Core Insights - Tectonic Therapeutic, Inc. announced favorable Phase 1a results for TX000045 (TX45), a long-acting Fc-relaxin fusion protein, supporting its further development for Group 2 Pulmonary Hypertension in HFpEF [1][2] - The Phase 1a trial demonstrated a favorable safety profile with no severe adverse events or immunogenicity observed [1][3] - Upcoming topline results from the ongoing clinical program include Phase 1b hemodynamic trial data expected in late Q1 or early Q2 2025, and APEX Phase 2 clinical trial data anticipated in 2026 [1][2] Phase 1a Clinical Trial Results - The Phase 1a trial assessed safety and tolerability in 55 healthy volunteers, showing TX45 was well tolerated with no drug-related severe adverse events [2][3] - The most common adverse event was transient orthostatic tachycardia, not linked to blood pressure drops [3] - No clinically meaningful changes in laboratory values, ECG intervals, or blood pressure were observed [3] Pharmacokinetic and Pharmacodynamic Findings - TX45 exhibited approximately 50% subcutaneous bioavailability and a half-life of 14-20 days [4] - Administration of TX45 resulted in increased renal plasma flow (RPF) across all doses, leading to the development of a robust exposure-response model for Phase 2 dose selection [5][6] - The exposure-response model indicated a maximum effect (Emax) of 33% on RPF, with mean dose cohort effects showing increases of up to 42% [6] APEX Phase 2 Clinical Trial Overview - The APEX Phase 2 trial aims to evaluate TX45's efficacy in a broad population of patients with Group 2 PH-HFpEF, enrolling up to 180 subjects [7] - The trial will assess changes in pulmonary vascular resistance (PVR) and six-minute walk distance as primary and secondary endpoints [7] - TX45 is expected to address physiological abnormalities in PH-HFpEF, potentially improving exercise capacity [7] About TX45 and Its Mechanism - TX45 is designed to activate the RXFP1 receptor, a target of the hormone relaxin, which has vasodilative, anti-fibrotic, and anti-inflammatory properties [8] - Relaxin is naturally expressed at low levels and is upregulated during pregnancy, facilitating increased cardiac output and reduced vascular resistance [8] Context of Group 2 Pulmonary Hypertension - Group 2 PH-HFpEF is characterized by increased pulmonary artery pressure due to left-sided heart disease, leading to severe strain on the right heart and worsening exercise capacity [9] - Currently, no medications have been approved specifically for the treatment of Group 2 PH, highlighting a significant unmet medical need [9] Company Overview - Tectonic Therapeutic focuses on developing therapeutic proteins and antibodies targeting G-protein coupled receptors (GPCRs) [10] - The company leverages its proprietary GEODe™ platform to address significant unmet medical needs in areas with limited therapeutic options [10]
Tectonic Therapeutic Announces Positive Phase 1a Results in AHA 2024 Presentation for TX45, a Long-acting, Fc-Relaxin Fusion Protein