SGLT2

Initial Data from Ongoing MyPeak™-1 Phase 1b of TN-201 for MYBPC3-associated HCM Expected in Second Half of 2024 On Track to Dose First Patient in RIDGE™-1Phase 1b Clinical Trial of TN-401 for PKP2-associated ARVC in Second Half 2024 $47 Million Net Proceeds from Recent Financing Extends Cash Runway into Second Half of 2025 SOUTH SAN FRANCISCO, Calif., March 18, 2024 (GLOBE NEWSWIRE) -- Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, today reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a corporate update. “Tenaya had a successful year of sustained execution in 2023 that meaningfully advanced our portfolio of genetic medicines for heart disease. We announced IND clearance for the TN-201 and TN-401 gene therapy programs; activated clinical trial sites in the USA, Canada, and Europe; dosed the first patient with TN-201; manufactured sufficient clinical trial material for both gene therapy programs at our own cGMP facility; and presented compelling preclinical data from our gene editing and capsid engineering efforts,” said Faraz Ali, Chief Executive Officer of Tenaya. “We look forward to focusing efforts in 2024 on generating early clinical data with TN-201 from the MyPeak-1 study and on initiating patient dosing with TN-401 in the RIDGE-1 study.” Business and Program UpdatesTN-201 – Gene Therapy for MYBPC3-Associated Hypertrophic Cardiomyopathy (HCM) In October 2023, the first patient was dosed in the MyPEAK-1 Phase 1b clinical trial of TN-201 for the treatment of Myosin Binding Protein C3 (MYBPC3)-associated HCM. MyPEAK-1 is a multi-center, open-label, dose-escalation trial designed to assess safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-201. Tenaya anticipates sharing initial safety, biopsy and biomarker data from the first cohort of patients in MyPEAK-1 trial in the second half of 2024. Tenaya is conducting two non-interventional studies to support the development of TN-201: MyClimb, a natural history study of pediatric patients with MYBPC3-associated HCM and a study evaluating seroprevalence to adeno-associated virus serotype 9 (AAV9) antibodies among adults with MYBPC3-associated HCM. In October 2023, Tenaya shared interim results indicating that a majority of MYBPC3-associated HCM patients could be eligible for TN-201 treatment due to low levels of preexisting neutralizing antibodies to AAV9. TN-401 – Gene Therapy for PKP2-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Tenaya is on track to begin dosing in the RIDGE-1 Phase 1b clinical trial of TN-401 in the second half of 2024. RIDGE-1 is a multicenter, open-label, dose-escalation trial designed to assess safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-401 for the treatment of ARVC caused by mutations to the Plakophilin-2 (PKP2) gene.In November, TN-401 received Fast Track Designation from the FDA.Tenaya is currently conducting a global, non-interventional seroprevalence and natural history study (RIDGE™) enrolling adult PKP2-associated ARV patients. TN-301 – Small Molecule HDAC6 Inhibitor for Heart Failure with Preserved Ejection Fraction (HFpEF) At the 2023 Heart Failure Society of America Annual Scientific Meeting in October 2023, Tenaya shared positive clinical and preclinical data for its small molecule HDAC6 inhibitor program, TN-301. Results from a Phase 1 dose-escalation study demonstrated that TN-301 was generally well tolerated across the broad range of doses studied. Pharmacokinetic (PK) results showed overall dose proportionality in the single- and multiple-ascending dose stages of the study with a half-life supportive of once-daily dosing. Robust HDAC6 inhibition was observed and increasing doses and exposures with TN-301 correlated with increased pharmacodynamic effects.New preclinical results demonstrated that the combination of Tenaya’s HDAC6 inhibitor with empagliflozin (a sodium-glucose cotransporter-2 inhibitor) achieved additive benefits in validated HFpEF mouse models compared to either compound alone. Follow-on FinancingIn February 2024, Tenaya completed a follow-on offering with net proceeds of $46.5 million after discounts, commissions, and other offering expenses. The offering consisted of approximately 8.89 million shares of common stock priced at $4.50 per share and, in lieu of common stock for one investor, pre-funded warrants to purchase up to an aggregate of approximately 2.2 million shares at a price of $4.499 per pre-funded warrant. The offering included participation from new and existing investors, The Column Group, RA Capital Management, Venrock Healthcare Capital Partners, Octagon Capital, funds and accounts managed by BlackRock, Armistice Capital, Integral Health Asset Management, PFM Health Sciences, LP and Soleus Capital. Fourth Quarter and Full Year 2023 Financial Highlights Cash Position and Guidance: As of December 31, 2023, cash, cash equivalents and investments in marketable securities were $104.6 million. Tenaya expects these funds, combined with net proceeds of $46.5 million from the recent financing, will be sufficient to fund the company into the second half of 2025.Research & Development (R&D) Expenses: R&D expenses were $22.9 million for the fourth quarter and $98.0 million for the full year ended December 31, 2023. Non-cash stock-based compensation included in R&D expense was $1.8 million for the fourth quarter and $7.0 million for the full year ended December 31, 2023.General & Administrative (G&A) Expenses: G&A expenses were $8.6 million for the fourth quarter and $33.2 million for the full year ended December 31, 2023. Non-cash stock-based compensation included in G&A expense was $2.1 million for the fourth quarter and $8.3 million for the full year ended December 31, 2023.Net Loss: Net loss was $29.9 million, or $0.40 per share for the fourth quarter ended December 31, 2023. For the full year 2023, net loss was $124.1 million, or $1.68 per share. About Tenaya TherapeuticsTenaya Therapeutics is a clinical-stage biotechnology company committed to a bold mission: to discover, develop and deliver potentially curative therapies that address the underlying drivers of heart disease. Leveraging integrated proprietary core capabilities enabling target identification and validation, design of AAV-based genetic medicines and in-house manufacturing the company is advancing a pipeline of novel therapies with diverse treatment modalities for rare genetic cardiovascular disorders and more prevalent heart conditions. Tenaya’s most advanced candidates include TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), and TN-301, a small molecule HDAC6 inhibitor being initially developed for heart failure with preserved ejection fraction (HFpEF). Tenaya also has multiple early-stage programs progressing through preclinical development. For more information, visit www.tenayatherapeutics.com. Forward Looking StatementsThis press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as “expected,” “on track,” “look forward,” “anticipates,” “expects,” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, Tenaya’s plans and expectations regarding its clinical development efforts and activities, including the planned timing of sharing initial data from MyPeak-1 and planned initiation of patient dosing in RIDGE-1; the clinical, therapeutic and commercial potential of, and expectations regarding, Tenaya’s product candidates; the sufficiency of Tenaya’s cash resources to fund the company into the second half 2025; and statements made by Tenaya’s chief executive officer. The forward-looking statements contained herein are based upon Tenaya’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: the timing and progress of Tenaya’s clinical trials; availability of data at the referenced times; unexpected concerns that may arise as a result of the occurrence of adverse safety events in Tenaya’s clinical trials; the potential failure of Tenaya’s product candidates to demonstrate safety and/or efficacy in clinical testing; the potential for any clinical trial results to differ from preclinical, interim, preliminary, topline or expected results; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenaya’s ability to develop, initiate or complete preclinical studies and clinical trials, and obtain approvals, for any of its product candidates; Tenaya’s continuing compliance with applicable legal and regulatory requirements; Tenaya’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; Tenaya’s reliance on third parties; Tenaya’s manufacturing, commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenaya’s ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. ContactMichelle CorralVP, Corporate Communications and Investor RelationsIR@tenayathera.com InvestorsAnne-Marie FieldsStern Investor RelationsAnnemarie.fields@sternir.com MediaWendy RyanTen Bridge Communicationswendy@tenbridgecommunications.com TENAYA THERAPEUTICS, INC. Condensed Statements of Operations (In thousands, except share and per share data) (Unaudited) Three Months EndedDecember 31, Year EndedDecember 31, 2023 2022 2023 2022 Operating expenses: Research and development $22,865 $25,748 $98,038 $94,537 General and administrative 8,581 8,802 33,155 31,084 Total operating expenses 31,446 34,550 131,193 125,621 Loss from operations (31,446) (34,550) (131,193) (125,621)Other income, net: Interest income 1,470 1,037 7,056 1,954 Other income (expense), net 41 (3) 53 2 Total other income, net 1,511 1,034 7,109 1,956 Net loss before income tax expense (29,935) (33,516) (124,084) (123,665)Income tax expense — — — — Net loss $(29,935) $(33,516) $(124,084) $(123,665)Net loss per share, basic and diluted $(0.40) $(0.61) $(1.68) $(2.76)Weighted-average shares used in computing net loss per share, basic and diluted 74,097,642 55,250,372 73,786,126 44,823,597 Condensed Balance Sheet Data (In thousands)(Unaudited) December 31, 2023 2022 Cash, cash equivalents and marketable securities $104,642 $204,230 Total assets $170,515 $278,945 Total liabilities $31,091 $35,569 Total liabilities and stockholders’ equity $170,515 $278,945

LEGEND achieved its primary efficacy endpoint by significantly lowering HbA1c level in both the lanifibranor arm and in the lanifibranor with empagliflozin arm compared to placebo.Statistical significance was also achieved on several markers of liver injury, markers of glucose and lipid metabolism, as well as hepatic steatosis.Patients treated with lanifibranor in combination with empagliflozin maintained a stable weight throughout the 24 weeks study, addressing the moderate, metabolically healthy, weight gain that has been observed in some patients treated with lanifibranor.Treatment with lanifibranor alone and in combination with empagliflozin decreased the ratio of visceral abdominal fat to subcutaneous fat, reflecting a shift from pro-inflammatory visceral fat towards metabolically healthy adipose tissue.The treatment with lanifibranor 800mg/once daily alone or in combination with empagliflozin for 24 weeks was well tolerated, with no safety concerns reported.Inventiva will host an investor webcast Tuesday, March 19th at 8am ET (details below). Daix (France), Long Island City (New York, United States), March 18, 2024 – Inventiva (Euronext Paris and Nasdaq: IVA), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), also known as non-alcoholic steatohepatitis (NASH), and other diseases with significant unmet medical needs, today announces positive results of its interim analysis of the Phase II, Proof-of-Concept clinical trial, LEGEND, evaluating lanifibranor in combination with empagliflozin in patients with MASH/NASH and poorly controlled Type 2 Diabetes (T2D). The LEGEND trial has been designed as a multi-center, randomized, 24-week treatment, placebo-controlled PhaseII Proof-of-Concept trial to assess the safety and efficacy of lanifibranor in combination with the SGLT2 inhibitor empagliflozin for the treatment of patients with non-cirrhotic MASH/NASH and T2D. The trial is double-blind for the placebo arm and lanifibranor (800mg daily) arm, and open-label for the combination of lanifibranor (800mg daily) and empagliflozin (10 mg daily) arm. The diagnosis of non-cirrhotic MASH/NASH was based on historic histology evaluation or a combination of non-invasive methods including diagnostic methods including imaging. As planned per protocol, the interim analysis was done once half of the 63 planned randomized patients with MASH completed the 24-week treatment period or prematurely discontinued from treatment. The study achieved the primary efficacy endpoint with an absolute reduction in Hemoglobin A1c (HbA1c) of 1.14% and 1.59% in patients with MASH and T2D treated with lanifibranor (800mg daily) or in combination with empagliflozin (10mg daily) at week 24 compared to an increase of 0.26% observed in the placebo arm.The study also demonstrated a statistically significant reduction in hepatic steatosis measured by MRI-PDFF1, in patients treated with lanifibranor alone and in combination with empagliflozin, -47% and -38% respectively, compared to placebo (0%). 83% and 67% of patients treated with lanifibranor alone or in combination with empagliflozin respectively, showed a reduction greater or equal to 30% of their hepatic fat, compared to 0% in the placebo arm. In addition, the study demonstrated a statistically significant effect on several secondary and exploratory endpoints, including liver enzymes (alanine aminotransferase (“ALT”) and aspartate aminotransferase (“AST”)), insulin resistance (HOMA-IR), HDL, and adiponectin (see tables below). Markers of liver inflammation and fibrosis (corrected T1 relaxation time (cT1) assessed by LiverMultiScan®) were assessed for the first time with lanifibranor and showed a significant effect with lanifibranor alone and in combination with empagliflozin. The study also demonstrated that patients treated with lanifibranor in combination with empagliflozin maintained a stable weight throughout the 24 weeks study, addressing the moderate, metabolically healthy, weight gain that can be observed in some patients treated with lanifibranor alone. Furthermore, these results demonstrated a significant relative reduction in the VAT/SAT ratio (visceral and subcutaneous adipose tissue) in patients treated with lanifibranor alone or in combination with empagliflozin, -5% and -17% respectively, compared to an increase of 11% in patients under placebo. This result reflects a shift from pro-inflammatory visceral fat towards metabolically healthy adipose tissue. The treatment with lanifibranor 800mg/daily alone and in combination with empagliflozin 10mg/daily for 24 weeks appears to be well tolerated, with no safety concerns reported. Dr. Michael Cooreman, M.D., Chief Medical Officer of Inventiva: “The results of the LEGEND study announced today further illustrate the potential of lanifibranor to address the broad spectrum of the disease biology of MASH and T2D. These data complement the already published dataset of lanifibranor demonstrating fibrosis improvement and MASH resolution but also its role as a potent insulin sensitizer. With roughly 50% of the U.S. population estimated to have either prediabetes or diabetes, and the well-established correlation between MASH and T2D, lanifibranor has a unique mechanism of action to potentially address the medical need of patients with both MASH and T2D. We wish to thank the patients who participated in the study and the investigators of LEGEND.” Dr. Onno Holleboom, MD PhD, endocrinologist and associate professor at Amsterdam UMC, co-principal investigator of the LEGEND Phase II clinical trial: “It is a big step seeing these positive results of LEGEND demonstrating the impact of lanifibranor on steatosis, inflammation and fibrosis while stabilizing weight with empagliflozin in patients with poorly controlled T2D and MASH. The study was designed as a proof of concept and these results are significant and strengthen confidence in the potential of lanifibranor to address the specific metabolic unbalance in patients with T2D while also addressing steatosis and fibrosis, a hepatic consequence of insulin resistance.” Prof. Michelle Lai, M.D., Ph.D., Beth Israel Deaconess Medical Center and co-principal investigator of the LEGEND Phase II clinical trial, said: “These LEGEND results provide valuable insights on the complementary mechanisms of action of an SGLT2 inhibitor and the panPPAR agonist, lanifibranor. MASH is a multifaceted disease that we believe will benefit from combination therapies in order to properly address the full cardiometabolic spectrum of the disease. These results of LEGEND suggest that lanifibranor in combination with empagliflozin could be an ideal combination for patients we care for in our clinic who suffer from T2D and MASH.” Given that the primary endpoint of LEGEND was met, and statistically significant results were achieved on several key additional markers, the Company has decided to stop the recruitment as defined per protocol. More details on these results are expected to be presented in upcoming scientific conferences and submitted for publication. Summary HbA1C improvement at Week 24 Full Analysis Seta (N=30) Placebo (n=9) Lani 800mg (n=11) Lani 800mg +Empa 10mg (n=10) HbA1c (%), LS Mean Absolute Change from Baseline to Week 24 0.26 -1.14* -1.59** Completersb (N=24) Placebo (n=5) Lani 800mg (n=11) Lani 800mg +Empa 10mg (n=8) Responders with HbA1C level < 6.5% at Week 24 (%) 0 55 63 Responders with HbA1c absolute decrease ≥1% from baseline, at Week 24 (%) 0 64 88 a Two patients were not considered in the Full Analysis Set because we do not have post-treatment HbA1c values available*p<0.01, **p<0.001, versus placebo (Mixed Model Repeated Measure [MMRM])b Eight patients were not considered in the Completers set because of premature discontinuation before Week 24 or missing data due to prior intercurrent events (Rescue medication or significant diet modification affecting the primary endpoint).LS=Least Square. Summary of improvement in non-invasive measures of hepatic steatosis, inflammation and fibrosis markers, and liver injury, at Week 24 Full Analysis Set Mean Change from Baseline to Week 24 Placebo Lani 800mg Lani 800mg +Empa 10mg MRI-PDFF (%)a 0 (n=5) -47* (n=12) -38* (n=9) cT1 (ms)b 15 (n=4) -82 (n=12) -85 (n=9) ALT (%)a 2.5 (n=9) -36.4** (n=12) -51.3*** (n=10) AST (%)a 17.1 (n=9) -24.7** (n=12) -34.6*** (n=10) a LS Mean relative change from baseline to week 24, from an Analysis of Covariance model (ANCOVA) or Mixed Model Repeated Measure (MMRM)b LS Mean absolute change from baseline to week 24, from an ANCOVA.*p≤0.05, **p<0.01, ***p<0.001, versus placebo (ANCOVA or MMRM)ALT: Alanine Aminotransferase, AST: Aspartate Aminotransferase, cT1: Corrected T1, LS=Least Square, MRI-PDFF: Magnetic resonance imaging-derived proton density fat fraction. Summary of improvement in Cardiometabolic Markers and Weight, at Week 24 Full Analysis Set Mean Change from Baseline to Week 24 Placebo Lani 800mg Lani 800mg +Empa 10mg HDL-C (mmol/L)a -0.01 (n=9) 0.17 (n=12) 0.22* (n=10) Insulin (pmol/L)a -58.3 (n=9) -93.9 (n=11) -155.1* (n=10) HOMA-IR (%)b -7 (n=9) -51* (n=11) -69** (n=10) Adiponectinc 1.1 (n=9) 2.8* (n=11) 3.0* (n=10) Body weightd (%) -0.8 (n=5) 3.6 (n=12) -0.4 (n=8) VAT/SAT (%)b 11 (n=4) -5 (n=8) -17** (n=7) a LS Mean absolute change from baseline to week 24b LS Mean relative change from baseline to week 24c LS Mean fold change from baseline to week 24 d Relative change from baseline to week 24*p<0.05, **p<0.01, ***p<0.001, versus placebo (Mixed Model Repeated Measure [MMRM] or Analysis of Covariance (ANCOVA)).HDL-C: High density lipoprotein cholesterol, HOMA: Homeostasic model assessment, LS=Least Square, SAT=Subcutaneous Adipose Tissue, VAT=Visceral Adipose Tissue. Conference call Inventiva will host a conference call and webcast with slide presentation on Tuesday, March 19, 2024 at 8:00 am ET (New York time) 1:00 pm CET (Paris time). Introduced by Frederic Cren, Chairman, CEO and cofounder of Inventiva, this event will be as follow: Presentation of LEGEND Results - Michael Cooreman, M.D., CMO of Inventiva Metabolic and hepatic benefits of lanifibranor - Stephen Harrison, M.D., Pinnacle Clinical Research and principal investigator of the exploratory cohort of NATiV3, Phase III clinical trial Vascular benefits of lanifibranor - Sven Francque, M.D., University Hospital Antwerp, co-principal investigator of NATiV3, Phase III clinical trialOpportunity for lanifibranor - Frederic Cren, CEO and cofounder of Inventiva The conference call and the slides of the presentation will be webcast live at: https://edge.media-server.com/mmc/p/hyuvxf9a and will also be available on Inventiva’s website: Investor Presentations - Inventiva Pharma. In order to receive the conference access information necessary to participate to the conference call, it is required to register in advance using the following link: https://register.vevent.com/register/BI334d62953abb41cea27de99dc5da974c . Participants will need to use the conference access information provided in the e-mail received at the point of registering (dial-in number and access code). About lanifibranor Lanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce anti-fibrotic, 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 ‑wellbalanced‑ 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 panPPAR‑ agonist in clinical development for the treatment of MASH/NASH. Inventiva believes that lanifibranor’s moderate and balanced panPPAR‑ binding profile contributes to the favorable tolerability profile that has been observed in clinical trials and preclinical studies to date. The FDA has granted Breakthrough Therapy and Fast Track designation to lanifibranor‑ for the treatment of MASH/NASH. 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 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 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 Contacts Inventiva Pascaline ClercEVP, Strategy and Corporate Affairsmedia@inventivapharma.com +1 202 499 8937 Brunswick GroupTristan Roquet Montegon /Aude Lepreux /Julia CailleteauMedia relationsinventiva@brunswickgroup.com +33 1 53 96 83 83 Westwicke, an ICR CompanyPatricia L. BankInvestor relationspatti.bank@westwicke.com +1 415 513-1284 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, forecasts and estimates with respect to Inventiva’s pre-clinical programs and clinical trials, including design, duration, timing, recruitment costs, screening and enrollment for those trials, including the ongoing NATiV3 Phase III clinical trial with lanifibranor in MASH/NASH and the LEGEND Phase II, Proof-of-Concept combination trial with lanifibranor and empagliflozin in patients with MASH/NASH and T2D, and the results and timing thereof and regulatory matters with respect thereto, , clinical trial data releases and publications, the information, insights and impacts that may be gathered from clinical trials, the potential therapeutic benefits including reduction in HbA1c, reduction in hepatic steatosis, the effect on liver enzymes (ALT and AST), insulin resistance (HOMA-IR), HDL, adiponectin, liver inflammation and fibrosis, and reduction in the VAT/SAT ratio, of lanifibranor alone and in combination with empagliflozin in patients with MASH/NASH and T2D, of Inventiva’s product candidates, including lanifibranor alone and in combination with empagliflozin, the effect of lanifibranor alone and in combination with empagliflozin on the weight of the patients receiving treatment, the tolerability and safety profile of lanifibranor observed during trials, the potential of lanifibranor to address the specific metabolic unbalance in patients with T2D while also addressing steatosis and fibrosis, a hepatic consequence of insulin resistance, the estimated market size and patient population, potential regulatory submissions, approvals and commercialization, Inventiva’s pipeline and preclinical and clinical development plans, the potential development of and regulatory pathway for odiparcil, and future activities, expectations, plans, growth and prospects of Inventiva and its partners. 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 pause on enrolment 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 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, 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 (the “SEC”) 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 statements. 1 MRI-PDFF: Magnetic resonance imaging-derived proton density fat fraction Attachment Inventiva - PR - Results LEGEND - EN - 03 18 2024

March 13, 2024 – 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 metabolic dysfunction-associated steatohepatitis (MASH), formerly known as NASH, and other diseases with significant unmet medical needs, will hold an investor conference on Tuesday, March 19, to share the results of the LEGEND Phase II trial, a placebo-controlled, study evaluating lanifibranor alone and in combination with the SGLT2 inhibitor empagliflozin in patients with MASH/NASH and type 2 diabetes (T2D). Conference Call / Webcast Details The Company will host a conference call and webcast, followed by a Q&A session, on Tuesday, March 19, 2024, at 8:00 am (New York), 1:00 pm (Paris). In order to participate to the conference call, please register at the following link: https://register.vevent.com/register/BI334d62953abb41cea27de99dc5da974c. The live webcast will be available here and on the “Investor Presentations” page of the Inventiva website, with the recording and presentation available following the event. The LEGEND (Lanifibranor in combination with the SGLT2 inhibitor empagliflozin in patients with NASH and type 2 diabetes) trial has been designed as a multi-center, randomized, 24-week treatment, placebo-controlled Phase IIa trial to assess the safety and efficacy of lanifibranor in combination with the SGLT2 inhibitor empagliflozin for the treatment of patients with non-cirrhotic MASH/NASH and T2D. The diagnosis of non-cirrhotic MASH/NASH is based on historic histology evaluation or a combination of non-invasive methods including diagnostic methods including imaging. The trial is double-blind for the placebo and lanifibranor arms and open-label for the combination of lanifibranor and empagliflozin arm. The results presented concern a pre-specified interim analysis on the first half of randomized patients, who have either completed the 24-week treatment period or prematurely discontinued from treatment earlier. The primary efficacy endpoint of the trial is the absolute change in Hemoglobin A1c (HbA1c) at week 24 compared to baseline. Secondary endpoints include changes in liver enzymes, markers of glucose and lipid metabolism, MRI-PDFF, markers of inflammation and fibrosis, body weight evolution and body fat composition. 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 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. 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, 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 MASH/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 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 The content above comes from the network. if any infringement, please contact us to modify.