A Device to Inhibit Heterotopic Ossification

PROJECT SUMMARY ABSTRACT Heterotopic ossificationHOis defined by bone formation in soft tissue and is a frequent debilitating complication of surgical procedures required by musculoskeletal and neurological injuriesUnfortunatelyit is not possible to accurately predict which patients will develop symptomatic HOwhich is characterized by pain and impaired functionThe current prophylactic standard of caresystemic NSAID treatmentis effective in reducing HO mineralizationbut has also has been associated with gastrointestinal bleedingincreased cardiovascular eventsand impaired fracture healingDue to this challenging risk reward ratioHO often remains untreated until symptomaticOnce symptomaticthe only treatment option is surgical excisionwhich is costly and has a high rate of reoccurrenceGiven the direct and indirect costs associated with HOit is not surprising that the associated health care burden exceeds $ B per year in the US aloneIn this contextIn Situ Therapeutic SolutionsIncISTheraSolhas developed novel IP demonstrating that distributedintramuscularIMtargeting of the neuromuscular inhibitor botulinum toxin ABTxAmitigates HO formationOur IP also suggests that inhibition of HO can be achieved using BTxA dosing that is approximatelyless than is currently used as an adjunct in orthopaedic procedures and that a prototype template enables superior tissue coverage compared to freehand injectionThusthe goal of ISTheraSol is to develop and commercialize disposable intraoperative devices that will focally inhibit HO for a variety of indicationsIn this proof of concept Phase I STTRwe will designfabricateand validate a prototype delivery device that will demonstrate superior tissue coverage of BTxA within a targeted soft tissue volume vs freehand injectionSAWe will then demonstrate that a single intraoperative application of BTxA using our prototype device will significantly reduce trauma induced HO in a pre clinical rabbit model that mimics human HO following acetabular fractureSAWe will also demonstrate that our proprietary technology will achieve significantly greater efficacy vs indomethacinan NSAID representing the current standard of careWe will then submit a Phase II STTR proposal to optimize dosing parametersminimizing dose while retaining efficacydemonstrate that the dose required for HO inhibition is gender independentand confirm an enhanced safety efficacy profile vs indomethacinIn collaboration with our clinical Co InvestigatorISTheraSol leadership has selected acetabular fracture as our first treatment indication as its low frequencyyrand high incidence of HOandgtwill support an FDA Orphan Drug ApplicationImportantlythis filing strategy will lower development costsreduce regulatory burdenand accelerate time to marketAs we anticipate that the optimal dose distribution will be independent of indicationwe believe that our IP can be rapidly leveraged to commercialize products to treat additional HO indications regardless of causal pathology Project Narrative Heterotopic ossificationHOis the formation of bone in soft tissue where bone normally does not exist and is a frequentdebilitatingand costly complication of musculoskeletal and or neurologic traumaISTheraSol has developed IP demonstrating that very small doses of BTxAwhen distributed within a tissue volumewill inhibit formation of HOThis Phase I STTR will establish proof of concept for our IP by developing a prototype device that will demonstrate superior efficacy to inhibit trauma induced HO compared to the current standard of caresystemic NSAIDs