Tectonic Therapeutic has announced favorable topline results from its Phase Ia clinical trial of TX45, a novel therapeutic being developed for Group 2 pulmonary hypertension-heart failure with preserved ejection fraction (PH-HFpEF). The single ascending dose trial assessed the safety, tolerability, and pharmacokinetic/pharmacodynamic (PK/PD) profile of TX45 in healthy volunteers, with a focus on its ability to enhance renal plasma flow.
Doses ranging from 0.3mg/kg to 3mg/kg administered intravenously and 150mg to 600mg given subcutaneously were evaluated. The data indicated that TX45 was well-tolerated, with minimal adverse events reported and no evidence of immune-mediated clearance. The trial successfully established a robust PK/PD relationship, which was then used to determine appropriate doses and dosing regimens for the upcoming Phase II trial.
Preclinical Correlation
Notably, the PK/PD model derived from the Phase Ia data closely mirrored the relationship observed in preclinical chronic pulmonary hypertension models. Trough exposures associated with maximal activity in preclinical studies also demonstrated near-peak renal plasma flow increase upon TX45 administration. This translation of preclinical findings to the clinic allowed Tectonic to confidently select dose regimens for the Phase II proof-of-concept clinical trial in PH-HFpEF patients.
Phase II Trial Design
The Phase II trial will be a randomized, placebo-controlled study evaluating the efficacy and safety of TX45 in PH-HFpEF patients. Participants will be randomized to receive either 300mg of TX45 subcutaneously once monthly, 300mg subcutaneously every other week, or placebo. Subject screening for the Phase II APEX trial has already commenced, following the US Food and Drug Administration's (FDA) clearance of the investigational new drug (IND) application for TX45. Topline results from the Phase II trial are anticipated in 2026.
Management Commentary
Tectonic CEO and president Alise Reicin commented on the results, stating, "These topline Phase Ia findings for TX45 validate the preliminary data previously presented at lower doses, and we look forward to sharing the full trial results at the AHA Scientific Sessions later this year. Furthermore, the Phase Ia data reveal the successful translation of a robust preclinical model into the clinic. This allowed us to select doses for our global Phase II randomized, six-month clinical trial evaluating the effect of TX45 on PH-HFpEF patients, enriched for those with combined pre- and post-capillary PH."
