Atea Pharmaceuticals, Inc. (Nasdaq: AVIR) (“Atea”), a
clinical-stage biopharmaceutical company engaged in the discovery
and development of oral direct acting therapeutics for serious
viral diseases, today announced the presentation of new Phase 1, in
vitro and in vivo data that demonstrate key profile attributes of
Atea’s lead drug candidate, bemnifosbuvir, for the treatment of
COVID-19 and hepatitis C (HCV). Additionally, new data for AT-752
for dengue and a nucleotide analogue are being presented. These
results are being presented at the 36th International Conference on
Antiviral Research (ICAR 2023) taking place March 13-17, 2023 in
Lyon, France.
Key highlights of the presentations include results from a Phase
1 human absorption, distribution, metabolism, and excretion (ADME)
study for bemnifosbuvir demonstrating a favorable ADME profile
supportive of the dosing regimen used in SUNRISE-3, a global,
multicenter Phase 3 registrational trial for the treatment of
COVID-19. In vitro metabolism and transporter interaction studies
showed bemnifosbuvir has a low risk for interactions with medicines
commonly prescribed to patients at risk for COVID-19 progression
and for those with HCV infection. In vitro studies also
demonstrated advantages of bemnifosbuvir’s mechanism of action,
which targets conserved regions of the viruses that cause COVID-19
and HCV infection. These advantages include a higher barrier to
resistance and maintenance of antiviral activity in the presence of
COVID-19 variants. Additionally, the combination of bemnifosbuvir
and ruzasvir for the treatment of HCV demonstrated potent in vitro
synergistic antiviral activity and in vivo preclinical safety
without adverse interactions.
“As COVID-19 becomes endemic, it is essential to have new oral
antiviral medicines that are safe, well tolerated and address the
current limitations of existing treatments,” said Bruno Canard,
Ph.D., lead investigator of the in vitro studies of bemnifosbuvir
conducted at Architecture et Fonction des Macromolécules
Biologiques, CNRS and Aix-Marseille University. “The data presented
at ICAR demonstrate bemnifosbuvir’s unique metabolic activation
pathway and how it inhibits enzymes essential to the viral
replication of COVID-19 and HCV and its potential to play an
important role in the treatment of these serious viral
diseases.”
Bemnifosbuvir is an investigational, oral, direct-acting
antiviral being evaluated in the Phase 3 SUNRISE-3 trial for the
treatment of COVID-19 in non-hospitalized patients at high risk for
disease progression, and in Phase 2 development for the treatment
of HCV in combination with ruzasvir, an oral NS5A inhibitor.
“As we continue to advance late-stage development of
bemnifosbuvir, these data demonstrate that our lead compound has
the potential to improve the current standard of care and address
key unmet needs and limitations for patients with COVID-19 and
HCV,” said Jean-Pierre Sommadossi, PhD, Chief Executive Officer and
Founder of Atea Pharmaceuticals. “These data support a favorable
safety and drug interaction profile of bemnifosbuvir to treat these
conditions and to provide vulnerable patients with another
therapeutic option.”
COVID-19
Oral Presentation Number: 019
Date/Time: Wednesday, March 15 from 10:35 am-10:45
am CET Title: Bemnifosbuvir (BEM, AT-527) a Potent
Inhibitor of SARS-CoV-2 Variants of Concern (VOC), and a Promising
Oral Antiviral with a High Resistance Barrier for Treatment of
COVID-19 and other Coronaviruses Infections
In vitro results demonstrate that bemnifosbuvir is a potent
inhibitor of all tested SARS-CoV-2 variants of concern as well as
other human coronaviruses such as HCoV-229E, HCoV-OC43, and
SARS-CoV-1. Results from an in vitro resistance study conducted
with the surrogate virus HCoV-229E in Huh7 cells suggest that
bemnifosbuvir may have a high barrier to drug resistance during
treatment of COVID-19 and other coronavirus infections.
Bemnifosbuvir
Oral Presentation Number:
047Date/Time: Thursday, March 16 from 5:20-5:30 pm
CETTitle: Five Cellular Enzymes in the Activation
Pathway of Bemnifosbuvir, a Drug Candidate Against SARS-CoV-2
Infections
Results from this in vitro study showed that bemnifosbuvir
required a minimal set of 5 cellular enzymes (Cat/CES1, HINT1,
ADALP1, GUK1, and NDPK) to be metabolized to its active
triphosphate form, AT-9010, with an obligate order of reactions, as
demonstrated by functional and structural data at each step. In
vitro, AT-9010 inhibits enzymes essential to viral replication such
as the SARS-CoV-2 bi-functional nsp12 RNA
polymerase/nucleotidyltransferase, the dengue virus bi-functional
NS5 RNA polymerase/RNA methyltransferase, and the HCV NS5B RNA
polymerase.
Poster Number: 537Date/Time:
Tuesday, March 14 from 5:00-7:00 pm CET and Wednesday, March 15
from 12:15-2:15 pm CETTitle: Low Risk of Drug-Drug
Interactions (DDIs) for Bemnifosbuvir (BEM) Based Upon In Vitro
Metabolism and Transporter Interaction Studies
Results from these in vitro studies suggest that bemnifosbuvir
has a low risk of drug-drug interactions when co-administered with
drugs that are substrates of CYP450 enzymes, UGT1A1 or ABC/SLC
transporters. The enzymes that support metabolic activation of
bemnifosbuvir are of high capacity and are not likely to be
inhibited by commonly prescribed drugs. The observations from these
in vitro studies have been subsequently validated with Phase 1
clinical drug-drug interaction studies.
Poster Number: 549Date/Time:
Tuesday, March 14 from 5:00-7:00 pm CET and Wednesday, March 15
from 12:15-2:15 pm CETTitle: Pharmacokinetics and
Metabolism of [14C]-Bemnifosbuvir in Healthy Male Participants
Results from a Phase 1, open-label, single-dose, mass balance
study demonstrated that bemnifosbuvir 550 mg was well absorbed and
nearly completely recovered in urine and feces. The data showed
bemnifosbuvir and its metabolites did not accumulate in red blood
cells, with similar exposure in plasma and whole blood, and that
bemnifosbuvir underwent rapid and extensive metabolic activation to
the intracellular active triphosphate metabolite and thereafter
entered general circulation mostly as nucleoside metabolites.
AT-273, the nucleoside metabolite considered a surrogate of the
intracellular phosphates, exhibited a long half-life in plasma,
supporting once- and twice-daily dosing.
Hepatitis C
Poster Number: 411Date/Time:
Tuesday, March 14 from 5:00-7:00 pm CET and Wednesday, March 15
from 12:15 pm-2:15 pm CETTitle: The Combination of
Bemnifosbuvir (BEM) and Ruzasvir (RZR), the HCV NS5B and NS5A
Inhibitors, Demonstrates Potent In Vitro Synergistic Antiviral
Activity and In Vivo Preclinical Safety Without Adverse
Interactions
In vitro, the combination of bemnifosbuvir and ruzasvir
demonstrated greater inhibition of HCV replication compared to the
sum of inhibition of each agent alone in HCV replicon cells,
suggesting a synergistic antiviral effect when bemnifosbuvir and
ruzasvir are administered together.
In a 13-week toxicity study in rats in which bemnifosbuvir and
ruzasvir were administered alone or in combination at 500 mg/kg
once daily, treatments were well tolerated, and no adverse events
were observed. Results demonstrated that systemic exposures of
bemnifosbuvir, its metabolites, and ruzasvir were similar when
administered independently or in combination, suggesting no
significant drug-drug interactions between bemnifosbuvir and
ruzasvir.
This synergistic activity and no significant drug-drug
interactions, together with the previously demonstrated potent,
pan-genotypic, antiviral activity of each agent alone, suggest the
combination of bemnifosbuvir and ruzasvir has the potential to
offer a differentiated, short duration, pan-genotypic, protease
inhibitor-sparing regimen for patients with HCV, with or without
cirrhosis.
Dengue
Oral Presentation Number:
046Date/Time: Thursday, March 16 from 4:50-5:00 pm
CET
Title: AT-752 Targets Multiple Sites and
Activities on the Dengue Virus Replication Enzyme NS5
Results from this in vitro study demonstrated the mechanism of
action of AT-752. AT-9010, the active triphosphate metabolite of
AT-752, inhibited the essential DENV NS5 enzyme. AT-9010 targets
two NS5-associated enzyme activities, the RNA 2'-O-MTase and the
RNA-dependent RNA polymerase (RdRp) at its RNA elongation step. RNA
synthesis inhibition occurred for all 4 DENV serotypes. These
results illustrate at atomic resolution (1.97 Å) how RNA cap
methylation was prevented by AT-9010.
Nucleotide Analogue
Poster Number: 504Date/Time:
Tuesday, March 14 from 5:00-7:00 pm CET and Wednesday, March 15
from 12:15-2:15 pm CETTitle: A Non-Excisable Nucleotide
Analogue Active against SARS-CoV-2AT-1000 is a 2'-ribose
modified nucleotide analog, related to bemnifosbuvir but bearing a
sulfur atom at its α-phosphate (i.e., α-thio). Results from this in
vitro study show that AT-1000 exhibited potent anti-SARS-CoV2
activity, similar to bemnifosbuvir in human airway epithelial
cells. Unlike bemnifosbuvir, neither the Sp or Rp isomer
binds or inhibits the NiRAN domain nucleotidylation activity.
The α-thio modification therefore creates a novel compound,
exhibiting an original mechanism of action. These results suggest
that this single atom modification may provide a general approach
to potentiate a wide array of nucleotide analogues against RNA
viruses carrying natural resistance to nucleotide analogue
antivirals, such as highly pathogenic coronaviruses.
About Bemnifosbuvir for COVID-19
Bemnifosbuvir, a nucleotide polymerase inhibitor, targets the
SARS-CoV-2 RNA polymerase (nsp12), a highly conserved gene that is
unlikely to change as the virus mutates and new variants continue
to emerge. This gene is responsible for both replication and
transcription of SARS-CoV-2. Bemnifosbuvir has a unique mechanism
of action, with dual targets consisting of chain termination (RdRp)
and nucleotityltransferase (NiRAN) inhibition, which has the
potential to create a high barrier to resistance. In vitro data
confirm that bemnifosbuvir is active with similar efficacy against
all variants of concern and variants of interest that have been
tested, including Omicron subvariants BA.4 and BA.5. Bemnifosbuvir
is currently being evaluated in SUNRISE-3, a global multicenter
Phase 3 registrational trial for the treatment of COVID-19.
About Bemnifosbuvir and
Ruzasvir for Hepatitis C
VirusBemnifosbuvir has been shown to be approximately
10-fold more active than sofosbuvir (SOF) in
vitro against a panel of laboratory strains and clinical
isolates of HCV genotypes 1–5. In vitro studies
demonstrated bemnifosbuvir remained fully active against SOF
resistance-associated strains (S282T), with up to 58-fold more
potency than SOF. The pharmacokinetic (PK) profile of bemnifosbuvir
supports once-daily dosing for the treatment of HCV and
bemnifosbuvir has been well tolerated at doses up to 550 mg for
durations up to 8-12 weeks in healthy and HCV infected
subjects.
Ruzasvir (RZR), an oral NS5A inhibitor, has demonstrated highly
potent and pangenotypic antiviral activity in preclinical
(picomolar range) and clinical studies. RZR has been administered
to over 1,200 HCV-infected patients at daily doses of up to 180 mg
for up to 24 weeks and has demonstrated a favorable safety profile.
RZR’s PK profile supports once-daily dosing.
The combination of bemnifosbuvir and ruzasvir for the treatment
of HCV is in Phase 2 development.
About Atea PharmaceuticalsAtea is a clinical
stage biopharmaceutical company focused on discovering, developing
and commercializing oral therapies to address the unmet medical
needs of patients with serious viral infections. Leveraging the
Company’s deep understanding of antiviral drug development,
nucleos(t)ide chemistry, biology, biochemistry and virology, Atea
has built a proprietary nucleos(t)ide prodrug platform to develop
novel product candidates to treat single stranded ribonucleic acid,
or ssRNA, viruses, which are a prevalent cause of serious viral
diseases. Atea plans to continue to build its pipeline of antiviral
product candidates by augmenting its nucleos(t)ide platform with
other classes of antivirals that may be used in combination with
its nucleos(t)ide product candidates. Currently, Atea is focused on
the development of orally-available antiviral agents for serious
viral infections, including severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, and
hepatitis C virus (HCV). For more information, please visit
www.ateapharma.com.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. All statements contained in this press release that do not
relate to matters of historical fact should be considered
forward-looking statements, including without limitation statements
regarding our expectations surrounding the potential of our product
candidates, including bemnifosbuvir combination product candidates,
and expectations regarding our pipeline, including trial design and
development timelines. These statements are neither promises nor
guarantees, but involve known and unknown risks, uncertainties and
other important factors that may cause our actual results,
performance or achievements to be materially different from any
future results, performance or achievements expressed or implied by
the forward-looking statements, including, but not limited to, the
uncertainty around and costs associated with the clinical
development of bemnifosbuvir as a potential treatment for COVID-19
and the combination of bemnifosbuvir and ruzasvir as a potential
treatment for HCV. These and other important factors discussed
under the caption “Risk Factors” in our Annual Report on Form 10-K
for the year ended December 31, 2022 and our other filings with the
SEC could cause actual results to differ materially from those
indicated by the forward-looking statements made in this press
release. Any such forward-looking statements represent management’s
estimates as of the date of this press release. While we may elect
to update such forward-looking statements at some point in the
future, we disclaim any obligation to do so, even if subsequent
events cause our views to change.
Contacts
Jonae BarnesSVP, Investor Relations and Corporate
Communications617-818-2985barnes.jonae@ateapharma.com
Will O’ConnorStern Investor Relations
212-362-1200will.oconnor@sternir.com
Atea Pharmaceuticals (NASDAQ:AVIR)
Historical Stock Chart
From Jul 2024 to Jul 2024
Atea Pharmaceuticals (NASDAQ:AVIR)
Historical Stock Chart
From Jul 2023 to Jul 2024