Diagnostic Preparedness PlatformWHO R&D Blueprint for Priority Infectious Diseases with Epidemic Potential

2nd round presentation

GenevaJuly 21st, 2016

Diagnostic Preparedness Platform

2

Aim

• Surveillance and monitoring of pathogens with high epidemic

potential in resource limited settings

• Capacities for fast ramp up of diagnostic testing in central lab settings

of epicentres of an outbreak and at the point of need

Strategy

• Early detection of onsets of outbreaks by diagnostic tools in

decentralized settings

• Corresponding central lab based confirmatory tests

• Scalability of production and implementation of POC and central lab

based tests by leveraging existing R&D and production capacities at

Alere and altona

• Capacity building and training in epidemiological hot spots

Diagnostic Preparedness Platform

3

Diagnostic Preparedness Platform

4

Alere Technologies

• Alere® q and lateral flow POC

system

• Proven applicability

• Decentralized testing

• Scalable in volume and number

of assays

• CE IVD, WHO PQ Dx for Alere q

HIV1/2 Detect

• Proven compatibility between

altona RealStar assays and

Alere q Filovirus Detect

altona Diagnostics

• RealStar® product line for

tropical infectious disease

• Proven high quality

• standardized real-time (RT)-PCR

kits

• CE IVD, FDA EUA, WHO EUAL

• Proven fast response to

outbreaks (SARS, MERS, flu,

CHIKV, EBOV, ZIKV)

• AltoStar automated high

thoughput central lab workflow

Solution

• Extension of Alere® q assay portfolio by tests for WHO listed pathogens

• Extension of existing RealStar® real-time PCR assay portfolio to complete

high priority list � transfer to the AltoStar automated workflow

• Creation of a scientific network of reference laboratories on a global scale

MH2

Folie 4

MH2 I would make two slides out of this oneMarkus Hess; 18.07.2016

Alere q Technology

5

ConnectedMolecular POC

Multiple

Assays

add sample

direct from

patient

Single use

Cartridge

Array based

detection

Automatic:

Extraction

Purification,

Amplification

and detection

Onboard

device and

assay controls

PCR

Extraction Target Isolation Amplification

- Chemical lysis

- Mechanical lysis

- Heat lysis

Integrated Cartridge Workflow

Real time & end point,

Melting curves

CMA technology; high

density arrays

Alere q Cartridge Features

� No cold chain requirements

� Real multiplexing capabilities

� Enables for diagnostic test panels

� SNP Detection

- Specific target capturing (e.g. RNA)

using biotinylated

probes on sepharose beads

- Unspecific DNA binding on silica

beads

Array Detection

6

Laboratory high throughput – altona RealStar / AltoStar

• RealStar: Open platform

• Application on commonly used real-time PCR instruments

• High throughput in centralised laboratories

• Flexible parallel testing for target organism and differential diagnostic

• Parallel testing of symptomatically similar pathogens: shared PCR profile,

shared internal control

• AltoStar workflow: Automated NA extraction from different sample matrices

and automated PCR set-up

altona RealStar Technology

7

MH7

Folie 7

MH7 Automated NA extraction from different sample matrices and automated PCR set-upMarkus Hess; 18.07.2016

SD Bioline Ab RDT’s

8

� Product Specification

� Sample Type : serum, plasma and whole blood

� Sample Volume : 10 uL

� Interpretation Time : 15-20 min

� Test procedure

� SD Color scale chart

(2) Dispense 4 drops of

assay diluent vertically into

the assay diluent well.

(1) Dispense 10 uL of

specimen into the sample

well (S).

(3) Interpret test results

in 15~20 minutes.

*Score rating

1+ positive: G1~G8

2+ positive: G9~G14

3+ positive: G15~G20

Absorbent pad

Control line

Sample Pad

Gold Conjugate Pad

Nitrocellulose membrane

Test line

DPP Assay Panels

9

Assay panels for Nucleic Acid Testing

1. VHF panel mandatorily including Ebola and Marburg viruses, Lassa virus,

Rift Valley fever virus, and CCHF virus

Optionally: Zika virus, dengue virus, and chikungunya virus, as well as malaria

2. Respiratory panel, mandatorily including SARS-CoV, MERS-CoV

Optionally: pandemic Influenza viruses, RSV, MPV, PIV

3. Encephalitis panel, mandatorily including Nipah virus

Optionally: Japanese encephalitis virus, Enterovirus species, rabies virus,

herpesviruses and measles virus

The lateral flow assays:

• Malaria and dengue on market

• Zika and chikungunya IgM/IgG/Ag in development.

• Other LF tests will be evaluated case by case to ensure appropriate use of

RDT‘s within their performance specifications.

DPP Assay Panels

10

Assay strategy

• POC assays to be spatially multiplexed in a multianalyte cartridge covering

clinically relevant pathogens

• Central lab assays to be designed to run in parallel using one sample

preparation offering flexibility to include region specific pathogens in the

panel testing

• Shared process controls for QC and proficiency testing

• Selected lateral flow assays to widen the diagnostic window

Platform Integration Pathway I

11

Transfer of existing RealStar assays to multiplexed Alere® q POC

system

Example:

Advantage: Same controls and uniform post-market-surveillance,

relatively low development risk

Filovirus

CCHFV

Rift Valley

fever virus

Platform Integration Pathway II

12

In case of new pathogens or new genotype parallel development of lab

based and POC system.

Advantage: Faster availability of outbreak control measures on all

levels.

DPP Advantages

13

Validation

• Shared validation protocols for Alere® q and RealStar® assays

• Leveraging biobanks, strain collections and BLS4 capacities of existing

network of reference laboratories for validation of panels with stored samples

and viral cultures

• Employment of developed panels in reference labs and their outstations for

usability testing � Laboratory Collaboration Network (LCN)

Production and Quality Control

• Utilisation of existing production capacities for Alere® q cartridges, lateral

flow assays and RealStar/AltoStar assays

• Establishment of quality control process for panels

Supply

• Fast ramp up of production capacity

• Own oligonucleotide production

• Own enzyme production

� Independence of suppliers for main components

• Example of ramp up potential: Filovirus assay

altona‘s Capacity

14

altona Portfolio and Pipeline

15* submitted

Panel Assay planed development verification validation launched regulatory status

Respiratory SARS CoV CE-IVD

MERS CoV CE-IVD, FDA EUA

Influenza A/B virus CE-IVD

Respiratory syncytial virus CE-IVD

Parainfluenza virus CE-IVD

Human metapneumovirus CE-IVD

VHF Filoviridae CE-IVD, WHO EUAL, FDA EUA

Lassa virus

CCHF virus CE-IVD

Rift Valley fever virus Research Use Only

Malaria parasites CE-IVD

Dengue virus CE-IVD

Chikungunya virus CE-IVD

Zika virus CE-IVD, WHO EUAL*, FDA EUA

Hantavirus

Yellow fever virus

Encephalitis Nipah virus

Japanese encephalitis virus

West Nile virus CE-IVD

Herpes simplex virus CE-IVD

Varizella zoster virus CE-IVD

Measles virus

Alere’s Global Capability

16

1716113906*20677**

210

0026184

| 16

80010*1654

R&DManufacturingCommercial T. SupportKey: * Excludes Contracted Workers (3582)

** Excludes Philippines Health Management Business (939)

Regional Distributors : 124Regional Distributors: 147 Regional Distributors: 50

Leading global supplier of POC diagnostics

• Shipped over 1 billion tests in 2015

• Highly automated, high throughput and scalable manufacturing across

sites in NA, Asia and Europe encompassing both lateral flow and

instrument-based POC assays

• ~1/3 of our business is in Infectious Diseases and this is spread very

evenly between regions (Sub-Saharan Africa, Latin America, Asia

Pacific, Europe and the Middle East and North America)

Our global reach

Alere q Assay Portfolio

FILOatj01 – SUDV

FILOatj02 – EBOV

FILOatj03 – BDBV

FILOatj04 – TAFV

FILOatj05 – MARV

FILOatj06 – RESTV

Alere q HIV-1/2 Detect

Qualitative HIV diagnosis test for whole blood and plasma samples

(CE-IVD marked, WHO PQ review)

Alere q Filovirus Detect

Pan-Filovirus screening assay panel for detection and discrimination

of 6 known Ebola and Marburg virus species (in clinical validation)

Alere q HIV-1/2 VL Plasma

Quantitative HIV monitoring test for plasma samples (in development)

Alere q Carba Profile

Qualitative test for the detection of 11 clinically most relevant

carbapenemase genes from swab samples (in feasibility)

other applications

MRSA profile, Respiratory Panel, Fever Panel, STI Panel,

Companion Diagnostics

17

Alere SD WHO Prequalified Product Pipeline

18

Completed 7 Under progress 2

In development

Data Management and Epidemiology

Incidence

Tracking

Geographic

Mapping

The MOFINA Project Showcase

The goals:

Develop, validate and deploy a fully integrated, POC, molecular pan-

Filovirus assay

The project:

Mobile Filovirus Nucleic Acid Test (MOFINA)

The consortium:

Technical/development: Alere Technologies and altona Diagnostics

Evaluation/validation: BNITM, INMI Lazzaro Spallanzani, PHE, FIND

The approach:

Integrate widely used, CE-IVD, FDA EUA, WHO EUAL RealStar®

Filovirus assay with the Alere® q analyzer and cartridge technology

incorporating fully-integrated sample preparation, target amplification and

detection

The Status:

Field validation in Sierra Leone, FDA EUA pre-submission complete

With support from

The MOFINA Project Showcase

21

The only POC Pan-Filovirus assay which detects

and discriminates all known Ebola species and

detects both known Marburg species

• In-field (Sierra Leone) clinical testing completed with 69

samples

• FDA EUA pre-submission completed, WHO EUAL in

process

• CE IVD submission in 2016

Molecular POC

Validation & Clinical Support - MOFINA

partners

Product

Development

FILOatj01 – SUDV

FILOatj02 – EBOV

FILOatj03 – BDBV

FILOatj04 – TAFV

FILOatj05 – MARV

FILOatj06 – MARV Ravn

FILOatj07 – RESTV

Multiplex

Screen

6 Species in a

Single Test

The MOFINA Project Showcase

With support from

The partnership

• Alere Technologies (an Alere Inc. company)

• altona Diagnostics

• Bernhard Nocht Institute for Tropical Medicine (BNITM)

• Istituto Nazionale Malatie Infettie (INMI) Lazzaro Spallanzani

• Public Health England Porton Down

• The Foundation for Innovative New Diagnostics (FIND)

Assay development

• Led by Alere and altona based on existing technology (Alere q platform,

altona Filovirus assay)

• Design inputs from all project partners

Assay validation

• Some work in house with purified nucleic acids

• Live cultured virus by BNITM, INMI and PHE in BSL4 facilities

• Retained patient sample testing in Sierra Leone facilitated by FIND and PHE

Laboratory Collaboration Network

The strategy

• Partner with national and international scientific institutions

• Global footprint to cover genetic background, environmental and ethnical

diversity

• Inclusion of most of the variety of strains and subspecies of the focal

pathogens

The management

• co-managed by Alere and altona

The role

• Definition of design input, user specifications, product profiles

• Prototype testing, verification and validation, field data

• Focal points for piloting the deployment of technologies, training and pilot

monitoring and surveillance programs

Laboratory Collaboration Network

Currently existing laboratory network (to be extended)

WORLD MAP to be added

Which ones do we have?

Bernhard-Nocht Institute

for Tropical Medicine

DPP project structure

DPP project plan

Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

1 Viral Hemorrhagic Fever Panel

RUO

RUO

RUO

CE-IVD

CE-IVD

CE-IVD

2 Respiratory Panel RUO

RUO

RUO

3 Encephalitis panel RUO

RUO

RUO

4 process control panels

4.1 Development4.4 Technical documentation

RealStar/ Altostar

Alere q

SD Bioline*

* single target assay

1.3 Validation

1.4 Technical documentation

1.5 deployment

1.2 Verification

Year 1 Year 2 Year 3

1.1 Development

DPP Development Estimates

27

Development cost and timelines

• Estimated 15,9 Mio. USD

• 3 years development and deployment project

• VHF panel CE IVD marked, respiratory and encephalitis panel RUO

Duration of validation phase is highly dependent on access to isolates and

specimens, Regulatory Authority requirements, appropriate ethical

approval(s), logistics and financing.

• Deployment, training and field studies on VHF in several geographically

distributed areas

Key DPP Development Challenges

28

Access to isolates and clinical specimens

• Despite intentions by stakeholders to establish repositories and banks access

to pathogen isolates and clinical specimens remains a major challenge for

product developers

Sustainability

• Lack of current business case for potential assay makes justifying R&D

spend and occupying precious R&D time very difficult

• Support in form of external financing of R&D and/or assay volume

guarantees need to be explored

IndustryImplementers, multilaterals,

academics

Develop and supply critical products

Design inputs, surveillance

information, samples and isolates