DRIVING INNOVATION

Aeras and the Global Effort to Develop New TB Vaccines

Ann M. Ginsberg, MD, PhD
J2J Workshop, Kuala Lumpur 14 November 2012

Tuberculosis: A Devastating Epidemic

Over 2 billion people or 1/3 of the worlds population is infected with M. tuberculosis

Globally, 8.7 million new cases and 1.4 million deaths in 2011
In SE Asia and Western Pacific, 5.2 million new cases and 610,000 deaths (excluding HIV) in 2011 Globally, 13% of TB patients are HIVinfected. MDR-TB = 3.7% of new cases, globally. XDR-TB identified in 84 countries. Surveillance inadequate in many countries.
3

Number of MDR-TB cases estimated to occur among notified pulmonary TB cases, 2011

XDR-TB: approximately 9% of MDR-TB cases are extensively drug-resistant TB (XDR-TB). As of Oct. 2012, 84 countries had reported at least one XDR-TB case.

Vaccines needed to turn the tide

The energy and approaches we have put into addressing TB over the past 20 years have led to insufficient progress.

Source: Christopher Dye, WHO

AERASDRIVING INNOVATION

Global Plan will not eliminate TB by 2050

10000

TB incidence/million/yr

1000

100
Projected incidence in 2050 >100x elimination threshold

10
Current trajectory -1.6%/yr Elimination -16% /yr Global Global Plan - 6%/yr -6% /yr

Current trajectory -1% /yr Elimination - 16%/yr

1 2000

2010

2020 Year

2030

2040

2050

BCG current TB vaccine

BCG developed 90 years ago, not improved upon since. Most widely delivered vaccine in the world. Reduces the risk of severe pediatric TB disease, but:
Unreliable protection against adult pulmonary TB, which accounts for most TB worldwide Not recommended for use in infants infected with HIV Many genotypes and phenotypes -- multiple BCGs Inadequate impact on the global TB epidemic

The Need for Improved TB Vaccines

(BCG)

The Potential of New TB Vaccines

New, more effective TB vaccines could:
Be safer and more effective in preventing TB in children, adolescents and adults, including people with HIV Protect against all forms of TB including MDR and XDR Reduce the cost and burden of TB on patients, health care systems and national economies Play a crucial role in global efforts to control TB

Save lives Break the cycle of transmission

A new vaccine

Reduce cost burden to health systems

Increase productivity

AERAS
Located in Rockville, Maryland, USA, Cape Town, SA and Beijing, China Nonprofit research organization operating as a product development partnership Mission:
Develop effective TB vaccines/biologics to prevent TB across all age groups in an affordable and sustainable manner.

Fully integrated biotechnology organization

Discovery

Preclinical Development

Process Development

cGMP Clinical Manufacture

Clinical Trials Support

Regulatory Clearance

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Aeras: a Product Development Partnership (PDP)

FUNDERS

PHARMA/
BIOTECH

ACADEMICS

AERAS
CLINICAL SITES
GOVERNMENTS

MANUFACTURERS

Collaborating, catalyzing, conducting

Strategies for TB Vaccine Development

Pre-infection: to prevent initial or latent infection or disease Improved priming vaccines Novel booster vaccines Infants; LTBI(-)s

Block Initial Infection

Post-infection: to prevent primary +/or reactivation disease Prevent Early Novel booster vaccines to extend and Disease enhance immune protection LTBI(+) adolescents and adults Immunotherapeutic: to improve therapy Shorten the course of chemotherapy for active TB or latent TB infection Improve efficacy of MDR/XDR/TDRTB treatment

Prevent Latent Infection

Prevent Reactivation Disease

Global Clinical TB Vaccine Pipeline 2012

Phase II
VPM 1002 Max Planck, VPM, TBVI M72 + AS01 GSK, Aeras Hybrid-I + IC31 SSI, TBVI, EDCTP, Intercell RUTI Archivel Farma, S.L

Phase IIb

Phase III
Mw DBY, India, M/s. Cadila

Ad5 Ag85A McMaster CanSino

MVA85A/AERAS485 OETC, Aeras

ID93 + GLA-SE IDRI, Aeras Hyvac 4/ AERAS404 + IC31 SSI, sanofi-pasteur, Aeras, Intercell H56 + IC31 SSI, Aeras, Intercell MTBVAC TBVI, Zaragoza, Biofabri

AERAS-402/ Crucell Ad35 Crucell, Aeras M. Vaccae Anhui Longcom, China

Viral vector rBCG Protein/adjuvant Attenuated M.tb Immunotherapeutic: Mycobacterial whole cell or extract

Our Approach

We work with partners to review and prioritize candidates with a goal of advancing at least two candidates to Phase III efficacy trials. With each advance, we collaborate to adjust site capacity, regimens, R&D, and regulatory approaches.

TB is complex and may require more than one vaccine to address geographic variations in the strains, stages of the disease, and populations. We continually invest in next-generation candidates, applying lessons learned and fostering novel partnerships and approaches.

In collaboration with partners, we evolve and standardize processes to focus on the most promising investigational vaccines. By using scientific approaches including challenge models, systems biology and innovative vaccine designs we accelerate advancement and cut costs.

We mobilize resources across public and private entities to sustain the growing costs of TB vaccine R&D efforts as we advance toward the finish line. Only by expanding our network of support and forging new partnerships can we address the immense scientific challenges and global need.

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Vaccines that prevent adolescents and adults from TB would be the single greatest advance against the disease.
4.2M

Vaccine adol/adult

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There is tremendous momentum in clinical development. Aeras and its global partners are currently testing six candidates in clinical trials.

Clinical Studies
Aeras partners globally to conduct epidemiological studies and clinical trials.

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TB Vaccine Development: a decade of progress but much more to do

2000
No new 2000 preventive TB vaccines in clinical trials

2002
1st preventive 202 vaccine enters clinical trials (MVA85A)

2009
1st Phase IIb 2009 proof-of-concept of preventive vaccine initiated

2012
15 vaccines have 2011 entered clinical trials, 13 currently in clinical trials

15 novel TB vaccine candidates have been in clinical trials in the last decade; no winner yet First human efficacy data expected early 2013 (MVA85A/AERAS-485); major milestone Pipeline of 2nd generation candidates, novel vaccine constructs and new delivery platforms continue to be explored Substantial challenges remain; solutions will require global partnership and commitment. With sufficient resources and positive results from current clinical trials, the first new TB vaccine could be approved within a decade.

The TB Vaccine Blueprint

Keys to Progress
Identifying five keys to progress Creativity in research and discovery Correlates of immunity and biomarkers for TB vaccines Clinical trials harmonization and cooperation Rational selection of TB vaccine candidates

Building support through advocacy communications,

and resource mobilization

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Collaboration is key in an unprecedented effort

Aeras serves as a catalyst by investing in the worlds most promisingTB vaccine candidates and coordinating a diverse community of global scientists, researchers, governments, and funders on a single mission:the development of effectiveTB vaccines.

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Funding and collaboration needed to advance global TB vaccine efforts

The next phase of new vaccine development is the most criticaland

requires that the global community significantly scale efforts .

This cannot be the work of a single foundation or a small set of government or biotech partners, but of a much larger global community.

$78M

$380M

2010 global TB vaccine funding Global Plan annual target

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from TAG Report 2011

Major Contributors

Aeras Gratefully Acknowledges the Volunteers in Our Clinical Trials, Hard Work of AERASDRIVING INNOVATION including Clinical Trial Sites, and Support of these Major Contributors 25 Many Partners

Thank You!
For more information: www.aeras.org aginsberg@aeras.org

Hello, my name is Mycobacterium tuberculosis! I am the king of the pathogens, killing more people than any other infectious agent except HIV From: http://ilovebacteria.com/