AliveGen USA Inc. (AliveGen), a clinical-stage biopharmaceutical company focused on developing novel therapies for serious cardiopulmonary diseases, today announced compelling new preclinical results for its investigational therapy ALG-801. The data show that ALG-801 delivered superior efficacy compared with current standard-of-care therapies in a well-established animal model of pulmonary arterial hypertension (PAH).
The results were presented at the European Respiratory Society (ERS) Congress, held September 27–October 1, 2025, in Amsterdam.
Addressing the Challenges of Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a progressive, life-threatening disorder characterized by abnormal narrowing and remodeling of pulmonary blood vessels. This process increases pulmonary vascular resistance and pulmonary arterial pressure, placing a growing strain on the right side of the heart. Over time, the added stress leads to right heart failure and ultimately premature death.
Although multiple therapies have been approved in recent years—including endothelin receptor antagonists, PDE5 inhibitors, prostacyclin analogs, and most recently, the activin receptor fusion protein Sotatercept (ActRIIA-Fc)—outcomes remain poor. Current treatments often slow disease progression but rarely reverse vascular damage or restore normal heart function.
Median transplant-free survival for patients with PAH remains only about six years, underscoring the urgent need for new, more effective treatment strategies.
Study Design and Comparative Approach
To evaluate the potential of ALG-801, researchers used the sugen-hypoxia (SuHx) rat model, a gold-standard preclinical system that closely mimics the pathophysiology of PAH in humans. This model is considered particularly rigorous, as it reproduces key features of the disease, including pulmonary vascular remodeling, elevated pressures, and right ventricular hypertrophy.
In the study, ALG-801 was directly compared with two widely recognized PAH therapies:
- Sildenafil (a phosphodiesterase type 5 inhibitor, long established as part of standard of care).
- ActRIIA-Fc (Sotatercept), recently approved and hailed as a breakthrough therapy for PAH.
This head-to-head comparison provided an opportunity to determine whether ALG-801 could meaningfully outperform current treatment options.
Data Highlights
The preclinical study yielded several key findings:
- Prevention of disease progression: During the early phase of disease development, ALG-801 prevented pulmonary hypertension more effectively than Sildenafil. It significantly reduced right ventricular hypertrophy (an enlargement of the heart muscle caused by high pressure) and inhibited pulmonary vascular remodeling—structural changes in the blood vessels that drive worsening of the condition.
- Reversal of established PAH: In animals with already established pulmonary hypertension, ALG-801 was significantly more effective than ActRIIA-Fc (Sotatercept). Treatment with ALG-801 reversed elevated pulmonary arterial pressures, reduced right ventricular hypertrophy, and normalized structural changes in the pulmonary vasculature.
- Biomarker normalization: ALG-801 also normalized circulating BNP (B-type natriuretic peptide) levels, a biomarker commonly used to measure heart strain in both clinical and preclinical settings.
- Improved survival: Most importantly, ALG-801 treatment extended overall survival in the SuHx model, suggesting its potential to deliver meaningful clinical benefits beyond symptom management.
AliveGen Leadership Perspective
“These results demonstrate ALG-801’s ability to outperform currently approved PAH therapies in rigorous preclinical testing,” said Dr. HQ Han, CEO of AliveGen. “We are encouraged by the strength of the data, which suggest ALG-801 could transform treatment outcomes for patients living with PAH. Despite major therapeutic advances, survival for PAH patients remains unacceptably poor. ALG-801’s performance in both prevention and treatment settings highlights its unique potential as a next-generation therapy.”
Dr. Han emphasized that the company is actively working to advance ALG-801 into the clinic, with the goal of addressing the urgent unmet medical need in PAH and related cardiopulmonary conditions.
A Promising Path Forward
The findings from this preclinical program position ALG-801 as a strong candidate for clinical development. By demonstrating both preventive and therapeutic efficacy—as well as superiority over established treatments—the therapy may represent a new paradigm in how PAH is managed.
If similar results are observed in human trials, ALG-801 could potentially change the standard of care, providing patients not only with improved symptom control but also with the possibility of disease modification and longer survival.
AliveGen believes the therapy may also have relevance for other conditions marked by pulmonary vascular remodeling and right heart strain, expanding its potential beyond PAH alone.
About Pulmonary Arterial Hypertension
PAH is a rare but severe disease that affects tens of thousands of patients worldwide. It disproportionately impacts women and often strikes in the prime of life, between ages 30 and 60. Symptoms—including shortness of breath, fatigue, chest pain, and fainting—are often nonspecific, leading to delayed diagnosis.
Even with multiple therapeutic classes available, the disease is progressive and incurable. Lung transplantation remains the only definitive option for patients who fail current therapies, but donor shortages and surgical risks limit this solution to a minority of patients.
This context highlights the critical importance of innovation and the urgent need for therapies that can deliver better outcomes.
About ALG-801
ALG-801 is a next-generation ActRIIA/IIB hybrid ligand trap designed to selectively block Smad2/3 pathway-activating ligands implicated in the pathogenesis of PAH and other diseases. ALG-801 has completed Phase 1a and 1b trials in healthy volunteers and is ready to advance into Phase 2 clinical studies. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to ALG-801 for the treatment of PAH.
About AliveGen
AliveGen is a privately held, clinical-stage biotechnology company based in Thousand Oaks, California. The company is dedicated to developing first-in-class and best-in-class biotherapeutics for diseases with high unmet medical needs, including cardiometabolic disorders, obesity, neuromuscular diseases, age-related osteosarcopenia, and various wasting disorders. AliveGen’s mission is to improve care and quality of life for patients through innovative therapies that are both safe and highly effective. For more information, visit www.alivegen.com.
