Chiesi and Arbor win EU orphan designation for ABO-101 in PH1
Chiesi Group and Arbor Biotechnologies have announced that ABO-101, their investigational gene editing therapy for primary hyperoxaluria type 1 (PH1), has received orphan drug designation (ODD) from the European Commission. The designation recognises PH1 as a rare condition affecting fewer than five in 10,000 people in the EU and unlocks a suite of development incentives, including protocol assistance, fee reductions and ten years of market exclusivity upon approval.
PH1 is an ultra-rare lifelong disorder caused by a mutation in the AGXT gene, which leads to a hepatic enzyme deficiency and chronic overproduction of oxalate. As oxalate accumulates in the kidneys and other tissues, patients face recurrent kidney stones, progressive renal damage and eventual end-stage kidney disease. In severe cases, dialysis and combined liver-kidney transplantation are the only current options, underscoring the high unmet need the two companies are targeting.
The therapy and its clinical programme
ABO-101 is designed as a one-time liver-directed treatment. It uses a lipid nanoparticle (LNP) platform, licensed from Acuitas Therapeutics, to deliver messenger RNA encoding a Type V CRISPR Cas12i2 nuclease. The nuclease targets and disrupts the HAO1 gene in liver cells, aiming for a permanent reduction in oxalate production. The approach differs from approved RNA-interference therapies for PH1, such as Alnylam's lumasiran, in that it seeks a durable gene-level edit rather than ongoing post-transcriptional silencing.
ABO-101 is currently being evaluated in the open-label, global, multi-centre redePHine Phase 1/2 dose-escalation study (NCT06839235). The trial enrolls adult participants first, using a single ascending dose to identify a recommended dose, before moving to a paediatric cohort. John Lieske, the study's principal investigator, is presenting a clinical programme update at the 15th International Hyperoxaluria Workshop in Prague on 26 June 2026, though no interim efficacy or safety data were included in the announcement.
Mitch Goldman, SVP Research and Development at Chiesi Global Rare Diseases, said the designation "provides meaningful support throughout the development lifecycle, which allows us to continue advancing this research with the resources and commitment the community deserves." Devyn Smith, chief executive of Arbor Biotechnologies, described the milestone as underscoring "the growing potential of gene editing therapies to evolve the treatment landscape for rare genetic diseases."
Regulatory context and competitive landscape
The EC designation follows FDA orphan drug designation and rare paediatric disease designation (RPDD), both granted in 2025. The RPDD is particularly notable commercially: it entitles the sponsor to a priority review voucher upon approval, which can be sold or transferred and has recently traded at values exceeding $100 million, providing a meaningful financial incentive alongside the regulatory benefits.
The broader PH treatment landscape has evolved considerably in recent years. Alnylam's lumasiran (Oxlumo) received EMA approval in 2020 and FDA approval in 2021 for PH1, establishing RNA interference as a standard-of-care option for many patients. A one-time gene editing approach, if it demonstrates comparable or superior oxalate reduction with a durable effect, could offer a compelling clinical alternative, particularly for paediatric patients and those who face adherence challenges with chronic dosing regimens.
Gene editing in the liver more broadly is a rapidly advancing field. Several programmes using base editing and prime editing have entered or are approaching the clinic for metabolic liver diseases, and the LNP delivery technology underpinning ABO-101 has been validated across multiple approved RNA therapeutics. However, long-term durability, off-target editing rates and the immunogenicity profile of the Cas12i2 nuclease remain key questions that the redePHine study will need to address before the therapy can progress to a pivotal programme.
The Chiesi-Arbor collaboration was established in 2025 and covers the global development and commercialisation of ABO-101. No financial terms for the partnership have been disclosed publicly.