Tenaya Therapeutics, Inc. provided a 2022 business update including the selection of TN-401 as the development candidate for the treatment of Genetic Arrhythmogenic Right Ventricular Cardiomyopathy(gARVC) due to PKP2 gene mutation. TN-401 - PKP2Gene Therapy Program for Genetic Arrhythmogenic Right Ventricular Cardiomyopathy (gARVC): Tenaya has nominated TN-401 as a clinical drug candidate to treat patients carrying PKP2 gene mutations. Mutations of the PKP2 gene are the leading genetic cause of ARVC and can cause severe disease including significant arrhythmia and sudden cardiac death in adults and children.

These mutations are estimated to affect more than 70,000 patients in the US alone. Based on publicly available information to date, the company believe there are no approved disease-specific therapies. Tenaya expects to present new preclinical data supporting the TN-401 program including dose-dependent efficacy, survival durability, and mechanistic insights at a scientific conference in 2022.

Tenaya has successfully scaled up production of TN-401 to 200L and is initiating IND enabling studies. Tenaya will also support establishment of a global natural history study in 2022 and expects to submit an IND in 2023. TN-201 – MYBPC3Gene Therapy Program for Genetic Hypertrophic Cardiomyopathy (gHCM): Tenaya has previously announced initiation of IND-enabling activities andexpects to submit an IND to the FDA in the second half of 2022.

The safety and efficacy of TN-201 will initially be explored in symptomatic adult patients with MYBPC3 mutations and the non-obstructive form of HCM (nHCM). Approximately 70% of patients with truncating MYBPC3 mutations have the nHCM form of the disease where surgical myectomy is not an option and the unmet need is high. Tenaya continues site activation and patient enrollment in the MyClimb global natural history study to support and potentially expedite the future evaluation of TN-201 in pediatric patients during clinical development after early safety has been established in adults.

TN-201 has been granted orphan drug designation by the FDA. TN-301 – HDAC6 Inhibitor (Small Molecule for Heart Failure with Preserved Ejection Fraction): Tenaya has continued to generate strong preclinical data supporting the multi-modal mechanism of action of TN-301 in multiple disease models and expects to present these at a scientific conference in 2022. Tenaya has previously announced initiation of IND-enabling activities and a cGMP manufacturing campaign and expects to submit an IND to the FDA in the second half of 2022.

The safety, tolerability, pharmacokinetics, and pharmacodynamics of TN-301 will initially be assessed in healthy volunteers, as well as possibly in pre-diabetic participants to assess target engagement and proof of activity. Manufacturing: Tenaya expects its, modular cGMP manufacturing facility in Union City, California will become operational in the first half of 2022, and will support the production of drug product at multiple scales for clinical studies for all AAV-based programs, including TN-201 and TN-401.