Full Press Release Details
Edgewise Therapeutics Reports Third Quarter
2024 Financial Results and Recent Business Highlights
- On track to announce top-line results
from Phase 2 CANYON trial of sevasemten in adults with Becker in December 2024 -
- Advanced Phase 2 LYNX and FOX trials
of sevasemten in children and adolescents with Duchenne -
- Advanced Phase 2 CIRRUS-HCM trial of
EDG-7500 in patients with obstructive and non-obstructive Hypertrophic Cardiomyopathy (HCM) -
- Announced positive top-line data from
Phase 1 trial in healthy subjects and Phase 2 CIRRUS-HCM trial in patients with obstructive HCM -
Boulder, Colo., (November 7, 2024) - Edgewise
Therapeutics, Inc., (Nasdaq: EWTX), a leading muscle disease biopharmaceutical company, today reported financial results for the
third quarter of 2024 and recent business highlights.
"We continue to make strong progress on our cardiac and skeletal
muscle programs," said Kevin Koch, Ph.D., President and Chief Executive Officer of Edgewise. "Based on the strength of clinical
and preclinical data to-date, we are treating patients with obstructive and non-obstructive HCM in the 28-day part of CIRRUS-HCM trial.
We look forward to sharing important updates on both our CIRRUS-HCM and CANYON Phase 2 programs over the coming months."
Muscular Dystrophy Program / Sevasemten
Becker Muscular Dystrophy (Becker)
Sevasemten is an orally administered first-in-class fast skeletal myosin
inhibitor designed to protect unstable muscle against contraction-induced muscle damage in muscular dystrophies including Becker and Duchenne.
There are currently no approved therapies for individuals with Becker,
a serious genetic, progressive neuromuscular disorder with significant unmet need.
CANYON Phase 2 placebo-controlled trial in adults with Becker:
CANYON, the largest interventional Becker trial, includes 40 adults and 29 adolescents with a sevasemten treatment period of 12 months.
The primary endpoint of CANYON is change from baseline in creatine kinase (CK) over the treatment period with additional measures collected,
including North Star Ambulatory Assessment (NSAA), North Star Assessment for Muscular Dystrophies (NSAD), 100-meter timed test, biomarkers
of muscle damage, MRI and patient-reported outcomes. The Company expects to report CANYON data in December 2024.
GRAND CANYON, a global pivotal cohort in Becker: GRAND CANYON,
an expansion of the CANYON placebo-controlled trial, is a multi-center, randomized, double-blind, placebo-controlled cohort to evaluate
the safety and efficacy of sevasemten over 18 months in 120 adults with Becker. The primary endpoint of GRAND CANYON is change from baseline
in NSAA. In addition, other functional assessments, biomarkers of muscle damage, MRI, patient-reported outcomes and safety will be assessed.
Data from GRAND CANYON, if positive, could support a marketing application. To learn more, go to clinicaltrials.gov (NCT05291091)
or the GRAND CANYON microsite: https://www.beckergcstudy.com.
MESA Phase 2 open label extension trial in adults with Becker:
The Company is advancing MESA, an open-label extension trial to assess the long-term effect of sevasemten in individuals with Becker.
MESA provides continued access to sevasemten to participants who were previously enrolled in ARCH, or completed CANYON, GRAND CANYON,
or DUNE. To date, MESA has enrolled 99% of eligible participants completing these prior trials.
Duchenne Muscular Dystrophy (Duchenne)
LYNX Phase 2 trial in boys with Duchenne: LYNX is a 2-part multi-center,
dose-finding Phase 2 trial to evaluate the effect of sevasemten on safety, PK, and biomarkers of muscle damage in children aged 4 to 9
years with Duchenne treated with oral, once-daily sevasemten. The trial will also explore changes from baseline in functional measures
such as NSAA, stride velocity 95th centile (SV95C) and self-reported/caregiver-reported outcomes.
The Company plans to report LYNX data in the fourth quarter of 2024.
The Company will rely on LYNX data, along with data from the FOX trial of Duchenne children previously
treated with gene therapy, to guide the design and powering of a Phase 3 trial in Duchenne, planned to be initiated in 2025. For
more information on LYNX go to clinicaltrials.gov to learn more about this trial (NCT05540860).
FOX Phase 2 trial in boys with Duchenne (previously treated with
gene therapy): The Company is advancing FOX, a Phase 2 placebo-controlled trial to assess the effect of sevasemten over 12 weeks
on safety, PK and biomarkers of muscle damage in children and adolescents aged 6 to 17 years with Duchenne who have been previously treated
with gene therapy. The trial will also explore changes in baseline in functional measures such as NSAA, SV95C and self-reported/caregiver-reported
outcomes. There has been exceptional enthusiasm from the Duchenne community for this trial, evident in the Company's ability to
over-enroll the trial within two months. Go to clinicaltrials.gov to learn more about this trial (NCT06100887).
Cardiovascular Program / EDG-7500
EDG-7500 is a novel oral, selective, cardiac sarcomere modulator,
specifically designed to slow early contraction velocity and address impaired cardiac relaxation associated with HCM and other diseases
of diastolic dysfunction. Preclinical data in models of both obstructive and non-obstructive HCM suggest the ability to drive beneficial
responses with a low risk of decreasing left ventricular ejection fraction (LVEF) below normal. The Company is enrolling CIRRUS-HCM,
a four-part, multi-center, open-label trial, in approximately 55 patients with HCM at up to 20 clinical sites in the U.S. The primary
objective of Part A of the trial was to evaluate the safety and tolerability of a single oral dose of EDG-7500. Other key outcome
measures included pharmacokinetics (PK), LVEF, and resting and provocable left ventricular outflow tract (LVOT) gradient. Parts B and
C are evaluating safety and effects of multiple doses of EDG-7500 over 28 days in patients with obstructive or non-obstructive HCM. The
Company expects to report CIRRUS-HCM 28-day data in the first quarter of 2025. To learn more about CIRRUS-HCM, visit clinicaltrials.gov, NCT06347159
Phase 1 Trial of EDG-7500: During the quarter, the Company announced top-line
data of EDG-7500 from the Phase 1 trial in healthy subjects and the single-dose arm of the Phase 2 CIRRUS-HCM trial in patients with
obstructive HCM. In the placebo-controlled Phase 1 single ascending dose (SAD) trial (n=48), healthy subjects received single
doses of EDG-7500, ranging from 5 to 300 mg. In the multiple ascending dose (MAD) portion of the trial (n=24), healthy subjects received
25 to 100 mg once daily for 14 days. EDG-7500 was well tolerated in both the SAD and MAD; there were no clinically meaningful changes
or trends in vital signs, clinical chemistry, hematology, or electrocardiograms. There were no meaningful changes in LVEF for all SAD
and MAD subjects across a broad range of EDG-7500 exposures. In the MAD, a half-life of approximately 30 hours was observed, and steady
state was achieved in approximately 4 days after the start of once-daily dosing. Generally, dose proportional increases in exposure were
observed in both SAD and MAD.
Phase 2 CIRRUS-HCM trial of EDG-7500: In CIRRUS-HCM Part A,
patients with obstructive HCM received a single dose of 50, 100 or 200 mg of EDG-7500. A 67% mean reduction in resting LVOT pressure gradient
(LVOT-G) and a 55% mean reduction in provokable (Valsalva) LVOT-G were observed in patients receiving the 100 and 200 mg single doses.
LVOT gradients less than 30 mmHg at rest and less than 50 mmHg with Valsalva were each observed in 60% of patients receiving a single
dose of 100 or 200 mg of EDG-7500. Importantly, gradient reduction was achieved without a meaningful change in LVEF. Treatment with a
single dose of EDG-7500 also led to a 64% mean reduction in NT-proBNP, a key biomarker of heart failure, in the 200 mg cohort. This reduction
highlights the potential of our mechanism in the treatment of diseases of diastolic dysfunction, including non-obstructive HCM.
Across the Phase 1 and CIRRUS-HCM trials, no subjects had a meaningful
change to LVEF or a reduction to below 50% across a broad range of EDG-7500 exposures.
Strengthened Engagement with the Scientific and Patient Communities
The Company continued its education and outreach in the HCM and muscular
dystrophy medical and patient communities. Presentations were made at the HCM Society Scientific Sessions and the 29th International Annual
Congress of the World Muscle Society. The Company served in a leadership role at the Becker Education and Engagement Day (BEED) events
in the US and in Europe in September. These were the largest events of their kind for the Becker community. The Company continues to sponsor
and participate in numerous other clinician and patient-focused events.
Third Quarter Financial Results
Cash, cash equivalents and marketable securities were approximately
$492.5 million as of September 30, 2024.
Research and development (R&D) expenses were $32.2
million for the third quarter of 2024, compared to $30.7 million for the immediately preceding quarter. The increase of $1.5 million
was primarily driven by an additional $1.6 million in manufacturing expenses related to our sevasemten and EDG-7500 clinical trials and
research programs and $1.5 million higher personnel related costs primarily driven by stock based compensation, offset by a $1.6 million
decrease in clinical and clinical development activities for the EDG-7500 clinical programs related to the substantial completion
of Phase 1 trial in the second quarter 2024 and a $0.1 million decrease in professional fees and other research costs.
General and Administrative (G&A) expenses were $8.2
million for the third quarter of 2024, compared to $7.4 million for the immediately preceding quarter. The increase of $0.8 million was
driven by increased personnel-related costs primarily related to stock-based compensation.
Net loss and net loss per share for the third quarter of