MYBPC3

AFTX-201, Affinia's gene therapy program in BAG3 dilated cardiomyopathy, demonstrates efficacy, safety, and differentiation in a genetically relevant preclinical model, with full restoration of cardiac function Additional data show Affinia's gene therapy program in MYBPC3 hypertrophic cardiomyopathy demonstrating efficacy, safety, and differentiation in a genetically relevant preclinical model, its second-generation CNS capsids based on novel BBB receptors, and the Company's proprietary plasmid design increasing yields more than 10-fold for AAVs WALTHAM, Mass., Oct. 22, 2024 /PRNewswire/ -- Affinia Therapeutics ("Affinia"), an innovative gene therapy company with a pipeline of rationally designed adeno-associated virus (AAV) gene therapies for devastating cardiovascular and neurological diseases, today announced the presentation of new preclinical data on its BAG3 dilated cardiomyopathy (DCM) and MYBPC3 hypertrophic cardiomyopathy (HCM) programs, as well as additional data covering its second generation of central nervous system (CNS) capsids based on novel blood-brain barrier (BBB) receptors, and its proprietary high-yielding plasmid design for manufacturing. These scientific advances will be featured in poster presentations at the European Society of Gene and Cell Therapy (ESGCT) 2024 31st Annual Congress, being held October 22-25, 2024 in Rome, Italy. "Our data at ESGCT highlight solutions addressing the key limitations in the gene therapy field, including transducing the majority of cells to deliver therapeutic payloads to cardiac muscle, skeletal muscle, or CNS as well as the ability to manufacture efficiently to serve prevalent adult populations," said Charlie Albright, Ph.D., Affinia's Chief Scientific Officer. "Affinia's programs, which use novel tissue-tropic capsids, are highly differentiated from those using conventional AAVs and we look forward to advancing them toward the clinic." Details of Affinia's poster presentations at ESGCT are as follows: Title: A novel AAV gene therapy for treatment of BAG3 dilated cardiomyopathy Abstract: P0252 Session: Poster Session II Date/Time: Wednesday, October 23, 1:30-3:00 PM CEST Location: Concourse Level-1 and Mezzanine Concourse Presenter: Lisa Stanek, Ph.D., Vice President, Translational Science, Affinia BAG3 DCM is a devastating monogenic heart disease affecting more than 70,000 patients in the U.S., Europe, and U.K. regions alone. The BAG3, or Bcl2-associated athanogene 3, gene encodes for a protein that is critical to the normal structure and function of heart cells. Patients affected by BAG3 DCM have a mutation in the BAG3 gene and a deficiency in functioning BAG3 protein, resulting in early onset heart failure that progresses rapidly. No disease-modifying treatment exists, and many patients require a heart transplant. In this poster presentation, Affinia reports the efficacy, safety, and differentiation of its rationally designed gene therapy product candidate, AFTX-201, to treat BAG3 DCM in a genetic mouse model that mirrors the human disease. The preclinical results showed production of BAG3 protein in the heart, improvement in the dilated cardiomyopathy pathophysiology, and full restoration of cardiac function four weeks after a one-time intravenous dose of AFTX-201. In contrast, a gene construct using the conventional capsid, AAV9, did not show improvement in cardiac function. AFTX-201 uses Affinia's novel second-generation cardiotropic capsid, ATC-0187, which has demonstrated robust transduction of iPSC-derived human cardiomyocytes and 90-100% transduction of cardiomyocytes in nonhuman primates (NHPs) following intravenous administration, significantly superior to the conventional capsid, AAV9. "Development of a one-time therapy that addresses the genetic root cause of BAG3 DCM would represent a significant advancement for patients affected by this devastating disease who are otherwise healthy. There is no disease-modifying treatment available," said Laura Richman, D.V.M., Ph.D. DACVP, Affinia's Chief Development Officer. "The preclinical data presented show the potential of AFTX-201 to replenish the BAG3 protein in the heart and to provide structural and functional restoration to normal." Title: A novel AAV gene therapy for treatment of MYBPC3 hypertrophic cardiomyopathy Abstract: P0270 Session: Poster Session II Date/Time: Wednesday, October 23, 1:30-3:00 PM CEST Location: Concourse Level-1 and Mezzanine Concourse Presenter: Lisa Stanek, Ph.D., Vice President, Translational Science, Affinia MYBPC3 HCM is a devastating monogenic heart disease affecting more than 110,000 patients in the U.S., Europe, and U.K. regions alone. MYBPC3, or myosin-binding protein C, is a gene that encodes for a protein that is critical to the normal structure and function of heart cells. Patients affected by MYBPC3 HCM present with early onset heart failure that progresses rapidly, resulting in serious complications such as life-threatening arrhythmia or sudden cardiac death. No treatment exists for the underlying genetic cause of the disease. In this poster presentation, Affinia reports the efficacy, safety, and differentiation of its rationally designed gene therapy product candidate to treat MYBPC3 HCM in a knock-in genetic mouse model, which mirrors the human disease. The preclinical results showed reversal of the hypertrophic cardiomyopathy pathophysiology and full restoration of cardiac function 11 weeks after a one-time intravenous dose of Affinia's product candidate using the novel cardiotropic capsid, ATC-0187. In contrast, a gene construct using the conventional capsid, AAV9, did not show improvement in cardiac function in this animal model and at the dose tested. Title: In vitro binding to human and NHP orthologs of candidate receptors identify novel systemically delivered AAVs with enhanced CNS tropism Abstract: P0144 Session: Poster Session II Date/Time: Wednesday, October 23, 1:30-3:00 PM CEST Location: Concourse Level-1 and Mezzanine Concourse Presenter: John Reece-Hoyes, Ph.D., Senior Director, Head of Vector Biology, Affinia Broad distribution to the brain regions remains a limitation of conventional capsids to treat many neurological diseases. Data will be presented on novel BBB-penetrant capsids that bind both human and NHP orthologs of 10 receptors, many of them novel, selected from among highly expressed GPI-anchored proteins in human brain endothelial cells. Results in human receptor knock-in mice and in NHPs revealed multiple novel capsids that utilize different receptors with improved CNS tropism compared to AAV9 when delivered systemically. Title: Affinia's proprietary AAV plasmid design produces industry leading manufacturability of novel and WT capsids Abstract: P0806 Session: Poster Session IV Date/Time: Thursday, October 24, 6:00-7:30 PM CEST Location: Concourse Level-1 and Mezzanine Concourse Presenter: Matt Edwards, MBA, Senior Director, Head of Process Science, Affinia The ability to produce AAVs cost-effectively has been a limitation to broadening the reach of gene therapy to prevalent adult diseases. Affinia's proprietary plasmid design significantly increases yields and packaging efficiency for all novel capsids with peptide inserts and for conventional capsids tested to date. Results show that Affinia's novel capsids yield greater than 3e15 vg/L and full capsids up to 60% at upstream harvest. Results with AAV9 show yields exceeding 4e15 vg/L upstream harvest, 10 times higher than that using conventional plasmid design. Rob May, Affinia's Chief Technical Operations Officer said, "Our proprietary plasmid design leads to industry-leading yields and packaging efficiency for AAV9 and for our novel capsids. These data provide confidence that, as we advance our product candidates to the clinic, they can benefit many adult populations. Beyond Affinia's pipeline, our technology improved yields and packaging efficiency across all AAV capsids tested." Abstracts can be found at . About Affinia Therapeutics Affinia Therapeutics is pioneering a shift to a new class of rationally designed gene therapies that treat rare and prevalent diseases. Affinia Therapeutics' pipeline of first-in-class or best-in-class product candidates in cardiovascular and neurological diseases leverages its proprietary next-generation capsids, payloads, or manufacturing approaches and have shown efficacy, safety, and differentiation in relevant animal models. For more information, visit . SOURCE Affinia Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Independent Data Safety and Monitoring Board Endorsed Dose Escalation and Broadening of Eligibility Criteria; Cohort 2 Now Enrolling Initial Data from Cohort 1 to be Reported in December 2024 Highlights Recently Presented Insights on Pediatric MYBPC3-associated HCM Disease Burden SOUTH SAN FRANCISCO, Calif., Oct. 17, 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 shared updates related to its ongoing Phase 1b/2 MyPEAK-1 clinical trial of TN-201. TN-201 is being developed for the potential treatment of MYBPC3 -associated hypertrophic cardiomyopathy (HCM), a condition caused by insufficient levels of myosin-binding protein C (MyBP-C). TN-201 gene replacement therapy is designed to increase protein levels of MyBP-C to slow or even reverse the course of disease by delivering a functional copy of the MYBPC3 gene to heart muscle cells. “The MyPEAK-1 study of TN-201 is primarily intended to establish the safety pro TN-201 gene therapy, and we are pleased to report that TN-201 has an appropriate tolerability pro the 3E13 vg/kg dose without unexpected adverse reactions,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “The DSMB’s recommendation to proceed with dose escalation and endorsement to expand eligibility criteria are further positive early indicators for TN-201’s safety pro enable Tenaya to explore the utility of TN-201 in different populations. We’ve implemented adjustments to the protocol, including the addition of a biopsy at baseline, broadening eligibility to include obstructive HCM patients and increasing the size of the overall MyPEAK-1 study.” Tenaya completed dosing of the first three patients (Cohort 1) at the 3E13 vg/kg dose in the MyPEAK-1 trial with no unexpected events or toxicities associated with study drug observed. Safety data from Cohort 1 were reviewed by an independent Data and Safety Monitoring Board (DSMB), showing a safety and tolerability pro with other AAV gene therapies at this dose. Accordingly, the DSMB recommended that Tenaya proceed with dose escalation to the 6E13 vg/kg dose (Cohort 2), per protocol. Enrollment of Cohort 2 is underway. Tenaya has implemented several changes in the MyPEAK-1 protocol intended to support future development, including: Adding a baseline biopsy, increasing the total number of cardiac biopsies from two to three, and permitting more flexible timing of post-dose biopsies to help characterize TN-201 expression over time Expanding eligibility to include participants who do not have an implantable cardioverter defibrillator device (ICD) and to permit adults with either obstructive or nonobstructive forms of HCM to enroll Increasing the potential number of total patients enrolled in the dose expansion portion of the clinical trial from nine to twenty-four adults Tenaya plans to report initial data from Cohort 1 in December of this year. This readout is expected to focus on TN-201’s safety and tolerability, analyses of cardiac biopsy, as well as changes from baseline in cardiac biomarkers. The MyPEAK-1 clinical trial is also collecting data to understand TN-201’s effect on imaging biomarkers, heart function, exercise capacity, functional status, and patient quality of life. As part of Tenaya’s ongoing efforts to characterize the disease burden for children and adolescents with MYBPC3 -associated HCM, Dr. Tingley recently presented data from a study conducted in partnership with the Sarcomeric Human Cardiomyopathy Registry (SHaRe): Of the nearly 1,800 MYBPC3 -associated HCM individuals identified in SHaRe’s database, approximately 13% were diagnosed prior to age 18. The cumulative lifetime risk of severe events for MYBPC3 -associated pediatric patients is very high, with 50% experiencing significant morbidity by age 40. Both adult and pediatric MYBPC3 -associated HCM individuals have high rates of serious complications, such as heart failure and ventricular arrhythmias, highlighting the need for timely diagnosis, active monitoring and new genetic medicines that can have a meaningful impact on outcomes . These data were presented at the virtual HCM Society Scientific Sessions and are available in the Publications page of Tenaya’s website. Tenaya also continues to characterize the pediatric MYBPC3 -associated HCM population through the MyClimb natural history study ( Clinicaltrials.gov ID: NCT05112237 ) with more than 200 children and adolescents enrolled across 29 sites in USA, Canada, Spain, and the United Kingdom. About the MyPEAK-1 Phase 1b/2 Clinical Trial The MyPEAK-1 Phase 1b/2 clinical trial ( Clinicaltrials.gov ID: NCT05836259 ) is an ongoing, multi-center, open-label, dose-escalating study designed to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-201 gene replacement therapy. The trial is enrolling symptomatic (New York Heart Association Class II or III) adults who have been diagnosed with MYBPC3 -associated HCM. MyPEAK-1 is testing doses of 3E13 vg/kg and 6E13 vg/kg in two cohorts of three patients each. Following DSMB assessment of safety at each dose, planned dose expansion cohorts may enroll up to 24 MYBPC3 -associated HCM adults with either nonobstructive or obstructive forms of HCM. To learn more about gene therapy for HCM and participation in the MyPEAK-1 study, please visit HCMStudies.com . About MYBPC3 -Associated Hypertrophic Cardiomyopathy Variants in the Myosin Binding Protein C3 ( MYBPC3) gene are the most common genetic cause of hypertrophic cardiomyopathy (HCM), accounting for approximately 20% of the overall HCM population, or 120,000 patients, in the United States alone. ( 1) MYBPC3 -associated HCM is a severe and progressive condition affecting adults, teens, children and infants. Mutations of the MYBPC3 gene result in insufficient expression of a protein, called MyBP-C, needed to regulate heart contraction. The heart becomes hypercontractile and the left ventricle thickens, resulting in symptoms such as chest pain, shortness of breath, palpitations and fainting. Patients whose disease is caused by MYBPC3 mutations are more likely than those with non-genetic forms of HCM to experience earlier disease onset and have high rates of serious outcomes, including heart failure symptoms, arrhythmias, stroke and sudden cardiac arrest or death. ( 2) There are currently no approved therapeutics that address the underlying genetic cause of HCM. About TN-201 TN-201 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy designed to deliver a working MYBPC3 gene to heart muscle cells via a single intravenous infusion, increasing MyBP-C protein levels to address the underlying cause of MYBPC3 -associated HCM with the aim of halting or even reversing disease after a single dose. The U.S. Food and Drug Administration has granted TN-201 Fast Track, Orphan Drug and Rare Pediatric Drug Designations. TN-201 has also received orphan medicinal product designation from the European Commission. 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. Tenaya employs a suite of integrated internal capabilities, including modality agnostic target validation, capsid engineering and manufacturing, to generate a portfolio of genetic medicines aimed at the treatment of both rare genetic disorders and more prevalent heart conditions. Tenaya’s pipeline includes TN-201, a gene therapy for MYBPC3 -associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2 -associated arrhythmogenic right ventricular cardiomyopathy (ARVC), TN-301, a small molecule HDAC6 inhibitor intended for heart failure with preserved ejection fraction (HFpEF), and multiple early-stage programs in preclinical development. For more information, visit . (1) Sedaghat-Hemedani, et al., Clin ical Res earch Cardiol ogy , 2017 (2) Ho, et al., Circulation 2018 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 “plans,” “will,” “expected,” 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, and expectations regarding TN-201; the planned timing to report initial data from MyPEAK-1 and related focus of the data readout; and statements made by Tenaya’s Chief Medical 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 MyPEAK-1; the potential failure of TN-201 to demonstrate safety and/or efficacy in clinical testing; availability of MyPEAK-1 data at the referenced time; the potential for any MyPEAK-1 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 continuing compliance with applicable legal and regulatory requirements; Tenaya’s ability to raise any additional funding it will need to continue to pursue its 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. Tenaya Contacts Michelle Corral VP, Corporate Communications and Investor Relations IR@tenayathera.com Investors Anne-Marie Fields Precision AQ annmarie.fields@precisionaq.com Media Wendy Ryan Ten Bridge Communications wendy@tenbridgecommunications.com

SOUTH SAN FRANCISCO, Calif., Sept. 03, 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 that Faraz Ali, Tenaya’s chief Executive Officer, will participate in several upcoming investment conferences. Details are as follows: Morgan Stanley 22nd Annual Global Healthcare Conference Date: Thursday, September 5, 2024 Format: Fireside chat 10th Annual World Medical Innovation ForumDate: Monday, September 23, 2024Format: Panel discussion Chardan’s 8th Annual Genetic Medicines ConferenceDate: Tuesday, October 1Formats: Fireside chat and panel discussion The live and archived webcast of the fireside chats may be accessed from the Investors section of Tenaya’s website. A replay of the webcasts will be available on the Tenaya website for approximately 30 days following each conference. 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 its integrated and interrelated Gene Therapy, Cellular Regeneration and Precision Medicine platforms and proprietary core capabilities, 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. ContactMichelle CorralVP, Corporate Communications and Investor RelationsIR@tenayathera.com InvestorsAnne-Marie FieldsPrecision AQ (formerly Stern Investor Relations)annemarie.fields@precisionaq.com MediaWendy RyanTen Bridge Communicationswendy@tenbridgecommunications.com