- The first patient was randomized in China in the NATiV3 Phase
III clinical trial, triggering a milestone payment of $3 million
from CTTQ to Inventiva.
- With this milestone payment Inventiva expects to have met the
operational and financial conditions precedent to draw the second
€25 million tranche of the EIB loan.1
- China’s National Medical Products Administration has granted
“Breakthrough Therapy Designation” to lanifibranor for the
treatment of NASH. Lanifibranor is believed to be the first drug
candidate to receive such designation from both the FDA and the
NMPA.
- As of December 20, 2023, a total of 793 patients have been
randomized in NATiV3 of which 657 in the main cohort and 136 in the
exploratory cohort. 607 patients are currently in the screening
process.
- The last patient first visit in the NATiV3 Phase III clinical
trial is now expected in the first quarter of 2024, and the target
number of randomized patients in the main cohort is expected to be
reached in the second quarter of 2024.
- Analysis of the baseline characteristics of all patients
randomized in the main cohort suggests a patient profile aligned
with those of patients randomized in the NATIVE Phase II clinical
trial.
- Lanifibranor continues to show a favorable tolerability profile
as confirmed by the third Data Monitoring Committee2 of November
2023.
- Topline results of the proof-of-concept Phase II clinical
trial, LEGEND, evaluating lanifibranor in combination with
empagliflozin are expected in the first quarter of 2024.
Daix (France),
Long Island City (New York, United States),
December 20, 2023 – Inventiva (Euronext Paris and
Nasdaq: IVA) (the “Company”), a clinical-stage biopharmaceutical
company focused on the development of oral small molecule therapies
for the treatment of non-alcoholic steatohepatitis (“NASH”) and
other diseases with significant unmet medical needs, today
announced that the first patient has been randomized in China in
the global NATiV3 Phase III clinical trial and provided an update
on its clinical development program.
Milestone payment from CTTQ and EIB
loan
Following the randomization of the first patient
in China, Inventiva is eligible to receive a $3 million milestone
payment from Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
(“CTTQ”). This would be the second of the two short-term milestone
payments following the $2 million milestone payment from CTTQ
received on July 19, 2023, under the license and collaboration
agreement with CTTQ. Upon the anticipated receipt in January 2024
of this $3 million milestone, Inventiva is expected to have met all
financial and operational conditions precedent required to draw the
second €25 million tranche under the finance contract with the
European Investment Bank (“EIB”) dated May 16, 2022 (the "Finance
Contract"). The Company expects to draw this second tranche in
early 2024, following the issuance of warrants to the EIB as
provided in the Finance Contract.
Breakthrough Therapy Designation for
lanifibranor in NASH by China’s NMPA
Lanifibranor was granted Breakthrough Therapy
Designation for NASH by China’s National Medical Products
Administration (NMPA). Similar to the U.S. Food and Drug
Administration’s (FDA) Breakthrough Therapy Designation, this
designation is intended to accelerate the development and review of
drugs for serious or life-threatening conditions. The NMPA granted
“Breakthrough Therapy Designation” based on the results of
Inventiva's Phase IIb NATIVE clinical trial. Inventiva believes
that lanifibranor is the first drug candidate to receive
“Breakthrough Therapy Designation” from both the FDA and the NMPA
for the treatment of NASH.
NATiV3 update
Frederic Cren, CEO and co-founder of
Inventiva said: ”While we are not reaching the first visit
of the last patient by the end of 2023 as previously projected, the
improvements in the randomization, screening numbers and screen
failure rate give us confidence that we can reach this milestone in
the first quarter of 2024. The recommendation of our third Data
Monitoring Committee (DMC) in November 20242 to continue the trial
without modification to the protocol is further confirmation of the
good safety profile of lanifibranor. Furthermore, we have high
hopes that the results of the LEGEND trial will show benefit of the
combination of lanifibranor with empagliflozin in patients with
NASH.”
As of December 20, 2023, 468 clinical sites have
been activated in 24 countries, including China, and a total of 793
patients have been randomized, of which 657 in the main cohort and
136 in the exploratory cohort. 607 patients are in the screening
process and, based on the recent screen failure rate of
approximately 80%, Inventiva expects 121 additional patients to be
randomized in the main cohort in the next 10 weeks.
Since July, with limited contribution from the
sites in China, the newly opened sites and a third party clinical
network in Mexico, between 250 to 300 patients are screened and
approximately 50 patients are randomized in the main cohort each
month, and the monthly enrolment rate is averaging 0.14
patient/site/month in the main cohort. Therefore, if the current
screen failure rate for the main cohort and the number of patients
entering the screening process are maintained, Inventiva now
expects the first visit of the last patient to be in the first
quarter of 2024 and to complete randomization in the second quarter
of 2024.
Topline results for the Phase III NATiV3
clinical trial are now expected to be published in the first half
of 2026 versus the second half of 2025, as previously
communicated.
If the results of the trial confirm sufficient
clinical benefit and a continued good safety profile, Inventiva
plans to submit an application for accelerated approval in the
United States and conditional approval in the European Union for
the marketing of lanifibranor. In addition, CTTQ would also be in
capacity to submit an application for a marketing authorization in
Greater China.
NATiV3 patients distribution and
characteristic
Approximately 70% of the patients randomized in
the main and exploratory cohorts are from the United States, ~20%
from Europe and ~10% from Latin America and the rest of the world.
At baseline, 13% of patients randomized in the main cohort are
receiving a stable dose GLP1 receptor agonists and 8% are receiving
stable SGLT2 inhibitors. The baseline characteristics of the
patients enrolled so far in the main cohort are in line with
expectations and the patient population in the NATIVE Phase IIb
clinical trial. The main difference in patient characteristics
observed thus far is that there is a higher percentage of patients
with type 2 diabetes (T2D) in the main cohort of the NATiV3 Phase
III trial compared to the NATIVE Phase IIb trial (55% vs 42%,
respectively). The effect size of lanifibranor therapy over placebo
in the Phase IIb clinical trial on the composite endpoint “NASH
resolution and fibrosis improvement” (which corresponds to the
primary efficacy endpoint in the NATiV3 Phase III clinical trial),
was higher in patients with T2D than in patients without diabetes:
21% and 26% for lanifibranor 800 and 1200 mg/day, respectively, in
patients with T2D compared to 7% and 22%, respectively, in patients
without T2D. Given the higher risk of hepatic and extrahepatic
morbidity in patients with T2D and NASH3, the higher effect size
observed in patients with NASH and T2D treated with lanifibranor in
the Phase IIb trial is an important result for this specific
patient population if confirmed in the larger clinical trial.
As of December 20, 2023, 136 patients are
randomised in the exploratory cohort including approximately 30%
of patients with fibrosis stage F4. Inventiva believes that
this subgroup of patients will provide valuable data on
lanifibranor efficacy and safety.
Lanifibranor continues to show a favorable
tolerability profile as confirmed by the third Data Monitoring
Committee (DMC) that took place late November 20232. This safety
assessment was based on the review of safety data from more than
500 patients, including patients that have been treated with
lanifibranor for more than 72 weeks.
Update on Phase II clinical trial
LEGEND
Enrolment in the proof of concept, LEGEND Phase
II clinical trial evaluating lanifibranor in combination with the
SGLT2 inhibitor empagliflozin in patients with NASH has been
stopped, and data collection and cleaning is ongoing. The first
topline results on primary and secondary endpoints are expected for
the end of the first quarter of 2024. The primary efficacy endpoint
of the trial is a change in Hemoglobin A1c (“HbA1c”) at the end of
the 24-week treatment compared to baseline. Secondary endpoints
include changes in liver enzymes, glycaemic and lipids parameters,
and inflammatory markers. The trial has been designed to provide
valuable information on body weight evolution in patients with NASH
and T2D when treated with lanifibranor and empagliflozin, and on
the reduction of hepatic steatosis using magnetic resonance imaging
(MRI).
About lanifibranor
Lanifibranor, Inventiva’s lead product
candidate, is an orally-available small molecule that acts to
induce antifibrotic, anti-inflammatory and beneficial vascular and
metabolic changes in the body by activating all three peroxisome
proliferator-activated receptor (“PPAR”) isoforms, which are
well-characterized nuclear receptor proteins that regulate gene
expression. Lanifibranor is a PPAR agonist that is designed to
target all three PPAR isoforms in a moderately potent manner, with
a well-balanced activation of PPARα and PPARδ, and a partial
activation of PPARγ. While there are other PPAR agonists that
target only one or two PPAR isoforms for activation, lanifibranor
is the only pan-PPAR agonist in clinical development for the
treatment of NASH. Inventiva believes that lanifibranor’s moderate
and balanced pan-PPAR binding profile contributes to the favorable
tolerability profile that has been observed in clinical trials and
pre-clinical studies to date. The FDA has granted Breakthrough
Therapy and Fast Track designation to lanifibranor for the
treatment of NASH.
About the NATiV3 Phase III
trial
NATiV3 is a randomized, double-blind,
placebo-controlled clinical trial designed to evaluate the
long-term efficacy and safety of lanifibranor (800mg/daily and
1200mg/daily) in adult patients with biopsy-proven non-cirrhotic
NASH and F2/F3 stage of liver fibrosis. The trial takes place in 24
countries and in more than 400 clinical sites and to recruit
approximately 900 patients to be treated over a 72-week period. The
effect of lanifibranor will be assessed on several histological
endpoints, including NASH resolution and improvement of fibrosis of
at least one stage.
An exploratory cohort is anticipated to enrol
approximately 200 patients with NASH and fibrosis screen-failed on
histology for the main NATiV3 clinical trial. Inventiva
anticipates that this exploratory cohort may allow the generation
of additional data using non-invasive tests and contribute to the
regulatory safety database requirement to support the planned
submission for potential accelerated approval to the Food and Drug
Administration (FDA) and potential conditional approval to the
European Medicines Agency (EMA) of lanifibranor for the treatment
of NASH.
Topline results of NATiV3 are expected for the
half 2026. For more information about NATiV3, visit
clinicaltrials.gov.
About Inventiva
Inventiva is a clinical-stage biopharmaceutical
company focused on the research and development of oral small
molecule therapies for the treatment of patients with NASH,
mucopolysaccharidoses (“MPS”) and other diseases with significant
unmet medical need. The Company benefits from a strong expertise
and experience in the domain of compounds targeting nuclear
receptors, transcription factors and epigenetic modulation.
Inventiva is currently advancing one clinical candidate, has a
pipeline of two preclinical programs and continues to explore other
development opportunities to add to its pipeline.
Inventiva’s lead product candidate,
lanifibranor, is currently in a pivotal Phase III clinical trial,
NATiV3, for the treatment of adult patients with NASH, a common and
progressive chronic liver disease for which there are currently no
approved therapies.
Inventiva’s pipeline also includes odiparcil, a
drug candidate for the treatment of adult MPS VI patients. As part
of Inventiva’s decision to focus clinical efforts on the
development of lanifibranor, it suspended its clinical efforts
relating to odiparcil and is reviewing available options with
respect to its potential further development. Inventiva is also in
the process of selecting an oncology development candidate for its
Hippo signalling pathway program.
The Company has a scientific team of
approximately 90 people with deep expertise in the fields of
biology, medicinal and computational chemistry, pharmacokinetics
and pharmacology, and clinical development. It owns an extensive
library of approximately 240,000 pharmacologically relevant
molecules, approximately 60% of which are proprietary, as well as a
wholly-owned research and development facility.
Inventiva is a public company listed on
compartment B of the regulated market of Euronext Paris (ticker:
IVA, ISIN: FR0013233012) and on the Nasdaq Global Market in the
United States (ticker: IVA). www.inventivapharma.com
Contacts
Inventiva Pascaline ClercEVP, Strategy and
Corporate Affairsmedia@inventivapharma.com +1 202
499 8937 |
Brunswick GroupTristan Roquet Montegon /Aude
Lepreux /Matthieu BenoistMedia
relationsinventiva@brunswickgroup.com +33 1 53 96 83
83 |
Westwicke, an ICR CompanyPatricia L. BankInvestor
relationspatti.bank@westwicke.com
+1 415 513-1284 |
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Important Notice
This press release contains “forward-looking
statements” within the meaning of the safe harbor provisions of the
Private Securities Litigation Reform Act of 1995. All statements,
other than statements of historical facts, included in this press
release are forward-looking statements. These statements include,
but are not limited to, preliminary analysis of clinical trials,
regulatory plans, forecasts and estimates with respect to
Inventiva’s pre-clinical programs and clinical trials, including
design, protocols, duration, timing, recruitment costs, screening
and enrolment for those trials, including the ongoing NATiV3 Phase
III clinical trial with lanifibranor in patients with NASH and the
ongoing LEGEND Phase II clinical trial evaluating lanifibranor in
combination with the sSGLT2 inhibitor empagliflozin in
patients with NASH, including the possibility for patients to
participate in those trials, the clinical development and
regulatory plans and pathway for lanifibranor of Sino Biopharm and
its affiliates, including the Phase III clinical trial in patients
with NASH, potential development of and regulatory pathway for
odiparcil, clinical trial data releases and publications, the
information, insights and impacts that may be gathered from
clinical trials, the potential therapeutic benefits of Inventiva’s
product candidates, including lanifibranor and its safety and
tolerability profile, expectations with respect to clinical
development and commercialization by CTTQ, including with respect
to potential clinical trials and regulatory approvals, expectations
with respect to the benefits of the agreement with CTTQ, including
potential acceleration of lanifibranor commercialization in the
event required regulatory approvals are obtained, potential
regulatory submissions and approvals, including a potential NDA
filing in China, the United States and Europe, the expected benefit
of having received Breakthrough Therapy Designation from the FDA
and NMPA, including its impact on the development and review
timeline of Inventiva’s product candidates, Inventiva’s future
activities, expectations, plans, growth and prospects of Inventiva,
and achievement of milestones, potential and expected milestone
payments, including milestone payments from CTTQ, potential
regulatory submissions and approvals, including potential
accelerated approval in the United States and conditional approval
Europe, the potential of Sino Biopharm’s products and future
activities, expectations, plans, growth and prospects of Sino
Biopharm, and Inventiva’s ability to satisfy the conditions
precedent for the drawing of the second tranche of the EIB loan
facility and the expected timing of the disbursement of the second
tranche. Certain of these statements, forecasts and estimates can
be recognized by the use of words such as, without limitation,
“believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”,
“estimates”, “may”, “will”, “would”, “could”, “might”, “should”,
“designed”, “hopefully”, “target”, “potential”, “possible,” “aim”,
and “continue” and similar expressions. Such statements are not
historical facts but rather are statements of future expectations
and other forward-looking statements that are based on management's
beliefs. These statements reflect such views and assumptions
prevailing as of the date of the statements and involve known and
unknown risks and uncertainties that could cause future results,
performance or future events to differ materially from those
expressed or implied in such statements. Actual events are
difficult to predict and may depend upon factors that are beyond
Inventiva's control. There can be no guarantees with respect to
pipeline product candidates that the clinical trial results will be
available on their anticipated timeline, that future clinical
trials will be initiated as anticipated, that product candidates
will receive the necessary regulatory approvals, or that any of the
anticipated milestones by Inventiva or its partners will be reached
on their expected timeline, or at all. Future results may turn out
to be materially different from the anticipated future results,
performance or achievements expressed or implied by such
statements, forecasts and estimates, due to a number of factors,
including that Inventiva is a clinical-stage company with no
approved products and no historical product revenues, Inventiva has
incurred significant losses since inception, Inventiva has a
limited operating history and has never generated any revenue from
product sales, Inventiva will require additional capital to finance
its operations, in the absence of which, Inventiva may be required
to significantly curtail, delay or discontinue one or more of its
research or development programs or be unable to expand its
operations or otherwise capitalize on its business opportunities
and may be unable to continue as a going concern, Inventiva's
future success is dependent on the successful clinical development,
regulatory approval and subsequent commercialization of current and
any future product candidates, preclinical studies or earlier
clinical trials are not necessarily predictive of future results
and the results of Inventiva's and its partners’ clinical trials
may not support Inventiva's and its partners’ product candidate
claims, Inventiva’s expectations with respect to the changes to the
clinical development plan for lanifibranor for the treatment of
NASH may not be realized and may not support the approval of a New
Drug Application, Inventiva and its partners may encounter
substantial delays in their clinical trials or fail to demonstrate
safety and efficacy to the satisfaction of applicable regulatory
authorities, the ability of Inventiva and its partners to recruit
and retain patients in clinical studies, enrolment and retention of
patients in clinical trials is an expensive and time-consuming
process and could be made more difficult or rendered impossible by
multiple factors outside Inventiva's and its partners’ control,
Inventiva's product candidates may cause adverse drug reactions or
have other properties that could delay or prevent their regulatory
approval, or limit their commercial potential, Inventiva faces
substantial competition and Inventiva’s and its partners' business,
and preclinical studies and clinical development programs and
timelines, its financial condition and results of operations could
be materially and adversely affected by geopolitical events, such
as the conflict between Russia and Ukraine and related sanctions,
impacts and potential impacts on the initiation, enrolment and
completion of Inventiva’s and its partners’ clinical trials on
anticipated timelines and the state of war between Israel and Hamas
and the related risk of a larger conflict, health epidemics, and
macroeconomic conditions, including global inflation, rising
interest rates, uncertain financial markets and disruptions in
banking systems. Given these risks and uncertainties, no
representations are made as to the accuracy or fairness of such
forward-looking statements, forecasts and estimates. Furthermore,
forward-looking statements, forecasts and estimates only speak as
of the date of this press release. Readers are cautioned not to
place undue reliance on any of these forward-looking
statements.
Please refer to the Universal Registration
Document for the year ended December 31, 2022 filed with the
Autorité des Marchés Financiers on March 30, 2023 as amended on
August 31, 2023, the Annual Report on Form 20-F for the year ended
December 31, 2022 filed with the Securities and Exchange Commission
on March 30, 2023, and the Half-Year Report for the six months
ended June 30, 2023 on Form 6-K filed with the SEC on October 3,
2023, for other risks and uncertainties affecting Inventiva,
including those described from time to time under the caption “Risk
Factors”. Other risks and uncertainties of which Inventiva is not
currently aware may also affect its forward-looking statements and
may cause actual results and the timing of events to differ
materially from those anticipated.All information in this press
release is as of the date of the release. Except as required by
law, Inventiva has no intention and is under no obligation to
update or review the forward-looking statements referred to above.
Consequently, Inventiva accepts no liability for any consequences
arising from the use of any of the above statement.
1 The disbursement of the second tranche of
€25 million is subject to, among other conditions, (i) the Company
issuing warrants to EIB in accordance with the terms and conditions
of the warrant agreements entered into July 1, 2022 in connection
with the EIB credit facility, (ii) the receipt by the Company from
the date of the EIB credit facility of an aggregate amount of at
least €70.0 million (as of today, the Company has received 68.5
million of euros, which includes the August 2023 financing, the
Hepalys upfront payment of $10.0 million and the €18.0 million that
was a condition for the disbursement of the first tranche of the
EIB loan), paid either in exchange for Company shares, or through
upfront or milestone payments; and (iii) operational conditions,
including criteria based on patient enrolment and number of sites
activated in the Company’s NATiV3 Phase III clinical trial of
lanifibranor in patients with NASH a condition that the Company
believes it has met in December 2023. 2
Inventiva-PR-3rd-DMC-NATiV3-EN-12-04-2023.pdf
(inventivapharma.com)3 Kenneth Cusi; Time to Include Nonalcoholic
Steatohepatitis in the Management of Patients With Type 2
Diabetes. Diabetes Care 1 February 2020;
43 (2): 275–279. https://doi.org/10.2337/dci19-0064
- Inventiva - PR - First patient randomized in China and NATiV3
status update - EN - 12 20 2023
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