TB Vaccine Stakeholder Meeting and Luncheon - Aeras€¦ · and ensure global market access ... • Inducing specific T cell functionality ... 46 Sources: 1WHO TB Surveillance Report,

TB Vaccine Stakeholder Meeting and Luncheon

3 December 2015

Cape Town, South Africa

Jacqueline E. Shea, PhD

CEO

Overview of Aeras’s Strategy and Progress

Agenda

• Mission

• Organizational overview and model

• Preclinical development

• Clinical development

• Global pipeline

• Challenges to TB vaccine development

• R&D strategy

• Collaboration

• Portfolio management

• Stakeholders

2

Developing new TB

vaccines that are

affordable and

accessible to all who

need them

Our Mission

4

• PDP founded in 2003

• Nonprofit biotechnology organization with

in-house capabilities in portfolio

management, preclinical development,

translational product development, policy,

advocacy, resource mobilization and

finance

• Offices

- Rockville, MD, USA (headquarters)

- Cape Town, South Africa

- Beijing, China

• Technical advisory groups incorporating expertise from around the world

• ~ 90 total employees globally

Overview of Aeras

5

Aeras Africa

• Founded in 2008

• Approx. 20 staff members and contractors with industry, academic and

CRO experience

6

• Real-time support to

collaborating clinical trial sites

• Extensive network of partners

Aeras Asia

• Aeras Biotech Beijing Limited opened

in 2013

• 2 staff and a contractor

• Several ongoing partnerships and

collaborations

• Landscape analysis of research

environment underway to identify other

partnership opportunities

7

Preclinical Development • In-house capabilities include:

– vaccine design

– program management

– research

– assay development

– immunology

– animal studies

• 12,000 sq. ft. of fully equipped

BSL-2 laboratory space

• Extensive experience in antigen

selection, platform development,

lead optimization, process

development, patent and

regulatory filings

• Wide range of animal modeling

and immunology proficiency

8

Clinical Development • Network of clinical trial partner sites in North

America, Europe, Africa and Asia

• Over 30 clinical trials with multiple candidates

and partners in the past 12 years

• In-house capabilities include:

- Clinical operations

- Safety

- Epidemiology and site assessment

- Stats and data management

- Medical writing

- Specimen and IP management

- Immunology lab

- Regulatory affairs group

- Diagnostic and mycobacteriology lab capacity at

sites with EQA

• Flexible operating model

– 100% Aeras managed

– Hybrid with CROs and/or collaborators (e.g. pharma

partners, NIH/HVTN)

9

Durban, Johannesburg, Klerksdorp,

Pretoria, Rustenburg, Soshanguve,

Soweto, and Tembisa, South Africa

Oxford and Birmingham, UK

Lausanne, Switzerland

St. Louis, MO, US

Lenexa, KS, US

Dakar, Senegal

Sichuan, China Guangxi, China

Bangalore, India

Kampala, Uganda

Svay Rieng, Cambodia

Kericho and Kisumu, Kenya

Lusaka, Zambia

Maputo, Mozambique

Cape Town, Paarl, Tygerburg,

and Worcester, South Africa

Clinical - Completed

Clinical - Current

Epidemiological – Completed

Epidemiological – Current

Stockholm, Sweden

Tampere, Finland

Hanoi, Vietnam

Clinical and Epidemiological Studies

Portland, OR, US

Lebanon, NH, US

Rochester, NY, US

Winston-Salem, NC, US

Henan, China Jiangsu, China

10

Phase 1 Phase 2a Phase 2b Phase 3

DAR-901

Dartmouth, Aeras

RUTI

Archivel Farma, S.L

VPM 1002

SII, Max Planck, VPM, TBVI

Vaccae™

Anhui Zhifei Longcom

MTBVAC Biofabri, TBVI, Zaragosa

H1/H56: IC31

SSI, Valneva, Aeras

M72 + AS01E

GSK, Aeras

Ad5 Ag85A

McMaster, CanSino

H4: IC31

Sanofi Pasteur, SSI, Aeras

ChAdOx1.85A / MVA85A

Oxford, Birmingham

ID93 + GLA-SE

IDRI, Wellcome Trust, Aeras

MVA85A / MVA85A (ID, Aerosol)

Oxford

TB / FLU-04L

RIBSP

Global Clinical Pipeline of

TB Vaccine Candidates

Viral Vector

Protein / Adjuvant

Mycobacterial – Whole Cell or Extract

Please note: Information is self-reported by vaccine sponsors.

Revised on Nov 18, 2015

Phase 1 Phase 2a Phase 2b Phase 3

DAR-901

Dartmouth, Aeras

RUTI

Archivel Farma, S.L

VPM 1002


Vaccae™



H1/H56: IC31

SSI, Valneva, Aeras

M72 + AS01E

GSK, Aeras

Ad5 Ag85A

McMaster, CanSino

H4: IC31



Oxford, Birmingham

ID93 + GLA-SE



Oxford

TB / FLU-04L

RIBSP

Global Clinical Pipeline of

TB Vaccine Candidates

Viral Vector

Protein / Adjuvant


Please note: Information is self-reported by vaccine sponsors.

Revised on Nov 18, 2015

DAR-901

Dartmouth, Aeras

RUTI

Archivel Farma, S.L

VPM 1002


Vaccae™



H1/H56: IC31

SSI, Valneva, Aeras

M72 + AS01E

GSK, Aeras

Ad5 Ag85A

McMaster, CanSino

H4: IC31



Oxford, Birmingham

ID93 + GLA-SE



Oxford

TB / FLU-04L

RIBSP

Viral Vector

Protein / Adjuvant


DAR-901

Dartmouth, Aeras

RUTI

Archivel Farma, S.L

VPM 1002


Vaccae™



H1/H56: IC31

SSI, Valneva, Aeras

M72 + AS01E

GSK, Aeras

Ad5 Ag85A

McMaster, CanSino

H4: IC31



Oxford, Birmingham

ID93 + GLA-SE



Oxford

TB / FLU-04L

RIBSP

Viral Vector

Protein / Adjuvant


DAR-901

Dartmouth, Aeras

RUTI

Archivel Farma, S.L

VPM 1002


Vaccae™



H1/H56: IC31

SSI, Valneva, Aeras

M72 + AS01E

GSK, Aeras

Ad5 Ag85A

McMaster, CanSino

H4: IC31



Oxford, Birmingham

ID93 + GLA-SE



Oxford

TB / FLU-04L

RIBSP

Viral Vector

Protein / Adjuvant


DAR-901

Dartmouth, Aeras

RUTI

Archivel Farma, S.L

VPM 1002


Vaccae™



H1/H56: IC31

SSI, Valneva, Aeras

M72 + AS01E

GSK, Aeras

Ad5 Ag85A

McMaster, CanSino

H4: IC31



Oxford, Birmingham

ID93 + GLA-SE



Oxford

TB / FLU-04L

RIBSP

Viral Vector

Protein / Adjuvant


DAR-901

Dartmouth, Aeras

RUTI

Archivel Farma, S.L

VPM 1002


Vaccae™



H1/H56: IC31

SSI, Valneva, Aeras

M72 + AS01E

GSK, Aeras

Ad5 Ag85A

McMaster, CanSino

H4: IC31



Oxford, Birmingham

ID93 + GLA-SE



Oxford

TB / FLU-04L

RIBSP

Viral Vector

Protein / Adjuvant


Translating Early Stage Discoveries

into Products

Discovery

Applied

Research

Clinical

Development

Regulatory

Clearance

Aeras Activities, Management, Oversight, Support

Process

Development*

cGMP Clinical

Manufacture* Clinical Trials

Preclinical

Development

13

*Provided by a strategic partner

Key Challenges — Scientific Questions

14

What constitutes a

protective immune

response?

Where do we need the

response? (local vs

systemic)

Key Challenges — Missing Tools

15

• Measure of level of exposure to the organism

• True measure of infection

• Measure of burden of Mtb during latency

• Better measure of cure

Enhancing knowledge about TB

• Validated, predictive animal models

• An in vitro functional assay of vaccine effect

• A correlate of vaccine-induced protection

• A human challenge model

Improving candidate selection

Aeras’s Primary R&D Strategic Goal

Ultimate goal is to develop, register

and ensure global market access

to a universal vaccine for all age

groups and populations

16

- Initial focus on a vaccine to

prevent TB disease in

adolescents and adults as

primary transmitters of disease

- Accessibility of new vaccines

must be considered alongside

product development

An Adolescent/Adult TB Vaccine Could Have

a Greater Impact on TB in Children 0-4 Years

Old than an Infant TB Vaccine

*Adult vaccine given every 10 years

17 White, R., Harris, R. “Potential public health impact of new TB vaccines: Prevention of disease,

infection and immunotherapy “. 4th Global Forum on TB Vaccines. Shanghai, China. 25 April

2015. Conference Presentation

Strategic Imperatives

1. Move the most promising candidates through to successful

registration and global access

2. Use translational and experimental medicine studies to de-risk

candidates at an earlier and less costly stage of development

3. Develop new and improved human challenge and animal models of

disease and leverage research findings to inform correlates of

protection and accelerate product development

4. Diversify the pipeline through innovation and select the best

candidates in each class for further development

5. Expand and diversify the funding base to support TB vaccine

development

6. Strengthen our partnerships and organization to enable TB vaccine

development

18

• Translational and

mycobacterial expertise

• Strong networks and

partnerships

• Flexible collaboration model

• Convener & coordinator

• Advocacy & resource

mobilization

Collaboration is Essential

19

20

Portfolio Management Approach

Active management

of projects and programs

Advance the most promising

candidates

Framework of harmonized criteria

Annual review process

Portfolio Management

Recent Major Funders and R&D Partners

21

And special thanks to the sites and participants

in our clinical trials!

Preclinical Development of TB Vaccines

Barry Walker, PhD

Vice President, Preclinical Development

Where we are now, where we need to be and how we will get there

Preclinical: The Toolbox

• The science

• Strategic vision

• Preclinical investigations, studies, experiments

– animal studies and immunology

• Collaboration and engagement

• Portfolio management

• Novel approaches – human challenge

23

Gaps in Pipeline Diversity

Portfolio Gaps

• CD4

– Other helper types

• Antibodies

– Specific pathways

• Inducing specific T cell

functionality

• Anatomical and

functional localization

• Novel Immune

regulation

• Quality vs Quantity –

Antigen selection

24

Preclinical Strategy

• Develop new and improved human challenge and animal models of disease

• Leverage research findings to inform correlates of protection and accelerate product development

• Diversify the pipeline through innovation and select the best candidates in each class for further development

• Select protective antigens

25

Model Development:

Sharpening the Tools

• NHP

– Lowering of challenge dose

– Enhanced diagnostics (i.e. PET/CT)

• Guinea Pig

– Continued refinement/harmonization of the platform

– Natural infection model

• Mouse

– Kitchen sink experiment – can we extend the dynamic range of the model?

26

• Robustness and reproducibility of all animal models is a key issue

Flexible Partnering Model

Accelerator

BCG Aerosol

Direct Investment

In Projects

Collaboration and

Engagement Active Management

with Partners

Improving the

tools, reagents

Viral Vectored

Strategies

27

Landscaping,

Thought

Leadership

New

Approaches

New

Vaccinology

The CTVD

Partnership

Novel

Immunology

Human Challenge Model • Benefits of a human challenge model

– Assess preliminary vaccine efficacy prior to

entering classical clinical trials

– Could help identify new vaccine candidates capable

of inducing protective immunity

• Using infectious, but ultimately controllable

(safe), and detectable strains of Mtb

• Human challenge model must reflect a

relevant vaccine effect

• Primary focus is on pulmonary delivery as

the natural portal of entry, although

intradermal delivery is also being explored

• This program is funded through Aeras and

the Bill & Melinda Gates Foundation, with a

consortium of partners in the US and the UK

28

Summary

29

Diversity

Partnerships & Collaboration

Translational Development

Update on Clinical Development and

Aeras’s Programs in Africa

Dereck Tait, MBChB, FRCPath

Clinical Director, Aeras Africa

Africa is a Key Region for

TB Vaccine R&D

• High incidence of TB

• Strong biomedical

research infrastructure

• Extensive experience in

TB vaccine development

31

Aeras’s Clinical Development Strategy

Goal: Accelerate and streamline clinical development of TB vaccines

Novel trial designs

Experimental medicine

Discovery and validation of correlates of

protection and/or risk

32

Experimental Medicine and

Novel Trial Designs

PHASE 3

PHASE 3

Prevention

of Infection

Prevention of

Recurrence

PHASE 1

PHASE 1

PHASE 2a

PHASE 2a PHASE 2b

PHASE 2b +/or

De-risking candidates at lower cost and earlier stages of

development

33

Clinical Studies in Africa

• Phase 1 safety and immunogenicity studies

• Intensive immunology study

• Dose ranging

• Prevention of infection

• Prevention of disease

34

Current Clinical Development Activities in

Collaboration with Partners in Africa

• 8 ongoing studies

• Phase 1 through Phase 2b

• ~5 000 participants

• 15 sites in three African countries

35

Month 6

QFT (-)

QF

T (+

)

Repeat QFT at 9

and 12 months

Screening

/enrollment

QFT (-)

Month 3

(Day 84)

QFT (-)

QF

T (+

)

Safety visit at Month

6 (BCG Group) or

Month 8 (AERAS-

404 or placebo

groups)

Month 12

QFT (-)

QF

T (+

)

Repeat QFT at 15

and 18 months

Month 18

QFT (-) Q

FT (+

)

Repeat QFT at 21

and 24 months

Month 24

QF

T (+

)

Repeat QFT at 27

and 30 months

If QFT (-), follow

up is complete

1st Prevention of Infection Trial of a New TB

Vaccine Underway in Adolescents

• H4; BCG; placebo – 1:1:1

• Primary Mtb infection endpoint - QFT conversion from a negative to positive test

at any time-point after Day 84

• Initial results expected 3Q2016

36

• 3506 participants. Sub-Saharan Africa

• Healthy, IGRA+ and HIV negative adults (18-50 years old)

• Stable, controlled chronic non-TB disease allowed

50% randomized to Placebo

(double blind)

50% randomized to

M72 AS01E

21 TB Endpoints

36 months follow-up

TB-018, Proof-of-Concept Phase 2B

Success criterion = log-rank p-value < 0.1 for definite Pulmonary TB (HIV-)

Two intramuscular doses of vaccine or placebo

One month apart

37

M72 Efficacy Study Biobank

• 90% of TB-018 participants enrolled in

biobank study

• Objectives

– Primary - to collect samples to evaluate potential biological markers correlated to the risk for TB

– Secondary - to evaluate immune correlates of protection from TB in participants vaccinated with M72/AS01E

38

H4, H56 & BCG Phase 1 Immune Correlates

in Adolescents

• Collaboration with Sanofi

Pasteur, SSI, DAIDS, HVTN

• Rationale – To generate

immunological data on a wide

range of immune responses to

increase the likelihood of detecting

responses correlating with risk or

protection in the prevention of

infection Phase 2 studies.

• Recruitment on-going

39

Ongoing Phase 1 and 2 Studies

• H4:IC31

– Collaboration with Sanofi Pasteur

– Infant dose escalation study

– 229 participants; 1 cohort still to enroll

• H56:IC31

– Collaboration with SSI

– Adult dose finding; Dose selected for further study

– Safety and immunogenicity study in patients recently treated for TB

– Fully recruited; Follow-up ongoing

40

H56:IC31 Phase 2 Prevention of Infection in

Adolescents (in planning)

• Collaboration with SSI, University of Bergen,

SATVI, AURUM and Mwanza

• Study design to mimic H4 POI study

• Projected start 2Q2016

41

Community Engagement in

Clinical Research

• Establish or augment CABs

for support of TB vaccine

trials

• TB, vaccine, and research

literacy training

• Establishment of a Regional

Africa TB Vaccine CAB

• Currently mapping and evaluating Community

Advisory Boards (CABs) at all clinical trial sites

42

Clinical Development: Looking Ahead

• Implementing novel clinical trial designs to

accelerate clinical development

• First results from new efficacy studies

• New preclinical candidates to diversify global

pipeline

43

Current Clinical Sites

44

Building Global Support for TB and TB

Vaccine R&D

Dara Erck

Vice President, External Affairs

TB R&D Funding Gap

• The estimated annual funding gap for TB R&D of US$1.3 billion1,2

• Full response to TB epidemic costs US$8 billion per year1

46 Sources: 1WHO TB Surveillance Report, 2015; 2TAG, Stop TB Partnership 2015 Report on TB Research Funding Trends

3G-FINDER Public Search Tools

21% 25% 20% 16% 19% 20% 19%

$456 M

$497 M

$613 M $636 M

$584 M $562 M

$580 M

0

100

200

300

400

500

600

700

2007 2008 2009 2010 2011 2012 2013

US

$ in

Millio

ns

Funding for TB R&D3

Other TB R&D

Vaccines

Resource Mobilization

47 Source: G-FINDER Public Search Tools (2013 Data)

• TB R&D and TB vaccine

R&D funding is dominated

by a small number of

donors

• Funding the ambitious

research agenda necessary

to support the WHO End TB

Strategy, The Global Plan to

Stop TB, and organizations

like Aeras, will require more

robust funding by more

donors

Bill & Melinda Gates

Foundation (33%)

Aggregate

Pharmaceutical and

Biotechnology

Companies (24%)

NIH (16%)

Funders Contributing

<2%

(9%)

DFID (5%)

DGIS (4%)

EDCTP (4%)

SSI (3%) UK MRC (2%)

TB Vaccines: $108.4 M

Advocating for TB R&D

48 Source: WHO Global TB Report 2015

Tuberculosis kills more people than any

other single infectious disease agent

The Cost of Inaction

• By 2030, a five-year delay in investing in new tools could result in a tremendous human and economic toll:

49 Source: Global Plan to End TB 2016-2020

8.4 million additional TB cases

US $181 billion in lost productivity

1.4 million additional TB deaths

US $5.3 billion in additional costs for TB

treatment

Thank You. To Contact Us:

Global Headquarters

Dara Erck, VP External Affairs

[email protected]

Aeras Asia

Sharon Chan, Head of Asia Office

[email protected]

Aeras Africa

Dereck Tait, Clinical Director

[email protected]

TB Vaccine Stakeholder Meeting and Luncheon - Aeras€¦ · and ensure global market access ... • Inducing specific T cell functionality ... 46 Sources: 1WHO TB Surveillance Report,

Documents