Company Overview - ProQR is pioneering ADAR-mediated RNA editing with its Axiomer platform, moving from invention to clinical trials [11, 17] - The company has a strong intellectual property estate and strategic partnerships with Eli Lilly and Rett Syndrome Research Trust [17, 135] - ProQR's cash and cash equivalents were €119.8 million as of the end of Q2 2025, providing a runway into mid-2027 [18, 136] Pipeline and Clinical Development - AX-0810, targeting NTCP for cholestatic diseases, has received CTA authorization and is entering a Phase 1 clinical trial [17, 21] - The Phase 1 trial aims to establish safety, PK, and target engagement in healthy volunteers [21] - AX-2402, for Rett syndrome, is rapidly advancing, positioning ProQR at the forefront of neurological RNA editing medicines [21] AX-0810 and Cholestatic Diseases - Cholestatic diseases, including Primary Sclerosing Cholangitis (PSC) affecting approximately 80,000 adults and Congenital Biliary Atresia affecting approximately 20,000 pediatrics, have high unmet medical needs [24, 38] - AX-0810 is a first-in-class RNA editing therapy designed to modulate the NTCP channel, limiting bile acid uptake while preserving other channel functions [31] - The therapeutic goal of AX-0810 is to reduce inflammation and fibrosis, alleviate symptoms in PSC and BA, and prevent or delay cirrhosis, organ failure, and transplant [36] AX-0810 Clinical Trial Design - The Phase 1 trial is a multiple ascending dose (MAD) study with N=33 participants (24 on treatment, 9 on placebo) across three cohorts: 3mg/kg, 6mg/kg, and 9mg/kg (TBC) [103, 104] - The trial will assess safety, tolerability, and PK of AX-0810, and confirm target engagement as measured by changes in bile acid levels, bile acid profile, and TUDCA challenge [107] - Initial Cohort 1 safety, tolerability, and PK data are expected toward the end of 2025, with target engagement data on all cohorts anticipated in H1 2026 [107, 131]