35Pharma Cleared to Initiate Clinical Development of HS235, Novel Activin and GDF Inhibitor for Cardiometabolic Disease and Obesity.

35Pharma, a clinical-stage biopharmaceutical company that designs and develops TGF-beta superfamily therapeutics, today announced it received a No Objection Letter from Health Canada for its Clinical Trial Application to initiate HS235-001, a Phase 1 study of HS235 in overweight and obese healthy subjects.

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“HS235 selectively and potently neutralizes pathological Activins and GDFs and demonstrated profound activity in preclinical models of heart failure and obesity.” said Ilia Tikhomirov, 35Pharma’s CEO. “HS235 effects include restoration of heart function and exercise tolerance, accompanied by fat-selective weight loss and increased skeletal muscle mass. We anticipate sharing initial data from the Phase 1 trial in overweight and obese healthy subjects during the second half of 2025.”

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HS235-001 is a Phase 1, single-center, double-blind, randomized, placebo-controlled clinical trial to evaluate single and multiple ascending sub-cutaneous doses of HS235 in overweight and obese healthy subjects. Key readouts of the study include safety, pharmacokinetics and pharmacodynamic effects. Dosing is expected to begin in late 2024.

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Pre-clinically, HS235 demonstrated the potential to treat a broad spectrum of cardiometabolic diseases, both as a monotherapy and in combination with glucagon-like peptide-1 receptor agonists (GLP-1 RAs):

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• In an obesity Heart Failure with Preserved Ejection Fraction (HFpEF) model, HS235 demonstrated both improved body composition and rescued left ventricular function. Specifically, HS235 monotherapy led to:
  - Increased skeletal muscle mass
  - Reduced fat mass
  - Rescue of left ventricular pressure
  - Restoration of exercise tolerance
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• In diet induced obesity (DiO) models, the addition of HS235 to GLP-1 RAs led to quantitatively and qualitatively superior responses. Specifically, the HS235 and GLP-1 RA combination demonstrated:
  - Up to 50% more fat loss than GLP-1 RA alone
  - Entirely preserved or increased skeletal muscle mass
  - All of the weight loss in the study occurred as a result of fat mass loss
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Taken together, these pre-clinical results support the potential of HS235 both as a monotherapy in obese HF, and in combination with a GLP-1 RA as a fat-selective treatment of obesity, a disease of excess adipose tissue.