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

6

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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 Wayne_Marasco@dfci.har 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

.

• 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 haydonh@kentuckybioprocessing.com

GE Global Research

GE Global Research- John Nelson, Ph.D. (john.nelson@ge.com) 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– tony.wang@sri.com and Kathlynn Brown- kathlynn.brown@sri.com

• 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: Eugene.Chow@parc.com

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