About TX45, a long-acting Fc-relaxin fusion protein
Tectonic’s lead program, TX000045 (TX45), is an Fc-relaxin fusion protein with optimized pharmacokinetics and biophysical properties that activates the RXFP1 receptor, the GPCR target of the hormone relaxin. Relaxin is an endogenous protein, expressed at low levels in both men and women. In normal human physiology, relaxin is upregulated during pregnancy where it exerts vasodilative effects, reduces systemic and pulmonary vascular resistance and increases cardiac output to accommodate the increased demand for oxygen and nutrients from the developing fetus. Relaxin also exerts anti-fibrotic effects on pelvic ligaments to facilitate delivery of the baby.
TX45’s pharmacological profile, with an extended half-life compared with native relaxin, is a direct result of applying Tectonic’s protein engineering capabilities. It has the potential to address patients with Group 2 PH-HFpEF as the initial disease setting. Treatment with TX45 could potentially improve hemodynamics through effects on pulmonary and systemic vasodilation, cardiac diastolic dysfunction and potential remodeling in both the pulmonary vessels and the heart, which could translate into a clinically meaningful improvement in exercise capacity in these patients.
The Phase 1a clinical trial of TX45 in healthy volunteers was designed as a single ascending dose trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (including renal blood flow) of TX45 administered intravenously (IV) (four doses ranging from 0.3 mg/kg to 10 mg/kg) and SC (three doses, 150 mg, 300 mg and 600 mg). Topline results are expected to be reported from this trial this September, followed by more detailed data at a later scientific meeting.
The Phase 1b clinical trial of TX45 in patients with Group 2 PH-HFpEF is a single dose, open-label trial to evaluate safety, tolerability and acute hemodynamic effects of IV administration of TX45, with study results expected in mid-2025. The trial will evaluate the change from baseline in PVR as determined by right heart catheterization, as well as improvement in mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWP), cardiac output, and systemic vascular resistance (SVR).
About Group 2 Pulmonary Hypertension in HFpEF
The World Health Organization has defined 5 groups of PH. Tectonic is focused on the Group 2 subtype, a condition that develops as a consequence of left-sided heart disease, specifically pulmonary hypertension secondary to left heart failure with preserved ejection fraction (PH-HFpEF). There are an estimated 6 million patients with heart failure in the United States, with HFpEF representing up to ~50% of heart failure cases. Tectonic estimates the combined Group 2 PH population with HFpEF at over 600,000.
In patients with PH-HFpEF, chronic heart failure leads to increased blood pressure in the pulmonary arteries, exerting severe strain on the right side of the heart, which adapts poorly to the increased pressure. This increased pulmonary pressure gradually causes worsening exercise capacity, shortness of breath and right-sided heart failure which can lead to death. Although several Group 1 PH (Pulmonary Arterial Hypertension, PAH) medications have been explored in Group 2 PH, to date, no medications have been approved for its treatment.
