Pandemic Prevention Platform (P3) Proposers Day: … Prevention Platform (P3) Proposers Day: ......
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Pandemic Prevention Platform (P3)Proposers Day: Lightning Talks
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ATCC
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ATCC Capabilities and Response to Recent PandemicsVirusReagents MERS CoV* Ebolavirus* Zika virus*, ** Influenza virus**
Clinical isolates and derivatives
• Virus isolates (n=2)
• Native viral RNA
• Inactivated virus
• Virus isolates (n=6)
• Native viral RNA• Inactivated virus• Monoclonal Ab• Plasmid clones
• Virus isolates(n=15)
• Native viral RNA
• Inactivated virus
• Monoclonal Ab
• Virus isolates (n= 17,H1N1pdm09, H3N2v, H7N9)
• Native viral RNA• Inactivated virus• Monoclonal Ab
Assays for detection and surveillance
• Zika in Infants & Pregnancy Study, longitudinal study in 5 countries
• Reagents to support detection and surveillance
• Annual WHO Kit• Annual IVD rRT-PCR
Kits• Annual RUO rRT-PCR
Kits• EUA rRT-PCR Kits
(H1N1pdm09, H3N2v, H7N9)
• Reagents to support detection and surveillance
*NIAID’s MID-BRR program (Microbiology and Infectious Disease Biological Resource Repository), www.beiresources.org** CDC’s International Reagent Repository program, www.influenzareagentresource.org
Batelle
NeuroLife™
Leveraging expertise across the institute to “translate scientific discovery and technology
advances into societal benefits”
Machine, deep, and transfer learning
• Pathogen testing up to BSL-3 In vivo, in vitro, ex-vivo
Rapid and Accurate Database Independent Antibody Profiling• Proteomics, genomics, and small
molecule forensics Human and microbial identification Algorithm development and application ExactID® DNA/ protein polymorphism analysis Chemical agent identification Immune system profiling
• Signal processing
-Gordon Battelle’s last will and testament
https://www.battelle.org/
Orion Integrated
Biosciences
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Global BiosurveillanceNear Real-time Biotracking
Unknown Pathogen IdentificationRational Prioritization of AbHigh Affinity Ab Targeted Evolution
Dana Farber Cancer
Institute
Technology/Techniques(1)Antibody discovery and engineering through different displaysystems and single B-cell cloning, antibody affinity maturation andhumanization with structure modeling and recombinant DNAtechniques,(2)Human B cell development, antibody repertoire (antibodyome)analysis through NGS and bioinformatics.(3)Human immune system reconstituted mice to set up diseasemodels, study immune responses, and develop antibody therapeuticsagainst infectious disease and cancer including vaccine studies.
Dr. Wayne A. Marasco, Dana Farber Cancer Institute / Harvard Medical School [email protected] vard.edu
Helm System Solutions
CONCEPT OACH
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HELM System SolutionsWoman-owned Small Business interested in joining a P3 team as a subcontractor
IMPACT
HELM System Solutions will contribute to a prime’s P3 success by helping to : Maximize Pwin
Ensure program execution through R&Dproficiency, quantitative techniques andinnovative scientific approaches
Evolve a sustainable capability by creating and implementing transition and commercialization pathways
APPR
1. Apply systems thinking and tools to identify solution components that drive the timeline and ideate around automation
2. Use optimization techniques and other mathematical concepts for test design
3. Characterize and leverage insights from previous work concerning emerging pathogens
4. Enable successful integration and smooth transition via stakeholder access
5. Accelerate commercialization potential through VC and other sources
CONTEXT• Brad Schneider, PhD (San Francisco)
• Experimental pathology, virology• CDC, Pasteur Institute
• Michael Glass, PhD (Charlottesville, VA)• Cellular, Viral, and Molecular Biology• Emerging pathogens SME
• Anne Hillegas, DSc (Arlington)• Systems engineering and optimization;
commercialization• Valerie Browning, PhD (Arlington)
• Multidisciplinary DARPA program management experience
Contact Info: HELM System Solutions Suite 200 4075 Wilson Blvd Arlington, VA 22203 (703) 310-8544
Complex response surface representing multi-criteria optimization over design variables with various degrees of dependency and correlation
Emergent
Emergent Medical Countermeasure Development Capabilities Include:
Vaccines HyperImmunesSmall molecules Devices
Monoclonal Antibodies
Kentucky Bioprocessing
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• Established 2006• FDA Regulatory Experience• Phase 1/Phase 2 and Pivotal
Studies• Robust System for mAbs,
Antigens, Enzymes• USG Contracting Experience
cGMP Production of Plant Expressed Antibodies
Transient Expression in Nicotiana
Antibody Platform Process
> 30 Different Antibodies Released
• API Production/Release in as little as 18 Days• Production from Master Seed Banks• Improved glycosylation• Controlled, indoor conditions for plant growth
Development of ZMapp®
• ZMapp® is a combination of 3 mAbs to treat Ebola• Developed by Mapp Biopharmaceutial in
collaboration with KBP• Production began August, three GMP mAbs
manufactured by October• IND/Clinical Study Initiated following January
Contact: Hugh Haydon, 270-663-6106 or [email protected]
GE Global Research
GE Global Research- John Nelson, Ph.D. ([email protected]) Partnering opportunity:TA3-More effectivenucleic acid delivery
• Isothermal, mg/ml product at anyvolume• No size limitations (>20kbtemplates)• Rapid (<24 hourreaction)• High fidelity• No extraneous sequences (minimalconstruct)• Potentially completelycell-free TCell
Ultrasound-Assisted DNA Delivery- We have demonstrated efficient DNA delivery to liver for the production ofApoA-I protein (doi:10.1016/j.atherosclerosis.2015.04.817). High-density lipoprotein cholesterol (HDL-C)was increased in rats following ultrasound-directed delivery of humanApoA-I expression plasmids by sonoporation. Amenable to many internal targets (ultrasound accessible) including intramuscular injection
GFPExpression ApoA-I mRNA ApoA-I Protein HDL-C inSerum
• Localizeddelivery• Visualizetarget• FDAapproved
device• Uses standard
imaging parameters
cont
ro
lG
FP
Rolling CircleAmplification (RCA)of Expression Constructs- We have demonstrated efficient cell-free amplification of plasmids to use for in vivo protein expression.
DNA VaccineResults(HAantigen coded in 7 kb contruct,mice)
gG AntibodyResponse
IFN-producing TcellsRa
tio
(tre
ated
/con
trol
)
CureVac
22 February 2017 - DARPA P3 Proposers Day slide from CureVac
Pandemic Prevention Platform and CureVac
Company Background Fully integrated biopharmaceutical company
including manufacturing, regulatory affairs and clinical development
R&D focus: mRNA-based drugs – cancerimmunotherapies, prophylactic vaccines,molecular therapy & adjuvants
Locations: Tübingen and Frankfurt, Germany, Boston, MA
Employees: ~290
DARPA Experience and AchievementsRNArmorVax Consortium
Partnered with Sanofi-Pasteur and In-Cell-Art
Technology Investment Agreement HR0011-11-3-0001
1 publication, 22 patents
RN-Shield
ADEPT-PROTECT Program (HR0011-14-2-0006) on mRNA encoded antibodies
Collaboration with USAMRIID
Key StrengthsmRNA know-how
Optimization, formulation, delivery
Specific experience with mRNA encoded antibodies
GMP manufacturing since 2006
Two manufacturing suites currently available (GMP I & II) supplying up to Phase II
Additional suite for industrial scale online 2018
Start construction of separate GMP production building for market supply in 2017
Anticipated P3 Role Lead: Clinical grade product manufacturing
Lead/Support: Deliver the product to patients to induce protection in < 3 days following administration
Support: Evolve the antibody or biologic product for increased potency
Team with partners who can: Grow virus
Identify an antibody or biologic product that targets the virus for use in medical countermeasure
BTS
SearchMetadata
Storage
Cloud Computing
Collaborate
Share
Visualize
AnalyzSecuree
SRI International
Tony Wang & Kathlynn Brown, SRI International
Teaming Overview and Objectives• Highly experienced team in rare cell identification and analysis with FASTcell™ platform technology• Needle free delivery device can rapidly administer passive immunization – ideal for pandemic scenarios• Experienced virology group with BSL3/ABSL3 capabilities• Looking for collaboration around:
• Rapid on-demand virus production systems• In vitro artificial immune system and/or affinity maturation technologies• Computation approaches assisting affinity maturation• GMP manufacturing of clinical-grade nucleic acid materials
Contact: Tony Wang– [email protected] and Kathlynn Brown- [email protected]
• FASTcell™ Cytometer is a rare cell detection platform that allows the sensitive and accurate detection of rare cells with a throughput of 25 million cells per minute
• Proven system for the detection and isolation of circulating tumor cells (CTCs), virally-infected cells and antibody-producing cells against a specific target antigen
• Nozzle design allows for intradermal or intramuscular injections with variable penetration depth, area coverage and volumes
• IM injection of plasmid DNA encoding for a monoclonalantibody produced clear antibody expression in animalmodel
VISTA-Jet Needle Free Injection System Versatile Delivery Device for DNA Vaccines
Parc, A Xerox
Company
MicroJet Particle Drug Delivery• Direct needle-free delivery of
powder payloads to tissue– physical penetration of particles
• Tunable array of collimated jets
– disposable ejector & drug cartridge• Advantages
– High patient throughput, mass population delivery
• Quiet, microjets• No –efield or custom biochem needed
– High dosing with single array scan over large area
– Simple formulations– Precision multi-particle delivery– Tunable dosing
Skin
Air accelerated post-Venturi nozzle
High speed jetGas inlet
Drug particles entrainment inlet
Drug reservoir
• Showed transdermal delivery of nucleic acid-based dry particles
– Biological response comparable to intradermal injections
Contact: [email protected]
serum SEAP activity
WRAIR
Rapid Evolution of Antibody CandidatesKayvon Modjarrad, MD, PhD; Gordon Joyce, PhD, Shelly Krebs, PhD; Morgane Rolland, PhD; Merlin Robb, MD; Nelson Michael, MD, PhD
Henry Jackson Foundation / Military HIV Research Program / Walter Reed Army Institute of Research
Longstanding capability for entire countermeasure development pathway
Antibody isolation, characterization, design and developmentRapid mAb discovery Antibody structure analysis Yeast display/Library panning
cGMP production & animal model testing in-house and/or with partners
Most extensive and robust Defense clinical trial infrastructure
Demonstration of accelerated countermeasure development during PHEIC
University of Virginia
The Galveston National LaboratoryWorld Reference Center for Emerging Viruses and Arboviruses (University of Texas Medical Branch)
University of Chicago University of VirginiaVi
rus G
row
th
Antib
ody
disc
over
yan
dop
timiza
tion
Coulter Department of Engineering,
GA Tech and Emory University
Single RNA sensitive imaging probes for tracking delivered mRNA
Phil Santangelo, PhD: Tools for characterizing mRNA trafficking, delivery, and expression in mice and macaques
mRNA trafficking, cellular uptake, and expression via PET/CT and near-IR fluorescence (Fluobeam and microscopy) in cynomolgus macaques
In vivo
mRNA trafficking, cellular uptake, and expression via visible and near-IR fluorescence (microscopy or flow cytometry) at the whole animal and cellular level in rodents
Skeletal muscle
Wyss Institute, Harvard University
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Generic Pandemic Countermeasure Development in < 60 daysDonald E. Ingber, MD,PhD and Michael Super, PhD
Wyss Institute for Biologically Inspired Engineering, Harvard University
0DARPA Sepsis DLT BAA 11-30, 12-36
(Ingber/Super)
Generic pathogen capture technology from blood
(Kang et al Nat Med. 2014; Cartwright et al., EBioMed. 2016)
> 90 species, including CMV, Dengue, Ebola, EBV, Hep B, C, HIV, HSV 1,2, Influenza, A,
Marburg, RSV, SARS-CoV, WNV
FcMBLCapture Protein
Hospital Trauma SepsisControls Patients Patients
‘Artificial Lymph Node’ Programs Dendritic Cells In Situ
(Mooney/Doherty)
Effective Cancer Vaccine(Ali et al Nat Material 2009)
Recruits DC, Macrophages T and B cells
Generates Systemic Immune Response
Generic Infection Vaccine(Ingber/Super/Mooney/Doherty)
Rapid Response Vaccine for Pandemic Threats
FcMBL Integrate in Scaffold Capture w/immune
+ Inactivate Virus adjuvants
Protect from Infection Generate Antibody Implant in Vulnerable Within 60 DAYS Titers IN VIVO Populations
Instant App
Integrated Systemic AAV-mediated Prevention Against Pandemic Pathogens (INSTANT-APP)
Single B cell
Antibody library
2.Identify antibody
In house experience with both
Candidate selection
1.Grow virus
Seeking collaboration
3.Increase potency
Proven experience Abs & proteins
4.Manufacturing
Tox: in house Clinical: CMOs
5.Clinical trial
4 active trials4 upcoming trials - 2017