Engineering Cell Therapies to Treat Inflammatory Bowel Disease (IBD)

ABSTRACT Inflammatory Bowel DiseaseIBDcomprises a collection of chronic autoimmune disorders that afflicts an estimatedmillion Americansand incidences are risingIn IBD patientsdysfunction of the immune system affects the gastrointestinalGItract causing diarrheaabdominal pain and rectal bleedingwhile the list of potential extraintestinal complications includes osteoporosiskidney stonesjoint pain and various soft tissue ailmentsThe complications can be seriousand more thaninIDB patients will require surgery within five years of diagnosisMoreoverdepression and elevated stress levels can contribute to disease flaresThere are no cures for IBDbut several categories of pharmacological treatment are availablemost of which cause terrible side effectsare not very effectiveor bothIn this SBIR projectSenti Biosciences will deploy its proprietary cell engineering technologies to create a safer and more efficacious IBD therapyThese technologies are engineered to accelerate the speed and precision at of genetic control circuits implemented into living cellsGene circuit technologies can turn mammalian cells into adaptive medicines that sense disease states and respond by producing combinatorial therapiesthus providing the right amount of treatment at the right place and the right timeBy enabling unprecedented control over cellular functionSenti s cell circuit technology is able to address diseases that are difficult to treat with existing drugsmaking it well suited for the control of immune mediated diseasesMajor challenges for immunotherapies are the need for to keep effects localizedspatially and temporallyin order to reduce often serious systemic side effectsAndbecause the immune system is extremely complexmaximizing treatment efficiency demands the ability to target multiple systemic componentsCell circuits are a natural fit for immune related diseases because they address all of these challengesThe feasibility of Senti s technology has been established in animal models of several disorders including IBDThis Phase I proposal will generate proof of concept data for a novel technology in which an engineered genetic circuit will enable mesenchymal stem cellsMSCsto sense the activation of a nuclear transcription factor that plays a key role in autoimmune disorders and responds by delivering anti inflammatory therapeuticsAimAfter the antiinflammatory activity of the circuits are confirmed in vitroAimproof of concept data will be collected in a mouse model of an autoimmune diseaseAimThese results will constitute the requisite first step towards the completion of the preclinical pharmacokineticssafety and efficacy studies enabling an Investigational New DrugINDapplication with the FDAThe market is ripe for the emergence of a new class of smart therapeuticssignaled by the converging clinical acceptance of celland gene based therapiesexponential improvements in synthetic biology technologiesand growing understanding of immuno biologyThe treatment being developed under this proposal will ultimately help chip away at the financial burden of IBDwhich costs Americans an estimated $billion each year and is expected to keep doubling every decade NARRATIVE Inflammatory Bowel DiseaseIBDis a collection of chronic autoimmune disorders of the gastrointestinalGItract that cause diarrheaabdominal painand a list of potential complications that includes osteoporosiskidney stonesjoint pain and various soft tissue ailmentsSenti Biosciences will deploy its proprietary cell engineering technologies to create a safer and more efficacious IBD therapyBy enabling unprecedented control over cellular functionSenti s cell circuit technology is able to address diseases that are difficult to treat with existing drugsmaking it well suited for the control of immune mediated diseases