Periodic Reporting for period 2 - Soraprazan (Soraprazan - a new regenerative therapy for Stargardt's disease) Reporting period: 2019-12-01 to 2021-11-30 Summary of the context and overall objectives of the project A consortium of eight partners prepared and started a phase 2, proof of concept, clinical study with Remofuscin in adult patients with Stargardt’s disease. Active ingredient of the drug is Soraprazan, which gave the name to this EU financed project. For the clinical study, the consortium has meanwhile used the acronym STARTT (STArgardt Remofuscin Treatment Trial).Participating partners include six clinical sites (Eberhard Karls Universität Tübingen, Radboud University Medical Center (Nijmegen), Ospedale San Raffaele (Milan), Leiden University Medical Center, University of Southampton, and Universitätsklinikum Bonn) supported by the international clinical research organization Smerud Medical Research (Oslo), and Katairo assuming the role of the sponsor by regulatory definition. Lipofuscin is a fluorescent waste material accumulated in the retinal pigment epithelium (RPE) which is a mono cell layer supporting the photoreceptors of the retina. Accumulation of lipofuscin is associated with various negative effects to the RPE and photoreceptors, and may ultimately lead to retinal degeneration and blindnessExcessive lipofuscin accumulation in Stargardt patients is caused by a genetic defect and is considered to play a major role in the disease process. Treatment with Soraprazan, the active ingredient of Remofuscin, has been shown to result in removal of lipofuscin of the RPE in various animal and cell models. The clinical trial performed under the EU funded project included 87 adult patients with Stargardt disease matching the inclusion criteria. All enrolled subjects were adults with genetically confirmed Stargardt disease with the onset of disease before the age of 45 years. The presence of lipofuscin accumulation above a certain level was assessed by autofluorescence measurement. Once enrolled, subjects were randomised so that 2 out of every 3 subjects received soraprazan. The rest received placebo. Primary endpoint of the study is the level of autofluorescence at months 12 compared to baseline. Secondary endpoints include functional assessments (visual acuity, retinal sensitivity) and morphological assessments from OCT imaging.Following the advice received from regulatory and clinical experts, the clinical study is being continued for a second year of treatment via amendment of the clinical protocol. The continuation of the trial was offered to all patients that participated in the first part. The double blinded and randomized regimen of the trial was maintained. 67 of 87 patients are participating in the extended part of the trial. This part is being funded from private sources. As a consequence of this trial extension, final results for the first part and the second part will not be available before Q4 2022.More information about the trial is available in the clinical trials register at www.clinicaltrialsregister.eu/ctr-search/trial/2018-001496-20/NL (EudraCT Number 2018-001496-20). Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The work performed so far includes- the manufacture and control of the pharmaceutical form (tablets) under GMP- the drafting of the clinical trial protocol- the seeking of regulatory advice for the draft protocol- the submission of the study for regulatory approval in the four countries of the clinical study- the initiation and performance of the study in four countries and six trial sites according to internationally accepted standards (GCP)- the information of patients via press releases, information of patient organizations, and setup and supply of newsletters or responding to individual patient requests- the information of key opinion leaders and the pharmaceutical industry in ophthalmic congresses by direct contact and publications- the contact, information and negotiation with interested financing and industry partners- the amendment of the clinical trial protocol to extend the study for an additional year- getting consent from 67 ( or the total of 87 patients completing the study’s first year ) for a continuation of the trial for an additional year Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) There is currently no approved treatment for patients with Stargardt disease. The results of the ongoing clinical study, if successful, may demonstrate the possibility of removal of lipofuscin as a key pathogenic component of Stargardt disease, and possibly in other ocular diseases e.g. age-related macular degeneration (AMD). Further, functional readout may demonstrate the potential of the drug to slow or stop disease progression or even improve the disease status of patients, meaning a reduction in vision impairment / blindness rates.