Development

OMass enters human testing with MC2R antagonist OMS1620 for congenital adrenal hyperplasia

OMass enters human testing with MC2R antagonist OMS1620 for congenital adrenal hyperplasia

UK-based OMass Therapeutics has registered a Phase I trial of OMS1620, an oral small-molecule melanocortin-2 receptor (MC2R) antagonist being developed for congenital adrenal hyperplasia (CAH) and other disorders driven by excess adrenocorticotropic hormone (ACTH).

The randomized, triple-blind study (NCT07811089) will enroll up to 84 healthy adults aged 18–55 across single ascending dose, multiple ascending dose, and food-effect cohorts. The trial is listed as not yet recruiting, with an estimated start in September 2026 and primary completion expected in May 2027. It is sponsored by OMass Therapeutics Australia Proprietary Ltd, a subsidiary of OMass Therapeutics.

CAH comprises a group of inherited disorders of adrenal steroidogenesis in which impaired cortisol production drives chronic ACTH elevation, leading to excess adrenal androgen production and, in some forms of the disease, aldosterone deficiency. Standard treatment relies on lifelong glucocorticoid replacement, with some patients requiring supraphysiologic doses to suppress ACTH and control androgen excess.

OMS1620 is designed to intervene directly at the adrenal gland by blocking MC2R, the receptor through which ACTH stimulates steroid production. This distinguishes the approach from CRF1 receptor antagonists such as Neurocrine Biosciences’ Crenessity (crinecerfont), which acts upstream by reducing pituitary ACTH drive and was approved by the US FDA in 2024 for classic CAH in adults and children aged four years and older.

OMass presented preclinical data on OMS1620 at the Endocrine Society’s ENDO 2025 meeting in July 2025, showing inhibition of adrenal responses to ACTH challenge in rats and improvements in body and adrenal weight in a chronic ACTH-excess model. The company has highlighted the molecule’s long receptor residence time as a potentially important feature for maintaining MC2R blockade during periods of sustained ACTH elevation.

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The Phase I study will assess safety, tolerability, pharmacokinetics, pharmacodynamics, and the effect of food on drug exposure. OMass has indicated that the findings will inform the design of a subsequent Phase II study in patients with CAH.

OMS1620 enters the clinic as interest in MC2R antagonism as a therapeutic strategy in CAH increases. The mechanism offers a distinct way to control adrenal hormone overproduction while potentially allowing patients to remain on physiologic glucocorticoid replacement, although whether direct adrenal receptor blockade offers advantages over existing and emerging upstream approaches remains to be established in human studies.

OMass also faces an unresolved patent infringement action filed in May 2026 by Nxera Pharma relating to miniG platform technology used in GPCR drug discovery. The potential commercial implications for OMS1620 have not been disclosed.


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