HS135 / 35Pharma - LARVOL DELTA

HS135, a Novel Investigational Activin Inhibitor for the Treatment of Pulmonary Hypertension (PH): Results From a Healthy Volunteer Phase 1 Trial Demonstrated Favourable Safety Profile and Pharmacodynamic Responses, Including Improved Body Composition and Cardiac Biomarkers (ATS 2025) - No abstract available

Biomarker • Clinical • Late-breaking abstract • P1 data • PK/PD data • Cardiovascular • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of HS135 for the Treatment of Pulmonary Arterial Hypertension in Adults (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: 35Pharma Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Study of HS135 in Obese Patients With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: 35Pharma Inc | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2024 ➔ Jan 2025

Enrollment open • Trial initiation date • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of HS135 for the Treatment of Pulmonary Arterial Hypertension in Adults (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: 35Pharma Inc | Phase classification: P1/2 ➔ P1

Phase classification • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of HS135 for the Treatment of Pulmonary Arterial Hypertension in Adults (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: 35Pharma Inc | Not yet recruiting ➔ Recruiting | Phase classification: P1 ➔ P1/2 | Trial completion date: Apr 2027 ➔ Jul 2027 | Initiation date: Jul 2024 ➔ Oct 2024 | Trial primary completion date: Feb 2026 ➔ Dec 2026

Enrollment open • Phase classification • Trial completion date • Trial initiation date • Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Phase Ib Study Of Hs135, A Novel Activin And Gdf Inhibitor, In Patients With Obesity-related Heart Failure With Preserved Ejection Fraction And Pulmonary Hypertension Leveraging Remote Pulmonary Artery Pressure Monitoring Technology (HFSA 2024) - "This is a Phase 1b trial in progress to assess the preliminary safety and efficacy of the novel Activin and GDF inhibitor HS135 in obese patients with PH-HFpEF. Ambulatory PA pressure measurements in addition to patient-reported outcomes, measures of exercise function, biomarker and body composition endpoints are expected to provide valuable data to evaluate safety, identify efficacy signals and inform further development."

Clinical • P1 data • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Phase Ib Study Of Hs135, A Novel Activin And Gdf Inhibitor, In Patients With Obesity-related Heart Failure With Preserved Ejection Fraction And Pulmonary Hypertension Leveraging Remote Pulmonary Artery Pressure Monitoring Technology (HFSA 2024) - "This is a Phase 1b trial in progress to assess the preliminary safety and efficacy of the novel Activin and GDF inhibitor HS135 in obese patients with PH-HFpEF. Ambulatory PA pressure measurements in addition to patient-reported outcomes, measures of exercise function, biomarker and body composition endpoints are expected to provide valuable data to evaluate safety, identify efficacy signals and inform further development."

Clinical • P1 data • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Study of HS135 in Obese Patients with Pulmonary Hypertension and Heart Failure with Preserved Ejection Fraction (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: 35Pharma Inc

New P1 trial • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Study of HS135 for the Treatment of Pulmonary Arterial Hypertension in Adults (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: 35Pharma Inc

New P1 trial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

HS135, A Novel Activin and GDF Trap, Is Highly Efficacious in Models of Group 1 and Group 2 Pulmonary Hypertension (PH) (ATS 2024) - "The use of the unmodified Activin receptor IIA ectodomain fused to Fc (ActRIIA-Fc, sotatercept) as a decoy trap to neutralize Activins and GDFs has recently been clinically validated as a promising new therapeutic modality in Group 1 PH. The best-in-class target engagement profile of HS135 translates into superior and differentiated heart and lung efficacy in relevant Group 1 and 2 PH preclinical models, normalizing both RV and LV gene expression. These data support HS135's further developmentas a novel agent in PH."

Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ACVR2A

HS135, A NOVEL ACTIVIN AND GDF TRAP, IS HIGHLY EFFICACIOUS IN PRECLINICAL MODELS OF PULMONARY HYPERTENSION AND OBESITY-ASSOCIATED HEART FAILURE WITH PRESERVED EJECTION FRACTION (ACC 2024) - "The use of the unmodified activin receptor II A ectodomain fused to Fc (ActRIIA-Fc, sotatercept) as a decoy trap to neutralize activins and GDFs has recently been clinically validated as a promising new therapeutic modality in PH. HS135 best-in-class target engagement profile uniquely improves PH, HF, and metabolism across in vivo models, which supports the development of HS135 as a novel agent in cardiopulmonary and cardiometabolic disease."

Preclinical • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Hypertension • Inflammation • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ACVR2A

HS135, A Best-in-class Activin And GDF Ligand Trap, Is Efficacious In Experimental Left Heart Failure (HFSA 2023) - "Obesity-associated HFpEF was established by feeding mice HFD in combination with L-NAME supplied in drinking water ad libitum for 5 weeks before initiating twice weekly treatment with HS135 (5 and 25 mg/kg), empagliflozin (10 mg/kg daily), or both (25 mg/kg twice weekly and 10 mg/kg daily, respectively) for three weeks. HS135’s best-in-class ligand neutralization profile uniquely improves HF and metabolism in preclinical models of experimental heart failure. Collectively, these data support the development of HS135 as a novel agent in cardiometabolic disease, including obesity-associated HF."

Cardiovascular • Congestive Heart Failure • Fibrosis • Genetic Disorders • Heart Failure • Immunology • Metabolic Disorders • Obesity

HS135, A Novel Activin and GDF Trap, is Highly Efficacious in Models of Group 1 and Group 2 Pulmonary Hypertension (PH) (ERS 2023) - "Sotatercept (ActRIIA-Fc), which targets activins and GDFs, has recently reported Phase 3 success in Group 1 PH. The best-in-class target engagement profile of HS135 translates into superior and differentiated heart and lung efficacy in Group 1 and 2 PH models, which warrants further exploration in clinical trials.; Cell and molecular biology; Physiology"

Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ACVR2A

HS135, a novel activin and GDF trap, is highly efficacious in preclinical models of pulmonary hypertension and obesity-associated heart failure with preserved ejection fraction (ESC 2023) - "Despite initial clinical success in PH, current inhibitors of Activin mediated signalling (eg, sotatercept, an ActRIIA receptor ectodomain Fc-fusion protein) cannot be dosed to full biological activity...HFpEF was established by feeding mice HFD in combination with L-NAME supplied in drinking water ad libitum for 5 weeks before commencing twice weekly treatment with HS135 or empagliflozin for three weeks... HS135 best-in-class target engagement profile uniquely improves PH, HF, and metabolism across in vivo models. Collectively, these data support the development of HS135 as a novel agent in cardiopulmonary and cardiometabolic disease, including PH and obesity-associated HF."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • ACVR2A

In vivo Efficacy of HS135, a Novel Activin and GDF Trap for the Treatment of Pulmonary Hypertension (PH) and Metabolic Syndrome (MetS) (AHA 2022) - "Contrary to other ActR-based therapies, HS135 did not lead to increases in hematocrit which would limit its dosing. HS135 was efficacious at treating PH while simultaneously improving body composition in preclinical models. Clinical trials with HS135 are expected to commence within 2023."

Preclinical • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Hematological Disorders • Hypertension • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

HS135, a Novel Activin and GDF Trap with Dual Cardiopulmonary and Metabolic Mode of Action, is Efficacious in an Obesogenic Model of Heart Failure (ENDO 2023) - "HS135 was also explored in combination with empagliflozin, a recently approved SGLT2 inhibitor in HFpEF which, though effective at reducing HF-related hospitalization, has minimal effect on body composition in patients. The ability of HS135 to improve heart function was assessed using a validated HFpEF rodent model. Potent and selective inhibition of activins and GDFs represents a novel treatment strategy in HFpEF targeting both cardiac effects as well as improvement in body composition in this largely obese patient population. Collectively, these data support the development of HS135 as a novel agent in cardiometabolic and cardiopulmonary diseases, including heart failure.*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Cardiovascular • Congestive Heart Failure • Heart Failure • Obesity • Respiratory Diseases • ACVR2A

HS135, a Novel Activin and GDF Trap, Is Efficacious in Models of Pulmonary Hypertension (PH) and Heart Failure (HF) (ATS 2023) - "In NHPs, HS135 did not lead to increases in hematocrit which have been dose-limiting for other ActRII-based traps such as ActRIIA-Fc (sotatercept). The best-in-class target engagement profile of HS135 translates into increased and differentiated efficacy improving the PH and HF phenotype in preclinical models. Collectively, these data support the development of HS135 as a novel agent in cardiometabolic and cardiopulmonary diseases including PAH and PH-associated with left heart disease."

Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ACVR2A

HS135, A NOVEL ACTIVIN AND GDF TRAP, IS EFFICACIOUS IN EXPERIMENTAL PULMONARY HYPERTENSION AND HEART FAILURE (ACC-WCC 2023) - "HS135 does not lead to increases in hematocrit and is thus expected to be amenable to dosing to full biological activity. HS135 is efficacious in disease models of cardiopulmonary disease. Further evaluation of HS135 in clinical trials is warranted."

Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Hypertension • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases