatin with SRK-015 may promote a clinically
meaningful increase in muscle strength. A Phase 2 clinical
trial in patients with Type 2 and Type 3 SMA is ongoing. The
U.S. Food and Drug Administration (FDA) has granted Orphan Drug
Designation (ODD), and the European Commission (EC) has
granted Orphan Medicinal Product Designation, to SRK-015 for the
treatment of SMA. The effectiveness and safety of SRK-015
have not been established and SRK-015 has not been approved for any
use by the FDA or any other regulatory agency.
About SMA Spinal muscular atrophy (SMA) is a
rare, and often fatal, genetic disorder that typically manifests in
young children. An estimated 30,000 to 35,000 patients are
afflicted with SMA in the United States and Europe.
It is characterized by the loss of motor neurons, atrophy of the
voluntary muscles of the limbs and trunk and progressive muscle
weakness. The underlying pathology of SMA is caused by insufficient
production of the SMN (survival of motor neuron) protein, essential
for the survival of motor neurons, and is encoded by two genes,
SMN1 and SMN2. While there has been progress in the
development of therapeutics that address the underlying SMA genetic
defect, there continues to be a high unmet need for therapeutics
that directly address muscle atrophy.
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 antibodies. 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.
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 future expectations, plans and
prospects, including without limitation, expectations regarding the
potential of SRK-015 as a therapy in SMA and the timeline for and
progress in developing SRK-015. 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 earlier
preclinical and clinical data and testing of SRK-015 may not be
predictive of the results or success of clinical trials, interim
clinical trial results will differ from final clinical trial
results, the development of SRK-015 will take longer and/or cost
more than planned, SRK-015 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, 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.
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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