TNYA

Tenaya Therapeutics announced the publications of positive preclinical data for TN-201, the company's gene therapy candidate for Myosin-Binding Protein C3-associated hypertrophic cardiomyopathy, in Nature Communications. Variants in the MYBPC3 gene resulting in insufficient levels of MyBP-C protein are the most common genetic cause of HCM. TN-201 is Tenaya's adeno-associated virus serotype 9-based gene therapy designed to deliver a working MYBPC3 gene to heart muscle cells via a single intravenous infusion, increasing MyBP-C protein levels to address the underlying cause of MYBPC3-associated HCM with the aim of halting or even reversing disease. Preclinical results published in Nature Communications show that Tenaya's MYBPC3 gene replacement therapy achieved dose-dependent increases in MyBP-C protein, improving multiple parameters of cardiac function at protein levels well below wild-type with doses as low as 1x1013 vg/kg. Of note, treatment with Tenaya's MYBPC3 gene therapy reversed left ventricular hypertrophy, a hallmark of HCM, as evidenced by decreases in posterior wall thickness relative to vehicle and normalization of left ventricular mass relative to body weight. TN-201 is currently being evaluated at doses of 3x1013 vg/kg and 6x1013 vg/kg in Tenaya's ongoing MyPEAK-1 Phase 1b/2 clinical trial for the treatment of MYBPC3-associated HCM. The article, titled, "AAV9-Mediated MYBPC3 Gene Therapy with Optimized Expression Cassette Enhances Cardiac Function and Survival in MYBPC3 Cardiomyopathy Models," describes the results from in vitro and in vivo preclinical studies. Studies conducted in human induced pluripotent stem cell-derived cardiomyocytes compared various cassette configurations and informed the final design of TN-201, which incorporates a full-length MYBPC3 gene with a proprietary cardiac promoter that maintains high specificity for heart cells. To test transduction and expression strength, additional analyses in human iPSC-derived cardiomyocytes showed transduction equivalent to 1 vector genome per diploid genome resulted in near-wild type levels of MYBPC3 RNA and MyBP-C protein at 3x1013 vg/kg. Researchers observed proportional increases in transgene RNA at doses of 3x1013 and 1x1014 vg/kg, while MyBP-C protein levels did not exceed wild type levels, indicating that RNA overexpression does not result in overexpression of protein, suggesting an attractive safety feature of MYBPC3 gene therapy. To measure the efficacy of TN-201, a mouse surrogate of TN-201 was tested against vehicle in a homozygous Mybpc3-deficient murine model that mimics severe disease in humans. Treatment with mTN-201 in Mybpc3 knock-out mice at the time of disease onset or in a more challenging model of advanced disease resulted in: Sustained increases in Mybpc3 RNA and MYBPC3 protein expression; Decreased cardiac biomarkers associated with fibrosis and heart failure; Improved cardiac function, including improved ejection fraction and diastolic function; Heart remodeling; Extended survival; These results were dose dependent, with near-maximal efficacy achieved at doses of 3x1013 vg/kg, and durable, lasting out to 20 months post-treatment. Additional experiments in human engineered heart tissue models that replicate the hypercontractility associated with MYBPC3-associated HCM demonstrated:; Resolution of calcium handling abnormalities; Enhanced diastolic activity.

Canaccord analyst Whitney Ijem lowered the firm's price target on Tenaya Therapeutics to $6 from $18 and keeps a Buy rating on the shares. The firm said its 4Q24 earnings report was straightforward, with the more notable news coming earlier in December with the announcement of positive clinical data from cohort 1 of TN-201's Ph1b/2 (MyPeak-1) for the treatment of MYBPC3-associated HCM.

Chardan lowered the firm's price target on Tenaya Therapeutics to $9 from $18 and keeps a Buy rating on the shares. The firm's updated model incorporates equity dilution from the March offering and reflects its reduced assumptions regarding earlier stage pipeline programs for the company, the analyst tells investors in a research note.

Morgan Stanley lowered the firm's price target on Tenaya Therapeutics to $5 from $15 and keeps an Overweight rating on the shares. Q4 was "uneventful" as data updates for TN-201 and TN-401 remain on track for later this year, says the analyst. The firm's lower target reflects dilution from a recent fundraising and a lower view of the odds of success for TN-201, which it now pegs at 30%, down from 45% previously, the analyst explained.