Tectonic Therapeutic completes APEX Phase 2 enrolment for TX45

Tectonic Therapeutic has completed enrolment in APEX, its Phase 2 clinical trial evaluating TX45 in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF). The NASDAQ-listed company said 191 patients were enrolled across 14 countries, with topline data expected in early Q1 2027.

The trial was designed to enrich for a more severe disease subtype: combined pre- and post-capillary pulmonary hypertension (CpcPH), defined by a pulmonary vascular resistance (PVR) greater than 3 Wood Units at baseline. Of the 191 participants, 137 — approximately 72% — met that criterion, in line with the company's stated enrolment target of around 70%. Mean baseline PVR in the CpcPH subgroup was 5.2 WU, compared with 4.2 WU across the overall population. Tectonic noted that these baseline figures are preliminary and subject to revision.

Trial design and mechanism

APEX is a randomised, double-blind, placebo-controlled proof-of-concept study assessing two subcutaneous dosing regimens of TX45: 300 mg once monthly and 300 mg every other week. Change from baseline in PVR in the enriched CpcPH population is the primary endpoint. The trial runs over 24 weeks.

TX45 is an Fc-relaxin fusion protein engineered to activate RXFP1, the G-protein coupled receptor target of the endogenous hormone relaxin. Relaxin acts as a pulmonary and systemic vasodilator and also carries anti-fibrotic and anti-inflammatory properties. Tectonic's rationale is that the heart-failure-driven pressure load on the pulmonary vasculature seen in PH-HFpEF represents a plausible target for those combined pharmacological effects.

Chief executive Alise Reicin said the pace of enrolment "underscores the significant unmet medical need in PH-HFpEF, especially in patients with CpcPH."

Market context and competitive landscape

PH-HFpEF falls within WHO Group 2 pulmonary hypertension — a classification historically overlooked by the pharmaceutical industry relative to Group 1 pulmonary arterial hypertension (PAH), which carries several approved therapies. To date, no drug has received regulatory approval specifically for Group 2 PH, and multiple trials of established PAH agents in Group 2 patients have either failed or produced inconclusive results, including large trials of phosphodiesterase-5 inhibitors. That track record sets a demanding bar for TX45.

Tectonic estimates that CpcPH accounts for between one-third and one-half of the approximately 1.4 million PH-HFpEF patients in the United States alone, pointing to a commercially significant opportunity if the mechanism proves out. Several other companies are exploring RXFP1 biology or relaxin-pathway agents for cardiovascular and fibrotic indications, and a positive APEX readout would likely draw attention from larger pharmaceutical groups seeking late-stage cardiovascular assets.

From a regulatory standpoint, the FDA has not established a formal precedent for approval pathways in Group 2 PH, meaning Tectonic will need to engage closely with the agency on endpoint acceptability and the evidentiary standard for the PVR primary endpoint — a haemodynamic measure that regulators have historically viewed as a surrogate rather than a clinical outcome. How the company resolves that discussion after the Q1 2027 readout will be a critical determinant of the development path to any potential NDA filing.