Tectonic Therapeutic Initiates Phase 1B Study for TX45 in Group 2 Pulmonary Hypertension in Patients with Preserved Ejection Fraction Heart Failure

Rhea-AI Summary

Tectonic Therapeutic, Inc. initiates enrollment in Phase 1B study for TX45, a potential therapy for Group 2 Pulmonary Hypertension with HFpEF. The study aims to evaluate safety, hemodynamic effects, and potential as a best-in-class therapy. TX45's promising Phase 1A data suggests significant therapeutic potential.

Insights

Medical Research Analyst

The advancement of Tectonic Therapeutic's TX45 into Phase 1B trials is a significant step in addressing the unmet medical needs of patients with Group 2 Pulmonary Hypertension (PH) secondary to Heart Failure with preserved Ejection Fraction (HFpEF). The focus on the drug's safety and hemodynamic effects is pivotal, considering the high morbidity and mortality rates associated with this condition, which affects a substantial patient population in the US. The therapeutic potential of relaxin, with its vasodilatory, anti-fibrotic and anti-inflammatory properties, is being harnessed in TX45, potentially offering a novel treatment pathway.

The biotechnology sector often grapples with the challenge of translating promising molecular biology into effective and durable treatments. TX45's development is addressing this by potentially offering a longer half-life and more sustained therapeutic effect than native relaxin proteins. The implications for stakeholders, including patients, healthcare providers and investors, hinge on the successful demonstration of efficacy and safety in these early trials. Positive outcomes could lead to increased investment and valuation for Tectonic, while negative results could have the opposite effect.

However, it is essential to consider the inherent risks of drug development, particularly in the early phases. The long-term impact will depend on consistent progress through subsequent trial phases and ultimately regulatory approval. The market potential for TX45, should it prove effective, is significant given the current lack of approved treatments for Group 2 PH with HFpEF.

Financial Analyst

From a financial perspective, the progression of TX45 into Phase 1B trials represents a critical value inflection point for Tectonic Therapeutic. The biotech industry is driven by milestones and successful Phase 1 results often lead to increased funding opportunities, partnerships and in some cases, acquisition interest from larger pharmaceutical companies. The fact that Tectonic is a privately-held entity adds a layer of complexity to the analysis, as financial data and valuations are not publicly disclosed.

Investors in the biotech space are accustomed to the high-risk, high-reward nature of drug development. The potential market size for a successful treatment for Group 2 PH with HFpEF is substantial, given the 600,000 patients in the US alone. The anticipation of topline data from the Phase 1A and 1B studies, as well as the commencement of a Phase 2 study in H2 2024, will likely be closely monitored by venture capitalists and private equity investors interested in the cardiovascular therapy space.

It's also important to note that the biotech sector can be highly volatile, with stock prices often reflecting the perceived potential of pipeline drugs long before they generate revenue. For Tectonic, favorable data from ongoing studies could significantly enhance its valuation and attractiveness for future funding rounds or an initial public offering (IPO).

Cardiologist

As a cardiologist, the development of TX45 is a beacon of hope for patients with Group 2 PH with HFpEF, a condition that lacks approved therapies and is characterized by high hospitalization rates and diminished quality of life. The unique approach of using a relaxin-Fc fusion molecule could address the underlying pathophysiology of this condition, which includes vascular stiffness, fibrosis and inflammation.

Understanding the hemodynamic parameters via right heart catheterization and echocardiography in the Phase 1B study is important for assessing the clinical benefits of TX45. Safety and tolerability are of utmost importance, as the patient population is often fragile and has multiple comorbidities. The therapeutic benefits of vasodilation and anti-fibrotic effects could translate into improved cardiac output and reduced pulmonary pressures, potentially improving symptoms and survival rates.

The data from this study will not only inform the clinical trajectory of TX45 but also contribute to the broader understanding of Group 2 PH with HFpEF treatment. Success in this trial could revolutionize the standard of care and provide a framework for future research in the field of cardiopulmonary disease.

Study to evaluate TX45 impact on cardiopulmonary hemodynamics in patients with Group 2 Pulmonary Hypertension, a patient population in urgent need of novel therapies

TX45 clinical program advancing on track based on promising initial Phase 1A data; confirmatory Phase 1A data expected mid-2024 and topline Phase 1B data expected in 2025

WATERTOWN, Mass.--(BUSINESS WIRE)-- Tectonic Therapeutic, Inc. (“Tectonic”), a privately-held biotechnology company developing GPCR (G-protein coupled receptor)-targeted therapeutic proteins, co-founded by Timothy A. Springer and Andrew C. Kruse of Harvard Medical School, today announced the initiation of enrollment in the Phase 1B study for TX45, an investigational long-acting relaxin-Fc fusion molecule. The study will evaluate the safety and hemodynamic effects of single-dose TX45 in patients with Group 2 Pulmonary Hypertension secondary to Heart Failure with preserved Ejection Fraction (Group 2 PH with HFpEF).

Group 2 PH with HFpEF impacts over 600,000 patients in the US and is associated with significant morbidity and mortality. Importantly, there are no approved therapies for this condition. “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,” said Alise Reicin, MD, President and CEO at Tectonic. “It has long been hypothesized that the unique biology of relaxin may offer substantial therapeutic potential in the treatment of cardiovascular disease. This study will provide us with valuable TX45 pharmacology and hemodynamic data in patients.”

Demonstrating a durable treatment effect with the native relaxin protein can be challenging due to its intrinsic short half-life; however, initial data from Tectonic’s ongoing Phase 1A study suggests that TX45 has the potential to overcome previous challenges and to be a best-in-class therapy. Topline results from the Phase 1A study are expected to be reported in mid-2024, followed by results from the Phase 1B study in Group 2 PH with HFpEF patients in 2025. A randomized Phase 2 study is planned to begin in H2 2024.

Phase 1B study overview

The Phase 1B study with TX45 in patients with Group 2 PH with HFpEF is a single dose, open-label study to evaluate safety, tolerability and acute hemodynamic effects of intravenous administration of TX45. The study will evaluate the effect of TX45 on hemodynamic parameters, as determined by right heart catheterization and echocardiography.

About TX45, a long-acting Fc-relaxin fusion protein

Known as a “pregnancy hormone,” relaxin is upregulated during pregnancy to help the expectant mother’s cardiovascular system meet the increased demand from the developing fetus, and to remodel tissues and musculoskeletal structures involved in childbirth. Because of these features, it offers a similarly broad range of potential therapeutic applications with significant benefits expected in cardio-pulmonary diseases.

Tectonic’s TX45 Fc-relaxin fusion protein is a potential best-in-class agent, resulting from protein engineering efforts to overcome limitations associated with the natural human hormone and achieve both optimal in vitro (biophysical and developability), as well as in vivo (pharmacokinetic and pharmacodynamic, or “PK/PD”) properties. Tectonic is leveraging relaxin’s vasodilatory and anti-fibrotic properties with the goal of improving treatment outcomes for patients with Group 2 PH.

About Pulmonary Hypertension and HFpEF

The World Health Organization has defined 5 groups of pulmonary hypertension (PH). Tectonic is focused on the Group 2 subtype, a condition that develops as a consequence of left-sided heart disease, specifically pulmonary hypertension secondary to left heart failure with preserved ejection fraction (PH-HFpEF). There are an estimated 6 million patients with heart failure in the United States, with HFpEF representing up to ~50% of heart failure cases. Tectonic estimates the combined Group 2 PH population with HFpEF at over 600,000. In this condition, chronic heart failure leads to increased blood pressure in the pulmonary arteries, exerting severe strain on the right side of the heart, which adapts poorly to the increased pressure. This increased pulmonary pressure gradually causes worsening exercise capacity, shortness of breath and right-sided heart failure which can lead to death. Although several Group 1 PH (PAH) medications have been explored in Group 2 PH, no medications have yet demonstrated consistent efficacy, and to date, none have been approved for its treatment.

About Tectonic Therapeutic

Tectonic Therapeutic, co-founded by Andrew Kruse and Tim Springer of Harvard Medical School, is transforming the discovery of antibodies and other biologic drugs targeting GPCRs to develop novel therapies for patients inadequately served by current treatments. With its proprietary GEODe™ platform, Tectonic aims to unlock the therapeutic utility of some of the most difficult receptors in the class, where small molecule pharmacology may be intractable. In January 2024, Tectonic entered into a definitive agreement to merge with AVROBIO, Inc. (Nasdaq: AVRO). Tectonic is headquartered in Watertown, Massachusetts. Learn more at www.tectonictx.com and follow us @TectonicTx.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240325487405/en/

Tectonic Therapeutic:



Investors:

Dan Ferry

LifeSci Advisors

daniel@lifesciadvisors.com

(617) 430-7576



Media:

Karen Sharma

MacDougall

ksharma@macdougall.bio

(781) 235-3060

Source: Tectonic Therapeutic, Inc.

FAQ

What is the purpose of the Phase 1B study for TX45?

The Phase 1B study aims to evaluate the safety, hemodynamic effects, and potential as a best-in-class therapy of TX45 in patients with Group 2 Pulmonary Hypertension secondary to Heart Failure with preserved Ejection Fraction (Group 2 PH with HFpEF).

Who are the co-founders of Tectonic Therapeutic, Inc.?

Tectonic Therapeutic, Inc. was co-founded by Timothy A. Springer and Andrew C. Kruse of Harvard Medical School.

What are the expected timelines for the Phase 1A and Phase 1B study results?

Topline results from the Phase 1A study are expected in mid-2024, followed by results from the Phase 1B study in Group 2 PH with HFpEF patients in 2025.

What is the unique biology of relaxin that may offer therapeutic potential in cardiovascular disease?

Relaxin's vasodilatory, anti-fibrotic, and anti-inflammatory properties are hypothesized to provide substantial therapeutic potential in the treatment of cardiovascular disease.

How many patients in the US are impacted by Group 2 Pulmonary Hypertension with HFpEF?

Over 600,000 patients in the US are impacted by Group 2 Pulmonary Hypertension with HFpEF, which is associated with significant morbidity and mortality.