Biotech research has made it possible to deliver treatments to patients by editing DNA, and Roche is focusing on RNA to become part of the next wave of gene therapy. The company’s latest move in this strategy is a partnership with Acidian Therapeutics, a startup with technology to edit RNA to address several disease-causing mutations.
Under terms of the collaboration announced last week, Roche will pay $42 million up front for the rights to use Acidian’s RNA exon editing technology for certain neurological targets. The specific targets were not disclosed, but Robert Bell, Acidian’s senior vice president and head of research, said they are for serious diseases with unmet medical need.
“These are devastating diseases, and patients are desperate for a solution, and some have tried solutions that have not worked for them,” he said. “Part of the reason is that we don’t fully understand the nature of these diseases. RNA exon editing has real potential to solve some of these problems that we haven’t been able to address before.”
Gene editing therapies use editing techniques such as CRISPR. The cuts are made by enzymes not native to the human body, which can trigger an immune response. Meanwhile, the act of cutting DNA carries the risk of off-target editing. Ascidian’s approach to genetic medicine is to focus on exons, the protein-coding parts of RNA. Mutated exons can lead to mutated proteins that cause disease.
Ascidian’s in vivo therapies are designed to excise disease-causing exons and replace them with functional exons. By editing RNA before it is translated into protein, Ascidian aims to enable the production of full-length, functional proteins. These proteins are expressed at the right levels at the right time in the right cells, Bell said. The approach does not use exogenous enzymes or cut DNA, avoiding immune responses and off-target editing, which are risks with DNA-editing therapies.
Boston-based Ascidian was founded and incubated by venture capital firm Apple Tree Partners, and the company was announced in 2022. Since then, the company has progressed to the clinical stage with its lead program, ACDN-01, a potential treatment for Stargardt disease, an inherited vision-loss disorder that currently has no FDA-approved treatment. Bell said Ascidian chose Stargardt because it has a genetically defined target in the ABCA4 gene. The gene’s large size makes it difficult to treat with gene therapy to replace the mutated gene. The challenge with editing ABCA4 is that more than 1,000 mutations in this gene are associated with retinal diseases, making it impossible to develop a gene-editing therapy that addresses each one. By editing the exon, Ascidian aims to address many of the mutations that cause Stargardt disease. Preclinical data for ACDN-01 was presented in May at the American Society for Gene and Cell Therapy annual meeting. A phase 1/2 clinical trial began earlier this year.
Chief Financial and Chief Business Officer Dan Rozan said that as a platform technology company, partnering has always been part of Ascidian’s long-term strategy. The startup’s progress with its leading internal programs has helped it accelerate discussions with pharmaceutical companies. Roche is Ascidian’s first pharmaceutical partner.
“They clearly knew the targets they wanted to explore, and we had very collaborative, scientifically rigorous discussions about whether and how the technology could be applied to those targets,” Rosan said. “This was a situation with a lot of scientific discussion from the beginning.”
Roche has long been interested in targeting RNA as a way to treat diseases, particularly neurological disorders. The Swiss pharmaceutical giant’s relationship with Ionis Pharmaceuticals dates back more than a decade and resulted in the development of Tominersen, an antisense oligonucleotide therapy that binds to messenger RNA and prevents the production of the mutant protein that causes Huntington’s disease. Tominersen is in mid-stage clinical development. The two companies teamed up again last year, when Roche licensed the rights to two of Ionis’ RNA-targeted therapeutic candidates for Alzheimer’s and Huntington’s disease.
Roche’s RNA ambitions have also led to collaborations with startups. The pharmaceutical giant is pursuing RNA interference therapies for neurodegenerative diseases in a partnership with Atalanta Therapeutics. It is also working with Shape Therapeutics, a startup developing programmable RNA medicines to repair the genetic causes of disease. When the collaboration with Shape Therapeutics began in 2021, the focus was on neuroscience and rare diseases. Late last year, the collaboration expanded to include undisclosed common diseases. Roche’s RNA-targeting strategy also includes small molecules, which it is pursuing through collaborations with Arakis Therapeutics, Rivometrix, and Remix Therapeutics.
James Sabry, Roche’s global head of pharmaceutical partnering, said in a prepared statement that the collaboration with Acidian is an opportunity to leverage RNA exon editing technology that could potentially edit multiple entire exons at the RNA level in a single treatment. The deal sees Acidian responsible for discovery and certain preclinical work in collaboration with Roche. The pharmaceutical giant will be responsible for other preclinical activities, clinical development, manufacturing and, if approved, commercialization. Acidian could earn up to $1.8 billion in milestone payments.
Losan said the upfront payment will give Acidian more capital to develop additional in-house programs in neurology and other therapeutic areas. Although Acidian’s lead program is for inherited eye diseases, the startup is not an ophthalmology company. Most of the genetically defined targets the company is studying are outside the eye, Bell said. The collaboration with Roche is not exclusive. Acidian may develop its own neurological treatments for targets not covered in the agreement. It may also pursue other targets in collaboration with other companies.
“I think we can learn a lot from[Roche]about how to partner,” Rosin said. “We look forward to other partnerships, with the right partners for the right targets.”
Photo courtesy of Ascidian Therapeutics
