RADIKAL THERAPEUTICS, INC. — Department of Health and Human Services SBIR Phase II: 300

Description

Radikal TherapeuticsRTXis developing a first in class cytoprotective small molecule agentRintended for the acute resuscitation of hemorrhagic shockHSthe leading cause of death in trauma patients worldwideNarrowly directed therapies for HS have fared poorly in the clinicsuggesting that the pathogenesis of clinical HS is complex and arguing that a broader multi faceted approach may be requiredTo this endRTX is testing the utility of combiningclassic approaches into a new single molecular entityRis a botha broad spectrum catalytic antioxidant that removes intracellular redox stressanda selective pharmacological activator of the ischemic preconditioningIPCresponseWe hypothesize that this combination will provide at least additive and potentially synergistic reduction in HS associated tissue injury and dysfunctionIn rats subjected to lethal hemorrhage and resuscitationRadministeredmin before resuscitation reduced the fall in mean arterial pressure byand attenuated the elevations in serum ASTcreatinineand pancreatic lipase byandrespectivelypltAimScale up Rsynthesis to multi kg level productionIn order to reduce manufacturing cost of goods and thereby strengthen our competitive positionRTX will carry out process research in order to minimize column chromatography steps in the manufacturing of Rand lessen manufacturing safety concerns related to the use of tetrazole catalysisAimEstablish the pharmacodynamics of Rin an ovine model of HSIn order to test the efficacy of Rin a large animal systemwe have selected a classic HS model in sheep created by the rapid withdrawal of blood to achieve a fixed level of hypotensive MAPWe will utilize anesthetized female Merino sheep subjected to fixed pressure hypotension formin via amin withdrawal of blood to an MAP ofmmHgmin prior to reperfusion with shed bloodsheep will receive Randmg kg IVA sham group will not undergo HS nor receive RIn addition to hemodynamic and respiratory measurementsterminal outcome endpoints ath will include markers of tissue injury and inflammationEach of the measures has been carefully selected so as to reveal a critical feature of organ injuryAimTransfer manufacturing technology to a GMP toll manufacturer to support Phaseclinical trialsIn order to prepare Rdrug product suitable for an IND submissionRTX will transfer its manufacturing methodology to a toll manufacturing firmRegis TechnologiesMorten GroveILwhere a multi kg GMP grade batch will be produced to support clinical investigationsAimPrepare IND documentation to support an FDA regulated study of the acute safetytolerancePKmetabolismand excretion profile of an IV bolus infusion of Rin healthy human volunteersIn order to position RTX to carry out clinical first in man safety and PK investigationswe will submit to the FDA a full IND application in support of the Phasesafety and pharmacokinetic studies