Heart Defects, Congenital

2024 Harrington Prize for Innovation in Medicine Recognizes Pioneering Work in Immunology CLEVELAND, March 19, 2024 /PRNewswire/ -- The eleventh annual Harrington Prize for Innovation in Medicine has been awarded to Arlene H. Sharpe, MD, PhD, Kolokotrones University Professor and Chair of the Department of Immunology at Harvard Medical School. The award recognizes her breakthrough discoveries in immune regulation, which have established foundational principles in immunology and led to new cancer therapies that act by boosting the immune response to cancer. The Harrington Prize for Innovation in Medicine, established in 2014 by the Harrington Discovery Institute at University Hospitals and the American Society for Clinical Investigation (ASCI), honors physician-scientists who have moved science forward with achievements notable for innovation, creativity and potential for clinical application. Dr. Sharpe's research in immunology has led to significant advances in medical treatments. Her work helped identify key pathways that restrain the activity of T lymphocytes (immune cells) to fight cancer. Her work defined the PD-1 pathway and its immunoinhibitory functions as well as the inhibitory functions of CTLA-4 to restrain the activity of the immune system. Dr. Sharpe's research thus laid the foundation for the development of 'immune checkpoint inhibitors', drugs that target PD-1 and related pathways. These therapies, including pembrolizumab and nivolumab, have been approved by the FDA for treating numerous types of cancer. They work by preventing inhibition of T cell function, thereby unleashing the body's immune system to fight cancer cells more effectively. This approach has become a cornerstone in cancer treatment strategies. "Dr. Sharpe's body of work has shaped our understanding of the role of the T cell in regulating the immune response. Her innovative scientific discoveries are among the best examples of bench-to-bedside work in the past three decades," said Benjamin D. Humphreys, MD, PhD, Joseph Friedman Professor of Renal Diseases in Medicine and Chief, Division of Nephrology, Washington University in St. Louis and 2023-2024 President of the ASCI. "Immune checkpoint inhibitors are drugs that allow for dramatic remission, and even cures, of cancers that had previously been considered untreatable. Dr. Sharpe's foundational insights have thus been harnessed to transform cancer therapy. Her work provides a beautiful example of physician impact through creative science," said Jonathan S. Stamler, MD, President, Harrington Discovery Institute, Robert S. and Sylvia K. Reitman Family Foundation Distinguished Professor of Cardiovascular Innovation and Professor of Medicine and of Biochemistry at University Hospitals and Case Western Reserve University. A committee composed of members of the ASCI Council and the Harrington Discovery Institute Scientific Advisory Board reviewed nominations from leading academic medical centers globally before selecting the 2024 Harrington Prize recipient. In addition to sharing the Prize's $20,000 honorarium, Dr. Sharpe will deliver the Harrington Prize Lecture at the 2024 AAP/ASCI/APSA Joint Meeting on April 5, will be a featured speaker at the 2024 Harrington Scientific Symposium May 22-23, and will publish an essay in the Journal of Clinical Investigation. The Harrington Prize has recognized outstanding and diverse innovations in medicine: 2014: Harry Dietz, MD, Johns Hopkins University, for his contributions to the understanding of the biology and treatment of Marfan syndrome, a disorder leading to deadly aneurysms in children and adults. 2015: Douglas R. Lowy, MD, The National Cancer Institute, in recognition of his discoveries that led to the development of the Human Papillomavirus vaccine to prevent cervical cancer. 2016: Jeffrey M. Friedman, MD, PhD, The Rockefeller University, for his discovery of leptin, which controls feeding behavior and is used to treat related clinical disorders. 2017: Jointly awarded to Daniel J. Drucker, MD, Mount Sinai Hospital, Canada, Joel F. Habener, MD, Massachusetts General Hospital, and Jens J. Holst, MD, DMSc, University of Copenhagen, Denmark, for their discovery of incretin hormones and for the translation of these findings into transformative therapies for major metabolic diseases such as diabetes. 2018: Helen H. Hobbs, MD, UT Southwestern Medical Center, for the discovery of the link between a gene mutation (PCSK9) and lower levels of LDL, which has improved the treatment of high cholesterol. 2019: Carl H. June, MD, University of Pennsylvania, for advancing the clinical application of CAR T therapy for cancer treatment, and for his sustained contributions to the field of cellular immunology. 2020: Stuart H. Orkin, MD, Harvard University, for breakthrough discoveries on red blood cells that offer new treatments for patients with sickle cell disease and beta-thalassemia, which are among the most common genetic disorders. 2021: Warren J. Leonard, MD, and John J. O'Shea, MD, NIH, for their respective contributions to the field of immunology, from fundamental discovery to therapeutic impact. 2022: James E. Crowe Jr., MD, and Michel C. Nussenzweig, MD, PhD, for their groundbreaking work, which has elucidated fundamental principles of the human immune response and enabled the use of human antibodies to treat COVID-19. 2023: Jean Bennett, MD, PhD, and Albert M. Maguire, MD, for their groundbreaking translational research to restore sight in inherited genetic diseases. SOURCE Harrington Discovery Institute

SBT-589 showed mitochondrial protection across models of Friedreich's ataxia SBT-589 displayed cardioprotective effects in aggressive mouse model of FA cardiomyopathy Ongoing studies are expected to build on these insights as SBT-589 progresses through developmental stage-gates NEEDHAM, Mass., March 19, 2024 /PRNewswire/ -- Stealth BioTherapeutics Inc. (the "Company" or "Stealth"), a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for diseases involving mitochondrial dysfunction, announced today the presentation of new SBT-589 data demonstrating cardioprotective effects across pre-clinical models of Friedreich's ataxia (FA). The data were presented at the Wellcome Trust Conference on Mitochondrial Medicine – Therapeutic Development, held March 18-20, 2024, in Cambridge, England. FA is a chronic disease of metabolic disruption that is typically diagnosed in childhood or adolescence, is inexorably progressive and usually results in premature death from cardiomyopathy or heart failure. There are no approved therapies for the progressive cardiomyopathy, which is linked to severe mitochondrial dysfunction, and is the leading cause of early death in this devastating disease. SBT-589 is a promising novel molecule that acts on mitochondrial pathways essential for cellular health and energy production that are impaired in FA cardiomyopathy. To evaluate the potential of SBT-589 in FA, a series of studies were conducted in FA patient-derived cells, isolated heart mitochondria, and an aggressive mouse model of FA cardiomyopathy. SBT-589 improved bioenergetics in FA patient-derived cells and mitochondria. In an FA mouse model with prominent cardiac hypertrophy and aggressive mortality, mice treated with once-daily SBT-589 displayed significantly reduced cardiac hypertrophy and a delay in the onset of mortality compared to vehicle-treated mice. "Mitochondrial dysfunction is a central contributor to pathology in Friedreich's ataxia, a disease in which heart failure and sudden cardiac events are among the leading causes of mortality," said David A. Brown, Senior Vice President, Discovery. "Mitigating heart disease in FA is central to Stealth's ongoing efforts to improve the lives of individuals with FA. The new findings presented today support continued development of SBT-589 as a potentially disease-modifying therapy to address the unmet need in cardiomyopathy associated with Friedreich's ataxia." The data were presented by Dr. Laura E. Kropp, Senior Manager of Discovery Biology at Stealth, and recipient of the Keith Michael Andrus Cardiac Award from the Friedreich's Ataxia Research Alliance. About Friedreich's Ataxia Friedreich's ataxia is a rare genetic disease affecting an estimated 1 in 50,000 individuals in the United States. The disease is caused by a defect in the frataxin gene resulting in a relative deficiency of frataxin, leading to mitochondrial iron accumulation and oxidative stress. More than 90% of patients with Friedreich's ataxia experience progressive cardiomyopathy which usually becomes fatal by early adulthood and is the leading cause of early mortality. About Stealth BioTherapeutics Stealth BioTherapeutics is a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for age-related and rare genetic diseases involving mitochondrial dysfunction. The Company is initiating Phase 3 clinical trials of elamipretide, its lead investigational product candidate, in dry age-related macular degeneration. Elamipretide is also being tested in a fully enrolled Phase 3 clinical trial in primary mitochondrial myopathy, a rare skeletal myopathic disease caused by nuclear DNA mutations, and is the subject of a New Drug Application for Barth syndrome, an ultra-rare cardioskeletal disease. The Company is evaluating its second-generation clinical-stage candidate, SBT-272, for ophthalmic and neurological disease indications. The Company has a deep pipeline of novel mitochondria-targeted compounds under evaluation as therapeutic product candidates. Several of these lead compounds, including SBT-589, have progressed through pre-clinical development stage-gates and toward IND-enabling studies. Investor Contact Kendall Investor Relations Adam Bero, Ph.D. [email protected] [email protected] Media Contact Anna Stallman Communications Anna Stallman [email protected] SOURCE Stealth BioTherapeutics Inc.

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