Precision BioSciences receives Rare Pediatric Disease and Orphan Drug designations for DMD therapy

Precision BioSciences Inc., a clinical-stage company developing gene editing therapies for diseases with high unmet need, has received another pair of regulatory boosts. The FDA recently granted the company’s PBGENE-DMD therapy Rare Pediatric Disease Designation and Orphan Drug Designation for the treatment of Duchenne muscular dystrophy (DMD).

“The FDA grants Rare Pediatric Disease Designation to programs being developed for pediatric rare diseases with very high unmet need, and Orphan Drug Designation to programs intended to treat rare diseases affecting fewer than 200,000 in the United States,” said Cindy Atwell, chief development and business officer at Precision BioSciences. “Receiving these designations for PBGENE-DMD is an acknowledgement of our goal to develop a transformational therapy for patients with our gene editing approach.”

DMD is a devastating disease that usually leaves patients wheelchair bound by their teens, and unfortunately, most patients succumb to the disease in their twenties. It is caused by mutations in the dystrophin gene, which prevent the production of fully functional dystrophin proteins that are essential for maintaining the structural integrity of muscle cells.

Creating a functional gene

Although there are some gene therapies based on shortened versions of the gene known as microdystrophins — which lack many of the functional pieces found in the normal protein — these therapies have had difficulty achieving clinical functional endpoints in patients and wear off over time as cells divide, according to Atwell.

PBGENE-DMD, which is based on the company’s ARCUS genome editing platform, is designed to work differently. For this therapy, two nucleases are used to cut the patient's genomic DNA, excising the portion with the mutation and then perfectly reassembling it to create a functional dystrophin gene.

Unlike the well-known CRISPR gene editing technology, gene editing with ARCUS doesn't require an RNA guide to find its target in the genome. It is a single-protein, single-component tool that both recognizes and cuts a 22-base pair DNA sequence. It's also very small — about one kilobase — making it well-suited for delivery using adeno-associated viruses that have limited packaging space. Because it is so small, genes for two ARCUS nucleases can be delivered together in a single adeno-associated viral capsid.

“Additionally, the ARCUS nucleases make a different type of cut — a 3' overhang — which helps DNA ends rejoin more efficiently,” said Atwell. “This is especially important for restoring a functional dystrophin gene in PBGENE-DMD.”

Based on preclinical studies, the company believes its DMD therapy could offer a more durable effect. By editing the patient’s own DNA, dystrophin is produced under its natural promoter, which may support more stable expression. The therapy also targets muscle stem cells, called satellite cells, which generate new muscle fibers and could help sustain long-term benefits. Additionally, unlike microdystrophin approaches that rely on continuous high expression from an external gene, the ARCUS therapy may require only a brief period of activity to produce lasting changes.

The company is working to complete the final IND-enabling toxicology studies, which are currently underway, and expects to begin generating initial clinical data in 2026.

Towards a cure for hepatitis B

Precision BioSciences has also applied its ARCUS technology to develop a therapy for chronic hepatitis B virus (HBV) infection, which has no curative options and affects about 300 million people globally. Precision’s PBGENE-HBV therapy is designed to potentially eliminate the key source of replicating HBV, known as cccDNA, while also inactivating HBV DNA that has integrated into the patient’s liver cells.

The ELIMINATE-B study phase 1 clinical trial is testing PBGENE-HBV at three dose levels and three dose administrations at each level. “The initial safety data from the lowest dose level was presented at the European Association for the Study of Liver (EASL) and initial safety at the second dose level was presented at the American Society for Gene & Cell Therapy (ASGCT) conference in May,” said Atwell. “We're continuing to administer additional doses to those patients in the first two cohorts while looking toward starting cohort three over the course of this year. The data we’ve gathered so far indicates a good safety profile and good antiviral activity, even in these lower dose cohorts.”

The company has received FDA clearance to conduct clinical trials in New Zealand, Moldova, Hong Kong and the UK, and most recently, received approval for a US site, which it plans to launch soon.

“With more sites, we can accomplish faster enrollment while also making sure we have a diverse population of patients from across the globe,” said Atwell. “We have been very pleased to see high engagement from both investigators and patients involved in the trials as well as key opinion leaders in the field.”

Thriving through collaboration

Atwell says that Precision BioSciences, originally spun out of Duke University in 2006, has thrived in the RTP area thanks to the strong scientific talent from nearby universities. It has also benefited from the region’s deep expertise in drug development and manufacturing, supported by the many local research organizations and production facilities.

Although the company is focusing its internal resources on its PBGENE-HBV and PBGENE-DMD programs, it remains open to partnerships and has several active collaborations. One example is a gene insertion program with Novartis for sickle cell disease and beta thalassemia. For this program, Precision is developing a nuclease and repair construct, and Novartis will take on future IND-enabling activities, clinical development and commercialization after a clinical candidate is identified.

Another partnership is with iECURE, a spinout from the University of Pennsylvania founded by James Wilson. iECURE is using the ARCUS platform for gene insertion to treat ornithine transcarbamylase (OTC) deficiency, an ultra-rare genetic disorder that is typically fatal within the first year of life without a liver transplant. The 3’ overhang generated by ARCUS when it cuts DNA is designed to improve the efficiency of gene insertion compared to other gene editing technologies and helps insert a healthy copy of the OTC gene into patients’ liver cells. In early clinical results, the first dosed infant showed a complete response: ammonia levels normalized, all scavenger medications were discontinued, and the patient was feeding normally.