Cardiomyopathy, Hypertrophic

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

TN-401 AAV9-Based Gene Therapy Being Developed to Treat the Underlying Cause of PKP2-associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) PKP2 Gene Replacement Therapy Normalized Heart Rhythms, Reversed Disease Progression and Extended Survival in a Severe Mouse Model of Disease Tenaya Anticipates Dosing First Patient in Phase 1b RIDGE™-1 Clinical Trial of TN-401 in Second Half of 2024 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 announced the publication of its preclinical research related to its gene therapy candidate, TN-401, in the current issue of Nature Communications Medicine. TN-401 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy being developed for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by Plakophilin-2 (PKP2) gene mutations. PKP2 mutations are the most common genetic cause of ARVC, also known as arrhythmogenic cardiomyopathy (ACM), and result in a loss of key proteins needed to maintain the structural integrity and cell-to-cell electrical signaling of heart muscle cells. TN-401 is designed to deliver a functional PKP2 gene to heart cells where it works to restore normal protein levels in order to halt or even reverse disease after a single dose. “Following a single infusion of our AAV9-based PKP2 gene therapy in a severe knock-out mouse model of the disease, PKP2 protein levels were restored. This led to dose-dependent improvements in right ventricular dilation and ejection fraction, reductions in arrhythmia frequency and severity, and prevention of adverse fibrotic remodeling, with near-maximal efficacy achieved at the 3E13 vg/kg dose.” said Tim Hoey, Ph.D., Chief Scientific Officer of Tenaya. “ARVC can have a devastating effect on patients’ lives, putting them at risk of life-threatening arrhythmias and placing limitations on their quality of life,” said Whit Tingley, M.D., Ph.D., Chief Medical Officer of Tenaya. “These promising preclinical results show the potential of TN-401 to prevent, halt or even reverse the steady progression of PKP2-associated ARVC by addressing the underlying genetic cause, and offer hope to patients. We look forward to commencing dosing of TN-401 in patients with PKP2-associated ARVC in our Phase 1b RIDGE-1 clinical trial in the second half of this year.” Tenaya’s RIDGE-1 Phase 1b clinical trial of TN-401 is a multi-center, open-label study to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-401. Tenaya is currently also conducting the RIDGE™ global non-interventional natural history and serotype study of PKP2-associated ARVC. Both studies are being conducted at leading centers for ARVC care. Key Findings The paper, titled “AAV9:PKP2 improves heart function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy,” describes results from preclinical studies in a Pkp2-deficient mouse model to understand gene therapy’s impact in both prevention mode before disease onset and in treatment mode after disease onset. A single dose of Tenaya’s AAV9:PKP2 gene therapy: Restored normal levels of PKP2 protein expression, Led to a highly coordinated and durable correction in structural genes encoding desmosome, sarcomere and calcium handling proteins with a role in maintaining cellular integrity and function, Reduced the frequency and severity of arrhythmias, Demonstrated durable efficacy in preventing disease development, Slowed or reversed disease progression after onset, Prevented fibrotic remodeling, and Improved long-term survival. Tenaya selected AAV9 as the vector for delivery for TN-401 based on its extensive clinical and commercial safety record in thousands of patients globally and its demonstrated ability in clinical studies to broadly distribute in all regions of the human heart and to more robustly express the PKP2 gene in cardiomyocytes as compared to other vectors. About PKP2-Associated ARVC Mutations in the desmosome gene PKP2 are the most frequent cause of ARVC, with greater than 40% of those diagnosed estimated to carry pathogenic PKP2 mutations. In the U.S. prevalence of PKP2-associated ARVC is estimated at more than 70,000, though the condition is frequently undiagnosed; in nearly one in four cases, sudden cardiac death is the first sign of disease. Mutations of the PKP2 gene result in insufficient expression of a protein needed for the proper functioning of the desmosomal complex that maintains physical connections and electrical signaling between heart muscle cells. As the desmosome structure degrades, cardiac muscle cells are replaced by fibrofatty tissue and electrical pulses in the heart become unstable, resulting in adverse remodeling and irregular heart rhythms. A progressive disease, ARVC is typically diagnosed before age 40 and symptoms may include arrhythmias, palpitations, lightheadedness, dizziness and fainting and sudden cardiac arrest. Current treatments include anti-arrhythmic medications, implantable cardioverter-defibrillators (ICDs) and ablation procedures, which do not address the underlying genetic cause of disease. About TN-401 Gene Therapy and the RIDGE Clinical Program TN-401 is an investigational AAV9-based gene therapy being developed for the treatment of ARVC due to mutations in the PKP2 gene. Tenaya has received clearance from the FDA to initiate its first-in-human RIDGE-1 Phase 1b clinical trial of TN-401 in patients with PKP2-associated ARVC. To support TN-401’s clinical development, the company is currently enrolling the RIDGE global non-interventional study to collect natural history and AAV9 antibody (seroprevalence) data among ARVC patients carrying PKP2 gene mutations. TN-401 has received Orphan Drug and Fast Track Designations from the FDA. About Tenaya Therapeutics Tenaya 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 . Forward Looking Statements This 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 “anticipates,” “promising,” “potential,” “look forward,” “plan,” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the clinical, therapeutic and commercial potential of TN-401 as a treatment for PKP2-associated ARVC and the plan for initiation of patient dosing in RIDGE-1. 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 potential failure of TN-401 to demonstrate safety and/or efficacy in clinical testing; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating TN-401; the timing and progress of the RIDGE-1 clinical trial; the timing, scope and likelihood of regulatory filings and approvals for TN-401; 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. Contacts Michelle Corral Vice President, Investor Relations and Corporate Communications Tenaya Therapeutics IR@TenayaThera.com Investors AnneMarie Fields Stern IR AnneMarie.Fields@SternIR.com Media Wendy Ryan Ten Bridge Communications wendy@tenbridgecommunications.com

Lexicon Pharmaceuticals' original Zynquista FDA rejection was in 2019. Since then, the company has persisted in its regulatory efforts. Ever since its first FDA rejection five years ago, Lexicon Pharmaceuticals hasn’t given up hope on its Type 1 diabetes prospect sotagliflozin. Now, the company’s approval dreams could be coming into focus as the drugmaker prepares to refile its application. After hearing recent regulatory feedback from the agency, Lexicon said it plans to submit the drug by the middle of the year, the company said in a press release. “We have remained steadfast in our support of sotagliflozin in type 1 diabetes and have worked diligently to identify a regulatory path forward for what we believe will be an important new therapy,” CEO Lonnel Coats noted in the release. Lexicon is hoping for an approval that clears the drug to be used as an add-on to insulin therapy for adults with Type 1 diabetes mellitus and chronic kidney disease, the company said in its fourth-quarter and full-year earnings presentation (PDF). If approved, the drug will be branded as Zynquista. Lexicon hit the first bump on its regulatory road in 2019, when the FDA rejected its bid with a safety-related complete response letter following a 8-8 vote from an advisory committee. At the time, Sanofi was partnered on the drug, but the French pharma jumped ship after the rejection and subsequent trial flops in Type 2 diabetes. In the rejection, the FDA cited concerns about the risk of diabetic ketoacidosis for patients taking insulin plus Zynquista. However, Lexicon maintains that the risk can be managed and may be outweighed by patients' unmet needs. Despite the FDA rejection, Zynquista was approved in Europe in 2019. Lexicon has a trove of phase 3 data proving Zynquista’s worth in diabetes with chronic kidney disease when paired with insulin, the company has said. The long-awaited nod would be highly beneficial to Lexicon, which took home $1.2 million in total 2023 revenues. Net losses for the year came out to $175.6 million. At one point, some analysts had blockbuster-level expectations for the drug. Meanwhile, the drugmaker has been able to take sotaglifozin into another indication. The med scored approval for heart failure last year—branded as Inpefa—and launched weeks later, marking the first SGLT1/SGLT2 inhibitor to hit the U.S. market. The company is also testing the drug in hypertrophic cardiomyopathy.