Crinetics Pharmaceuticals (CRNX) Study Result summary

Study design and patient population

• Open-label, global Phase II TOUCAN trial evaluated atumelnant in 28 adults with classic CAH due to 21-hydroxylase deficiency, aged 16–75, across 40, 80, and 120 mg daily doses for 12 weeks, with stable glucocorticoid therapy.

• Patients had uncontrolled disease despite high glucocorticoid doses and elevated baseline A4 (>1,000 ng/dL) and 17-OHP (>11,000 ng/dL) levels.

• Primary endpoint was change from baseline in morning serum A4 at week 12; secondary endpoints included 17-OHP, safety, and clinical outcomes.

• Blood draws for biomarkers were standardized to pre-morning glucocorticoid dosing to capture peak disease activity.

• Clinical assessments included menstrual function, adrenal gland volume by MRI, and other relevant endpoints.

Efficacy and biomarker results

• Atumelnant produced rapid, dose-dependent, and statistically significant reductions in A4, with up to 80% mean reduction at 120 mg and normalization in most high-dose patients within two weeks.

• 17-OHP levels were reduced by up to 67%, with sustained effects over 12 weeks across all dose groups.

• Female participants experienced normalization of testosterone and resumption of menses; 6 of 11 eligible women resumed menses, including those with longstanding amenorrhea.

• Consistent reductions in adrenal gland volume and resolution of androgen-mediated polycythemia observed.

• After treatment cessation, biomarker levels rebounded toward baseline, supporting chronic use.

Safety and tolerability

• Atumelnant was well tolerated at all doses, with no severe or serious treatment-related adverse events reported.

• 71% of participants experienced at least one TEAE, mostly mild or moderate and transient; most common were headache, fatigue, decreased appetite, and mild adrenal insufficiency.

• No dose reductions or discontinuations due to adverse events; all participants completed 12 weeks of dosing.

• Two cases of transient adrenal insufficiency resolved without sequelae; isolated liver enzyme elevations were monitored and resolved post-treatment.

• No negative trends in vital signs, ECGs, or laboratory parameters.