Tectonic Therapeutic Reports Positive Phase 1a Safety, Tolerability, and PK/PD Results for TX45

Tectonic Therapeutic, Inc., a biotechnology firm based in Watertown, Massachusetts, announced promising topline Phase 1a data for its leading asset, TX45, intended for Group 2 Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction (PH-HFpEF). This announcement comes ahead of the detailed results set to be presented at the American Heart Association (AHA) Scientific Sessions in November 2024.

TX45, a long-acting relaxin, was well-tolerated with no observed immunogenicity and demonstrated a favorable pharmacokinetic (PK) and pharmacodynamic (PD) relationship, which has informed the dosing strategies for upcoming clinical trials. Specifically, the Phase 1a trial, which evaluated single ascending doses in healthy volunteers, showed minimal adverse events and no evidence of immune-mediated clearance. The trial explored doses of 0.3, 1, and 3 mg/kg administered intravenously, as well as 150, 300, and 600 mg doses given subcutaneously. The resulting PK/PD data were used to identify effective doses for the next phase of clinical testing.

The Phase 1b clinical trial in patients with PH-HFpEF has escalated to the highest dose of TX45 based on favorable tolerability. The results of this trial are anticipated in the second quarter of 2025. Tectonic's President and CEO, Alise Reicin, M.D., emphasized that the Phase 1a findings validate earlier preclinical data and are instrumental in advancing to a global Phase 2 randomized trial. This upcoming trial will evaluate the effect of TX45 over six months in PH-HFpEF patients, particularly those with combined pre- and post-capillary pulmonary hypertension.

The preclinical model for TX45 showed that the exposures associated with maximal activity also led to significant increases in renal plasma flow. The alignment between the preclinical and Phase 1a clinical data allowed Tectonic to select dose regimens for the Phase 2 trial confidently. In this trial, patients will be randomized to receive either 300 mg subcutaneously once monthly, 300 mg subcutaneously every other week, or a placebo.

Group 2 PH-HFpEF, a condition arising from left-sided heart disease, affects a substantial number of patients, with estimates suggesting over 600,000 individuals in the U.S. alone. Currently, there are no approved treatments specifically for this condition, highlighting the significant unmet medical need that TX45 aims to address.

In addition to the ongoing trials, Tectonic recently received clearance from the U.S. Food and Drug Administration for its Investigational New Drug application for TX45. Screening for the Phase 2 APEX clinical trial has already begun, with topline results expected in 2026.

TX45 is an Fc-relaxin fusion protein designed to activate the RXFP1 receptor. Relaxin, a naturally occurring hormone, is upregulated during pregnancy to facilitate various physiological adaptations, including vasodilation and increased cardiac output. TX45 leverages these properties to potentially provide therapeutic benefits for PH-HFpEF patients.

Tectonic Therapeutic focuses on developing biologic medicines that modulate G-protein coupled receptors (GPCRs) using its proprietary GEODe™ technology platform. The company targets areas of significant unmet medical need where effective treatments are lacking, aiming to improve patient quality of life through innovative therapies.