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Fnl Operations and Additional Updates Frederick National Laboratory Operations and Additional Updates Ethan Dmitrovsky, M.D. President, Leidos Biomedical Research and Laboratory Laboratory Director, Frederick National Laboratory for Cancer Research DEPARTMENT OF HEALTH AND HUMAN SERVICES • National Institutes of Health • National Cancer Institute Frederick National Laboratory is a Federally Funded Research and Development Center operated by Leidos Biomedical Research, Inc., for the National Cancer Institute Session Objectives • Review the Frederick National Laboratory rapid response to the pandemic. This is a case study for a Federally Funded Research and Development Center. • Show that this pivot did not prevent decisive quantitative or discovery science, translational research, and clinical trials. • Cite NCI and NIAID programs with major recent progress. • Answer your questions. Federally Funded Research and Development Center Operations Federally Funded Research and Development Center Contract Task Order Portfolio: • 5 Operational Task Orders - Benefits of services are recurring with annual funded appropriations. • NCI Task Order, 3 NIAID Task Orders, 1 Lease Task Order • 98 are Non-operational Task Orders • 38 are in Clinical Group • 47 are in Scientific Group • 13 are Facility or Infrastructure Refurbishments Task Orders • Extensive outreach to the broader research community is through subcontracting. Frederick National Laboratory Pivot with National Cancer Institute to Combat COVID-19 COVID-19 Publications ●Liu, G., et al. Cell Sys., In press, 2020. Pivot to ●Beigel, J.H. et al. New Engl. J. COVID-19 Med., 2020 ●Hicks, J., et al. medRxiv Response doi: https://doi.org/10.1101/2020.06 .22.20137695 Identifying genetic Testing and Clinical Trials to ●Klumpp-Thomas C., et al. determinants of validating Combat COVID-19 ► Identifying medRxivdoi: https://doi.org/10.110 SARS CoV 2 serologic assays Small molecule 1/2020.05.21.20109280. susceptibility and Antibody based ●Klumpp-Thomas C, et al, Nat. for SARS CoV 2 ► Testing Commun. 2021 outcome ► ●Kalil AC, et al, New Engl J. Med., Screening 2020 Recent Major Publications Beyond Cancer Genomics Serology Laboratory of Vaccine, Clinical Monitoring COVID-19 Research Laboratory Immunity, and Cancer Program Research Program ●Petersdorf, E.W., et al, J. Clin. Oncol., 2020 Protein Production ●Li, Z., et al, Nat Struc. and Molec. Pivot and sustain Pivot and sustain Biol., 2020 ●Pérez-Guijarro E, et al. Nat Identify space Med, 2020 ●Kriemer, A.R., et al. J Natl Implement flexible Cancer Inst, 2020. infrastructure and network ●Yan, W., et al. Cell Reports. In press. assess cyber security needs ●Liu J, et al. Cell, 2020. Does Recognition of Specific SARS CoV2 Peptides Result in Protection? Dr. Mary Carrington Dr. Stephen Chanock Specimens received: N ~2200 • Massachusetts General Hospital • Brigham and Women’s Hospital • University of California-San Francisco • Emory University Specimens genotyped: N ~1607 HLA loci are highly polymorphic in humans and some allotypes of these genes appear better able to present peptides that elicit a protective immune response. SARS-CoV-2 Serology Protein Production for Collaborators Dr. Dominic Esposito ●Produce >2 g spike, RBD (binds to ACE2 receptor) and nucleocapsid proteins. Dr. Kaitlyn Sadtler ●Improved production yields for spike and RBD proteins. ●Published in Nat. Comm. and elsewhere on production and assay optimization. ●Proteins utilized for serology applications by multiple collaborators. Trans-NIH nationwide serosurvey for Protein production for NCI SeroNet Rapid response for external CoV-2 antibody detection serology efforts serology needs from collaborators • 10,000 volunteers provided blood • Initial protein production used for • Proteins given to NIAID for critical samples across the United States. internal development and Moderna vaccine trial serology. validation of serology assays. • Proteins used for high sensitivity • Proteins given to Mali scientists ELISA-based serology study. • Proteins provided to SeroNet for serosurvey projects. collaborators at NIAID and NIST • Manuscript submitted. • Proteins to USUHS for multiplex for assay validation. Luminex serology assays. • Follow-up longitudinal studies • Proteins shared with extramural approved by NCI. • Serosurvey collaborations with members of the SeroNet program. NHTSA, NCATS and DoD. Serological Sciences Network (SeroNet): A View from Within ● Designed to be a highly interactive network. Dr. Dinah Singer U54 Dr. Jim Cherry Dr. Ligia Pinto CBC U01 Dr. Len Freedman ● Sharing of data and resources within SeroNet. Dr. Sara Hook Dr. Doug Lowy CBC U54 Dr. Ned Sharpless ● Open access publication. and many others ● Data and resources made publicly available. U54 Network Coordinating U01 Center U01 CBC Frederick National Laboratory Serology Laboratory FNL U01 ●Implement and qualify SARS-CoV-2 assays. Serology Lab U54 ●Develop qualified assay standards and generate novel reagents. 4-8 CBCs: Serological Sciences Capacity Building Centers ( ●Procure and characterize serum samples from SARS- 4-8 U54s: Serological Sciences Centers of Excellence CoV-2 patients and controls and establish serum panels. 5-10 U01s: Serological Sciences research projects Frederick National Laboratory Serology Laboratory ●Share assays, reagents, and standards within SeroNet. Network Coordinating Center Frederick National Laboratory COVID-19 Clinical Trials with NIAID • ACTT: Adaptive COVID-19 Treatment Trial – a Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in hospitalized patients. • Four versions; 1-3 completed, 4 enrolling at US and international sites: o ACTT-1: Remdesivir vs. placebo o ACTT-2: Remdesivir +/- Baricitinib/placebo o ACTT-3: Remdesivir +/- Interferon beta 1a/placebo o ACTT-4: Remdesivir + Dexamethasone/placebo vs. Baricitinib/placebo • 3,500 subjects enrolled into four Phase 3 studies since February 2020. • Studies Outcomes are: FDA Emergency Use Authorizations (EUAs) for Remdesivir and Baricitinib FDA approval of Remdesivir for treatment of COVID-19 COVID-19 Clinical Trials in Concert with NIAID NIAID/DMID and CMRP Beth Baseler Remdesivir Laura McNay International placebo-controlled trial of hospitalized Dr. Barry Gause COVID-19 patients on ventilators or oxygen- Dr. John Beigel dependent. Emergency Use 60 sites and 1063 cases. Authorization Completed accrual in ~2 months. FDA-approved Remdesivir +/- Baracitinib International double-blind randomized placebo- controlled trial of hospitalized COVID-19 cases on Emergency Use ventilators or oxygen-dependent. Authorization 71 sites and 1034 cases. Completed accrual in ~1.5 months. Democratic Republic of the Congo and Course of the Latest Ebola Virus Outbreaks In-country protocol training PALM Trial received FDA approves Sacket Award Inmazed (Regeneron) Rapid research PALM I trial reported in NEJM response began PALM I PALM I Extension Last enrollment (n = 681) (n = 363) New Ebola Case FDA approves Ebanga (mAb114) Outbreak (Eastern DRC) Outbreak DRC (Equateur) 7/1/18 10/1/18 1/1/19 4/1/19 7/1/19 10/1/19 1/1/20 4/1/20 7/1/20 10/1/20 12/31/20 2/8/2021 Transition to PALM Base Operations Outbreak with 3,470 cases and 2,287 deaths (66% mortality rate) Outbreak with130 cases with WHO declares 55 deaths (42% mortality rate) Outbreak ended PALM Consortium: Institut National de Recherche Biomédicale • NIAID/DCR • Leidos Biomedical Research • The Mitchell Group, • Other Multilateral Partners NIAID and Frederick National Laboratory Ebola Trial: A Cycle of Discovery PALM Consortium Remdesivir ZMapp Orphan Drug and Breakthrough Therapy REGN-EB3 FDA approval designation (Inmazeb) Regeneron and European October 2020 Medicines Agency mAb114 (Ansuvimab FDA approval or Ebanga) Orphan Drug and Breakthrough Ridgeback PALM NIAID Therapy designation Biotherapeutic Consortium VRC and DCR December 2020 CMRP VCMP Continuity of Veterinary and Clinical Services During the Pandemic Dr. Ligia Pinto Dr. Michael Vaccine, Baseler Dr.Dr. StephenStephen Jones Jones Immunology and Applied and LaboratoryLaboratoryDr. Stephen Animal Animal Jones Cancer Developmental SciencesSciences ProgramProgram Directorate (VICD) Research (LASP)(LASP) Directorate (ADRD) Dr. Barry Gause Dr. Ethan Clinical Research Dmitrovsky Directorate (CRD) and Executive Leadership Team Beth Baseler Clinical Monitoring Research Program Dr. George Mitra (CMRP) Dr. David Lindsay Biopharmaceutical Vaccine Clinical Development Materials Program Program (BDP) (VCMP) 227 Leidos Biomedical Research Staff engaged in continuity of services Case Study: Continuity of Essential Services for Laboratory Animal Sciences LASP (pre-pandemic) LASP (during pandemic) Team A Team B NCI vivarium (Bethesda and Frederick) essential veterinary and husbandry services Team C standard work schedule split shifts / elongated workday and week Laboratory Animal Sciences Program (LASP) Directorate Funding Source: NCI Office of the Director Zoe Head Supports Weaver Ohler Stephen Jones NCI Intramural Animal Facility Center for Cancer Research and Colony Center for Advanced Management Animal Diagnostics OD (Animal Health Monitoring) Preclinical Research Laboratory (CAPR) Serguei & Genotyping Division of Cancer Epidemiology Kozlov Core (ADL) Wang-Ting Hsieh and Genetics Pathology / NCI Extramural Genome Histotechnology Modification Laboratory NCI Division of Cancer Treatment Core (GMC) (PHL) and Diagnosis Lawrence Division of Cancer Biology Raj Sternberg Chari NIAID, NIAMS, FNLCR LASP Small
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