BUSINESS OVERVIEW 6 to six weeks after birth. When the retinas of such mice are AAV2 7 m8 has markedly improved expression in RGCs and other dissected post-mortem and connected to a multi-electrode array, retinal cells compared to AAV2 in both rodents and non-human an electrical response to light is not detected. Using the same primates. method with the retinas from rd1 mice that have received an IVT Optoelectronic External Wearable Medical Device: The Biomimetic injection of GS030, an electrical response to light is produced and Goggles detected with the multi-electrode array and this response is a function of light intensity. The natural range of light sensitivity of human photoreceptor cells is broader than that of channelrhodopsins. To achieve adequate A New Generation of Channelrhodopsin-Based Gene Therapy stimulation of transduced RGCs, we combine our gene therapy- An Optimized Optogenetic Protein based treatment with an external wearable medical device, We have conducted proof-of-concept studies with which allows the amplification of the image at specific optimal channelrhodopsin-2, or ChR2, which when introduced into RGCs, wavelength of the selected opsin. has proven to restore vision in a murine model of RP. However, We are developing an external wearable medical device composed activation of ChR2 requires high-intensity blue light at 470 nm of: wavelength which has been shown to be toxic for the retina and is • a visual interface integrating an asynchronous time-based not practical for clinical use. image sensor, or ATIS (also cal led a neuromorphic video We have therefore developed a novel channelrhodopsin protein, camera), and a digital micromirror array, or DMD, driven by a known as ChrimsonR, which responds to light at near-red microprocessor, that convey the visual information signal and wavelength, where light scattering decreases and absorption light to the macula; and by endogenous chromophores is reduced, meaning that long- • a pocket processor connected to an optoelectronic stimulation term safety should be significantly improved compared to other device that processes the visual information and controls a channelrhodopsins. light source in order to encode and amplify corresponding light signals at a specific wavelength of 550-640 nm. A Powerful Gene Delivery Vector Since RGCs are the cel ls closest to the vitreo-retinal surface, Software wil l be provided to medical centers that wil l al low they are amenable to AAV infection with IVT injection, a major the tuning and definition of parameters to optimize the patient advantage from a surgical standpoint given the relative ease of response. administration. Our AAV is an AAV2 modified in its capsid with The figure set forth below presents the components of the an inserted 7 m8 sequence. Experiments have demonstrated that external wearable medical device: External Wearable Medical Device Components 80 – GENSIGHT BIOLOGICS – 2017 Registration Document