InnovStone Therapeutics Limited, the small-molecule drug discovery subsidiary of HKEX-listed CSPC Pharmaceutical Group (HKEX: 1093), has initiated a first-in-human Phase I trial of SYH2072, an oral aldosterone synthase inhibitor, in healthy adult volunteers. The study marks CSPC's entry into a class that has attracted renewed clinical interest following positive late-stage data for other aldosterone synthase inhibitors in resistant hypertension and heart failure — conditions where the renin-angiotensin-aldosterone system remains inadequately controlled by existing therapies.
The Phase I study (NCT07647783), conducted at Beijing Anzhen Hospital, Capital Medical University, enrolls up to 112 healthy adults aged 18 to 55 across three sequential parts: six single ascending dose cohorts, a food-effect cohort of 12 participants, and four multiple ascending dose cohorts. Within the randomized parts, participants are assigned in a 4:1 ratio to SYH2072 or placebo under quadruple-blind conditions. Primary endpoints assess the rate of adverse events and ECG abnormalities across the study period, with primary completion anticipated in February 2027. The food-effect cohort, embedded as a discrete part rather than a separate study, indicates that oral bioavailability under fed versus fasted conditions is a design priority — a practical consideration for any agent intended for chronic cardiovascular use. The trial identifier is NCT07647783.
Aldosterone synthase (CYP11B2) catalyzes the final steps of aldosterone biosynthesis in the adrenal cortex. Excess aldosterone drives sodium retention, potassium wasting, and direct fibrotic effects on the heart and kidney — pathophysiological consequences that are only partially addressed by mineralocorticoid receptor antagonists such as spironolactone or eplerenone, which block aldosterone's downstream receptor but leave circulating aldosterone levels elevated. Inhibiting CYP11B2 directly suppresses aldosterone production, offering a mechanistically distinct approach. The principal selectivity challenge for this class is avoiding co-inhibition of CYP11B1, the enzyme responsible for cortisol synthesis, which shares approximately 93% sequence identity with CYP11B2.