The NIH intramural research program has shifted all non-mission-critical laboratory operations to a maintenance phase in order to promote physical distancing and diminished transmission risk of COVID-19. Effective Monday, March 23, 2020, only mission-critical functions within NIH research laboratories will be supported.

Preclinical Working Group

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Charge

Standardize and share preclinical evaluation resources and methods and accelerate testing of candidate therapies and vaccines to support entry into clinical trials.

Objectives

Check mark indicates completion.

✓ Preclinical Resource Map

The working group has developed a master inventory of preclinical testing resources, including for nonhuman primates (NHPs), small animal models, and biosafety level 3/4 laboratories. To facilitate up-to-date information on this inventory of testing resources, the working group created a web-based form to use for collection of data on facilities that can carry out SARS-CoV-2 assays and animal models. The collection of this information is aiding in standardization of animal model testing efforts.

✓ National Strategy for NHP Preclinical Resources

The working group has helped develop a strategy for COVID-19-related NHP studies, in collaboration with the National Primate Research Centers, which aims to maximize the research value of scarce NHP resources that are needed to test vaccines and certain therapeutics during the pandemic. The strategy includes:

  • A staged approach for animal use aligned with immediate need
  • Defined points of interaction between an ACTIV expert panel and the National Primate Research Center directors
  • Recommended clear guidance for animal use and therapeutic testing, including the first ever master protocol for non-human primate research

✓ Pandemic Response Framework

  • The working group has developed “Pandemic Mode” operating procedures for accelerated preclinical agent development, including antivirals, immunomodulators, and anticoagulants. The approach to accelerated therapeutic development focuses on critical path activities to capture key aspects of efficacy and safety, as shown in the figure below. This approach is most easily associated with therapeutics that already have clinical data in another therapeutic area.

The standard “traditional” approach to drug development with an abbreviated approach suitable for pandemic conditions. In traditional drug development many experimental studies are done in series: as one study ends, the results are analyzed, and a decision is made whether to begin the next study. In pandemic mode, a therapeutic sponsor could carry out some of these studies in parallel, such that significant time is reduced. In addition, in pandemic mode, it is beneficial to begin the process with a therapy that has already been in humans, but for a different disease; repurposed compounds. These repurposed compounds offer the advantage of being known to be safe in humans. The risk of a repurposed compound is that it was initially made for a different disease and will probably not work as well as a compound made specifically for COVID-19. However, something that shows some efficacy could be the difference between life and death in the pandemic.

Preclinical Testing Network

The working group is in the process of creating a virtual testing network of biosafety level 3/4 laboratories for triaged drug candidates. The sites that will be needed are those that can carry out the essential experiments that have been described in the Pandemic Mode process and could rapidly deploy clinical testing in COVID-19 patients.

✓ Preclinical Prioritization

The working group has completed a prioritization framework, using the “Pandemic Mode” procedures described above as a basis, for evaluating and prioritizing preclinical compounds for further preclinical testing. The compounds that have been submitted to ACTIV for review are being evaluated for further preclinical development with the expectation that they may proceed into one of the ACTIV clinical master protocols (see Therapeutics Clinical Working Group).

✓ Preclinical Compound Survey

To assist in developing and prioritizing a complete inventory of potential candidates with different approaches to preventing or mitigating COVID-19 infection, an ACTIV COVID-19 Clinical & Preclinical Candidate Compound Survey has been established in conjunction with the Therapeutics Clinical Working Group. The survey collects detailed information from sponsors such as preclinical and clinical data on therapeutic candidates. Stakeholders throughout the biopharmaceutical, academic, scientific research, advocacy, and clinical practice communities are welcome to participate in the survey.

✓ Preclinical Data Sharing

The working group is creating a public database for sharing preclinical data using the NCATS OpenData Portal. Importantly, the portal will allow for both the comprehensive sharing of data as well as information on how the data were generated. This will facilitate interpretation and comparison of results from multiple experiments on multiple agents that could provide insight on SARS-CoV-2 and treatment approaches not apparent from a single study.

Animal model summaries and descriptions have been curated and released on the NCATS OpenData Portal. Additional information will continue to be added as it becomes available.

Members

Peter Adams, Ph.D.
Health Scientist, Influenza Division
Biomedical Advanced Research and Development Authority, HHS

Annaliesa Anderson, Ph.D., F.A.A.M.
Vice President and Chief Scientific Officer, Bacterial Vaccines
Pfizer

James Anderson, M.D., Ph.D.
Director, Division of Program Coordination, Planning, and Strategic Initiatives
Office of the Director, NIH

Ralph Baric, Ph.D.
Professor, Deptartment of Epidemiology and Deptartment of Microbiology and Immunology
University of North Carolina

Kara Carter, Ph.D.
Executive Vice President, Infectious Disease
Evotec

Marc Charette, Ph.D.
Program Director
Division of Cardiovascular Diseases
National Heart, Lung, and Blood Institute, NIH

Tomas Cihlar, Ph.D.
Vice President and Head of Virology
Gilead Sciences, Inc.

Christine Colvis, Ph.D. (Co-Chair)
Director, Drug Development Partnership Programs
National Center for Advancing Translational Sciences, NIH

Michael Diamond, M.D., Ph.D.
The Herbert S. Gasser Professor, Departments of Medicine, Molecular Microbiology, Pathology & Immunology
Washington University School of Medicine in St. Louis

Ken Duncan, Ph.D.
Deputy Director, Discovery – Therapeutics
Bill & Melinda Gates Foundation

Prabhavathi Fernandes, Ph.D.
SAC of GARDP, Chair; National Biodefense Science Board

Joshua Fessel, M.D., Ph.D.
Program Director, Lung Vascular Biology Program
Division of Lung Disease
National Heart, Lung, and Blood Institute, NIH

Clint Florence, Ph.D.
Program Officer, Research Resource Section, OBRR, DMID
National Institute of Allergy and Infectious Diseases, NIH

Greg Gatto, Ph.D.
Drug Development Regulatory Project Leader
RTI International

Jay Grobler, Ph.D.
Executive Director, Infectious Disease and Vaccines
Merck & Co., Inc.

Nancy Haigwood, Ph.D.
Director and Professor
Oregon National Primate Research Center
Oregon Health & Science University

Judith Hewitt, Ph.D.
Deputy Director, Office of Biodefense, Research Resources and Translational Research
National Institute of Allergy and Infectious Diseases, NIH

Samantha Jonson, M.P.S.
Special Assistant to the Director
National Center for Advancing Translational Sciences, NIH

Cat Lutz, Ph.D.
Senior Director, Mouse Repository & In Vivo Pharmacology, Rare and Orphan Disease Center
The Jackson Laboratory

Frank Nestle, M.D.
Global Head of Immunology Therapeutic Research Area and Chief Scientific Officer North America
Sanofi

Elizabeth Ottinger, Ph.D.
Senior Program Manager, Division of Preclinical Innovation
National Center for Advancing Translational Sciences, NIH

David Payne, Ph.D.
Vice President & Head, Medicine Opportunities Research Unit
GlaxoSmithKline

Louise Pitt, Ph.D.
Director, Center for Aerobiological Sciences
United States Army Medical Research Institute of Infectious Diseases

Antonello (Tony) Punturieri, M.D., Ph.D.
Program Director
Division of Lung Diseases
National Heart, Lung, and Blood Institute, NIH

Srinivas Rao, D.V.M., Ph.D.
Global Head, Translational In Vivo Models Global Research Platform
Sanofi

Jay Rappaport, Ph.D.
Professor of Microbiology and Immunology
Director and Chief Academic Officer
Tulane University National Primate Research Center

Frank Stegmeier, Ph.D.
Chief Scientific Officer
KSQ Therapeutics

John Young, Ph.D. (Co-Chair)
Global Head Infectious Diseases and Vice President
Roche

This page last reviewed on September 17, 2020