Tectonic planning trial to test TX45 impact on blood flow in PH-ILD
Therapy now showing positive results for PH patients with heart failure
Tectonic Therapeutic plans to launch a Phase 2 clinical trial to test the impact of its therapy candidate TX45 on blood flow, or hemodynamics, in people with pulmonary hypertension and interstitial lung disease (PH-ILD).
The move comes on the heels of positive results from part A of a Phase 1b clinical trial, which showed that TX45 improved left heart function and pulmonary hemodynamics in people with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).
Part B of that study has completed its enrollment of pulmonary hypertension patients in heart failure with reduced ejection fraction (PH-HFrEF). Topline results are expected by the end of the year, according to a new Tectonic press release outlining the company’s financials and recent business highlights.
“Our team is excited to announce PH-ILD as an additional indication for TX45 that we plan to explore in a Phase 2, proof of concept trial,” said Alise Reicin, MD, president and CEO of Tectonic. “Data from Part A of the Phase 1b trial in … 2 PH-HFpEF supports expanding into PH-ILD.”
Meanwhile, the ongoing global Phase 2 APEX trial (NCT06616974), which is evaluating TX45 in as many as 180 adults with PH-HFpEF, continues to enroll participants. Some sites in the U.S., Europe, Australia, and New Zealand are open, with other sites expected to open soon. Topline results are expected in 2026, per the company.
Pulmonary hypertension, called PH for short, is characterized by elevated pressure in the blood vessels, known as the pulmonary arteries, that carry blood from the heart to the lungs. PH puts strain on the right side of the heart, which can eventually lead to heart failure.
Interstitial lung diseases, or ILDs, are a group of disorders marked by inflammation and scarring, or fibrosis, in the lungs. Such scarring causes stiffness that makes it difficult to breathe, and also increases blood pressure in the lungs, resulting in PH.
People with both PH and ILD have worse survival than those with ILD without PH.
‘Limited’ treatment options now available for PH-ILD
“PH-ILD is a devastating disease with high mortality, significant unmet medical need and limited therapeutic alternatives,” Reicin said.
TX45 is a modified version of relaxin, a naturally occurring hormone with anti-inflammatory and antifibrotic properties that causes blood vessels to relax and widen — a process known as vasodilation. The therapy is modified with a protein called Fc-fusion, which allows it to last longer in the bloodstream. This should help lower blood pressure and reduce inflammation and scarring, thereby easing the symptoms of PH-ILD.
“We believe TX45’s mechanism is well suited to PH-ILD’s disease [processes] because of its pulmonary vasodilation, anti-inflammatory, remodeling and antifibrotic activity,” the company stated in its release.
With plans to launch in 2026, the Phase 2 study will enroll as many as 20 people with PH-ILD. All participants will receive 300 mg of TX45 every two weeks by subcutaneous, or under-the-skin, injection, over a total of 16 weeks, or about four months.
We believe TX45’s mechanism is well suited to PH-ILD’s disease [processes] because of its pulmonary vasodilation, anti-inflammatory, … and antifibrotic activity.
The study’s primary outcome will be a change in the pulmonary vascular resistance (PVR), a measure of the effort required by the heart to pump blood through the lungs.
TX45 now being tested in PH-HFpEF, PH-HFrEF patients
PH-HFpEF is a type of PH characterized by the heart muscle contracting normally, but the heart’s left ventricle not relaxing properly between heartbeats. For patients, the heart can’t fill up with enough blood.
In individuals with PH-HFrEF, the heart muscle doesn’t contract properly, and the left ventricle is too weak to pump blood effectively.
In both scenarios, left heart disease leads to increased pressure in the heart that backs up into the lungs, triggering PH. Both types are also referred to as Group 2 PH per the World Health Organization’s classification system.
Part A of the Phase 1b clinical trial tested TX45, given via infusion into the bloodstream, in 19 people with PH-HFpEF. TX45 treatment led to a 19% reduction in pulmonary capillary wedge pressure, or the pressure in the left side of the heart, and an 18.5% improvement in cardiac output, or the amount of blood the heart pumps out per minute, data showed.
There was also a greater than 30% reduction in PVR in participants with pre- and post-capillary pulmonary hypertension, or CpcPH. This is a more severe disease subtype marked by elevated pressure in both the pulmonary arteries and the pulmonary veins that carry blood from the lungs to the left side of the heart.
Part B of the study, meanwhile, has completed enrolling people with PH-HFrEF; dosing began in March. Topline results of this part are expected by the end of the year.
Now, enrollment continues in APEX, in which PH-HFrEF patients, enriched for CpcPH, will be randomly assigned to receive either the therapy or a placebo for about six months. TX45 will be given at a dose of 300 mg via subcutaneous injection every two weeks or once a month. Topline results are anticipated in 2026, Tectonic said.
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