- New data presented in two separate oral presentations at the
European Association for the Study of the Liver's International
Liver Congress 2022 (EASL ILC 2022)
- Following 90 days of dosing, ATI-2173, in combination with
tenofovir disoproxil fumarate (TDF), was generally well-tolerated
with alanine aminotransferase (ALT) normalization and no ALT flares
off-treatment
- Antios' capsid assembly modulators (CAMs) ATI-1428 and ATI-1645
show safe and potent in vitro and in vivo activity
and excellent pharmacokinetic profiles
DOYLESTOWN, Pa., June 25,
2022 /PRNewswire/ -- Antios Therapeutics, Inc.
(Antios), a clinical-stage biopharmaceutical company developing
transformative treatments for hepatitis B virus (HBV), today
announced new data from the Phase 2a clinical trial of ATI-2173,
its lead investigational proprietary drug candidate and the only
Active Site Polymerase Inhibitor Nucleotide (ASPIN) in clinical
development for HBV. Antios also announced new data on its 4th
generation capsid assembly modulator (CAM) program evaluating
ATI-1428 and ATI-1645. In the 90-day Phase 2a trial, adult patients
receiving ATI-2173 in combination with tenofovir disoproxil
fumarate (TDF) showed slower virologic rebound than patients
receiving TDF plus placebo after stopping treatment. Additionally,
in a nonclinical study, low oral doses of ATI-1428 and ATI-1645
given once-daily blocked hepatic HBV replication and reduced both
serum HBV DNA and RNA to undetectable levels. These data were
presented at the European Association for the Study of the Liver's
International Liver Congress 2022 (EASL ILC 2022).
Highlights from the EASL Oral
Presentation on ATI-2173
- In the 90-day Phase 2a study, at 24 weeks off-treatment, 75%
(n=16) of ATI-2173 plus TDF patients did not meet criteria to
restart TDF treatment vs. 0% (n=4) in the TDF alone arm
- In the ATI-2173 plus TDF arms (n=16), alanine aminotransferase
(ALT) levels normalized on-treatment and no patients receiving
ATI-2173 plus TDF experienced ALT flares during the 24-week
off-treatment follow-up period
- All patients completed 90 days of dosing with no serious
adverse events or dose-limiting toxicities
"These data reinforce our belief that ATI-2173 can act as a
bridge on the path to an HBV cure, with the potential to provide a
meaningful clinical benefit to patients," said Douglas Mayers, M.D., Chief Medical Officer, and
Co-Founder of Antios. "The slower virological rebound, ALT
normalization on-treatment and no off-treatment ALT flares among
those on the ATI-2173 combination regimen highlight the promise of
the ASPIN mechanism of action – which we believe can be
complementary to all other approaches."
Highlights from the EASL Oral
Presentation on ATI-1428 and ATI-1645
- ATI-1428 and ATI-1645 are 4th generation class II CAMs with a
novel and unique ultra-potent mechanism of action designed to
provide for a more targeted and beneficial antiviral response with
an improved clinical safety profile due to the lack of HBV capsid
accumulation in liver cells
- ATI-1428 and ATI-1645 have displayed strong nonclinical
antiviral activity in a mouse model against the various HBV
genotypes and low EC50 shift against naturally occurring variants
associated with resistance to past and current CAMs
- In in vivo mouse experiments, ATI-1428 or ATI-1645
blocked HBV replication in the liver of immunocompetent
HBV-replicating mice and prevented unnecessary T-cell mediated
liver damage through non-accumulation/degradation of empty capsids
in the hepatocyte
- Both compounds show safe and potent in vitro and in
vivo activity and excellent pharmacokinetic profiles
"The nonclinical data supports our view that clinical
development of 4th generation CAM compounds has the potential to
provide a safe and effective approach for treating HBV," said
Luca Guidotti, M.D., Ph.D., Deputy
Scientific Director of San Raffaele Hospital and Scientific Advisor
to Antios. "By preventing the abnormal capsid accumulation that
less potent CAMs induce, these ultra-potent CAMs are designed to
not sensitize hepatocytes to unnecessary T cell-mediated killing.
This may allow the development of safe and effective combinations
with therapeutic strategies aimed at immune reactivation."
These presentations can be found on the Antios website at
https://www.antiostherapeutics.com/scientific-approach/publications-presentations/.
About ATI-2173
ATI-2173, Antios Therapeutics' lead once-daily, oral drug
candidate for treating HBV, is an investigational phosphoramidate
prodrug of clevudine monophosphate. ATI-2173 has the potential, if
approved, to be a bridge to a potential cure for HBV. It is the
only Active Site Polymerase Inhibitor Nucleotide (ASPIN) for HBV in
clinical development, and its mechanism of action is designed to be
complementary to other approaches that also seek to achieve a
functional cure.
About ATI-1428 and
ATI-1645
ATI-1428 and ATI-1645 are 4th generation, class II capsid
assembly modulators (CAMs) both with a novel and unique
ultra-potent mechanism of action design that may provide for a
safer and more productive interaction with the immune system.
Derived from a novel chemical scaffold, these CAMs have shown
strong in vitro and in vivo activity in a transgenic
mouse model of HBV infection. As CAMs with an ultrapotent design
preclinically inducing no abnormal accumulation of empty capsids
based on an initial preclinical mouse study, ATI-1428 and
ATI-1645 represent promising candidates for clinical
development and have entered investigational new
drug enabling development. ATI-1428 and ATI-1645 were
acquired by Antios in November of 2021 from San Raffaele Hospital
(OSR), Istituto Nazionale Genetica Molecolare (INGM), and
IRBM/Promidis, a collaboration of Italian research institutes and a
global contract research organization.
About HBV
Hepatitis B is a potentially life-threatening liver infection
caused by HBV. HBV can cause chronic infection, which leads to a
higher risk of death from cirrhosis and liver cancer. Chronic HBV
infection represents a significant unmet medical need. The World
Health Organization estimates that up to 300 million people
worldwide suffer from chronic HBV infection, while other estimates
indicate that approximately two million people in the United States suffer from chronic HBV
infection. Approximately 900,000 people die every year from
complications related to chronic HBV infection despite the
availability of effective vaccines and current treatment
options.
About Antios Therapeutics,
Inc.
Antios Therapeutics is a clinical-stage biopharmaceutical
company focused on the development of innovative therapies to treat
and cure viral diseases. Its lead drug candidate ATI-2173 – the
only Active Site Polymerase Inhibitor Nucleotide (ASPIN) for HBV in
clinical development – has the potential, if approved, to become a
potential bridge to a cure for chronic HBV. Antios is also
developing a novel series of 4th generation Class II capsid
assembly modulators (CAMs) to further expand Antios' portfolio of
differentiated molecules that could lead to a cure for HBV. HBV is
a major unmet global health problem affecting up to 300 million
people worldwide, more than hepatitis C and HIV combined. For more
information, please visit www.antiostherapeutics.com.
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