Roche builds gene therapy portfolio with SpliceBio deal

Roche’s gene therapy unit Spark has added to its pipeline in inherited retinal diseases (IRDs) with a $216 million alliance with Spanish biotech SpliceBio.

Under the terms of the deal, Spark will get access to the Barcelona-based company’s Protein Splicing platform, designed to get around the problem that some gene therapies have amino acid sequences that are simply too large to be delivered using standard adeno-associated virus (AAV) vectors.

The technology has developed from a collaboration with Princeton University in the US and involves splitting the gene into two and packaging it in dual AAV vectors, one delivering the N terminal of the sequence and the other the C terminal.

Once in the cell, the two halves – known as inteins – work in tandem to create a functional version of the protein coded by the gene.

SpliceBio’s lead in-house pipeline project is in Stargardt disease, an IRD with no approved therapies that is caused by changes in a gene called ABCA4 and results in fatty material building up in the macula of the eye. The protein coded by ABC4 is too long to be entirely inserted into current vectors, so researchers have been looking at other ways to treat it, including the use of CRSPR gene editing.

Spark – which was acquired by Roche in a $4.8 billion takeover deal in 2019 and has already brought one gene therapy to market – will get exclusive rights to a therapy for an as-yet undisclosed IRD in return for upfront, opt-in and milestone payments.

“In addition to the Spark collaboration, we continue to develop our lead programme in Stargardt disease and further build our capabilities and pipeline of wholly-owned gene therapy programmes to develop life-changing therapies for patients in need,” commented SpliceBio’s chief executive, Miquel Vila-Perelló.

Spark’s first commercial gene therapy, Luxturna (voretigene neparvovec), was approved by the FDA in 2017 as a treatment for Leber’s congenital amaurosis, a rare genetic eye disease, getting a green light in Europe the following year.

Sales have not grown as hoped – Roche still doesn’t disclose the figures after several years on the market – but Roche is hoping for better results with Spark’s following pipeline, which includes candidates for haemophilia A and B and other genetic disorders.

Roche recorded a sizeable impairment charge in connection with the Spark gene therapy projects in its 2022 annual results, but has said that is a consequence of slower-than-expected development of the market for this type of medicine and has affected all players in the category.

Spark’s chief science and technology officer, Federico Mingozzi, said that, by combining his company’s technical knowledge with SpliceBio’s platform, they "aim to further advance progress in the treatment of inherited retinal diseases, bringing new transformational gene therapies into the clinic and eventually to the global market.”

Photo by David Underland on Unsplash.