ALKEUS PHARMACEUTICALS, INC. — Department of Health and Human Services SBIR Phase II: NEI

Description

DESCRIPTION provided by applicant The long term goal of this work is to develop an oral drug for the prevention of age related macular degeneration AMD AMD is the leading cause of blindness in the United States with million Americans diagnosed or at risk of irreversibly losing vision and over million people who already have debilitating vision loss Currently there is no FDA approved preventative treatment for AMD One of the earliest changes in the retina that precede symptoms of AMD is the formation of toxic vitamin A dimers ALK is a chemically modified vitamin A in which hydrogen atoms have been replaced by deuterium atoms at carbon number Replacing the retinaandapos s vitamin A with ALK slows the formation of toxic vitamin A dimers To date ALK is the only small molecule designed to prevent the dimerization of vitamin A that has demonstrated functional preservation of visual function in animal models The central hypothesis of this work is that retarding vitamin A dimerization will slow the development and or progression of AMD The specific objective of this application is to further develop ALK and generate clinical data so that phase or confirmatory clinical trials can be designed to assess the extent to which inhibiting the dimerization of vitamin A slows the development and or progression of AMD We plan to achieve this goal by completing the following specific aims AIM Determine the feasibility of manufacturing ALK on a commercial scale This will be achieved by assessing the limitations of our current synthetic route to determine if it can be used to manufacture ALK on a commercial scale AIM Evaluate the effect size of ALK on the progression of geographic atrophy GA due to AMD This will be achieved by performing an month double masked placebo controlled study in subjects with geographic atrophy An oral drug to prevent the development and or worsening of AMD would have a tremendous impact on the quality of life of millions of Americans The dimerization of vitamin A has long been hypothesized to be a major contributor of the development of AMD However we lack clinically amiable strategies to safely prevent its dimerization This limits our ability to determine the extent to which dimerization participates in the progression of AMD ALK is a new compound that has been shown to prevent the dimerization of vitamin A without negatively affecting the visual cycle or depriving the photoreceptors of vitamin A and thus could possibly slow the progression of AMD PUBLIC HEALTH RELEVANCE The proposed research is relevant to overall public health because it seeks to evaluate the safety and efficacy of ALK a potential treatment for age related macular degeneration AMD the leading cause of blindness in the United States The prevalence of intermediate and advanced AMD increases steadily with age of the year old group of the year old group As the number of elderly is also increasing the number of people at risk of AMD will increase in by close to from todayandapos s numbers Despite constantly improving treatments for wet AMD also known as choroidal neovascularization CNV over of patients have the dry form of AMD and remain without any approved treatment today It is therefore imperative to develop safe and effective prophylactic treatments to prevent the development of the disease To date direct costs of healthcare due to AMD are estimated to be over $ billion per year AMD Alliance Report As such a treatment that could slow stop or prevent AMD could have significant public health impact and is also relevant to the NIHandapos s mission of developing fundamental and clinical knowledge to help and reduce the burdens of human disability