Keros Therapeutics, Inc. (“Keros”) (Nasdaq: KROS), a clinical-stage
biopharmaceutical company focused on developing and commercializing
novel therapeutics to treat a wide range of patients with disorders
that are linked to dysfunctional signaling of the transforming
growth factor-beta (“TGF-ß”) family of proteins, today announced
results from preclinical studies evaluating the treatment effect of
a research form of KER-065 (“RKER-065”) in a mouse model of
Duchenne muscular dystrophy (“DMD”) and in prednisolone-treated
mice, which were presented at the 28th International Annual
Congress of the World Muscle Society (“WMS”) on Wednesday, October
4, 2023.
“We are pleased to present promising preclinical data from our
KER-065 program at WMS this year, showing that treatment with
RKER-065 led to a robust increase in muscle mass, muscle function
and bone mass in a mouse model of DMD and in prednisolone-treated
mice,” said Jasbir S. Seehra, Ph.D., President and Chief Executive
Officer of Keros. “We believe these data support the potential of
KER-065 to treat multiple pathophysiologies of DMD and other
neuromuscular diseases, and we look forward to commencing a Phase 1
clinical trial of KER-065 in healthy volunteers in the first
quarter of 2024.”
RKER-065 treatment led to a robust increase in muscle
mass, functional strength, and bone formation in a DMD mouse
model
- RKER-065 ameliorated
muscle and bone loss in a progressive murine model of Duchenne
muscular dystrophy
Keros studied the effect of RKER-065 in a progressive and
phenotypically severe DMD mouse model. DMD mice were dosed with
vehicle or 10 mg/kg of RKER-065 once weekly for four or six weeks.
A cohort of healthy mice received only vehicle.
In DMD mice, treatment with RKER-065 led to significant
increases in body weight and lean mass by four weeks compared to
vehicle-treated DMD mice. Additionally, an increase in forelimb
grip strength was observed, which is supportive of improved muscle
function. DMD mice treated with RKER-065 demonstrated significant
increases in muscle mass in the pectoralis and tibialis anterior
(“TA”) as compared to vehicle-treated DMD mice. In addition,
expression of utrophin, a functional analog of dystrophin, was
higher in the TA of DMD mice treated with RKER-065 compared to
vehicle-treated DMD mice.
Concomitant with neuromuscular decline, vehicle-treated DMD mice
had significant decreases in bone mineral density (“BMD”), while
DMD mice treated with RKER-065 showed no significant difference
compared to healthy adult mice. RKER-065 treatment led to a
significant increase in trabecular bone volume fraction by six
weeks as compared to vehicle-treated DMD mice and a significant
increase in trabecular thickness as compared to healthy mice. The
RKER-065-treated DMD mice also had a significant decrease in
trabecular spacing and a significant increase in trabecular number
compared to both healthy mice and vehicle-treated DMD mice.
Overall, treatment with RKER-065 led to a robust increase in
muscle mass, functional strength and bone formation in the DMD
mouse model. These studies suggest that KER-065 has the potential
to benefit DMD patients who suffer from severe muscle loss and
impaired muscle function and are at higher risk of fractures.
RKER-065 increased muscle mass, improved muscle function
and prevented bone loss in prednisolone-treated mice
- RKER-065, a novel
ActRII ligand trap, counteracted the negative impact of
glucocorticoid treatment on bone and muscle in mice
In order to evaluate if RKER-065 can prevent the negative effect
of glucocorticoids, the standard of care for DMD, on bone and
muscle mass function, Keros treated healthy mice, divided into two
groups matched by body weight, with 5.0 mg/kg prednisolone daily
(“Pred”) and 10.0 mg/kg of RKER-065 weekly (“Pred-RKER-065”) or
Pred daily and vehicle weekly (“Pred-vehicle”) for 9 weeks. A
cohort of vehicle-treated mice were fed daily with cherry
syrup.
The Pred-vehicle mice exhibited reduced weight gain relative to
vehicle – which is consistent with the use of glucocorticoid
treatment – while weight gain was maintained in
Pred-RKER-065-treated mice. The Pred-vehicle mice also exhibited
reduced lean mass gain relative to vehicle, while
Pred-RKER-065-treated mice had a robust increase in lean mass
compared to Pred-vehicle mice. The observed increase in lean mass
in the Pred-RKER-065 mice was associated with an increase in
forelimb grip strength compared to Pred-vehicle and vehicle, which
was apparent by day 34.
At day 32, both right femoral and whole-body BMD in the
Pred-vehicle mice were lower than vehicle. No difference in BMD
reduction was observed between the Pred-RKER-065 and vehicle
cohorts, suggesting that RKER-065 treatment prevented
prednisolone-associated BMD reduction. A similar trend was observed
at day 52. Additionally, Pred-RKER-065-treated mice showed
increases in trabecular bone parameters relative to both vehicle
and Pred-vehicle cohorts.
These data demonstrate that RKER-065 can increase muscle mass,
improve muscle function, and prevent bone loss in
prednisolone-treated mice. These data further support that
targeting activin and myostatin can potentially increase muscle and
bone strength in muscular dystrophic patients under glucocorticoid
therapy.
About KER-065
KER-065, Keros’ fourth product candidate, is designed to bind to
and inhibit select TGF-ß ligands, including myostatin and activin
A, which are negative regulators of muscle and bone mass and
strength. Through inhibition of these TGF-ß ligands, we believe
that KER-065 has the potential to induce muscle and bone anabolic
effects, increase fat metabolism and reduce fibrosis. KER-065 is
being developed for the treatment of neuromuscular diseases, with
an initial focus on DMD.
About Keros Therapeutics, Inc.
Keros is a clinical-stage biopharmaceutical company focused on
developing and commercializing novel therapeutics to treat a wide
range of patients with disorders that are linked to dysfunctional
signaling of the TGF-ß family of proteins. We are a leader in
understanding the role of the TGF-ß family of proteins, which are
master regulators of the growth, repair and maintenance of blood
cells and a number of tissues, including bone, skeletal muscle,
adipose and heart tissue. By leveraging this understanding, we have
discovered and are developing large and small molecules that have
the potential to provide meaningful and potentially
disease-modifying benefit to patients. Keros’ lead protein
therapeutic product candidate, KER-050, is being developed for the
treatment of low blood cell counts, or cytopenias, including anemia
and thrombocytopenia, in patients with myelodysplastic syndromes
and in patients with myelofibrosis. Keros’ lead small molecule
product candidate, KER-047, is being developed for the treatment of
functional iron deficiency. Keros’ third product candidate,
KER-012, is being developed for the treatment of pulmonary arterial
hypertension and for the treatment of cardiovascular disorders.
Keros’ fourth product candidate, KER-065, is being developed for
the treatment of neuromuscular diseases, with an initial focus on
DMD.
Cautionary Note Regarding Forward-Looking
Statements
Statements contained in this press release regarding matters
that are not historical facts are “forward-looking statements”
within the meaning of the Private Securities Litigation Reform Act
of 1995, as amended. Words such as “believe,” “can,” “look
forward,” “potential” and/or similar expressions are intended to
identify forward-looking statements. Examples of these
forward-looking statements include statements concerning: Keros’
expectations regarding its growth, strategy, progress and the
design, objectives and timing of its clinical trial for KER-065;
and the potential of KER-065 to treat DMD and other neuromuscular
diseases. Because such statements are subject to risks and
uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. These
risks and uncertainties include, among others: Keros’ limited
operating history and historical losses; Keros’ ability to raise
additional funding to complete the development and any
commercialization of its product candidates; Keros’ dependence on
the success of its product candidates, KER-050, KER-047, KER-012
and KER-065; that Keros may be delayed in initiating, enrolling or
completing any clinical trials; competition from third parties that
are developing products for similar uses; Keros’ ability to obtain,
maintain and protect its intellectual property; and Keros’
dependence on third parties in connection with manufacturing,
clinical trials and preclinical studies.
These and other risks are described more fully in Keros’ filings
with the Securities and Exchange Commission (“SEC”), including the
“Risk Factors” section of the Company’s Quarterly Report on Form
10-Q, filed with the SEC on August 7, 2023, and its other documents
subsequently filed with or furnished to the SEC. All
forward-looking statements contained in this press release speak
only as of the date on which they were made. Except to the extent
required by law, Keros undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made.
Investor Contact:Justin
Frantzjfrantz@kerostx.com 617-221-6042
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