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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: $2,907,798.00
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
United States
DUNS: 945753622
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 AARON MCCABE
 (651) 917-4060
 amccabe@minnetronix.com
Business Contact
 KERA VANT
Phone: (612) 750-1030
Email: kwest@minnetronix.com
Research Institution
 DUKE UNIVERSITY
 
2200 W MAIN ST, SUITE 820
DURHAM, NC 27705-4673
United States

 Nonprofit college or university
Abstract

ABSTRACT
When Cryptococcus is manifested as cryptococcal meningitis (CM), it creates a large burden of mortality and
morbidity to the patient and is very difficult for the clinician to treat. There are now an estimated 2600-7800 US
cases and 400,000 cases of CM worldwide annually, with estimated mortality of 15-50% per year. CM is caused
when Cryptococcus neoformans, a basidiomycete fungal pathogen, invades the central nervous system (CNS).
It is seen most commonly in immunocompromised patients, such as those with HIV or post organ-transplant.
Current treatments include anti-fungal agents that have limited effectiveness in penetrating the CNS and various
systemic side effects. Early reduction in pathogen burden is the best predictor of reduced morbidity and mortality.
Minnetronix, a medical device development and manufacturing company, proposes this Phase II STTR in
collaboration with experts from the Infectious Diseases and Neurosurgery Departments at Duke University.
Phase I demonstrated the dramatic results of Neurapheresis, a cerebrospinal fluid (CSF) processing
platform, with the ability for targeted delivery of Amphotericin B (AMB) along with rapid clearance of organisms
both in vitro and in vivo, in a rabbit CM model. Phase II will optimize and validate a tailored human system
to deliver the first-ever fungicidal platform. It will allow for delivery and circulation of AMB intrathecally,
control of drug concentration and toxicity, rapid removal of C. neoformans and downstream mediators from the
CSF, sampling of CSF to follow CFU reduction, and drainage of CSF to normalize ICP. Specific Aim 1 will
understand and optimize the delivery, circulation, and dosing of AMB via the Neurapheresis system in a
cranial/spinal model and develop a PK/PD model. Specific Aim 2 will demonstrate the safety and efficacy of
Neurapheresis filtration and AMB circulation in a pivotal rabbit CM model study. Specific Aim 3 will complete
development of the validated Neurapheresis system for intrathecal AMB delivery and targeted removal of
organism from the CSF.
Neurapheresis is an innovative, new therapeutic option that provides direct access to the CSF and allows for
delivery and active circulation of intrathecal drug, combined with targeted pathogen removal through filtering.
This treatment is complementary and does not replace standard interventions with systemic, intravenous
antifungal regimens. Successful completion of this Phase II STTR will provide Minnetronix with the ability to
complete development of a GLP-quality system for the treatment of CM. Concurrent regulatory and clinical study
planning will be conducted to prepare for an investigational device exemption (IDE) application at the end of
Phase II. The 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 STTR, Minnetronix plans to validate an innovative, new therapeutic platform for treating
devastating central nervous system (CNS) infections. Cryptococcal meningitis (CM) occurs when a fungal
pathogen (C. neoformans) invades the CNS and is seen most commonly in immunocompromised patients,
including HIV or post organ-transplant. CM is a deadly, infectious neurological disease that affects up to 8,000
people annually in the US, and 400,000 people worldwide, resulting in a 15-50% mortality rate. This 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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