Roche’s gene therapy arm, Spark, has made a significant stride in bolstering its inherited retinal disease (IRD) portfolio, sealing a $216 million partnership with Spanish biotech company SpliceBio. This alliance opens doors for Spark to harness SpliceBio’s cutting-edge Protein Splicing platform, a pioneering solution aimed at surmounting a common gene therapy challenge – the delivery of extensive amino acid sequences that conventional adeno-associated virus (AAV) vectors struggle to accommodate.
The core of the Protein Splicing technology evolved through a collaboration with Princeton University in the United States. This innovation entails the fragmentation of the gene into two segments, each thoughtfully packed into dual AAV vectors. One vector is tailored to deliver the N-terminal of the sequence, while the other is responsible for the C-terminal. Within the target cell, these complementary halves, known as inteins, function harmoniously to yield a fully functional iteration of the protein encoded by the gene.
SpliceBio’s flagship in-house project focuses on Stargardt disease, an IRD devoid of approved therapeutic interventions. This ailment results from genetic mutations in a gene called ABCA4, leading to the buildup of lipid deposits in the eye’s macula. The considerable length of the protein coded by ABC4 presents formidable challenges for integration into existing vectors, prompting scientists to explore alternative strategies, including the application of CRISPR gene editing.
In return for upfront payments, opt-in opportunities, and the attainment of key milestones, Spark, a company that found its home within Roche through a $4.8 billion acquisition in 2019, secures exclusive rights to an undisclosed IRD therapy.
Miquel Vila-Perelló, Chief Executive of SpliceBio, underscores their commitment to advancing Stargardt disease treatment and expanding their proprietary gene therapy programs. He states, “In addition to the Spark collaboration, we continue to develop our lead program in Stargardt disease and further build our capabilities and pipeline of wholly-owned gene therapy programs to develop life-changing therapies for patients in need.”
Spark’s maiden commercially available gene therapy, Luxturna (voretigene neparvovec), earned FDA approval in 2017 as a remedy for Leber’s congenital amaurosis, an infrequent genetic eye disorder. Although initial sales may not have met expectations, Roche remains optimistic about Spark’s evolving pipeline, which encompasses candidates targeting conditions like hemophilia A and B, as well as various other genetic disorders.
In its 2022 annual financial report, Roche revealed a significant impairment charge linked to the Spark gene therapy initiatives. The corporation ascribes this to the slower-than-expected advancement within the domain of this particular medical sector, an issue that has repercussions for all stakeholders in the field.
