BUSINESS OVERVIEW 6 • Our MTS technology platform allows for efficient expression of gene, a rare mitochondrial genetic disease that leads to blindness a mitochondrial gene by active delivery ofmRNA to polysomes in teens and young adults. We believe that GS010 has the located at the mitochondrial surface. This allows for the synthesis, potential to be the first therapy approved by the FDA for the translocation, internalization and proper localization of the treatment of LHON. We have received orphan drug designation mitochondrial protein into the matrix of the mitochondrion. We for GS010 in the United States and the European Union. GS010 believe that our MTS technology is the only existing technology is currently being studied in Phase I I I clinical trials. We reported that permits missing mitochondrial proteins to be actively top-line data from our first Phase I I I clinical trial REVERSE in April shuttled into the mitochondrion, to enable the restoration of 2018, and expect to report top-line results of our second Phase I I I mitochondrial function necessary to potentially treat a variety of trial RESCUE in the third quarter of 2018. diseases involving defects of the mitochondrion. LHON Overview • Our novel optogenetics technology platform permits the LHON is a rare maternally inherited disease caused by defects introduction of proteins sensitive to light stimulation and may in mitochondrial genes encoding for proteins cal led NADH have broad applicability to indications within ophthalmology and dehydrogenase. LHON causes sudden and dramatic loss of vision, others that are receptive to light stimulation, such as congenital leading to bilateral blindness in less than a year, which reduces deafness, pain treatment and vagus nerve stimulation. patients’ autonomy and greatly alters the patient’s ability to perform daily life activities, including recognizing facial features and expressions. In addition, LHON causes patients and their 6.5 families trauma socially, emotionally and financially, and the quality OUR LEAD PRODUCT CANDIDATE: of life of patients with LHON is generally poor. The onset of vision GS010 FOR THE TREATMENT OF LHON loss due to LHON typically occurs between 15 and 35 years of We are leveraging our MTS technology platform to develop age. The following images are representative of the early onset of GS010 as a treatment for LHON due to a mutation in the ND4 vision loss due to LHON, as described by patients. LHON is caused by defects in mitochondrial genes encoding for Commonly, vision loss is sequential, although some patients proteins called NADH dehydrogenase. These proteins are part of report simultaneous bilateral onset. Within six months after a large enzyme complex known as the respiratory chain complex I, onset, there is atrophy of the optic nerve. Although maintaining or complex I, which is active in the mitochondrion. Complex I is some small element of peripheral vision, the majority of patients one of several enzyme complexes necessary for the creation of with the ND4 mutation become legally blind. For most patients adenosine triphosphate, or ATP, which is the main energy source with the ND4 mutation, vision is not recovered. within the cell. Three different genes encoding for three NADH For ND4 patients, the delay between the first affected and second dehydrogenases have been linked to LHON and are considered to affected eye averages 1.8 month and the duration of progression be the primary mutations for the disease to manifest: ND1, ND4 of vision loss averages 3.2 months. The mean Early Treatment and ND6. Diabetic Retinopathy Study, or ETDRS, score at 12 months is Although the genetic mutation is present throughout the 14.4 letters in patients. The normal visual acuity score is 20/20 body, LHON symptoms are almost uniquely limited to retinal or 20/25, equivalent to an ETDRS score of 85 and 80 letters, ganglion cells, or RGCs. RGCs receive visual information from respectively. photoreceptors, and col lectively transmit visual information For patients with the most severe vision loss, specifically those from the retina to the brain via the optic nerve. Over the months who cannot count the fingers of the examiner held very close after onset, LHON is associated with a significant thinning of the to their face, even small improvements such as going from off- RGC layer. Once the RGCs degenerate, signals can no longer be the ETDRS chart to on the-chart or an improvement by five to transmitted to the brain. 10 ETDRS letters can have a positive impact on functionality and Patients with LHON typically suffer vision loss over a period of quality of life. weeks and overwhelmingly both eyes are ultimately affected. 70 – GENSIGHT BIOLOGICS – 2017 Registration Document