ProQR Reports Positive Phase 1 Safety Data for RNA Editing Therapy AX-0810, Advances Pipeline Programs
核心洞察
ProQR Therapeutics announced encouraging initial safety and pharmacokinetic data from the first cohort of healthy volunteers in its Phase 1 trial of AX-0810, showing no serious adverse events after 4 weeks of dosing.
The company selected development candidates for two pipeline programs: AX-2402 targeting MECP2 (搜索) for Rett syndrome (搜索) and AX-2911 targeting PNPLA3 for metabolic-associated steatohepatitis (搜索) (MASH (搜索)).
AX-2402 demonstrated statistically significant functional improvements in a mouse model of Rett syndrome (搜索), while AX-2911 showed over 80% reduction in hepatic fat content in preclinical studies.
ProQR Therapeutics announced encouraging initial safety and pharmacokinetic data from its lead RNA editing therapy AX-0810, marking a significant milestone for the company's proprietary Axiomer™ platform. The Phase 1 trial data, along with pipeline advances across multiple programs, positions the clinical-stage biotechnology company for continued progress in 2026.
AX-0810 Demonstrates Favorable Safety Profile in First Human Study
The ongoing Phase 1 study of AX-0810 showed no safety signals after 4 weeks of dosing in healthy volunteers, with preliminary pharmacokinetic observations consistent with non-clinical data. Based on initial data from Cohort 1 participants receiving 3mg/kg doses, AX-0810 demonstrated a safety profile with no serious adverse events or clinically meaningful laboratory abnormalities observed to date.
"The initial human data from AX-0810 mark an important early milestone for ProQR, providing safety and pharmacokinetic observations in healthy volunteers," said Cristina Lopez Lopez, MD, PhD, Chief Medical Officer of ProQR. "These data support continued dosing and position us well for the upcoming target engagement readout in the first half of 2026."
The Phase 1 study is a single-center, randomized, double-blind, placebo-controlled, multiple dose escalation trial being conducted in the Netherlands. Up to 33 participants will be enrolled, including 24 receiving AX-0810 and 9 receiving placebo, across 3 dose cohorts. Participants receive 4 subcutaneous injections over 4 weeks followed by a 12-week safety follow-up period.
AX-0810 is a first-in-class investigational RNA editing oligonucleotide targeting NTCP (搜索) for the treatment of cholestatic diseases (搜索), including primary sclerosing cholangitis (搜索) and biliary atresia (搜索). The therapy harnesses endogenous ADAR (搜索) enzymes to selectively modulate NTCP function, aiming to reduce toxic bile acid accumulation in the liver.
Pipeline Expansion with Development Candidates for Rett Syndrome and MASH
ProQR selected development candidates for two additional pipeline programs, demonstrating the versatility of its Axiomer RNA editing platform. AX-2402 targets MECP2 (搜索) for Rett syndrome (搜索) (R270X), while AX-2911 targets the PNPLA3 I148M mutation for metabolic-associated steatohepatitis (搜索) (MASH (搜索)).
AX-2402 Shows Promise in Rett Syndrome Model
The company announced non-clinical proof-of-concept data generated in a mouse model of Rett syndrome (搜索) with the MECP2 (搜索) R270X mutation. Treatment with AX-2402 resulted in statistically significant and clinically relevant functional improvements, including improvement in cumulative Bird score driven in part by robust improvements in hindlimb clasping score. ProQR plans to initiate a first-in-human clinical trial for AX-2402 in the first half of 2027, supported by up to $9.2 million in funding from the Rett Syndrome Research Trust.
AX-2911 Demonstrates Superior Efficacy in MASH Studies
For AX-2911, ProQR reported new non-clinical functional proof-of-concept data showing greater than 80% reduction in hepatic fat content in a humanized PNPLA3-148M mouse model fed a Western diet. Notably, this outperformed a clinical-stage PNPLA3-directed antisense therapy that achieved approximately 36% reduction in a head-to-head comparison in vivo.
The PNPLA3 I148M mutation represents a key genetic driver for metabolic liver disease, with approximately 8 million individuals in the United States and European Union homozygous for the 148M variant. The development candidate was selected based on a robust preclinical profile demonstrating on-target RNA editing, favorable potency, and supportive functional data.
Strategic Partnership Delivers Milestone Achievements
ProQR's collaboration with Eli Lilly and Company continued to progress, resulting in $4.5 million in milestones achieved during 2025. The collaboration provides external validation of ProQR's Axiomer RNA editing platform while contributing non-dilutive capital to the company's operations.
"Together with continued momentum from our strategic collaboration with Lilly, which achieved $4.5 million in milestones in 2025, these advances underscore the strength and versatility of our Axiomer platform," said Daniel A. de Boer, Founder and Chief Executive Officer of ProQR.
2026 Clinical and Corporate Milestones
ProQR outlined several key objectives for 2026, including reporting target engagement data from the AX-0810 Phase 1 trial in healthy volunteers during the first half of the year. The company also plans to initiate a patient cohort in the AX-0810 first-in-human Phase 1 trial following completion of healthy volunteer cohorts.
Additional 2026 priorities include advancing development activities for AX-2402 toward its planned first-in-human trial, disclosing additional preclinical data across earlier-stage programs, and continuing execution of the Eli Lilly partnership. The company maintains a strong financial position with runway extending into mid-2027.
The Axiomer platform represents a next-generation RNA base editing technology that uses endogenous ADAR (搜索) enzymes to make specific single nucleotide edits in RNA. This approach can correct disease-causing mutations back to normal RNA, modulate protein expression, or alter proteins to gain new therapeutic functions, potentially yielding treatments for both rare and prevalent diseases with unmet medical needs.