Tectonic Therapeutic Secures US IND Clearance for TX45 Lead Program

Tectonic Therapeutic, Inc. (NASDAQ: TECX), an innovative clinical-stage biotechnology firm, has announced that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for TX45. TX45 is an Fc-relaxin fusion protein targeted at treating patients with Group 2 Pulmonary Hypertension due to Heart Failure with Preserved Ejection Fraction (PH-HFpEF), a condition that affects over 600,000 individuals in the United States alone and currently lacks approved treatment options.

TX45 aims to address the underlying physiological issues of PH-HFpEF by promoting pulmonary and systemic vasodilation, improving cardiac diastolic function, and potentially remodeling both the pulmonary vessels and cardiac muscle. This could lead to significant improvements in exercise capacity for affected patients.

Alise Reicin, M.D., President and CEO of Tectonic, expressed optimism about TX45, noting that the Fc-relaxin fusion protein was engineered to optimize its pharmacological profile. Reicin highlighted the promising safety, pharmacokinetic, and pharmacodynamic data that support the launch of their Phase 2 clinical trial in the target patient population. The company is set to release topline results from their ongoing Phase 1a clinical trial involving healthy volunteers this September and expects results from the Phase 1b patient trial by mid-2025.

The Phase 2 clinical trial for TX45 is slated to begin globally in the third quarter of 2024, with topline results anticipated in 2026. This trial is designed to assess the efficacy of TX45 in a broad PH-HFpEF population and will also focus on a subset of Group 2 PH patients with a more severe form of the disease, known as combined post- and pre-capillary pulmonary hypertension (CpcPH), characterized by a baseline pulmonary vascular resistance (PVR) greater than 3 Wood units. Up to 180 subjects will be enrolled and randomized into two different dose regimens of TX45 or placebo. The treatment will be administered subcutaneously over a 24-week period, followed by an additional 8-week follow-up. Primary and secondary endpoints will include changes in PVR and other relevant hemodynamic parameters, with an exploration of the six-minute walk distance as well.

TX45 is an Fc-relaxin fusion protein with enhanced pharmacokinetics and biophysical properties designed to activate the RXFP1 receptor, the GPCR target of the hormone relaxin. In human physiology, relaxin is typically upregulated during pregnancy, where it plays roles in vasodilation, reducing vascular resistance, and increasing cardiac output. Additionally, relaxin has anti-fibrotic effects, which could be beneficial in the context of PH-HFpEF.

The Phase 1a clinical trial involved healthy volunteers and evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of TX45 administered both intravenously and subcutaneously. Results from this trial are expected to be reported in September, with detailed findings to be presented at a later scientific meeting.

A Phase 1b trial is also ongoing, focusing on patients with Group 2 PH-HFpEF. This open-label trial aims to assess the safety, tolerability, and acute hemodynamic effects of intravenous TX45. Results are expected by mid-2025, with key measures including changes in PVR, mean pulmonary artery pressure (mPAP), pulmonary capillary wedge pressure (PCWP), cardiac output, and systemic vascular resistance (SVR).

The World Health Organization categorizes Pulmonary Hypertension into five groups, with Tectonic's focus on Group 2, which stems from left-sided heart disease including PH-HFpEF. This condition results in elevated pulmonary artery pressure, leading to severe complications like right-sided heart failure and reduced exercise capacity. Despite the exploration of several medications initially developed for Group 1 PH, no treatments have been approved for Group 2 PH, highlighting a significant unmet medical need.

Tectonic Therapeutic is committed to leveraging its proprietary GEODe™ platform to develop therapeutic proteins and antibodies that modulate GPCR activity. The company targets diseases with significant unmet medical needs, aiming to improve patient quality of life through innovative biologic medicines. Tectonic is based in Watertown, Massachusetts.

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