Tenaya’s share slump following the TN-201 data drop could be due to its “significantly lower” level of RNA expression in the Phase Ib/II trial than in preclinical models, according to William Blair analysts.
Tenaya Therapeutics on Tuesday released early findings from the Phase Ib/II MyPEAK-1 study, demonstrating what it called “robust” delivery of its investigational gene therapy TN-201 into the heart muscle cells of patients with hypertrophic cardiomyopathy.
Investors, however, didn’t seem to be impressed with Tenaya’s readout. The biotech’s stocks took a nosedive on Tuesday, tanking more than 50% following the data drop.
Preliminary data from three patients showed that at a dose level of 3E13 vg/kg, TN-201 treatment resulted in readily detectable levels of the vector DNA in heart tissues, alongside evidence of the transgene RNA expression. The patients also showed increasing concentrations of the TN-201 mRNA and myosin-binding protein C (MYBPC) over time.
Clinical disease markers were stable or showed directional improvement in the first two patients dosed with TN-201, while circulating biomarkers of cardiac muscle injury and strain remained stable.
TN-201 was also well-tolerated overall, with no cardiac toxicities, thrombotic microangiopathy-related events or complement-related side effects. Adverse events in the study were primarily mild, transient or reversible, and most were consistent with the safety profile of adeno-associated viral vector (AAV)-based gene therapies.
Still, Tenaya documented “isolated” cases of heightened liver enzyme in all three treated patients, one of whom required a corticosteroid bolus in the hospital. None of the enzyme elevations were linked to signs of liver damage, and all patients were managed with corticosteroids.
William Blair analysts explained in an investor note that the sell-off might be linked with the liver signals, though they pointed out that TN-201’s overall safety profile “appears consistent with other AAV gene therapies.” There were also no reports of cardiotoxicity in MyPEAK-1.
A more likely reason for the share slump is that the “level of RNA expression” in the Phase Ib/II study “is significantly lower than what was observed in preclinical models,” according to the William Blair analysts. This means that “a higher dose may elicit higher levels of therapeutic mRNA and protein.”
The MyPEAK-1 data is also limited, coming only from three patients with no baseline biopsy samples, which according to the analysts makes it “challenging to interpret how [TN-201 transduction and RNA expression] correlate with MYBPC3 protein expression and measures of clinical benefit.”
Overall, William Blair finds Tenaya’s data “validating” and demonstrative of TN-201’s transduction efficacy and safety. “We look to additional updates in 2025 for more clarity on TN-201’s potential clinical benefit and if a registrational pathway based on changes in MYBP-C expression and cardiac function is a possibility,” the analysts added.
