Tenaya Therapeutics Unveils Preclinical Research Supporting Product Candidate for Rare and Prevalent Heart Disease Indications at ESC Heart Failure 2021

  • Highly specific HDAC6 inhibitors (HDAC6i) demonstrated improved cardiac function in mouse models of heart failure with preserved ejection fraction (HFpEF) and genetic dilated cardiomyopathy (gDCM)
  • Potential utility of HDAC6 as a target in heart disease was validated using Tenaya’s Precision Medicine platform
  • HDAC6i product candidate TYA-11631 is currently in IND-enabling studies

SOUTH SAN FRANCISCO, Calif – July 12, 2021 – Tenaya Therapeutics, a biotechnology company with a mission to discover, develop and deliver curative therapies that address the underlying causes of heart disease, has unveiled preclinical data supporting drug discovery efforts involving its Precision Medicine Platform at the European Society of Cardiology Heart Failure 2021 (ESC-HF) meeting. The company shared data illustrating the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to identify cardioprotective agents, as well as data supporting the beneficial effect of its proprietary and highly specific histone deacetylase 6 inhibitors (HDAC6i) – including TYA-11631 and TYA-11018 – in models of heart failure with preserved ejection fraction (HFpEF) and genetic dilated cardiomyopathy (gDCM).

“We are very encouraged by the preclinical data that supports the potential multi-modal benefit of TYA-11631 in HFpEF, one of the greatest areas of unmet need in heart disease,” said Faraz Ali, Chief Executive Officer of Tenaya Therapeutics. “The data presented also provide important proof of concept for the utility of Tenaya’s Precision Medicine platform that combines human disease models with machine learning algorithms to support modality agnostic drug discovery.”

The data shared at ESC-HF demonstrated significant reversal of cardiac disease in two HFpEF models following once-daily oral dosing with TYA-11631, Tenaya’s highly specific HDAC6i compound (see abstract titled “HDAC6 Inhibition Improves Diastolic Function in a Mouse Model of Heart Failure with Preserved Ejection Fraction”). HFpEF is a condition involving systemic inflammation, left ventricular hypertrophy, fibrosis, and diastolic dysfunction. It affects an estimated more than 3 million patients in the U.S. and there are no approved disease-modifying therapies. TYA-11631 has been well-tolerated in small and large animal models and is currently in IND-enabling studies.

Additional data shared at ESC-HF also illustrate Tenaya’s ability to successfully use phenotypic screening of iPSC-CMs coupled with deep learning algorithms for target discovery (see abstract titled “Phenotypic Screening Identifies HDAC6 Inhibitors as Cardioprotective Agents in BAG3 Cardiac-Knockout Mouse Model of Dilated Cardiomyopathy”). HDAC6i were one of many potentially cardioprotective agents identified in vitro via a blinded screen of hiPSC-CMs mimicking gDCM due to BAG3 deficiency. The benefit of HDAC6i was subsequently verified in vivo in a BAG3 deficient mouse model as well as the HFpEF models, confirming that the hiPSC-CM disease models can yield biologically relevant targets. Tenaya has established more than 40 in-house hiPSC-CM disease models and is pursuing more targets identified through ongoing screening efforts.

About Tenaya Therapeutics

Tenaya Therapeutics is a biotechnology company committed to a bold mission: to discover, develop and deliver curative therapies that address the underlying drivers of heart disease. Tenaya is developing therapies for rare genetic disorders as well as for more prevalent heart conditions through three distinct but interrelated product platforms: Gene Therapy, Cellular Regeneration and Precision Medicine. Founded by leading cardiovascular scientists from the Gladstone Institutes and the University of Texas Southwestern Medical Center, Tenaya is backed by an established syndicate of investors. For more information, please visit www.TenayaTherapeutics.com and follow us on LinkedIn.

Media Contact:
Wendy Ryan
Ten Bridge Communications
wendy@tenbridgecommunications.com
(781) 316-4424

Tenaya Therapeutics Announces New Appointments to Leadership Team

  • Gene therapy industry veteran Leone Patterson joins Tenaya as Chief Financial and Business Officer
  • Cardiologist Matthew Pollman appointed as Senior Vice President, Clinical Development

SOUTH SAN FRANCISCO, Calif. – Tenaya Therapeutics, a biotechnology company with a mission to discover, develop and deliver curative therapies that address the underlying causes of heart disease, today announced the hires of Leone Patterson, MBA, as Chief Financial and Business Officer and Matthew Pollman, MD, MS, as Senior Vice President, Clinical Development. Ms. Patterson will lead corporate finance, investor relations, business development and corporate communications, as well as various operational functions, while Dr. Pollman will lead clinical development as well as efforts to develop novel delivery methods for cardiac gene therapy.

“We are thrilled to welcome Leone and Matt to Tenaya. Both are proven industry leaders with highly relevant prior experiences building and leading teams at clinical stage gene therapy companies,” said Faraz Ali, CEO of Tenaya. “Leone’s strategic, operational and financial expertise and Matt’s experience with cardiovascular drug and device development will be critical assets as we prepare for the next stage of our growth and maturity.”

Ms. Patterson joins Tenaya from Adverum Biotechnologies, an ocular and rare disease gene therapy company, where she served in several different roles over the course of her five-year tenure including CEO and director, most recently holding the positions of President and Chief Financial Officer in which she was responsible for several core business functions including operations, finance, investor relations and corporate communications. She previously also held Chief Financial Officer roles at Diadexus and Transcept and senior finance roles at Exelixis, Novartis and Chiron. Ms. Patterson earned a B.S. in business administration and accounting from Chapman University and an executive M.B.A. from St. Mary’s College. Ms. Patterson is also a Certified Public Accountant (inactive status). Ms. Patterson currently serves on the board of directors of Nkarta and Eliem Therapeutics.

Dr. Pollman comes to Tenaya with extensive experience in cardiovascular research and development. He most recently served as Executive Vice President at NaviGate Cardiac Structures, a clinical stage company focused on developing transcatheter solutions to treat valvular disease. Prior to that, he served as Chief Medical Officer at Juventas Therapeutics, a clinical stage non-viral gene therapy company focused on cardiovascular conditions. He has authored 17 peer-reviewed journal articles and has been the recipient of two investigator-initiated NIH NHLBI R01 grants in basic cardiovascular research. Dr. Pollman completed his medical training at the University of California San Francisco, Stanford University and Brigham and Women’s Hospital. Dr. Pollman currently serves on the board of directors of Navigate Cardiac Structures and Perfusion Solutions.

About Tenaya Therapeutics

Tenaya Therapeutics is a biotechnology company committed to a bold mission: to discover, develop and deliver curative therapies that address the underlying drivers of heart disease. Tenaya is developing therapies for rare genetic disorders as well as for more prevalent heart conditions through three distinct but interrelated product platforms: Gene Therapy, Cellular Regeneration and Precision Medicine. Founded by leading cardiovascular scientists from Gladstone Institutes and the University of Texas Southwestern Medical Center, Tenaya is backed by an established syndicate of investors. For more information, please visit www.TenayaTherapeutics.com and follow us on LinkedIn.

Media Contact:
Wendy Ryan
Ten Bridge Communications
wendy@tenbridgecommunications.com
(781) 316-4424

Tenaya Therapeutics Receives Orphan Drug Designation and Presents Pre-Clinical Data for its Most Advanced Gene Therapy Product Candidate for Genetic Hypertrophic Cardiomyopathy

  • TN-201 is a potentially curative gene therapy intended to address genetic hypertrophic cardiomyopathy (gHCM) caused by mutations in the Myosin Binding Protein C3 (MYBPC3) gene, that is currently in IND-enabling studies.
  • TN-201 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration.
  • Preclinical data supporting TN-201 presented at the American Society of Gene & Cell Therapy conference demonstrated significant and durable disease reversal in a severe murine model of disease.

SOUTH SAN FRANCISCO, Calif – May 20, 2021 – Tenaya Therapeutics, a biotechnology company with a mission to discover, develop and deliver curative therapies that address the underlying causes of heart disease, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) for TN-201, its most advanced product candidate from its proprietary Gene Therapy Platform.

TN-201 is a potentially curative, one-time, adeno-associated virus (AAV)-based gene therapy to address genetic hypertrophic cardiomyopathy (gHCM) caused by Myosin Binding Protein C3 (MYBPC3) gene mutations. TN-201 is in IND-enabling studies following candidate selection in 2020 and having obtained feedback from multiple regulatory agencies, including the FDA, to guide its path to clinical development.

Mutations of the MYBPC3 gene cause the heart walls of affected individuals to become significantly thickened, leading to abnormal heart rhythms, cardiac dysfunction, heart failure and sudden cardiac death in some adults and children. Mutations of this gene are the most common genetic cause of HCM, estimated to represent approximately 19% of the overall HCM population and to affect approximately 115,000 patients in the United States alone. Current treatments do not address the underlying genetic cause​, do not address all the symptoms of the disease, and do not appear to affect disease progression.

Tenaya presented pre-clinical data supporting TN-201 at the American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting (see Abstract 523 titled “Reversal of Cardiac Hypertrophy with an Optimized MYBPC3 Gene Therapy”). These data demonstrated significant reversal of left ventricular hypertrophy, cardiac dysfunction, and electrophysiological deficits using a murine orthologue of TN-201 in a severe murine model of the disease. This disease reversal was dose-dependent and stable for more than one year following a single infusion, and a survival benefit was observed vs untreated controls. No safety signals have been observed to date.

“We are pleased that the FDA has granted orphan drug designation for TN-201,” said Faraz Ali, CEO of Tenaya. “The feedback we have received from multiple regulatory agencies supports our IND-enabling studies, planned scale-up of AAV manufacturing at our new cGMP facility, and the design of planned first-in-human clinical studies. The data presented at ASGCT provides new hope for individuals with HCM due to MYBPC3 mutations who lack therapies to address the underlying genetic cause of their disease.”

Orphan designation qualifies Tenaya for various development incentives as part of the Orphan Drug Act, including tax credits for certain clinical trials. This designation is not an assurance that regulatory approval will be received but would grant TN-201 with 7 years of market exclusivity if such approval is achieved.

About Tenaya Therapeutics

Tenaya Therapeutics is a biotechnology company committed to a bold mission: to discover, develop and deliver curative therapies that address the underlying drivers of heart disease. Tenaya is developing therapies for rare genetic disorders as well as for more prevalent heart conditions through three distinct but interrelated product platforms: Gene Therapy, Cellular Regeneration and Precision Medicine. Founded by leading cardiovascular scientists from the J. David Gladstone Institutes and the University of Texas Southwestern Medical Center, Tenaya is backed by an established syndicate of investors. For more information, please visit www.TenayaTherapeutics.com and follow us on LinkedIn.

Media Contact:
Wendy Ryan
Ten Bridge Communications
wendy@tenbridgecommunications.com
(781) 316-4424

Tenaya Therapeutics Secures $106 Million in Series C Funding to Accelerate Pipeline of Potentially Curative Therapies for Heart Disease

  • Series C round led by RTW Investments, LP; RA Capital Management; Fidelity Management & Research Company; and funds and accounts advised by T. Rowe Price Associates, Inc.; and joined by existing investors including The Column Group, Casdin Capital and GV.
  • Funds will help advance lead gene therapy program in hypertrophic cardiomyopathy (HCM) as well as multiple programs across three therapeutic platforms: Gene Therapy, Cellular Regeneration and Precision Medicine.
  • Company will establish dedicated cGMP facility for AAV manufacturing in the San Francisco Bay Area in 2021.

SOUTH SAN FRANCISCO, Calif. — March 1, 2021 — Tenaya Therapeutics, a biotechnology company whose mission is to discover, develop and deliver curative therapies that address the underlying causes of heart disease, today announced that it has secured $106 million in Series C funding. Founded by leading cardiovascular scientists from the Gladstone Institutes and UT Southwestern (UTSW), Tenaya is advancing programs across three therapeutic platforms to address heart disease: Gene Therapy, Cellular Regeneration and Precision Medicine.

The Series C financing was led by RTW Investments, LP and adds new investors RA Capital Management, Fidelity Management & Research Company and funds and accounts advised by T. Rowe Price Associates, Inc. with additional participation from all existing investors including The Column Group, Casdin Capital, GV and others.

The new funding will allow Tenaya to advance its lead gene therapy program towards clinical studies; progress new programs towards IND-enabling studies; build on existing drug discovery and development capabilities across its three platforms; and invest in cGMP manufacturing capabilities.

“Heart disease remains the leading cause of death in the world despite improvements in standards of care,” said Faraz Ali, Chief Executive Officer of Tenaya. “There is tremendous promise in the use of vastly more sophisticated tools for drug discovery available today to pioneer new classes of targeted treatments for heart failure, including potentially one-time curative gene therapies for genetic cardiomyopathies. We appreciate the strong support of new and existing investors who are helping us advance therapies to improve and extend the lives of patients.”

 

Emerging Portfolio

Tenaya is advancing diverse and differentiated therapeutic approaches to gene therapy and small molecules for both prevalent and rare forms of heart disease:

  • Gene Therapy:
    • MYBPC3: Tenaya’s lead program is an adeno-associated virus (AAV) gene therapy targeting genetic hypertrophic cardiomyopathy (HCM) in adults and children due to mutations in the MYBPC3 gene. Tenaya’s product candidate uses a proprietary, best-in-class approach with significant and durable disease reversal demonstrated in a relevant murine model. The program is currently in IND-enabling studies.
    • DWORF: Tenaya is developing a first-in-class AAV gene therapy involving DWORF, a muscle-specific micro-peptide acting on the SERCA pathway first discovered by Tenaya co-founder Eric Olson, Ph.D. Tenaya and its academic collaborators have accumulated significant preclinical proof-of-concept evidence for the efficacy and safety of DWORF over-expression in multiple models. These findings support the broad utility of this approach for patients with genetic cardiomyopathies due to specific mutations as well as more prevalent heart failure populations.
  • Cellular Regeneration: Tenaya has made significant advances in its unique approach to cellular regeneration using a single AAV vector to deliver proprietary combinations of multiple genes that drive in vivo reprogramming of resident cardiac fibroblasts to create new cardiomyocytes. Results of this approach in a chronic post-myocardial infarction (MI) pig model were first presented at scientific conferences in 2020 and represent the first-ever successful demonstration of the efficacy and safety of this approach in a large animal model with a human-sized heart.
  • Precision Medicine: Tenaya is developing a small molecule therapy against an unnamed target and has demonstrated compelling in vivo efficacy in a model for genetic dilated cardiomyopathy as well as in additional models that support its use in more prevalent heart failure populations. Medicinal chemistry for a best-in-class molecule has been completed and IP has been filed for multiple chemical series.

 

Drug Development Capabilities

Since its Series B funding round announced in 2019, Tenaya has added to the depth and breadth of its drug discovery capabilities to support the efficacy, safety and differentiation of current and future products:

  • Disease Modeling: Tenaya has made significant advancements to its Precision Medicine platform to identify and validate targets for heart disease for modality-agnostic drug discovery. The company has successfully demonstrated the feasibility of phenotypic screening of human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) disease models using proprietary imaging and machine learning algorithms. The target for the company’s first small molecule project was identified through such screening and provides important proof-of-concept for the utility of this novel approach.
  • AAV Capsids: Tenaya has established in-house AAV capsid engineering capabilities and has successfully screened hundreds of millions of variants from diverse, proprietary libraries to discover novel AAV capsids with higher tropism for the heart vs. other organs, as well as capsids that can more specifically target cardiomyocytes vs. cardiac fibroblasts in the heart. The company has filed IP on several variants that out-perform parental capsids in multiple models including non-human primate (NHP) models.
  • Regulatory Elements: Tenaya has developed and filed IP on proprietary regulatory elements, including novel cardiac-specific promoters, to more selectively target gene expression in cardiomyocytes or cardiac fibroblasts and to significantly increase gene expression over what can be achieved with traditional promoters. 

 

AAV Manufacturing

Tenaya also announced important steps towards internalizing its AAV manufacturing capabilities, expertise and IP to support its emerging portfolio of gene therapy products:

  • Pilot Plant Operation: Tenaya has established an in-house Pilot Plant Operation at the 200L scale with the key Process Development (PD), Analytical Development (AD) and Quality Control (QC) personnel to support all non-clinical studies including those involving large animal models under Good Laboratory Practice regulations.
  • cGMP Facility: Tenaya will establish a dedicated cGMP facility in 2021 for drug product manufacturing and has leased space for this new site in the San Francisco Bay Area. The facility will produce drug product at the 1000L scale to support first-in-human studies for the company’s lead gene therapy program and has a modular design that will support scale-out and scale-up of manufacturing capacity in response to evolving needs.
  • Platform Comparability: Tenaya has established necessary PD expertise to ensure comparable product efficacy using different capsids – including novel capsids developed in-house at Tenaya – in both HEK293 and Sf9/rBV manufacturing platforms.
  • Intellectual Property: Tenaya has filed IP on process improvements that will support scale-up of AAV manufacturing to larger bioreactors necessary for product supply of therapies intended for more prevalent heart disease populations. The company has also in-licensed foundational manufacturing IP necessary to support current and future programs.

“Tenaya has successfully built on its distinguished scientific heritage to advance a bold research strategy and differentiated drug discovery capabilities uniquely focused on heart disease,” said Roderick Wong, M.D., Managing Partner and Chief Investment Officer at RTW Investments, LP. “We are strong believers in the potential for new approaches in this area of high unmet need and are encouraged by early results we are seeing in the industry with the use of AAV to treat genetic forms of heart disease. We are excited to partner with Tenaya to accelerate their leadership position in this exciting field and to advance novel therapies that can benefit individuals and families fighting heart disease.”

 

About Tenaya Therapeutics

Tenaya Therapeutics is shaping the future of heart disease treatment driven by a bold mission: to discover, develop and deliver curative therapies that address the underlying drivers of heart disease. Tenaya is developing therapies for rare genetic disorders as well as for more prevalent heart conditions through three platforms: Gene Therapy, Cellular Regeneration and Precision Medicine. Founded by leading cardiology researchers at the Gladstone Institutes and UT Southwestern, Tenaya is backed by a top-tier syndicate of investors. For more information, please visit www.TenayaTherapeutics.com and follow us on LinkedIn.

Media Contact:
Wendy Ryan
Ten Bridge Communications
wendy@tenbridgecommunications.com
(781) 316-4424

Navigating the Complexities of AAV Scale-Up and Manufacturing

Tenaya’s senior vice president of manufacturing, Kee-Hong Kim, Ph.D., spoke with John Sterling, editor of Genetic Engineering & Biotechnology News in an executive roundtable interview to discuss the challenges and complexities involved with AAV manufacturing for gene therapy. Kee shared his perspective on the resources, tools and expertise needed to scale up production, as well as how Tenaya is innovating and strategizing to overcome these challenges.

Read Article

Talent, culture, and ethics are all necessary ingredients in the biotech recipe for success

Our CEO, Faraz Ali, spoke with Peter Kaplan for an article in STAT to discuss the core values that are essential for a biotech company’s success. Faraz outlined the ways in which strong ethics and the right moral compass are crucial for creating a culture that empowers all employees. Our mission: find talented people who want to do the right thing.

Read More

The heart of market access: opportunities and challenges for cell and gene therapy development for orphan and prevalent cardiovascular diseases

Our CEO, Faraz Ali, authored an article for Cell & Gene Therapy Insights discussing the opportunities and challenges of developing cell and gene therapies for cardiovascular disease. Cardiovascular diseases, especially orphan indications, are vastly underrepresented in research on regenerative medicine and advanced therapy, but recent advancements suggest an evolving landscape for treating heart disease with cell and gene therapies.

Learn more about these advancements and challenges, as well as Tenaya’s dedication to discovering and developing transformative therapies for cardiovascular disease, in the article.

Read Article

Tenaya Therapeutics to Present Preclinical Data at 2020 Annual Meeting of the American Society of Gene & Cell Therapy

SOUTH SAN FRANCISCO, Calif., May 11, 2020 – Tenaya Therapeutics, Inc., a company with a mission to discover, develop, and deliver potentially curative therapies that target the underlying causes of heart disease, today announced that it will present preclinical data from four studies as posters at the 23rd Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), being held May 12-15, 2020, in a virtual format.

Three posters illustrate advances made with Tenaya’s Cellular Regeneration platform using direct reprogramming of resident cardiac fibroblasts to create new cardiomyocytes. The fourth poster illustrates advances made with the Company’s Gene Therapy platform to identify novel adeno-associated virus (AAV) variants with superior attributes to parental serotypes, that can be used develop best-in-class therapies for several undisclosed genetic cardiomyopathies under development.

Faraz Ali, Chief Executive Officer, stated, “These data highlight important advances in our science, our capabilities, and our intellectual property since Tenaya was founded in 2016. They confirm the potential for our three product platforms to address both rare and prevalent forms of heart disease, the leading cause of death in the world. The compelling efficacy demonstrated with our cardiac reprogramming project in a relevant large animal model is an important step forward for the field of cardiac regeneration, and supports advancement of this innovative approach toward the clinic as a first-in-class therapy for patients with heart failure following a myocardial infarction.”

Details of Tenaya’s poster presentations at ASGCT are as follows:

Abstract 273
Lombardi et al., Cardiac Direct Reprogramming Gene Therapy for Ischemic Injury
Poster Session Date/Time: Tuesday, May 12, from 5:30 to 6:30pm ET
Session Title: Cardiovascular and Pulmonary Diseases

Abstract 279
Yang et al., Efficacy of Cardiac Reprogramming via Gene Therapy in Rat with Chronic Heart Failure
Poster Session Date/Time: Tuesday, May 12, 5:30 to 6:30pm ET
Session Title: Cardiovascular and Pulmonary Diseases

Abstract 280
Reid et al., Engineering Novel rAAV Vectors with Enhanced Cardiac Tropism
Poster Session Date/Time: Tuesday, May 12, 5:30 to 6:30pm ET
Session Title: Cardiovascular and Pulmonary Diseases

Abstract 599
Srinath et al., Developing an Optimized Cardiac Reprogramming Cocktail for Gene Therapy in Humans
Poster Session Date/Time: Wednesday, May 13, 5:30 to 6:30pm ET
Session Title: AAV Vectors – Preclinical and Proof-of-Concept Studies

All abstracts for the ASGCT Annual Meeting will be available on ASGCT’s website at https://www.asgct.org/. These poster presentations will later be available on the Company’s website at http://www.tenayatherapeutics.com.

About Tenaya’s Three Product Platforms for Heart Disease
Tenaya is advancing first-in-class product candidates from three separate platforms – Cellular Regeneration, Gene Therapy, and Precision Medicine. The Cellular Regeneration platform uses novel adeno-associated virus (AAV) vectors to deliver proprietary transcription factors that can drive in vivo reprogramming of resident cardiac fibroblasts into cardiomyocytes, with an initial focus on acute and chronic injury following a myocardial infarction. The Gene Therapy platform uses AAV vectors for the targeted delivery and expression of therapeutic payloads to specific cells in the heart, with an initial focus on the treatment of genetically defined cardiomyopathies. The Precision Medicine platform uses isogenic iPSC-derived cardiomyocytes as human disease models to identify and validate new heart failure targets and to screen for therapeutic compounds, with an initial focus on small molecules for the treatment of several genetically defined dilated cardiomyopathies.

About Tenaya Therapeutics, Inc.
Tenaya Therapeutics is a biopharmaceutical company with a mission to discover, develop, and deliver potentially curative treatments that target the underlying causes of heart disease. Tenaya is advancing multiple candidates from three product platforms – Cellular Regeneration, Gene Therapy, and Precision Medicine. Headquartered in South San Francisco, California, Tenaya was founded by world-leading scientists from the Gladstone Institute’s Cardiovascular Division and from the University of Texas Southwestern Medical Center. For more information, please visit www.tenayatherapeutics.com.

Media contact:
Kathy Vincent
(310) 403-8951
kathy@kathyvincent.com

# # #

Tenaya Therapeutics Closes $92 Million Series B Financing

– Proceeds advance heart disease projects from three product platforms toward the clinic –

SOUTH SAN FRANCISCO, Calif., October 3, 2019 – Tenaya Therapeutics, Inc., a company with a mission to discover, develop, and deliver curative therapies that target the underlying causes of heart disease, today announced the successful completion of a $92 million Series B financing.

The financing round was led by Casdin Capital and included GV, The Column Group, and additional undisclosed new and existing investors. Tenaya has raised $142 million since its founding by scientists at the Gladstone Institutes and University of Texas Southwestern Medical Center in October 2016.

Proceeds from the financing will be used to advance and to expand Tenaya’s pipeline and to strengthen the science, capabilities, and intellectual property that provide the foundation for Tenaya’s multi-modality product platforms – Cellular Regeneration, Gene Therapy, and Precision Medicine.

“We are now well-resourced to build on our capabilities in research and manufacturing, and to accelerate the development of our lead gene therapy and small molecule projects for both orphan and prevalent heart diseases towards the clinic,” said Faraz Ali, Chief Executive Officer of Tenaya. “We are pleased to have a group of experienced private and public investors led by Casdin Capital and The Column Group who support the potential for Tenaya’s science to transform the treatment of heart failure, the leading cause of death in the world.”

In connection with the Series B round, Eli Casdin, Chief Investment Officer, Casdin Capital, will join Tenaya’s Board of Directors, and Anthony Philippakis, M.D., Ph.D., Venture Partner, GV, will join as Board Observer.

“Tenaya is building a new type of company that views heart disease through the lens of human genetics and that is advancing a diverse set of therapeutic tools to correct it,” said Mr. Casdin. “It is a unique company in the field of cardiovascular disease, built on a world-class scientific foundation and driven by a growing team of entrepreneurs and drug developers. We look forward to being a supportive partner in the company’s important and exciting future.”

About Tenaya’s Three Product Platforms for Heart Disease

Tenaya is advancing first-in-class product candidates from three separate platforms – Cellular Regeneration, Gene Therapy, and Precision Medicine. The Cellular Regeneration platform uses novel adeno-associated virus (AAV) vectors to deliver proprietary transcription factors that can drive in vivo reprogramming of resident cardiac fibroblasts into cardiomyocytes, with an initial focus on acute and chronic injury following a myocardial infarction. The Gene Therapy platform uses AAV vectors for the targeted delivery and expression of therapeutic payloads to specific cells in the heart, with an initial focus on the treatment of genetically defined cardiomyopathies. The Precision Medicine platform uses isogenic iPSC-derived cardiomyocytes as human disease models to identify and validate new heart failure targets and to screen for therapeutic compounds, with an initial focus on small molecules for the treatment of several genetically defined dilated cardiomyopathies.

About Tenaya Therapeutics, Inc.

Tenaya Therapeutics is a biopharmaceutical company with a mission to discover, develop, and deliver potentially curative treatments that target the underlying causes of heart disease. Tenaya is advancing multiple candidates from three product platforms – Cellular Regeneration, Gene Therapy, and Precision Medicine. Headquartered in South San Francisco, California, Tenaya was founded by world-leading scientists from the Gladstone Institute’s Cardiovascular Division and from the University of Texas Southwestern Medical Center. For more information, please visit www.tenayatherapeutics.com.

Media contact:
Kathy Vincent
(310) 403-8951
kathy@kathyvincent.com

# # #

Unlocking a cell’s potential to regenerate the heart

March 1, 2018 – ScienceDaily – Some organisms have a remarkable capacity for regenerating tissue. If a fish or salamander suffers heart damage, for instance, their cells are able to divide and successfully repair the injured organ. Imagine if you could do the same.

In the embryo, human heart cells can divide and multiply, allowing the heart to grow and develop. The problem is that, right after birth, cardiomyocytes (heart muscle cells) lose their ability to divide. The same is true for many other human cells, including those of the brain, spinal cord, and pancreas.

“Because so many adult cells can’t divide, your body can’t replace cells that are lost, which causes disease,” explained Deepak Srivastava, MD, president of the Gladstone Institutes and senior investigator. “If we could find a way to get these cells to divide again, we could regenerate a number of tissues.”

For decades, the scientific community has been trying to do just that, with limited success. Until now, attempts have been ineffective and poorly reproducible.

In a new study published in the scientific journal Cell, Srivastava and his team finally reached this long-sought goal. They developed the first efficient and stable method to make adult cardiomyocytes divide and repair hearts damaged by heart attacks, at least in animal models.

Over 24 million people worldwide suffer from heart failure, with few treatment options available other than heart transplants for end-stage patients. The potential to create new muscle cells through cell division, much like a salamander does, could offer new hope to the millions living with damaged hearts.

Unlocking an Adult Cell’s Potential to Multiply

Srivastava and his team identified four genes involved in controlling the cycle of cell division. They found that when combined — and only when combined — these genes cause mature cardiomyocytes to re-enter the cell cycle. This results in the cells dividing and rapidly reproducing.

“We discovered that when we increased the function of these four genes at the same time, the adult cells were able to start dividing again and regenerated heart tissue,” said Tamer Mohamed, scientist at Tenaya Therapeutics and former postdoctoral scholar in Srivastava’s laboratory, who is first author of the study. “We also showed that, after heart failure, this combination of genes significantly improves cardiac function.”

The scientists tested their technique in animal models and cardiomyocytes derived from human stem cells. They used a rigorous approach to track whether the adult cells were truly dividing in the heart by genetically marking newly divided cells with a specific color that could be easily monitored. They demonstrated that 15-20 percent of the cardiomyocytes were able to divide and stay alive due to the four-gene cocktail.

“This represents a considerable increase in efficiency and reliability when compared to previous studies that could only cause up to 1 percent of cells to divide,” said Srivastava, who is also a professor at UC San Francisco. “Of course, in human organs, the delivery of genes would have to be controlled carefully, since excessive or unwanted cell division could cause tumors.”

To further simplify their technique, the team looked for ways to reduce the number of genes needed for cell division while maintaining efficiency. They found they could achieve the same results by replacing two of the four genes with two drug-like molecules.

Regenerating Multiple Human Tissues

The researchers believe that their technique could also be used to coax other types of adult cells to divide again, given that the four genes they used are not unique to the heart.

“Heart cells were particularly challenging because when they exit the cell cycle after birth, their state is really locked down — which might explain why we don’t get heart tumors,” said Srivastava. “Now that we know our method is successful with this difficult cell type, we think it could be used to unlock other cells’ potential to divide, including nerve cells, pancreatic cells, hair cells in the ear, and retinal cells.”

This could lead to a powerful regenerative approach to treat not only heart failure, but also brain damage, diabetes, hearing loss, and blindness. And one day, the human might just outperform the salamander.