Validation of a Novel Fungicidal Approach for Cryptococcal Meningitis

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R42AI120751-02A1
Agency Tracking Number: R42AI120751
Amount: $1,968,647.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA17-303
Timeline
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-06-01
Award End Date (Contract End Date): 2021-05-31
Small Business Information
1635 ENERGY PARK DR, Saint Paul, MN, 55108-2703
DUNS: 945753622
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 AARON MCCABE
 (651) 917-4060
 amccabe@minnetronix.com
Business Contact
 KERA VANT
Phone: (651) 917-4060
Email: kwest@minnetronix.com
Research Institution
 DUKE UNIVERSITY
 2200 W MAIN ST, SUITE 820
DURHAM, NC, 27705-4673
 Nonprofit college or university
Abstract
ABSTRACT When Cryptococcus is manifested as cryptococcal meningitisCMit creates a large burden of mortality and morbidity to the patient and is very difficult for the clinician to treatThere are now an estimatedUS cases andcases of CM worldwide annuallywith estimated mortality ofper yearCM is caused when Cryptococcus neoformansa basidiomycete fungal pathogeninvades the central nervous systemCNSIt is seen most commonly in immunocompromised patientssuch as those with HIV or post organ transplantCurrent treatments include anti fungal agents that have limited effectiveness in penetrating the CNS and various systemic side effectsEarly reduction in pathogen burden is the best predictor of reduced morbidity and mortalityMinnetronixa medical device development and manufacturing companyproposes this Phase II STTR in collaboration with experts from the Infectious Diseases and Neurosurgery Departments at Duke UniversityPhase I demonstrated the dramatic results of Neurapheresisa cerebrospinal fluidCSFprocessing platformwith the ability for targeted delivery of Amphotericin BAMBalong with rapid clearance of organisms both in vitro and in vivoin a rabbit CM modelPhase II will optimize and validate a tailored human system to deliver the first ever fungicidal platformIt will allow for delivery and circulation of AMB intrathecallycontrol of drug concentration and toxicityrapid removal of Cneoformans and downstream mediators from the CSFsampling of CSF to follow CFU reductionand drainage of CSF to normalize ICPSpecific Aimwill understand and optimize the deliverycirculationand dosing of AMB via the Neurapheresis system in a cranial spinal model and develop a PK PD modelSpecific Aimwill demonstrate the safety and efficacy of Neurapheresis filtration and AMB circulation in a pivotal rabbit CM model studySpecific Aimwill complete development of the validated Neurapheresis system for intrathecal AMB delivery and targeted removal of organism from the CSFNeurapheresis is an innovativenew therapeutic option that provides direct access to the CSF and allows for delivery and active circulation of intrathecal drugcombined with targeted pathogen removal through filteringThis treatment is complementary and does not replace standard interventions with systemicintravenous antifungal regimensSuccessful completion of this Phase II STTR will provide Minnetronix with the ability to complete development of a GLP quality system for the treatment of CMConcurrent regulatory and clinical study planning will be conducted to prepare for an investigational device exemptionIDEapplication at the end of Phase IIThe long term goal of the project is to develop a novel fungicidal approach that rapidly eliminates the CSF fungal burden and translates to reduced morbidity and mortality for CM patients worldwide NARRATIVE In this Phase II STTRMinnetronix plans to validate an innovativenew therapeutic platform for treating devastating central nervous systemCNSinfectionsCryptococcal meningitisCMoccurs when a fungal pathogenCneoformansinvades the CNS and is seen most commonly in immunocompromised patientsincluding HIV or post organ transplantCM is a deadlyinfectious neurological disease that affects up topeople annually in the USandpeople worldwideresulting in amortality rateThis project will save lives by providing the first ever fungicidal platform capable of safely targeting and rapidly eliminating the CSF fungal burden

* Information listed above is at the time of submission. *

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