* 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 EUR25 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 Committee(2) 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 EUR25 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 2024(2) 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 NASH(3), 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
2023(2). 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 PPAR? and PPAR?, and a partial
activation of PPAR?. 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
(http://www.inventivapharma.com)
Contacts
Brunswick Group
Tristan Roquet Montegon Westwicke, an ICR
Inventiva / Company
Aude Lepreux / Patricia L. Bank
Pascaline Clerc Matthieu Benoist Investor relations
EVP, Strategy and Media relations patti.bank@westwicke.c
Corporate Affairs inventiva@brunswickgrou om
media@inventivaphar p.com (mailto:patti.bank@wes
ma.com (mailto:inventiva@bruns twicke.com)
(mailto:media@inven wickgroup.com)
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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 EUR25 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 EUR70.0
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 EUR18.0 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)
(https://inventivapharma.com/wp-content/uploads/2023/12/Inventiva-PR-3rd-DMC-
NATiV3-EN-12-04-2023.pdf)
(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
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