Chemomab Therapeutics Ltd. (Nasdaq: CMMB) (Chemomab) a clinical
stage biotechnology company developing innovative therapeutics for
fibro-inflammatory diseases with high unmet need, today reported
positive topline results from the Phase 2 SPRING trial assessing
its first-in-class monoclonal antibody, CM-101, in patients with
primary sclerosing cholangitis (PSC). Treatment with CM-101
achieved its primary endpoint of safety and tolerability and
demonstrated anti-fibrotic, anti-inflammatory and anti-cholestatic
effects across a broad range of disease-related secondary efficacy
endpoints, including statistically significant improvement in liver
stiffness, a key PSC disease marker. CM-101 is the first
investigational drug being developed for PSC to exhibit broad,
clinically relevant effects on all three components of the disease,
providing further evidence of its multifactorial mechanism of
action and disease-modifying potential.
“We are thrilled to report the positive results of the Phase 2
SPRING trial that represent a major milestone for Chemomab and
establish clear clinical proof-of-concept for CM-101 in PSC and
potentially other fibrotic diseases,” said Adi Mor, PhD,
co-founder, Chief Executive Officer and Chief Scientific Officer of
Chemomab. “CM-101 achieved the primary and key secondary endpoints
in the trial and is the first therapy to demonstrate broad,
clinically relevant effects on the three main components of PSC.
This is also the first PSC trial to show, after just 15 weeks of
treatment, a statistically significant reduction in liver
stiffness, a widely used and well validated measure for assessing
disease progression in PSC. Moreover, CM-101 is among the first
investigational drugs to show a reduction in total bilirubin, an
important marker of cholestasis and liver health, as well as
reductions in pruritis, a cholestatic indicator of great relevance
to patients. We believe these results provide strong support for
advancing CM-101 to a Phase 3 PSC trial, which we are planning to
initiate in 2025 after our interactions with the FDA later this
year. I would like to thank the patients, caregivers and
investigators, clinical staff and patient advocacy groups whose
commitment and hard work were invaluable.”
The double-blind placebo-controlled SPRING study assessed two
doses of CM-101 (10 mg/kg and 20 mg/kg) administered to PSC
patients every three weeks over 15 weeks. A total of 76 patients
from the U.S., Europe and Israel were treated in the trial. The
study analysis included assessments of all patients who completed
all doses and the Week 15 visit, as well as a prespecified subgroup
analysis of moderate/advanced patients with a higher risk of more
rapidly progressing disease. This population was defined as
patients with a vibration-controlled transient elastography (VCTE)
measure at baseline of greater than 8.7 kPa. Approximately half of
the SPRING study patients were classified as having
moderate/advanced disease, which is similar to the overall PSC
patient population.
Douglas Thorburn, MD, Divisional Clinical Director for Liver and
Digestive Health at the Royal Free London NHS Trust and Professor
of Hepatology within the Institute for Liver and Digestive
Health at UCL, is Principal Investigator of the SPRING trial.
Professor Thorburn said, “It is very encouraging that 15 weeks
of treatment with CM-101 for people with PSC was both generally
well tolerated and resulted in improvements across such a broad
range of disease-related biomarkers, including liver stiffness,
ELF, liver enzymes and even pruritis. This is a very positive
development for patients with this life-threatening disease that
has no approved treatments, and I look forward to the continued
clinical progress of CM-101.”
CM-101 SPRING Trial – Overview of
Key Results
CM-101 met the primary study endpoint, demonstrating a favorable
safety profile over the 15-week treatment period. CM-101-treated
patients with moderate/advanced disease showed improvements on a
wide range of disease-related secondary endpoints, including
assessments of changes from baseline relative to placebo at Week 15
in liver stiffness; in liver fibrosis biomarkers, including the
Enhanced Liver Fibrosis (ELF) score and PRO-C3 levels; in total
bilirubin and liver function tests; in pruritis (itch) and in
markers of inflammation.
Dose-dependent responses were observed for multiple
disease-related biomarkers. A consistent pattern of greater
improvement on the secondary endpoints was observed in the study
arm receiving 20 mg/kg of CM-101 and in the prespecified subgroup
of PSC patients with moderate/advanced disease. Since PSC is a
slowly progressive disease, longer duration of treatment with
CM-101 could potentially result in greater improvement in patient
populations with lower disease burden, with the goal of slowing or
preventing disease progression.
Primary Endpoint
CM-101 demonstrated a favorable safety profile and was generally
well-tolerated over the 15-week treatment period. It also exhibited
favorable and dose-dependent pharmacokinetic profiles. Adverse
events, which most commonly included fatigue, headache, and
pruritis, were generally mild/moderate and distributed similarly
between the placebo and CM-101-treated dosing arms.
Key Secondary Endpoints
Liver Stiffness Measures
Improved in CM-101-Treated PSC
PatientsNotably, both doses of CM-101 improved
liver stiffness relative to placebo at Week 15, with a
statistically significant improvement achieved in patients with
moderate/advanced disease This is the first time that an
investigational drug for the treatment of PSC has demonstrated
significant improvements in liver stiffness in a relatively short
study.
5-D Itch Scale Total
Pruritis Scores Improved
in CM-101-Treated PSC
PatientsPruritis total scores on the 5-D Itch
Scale relative to placebo improved in CM-101-treated patients, who
demonstrated decreased pruritis scores compared to placebo starting
as soon as six weeks after their first dose. CM-101-treated
patients experienced decreased pruritis scores across all
timepoints compared to placebo and the decrease reached statistical
significance in patients receiving the 10 mg/kg dose at Week
15.
ELF Score Improved
in CM-101-Treated PSC
PatientsPatients treated with the 20 mg/kg dose of
CM-101 with moderate/advanced disease had reduced ELF scores
relative to placebo at all time points in the trial. In addition,
in all patients treated with the 20 mg/kg dose of CM-101, ELF
changes from baseline remained consistently below 0.19, a
recognized threshold for predicting long-term PSC-related clinical
outcome events.1
PRO-C3 Improved in
CM-101-Treated in PSC Patients Reductions
in PRO-C3 levels at Week 15 relative to placebo were
observed in patients receiving both the 10 mg/kg and
20 mg/kg doses of CM-101. PRO-C3, a serum biomarker of type III
collagen synthesis, has been shown to be elevated in patients with
PSC and has been identified as an independent predictor of
transplant-free survival in PSC.2
Total Bilirubin Improved
in CM-101-Treated PSC
PatientsBilirubin is a key biomarker that is an
indicator of bile duct health. CM-101-treated patients showed a
dose-dependent improvement in total bilirubin relative to placebo
at Week 15 that provides further support for the anti-cholestatic
activity of CM-101.
Liver Function
Tests Improved
in CM-101-Treated PSC
PatientsAll liver function tests improved in
CM-101-treated patients relative to placebo at Week 15. Levels of
alkaline phosphatase (ALP), alanine aminotransferase (ALT)
aspartate aminotransferase (AST) and gamma-glutamyl transferase
(GGT) decreased in CM-101-treated patients receiving the 20 mg/kg
dose.
Anti-inflammatory Activity
Demonstrated in
CM-101-Treated PSC PatientsLevels
of the inflammatory cytokines IL-6 and TGFβ1, which are
well-characterized markers that are downstream from our novel CCL24
target and are known to play an important role in inflammation and
fibrosis, were reduced in CM-101-treated patients relative to
placebo at Week 15. The reduction reached statistical significance
in moderate/advanced disease patients receiving the 20 mg/kg
dose.
Christopher Bowlus, MD, the Lena Valente Professor and Chief of
the Division of Gastroenterology and Hepatology at the University
of California Davis School of Medicine, commented, “These positive
trial results come at an opportune time, with promising therapies
like CM-101 ready to advance into late-stage trials and recent
progress to develop non-invasive biomarkers as registration
endpoints in PSC that will meet FDA standards. This is welcome news
for the many patients with PSC desperate for new therapeutic
options to combat this challenging disease.”
CM-101 in PSC Patients: Next Steps
Chemomab is preparing for an End-of-Phase 2 meeting with the FDA
to discuss the SPRING trial results and the design of a proposed
Phase 3 PSC trial for accelerated approval. The company anticipates
completing these discussions by the end of the year and receiving
official written feedback from the FDA in the first quarter of
2025.
An Open Label Extension (OLE) portion of the SPRING trial, which
offers patients the opportunity to receive CM-101 for an additional
33-weeks, is ongoing. More than 90% of the eligible study patients
elected to join the OLE. Topline treatment results from this
portion of the study, which will include patients with up to
48-weeks of exposure to CM-101, are on track to be reported in the
first quarter of 2025.
CM-101’s novel CCL24 target has been of interest to potential
partners for several years. The company intends to further explore
opportunities to collaborate with strategic partners in light of
the positive topline data reported from the SPRING trial.
About the Phase 2 SPRING Trial
Chemomab’s Phase 2 SPRING trial (NCT04595825) is a double-blind,
placebo-controlled, multiple dose study assessing the safety and
tolerability of CM-101 administered to PSC patients with
established large duct disease. The trial treated 76 patients in
the U.S., Europe and Israel. Patients received either 10 mg/kg or
20 mg/kg of CM-101 or placebo via an intravenous infusion every
three weeks over the 15-week treatment period. The study analysis
focused on double-blind completers, defined as participants who
received all five doses of CM-101 and had both a baseline and
at least one post-baseline measurement of both ALP and ELF. There
were 66 patients in the double-blind completer analysis set (50
CM-101-treated patients and 16 placebo patients.) The study
analysis plan included a prespecified subgroup of patients with
moderate/advanced disease, defined as patients with a VCTE measure
at baseline of greater than 8.7 kPa, a well-accepted indicator in
PSC of more progressive disease. The SPRING trial includes an OLE
that was available to those study participants who completed the
double-blind portion once the OLE had been established. OLE
participants receive infusions of either 10 mg/kg or 20 mg/kg of
CM-101 every three weeks for an additional 33 weeks. In addition to
safety, the trial is measuring a wide range of secondary outcomes
including serum biomarkers and physiological parameters. These
include well-validated liver biomarkers such as assessments of
liver stiffness, ELF and PRO-C3, as well as pruritus and liver
function tests.
About Primary Sclerosing CholangitisPSC is a
rare, progressive liver disease characterized by inflammation and
fibrosis (scarring) of the bile ducts that can lead to cirrhosis of
the liver, liver failure and death. PSC also increases the risk of
various cancers, which account for about half of PSC-related
mortality. PSC affects an estimated 30,000 patients in the U.S. and
about 80,000 worldwide. The underlying cause of PSC is unknown, but
about 75% of patients also have inflammatory bowel disease. Liver
transplantation is common in end stage disease cases, but even
then, PSC re-occurs in about 20% of transplanted patients. With no
approved therapies to date, there is a high unmet medical need for
new drugs to address the symptoms of PSC and slow or stop the
progression of this devastating illness.
1 Muir et al, Hepatology, 20192 Nielsen et al, Aliment Pharmacol
Ther 2018
Conference Call and Webcast Chemomab management
will host a conference call for investors today, Thursday,
July 25, 2024, beginning at 8:00 a.m. Eastern Time to
discuss the SPRING trial topline results and answer
questions.
Click this Webcast link to access the live webcast or replay.
The live webcast and replay can also be accessed at the News &
Events section of the Investors page on the Chemomab website at
investors.chemomab.com/events.
To access the conference call via telephone, shareholders and
other interested parties can dial +1 (877) 451-6152 (in the U.S.)
or +1 (201) 389-0879 (outside the U.S., including Israel) and enter
passcode 13748170. Please call 5-10 minutes before the scheduled
start time, enter the conference passcode and ask the operator for
the Chemomab conference call.
Or click on Call me™ starting 15 minutes before the
scheduled start time for instant telephone access without having to
wait for an operator.
Forward Looking Statements This press release
contains forward-looking statements within the meaning of the “safe
harbor” provisions of the Private Securities Litigation Reform Act
of 1995 that involve substantial risks and uncertainties. All
statements other than statements of historical facts contained in
this presentation, including statements regarding our future
financial condition, results of operations, business strategy and
plans, and objectives of management for future operations, as well
as statements regarding industry trends, are forward-looking
statements. In some cases, you can identify forward-looking
statements by terminology such as “estimate,” “intend,” “may,”
“plan,” “potentially” “will” or the negative of these terms or
other similar expressions. We have based these forward-looking
statements largely on our current expectations and projections
about future events and trends that we believe may affect our
financial condition, results of operations, business strategy and
financial needs. These forward-looking statements are subject to a
number of risks, uncertainties and assumptions, including, among
other things: the risk that the full data set from the CM-101 study
or data generated in further clinical trials of CM-101 will not be
consistent with the topline results of the CM-101 Phase 2 PSC
trial; failure to obtain, or delays in obtaining, regulatory
approvals for CM-101 in the U.S., Europe or other territories;
failure to successfully commercialize CM-101, if approved by
applicable regulatory authorities, in the U.S., Europe or other
territories, or to maintain U.S., European or other territory
regulatory approval for CM-101 if approved; uncertainties in the
degree of market acceptance of CM-101 by physicians, patients,
third-party payors and others in the healthcare community;
inaccuracies in the Company's estimates of the size of the
potential markets for CM-101 or in data the Company has used to
identify physicians; expected rates of patient uptake, duration of
expected treatment, or expected patient adherence or
discontinuation rates; development of unexpected safety or efficacy
concerns related to CM-101; failure to successfully conduct future
clinical trials for CM-101, including due to the Company's
potential inability to enroll or retain sufficient patients to
conduct and complete the trials or generate data necessary for
regulatory approval, among other things; risks that the Company's
clinical studies will be delayed or that serious side effects will
be identified during drug development; failure of third parties on
which the Company is dependent to manufacture sufficient quantities
of CM-101 for commercial or clinical needs, to conduct the
Company's clinical trials, or to comply with the Company's
agreements or laws and regulations that impact the Company's
business or agreements with the Company; the strength and
enforceability of the Company’s intellectual property rights or the
rights of third parties; the cost and potential reputational damage
resulting from litigation to which the Company may become a party,
including product liability claims; changes in laws and regulations
applicable to the Company's business and failure to comply with
such laws and regulations; business or economic disruptions due to
catastrophes or other events, including natural disasters or public
health crises; and inability to repay the Company's existing
indebtedness and uncertainties with respect to the Company's need
and ability to access future capital; and the intensity and
duration of the current war in Israel, and its impact on our
operations in Israel. These risks are not exhaustive. You should
carefully consider the risks and uncertainties described in the
“Risk Factors” sections of our 20-F for the year ended December 31,
2023. New risk factors emerge from time to time, and it is not
possible for our management to predict all risk factors, nor can we
assess the impact of all factors on our business or the extent to
which any factor, or combination of factors, may cause actual
results to differ materially from those contained in, or implied
by, any forward-looking statements. You should not rely upon
forward-looking statements as predictions of future events.
Although we believe that the expectations reflected in the
forward-looking statements are reasonable, we cannot guarantee
future results, levels of activity, performance or achievements.
Except as required by law, we undertake no obligation to update
publicly any forward-looking statements for any reason after the
date of this presentation. This presentation shall not constitute
an offer to sell or the solicitation of an offer to buy these
securities, nor shall there be any sale of these securities in any
state or jurisdiction in which such offer, solicitation, or sale
would be unlawful prior to registration or qualification under the
securities law of any such state or jurisdiction.
About Chemomab Therapeutics Ltd. Chemomab is a
clinical stage biotechnology company developing innovative
therapeutics for fibro-inflammatory diseases with high unmet need.
Based on the unique and pivotal role of CCL24 in promoting fibrosis
and inflammation, Chemomab developed CM-101, a monoclonal antibody
that neutralizes CCL24 activity. In clinical and preclinical
studies, CM-101 has been shown to have a favorable safety profile
and has been generally well-tolerated to date, with the potential
to treat multiple severe and life-threatening fibro-inflammatory
diseases. Chemomab has reported positive results from four clinical
trials of CM-101, including a Phase 2 trial in patients with
primary sclerosing cholangitis, a Phase 2a liver fibrosis trial in
patients with metabolic-dysfunction associated-steatohepatitis, a
Phase 1b study in patients with metabolic dysfunction–associated
fatty liver disease and an investigator-initiated study in patients
with severe lung injury. Chemomab’s CM-101 program for the
treatment of systemic sclerosis is Phase 2-ready with an open U.S.
IND. For more information about Chemomab, visit chemomab.com.
Contact:
Media & Investors:Chemomab
TherapeuticsBarbara LindheimConsulting Vice PresidentInvestor &
Public Relations, Strategic CommunicationsPhone: +1
917-355-9234barbara.lindheim@chemomab.com IR@chemomab.com
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