NEW YORK, Feb. 18, 2021 /PRNewswire/ -- Immunic,
Inc. (Nasdaq: IMUX), a clinical-stage
biopharmaceutical company developing a pipeline of selective oral
immunology therapies aimed at treating chronic inflammatory and
autoimmune diseases, today announced positive top-line data from an
investigator-sponsored phase 2 proof-of-concept clinical trial of
IMU-838 in primary sclerosing cholangitis (PSC). This single-arm,
open-label, exploratory study was designed to investigate IMU-838's
potential to improve various biochemical parameters in PSC patients
and help determine whether any such activity warrants further
investigation in randomized PSC trials. As previously announced,
due to the COVID-19 pandemic, only 18 of the targeted 30 patients
were enrolled in the study (intent-to-treat population, ITT), of
whom only 11 patients completed the full IMU-838 treatment course
and were evaluable over the 24-week treatment period (per-protocol
population, PP).
The PP population experienced a statistically significant
decrease in serum alkaline phosphatase (ALP) levels (p=0.041) after
24 weeks of treatment using 30 mg IMU-838 once daily, as compared
to baseline. A consistent individual pattern of a stable decrease
in ALP values was observed in the PP population between baseline
and week 24, without any single patient showing an increase of more
than 20% of ALP. As per the definition of the primary objective of
the study, 27.3% of the patients in the PP population had a
clinically relevant reduction of serum ALP higher than 25% at week
24, without an increase in liver biochemistry of more than 33%, as
compared to baseline. Biochemical endpoints, such as changes in
serum ALP, have been used in PSC trials performed by third
parties.
Regarding the secondary objectives of the study, no changes in
aspartate aminotransferase (AST), alanine aminotransferase (ALT),
or total, direct or indirect bilirubin were observed in the ITT or
PP populations, as compared to baseline. In addition, despite the
limited scope of the data, encouraging results were observed
regarding symptoms of inflammatory bowel disease, a common
comorbidity for PSC patients, and patient assessments of
health-related quality of life. The study also found that IMU-838
is a safe and well-tolerated oral drug for PSC patients and
treatment-emergent adverse events were rare and generally mild.
"I am very excited about the effects we have seen in this highly
underserved patient population where there is only a small number
of cases worldwide and where no pharmaceutical treatment option is
currently available," noted Daniel
Vitt, Ph.D., Chief Executive Officer and President of
Immunic. "We are also very pleased to see that IMU-838's safety
and tolerability profile was confirmed in this patient group. The
results from this small, open-label study suggest that IMU-838
merits further clinical testing in PSC. We are in discussions with
investigators and leading clinical experts to further evaluate the
data set and to explore potential next steps for this
indication."
"Currently, no effective treatment options are available for PSC
patients and the hepatology community is very keen to see new
approaches and clinical programs for the investigation of promising
new approaches. I am grateful that Mayo Clinic and Immunic are
collaboratively exploring this underserved indication for which
liver transplantation is often the only effective option," stated
Keith Lindor, M.D., Professor of
Medicine Emeritus and former President of the American Association
for the Study of Liver Diseases. "Although we are mindful of
the small size of this dataset, I do believe the results are
noteworthy and merit further exploration. Notable in this small
patient cohort is the absolute consistency with which these
patients experienced decreases in serum alkaline phosphatase at the
24-week time point."
Study Background and Baseline Characteristics
The single-arm, open label, exploratory study was an
investigator-sponsored trial led by Elizabeth Carey, M.D., Professor of Medicine,
Division of Gastroenterology and Hepatology, Department of Internal
Medicine, Mayo Clinic, who had
received Investigator Investigational New Drug (IND) approval from
the U.S. Food & Drug Administration (FDA) and had been granted
Institutional Review Board (IRB) approval to conduct the study. The
study was supported by a grant from the National Institutes of
Health (NIH) and was conducted at two sites: Mayo Clinic,
Phoenix, Arizona (Dr. Carey) and
Mayo Clinic, Rochester, Minnesota
(John E. Eaton, M.D.), both of which
are tertiary referral centers for PSC patients.
The study, for which Immunic provided the study medication,
planned to enroll 30 patients with PSC, aged 18 to 75 years, who
received 30 mg of IMU-838 once daily for a period of 24 weeks.
Enrollment for the study took place between July 2019 and September
2020, but almost all enrollment occurred in 2019 and early
2020. During the COVID-19 pandemic, recruitment for this study was
hampered, as patients with PSC are at a high risk of COVID-19
infections and were advised to avoid travel and unnecessary social
contacts such as those required to participate in a clinical trial.
Together with the investigators, Immunic determined to readout data
of the 18 patients who were enrolled prior to the COVID-19
pandemic. The ongoing COVID-19 pandemic also triggered the
principal investigator's decision to terminate the study in late
2020, before the intended recruitment goal of 30 patients was
reached.
A total of 18 patients started treatment of 30 mg IMU-838 once
daily (intent-to-treat population, ITT, n=18). Of these 18
patients, 11 patients received the full 24-week treatment with
IMU-838 (per-protocol population, PP, n=11). Due to the high number
of discontinued patients during the COVID-19 pandemic and the fact
that all discontinued patients in an ITT statistical analysis will
be counted as treatment failures at week 24, this analysis focuses
mainly on the 11-patient PP population.
Primary Objective
The primary objective of this study was to determine whether
IMU-838 reduces serum ALP in adult patients diagnosed with PSC. The
main analysis for the primary objective was whether patients could
achieve a reduction of ALP at week 24 which is greater or equal to
25%, as compared to baseline, while the AST increase at week 24 is
no more than 33%, as compared to baseline. This positive primary
outcome was achieved by 3 of 11 patients in the PP population
(27.3%, 95% CI: 6-61%). By virtue of inclusion criteria, patients
at baseline had to have an elevated ALP value of at least 1.5 times
upper limit of normal (ULN).
In addition, time from baseline was calculated as a continuous
variable and treated as the primary predictor using a random
intercept model which was adjusted for age at baseline and gender.
For this longitudinal analysis of ALP from baseline to week 24 in
the PP population, the ALP value statistically significantly
(p=0.041) decreased by an average of 5.76 IU/L every 30 days (95%
CI: -11.29, -0.23; statistical model). The time trend was not
statistically significant in the ITT analysis (p=0.578) due to
missing data following the high rate of treatment discontinuations
during the COVID-19 pandemic.
Secondary Objectives
Secondary objectives were to investigate the liver biochemistry
parameters, AST, ALT, and total/direct/indirect bilirubin, as well
as the concentrations of proinflammatory cytokines, as compared to
baseline. The longitudinal analysis of both AST and ALT as well as
total, direct and indirect bilirubin values showed a stable pattern
in the PP population with no statistically significant change over
time and the confidence interval to include the no-change scenario
(AST: average 30 day change 1.22 IU/L, 95% CI: -0.53, 2.97,
p=0.170; ALT: average 30 day change 0.85 IU/L, 95% CI -1.46, 3.15,
p=0.467, total bilirubin: average 30 day change 0.00 mg/dL, 95% CI
-0.01, 0.02, p=0.561, direct bilirubin: average 30 day change 0.00
mg/dL, 95% CI -0.01, 0.01, p=0.861, indirect bilirubin: average 30
day change 0.00 mg/dL, 95% CI -0.01, 0.01, p=0.556). Similar
results were found in the ITT population. In addition, a decrease
in the Ulcerative Colitis Clinical score was observed in evaluated
patients, although the number of assessed patients was limited.
"This was a feasibility study to explore activity of IMU-838 in
PSC patients based on biochemical parameters. IMU-838 was found to
lead to a statistically significant reduction of serum ALP over
time in the PP population, while no trend for increases in ALT, AST
or bilirubin was observed," commented Andreas Muehler, M.D., Chief Medical Officer of
Immunic. "Despite the challenges we faced due to COVID-19,
which severely hindered the enrollment at the two Mayo Clinic sites
and which led to an unusually high discontinuation rate and an
early termination of the study, we have seen encouraging activity
signals for IMU-838 in this patient population. Based on these
promising data and, in particular, the improvement in biochemical
liver parameters, we will continue to evaluate the potential of
IMU-838 as a treatment option for PSC patients. It may also be
worthwhile to optimize dose levels of IMU-838 in PSC patients in
the future."
For more information on this clinical trial, please visit:
www.clinicaltrials.gov, NCT03722576.
Conference Call and Webcast Information
As previously announced, Immunic's management team will host a
public conference call and webcast today, February 18, 2021 at 8:00 a.m. Eastern
Time to discuss the data from the main phase 2 analysis of the
CALVID-1 trial of IMU-838 in hospitalized patients with moderate
COVID-19, as well as data from the investigator-sponsored phase 2
clinical trial of IMU-838 in primary sclerosing cholangitis.
To participate in the conference call, dial 1-877-870-4263
(USA) or 1-412-317-0790
(International) and ask to be joined into the Immunic, Inc. call. A
live, listen-only webcast of the conference call can be accessed at
https://www.webcaster4.com/Webcast/Page/2301/39950 or on the
"Events and Presentations" section of Immunic's website at
ir.imux.com/events-and-presentations.
An archived replay of conference call and webcast will be
available approximately one hour after the completion for one year
on Immunic's website at: ir.imux.com.
About Primary Sclerosing Cholangitis (PSC)
PSC is a
rare liver disease with a prevalence of approximately 4.15 per
100,000 in the United States, in
which the bile ducts in the liver become inflamed, narrow and
prevent bile from flowing properly. The exact cause and disease
mechanism of PSC are still unknown, but an autoimmune mechanism may
play a role. There is an association with inflammatory bowel
diseases, most often with ulcerative colitis and less commonly with
Crohn's disease. PSC is a progressive disease and, other than liver
transplantation, there are currently no approved therapies that
have been shown to improve survival in patients with PSC. The
estimated time from diagnosis of PSC to death or liver transplant
has been shown to be less than 15 years.
About IMU-838
IMU-838 is an orally available,
next-generation selective immune modulator that inhibits the
intracellular metabolism of activated immune cells by blocking the
enzyme dihydroorotate dehydrogenase (DHODH). IMU-838 acts on
activated T and B cells while leaving other immune cells largely
unaffected and allows the immune system to stay functioning, e.g.
in fighting infections. In previous trials, IMU-838 did not show an
increased rate of infections compared to placebo. In addition,
DHODH inhibitors, such as IMU-838, are known to possess a
host-based antiviral effect, which is independent with respect to
specific virus proteins and their structure. Therefore, DHODH
inhibition may be broadly applicable against multiple viruses.
IMU-838 was successfully tested in two phase 1 clinical trials in
2017 and is currently being tested in a phase 2 trial in patients
with ulcerative colitis. In the third quarter of 2020, the company
reported positive results from its phase 2 EMPhASIS trial of
IMU-838 in relapsing-remitting multiple sclerosis, achieving both
primary and key secondary endpoints with high statistical
significance. In the first quarter of 2021, Immunic announced that
IMU-838 has shown evidence of clinical activity in its phase 2
CALVID-1 trial in hospitalized patients with moderate COVID-19.
Also, in the first quarter of 2021, the company reported positive
top-line data from an investigator-sponsored phase 2
proof-of-concept clinical trial of IMU-838 in primary sclerosing
cholangitis which was conducted in collaboration with Mayo Clinic.
To date, IMU-838 has been tested in more than 800 individuals and
has shown an attractive pharmacokinetic, safety and tolerability
profile. IMU-838 is not yet licensed or approved in any
country.
About Immunic, Inc.
Immunic, Inc. (Nasdaq: IMUX) is a
clinical-stage biopharmaceutical company with a pipeline of
selective oral immunology therapies aimed at treating chronic
inflammatory and autoimmune diseases, including relapsing-remitting
multiple sclerosis, ulcerative colitis, Crohn's disease, and
psoriasis. Immunic is developing three small molecule products: its
lead development program, IMU-838, is a selective immune
modulator that inhibits the intracellular metabolism of activated
immune cells by blocking the enzyme DHODH and exhibits a host-based
antiviral effect; IMU-935 is an inverse agonist of RORĪ³t; and
IMU-856 targets the restoration of the intestinal barrier function.
For further information, please visit: www.imux.com.
Cautionary Statement Regarding Forward-Looking
Statements
This press release contains "forward-looking
statements" that involve substantial risks and uncertainties for
purposes of the safe harbor provided by the Private Securities
Litigation Reform Act of 1995. All statements, other than
statements of historical facts, included in this press release
regarding strategy, future operations, future financial position,
future revenue, projected expenses, prospects, plans and objectives
of management are forward-looking statements. Examples of such
statements include, but are not limited to, statements relating to
Immunic's three development programs and the targeted diseases; the
potential for IMU-838 to safely and effectively target diseases;
the proof-of-concept study of IMU-838 for the treatment of patients
with primary sclerosing cholangitis; the timing of current and
future clinical trials; the potential for IMU-838 as a treatment
for primary sclerosing cholangitis that may be supported by the
investigator-sponsored phase 2 proof-of-concept trial data, and any
clinical trials, collaborations and approvals relating to such
potential treatment; the nature, strategy and focus of the
company; and the development and commercial potential of any
product candidates of the company. Immunic may not actually achieve
the plans, carry out the intentions or meet the expectations or
projections disclosed in the forward-looking statements and you
should not place undue reliance on these forward-looking
statements. Such statements are based on management's current
expectations and involve risks and uncertainties. Actual results
and performance could differ materially from those projected in the
forward-looking statements as a result of many factors, including,
without limitation, the COVID-19 pandemic, risks and uncertainties
associated with the ability to project future cash utilization and
reserves needed for contingent future liabilities and business
operations, the availability of sufficient resources to meet
business objectives and operational requirements, the fact that the
results of earlier studies and trials may not be predictive of
future clinical trial results, the protection and market
exclusivity provided by Immunic's intellectual property, risks
related to the drug development and the regulatory approval process
and the impact of competitive products and technological changes. A
further list and descriptions of these risks, uncertainties and
other factors can be found in the section captioned "Risk Factors,"
in the company's Annual Report on Form 10-K for the fiscal year
ended December 31, 2019, filed with
the SEC on March 16, 2020, the
company's Quarterly Report on Form 10-Q for the quarter ended
September 30, 2020, filed with the
SEC on November 6, 2020, and in the
company's subsequent filings with the Securities and Exchange
Commission. Copies of these filings are available online at
www.sec.gov or ir.imux.com/sec-filings. Any forward-looking
statement made in this release speaks only as of the date of this
release. Immunic disclaims any intent or obligation to update these
forward-looking statements to reflect events or circumstances that
exist after the date on which they were made. Immunic expressly
disclaims all liability in respect to actions taken or not taken
based on any or all the contents of this press release.
Contact Information
Immunic, Inc.
Jessica Breu
Head of Investor Relations and Communications
+49 89 2080 477 09
jessica.breu@imux.com
US IR Contact
Rx Communications Group
Paula Schwartz
+1 917 322 2216
immunic@rxir.com
US Media Contact
KOGS Communication
Edna Kaplan
+1 781 639 1910
kaplan@kogspr.com
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