Chiesi Group will partner with Arbor Biotechnologies to develop Arbor’s lead candidate ABO-101, a treatment for primary hyperoxaluria type 1 (PH1), and potentially other gene editing programs to treat rare diseases, through a partnership that could generate more than $2.1 billion for the Cambridge, MA-based gene editing therapy developer.

The partnership marks the first effort by Chiesi to develop a gene editing therapy and comes as the Italian biopharma is building a pipeline of rare disease treatments as one of its three therapeutic areas of focus, the other two being respiratory and pulmonary diseases and neonatal care. The companies plan to build out some of Chiesi’s rare disease pipeline, developing and globally commercializing ABO-101 through an exclusive collaboration and license agreement announced earlier this week.

Arbor and Chiesi will collaborate on the ongoing Phase I/II redePHine trial (NCT06839235), designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABO-101 in patients with PH1. The study’s primary outcome measure is incidence and severity of treatment-emergent adverse events (TEAEs), including ABO-101-related TEAEs and serious adverse events (SAEs), at six months.

ABO-101 is a one-time liver-directed gene editing therapy designed to reduce PH1-associated oxalate production by permanently knocking out the HAO1 gene in the liver. ABO-101 consists of a lipid nanoparticle (LNP) licensed from Acuitas Therapeutics, which encapsulates messenger RNA (mRNA) expressing a Type V CRISPR Cas12i2 nuclease and an optimized guide RNA that specifically targets HAO1.

As a PH1 treatment, ABO-101 is adjacent to one of Chiesi GRD’s three rare disease areas of focus, lysosomal storage disorders. The others are rare lipid disorders and a variety of diseases that include rare dermatology, rare optometry, rare primary immune deficiencies, and rare benign hematology.

In addition, Chiesi has signed a multitarget research collaboration and option agreement giving it access to Arbor’s gene editing platform technology to develop therapies against multiple targets associated with rare liver diseases. The option would allow Chiesi to apply Arbor’s knockout (KO) and reverse transcriptase (RT) editing technology.

“We continue to be very laser-focused on execution, and pushing ahead our programs as quickly as possible into the clinic and beyond, and we’re pretty excited to be able to partner with Chiesi’s team to do this in rare liver diseases, which we believe are the perfect space for this type of technology,” Devyn Smith, PhD, CEO of Arbor Biotechnologies, told GEN. “People just want a disease to go away, particularly parents and caregivers, and this is an opportunity to do that, rather than have them be treated chronically for the rest of their lives. So, I’m pretty excited to be able to apply our approach to some of these diseases.”

“Patient friendliness” approach

Both Chiesi and Arbor spoke with numerous companies about partnering, with Chiesi saying it considered prospective partners specializing in a variety of treatment modalities.

What sold Chiesi on ABO-101 and in vivo gene editing?

“We were very impressed by, number one, the quality of the team; number two, how collaborative they are; and number three, certainly last but not least, the quality of the science,” Giacomo Chiesi, executive vice president, Chiesi Global Rare Diseases (GRD), told GEN. Chiesi GRD is the business unit of Chiesi Group focused on research, development, and commercialization of therapies for rare and ultra-rare conditions. “We looked at siRNAs [silent RNAs], at mRNAs, at various types of gene therapies, cell and gene therapies. And for a number of reasons, including patient friendliness, we decided to prioritize in vivo gene editing approaches.”

Because ABO-101 is an in vivo gene-editing therapy, it does not require patients to undergo a preconditioning regimen before dosing. That’s an example, according to Chiesi, of a patient-friendly approach shared by his company and Arbor, which is supporting clinical development of ABO-101 in part with proceeds from the $73.9 million Series B financing it completed in March.

“We put patients really at the beginning and at the end of everything we do. And we also felt that they had done a very exhaustive, interesting exercise to identify which diseases best to apply their technology to, which we felt was very exhaustive, very convincing. And that was ultimately one of the reasons why we decided to partner with them,” Chiesi explained.

Added Smith: “We didn’t want to partner with an entity that doesn’t have a sustained, driven commitment to rare diseases. The last thing you want is you do a partnership with someone, and then two years later, strategically they’re off on the next big thing, which happens with some companies. Giacomo and his team have demonstrated how to basically build a rare disease business from scratch over the last seven or eight years.”

Rare diseases are a growing portion of Chiesi’s business, accounting for 25% of the group’s total €1.86 billion sales in the first half of 2025 (about €465 million or roughly $541 million), a 31% jump from H1 2024. The rare disease business has grown from 22% of group sales last year (up four percentage points from 2023), with revenues of €763 million (about $887.5 million), up 41% year-over-year.

Chiesi’s rare disease pipeline features 13 programs, including programs partnered with Amgen (in neophropathic systinosis) and Protalix Biotherapeutics.

Differentiated dosing

In addition to eliminating conditioning, Chiesi and Arbor hope to draw patients to ABO-101 with its differentiated dosing requirement, which, as a one-time therapy, contrasts with the monthly to quarterly dosing of the two PH1 treatments that have won FDA approval over the past five years.

In 2020, Alnylam Pharmaceuticals received FDA authorization for Oxlumo^® (lumasiran), which silences HAO1 through small interfering RNA (siRNA) to lower urinary and plasma oxalate levels in children and adults. And in 2023, the agency approved Novo Nordisk’s Rivfloza^® (nedosiran), also an siRNA but one that targets the liver’s lactate dehydrogenase A (LDHA) enzyme to lower urinary oxalate levels in patients ages two and up.

Oxlumo generated $89 million in global net product revenues during the first half of this year (of which $47 million came in the second quarter) and $167 million last year. Rivfloza sales are not disclosed separately; the drug is within the portion of Novo Nordisk’s rare disease segment outside of drugs for rare blood disorders and rare endocrine disorders. The “other rare disease” sub-segment finished the first half of this year with sales of DKK 789 million ($122.884 million) (DKK 403 million or $62.766 million during Q2), up 3% from DKK 765 million ($119.139 million) in H1 2024 and racked up DKK 1.508 billion ($234.846 million) last year, down nearly 3% from DKK 1.551 billion ($241.543 million) in 2023.

“The siRNAs are great therapies. They’re good for patients, and we certainly hope and want them to continue to be available for patients in the future,” Chiesi said. “We also believe that for many rare diseases, polytherapy, or the availability of multiple opportunities in the therapeutic algorithm is important for patients with some rare diseases.”

Chiesi has agreed to pay Arbor up to $115 million in upfront and near-term payments, plus up to $2 billion in payments tied to achieving development, regulatory, and commercial milestones, and low double-digit tiered royalties for products licensed through the companies’ agreements.

Headquartered in Parma, Italy, the Chiesi Group employs more than 7,500 people worldwide, including 900 in R&D positions. “We’re looking to add several dozen people to the R&D contingent,” Chiesi said. “I think we’re looking at 40, maybe 50 in total, and that’s going to be across the different continents.”