Targeted lympho-ablation as an alternative to HSCT to cure T1D

With insulin being the only approved treatment of Typediabetes mellitusT DMthere is a very large unmet medical need for a definitive cure for pediatric and adult patientsIncrease in obesityunhealthy dietand physical inactivity are driving the prevalence of diabetes among all agesIn the U Sdiabetes currently affectsof the population of all agesand it is the seventh leading cause of deathwith an estimated cost of $billion every year to the healthcare systemThe medical community has recognized diabetes as an autoimmune disease and proposed different immunotherapeutic approaches to cure itHoweveronly hematopoietic stem cell transplantationHSCTafter reset of the immune system with toxic chemotherapyhas so far shown temporary restoration of insulin independenceThe mission of AVM Biotechnology is to develop a disruptive solution for diabetes based on a novel regimen for immunologic reset that safely removes the complete autoimmune pathophysiologic substrates from diabetes patients and can be safely re administered in case of relapseThe goal of this project is to establish proof of concept data for AVMa novel proprietary oral formulation for the treatment of diabetesIn our early stage preclinical validationwe verified that a single oral dose of AVMinduces complete non myeloablative lymphodepletion without side effectsIn this Phase I applicationwe have two specific aimsDetermine the optimal doses of AVMfor immunologic reset in the pre clinical Non Obese DiabeticNODmouse modelAssess the therapeutic effect AVMin NOD mice and compare it with the one of other standard immunosuppressive medicationsWe expect to identify one concentration of AVMthat is able to safely remove andgtof autoimmune pathophysiologic substrates withinhours from its oral administration in NOD miceAimand that AVMtreated mice will achieve normal urine glucose levels withindays from dosing preventing insulitis in more thanof the casesAimThe successful conclusion of the proposed phase I studies will lay a solid foundation for IND enabling PK and PD studies in the SBIR phase II period that will lead to clinical trials to evaluate the effects of this novel therapeutic lead in recent onset juvenile type I diabetes patients Novel safe immunomodulation strategies to arrest diabetes progression are a global necessity to combat the rising incidence of diabetes to the epidemic proportionThis project proposes the feasibility assessment of an innovative best in class lymphodepleting regimen for diabetes that removes the associated autoimmune pathophysiologic substratesThe project is expected to introduce a novel lead therapeutic for diabetes and hopefully other autoimmune diseases