Fetal Hemoglobin Induction by EdX 17 to Treat Sickle Cell Disease

DESCRIPTION provided by applicant The CDC and WHO have declared Sickle Cell Disease SCD a public health priority In the U S alone some patients suffer with SCD with annual healthcare costs estimated at $ billion SCD patients have a mutant form of hemoglobin Hb that can change the shape of their red blood cells RBCs and cause the cells to clump together and stick to vessel walls resulting in blocked blood flow that causes extreme pain heightened stroke risk and organ damage The prognosis for SCD patients is grim Pain crises and other complications require frequent ER visits and hospitalizations Current SCD healthcare options primarily treat complications via antibiotics psychological support pain management intravenous fluids blood transfusions palliative drugs and surgery However fetal hemoglobin HbF which normally drops soon after birth shows promise as a therapeutic target Numerous studies indicate that higher HbF levels result in decreased SCD complications Epidemiological and lab studies have shown that reconstitution of HbF levels to is sufficient to ameliorate SCD symptoms Yet the only available FDA approved pharmaceutical HbF inducer hydroxyurea does not achieve the HbF levels required to prevent symptoms and is associated with a number of side effects Achieving a consistent level of at least HbF in patients is expected to enhance patient quality of life by alleviating symptoms eliminating pain crises and increasing lifespan The goal of this Phase I SBIR project is thus to demonstrate that our candidate drug EdX can reconstitute HbF to levels e safely without significant side effects Preliminary work done by the interdisciplinary EpimedX team demonstrates that EdX can produce HbF in mice and supports this approach Section For this Phase I feasibility project EpimedX will pursue three Aims establish a dose response relationship between EdX levels and HbF expression in vitro determine the time dependence of HbF production with EdX treatment in vitro and establish the feasibility of achieving e HbF expression with EdX treatment in vivo This project will provide data to address the key research question Can we demonstrate that daily EdX treatment enhances endogenous production of HbF to therapeutic levels for SCD treatment with low toxicity within days in vivo Phase I success will lead to a larger Phase II project focused on FDA required toxicology studies in preparation for an IND and human clinical trials in Phase III The Randamp D team for this project includes PI Dr Robert Broyles EpimedX founder CSO and President of the Sickle Cell Cure Foundation a year pioneer in sickle cell research co founder Dr Robert Floyd COO who helped found and manage two other biotech companies Centaur Pharmaceuticals and Otologic Pharmaceutics and a team of seasoned technical experts and biotech investors Development commercialization of this novel therapeutic is expected to ameliorate SCD symptoms decreasing pain and morbidity increasing lifespan greatly improving patient quality of life and significantly reducing treatment costs PUBLIC HEALTH RELEVANCE Sickle Cell Disease SCD affects patients in the U S and millions worldwide particularly those with African Spanish Mediterranean and Indian ancestry and it costs billions to treat and causes a lifetime of health problems including acute pain severe anemia stroke infections and vascular blockages that can lead to widespread organ damage and death Current treatments for SCD patients short of relatively rare and very expensive bone marrow transplants are lacking in efficacy and safety although research has shown that raising fetal hemoglobin HbF levels to of relative hemoglobin content has the potential to ameliorate SCD symptoms Thus the goal of this EpimedX Phase I SBIR project is to demonstrate the feasibility of a novel therapeutic candidate for inducing high HbF levels that will provide SCD patients significantly improved treatment and quality of life while greatly reducing healthcare costs