PRECISION MEDICINE PLATFORM
We use human cell-based disease models to screen for targets that are relevant in the progression of various forms of heart disease. Our vision is that through such models, we will be able to discover treatments that address the underlying causes of disease.
Leveraging the seminal discovery of induced pluripotent stem cells (iPSCs) in 2006, Tenaya has developed proprietary libraries of iPSC-derived cardiomyocytes (iPSC-CMs), including patient-derived cell lines as well as isogenic lines engineered with the help of gene editing tools to carry human disease-causing mutations. These cells are matured to create both two-dimensional (2D) and three-dimensional (3D) disease models, with broad applicability for our research and clinical development:
- We use iPSC-CM cells as disease models to more clearly identify which genetic disruptions create cellular defects relevant to human disease, especially where animal models are not sufficiently representative.
- We conduct phenotypic screening of iPSC-CMs leveraging next generation high content imaging and machine learning algorithms to both identify new targets and screen for different types of treatments – including gene therapy and small molecules – against new targets.
Our initial focus is in genetically-defined dilated cardiomyopathy (DCM), a major cause of heart failure and the most common reason for needing a heart transplant. We have also expanded to other forms of heart failure, such as genetically-defined hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC).
GENE THERAPY PLATFORM
Gene therapy has been shown to be highly effective in targeting multiple organs, including the eye, the liver and the brain. We are building on these advances to bring gene therapy to the heart.
The field of gene therapy is based on viruses that already exist in humans and that do not cause human disease, for example, AAV1, AAV2, AAV5, AAV6, AAV8, AAV9, AAVrh10 and others. These viruses have been used to safely treat thousands of patients in clinical studies around the world. There are now several therapies that use such viruses that have been approved by the Food and Drug Administration (FDA) and other regulatory agencies.
Tenaya is not only bringing the use of such viruses to the treatment heart disease, but we are taking the idea to the next level. Our proprietary capabilities allow us to identify, engineer, validate and manufacture best-in-class novel adeno-associated viral (AAV) vectors to optimize the delivery and expression of therapy more selectively to cells of interest in the heart. These capabilities open up the opportunity to deliver novel gene therapies to patients with heart disease and position us to become the leader in gene therapy for cardiology.
We are leveraging those capabilities to develop gene therapies for both prevalent and rare forms of heart disease. Our lead gene therapy program is currently in IND-enabling studies for treatment of genetic hypertrophic cardiomyopathy (HCM), a leading genetic cause of heart failure in both adults and children.
There are two abundant cell types in the heart: cardiomyocytes, muscle cells which contribute to heartbeat, and cardiac fibroblasts. Cardiomyocytes are post-mitotic, which means they are not capable of regenerating, while cardiac fibroblasts are able to divide and proliferate. The damage to the heart muscle that occurs as a result of myocardial infarction (heart attack), infection or aging is permanent and irreparable with current therapies. Cardiomyocytes that are lost do not come back.
Tenaya is pursuing multiple approaches to restore lost heart function by regenerating cardiomyocytes. One approach achieves this by using viral vectors to deliver a proprietary cocktail of genes to permanently convert – or “reprogram” – a patient’s own existing cardiac fibroblasts into new cardiomyocytes. Another approach achieves this by using viral vectors to deliver a proprietary cocktail of genes to transiently induce a patient’s own existing cardiomyocytes to divide into new cells. In both cases, the newly formed cardiomyocytes electrically and mechanically connect with their surrounding cell and contribute to heart function.
Tenaya’s initial focus is on developing disease-modifying treatments for myocardial infarction and for disorders involving cardiac fibrosis and cardiomyocyte loss.