A novel glutaminase-free mammalian asparaginase with minimized immunogenicity to enable expanded use in cancer therapy

PROJECT SUMMARY Enzyme by DesignIncEbDis developing a safer version of L asparaginase that can be used routinely in the treatment of adult ALL patients whose hypersensitivity to todayandapos s bacterial L asparaginases deprives them from this efficacious therapyEbDandapos s L asparaginase is novel due to its mammalianguinea pigorigin and its lack of L glutaminase co activityThe need for better therapeutics for adult ALL is clearthe cure rate is andltandof the deaths from ALL involve adultsIn the USthe standard of care is the PEGylated Ecoli enzymeOncasparPatients who develop complications with thisst line agent are moved to the Lasparaginase from EchrysanthemiErwinazeIssues that plague both drugs are their highly immunogenic naturedue to being of bacterial originthough PEGylation decreases but not eliminates this challengeand their L glutaminase co activityThe latter is source of many of the toxicities observed in patientssuch as hepatotoxicitypancreatitiscoagulation abnormalities and neurotoxicityThe manufacturers of both of these approved L asparaginases are currently developing newer versionsHoweverthose newer versions will still have the same toxicity issues since the underlying causestheir bacterial origin and L glutaminase co activityremain in the products in developmentIn contrastEbDandapos s mammalian enzyme that is devoid of the Lglutaminase co activity promises superiority by having reduced toxicityIn Aimof the work supported by the STTR grantEbD is finalizing the site specific PEGylation strategy for GpA in order to achieve full masking of the enzyme by the PEGAimwill identify the PEGylated variants with the best pharmacokineticPKpropertieswhich will proceed to Aimwhere it will be benchmarked against OncasparOur data predicts that EbDandapos s PEGylated GpA will exhibit significantly reduced toxicity compared to the currentst line treatmentSuch a finding will provide the rationale for advancement to a STTR Phase IIwhere we will perform the pre clinical studies required for an IND applicationOur proposed I CORPs team will include DrArnon Laviefounder andampCEOMrStephen MoralesMBAindustry expertand DrHien Anh NguyenPI of STTR grantfounder andampCSOAll three I CORPs team members are committed to the time and effort requirements of the programEbD has already conducted background research into the competitive landscape of the technology and identified the most commercially viable indication for the launch of the productDuring the execution of the ICORPS programwe plan to conduct an in depth analysis with health care providers and payers to prepare to answer some of the key questions that angel venture investors may haveThe team expects to modify refine the overall commercialization strategy based on the knowledge gained during the I CORPS program PROJECT NARRATIVE Enzyme by DesignIncEbDis a University of Illinois at Chicago spin off developing novel biologics for the treatment of diverse cancersThe most advanced biologic drug candidate in EbDandapos s pipeline is an engineered variant of a mammalian L asparaginaseThe team expects to modify refine the overall commercialization strategy of this biologic based on the knowledge gained during the I CORPS program