Global Disease landscape Competitive Landscape Sanofi Vaccine SWOT Analysis of Dengue Vaccine by Sanofi Analysis by: Ashish Jaiswal | Email: ashish.jaiswal8@gmail.com July 2021

1. Dengue Vaccines Overview
Current status and future prospects
03 June 2021
Submitted by - Ashish Jaiswal
Case study

2. GLOBAL DISEASE LANDSCAPE

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© 2018 Grail Insights
Disease overview for dengue – its geographical spread, global burden and epidemiology
The America, South-East Asia and Western Pacific regions are the most seriously affected regions, with South Asia
representing ~70% of the global burden of disease
Sources: 1WHO, 2Sanofi company website, 3Verified Market Research Report, accessed as on June 2021
0.57
2.40
5.20
2000 2010 2020
2# of dengue cases increased 9 times
Cases in millions (Global)
1Global presence of dengue (2020)
3Global CAGR 16.8%
(2018-2026)
Disease overview
▪ Dengue is the fastest spreading mosquito-borne viral disease and
remains one of the WHO’s top 10 threats to global health in
2020
▪ Dengue is mainly spread by Aedes aegypti mosquitoes and
Aedes albopictus mosquitoes
▪ There is no recommended treatment for dengue other than
rest, fluids and antipyretics
$972.3 m
2018 2026
$279 m
High
Medium
Low
Presence of Dengue
No risk

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Data suggest that the disease has high mortality and morbidity rates with limited treatment
options available
Dengue is distributed across the globe, usually in tropical and sub-tropical climates with four virus serotypes
Sources: WHO Dengue Facts and Overview, Company websites
50%
Of the world's
population
lives under the
threat of
dengue
Disease burden remains global threat
Of the actual
burden is in Asia,
though risk of
infection exists in
129 countries
Deaths globally
each year
occur due to
Dengue
70%
20K
3.9 Bn
people are at
risk of infection
with dengue
viruses
0.4 Bn
dengue virus
infections occur
per year of which
96 million
manifest clinically
40%
Of the world
population or ~3
billion people,
live in areas with
a risk of dengue
✓ Dengue poses burden of over 5
million hospitalizations cases per
year globally, with limited options for
prevention
✓ Global economic burden of dengue
towards annual direct and indirect
treatment costs is US$ 9 billion
✓ # of dengue cases annually
diagnosed in India is nearly 6 million
✓ Developing dengue vaccine is
challenging due to four dengue
virus serotypes DENV-1 to DENV-4

5. COMPETITIVE LANDSCAPE

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Currently dengue vaccine market is witnessing three different scenarios
There is currently only one approved vaccine in the market, second one is expected soon and rest are under investigation
1
A
2
3
Vaccine with marketing approval rights
Vaccine to be launched in 2021 or early 2022
Vaccine under clinical investigation

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Competitive landscape consists of established vaccine players however many of them are still
under development phase
Vaccine market is dominated by Sanofi and could face strong competition from Takeda’s upcoming TAK -003
Market Presence
Market
Potential
Marketed
Launch expected soon
New entrants
Emerging players
▪ The dengue vaccines market is likely to
expand rapidly post the launch of TAK-
003 in 2021/22
▪ Due to safety concerns, Sanofi's’
Dengvaxia has been a commercial
failure with reported low sales of $4
million (2017)
▪ Panacea Biotec, Serum Institute of
India, and Biological E have obtained
non-exclusive licenses for clinical
development and marketing of
TetraVax-DV in India
▪ Panacea Biotec has initiated Phase I/II
clinical trials in India.
High
Low
High
Emerging market for vaccine players
Note: Tier level has been captured basis clinical stages and expected launch in the market

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Currently Dengvaxia developed by Sanofi enjoys monopoly of only marketed vaccine, however
competitive landscape is likely to change with the launch of other vaccines
Dengue vaccine market seems to be lucrative for other players arising from limitations from Dengvaxia
STRENGTH
WEAKNESS
THREAT
OPPORTUNITY
✓ March 2021, the EMA
accepted Takeda’s - TAK-
003 intended for markets
outside of the EU
✓ Takeda is expected to
prepare for regulatory filings
by 2021 for TAK-003
EMA - European Medicines Agency
SWOT analysis for Vaccine Market
✓ Merck plans to launch
dengue TetraVax-DV in
vaccine in 2022/2023
✓ Takeda to cannibalize dengue
market share from Sanofi
post launch in 2021/22
✓ Developing dengue vaccine is
challenging due to four dengue virus
serotypes DENV-1 to DENV-4
✓ Currently marketed Dengvaxia has
limitations due to clinical safety and
efficacy
✓ Evaluation of existing COVID-19
vaccines as a potential solution to
Dengue could be s set back to
dedicated target pipeline

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Vaccine players are overlooking to create robust pipeline either alone or in partnership
Several promising vaccine candidates are under pipeline both in public and private sector
dengue vaccine candidates are currently in the pipeline, both in
the public and private sectors
dengue vaccine candidates are currently in the pipeline, both in
the public and private sectors
Note: Tier level has been captured basis clinical stages and expected launch in the market
Company Tier level Phase
Vaccine
candidates
Type Sponsor
Tier I
Clinical license in ~20
countries with
restricted use
CYD-TDV
Live attenuated chimeric
vaccine (LAVs)
• Sanofi Pasteur
Tier II Phase III TAK-003
Live attenuated chimeric
vaccine (LAVs)
• Inviragen (DENVax)
• Takeda
Tier II Phase III
TV003/TV005
(TetraVax-DV)
• NIH, NIAID (US)
• Butantan Institute,
Brazil
Tier III Phase I V180 Recombinant subunit vaccines • Merck
Tier III Phase I TDENV-LAV & PIV Inactivated virus vaccine
• Walter Reed Army
Institute of Research
and GSK
Tier II Phase II DengiAll Single dose LAVs • Panacea
Tier III Pre clinical DSV4 Recombinant subunit vaccines • ICGEB
Tier III Phase I D1ME100, TVDV
prM/E-expressing plasmid
DNA Vaccine
• U.S. Army Medical
Research
Abbreviations: CGEB - International Centre for Genetic Engineering and Biotechnology

10. SANOFI PASTEUR - DENGVAXIA

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Sanofi’s Dengvaxia is the first licensed vaccine against dengue that is available internationally
Source: Sanofi Company's website
Sanofi’s recombinant DNA technology vaccine Dengvaxia (CYD – TDV)
Indication
▪ DENGVAXIA is a vaccine indicated for the prevention of dengue disease caused by
dengue virus serotypes 1, 2, 3 and 4.
▪ Typically 9-45 years
▪ Singapore (12-45 year age), Indonesia (9-16 year age) and Paraguay (9-60 year age)
Description and Mechanism of Action (MOA)
▪ Dengue Tetravalent Vaccine, Live, DENGVAXIA elicits dengue-specific immune
responses against the four dengue virus serotypes (s (CYD-1, CYD-2, CYD-3, and
CYD-4)
Efficacy
▪ Vaccine efficacy varied according to Age: increased with age; Serotype: higher against
serotypes 3 and 4; Disease severity: higher against hospitalized and severe dengue;
Serostatus at vaccination: higher in Seropositive
Limitations
▪ licensed and available in some countries for people aged 9 to 45 years. The WHO
recommends that the vaccine only be given to persons with confirmed previous dengue
virus infection
Dosing ▪ Three doses 0.5 mL each 6 months apart (at month 0, 6, and 12).
Adverse Dug Reactions ▪ The value of the vaccine is limited by the fact that it may increase the risk of severe
dengue in those who have not previously been infected
Market Opportunity
▪ It was first licensed in Mexico in December 2015 and first commercially available in
2016 in the Philippines and Indonesia.
▪ The vaccine has been licensed in 20 countries

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Study design overview of CYD 14 & 15
• Only ~13% (~4000) sample had serum sample stored prior to vaccination
• All had serum sample stored at M13, one month after 3rd dose

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Phase 3 Trials of CYD-TDV
Included >30,000 children aged 2-16 years in 10 endemic countries in Asia and Latin America Also a previous Phase
2b trial (CYD23/57) with
~4000 participants in
Thailand

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Basis for SAGE recommendations for Dengvaxia
SAGE- Scientific Advisory Group for Emergencies
• During the clinical investigations it was unclear whether safety signal in 2-5 years olds was due to age or to a higher
proportion of this age group being seronegative at vaccination, or both
• Finding led Sanofi to seek vaccine licensure from age 9+ years, distant from the age group in which the signal was
apparent. There was no signal in other age groups reported
• Modelling of cost-effectiveness of the vaccine suggested most efficient to use when the target population had
seroprevalence 70% or greater
• Question remained as to whether vaccinated seronegative 9 year+ might be at increased risk of severe disease
• This was highlighted as important unanswered question by both GACVS and SAGE.
Findings listed below served for SAGE recommendation for approval of Dengvaxia

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SWOT analysis of Dengvaxia
Despite the current controversies, if this vaccine is integrated into the overall dengue prevention programs in dengue endemic
countries, it has the potential of achieving the WHO goals of reducing mortality by 50% and morbidity by 25% by 2020
STRENGTH
WEAKNESS
THREAT
OPPORTUNITY
✓ EMA and US FDA and
more than 20 countries
worldwide have authorized
the use of Dengvaxia
EMA - European Medicines Agency
✓ Dengvaxia vaccination has led to
controversial death in Philippines and
litigations has tarnished the company's image
globally
✓ Approvals of TV003/TV005 and domestic
vaccines will lead to considerable competition
✓ Poor clinical results
compared TAK-003 clinical
results
✓ Dengvaxia's uptake will
remain minimal before
pipeline rivals launch
✓ Dengvaxia is explores
market access opportunities
beyond approved countries
for marketing authorization
including India

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 Dengue vaccine market is projected to be valued over US$ 1.25 billion by 2027
 Globally, an estimated 70% of global dengue vaccines market will be dominated by Asia-Pacific
 Latin America will be the second-largest market for dengue vaccines, and is expected to be US$ ~300 million by 2027
Market
Market Leader
Vaccine
Pipeline
 There are currently five type of dengue vaccine under clinical investigation – live attenuated vaccine, chimeric live
attenuated vaccine, inactivated vaccine, subunit vaccine and nucleic acid based DNA vaccine
 Takeda’s TAK-003 is the most promising pipeline candidate and is expected to supersede Dengvaxia
 TAK-003 will become the new market leader, driving considerable market growth
Conclusion and key takeaways
While Dengvaxia is only available marketed product, dengue vaccine market presents unparallel opportunity to new rivals
since existing global burden remains a major concern

17. Ashish Jaiswal
Comes with 10+ years of industry experience and has been
an asset to the organizations employed
He is certified Six sigma Green Belt (ASQ), EY data
analytics bronze level, and a trained project management
professional
Three qualities makes him a good bet –
* Meets project deadlines * Deliver what is promised * As a
result, have always made his managers look good
Professional Memberships: India Pharmaceutical
Association; TIE Delhi and TIE Global
He is also a IPF-CCE certified coach and upcoming author
for “Your Success Blueprint”
Current location: Gurgaon
Open for
Q&A
Organizations served