SpliceBio Secures $135M Series B for Protein Splicing Drugs Advancement

Barcelona-based company SpliceBio, specializing in genetic medicines, has successfully secured $135 million in a series B funding round, as announced recently. This substantial investment will be allocated towards advancing the development of their leading gene therapy specifically targeted for Stargardt disease, a type of inherited macular degeneration. Stargardt disease, caused by a mutation in the ABCA4 gene, results in progressive vision degradation, ultimately leading to blindness. The ABCA4 gene's full length is too substantial to be accommodated within a standard adeno-associated viral (AAV) vector, which is traditionally used in gene therapies.

SpliceBio's approach deviates from conventional methods such as gene splicing, exon-skipping, or gene editing. Instead, their innovative strategy involves delivering a replacement protein for the faulty gene in segments. The company's flagship gene therapy, SB-007, ingeniously divides the oversized ABCA4 gene into two segments, with each fragment being conveyed via a separate AAV vector. Once delivered, these gene segments are individually translated, and engineered sequences known as inteins are designed to splice the segments together, reconstructing the complete functional protein. This process is akin to assembling pieces of a puzzle, as described by CEO Miquel Vila-Perelló.

The decision to focus on Stargardt disease was intentional, given the current lack of approved treatments for this condition. Additionally, targeting the eye, an area of the body with relative immune privilege, permits the use of significantly lower doses of AAVs—up to ten thousand times less compared to other bodily regions, as explained by Vila-Perelló. In March, SpliceBio administered SB-007 to its first patient as part of the Phase I/II ASTRA trial. The funds from this latest investment round will further support the ongoing trial, which is presently in its dose escalation stage. In tandem, the therapy is under investigation in an observational natural history study named POLARIS, which commenced in early 2024.

The series B funding round marks the company's third, following a seed round in 2020, backed by Ysios Capital and Asabys Partners, and a series A round in 2022, which raised $57 million and was supported by an international consortium of investors. Notably, Novartis Venture Funds, the venture capital branch of Novartis, played a key role in these funding efforts and continues its support in the series B. They are joined by the investment arms of other major pharmaceutical companies, Sanofi and Roche.

SpliceBio's proprietary intein-based technology originates from research conducted in Thomas Muir’s chemistry lab at Princeton University, with both Vila-Perelló and CTO Silvia Frutos being former scientists from this lab. Inteins, known for their ability to cut protein sequences, have a variety of applications within biotechnology, particularly in biopurification. However, their use in biopharmaceuticals remains largely in the preclinical research stage, mainly focusing on antimicrobial treatments.

In addition to SB-007, SpliceBio is developing other molecular therapies targeted at undisclosed conditions. Vila-Perelló expressed confidence in the company's intein technology, noting that it has demonstrated efficacy across multiple diseases and organs, which has been acknowledged by investors recognizing its potential value.