Tectonic Therapeutic (TECX) Status Update summary

Disease overview and unmet need

• Group 2 pulmonary hypertension (PH) is the most prevalent form, primarily triggered by left heart disease, especially HFpEF, affecting over 1.2 million US citizens and up to 52% of HFpEF patients.

• CpcPH, a severe Group 2 PH subtype, carries the highest mortality and risk of right heart failure due to permanent vascular changes.

• Elevated pulmonary vascular resistance (PVR) and pulmonary capillary wedge pressure (PCWP) are linked to worse outcomes, impacting survival, quality of life, and exercise capacity.

• Current therapies for HFpEF do not address pulmonary vascular remodeling, and there are no approved therapies specifically for PH-HFpEF.

• New treatments are needed to lower wedge pressure and induce vascular remodeling to improve outcomes.

Mechanism and rationale for TX45

• TX45 is a long-acting relaxin-2-Fc fusion protein for subcutaneous dosing, with a 2–3 week half-life, designed to address both cardiac and vascular dysfunction in PH-HFpEF.

• Relaxin, the natural ligand for RXFP1, has vasodilatory, anti-fibrotic, anti-inflammatory, and organ-protective effects, demonstrated in pregnancy and acute heart failure studies.

• TX45 targets RXFP1, offering sustained activation without desensitization, and is expected to improve diastolic function, reduce fibrosis, enhance renal function, and decrease vascular resistance.

• Clinical data with serelaxin, a related agent, showed reductions in wedge pressure, pulmonary artery pressure, vascular resistance, and improved renal function and mortality in acute heart failure.

• TX45's pleiotropic effects may increase the odds of success in PH-HFpEF and could be explored in other indications such as HFrEF and chronic kidney disease.

Clinical development and trial design

• Phase 1a trial in healthy volunteers showed TX45 was well-tolerated, with no serious adverse events and a 33% increase in renal plasma flow.

• Phase 1b open-label trial in PH-HFpEF patients is assessing safety and acute hemodynamic effects, with endpoints including wedge pressure (PCWP) and PVR; data expected late Q1 or early Q2 2025.

• Phase 2 APEX study is a 24-week, double-blind trial randomizing patients to TX45 or placebo, with primary endpoint change in PVR and secondary endpoints including PCWP, 6-minute walk distance, and quality of life; data expected in 2026.

• Reductions in PCWP and PVR are expected to correlate with improved exercise capacity and outcomes, as shown in prior studies.

• A 15–20% reduction in wedge pressure and PVR is considered a meaningful target for efficacy.