Following the closure of Spain’s largest round of Serie A biopharmaceuticals, SpliceBio has laid the groundwork for gene therapy and joined efforts to deliver more therapeutic genes to patients.
SpliceBio was founded in 2012 to work with a type of protein called inteins that can bond peptides to form new proteins. The firm, originally named ProteoDesign, has faced a dazzling array of potential applications for the technology and has spent several years formulating its therapeutic mission: to push the boundaries of gene therapy technology.
«We explored several areas, including antibody and drug conjugates, and realized that gene therapy is an area where our technology can have a huge impact, unmatched by any other technology, to address an urgent problem that remains unresolved – the delivery of large genes. in gene therapy“- said Michel Villa-Perello, CEO of SpliceBio.
This week, UCB Ventures and Ysios Capital topped the 50 million euro round of the SpliceBio series A – the largest in the Spanish biotechnology industry to date. It happened a few months after Spain saw one of them the largest acquisition transactions in biopharmacy: Sanifit’s acquisition by Vifor Pharma worth up to 375 million euros.
Thanks to this new funding, SpliceBio has firmly established its focus on gene therapy and is creating a range of treatments for a state of genetic blindness. SpliceBio’s flagship program focuses on Stargardt’s disease, a condition caused by mutations in the retina gene ABCA4.
According to Joel Jean-Marie, managing partner of Ysios Capital, Stargardt’s disease is a great attraction for investors and major pharmacists because it is a well-studied condition and relatively easy to achieve gene therapy in the retina.
«Although it is the most common inherited retinal disease caused by mutations in a single gene, patients currently do not have any therapeutic treatment options. [Stargardt] disease“- added Jean-Mayor.
The biggest snag with Stargardt’s disease is the healthy version ABCA4 the gene is too large to deliver using the gold standard vector of gene therapy: adeno-associated viruses (AAVs). AAV vectors can carry genes up about 5,000 base pairs in length; ABCA4 ahead of this figure of 6,800 base pairs. And other types of viral vectors with higher bandwidth than AAV, for example adenoviruses present other problems.
«Adenoviruses are an excellent choice if your goal is to generate an immune response, for example in the case of Covid-19 vaccines, however their immunogenicity is problematic if the intention is to treat diseases of genetic origin.“- said Michel Villa Perello. «Lentiviruses also pose significant safety risks and production problems for in vivo gene therapy. We believe that none of them is a viable option for in vivo gene therapy.”
SpliceBio intein technology is designed to eliminate size barriers by causing some AAVs to carry one half of the DNA sequence while others AAV carry the other half. AAVs are also equipped with DNA sequences for inteins. When AAV transfers DNA to a cell, the cell converts the DNA sequence into half the ABCA4 protein plus intein. The viscera are then connected to the two halves to obtain a complete protein.
The technology is reminiscent double vectors AAV, an old form of gene therapy technology. The main difference from SpliceBio technology is that parts of the gene are fused into the cell in the form of DNA or RNA sequences before becoming a protein. However, Jean-Marie told me that this approach is much less effective than the SpliceBio platform.
In development, there are other treatments for Stargardt’s disease through gene therapy. The most advanced contender is the American company Nanoscope Therapeutics, which plans to phase I / IIa trials of its gene therapy later this year. Instead of delivering healthy ABCA4 gene, Nanoscope’s strategy is to get viral vectors to deliver a gene for a light-sensitive, or “optogenetic,” protein. In this way, the company can cause retinal cells to respond to light regardless of the mutation that causes the disease.
Another firm fighting for gene therapy for Stargardt’s disease is Coave Therapeutics in France. Formerly known as Horama, Coave is committed to delivering health ABCA4 gene using specially designed AAV vectors, raising 33 million euros in the B Series round in July 2021 to advance its pipeline.
Many companies are also developing non-viral methods to deliver genes to patients who face smaller size constraints than viral vectors. For example, Nanoscope Therapeutics is developing a laser-based method to deliver genes directly to the eye, while Eyevensys in France uses electric currents. In late 2021, the Swiss firm Anjarium Biosciences raised a € 51 million series of A series funding to promote its own gene delivery system based on DNA vectors and nanoparticles.
«Non-viral gene therapy vectors are relatively easy to produce and scale to therapeutic amounts, which is still a problem for viral vectors“, Said Matthew Booth, senior vice president and head of global therapy at consulting firm GenEra Consulting. «With this in mind, non-viral vectors may be the means of choice in diseases with a large number of patients.”
However, non-viral vectors are still at an early stage, with particular problems when targeting specific organs. Villa Perello believes that viral vectors continue to play a crucial role in the evolution of gene therapy over the next decade.
«There is a reason why viral vectors and especially AAVs are the vector of choice for gene therapy in vivo: they have evolved in nature over millions of years to perform precise functions, and are undoubtedly the most advanced vectors for providing treatments that change lives. patients“- concluded Villa Perello.
Cover image by Elena Reska
https://www.labiotech.eu/trends-news/splicebio-gene-therapy-spain/ SpliceBio Bags € 50 Million, Series A to Break the Vector Limits of Gene Therapy