Patients

A chronic, progressive condition, hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, and variations in the Myosin Binding Protein C3 (MYBPC3) gene are the most common genetic cause of HCM. Mutations of the MYBPC3 gene result in insufficient expression of a protein needed to regulate heart contraction. This can lead to serious complications including debilitating symptoms such as shortness of breath, fainting and palpitations; heart failure; significant impairment in overall quality of life; and sudden cardiac death in some adults and children. People with HCM whose condition is caused by mutations in the MYBPC3 gene may have more severe disease, where they develop symptoms at a younger age and/or their symptoms may be more severe. There are currently no approved therapeutics that address the underlying genetic cause of HCM.

Tenaya is developing TN-201, a gene therapy intended to deliver a working MYBPC3 gene to heart muscle cells via a single dose to address the underlying cause of MYBPC3-associated HCM. We are currently enrolling clinical and natural history studies to support TN-201’s development, including MyPeak™-1, the first clinical trial to study the effects of gene therapy for HCM in patients. To learn more about MYBPC3-associated HCM, TN-201 and Tenaya’s research studies, please visit HCMStudies.com.

Variations in the plakophilin-2 (PKP2) gene are the most common cause of arrhythmogenic right ventricular cardiomyopathy (ARVC), also known as arrhythmogenic cardiomyopathy or ACM. In PKP2-associated ARVC, mutations of the PKP2 gene results in a lack of the proteins needed for the proper functioning of the structure between heart muscle cells (called the desmosome) that maintains physical connections and electrical signaling. As that structure degrades, electrical pulses in the heart become unstable and cardiac muscle cells are replaced by fibrofatty tissue. This results in irregular heart rhythms and remodeling of the heart. ARVC symptoms include arrhythmias, palpitations, lightheadedness, dizziness and fainting. PKP2-associated ARVC is typically diagnosed before age 40, and sudden cardiac arrest due to life-threatening ventricular arrhythmias is frequently the first sign of disease.

TN-401 is Tenaya’s gene therapy candidate designed to deliver a working PKP2 gene to the heart to restore healthy function and halt disease progression. In order to better understand ARVC and to prepare for a planned Phase 1b interventional clinical trial (known as RIDGE™-1) in the coming months, we are conducting a global non-interventional natural history and serotype study of PKP2-associated ARVC. To learn more about PKP2-associated ARVC, TN-401 and Tenaya’s research studies, please visit ARVCStudies.com.

HFpEF occurs when the heart muscle becomes stiff and unable to relax and fill properly to meet the demands of the body. It is a complex syndrome, with multiple risk factors including aging, obesity, diabetes, kidney disease and hypertension, which in turn contribute to the inflammation and metabolic dysfunction thought to underly disease.

TN-301 is Tenaya’s small molecule inhibitor of HDAC6 (histone deacetylase 6). TN-301 has a multi-pronged mechanism of action that includes modifying proteins to coordinate cellular processes. In preclinical studies, TN-301 has been shown to reverse many of the signs and symptoms of HFpEF, with evidence of improved cardiac function, improved glucose tolerance and reduced inflammation and fibrosis.

Tenaya has completed a Phase 1 clinical trial of TN-301 in healthy volunteers. TN-301 was generally well tolerated, with dose-proportional pharmacokinetics supportive of once-daily dosing. Robust HDAC6 inhibition was observed at levels that met or exceeded those observed as effective in preclinical studies. Other histones were not impacted, indicating that TN-301 is highly selective.