Tenaya Therapeutics, Inc. released new data for TN-301 at the 2023 Heart Failure Society of America (HFSA) Annual Scientific Meeting. TN-301 is Tenaya's highly selective small molecule inhibitor of histone deacetylase 6 (HDAC6) being developed for the potential treatment of heart failure with preserved ejection fraction (HFpEF). taken together, these data support continued development of TN-301 as a potential treatment to address the many HFpEF patients underserved by today's treatment options.

Results from the Phase 1 clinical trial of TN-301 were presented in an ePoster, Phase 1 Clinical Trial Of TN-301, A Highly Selective HDAC6 Inhibitor with Potential in HFpEF, Shows Target Engagement (#417). Tenaya initiated the randomized, double-blind, placebo-controlled Phase 1 clinical trial in September 2022 to assess the safety and tolerability of escalating, oral doses of TN-301, as well as pharmacokinetics (PK) and pharmacodynamics (PD) measures. The Phase 1 trial enrolled a total of 72 healthy adult participants in two stages.

In Stage 1, participants received single ascending doses (SAD) of either TN-301 at doses ranging from 1mg - 700mg or placebo.ubulin acetylation was previously established as a relevant PD marker of HDAC6 inhibition in preclinical studies and utilized in the Phase 1 clinical trial to confirm target engagement. Upon achieving evidence of target engagement at single doses of 5mg, participants were enrolled in Stage 2 and received multiple ascending doses (MAD) of TN-301 at once daily doses of 25mg, 100mg and 300mg for 14 days. These occurred with similar frequency among those who received placebo or TN-301 and did not increase with TN-301 dose.

All participants completed the study. PK results showed overall dose proportionality in both the SAD and MAD stages of the study with a half-life supportive of once-daily dosing. Robust HDAC6 inhibition was observed and increasing doses and exposures with TN-301 correlated with increasing PD effects.

Future studies of TN-301 in HFpEF patients may evaluate a range of doses starting at approximately 25 mg and higher. Additive Benefit Observed with Combination of Tenaya's HDAC6 inhibitor with Approved SGLT2 inhibitor in HFpEF Model. The ePoster titled, Co-Administration of Inhibitors of HDAC6 and SGLT2 in Murine HFpEF Models Results in Additive Improvements in Cardiac Structural and Functional Measures (#104), describes an effort by Tenaya researchers to examine the effect of combining TYA-018 (an HDAC6 inhibitor structurally and functionally similar to TN-301) with empagliflozin (a sodium-glucose cotransporter-2 (SGLT2) inhibitor) which is approved for the treatment of HFpEF) in the company's proprietary HFpEF mouse model.

This study compared healthy controls with those treated with TYA-018 and empagliflozin administered alone or in combination vs. untreated HFpEF mice. 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 potential failure of TN-301 to demonstrate safety and/or efficacy in clinical testing; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating TN-301 as well as clinical trials evaluating TN-301.