A Critical Juncture: progress in TB vaccine

clinical development

5th Global Forum on TB Vaccines

New Delhi, India

Ann M. Ginsberg, MD, PhD

February 21, 2018

Global Clinical Pipeline

2

Viral Vector

Protein / Adjuvant

Mycobacterial – Whole Cell or Extract

Information on candidates in clinical development is self-reported by vaccine sponsors, coordinated by the Working Group on New TB Vaccines and updated

September 2017

Mycobacterial – Live

ID93 + GLA-SEIDRI, Wellcome Trust

Phase 3Phase 2bPhase 2a

VaccaeTM

Anhui Zhifei Longcom

Ad5 Ag85A

McMaster, CanSino

ChAdOx185A/MVA85A (ID/IM/Aerosol)

U. Oxford

DAR-901

Dartmouth, GHIT

RUTI

Archivel Farma, S.L

H56: IC31

SSI, Valneva, Aeras

H4: IC31Sanofi Pasteur, SSI, Aeras

M72 + AS01E

GSK, Aeras

TB/FLU-04L

RIBSP

Phase 1

VPM 1002

SII, Max Planck, VPM, TBVI

(Phase 2/3)

MTBVAC

Biofabri, TBVI, Zaragoza, Aeras

BCG Revaccination

Target Populations

3

• Infants (healthy)

• Adolescents/Adults

(healthy)

• TB patients

4

Increasing focus on adolescent/adult vaccines:

to stop the cycle of transmission - will prevent the spread of TB

to children as well.

See presentation by R. White (LSHTM)

Therapeutic Indications

5

• Prevention of TB disease

– BCG replacement (infants)

– BCG boost (proximal – infants)

– BCG boost (distal – adol/adults)

• Prevention of recurrent TB

• TB treatment shortening +/or

increased cure rates (adjunct

to treatment)

Key Challenges in TB Vaccine Development

6

• Complicated pathogen and disease

• No known correlate of protection

• Not yet known if animal models are

predictive of human TB/protection

• Multiple vaccine candidates in

clinical development

• Licensure trials long and expensive

• Severely underfunded

Approaches to Streamlining Efficacy Trials

7

• Conduct Proof of Concept

trials in high-risk

populations (see Tait et al)

• Use Phase 2 trials to

establish “meaningful

biological effect” of

vaccine (triaging tool)

Decreasing:

₋ Risk

₋ Cost

₋ Time

Clinical Trial Endpoints

8

Prevention of TB disease (POD)

Prevention of Mtb infection (POI)

Prevention of TB disease recurrence (POR)

9

ID93 + GLA-SE

Ph3 in infants

Phase 3Phase 2Phase 1

VaccaeTMMTBVAC

Ad5 Ag85A

ChAdOx185A/MVA85A

TB/FLU-04L

DAR-901

RUTI

H56: IC31

H4: IC31 and BCG revaccination

VPM 1002

M72 + AS01E

Ph2a S&I - infants

Ph1b/2a S&I - adults

Ph1 – FIH Aerosol; adults

Ph1 - ID/IM/Aerosol; adults

Ph2a S&I – MDR-TB pts

Ph2 – POI in QFT- adolescents (in planning)

Ph2 – POR in adult TB pts post-cure (FPI – April 2018)

Ph2 – POI in QFT- adolescents

Ph2 – POI in QFT- adolescents

Ph3 in TST+ adultsPh2b POD – QFT+ Adults

Ph2 – POR in adol/adult TB pts post-cure

Ph1 – FIH; BCG+ adults

Ph2a S&I - adults

Viral Vector Protein / Adjuvant

Clinical

Trials(Not an exhaustive list)

Mycobacterial – Killed Whole Cell or Extract

Mycobacterial – Live attenuated

Efficacy

trials

M72/AS01E

GSK, Aeras

Anhui Zhifei Longcom: AnHui Zhifei Longcom Biologic Pharmacy Co., Ltd; SSI: Statens Serum Institute; VPM: Vakzine Projekt Management GmbH;

SII : Serum Institute of India

Vaccae TM

Anhui Zhifei Longcom

DAR-901

Dartmouth Medical

School, GHIT

VPM1002

Max Planck, VPM, SII

Completed (April 2017)

Awaiting for resultsPhase III 10000 PPD+ 15-65y Prevention of disease China 2018

Phase II 990 Q- 12-17y Prevention of infection South Africa 1Q2018

Phase IIb 3573 Q+ 18-50y Prevention of disease South Africa, Kenya, Zambia 2Q2018

Phase IIb 650 Q- 13-15y Prevention of infection Tanzania 2018

Phase II/III 2000 TB+ 18-65y Prevention of

recurrence

India 2020

Upcoming Data in TB Vaccine Efficacy Trials

Modified from M-A Demoitie, GSK

PHASE PARTICIPANTS EFFICACY LOCATION RESULTS

H4:IC31/BCG revacc

SP, SSI, Aeras

Presentation of results this session, M. Hatherill

New TB

Vaccines are

Achievable

11

Evidence:

− BCG vaccine provides partial protection; for

longer duration than previously recognized

− QFT/TST reverters

− QFT/TST resisters

− 90% of infected indivs. remain ‘LTBI’

− LTBI is partially protective against disease

➢ Vaccines can improve on natural immunity

(e.g., diptheria, tetanus, pneumococcal

conjugate vaccines)

A Critical

Juncture

12

• Improved animal models

• More diverse pipeline under development

• Progress towards a human challenge model

• Novel Phase 2 trial designs in high risk

populations

• Imminent results from multiple efficacy trials

• Biomarker/signature/correlate discovery

TB Vaccine R&D is Severely Underfunded

13

• Annual global cost of TB ~ $20B ($200B

over next 10 years)1

• Cost to develop one vaccine ~ $1.25B over

10 years2

• 2016 funding for TB vaccine R&D: $79M3

• 2016 funding for HIV vaccine R&D: $733M3

Sources: 1. WHO. Trade, foreign policy, diplomacy and health; Tuberculosis Control; 2. Stop TB Partnership. The Global

Plan to End TB 2016-2020; 3. G-Finder 2017; 3. WHO. Global TB Report 2016;

Now more than ever is the time to ensure TB

vaccine R&D gets the funding it needs.

Recent Major Funders and Aeras R&D Partners

14

Current Clinical Sites and Networks

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With special thanks to the sites and participants and their families in our clinical trials

Thank You

aginsberg@aeras.org

www.aeras.org