LB941 Importance of six-month dosing with QTORIN rapamycin to achieve maximal effect in patients with pachyonychia congenita

PC is a rare, debilitating disease with lifelong limited mobility caused by mutations in KRT6, 16, or 17. There are no approved therapies. mTOR regulates expression of KRT6 and its binding partners KRT16 We completed Ph. 2/3 3b trials QTORIN rapamycin for PC. identified cohort subjects, gradual responders, who accrued higher response between 12 24 weeks therapy. The trial was randomized withdrawal trial, where all subjects received 12-weeks rapamycin. primary endpoint the Patient Global Assessment Activities Difficulty (PGA-AD). To enrich study, met 2-point improvement seamlessly rolled into 3 period. All (Ph.3 qualifiers non-qualifiers) were invited OL after washout. 21 study reported mean PGA-AD 2.74 points (p<0.0001). Improvements observed Worst Pain, CGI-S, PROMIS-PF At weeks, “qualifiers” had 3.02-point (n=13) while “non-qualifiers” (n=8) 1.41-point at reached 2.28-point indicating these responders since they continued to improve weeks. clinically meaningful responses rapamycin: responders. After treatment, achieved <2 but over 12-24, have full clinical benefit that takes >12 achieve. This result supports 24-week treatment period ongoing