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 that it presented additional data from
its two ongoing Phase 2 clinical trials of KER-050, one in patients
with very low-, low-, or intermediate-risk myelodysplastic
syndromes (“MDS”) and one in patients with myelofibrosis (“MF”), at
the 65th American Society of Hematology (“ASH”) Annual Meeting and
Exposition, held in person in San Diego and virtually from December
9 through 12, 2023. In addition, Keros presented preclinical data
showing that a research form of KER-050 promoted erythropoiesis in
an animal model of MF, as well as preclinical data evaluating the
treatment effect of activin receptor-like kinase 2 inhibition in a
mouse model of iron-refractory iron deficiency anemia.
“We believe the data presented at ASH from our ongoing KER-050
Phase 2 clinical trial in MDS supports the potential of KER-050 to
ameliorate ineffective hematopoiesis and treat anemia and
thrombocytopenia in difficult to treat patient populations,
including those with greater transfusion burden and bone marrow
dysfunction,” said Simon Cooper, MBBS, Chief Medical Officer of
Keros. “Additionally, we are encouraged by the preliminary data
from the lowest three dose cohorts from our ongoing Phase 2
clinical trial in MF. KER-050 treatment in combination with
ruxolitinib and as KER-050 monotherapy led to improvements as
assessed by changes in markers of hematopoiesis, reductions in
spleen size and improvement in Total Symptom Score. We look forward
to confirming this profile of benefit in the now enrolling dose
confirmation part of our trial.”
“The encouraging broad profile of KER-050 that we have observed
supports its potential to treat not just the disease-associated
cytopenias, but also impact the pathogenesis of the respective
diseases, as supported by the observed improvements in bone health
and reduction of cardiac stress,” said Jasbir S. Seehra, Ph.D.,
President and Chief Executive Officer. “We are excited by the
results we presented including the durability of transfusion
independence observed with KER-050 and to engage with regulators in
the first half of next year and look forward to sharing the design
of a Phase 3 clinical trial evaluating KER-050 in lower-risk MDS
following that feedback.”
Clinical Presentations
- Durable Clinical Benefit with KER-050 treatment: Findings From
an Ongoing Phase 2 Study in Participants with Lower-Risk MDS
This ongoing, open-label, two-part, Phase 2 clinical trial is
evaluating KER-050 in patients with very low-, low-, or
intermediate-risk MDS. As of September 1, 2023 (the “data cut-off
date”), 79 patients had received at least one dose of KER-050 at
the recommended Part 2 dose (“RP2D”) (collectively, the “safety
population”). Of these patients, 60 had completed at least 24 weeks
of treatment or discontinued as of the data cut-off date
(collectively, the modified intent to treat 24-week population, or
the “mITT24 patients”). Data for hematological response and markers
of hematopoiesis were presented from exploratory analyses of these
mITT24 patients. All data presented from this trial is as of the
data cut-off date.
Of the 79 patients in the safety population, 55.7% (n=44) were
high transfusion burden (“HTB”) while 25.3% (n=20) were low
transfusion burden and 19.0% (n=15) were non-transfused
(“NT”).KER-050 was generally well tolerated by the 79 patients in
the safety population. The most commonly reported
treatment-emergent adverse events (“TEAEs”) (in ≥15% of patients)
were diarrhea, dyspnea, fatigue, nausea and headache. No patients
had progressed to acute myeloid leukemia.
50% (n=30/60) of the mITT24 patients achieved an overall
erythroid response over the first 24 weeks of treatment, which is
defined as meeting either modified IWG 2006 Hematological
improvement-erythroid (“HI-E”) or transfusion independence (“TI”)
for at least eight weeks in transfusion-dependent patients who
required ≥ 2 red blood cell (“RBC”) units transfused at
baseline.
Additional data from the mITT24 patients include:
- 39.1% (n=18/46) of the TI-evaluable patients achieved TI for at
least eight weeks over the first 24 weeks of treatment. 13 of those
18 patients (72.2%) achieved TI for at least 24 weeks over the
first 48 weeks of treatment.
- Of the patients with HTB, 33.3% (n=11/33) achieved TI for at
least eight weeks during the first 24 weeks of treatment. 7 of
those 11 patients (63.6%) achieved TI for at least 24 weeks over
the first 48 weeks of treatment.
- Of the patients with baseline erythropoietin level less than
500 U/L, 44.7% (n=17/38) achieved TI for at least eight weeks over
the first 24 weeks of treatment. Of the patients with baseline
erythropoietin level less than 500 U/L and HTB, 38.5% (n=10/26)
achieved TI for at least eight weeks over the first 24 weeks of
treatment.
The FACIT-Fatigue scale, a measure of self-reported fatigue and
its impact upon daily activities and function, was utilized to
assess health-related quality of life in 45 of the mITT24 patients
who were TI-evaluable and with baseline FACIT-F assessment. A
difference of three in the FACIT-Fatigue scale is considered a
minimally clinically important difference. In this group, patients
who achieved TI had durable and clinically meaningful improvements
in self-reported fatigue. At Week 24, patients achieving TI of
eight weeks or longer within first 24 weeks had a mean score of 5.8
(n=10) versus patients who did not achieve TI who reported a mean
score of -3.2 (n=11), for a mean difference of 9.0. At Week 24,
patients achieving TI of 24 weeks or longer with first 48 weeks had
a mean score of 7.8 (n=9) versus patients who did not achieve TI
who reported a mean score of -3.9 (n=12), for a mean difference of
11.7.
The majority of patients enrolled in this ongoing trial had HTB
or multi-lineage dysplasia, indicating a difficult-to-treat trial
population. Durable TI responses were observed in a broad range of
patients with lower-risk MDS, including in those with HTB, which
support the potential for KER-050 to ameliorate ineffective
hematopoiesis across multiple lineages in patients with MDS.
Patients who achieved TI showed clinically meaningful improvements
in FACIT-Fatigue scores, indicating that KER-050 may improve
quality of life in patients with lower-risk MDS.
- KER-050 Treatment Reduced Iron Overload and Increased Bone
Specific Alkaline Phosphatase in Participants with Lower-risk MDS
Supporting Potential to Restore Balance to the Osteohematopoietic
Niche
Exploratory analysis of biomarkers that may indicate MDS disease
modification were evaluated as of the data cut-off date in the
ongoing Phase 2 clinical trial of KER-050 in patients with MDS.
Observations from these biomarkers included improvements in:
- Iron metabolism: 48.3% (n=14/29) of patients with baseline
ferritin ≥ 1,000 ng/ml had a decreased ferritin to < 1000 ng/ml
and 69.0% (n=20/29) of patients decreased ferritin by ≥20%. Two
patients, including one who was NT, discontinued iron chelator
therapy due to observed decreases in ferritin. These data support
potential of KER-050 to ameliorate iron overload.
- Hematopoiesis: Sustained increases in hemoglobin for 24 weeks
coincided with observed increases in soluble transferrin receptor
and concomitant decreases in serum ferritin, suggesting KER-050
resulted in durable restoration of erythropoiesis and improved iron
metabolism.
- Bone turnover: Increases in bone-specific alkaline phosphatase,
a marker of osteoblast activity, were observed with KER-050
treatment regardless of hematological response, baseline
transfusion burden or RS status, suggesting KER-050 can potentially
restore a bone marrow microenvironment conducive to functional
hematopoiesis.
- Cardiac stress: Levels of N-terminal prohormone of brain
natriuretic protein, a biomarker of myocardial stress, decreased in
both HI-E and/or TI responders and non-responders, suggesting that
KER-050 may ameliorate cardiac strain directly via inhibition of
activin A and indirectly by improving anemia and reducing
transfusion burden.
Collectively, these exploratory data suggest that KER-050 has
the potential to provide benefit to patients with MDS beyond
treatment of anemia, such as reestablishing hematopoiesis across
multiple cell lineages, restoring homeostasis within the
osteohematopoietic niche and ameliorating myocardial strain.
- Modulation of TGF-β Superfamily Signaling by KER-050
Demonstrated Potential to Treat Myelofibrosis and Mitigate
Ruxolitinib-Associated Cytopenias
This ongoing, open-label, two-part Phase 2 clinical trial is
evaluating KER-050 administered with or without ruxolitinib in
patients with MF who have anemia and were either currently on,
failed, or ineligible for ruxolitinib at baseline. Safety data are
presented for all patients that received at least one dose of
KER-050 in Part 1 (n=41) as of September 14, 2023. Evaluations of
markers of hematopoiesis and anemia over 12 weeks, along with
measurements of spleen volume and symptom scores (by the MF-symptom
assessment form-Total Symptom Score, or “MF-SAF-TSS”) over 24
weeks, were presented for dose levels 1 through 3, ranging from
0.75 mg/kg to 3.0 mg/kg (collectively, the “efficacy evaluable
patients”). Data for dose level 4 (4.5 mg/kg), the highest dose
level being evaluated in Part 1, are not included due to limited
exposure as of the data cutoff date. All data presented from this
trial is as of the September 14, 2023, data cut-off date.
KER-050 was generally well tolerated by the safety population.
There was one dose-limiting toxicity reported from a patient in the
1.5mg/kg dose level of the monotherapy arm. The patient had an
increase in hemoglobin of at least 2 g/dL, which met protocol
criteria for dose reduction at the end of cycle 1. There were no
adverse events associated with this event, and the maximum observed
hemoglobin remained within normal limits. There were three cases of
fatal TEAEs in the trial that were each deemed unrelated to
treatment. The most commonly reported TEAEs (in ≥10% of patients)
were diarrhea, thrombocytopenia, asthenia (weakness), fatigue and
pyrexia (fever). Treatment-related TEAEs were relatively
infrequent, most of which were mild to moderate, with two patients
experiencing Grade 3 or higher worsening cytopenias.
Additional data from the efficacy evaluable patients
include:
- Increases in hemoglobin were observed in non-transfusion
dependent patients in both arms, suggesting that KER-050 has the
potential to address anemia due to MF and ruxolitinib-associated
anemia.
- Additionally, most patients had reductions in transfusion
burden, including patients receiving up to 15 RBC units per 12
weeks at baseline.
- Non-transfusion dependent patients, who received a median of
three RBC units per 12 weeks at baseline, experienced sustained
increases in hemoglobin within the first 12 weeks of treatment in
both the monotherapy and combination arms (pooled across dose
cohorts).
- Additionally, observed increases in soluble transferrin
receptor, reticulocytes and hemoglobin were generally higher with
increasing dose levels between 0.75 mg/kg to 3.0 mg/kg (pooled
across both monotherapy and combination arms at each dose
level).
- At week 24, reduction in spleen size was observed in 57.1%
(n=4/7) of patients with baseline spleen size ≥ 450 cm3 and a week
24 spleen assessment, including one of three patients in the
monotherapy arm and three of four patients in the combination
arm.
- At week 24, decrease in disease symptoms was observed in 66.7%
(n=8/12) of patients with at least two symptoms with an average
score ≥ 3 or an average total score of ≥ 10 on the MF-SAF-TSS
questionnaire at baseline and a week 24 MF-SAF-TSS assessment.
The data support the potential of KER-050 to ameliorate
ineffective hematopoiesis and address cytopenias due to MF and
associated with ruxolitinib, and provide broader clinical benefit
in patients as observed by the reduction in spleen size and
improvement in symptoms.
Conference Call and Webcast Information
Keros will host a conference call and webcast today, December
11, 2023, at 8:00 a.m. Eastern time, to discuss the additional data
from its two ongoing Phase 2 clinical trials of KER-050, one in
patients with MDS and one in patients with MF, which was presented
at the 65th ASH Annual Meeting and Exposition.
The conference call will be webcast live at:
https://event.webcasts.com/starthere.jsp?ei=1645187&tp_key=cad9574144.
The live teleconference may be accessed by dialing (877) 407-0309
(domestic) or (201) 389-0853 (international). An archived version
of the call will be available in the Investors section of the Keros
website at https://ir.kerostx.com/ for 90 days following the
conclusion of the call.
About the Ongoing Phase 2 Clinical Trial of KER-050 in
Patients with MDS (NCT04419649)
Keros is conducting an open label, two-part, multiple ascending
dose Phase 2 clinical trial to evaluate KER-050 in patients with
very low-, low-, or intermediate-risk MDS who either have or have
not previously received treatment with an erythroid stimulating
agent.
The primary objective of this trial is to assess the safety and
tolerability of KER-050 in patients with MDS that are RS positive
or non-RS. The primary objective of Part 2 of this trial is
confirmation of the safety and tolerability of the RP2D (3.75 mg/kg
and 5.0 mg/kg). The secondary objectives of this trial are to
evaluate the pharmacokinetics, pharmacodynamics and efficacy of
KER-050.
About the Ongoing Phase 2 Clinical Trial of KER-050 in
Patients with MF-Associated Cytopenias (RESTORE trial)
Keros is conducting an open label, two-part, multiple ascending
dose Phase 2 clinical trial to evaluate KER-050 as a monotherapy
and in combination with ruxolitinib in patients with MF-associated
cytopenias.
The primary objective of this trial is to assess the safety and
tolerability of KER-050 in patients with MF-associated cytopenias.
The primary objective of Part 2 of this trial is confirmation of
the safety and tolerability of the RP2D (3.75 mg/kg and 5.0 mg/kg).
The secondary objectives of this trial are to evaluate the
pharmacokinetics, pharmacodynamics and efficacy of KER-050
administered with or without ruxolitinib.
About KER-050
Keros’ lead protein therapeutic product candidate, KER-050, is
an engineered ligand trap comprised of a modified ligand-binding
domain of the TGF-ß receptor known as activin receptor type IIA
that is fused to the portion of the human antibody known as the Fc
domain. KER-050 is being developed for the treatment of low blood
cell counts, or cytopenias, including anemia and thrombocytopenia,
in patients with MDS and in patients with MF.
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 (elritercept), is being
developed for the treatment of low blood cell counts, or
cytopenias, including anemia and thrombocytopenia, in patients with
MDS and in patients with MF. Keros’ second product candidate,
KER-012, is being developed for the treatment of pulmonary arterial
hypertension and for the treatment of cardiovascular disorders.
Keros’ third product candidate, KER-065, is being developed for the
treatment of neuromuscular diseases, with an initial focus on
Duchenne muscular dystrophy.
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 “believes,” “expects,”
“intends,” “plans,” “potential,” “projects,” “would” and “future”
or similar expressions such as “look forward” 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 trials for KER-050,
including its regulatory plans; the potential of KER-050 to treat
beyond MF- and MDS-associated cytopenias to have a direct effect on
the pathogenesis of MF and MDS, respectively; the potential of
KER-050 to ameliorate ineffective hematopoiesis across multiple
lineages in patients with MDS and to improve quality of life in
patients with lower-risk MDS; and the potential of KER-050 to
address anemia due to MF and ruxolitinib-associated anemia. 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-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 November 6, 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
Keros Therapeutics (NASDAQ:KROS)
Graphique Historique de l'Action
De Août 2024 à Sept 2024
Keros Therapeutics (NASDAQ:KROS)
Graphique Historique de l'Action
De Sept 2023 à Sept 2024