At the American Thoracic Society (ATS) conference 2024, 35Pharma  is unveiling a compelling oral presentation titled “6036 – HS135, A Novel Activin and GDF Trap, Is Highly Efficacious in Models of Group 1 and Group 2 Pulmonary Hypertension (PH)” on May 19 at San Diego Convention Center elucidating the preclinical data of HS135 as well as the presentation will feature data on HS135, the company’s Phase I novel Activin and GDF inhibitor, in models of Pulmonary Hypertension. The upcoming Phase I clinical development will be a single-center, double-blind, randomized, placebo-controlled clinical trial in healthy postmenopausal women. Key readouts of the study include safety, pharmacokinetics, and changes in biomarkers related to Activin and GDF biology following subcutaneous administration of HS135; dosing is expected to begin in H1 2024.

Pulmonary hypertension is a cardiopulmonary disorder that increases mean pulmonary artery pressure (mPAP) by 25 mmHg at rest, leading to right heart failure and, ultimately, death. Pulmonary hypertension is associated with dysregulated activin and growth differentiation factor (GDF) signaling. 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.

35Pharma is a clinical-stage biopharmaceutical company focused on discovering and developing best-in-class ligand traps for disorders associated with the TGF-beta superfamily. Their key focuses include pulmonary hypertension, heart failure, and obesity. Their centerpiece drug, HS135, is a new Activin/GDF trap in Phase I clinical development. 

• HS135 is an extremely potent activin receptor-based Activin/GDF trap that has been rationally engineered to have a wider therapeutic window than ActRIIA-Fc, best-in-class in vivo target engagement, and a distinct effectiveness profile. 
• HS135 is designed to avoid increases in hematocrit, which are dose-limiting for other traps in this class. 

As per Pulmonary Hypertension – Market Insight, Epidemiology, and Market Forecast – 2034, it is estimated that approximately 56 million individuals were diagnosed in the 7MM (including the United States, France, Germany, Italy, Spain, the United Kingdom, and Japan) in 2023. However, the trajectory of this widespread condition is poised to evolve in the coming years. By 2034, DelveInsight analysts predict a notable surge in Pulmonary hypertension cases within these regions, reflecting the urgent need for continued research, improved treatments, and enhanced public health initiatives to address this growing global health concern. 

Recently, 35Pharma presented pharmacodynamics data from preclinical studies in heart failure for its drug candidate HS135 at the Annual Congress of the European Society of Cardiology (ESC-2023),  held on Aug 25, 2023, Annual Meeting of the Endocrine Society (ENDO-2023) held on Aug 09 2023 where they had presented HS135’s study highlights, such as best-in-class potency profile translates into full in vivo target engagement in mice as measured by complete suppression of FSH, a biomarker of Activin and GDF inhibition. On Jan 03, 2024, 35Pharma received a “no objection letter” from Health Canada for its clinical trial application to initiate HS135-001, a Phase I study of HS135 in healthy volunteers.

In conclusion, during the ATS conference 2024, 35Pharma will highlight HS135, the company’s Phase I novel Activin and GDF inhibitor, as a potential Phase I therapeutic candidate based on preclinical evidence. HS135’s best-in-class target engagement profile leads to superior and differentiated heart and lung effectiveness in relevant Group 1 and 2 PH preclinical models, normalizing both RV and LV gene expression. These findings support HS135’s ongoing development as a new pulmonary hypertension agent.