Trial enrollment begins to test long-acting relaxin formula in PH-HFpEF

TX45 is an investigational treatment by Tectonic Therapeutics

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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A man sits at a computer monitor to enroll in a clinical trial.

Enrollment has begun in a Phase 1b study of Tectonic Therapeutic’s TX45, an investigational treatment for people with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).

TX45 is a long-acting formulation of relaxin, a protein involved in reproduction and cardiovascular function. It has anti-fibrotic, or anti-scarring, and anti-inflammatory properties and can relax or widen blood vessels.

“It has long been hypothesized that the unique biology of relaxin may offer substantial therapeutic potential in the treatment of cardiovascular disease,” Alise Reicin, MD, president and CEO at Tectonic, said in a company press release.

Early data from an ongoing Phase 1a study supports TX45’s sustained mechanism of action, according to Tectonic. Topline results are expected by June and a randomized Phase 2 study is planned to begin this year, while data from the Phase 1b study are anticipated in 2025.

Cofounded by Andrew C. Kruse, PhD, and Tim A. Springer, PhD of Harvard Medical School, Tectonic is focused on the World Health Organization group 2 subtype of pulmonary hypertension, which is associated with left-sided heart disease.

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Relaxing, widening blood vessels

People with PH-HFpEF pump a normal or near normal amount of blood with each heartbeat, called the ejection fraction. Because the heart muscle is too stiff to relax after a heartbeat, its left side fails to keep up with the demands of the body, leading to high blood pressure in the pulmonary arteries.

Over time, elevated pulmonary pressure worsens exercise capacity and leads to shortness of breath and right-sided heart failure. Although medications used in other types of pulmonary hypertension have been assessed, none have been consistently effective and none have been approved for PH-HFpEF.

Known as a “pregnancy hormone,” relaxin is increased during pregnancy to help the mother’s cardiovascular system meet the extra demand from the developing fetus. Relaxin is also secreted by the heart and functions as a vasodilator to widen blood vessels.

These properties suggest it may be effective for diseases that affect the heart and lungs. However, the therapeutic potential of its naturally occurring form is limited by its short half-life, that is, the time needed for a therapy’s initial levels to drop by half.

Administered intravenously, or directly into the bloodstream, TX45 is a fusion of relaxin and the protein Fc, which prolongs the half-life of protein therapeutics.

In the Phase 1b study, all the PH-HFpEF patients will receive a single dose of TX45. Outcomes include its safety, tolerability, and impact on blood flow parameters, called hemodynamics.

“Our goal is to leverage relaxin’s vasodilatory, anti-fibrotic and anti-inflammatory properties to provide improved treatment outcomes for patients with Group 2 PH,” Reicin said. “This study will provide us with valuable TX45 pharmacology and hemodynamic data in patients.”

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