Pharmaceutical-style Cores

Pharmacology and Mycology Core
PIs: Vidmantas Petraitis, M.D. and Milena Kordalewska, Ph.D.

The CETR Pharmacology and Mycology (Pharm/Myco) Dual Core was established to provide comprehensive in vitro and in vivo assessments of antifungal efficacy and pharmacologic suitability of novel compounds undergoing advanced lead optimization for selection of preclinical development candidates (PDCs) and entry into IND enabling and de-risking studies. The Core provides timely assessments of key drug attributes including pharmacokinetics (PK), pharmacodynamics (PD), absorption, distribution, metabolism, and excretion (ADME), tiered toxicology, other key parameters, as well as microbiologic support to facilitate metric-based ‘go, no-go’ assessments of compounds for PDC selection and IND-enabling studies. The Pharm/Myco Core functions as an integrated component of the overall drug accelerator, which involves close interactions with all Projects and Cores.
Vidmantas.Petraitis@hmh-cdi.org
Matthew.Zimmerman@hmh-cdi.org

Medicinal Chemistry Core
PIs: James Merritt, Ph.D. and Joel Freundich, Ph.D.

The Medicinal Chemistry Core (MCC) will provide synthetic and medicinal chemistry, cheminformatics, and structure-based design resources complementary to those existing within the respective project teams. It will integrate tightly with the other Cores. The MCC resource will distinguish itself by relying on extensive pharmaceutical medicinal chemistry experience in antifungals melded with academic strengths in drug discovery and development. Critically, the MCC staff leadership has demonstrated an ability to produce drug candidates by evolving small molecules to address a wide range of problems encountered during the lead optimization process. Overall, the spectrum and depth of the MCC staff's industrial and academic background will prove critical to their ability to optimize leads within the individual projects to molecules with significant potential for positively impacting the antifungal clinical landscape to address the global health crisis.

James.Merritt@hmh-cdi.org
freundjs@njms.rutgers.edu

Animal Models Core 
PIs: Andrew Nelson, DVM and Barry Krieswirth, Ph.D.

Evaluating the efficacy of candidate compounds against drug resistant fungal pathogens in robust and reproducible animal models of infection is critical to advancing these compounds towards preclinical candidacy. To contribute to the rapid development of such medical countermeasures, the Animal Model Core will provide clinically relevant systemic, pulmonary, and urinary tract fungal infection models. Specifically, the Aims of the core are to 1) assess lead compounds against high threat fungal pathogens including Candida spp. and A. fumigatus in small animal infection models and 2) provide state of the art analytical services on host response and fungal bio-burden distribution to assess and quantify lead compound treatment efficacy. The Core leverages the AAALAC accredited, 40,000 sq ft Center for Discovery and Innovation Research Animal Facility (CDI RAF), which has dedicated space for the study of BSL2 pathogens.

Andrewm.Nelson@hmh-cdi.org
Barry.Kreiswirth@hmh-cdi.org

Administrative Core
PI: David Perlin, Ph.D.

The Administrative Core will play a crucial role in optimizing research operations and resource allocation through a lean framework that closely integrates Project Leaders and Core Directors. This centralized organization will facilitate seamless communication across multiple entities and manage all operational aspects of the Projects and Cores, ensuring efficiency and cohesion. We will provide a comprehensive support system for grant management and commercialization efforts. This includes solutions for secure data sharing and intellectual property protection, administrative systems for reporting and fiscal management, and communication protocols for collaboration and dissemination of secure and public data, as well as project reviews and updates. We will also provide support for product development, and regulatory compliance, ensuring successful initiatives. The administrative structure ensures maximal efficiency in project execution by streamlining operations and resource allocation. A robust plan led by experienced drug development experts and a world-class Scientific Advisory Board (SAB) helps guide drug candidate development and evaluate progression metrics. Pharma-style decision making with clear 'go, no-go' criteria will be used to expedite and prioritize promising candidates. External regulatory support aids in navigating requirements for pre-IND, IND-enabling and 510(k) submissions. These efforts strengthen the administrative core of the CETR-based accelerator. By leveraging the expertise of academic and industry partners and establishing a robust administrative infrastructure, we aim to combat drug-resistant fungal pathogens. This comprehensive administrative approach embodies our commitment to advancing research and translating discoveries into impactful solutions for patients.

Madhuvika Murugan, Ph.D.
Madhuvika.Murugan@hmh-cdi.org