Mitochondria, the power plants of the cell, bear their own DNA, a small remnant of their origin as symbiotic bacteria. Unfortunately, this DNA is more vulnerable than the DNA found in the cell nucleus, and can become damaged in ways that contribute significantly to the aging process. How to address this problem? Allotopic expression of a mitochondrial gene is a process by which an altered version of the gene is placed into the cell nucleus in order to provide a backup source of the protein encoded by the gene. In this age of genetic engineering, inserting the gene isn't really the challenge, instead the difficulty lies in figuring out how to alter the gene in order for the protein produced to be transported back to the mitochondria where it is needed.
Funded by philanthropic donations, the SENS Research Foundation has been supporting allotopic expression research for a decade now, seeking to accelerate the development of therapies that can remove this contribution to the aging progress. The first programs funded gave rise to Gensight Biologics, a company that is pioneering the use of allotopic expression of the ND4 gene to address an inherited blindness condition in which the gene is mutated and dysfunctional. This effort is well on the way to proving out the technology in human trials and thereby providing a solid foundation for work on the other genes that must be backed up. Three mitochondrial genes are demonstrated so far, including ND4, and there are another ten to go after that. Commercial efforts of this nature are an important part of the overall development process, and it is a good thing to see a company pulling in significant funding for a technology that will become a part of later rejuvenation therapies.
GenSight Biologics has raised €22.5 million to prepare to bring gene therapy GS010 to market in the U.S. and Europe. The financing gives the Novartis-backed biotech enough cash to deliver data from two phase 3 trials next year and gear up for anticipated approvals on both sides of the Atlantic. Paris-based GenSight raised the cash from a mix of new and existing institutional investors, most of which are based in the US. Strong interest from these backers saw GenSight ease past its initial target of €20 million to pull in €22.5 million in the private placement. When added to the €48.8 million GenSight had in the bank at the end of March, management thinks the money moves its runway out to the first quarter of 2019.
That runway covers a critical period for GenSight. Topline 48-week data from two phase 3 trials of GS010 in patients with Leber hereditary optic neuropathy (LHON) are due in the second and third quarters of next year. GenSight is looking to the trials for evidence GS010 improves the clarity of the vision of patients with LHON, a hereditary form of vision loss caused by mitochondrial defects. GS010 is injected into the eye to deliver the human wild-type ND4 gene via an adeno-associated virus to deliver. This gene encodes for a protein typically produced by mitochondria.
One trial is assessing GS010 in patients who started losing their vision in the six months prior to enrolling in the study. The other is recruiting patients whose vision started deteriorating between seven and 12 months ago. Both trials are injecting GS010 into one eye of each participant and pretending to inject it into the other eye. Data from an earlier phase 1/2 trial suggest the gene therapy is most effective in patients whose vision started deteriorating less than two years ago. A recent 96-week update found the treated eyes of such patients had a mean gain of 29 ETDRS letters, as compared to an increase of 15 letters in untreated eyes. ETDRS is the test showing progressively smaller letters opticians use to gauge vision. The performance of GS010 to date has enabled GenSight to secure the support of some big-name backers. Following the latest financing, its biggest shareholders are Novartis, Versant, Abingworth, and Fidelity.