tb and vaccines

8/14/2019 TB and Vaccines

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Tuberculosis

History, Now, and Why the Future Depends on NewVaccines

J2J Lung Health Media TrainingOctober 31, 2013

Kari Stoever


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Aeras: Background

Founded in 2003

Fully integrated, nonprofitbiotechnology organization within-house capabilities in finance,portfolio management, GMP pilotmanufacturing, translational productdevelopment and policy,advocacy and resource mobilization

501(c)(3) organization registeredin Washington DC

Offices

Rockville, MD (headquarters)

Cape Town, South Africa

Beijing, China

Governed by a Board of Directors

5 technical advisory groups incorporating expertise from around the world

Executive leadership team with decades of experience developing andcommercializing new vaccines/biologics

~ 160 employees with annual budget of approx. USD $55 million


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Mother Nature is

a Serial Killer

3
http://www.youtube.com/watch?v=9sqfYPRrc2M


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The Scale of the Problem

4

Source: Nature/ World Tuberculosis Report,

2012


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TB decline in the pre-antibiotic era

5


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R i dd i h TB id i h
http://www.youtube.com/watch?v=BYphnE-4DQI


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Recent progress in addressing the TB epidemic hasbeen enabled through enhanced global coordination

and large investments

0

50

100

150

200

250

300

1990 1995 2000 2005 2010 2015

Year

Mortality

HIV co -infect ion

incidence

Incidence

Prevalence

TB rates per 100,000 population

DOTSDOTS-Plus

Launch of global partnerships and new control tools in the 1990s contributed to decreasing TB rates

Source: Global Tuberculosis Report 2012, WHO (2012), Nature Vol 502, No. 7470 Suppl, S2 (2013)

Stop TB Partnership

WHO/IUTLD GlobalProject on MDR-TBSurveillance

UN Millennium Development Goals


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Incidence of TB is falling so slowly

that it will take a millennium to end TB

Vaccines needed to turn the tide

Source: Christopher Dye, WHO


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Underinvestmentin new drugs, diagnostics and

vaccines has led to growth of drug-resistant TB.

TB evolving with some strains

becoming virtually untreatable

New, novel TB vaccines will aim to

prevent all strains of TB.

Failure to innovate has ledto drug resistance strains

> 500,000 MDR-TB cases in 2011

92 countries have reported XDR-TB


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Extensively Drug-Resistant TB: 92 Countries

10

Source: WHO Global TB Report, 2013


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The problem of microbes becoming increasinglyresistant to the most powerful drugs should be

ranked alongside terrorism and climate change onthe list of critical risks to the nation.

Sally Davies, UK Government Chief MedicalOfficer

11


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Full implementation of Global Plan: 2015 MDG target reached

but TB will not be eliminated by 2050

Current rate of decline-2%/yr (globally)

W Europe after WWII

-10%/yr (Historical

example)

China, Cambodia

-4%/yr (the best

observed nowadays)

Elimination target:100x higherthan elimination

target in 2050


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What are the challenges if we target elimination

1. Still only two-thirds of the estimated total of 8.6 million people whofell ill with TB in 2012 were notified.

2. Despite a reduction of 45% since 1990, still over a million people diedof TB out of the estimated 8.6 million new cases in 2012.

3. Currently, only one in five of the notified patients estimated to have

MDR-TB is being diagnosed and treated.

4. The BCG vaccine does not have efficacy in preventing transmissionand there is no global strategy to protect against development ofdiseases in those who are infected with M. tuberculosis.

5. Insufficient tools to detect, treat or prevent TB,R&D underfunded, and even when tools areavailable, inefficient transfer of tools/technology.


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Controlling and reducing TB incidence requires

the application of transformational interventions

Infected ind ividu als

Preventing

transmission and

infection

Blocking progression

to infectious TB

Treating and

sterilizing active TB

A

B

C

Infect ious

TB

Transmissi

on

A2B

C

Transmission

cycle

breakpoints

A1Breakpoints


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Ill-equipped for this Complex Epidemic

We are beginning to see the winds of change, but

what we really need is a storm. It is imperative thatwe transform the way we diagnose, treat, prevent,

and control TBthrough biomedical research andpublic health measures

Anthony Fauci, Director of NIAID


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EXPOSED: The Race Against Tuberculosis

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A Global Problem

17

Source: Nature/ World Tuberculosis Report,

2012


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A U.S. Problem: Recent Outbreaks

Nearly 10,000 cases in 2012

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https://mapsengine.google.com/map/edit?mid=zGX1CK45yhq8.kaiucqJ3DbAc


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A U.K. Problem: Outbreaks in London

19


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A European Problem

Economic burden of TB in Europe: >5billion/year

Lost productivity and treatment costs

>80,000 cases/year of MDR-TB in Europe

Highest in Eastern Europe and Central Asia

UK: Cost to treat drug-resistant TB>50,000/patient

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South Africa

21


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He that will not apply newremedies must expect newevils; for time is the greatest

innovator.Sir Francis Bacon

Russia: Drug Resistance


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India: Healthcare Workers at Risk & TDR-TB

23


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China: Biggest Disease Burden &Urbanization

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Photo: NPR/Ng Han Guan/AP New York Times, June 15, 2013


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Vaccines: The Future

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Nature will continue to evolve infectiousdisease threatsboth endemic andpandemic

Rather than resigning ourselves tocatastrophic outbreaks, we have thepower to disrupt historical trend lines

through the use of new vaccines tocombat these threats

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In the same way that during my Microsoft

career I talked about the magic of software, Inow spend my time talking about the magic

of vaccines. Vaccines have taken us to thethreshold of eradicating polio. They are themost effective and cost-effective health toolever invented. I like to say vaccines are a

miracle.Bill Gates


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Vaccine Success: Smallpox, Measles & More


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Vaccine Success: Polio

Source: WHO/IVB Database, July, 2013


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1908 2013

TB and Progress?

90-year-old BCG vaccine is the mostwidely used vaccine in the world


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The Need for New Vaccines

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A century of neglect followed by a decade ofprogress

2000 2002 2009 2012

No new

preventive TB

vaccines in

clinical trials

1st preventive

vaccine enters

clinical

trials (MVA85A)

Phase IIb proof-of-

concept trials of

preventive

vaccines initiated

16 vaccines have

entered clinical

trials, 12 currently

in clinical trials


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The Global Pipeline of TB Vaccine Candidates

Ad5 Ag85A

McMaster CanSino

VPM 1002

Max Planck, VPM, TBVI, SII

MVA85A/AERAS-485

Oxford, Aeras

M. Vaccae

Anhui Zhifei Longcon, China

MTBVAC

TBVI, Zaragoza, Biofabri

H1 + IC31

SSI, TBVI, EDCTP, Intercell

M72 + AS01E

GSK, Aeras

ID93 + GLA-SEIDRI, Aeras

RUTIArchivel Farma, S.L

Crucell Ad35/MVA85A

Crucell, Oxford, Aeras

H4/AERAS-404 + IC31

SSI, Sanofi-Pasteur, Aeras, Intercell

H56/AERAS-456 + IC31

SSI, Aeras, Intercell

Crucell Ad35/AERAS-402

Crucell, Aeras

VIRAL VECTOR

rBCG

PROTEIN/ADJUVANT

ATTENUATED M.Tb

IMMUNOTHERAPEUTIC:

MycobacterialWhole Cell orExtract

AERAS SPONSORED

PHASE I PHASE IIa PHASE IIb PHASE III


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Global partners for epidemiological studies and clinical trials

Clinical Studies


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Public Health Impact of a TB Vaccine

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Investing in prevention is the

greatest austerity measure

At a global level, an estimated US $1-3trillion over the next 10 years

X/MDR TB can be 200-1000 x more

expensive to treat than drug-sensitive

cases

MDR-TB utilizes 33% of South Africas

TB control budget (2% of all TB cases)

Control and treatment would cost us~$80 billion over the next decade.

Yet it could take $800 million over 10-15

years to develop new vaccines.


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Deciphering the Tower of Babble?

If we had an AIDS

vaccine we wouldnt

have to worry aboutTB

We will have a TBvaccine in the next

decade

The vaccine science isnt

there, Ill believe it when I

see it.

We should be investing indrugs and diagnosticsinstead of vaccines

2ndleading cause of deathfrom a single infectiousdisease

Zero deaths, zero infections,

zero suffering

SUPERBUG

TB is a disease of poverty

London is the TB capital of the

EuropeTB outbreak in Los An eles

TB is preventable, treatable and

cost effective.

Cost of XDR treatment up to 1000xmore expensive

Control efforts are working,40% reduction in deaths over

the past 20 years

More absolute cases of TB inthe world today than in 1990

Drug-resistant cases on the rise

New vaccines would be the single-most cost-effective tool in our fightagainst TB.

I was vaccinated against TB


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http://www.gapminder.org/videos/swine-flu-alert-news-death-ratio-tuberculosis/


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Communications

Compelling stories from many angles

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A Woman's Drug-Resistant TB Echoes Around the WorldBy GEETA ANANDUpdated Sept. 8, 2012 9:03 a.m. ET Dangerous TB Patient Detained on U.S. BorderByBETSY MCKAY

March 1, 2013

Action Urged Against Fake Tuberculosis DrugsPoor-Quality Medications Are Contributing to Treatment Resistance, Researchers Say

ByBETSY MCKAYJuly 4, 2013

Winners of the 2013 Daniel Pearl award for theworlds best cross-border investigative reporting

Source: wsj.com
http://vimeo.com/62215694


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http://vimeo.com/62215694


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A four-part series of 9-13 minute films about the deadly global epidemic of tuberculosis.

By telling the stories of four inspiring individuals, interspersed with expert commentaryfrom some of the worlds top TB physicians, scientists, advocates and policymakers,

EXPOSED brings viewers to the forefront of the fight against TB.

1: The Global Epidemic

Natalie Skipper, an MDR-TB

survivor from the United

States, and medical experts

give a sense of the global TB

epidemic.

2: The Rise of a Superbug

Dr. Jayant Banavaliker, a

leading TB doctor in Delhi,

chronicles his daily struggle to

save patients using todays

limited tools. Plus, Phumeza

Tisile fights XDR-TB in South

Africa.

3: The Innovation Movement

A profile of Unathi Gwintsa, a

passionate participant in a TB

vaccine clinical trial in South

Africa, who is driven by her

desire to protect her daughter

from TB.

4: The Last Mile

Prof Helen McShane, who

has spent the last 12 years

developing new TB vaccines

in the UK, explores why now

is a pivotal moment in history

to save millions from TB.



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~ 80,000 views, either on Facebook, Vimeo,YouTube, or the Aeras website, with about 1,500new views in the last month 1000 non-English views; seen in 135 different countries

Screened for >1,350 government decision-makers,biotech and pharmaceutical leaders, TB vaccinedevelopers, national treatment program managers,research advisors, and more at >20 global events

Won PR Dailys Digital PR Award for Best Cause-

Related Video and received an honorable mentionfor Best Digital PR Campaign in the Nonprofit Sector


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Building momentum

through the

development of microcampaigns


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Engage new audiences by focusing on key issue areas and communities connected to the TB issue. In additionto helping us reach new audiences and constituencies, these issues have been selected because they arepriority areas for target funders as well as the media.

Key Issues

TB & MiningTB & Health

WorkersHuman & Animal TB

Launch mid-Nov. 2013 April - June 2014 Launch TBD


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TB vaccine R&D is a long-term, high-risk endeavor. There are no major scientificmilestones on the horizon in 2014.

Therefore, we need to engage in key current issues in the broader field of TB to growand sustain interest and support for TB vaccine R&D on the global health agenda.

The key issues identified provide a potential for increased scientific and/or advocacycollaborations.

With a focus on key issues in the broader field of TB, Aeras will build new partnershipswith stakeholder groups and expand our audience. New constituencies will help

increase demand for TB vaccine R&D prioritization.

Why Focus on these Key Issues?


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TB and Mining

46

Source: Dharmadhikari et. Al., 2013


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Human and Animal TB

TB in animals and humanscontinues to be an enormouspublic health problem and aneconomic burden on agriculturaland health budgets UK: In 2012, >37,000 cattle

slaughtered at a cost of 100Mto the taxpayer

DEFRA estimates >1 billionwill be spent over the nextdecade for bovine TB control

We can inform vaccinedevelopment in both animal andhuman TB by combiningexpertise, learning & resources

47

Source: Department for Environment, Food and Rural Affairs, 2013


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TB and Healthcare Workers

Increased risk ofTB infection

Short, mediumand long-term

activities canhelp protect at-risk populations We can

educate, andmotivate aglobalpreventionresearch

agenda 48

C t t t t


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Content strategy

We are building a robust and integrated communications, resource mobilizationand advocacy strategy and process that drives efficiency and scale up in

content development and distribution. Every time we publish a fact sheet,report or press release, every time someone speaks on a panel or writes ablog, every time we hold a briefing, we will seek to distribute our contentthrough as many relevant channels as possiblebuilding new audiences andsupport along the way.

Content

Web

Feature

Fact

Sheet

Email Social

MediaEvent /

Conf. CallPress

Stakeholder


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Activities/Message Vehicles

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Conferences and Events

Leverage national, regional and global fora on key issues platform to place vaccine R&D onthe agenda

Microsite and multimedia

Maximize reach of new website capabilities and deepen our social media presence tostrengthen Aeras voice in global dialogue on key issues

Fact sheets

Build issue-specific messaging to reach new audience, engage new constituencies, andcreate TB vaccine R&D advocates

Outreach avenues

Blogs

Social media

Traditional media

Email


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Introduction to the TB Vaccine Investment

Case

A dynamic model was developed to address four key objectives:

1. To identify a product development strategy that maximized thepublic health impact of new TB vaccines;

2. To conduct a strategic market analysis to assess the

commercial viability of new TB vaccines;3. To evaluate portfolio development costs in order to inform on

investment strategies by phase of development over time, tosupport the successful commercialization of at least one newTB vaccine;

4. To demonstrate the cost efficiencies of implementing a portfoliomanagement approach.


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TB vaccines are our best hopeto end the TB epidemic

Shared public and privatesector investment at keystages will offset risk

Even partially effective TBvaccines for adults and

adolescents will have asignificant public health impact

A viable market for TBvaccines exists

Greater diversification needed

in TB vaccine portfolio A disciplined portfolio

management approach isnecessary

Business Case Key Messages


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Countries in analysis 197 countries included in the Applied Strategy Model

14 countries excluded (no TB and/or birth data 2009)

183 countries included for analysis

183 countries geographic segmentation

Economies are divided according to 2011 GNI per capita, calculatedusing the World Bank Atlas method

low income - $1,025 or less;

middle income - $1,026 - $12,475

lower middle income, $1,026 - $4,035;

upper middle income, $4,036 - $12,475

high income - $12,476 or more

Global TB Market Segmentation

TB Vaccines Target Product Profiles


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TB Vaccines Target Product Profiles

Adolescents & Adults

Vaccine

To prevent active disease

10yo

without known active TB

2 doses

Routine vaccination of 10yo, andMass campaigns in 11yo, every

10 yrs

HPV coverage rate proxy for 10yo

60% improvementin relative efficacy compared

to the control arm

No safety concerns

Indication

Target Population

# Doses

Vaccination

Strategy

Vaccination

Coverage Rate

Proxy

Expected Efficacy

Expected Safety

Infant Vaccine

To prevent active disease

Newbornsindependent of

HIV status

1 dose

Routine vaccinationof newborns

BCG

60% improvementin relative efficacy compared to

current BCG

As safe ascurrent BCG

Portfolio Evolution 2014-2027 using


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$0

$20,000

$40,000

$60,000

$80,000

$100,000

$120,000

Projected Annual Development Costs by Stage

Discovery / Pre-Clinical 1 Pre-Clinical 2 Phase 1 / 2A

Phase 2B Phase 3 Pre-Commerce

Total Development C osts

$846,786

0

5

10

15

20

25

NumberofVaccines

Number of Vaccines in Portfolio by Development Stage Over Time

Discovery / Pre-Clinical 1 Pre-Clinical 2 Phase 1 / 2APhase 2B Phase 3 Pre-CommercePost-Commerce

Portfolio Evolution 2014 2027 using

Monte Carlo Simulations

Portfolio Development Probability of


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Portfolio Development Probability of

Success The key outputs of the portfolio development analysis are:

Probability of successful commercialization of a vaccine by year

Costs to develop the portfolio to commercialization

Given that there are numerous potential outcomes related to the various probabilitiesof success, the model incorporates Monte Carlo simulation to analyze the variouspotential outcomes.

Based on the base assumptions and the initial portfolio, there is a 55%probability of having one vaccine commercialized by 2024 and greater than 80%chance of having one vaccine commercialized by 2030

16% 16%

55% 56%

70%

77%79% 82%

83%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

By Year2022

By Year2023

By Year2024

By Year2025

By Year2026

By Year2027

By Year2028

By Year2029

By Year2030

Probability of 1 Vaccine Reaching Commercialization

O ll P tf li D l t C t


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Overall Portfolio Development Costs

As highlighted in the histogram above (based on Monte Carlo simulation of the variouspotential outcomes), the estimated cost range for developing one vaccines throughcommercialization can range from $435m to $1,050m, with and average development costof $630m.

0

1020

30

40

50

60

70

80

90100

$250 -$300

$300 -$350

$350 -$400

$400 -$450

$450 -$500

$500 -$550

$550 -$600

$600 -$650

$650 -$700

$700 -$750

$750 -$800

$800 -$850

$850 -$900

$900 -$950

$950 -$1,000

$1,000 -$1,050

Total Portfolio Development Costs - 1 Vaccine Commercialized

Std. Deviation - 97,254

630,592Average -

Min -

Max - 1,050,286

435,250


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Portfolio Development Funding Analysis

The financial model also analyzes various funding alternatives for the

development of the current TB vaccine portfolio This component of the model leverages the first two components of

the model

Total development costs required to develop the portfolio - i.e.what amount of funding is going to be needed?

Potential royalty stream that can be realized uponcommercializationi.e. how is the funding going to be repaid?

The model allows for analysis of various non-traditional fundingalternatives to facilitate the development of the portfolio, including bothdebt like investments and equity investments (in addition to grants)

The key outputs of this component of the model include: Analysis of the financial returns to the funding sources

The optimal funding sources and security structures will ultimately be determined by

the composition of the portfolio and associated risks of development

P bli d P i t S t Ri k Sh i


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Public and Private Sector Risk-SharingA blended-capital financing structure will enable appropriate risk-sharing betweenprivate and public sectors:

With governments strong economic and public health interest in new TB vaccines,public funding will be required to support the earlier phases of vaccine

development, where the scientific risk is the greatest

In return, industrial partners will be expected to cost-share in the later, moreexpensive phases of development

I iti l T k f A l i T D t


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Initial Takeaways from our Analysis To-Date

There is a significant market potential for commercialized

TB vaccines, particularly an adult/adolescent vaccine The overall market potential of a successful

adult/adolescent vaccine seems sufficient enough tosupport meaningful financial returns to industry and potential

niche public/private investors in the development of thevaccine portfolio.

Having a robust and diverse pipeline of vaccine

candidates in early development stages is critical to

attracting investment capital as the portfolio approachincreases the likelihood of successful commercialization andthus financial returns.

There might be poss ible RSFF direct and /or ind irectf inancing opportunities in late stage R&D phases

Global Portfolio Management


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Global Portfolio Management

Principles

Optimizat ion: The framework will utilize existing technical expertise, scientific advisorycommittees and governance structures of key parties and build new capacity whereneeded in order to enhance portfolio decision-making and maximize organizationalsynergies and knowledge sharing.

Transparency: Procedures and decision-making will be clear and objective based on

objective gating and priority setting criteria that disclose and avoid any conflict ofinterest.

Sound Financ ial Management: Funds will be managed in a rational manner withsufficient control over the use of those resources to ensure that stage gate decisionprocesses are adopted and utilized.

Diversi f icat ion: The portfolio will be global and diverse to minimize financial risks andcreate the best opportunity for success; similarly, funding sources should include abroad array of different types of financing to increase the pool of available resources asmuch as possible.

Effect iveness: The collaboration will offer donors and investors a highly efficientmechanism in order to show value for money, participate in risk-sharing and reduce timeto market.

Affordabi l i ty : Vaccines to be developed will have to be available worldwide at

affordable prices. 61

A streamlined decision-making framework in order to advance the global TBvaccine portfolio and realize overall R&D cost efficiencies through effective portfolio

management will follow the principles:


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Enhancing Portfolio Management Capabilities

Leverage Aeras and TBVI scientific expertise in the Global TB

vaccine partnership regarding decisions on development of projects

within the TB vaccines portfolio.

Link funding decisions to scientific decisions made by Global TB

Vaccine Partnership

Incorporates both preclinical and clinical portfolios to optimizediversity

Prioritizes around a set of predefined targeted product profiles(TPPs) that seeks to maximize the public health impact of new TBvaccines

Implements 1 universal and shared set of rigorous stage gatingcriteria and milestone based finance through contractualagreements

Shares information from all trials successful or failing to improveselection and design of future trials.

Consults outside expertise to review and offer expertise on the


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Funding priorities have lagged relative to the
http://www.youtube.com/watch?v=OaiSHcHM0PA


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g p gg

morbidity and mortality of tuberculosis

1,000,000,000Tuberculosis death

Small pox

PlagueInfluenzaCholera

30,000,000HIV/AIDS death

Malaria

Tuberculosis has led to more deaths in the last200 years than any other infectious disease

Source: Global Tuberculosis Report 2012, WHO (2012), Nature Vol 502, No. 7470 Suppl, S2 (2013), Financing GlobalHealth 2012, IHME

but has received significantly less funding in the

last 10 years as compared to HIV and malaria1

Malaria

$43 billionHIV/AIDS global funding

1 Based on OECD and IHME Development Assistance for Health (DAH) funding data

HIV/AIDS

Tuberculosis

$7 billionglobal funding


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TB R&D funding overview

US $600 million was invested in TB vaccine R&D between 2005 and2011

5 institutions/agencies provided nearly 80% of funding (BMGF, NIH, EC,DFID, DGIS)

To date, EDCTP has invested approximately42 million towards site

preparedness and capacity building for TB vaccines in Africa, withadditional direct funding for specific clinical trials

PDPs across the board have seen cuts in the order of US $30-50million per year over the past three years.

Only 3 new G8 governments are exploring new or increased funding forPDPsGermany, Australia and Japan

Global trends show declining support for neglected disease R&D

overall

TB R&D has seen an 8.3% drop from 2010 The majority of funding is allocated to drugs (42.5%), followed by basic research

(26.8%), preventative vaccines (18.8%), diagnostics (9.1%) and therapeutic vaccines

(0.01%)

E j l i US f di f l b l h lth i i h d th k


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Every major scale-up in US funding for a global health crisis has occurred thanks

to strategically executed communications campaigns, constituency building and

active advocacy efforts.

US Malaria YOY Funding:

From $146 Million to $834 MillionUS Global HIV/AIDS YOY Funding:

From $614 Million to $5.5 Billion

US TB Funding Fails to Keep Pace


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$85.1 $92.0 $91.5$94.9

$163.2$176.6

$243.2$238.4

$254.4

$0.0

$50.0

$100.0

$150.0

$200.0

$250.0

$300.0

2004 2005 2006 2007 2008 2009 2010 2011 2012

US TB funding has failed to keep pace with that of malaria and HIV/AIDS which

increased 6x and 9x respectively in the past decade. Had TB funding kept pace with

these diseases, support would be between $500 million to $760 million per year.

US Global TB Funding:From $85 million to $254 million.

Source: Congressional Resource Service

In 2011 HIV vaccine R&D received ~9x ($845M) more funding


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In 2011, HIV vaccine R&D received ~9x ($845M) more fundingcompared to TB vaccine R&D ($95M). Public sector support was ~19xhigher.

Source: TAG, 2012Source: HIV Research Tracking, 201


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We Must Increase Momentum


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Thank You.

tb and vaccines

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