* Recruitment in NATiV3 clinical trial continues in both cohorts with over
80% of the targeted number of patients enrolled in the main cohort and 100%
in the exploratory cohort of NATiV3.
* Analysis of the baseline characteristics of all patients randomized in the
main cohort of NATiV3 show a patient profile similar to patients randomized
in the NATIVE Phase IIb clinical trial.
* A blinded analysis of all randomized patients suggests weight gain plateaus
and stabilizes between week 24 and 36.
* First visit of the last patient of NATiV3 is anticipated to occur during the
second half of 2024, and topline results are expected at the beginning of
the second half of 2026.
* Patent portfolio strengthened with new patent secured protecting the
compound until 2043.
* The Company is currently working on multiple fronts to secure financing to
fund the continuity of its activities.
Daix (France), Long Island City (New York, United States), July 5, 2024
- Inventiva (Euronext Paris and Nasdaq: IVA) ("Inventiva" or the "Company"), a
clinical-stage biopharmaceutical company focused on the development of oral
small molecule therapies for the treatment of patients with metabolic
dysfunction-associated steatohepatitis ("MASH"), also known as non-alcoholic
steatohepatitis ("NASH"), and other diseases with significant unmet medical
needs, today provided an update on its clinical program evaluating lanifibranor
for the treatment of MASH/NASH and its financial position.
Frederic Cren, Chairman, Chief Executive Ofiicer, and cofounder of Inventiva
stated: "We have made good progress with the recruitment in our Phase III
clinical trial and continue to see a strong engagement of clinical trial sites
in NATiV3. We are encouraged by the patient characteristics we are seeing in the
main cohort of NATiV3 compared to those of our Phase IIb trial and above all by
the plateau effect we see in the weight gain curve which confirms the
differentiated profile of our panPPAR compound versus single PPAR gamma
compounds such as pioglitazone. The data obtained from our various clinical
studies demonstrate that lanifibranor could fully address the broad spectrum of
the disease and recent presented data at the EASL Liver Congress from other
compounds in development further bolster our belief in the potential of oral
lanifibranor for use alone or in combination therapy. We are continuing to
evaluate financing options to extend our current cash runway and continue our
activities as we are determined to bring lanifibranor to market as a treatment
option for patients with MASH."
Update on its clinical program evaluating lanifibranor for the treatment of MASH
The recruitment in NATiV3 is advancing with screening ongoing at 347 sites
across 19 countries. As of July 5, 2024, 1,027 patients have been randomized of
which 784 patients in the main cohort of NATiV3, representing 82% of the
targeted number. The geographical distribution of the main cohort confirms that
North America and Western Europe are the key contributors to patient recruitment
(67% and 21% respectively) while China has only contributed marginally (2% of
patients). The targeted number of 200 patients to be recruited in the
exploratory cohort has been met with 243 patients randomized to date. The
recruitment in the exploratory will continue until recruitment is complete in
the main cohort.
The Company estimates that, given the number of patients currently in screening
who are eligible for enrolment in the main cohort, the Company must recruit an
additional 165 patients. Due to a delay of approximately 3 to 5 months in
recruitment, the Company is currently now targeting: the last patient first
visit for the second half of 2024 and the publication of the topline results in
the beginning of the second half of 2026.
The baseline characteristics of the patients enrolled so far in the main cohort
are in line with the expectations of the Company and are consistent with those
from the NATIVE Phase IIb clinical trial of lanifibranor in patients with
MASH/NASH ("NATIVE"). In addition, 13% of patients enrolled in the main cohort
were receiving a stable dose of GLP1 receptor agonist and 9% a stable dose of
SGLT2 inhibitors at baseline and should provide the Company with insights on the
potential of the benefits of a combination of these class of products with
lanifibranor.
Importantly, a blinded review which included 780 patients enrolled in the main
cohort of NATiV3 (placebo and treatment arms pooled) showed a similar weight
gain as the one observed during the NATIVE Phase IIb trial which seems to
plateau and stabilize after 24 to 36 weeks of treatment, and this even in the
subgroup of patients who have gained more than 5% weight. If confirmed, this
encouraging result highlights the particular profile of lanifibranor versus
single PPAR gamma in particular pioglitazone, where such a plateau effect has
not been observed(1).
Intellectual property strategy
We continue to work to reinforce lanifibranor patent portfolio. As of today,
lanifibranor patent portfolio is made up of 20 patent families comprising both
patents and patent applications fully owned by Inventiva. These patent families
are respectively directed to lanifibranor product, method of treatment,
combination therapy, process, formulation and diagnostic methods. With our
patent family directed to crystalline forms of lanifibranor (patent applications
pending), the company expects to potentially extend protection on lanifibranor
product until at least 2043.
Financial update
Considering the Company's cost structure and forecasted expenditures, and
without taking into account additional cash preservation measures that the
Company may implement in the short term, the Company estimates that its cash,
cash equivalents and deposits will allow the Company to fund its operations as
planned through the second half of July 2024(2). The Company estimates that, as
of May 31, 2024, the Company's cash and cash equivalents were (non-audited) EUR9.6
million, short-term deposits were EUR0.1 million(3), and long-term deposits were
EUR10.0 million(4), compared with EUR26.9 million, EUR0.01 million and EUR9 million,
respectively, as of December 31, 2023.
In order to finance its activities and advance its development objectives for
its research and development programs, the Company will need to raise additional
funds. To date, the Company has explored a variety of transactions, including
the issuance of debt, equity and other instruments, which thus far have not been
successful. However, the Company is working to complete a royalty-based
financing that would extend its cash runway through the summer of 2024, which it
anticipates announcing in the near-term. Even if the royalty-based financing is
successful (of which there can be no assurance), the Company will need to raise
additional funds, and it is continuing to actively evaluate potential financing
(including debt, equity and equity-linked or other instruments) and strategic
options.
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 MASH/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 MASH/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 MASH/NASH and
F2/F3 stage of liver fibrosis. The trial takes place in 24 countries and in more
than 400 clinical sites and recruits approximately 900 patients to be treated
over a 72-week period. The effect of lanifibranor will be assessed on several
histological endpoints, including MASH/NASH resolution and improvement of
fibrosis of at least one stage. An exploratory cohort is anticipated to enroll
approximately 200 patients with MASH/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 MASH/NASH. Topline
results of NATiV3 are expected for the second 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 MASH/NASH 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
MASH/NASH, a common and progressive chronic liver disease.
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 a
candidate for its Hippo signaling 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
Inventiva Brunswick Group
Tristan Roquet
Pascaline Clerc, Montegon /
PhD Aude Lepreux / Westwicke, an ICR
EVP, Strategy and Julia Cailleteau Company
Corporate Affairs Media relations Patricia L. Bank
inventiva@brunswickgro Investor relations
media@inventivaph up.com patti.bank@westwicke.com
arma.com (mailto:inventiva@brun (mailto:patti.bank@westw
(mailto:media@inve swickgroup.com) icke.com)
ntivapharma.com)
+1 202 499 8937 +33 1 53 96 83 83 +1 415 513-1284
Important Notice
This press release contains certain "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, statements with respect to Inventiva's
estimated cash position, including its estimated cash runway, Inventiva's review
of potential financing and strategic options and their outcome and likelihood of
success, the completion of a royalty-based financing that would extend its cash
runway through the summer, the success of Inventiva's intellectual property
strategy, as well as statements regarding Inventiva's clinical trial, including
the design, duration, timing, recruitment, costs, screening and enrollment for
those trials, including the ongoing NATiV3 Phase III clinical trial with
lanifibranor in MASH/NASH, 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 alone and in combination with other treatments, potential
regulatory submissions and approvals, and Inventiva's pipeline and preclinical
and clinical development plans, business and regulatory strategy, the
anticipated timing of Inventiva's Phase III clinical trial of lanifibranor, the
commercialization of lanifibranor and achievement of any sales related thereto,
and anticipated future performance. 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", "opportunity", "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 cannot
provide assurance on the impacts of the SUSAR on enrollment or the ultimate
impact on the results or timing of the NATiV3 trial or regulatory matters with
respect thereto, 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 ability to obtain financing and to enter into
potential transactions, 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 its clinical trials may prove to be wrong and
regulatory authorities may require holds and/or amendments to Inventiva's
clinical trials, Inventiva's expectations with respect to the clinical
development plan for lanifibranor for the treatment of MASH/NASH may not be
realized and may not support the approval of a New Drug Application, Inventiva
and its partners may encounter substantial delays beyond expectations 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, enrollment 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,
enrollment 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, 2023, filed with the Autorité des Marchés Financiers on April 3, 2024, and
the Annual Report on Form 20-F for the year ended December 31, 2023, filed with
the Securities and Exchange Commission (the "SEC") on April 3, 2024 for other
risks and uncertainties affecting Inventiva, including those described under the
caption "Risk Factors", and in our future filings with the SEC. 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
statements.
(1) Sanyal A et al. NEJM, 362 ; 18, 2010
(2) This estimate is based on the Company's current business plan and excludes
any potential milestones payable to or by the Company and any additional
expenditures related to the potential continued development of the odiparcil
program or resulting from the potential in licensing or acquisition of
additional product candidates or technologies, or any associated development the
Company may pursue. The Company may have based this estimate on assumptions that
are incorrect and the Company may end up using its resources sooner than
anticipated.
(3) Short-term deposits are classified as "other current assets" in the
consolidated statement of financial position under IFRS and are considered by
the Company to be liquid and readily available.
(4) The two-year long-term deposit can be accessed before expiry of the term
with 31 days' notice and is considered liquid by the Company.
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