Nov2016 © 2016 Butantan Institute - Reproduction forbidden without prior authorization

OIWEEK 2017

1901Established to produce serum against the bubonic plague

Vital Brazil, first director, investigated antivenoms against snake bites

One of the main public producers of vaccines and

antivenoms in Latin America2016

mission

To contribute to public health through research, innovation, production and

development of biological products, sharing knowledge with the society

vision

To be a world-class public institution dedicated to research, development,

dissemination, education and the manufacturing of biological products for public

health demands

Instituto Butantan

Vaccine and Sera Production

Scientific Research & Development

Cultural Center Other areas

Butantan Foundation

organizational structure

Source: Instituto Butantan (Jun2016)

1.948 direct employees

35% public employees

65% Foundation workers

~100 outsourced employees

~750,000 sq m 300,000 60%in the heart of visitors/year preserved

the urban area green area

Bu

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USP

4museums

microbiology museum

Emílio Ribas museum

Bu

tanta

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am

pus

history museum

biology museum

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ntific

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• Research units

- Scientific Development Division [19 labs]

- Center of Biotechnology [8 labs]

• Hospital Vital Brazil [10 beds]

• Central Animal Facility

• 180 PhD researchers

• 500 graduate students

Labs

Arthropods

Bacteriology

Biochemistry

Biotechnology Center

Cell Cycle

Cellular Biology

Ecology and Evolution

Genetic

Herpetology

Immunochemistry

Immunogenetics

Immunopathology

Pain and Signaling

Parasitology

Pathophysiology

Pharmacology

Special Lab of Applied Toxinology

Viral Immunology

Virology

Zoological Collections

4 major areas

animal

biology

vaccinology development

toxinology

scie

ntific

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bs

ed

uca

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• scientific knowledge coursesvenomous animals; sera and vaccines; pharmacovigilance; amphibian biology etc.

• more than 20 graduate extension courses

• PAP - Professional Advancement

ProgramHealth sector professional training

• Scientific Initiation

• MBA in Health Innovation Management

Trains professionals for the management of

critical functions of the innovation process,

promoting the creation of mechanisms to

facilitate technology transfers.

• Inter-institutional Graduate Studies in Biotechnology

[University of São Paulo, Institute for Technological Research - IPT, Instituto Butantan]

• Graduate Studies in Toxinology

approved by CAPES in August 2010, with a grade of 5 (out of 7 points), for Masters and PhDs

an

tive

no

mp

rod

uct

ion

horse immunizationSão Joaquim Farm

50 km from São Paulo

~ 800 horses

22,000 liters of plasma/year

snake facility

~1,000 animals

- Bothrops - 5 species

- Crotalus - 2 subspecies

- Lachesis - 1 species

- Micrurus - 2 species

spider / scorpion facility~ 15,000 animals

- Loxosceles spider (brown spider)

- Phoneutria spider (banana spider)

- Tityus scorpion (yellow scorpion)

caterpillar lab ~ 600 animals

- Lonomia caterpillar

ven

on

for

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tive

no

mp

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ion

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ust

rial c

om

ple

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pro

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7 plants

• Anaerobic vaccines - Tetanus and Botulism

• Bacterial Purification Center

• Aerobic Vaccines- Diphtheria and Pertussis

• Hepatitis B

• Influenza

• Rabies

• Sera

1 Formulation and Filling Center

5 multifunctional pilot plantso Dengue

o Rotavirus

o Monoclonal antibodies

o Influenza - H5N1

o Blood products

po

rtfo

lio o

f se

rum

pro

duct

s

13immunoglobulins

5 snake antivenoms diphtheria antitoxin

spider antivenom

caterpillar antivenom

tetanus antitoxin

botulism E antitoxin

rabies antiviral

botulism AB antitoxin

scorpion antivenom

2016 capacity 500,000 vials/ year

Ministry of Health demand 900,000 vials/ year

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f va

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es

9 vaccines of the national calendar

88 million doses (2015)

DTP

Diphtheria-Tetanus-Pertussis(celular)

DT

Diphtheria-Tetanus(for children)

dT

Diphtheria-Tetanus

(for adults)

rabies

hepatitis B

influenza

HPV

tetravalent

hepatitis A

DTP

Diphtheria-Tetanus-Pertussis(acelular)

Programa Nacional de Imunizações - PNI

[National Immunization Program]

free of charge vaccination

5.570 cities - 27 states (all Brazilian states)

7 official vaccine manufacturers

Hepatitis B

- 1st recombinant vaccine produced

in Brazil

- 100% produced by Instituto Butantan

- target audience (2013):150 million people

under the age of 49 years

(75,6% of the population)

- 800.000 carriers in Brazil

HPV

- 685,400 infected people/year

- 95% of the cases of cervical cancer

- second most common cancer in women

Sources: SINAN; website Portal da Saúde - SUS; Ministry of Health (2013)

Influenza

- TT concluded

- 50 million doses produced in 2016

Instituto Butantan: complete biological production lines certified with Anvisa GMP

Pro

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-P

NI

29%

42%36%

40%

48%

40% 40%

28%

21%

34%

39%

40%

15%35%

32%

34%

5%

5%3%

4%

5%

4%4%

6%

2%

4%

5%

5%

4%

11%

8%7%

6%

4%

6%

34%

11% 13%

6%

27%

12%

24% 22%

0%

20%

40%

60%

80%

100%

120%

2008 2009 2010 2011 2012 2013 2014 2015

% o

fac

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ired

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ses

Opas

Tecpar

Funed

FAP

Butantan

Bio-Manguinhos /Fiocruz

328 m 306 m 452 m 311 m 211 m 230 m 235 m 244 m doses

PAHO

Ministry of Health acquisitions

po

iso

no

us

an

imals

study of bioactive components of poisonous animals

pharmacological activities

• analgesic

• anti-inflammatory

• anticoagulant

• antitumor

• nervous system related action

• anti-hypertensive

pate

nts

* others include: propolis extract, protein from

Leptospira, spider proteins, recombinant protein for

AIDS diagnosis, etc.

Lopap – 4 patents

Biolab / Fapesp

Amblyomin-X – 2 patents

União Química / Fapesp

Silica (SBA-15) – 1 patent

Cristália / Fapesp

patents quantityvaccine 12

serum 3

immunotherapy 3

haemostasis 2

analgesic 2

peptide 2

tissue regeneration 2

anti cancer 1

antibody 2

others* 11

total 40

Pertussis low – 1 patent Crotalphine – 2 patents

Biolab / Fapesp

Immunosuppressor – 1 patent

Cristália / Fundação Butantan

pip

elin

e

nr Products description1 Dengue Vaccine Attenuated tetravalent vaccine (serotypes DEN1, DEN2, DEN3, DEN4) –

Phase 3 of clinical trials

2 Zika vaccine Inactivated, DNA, attenuated

3 Rotavirus vaccine Attenuated pentavalent vaccine (serotypes G1, G2, G3, G4, G9) –

Phase 2 of clinical trials

4 Pertussis low vaccine B. pertussis whole cell with lower content of LPS for adults and combinations

5 Pneumococcal vaccine Inactivated non-encapsulated pneumococcal whole cell

6 Hepatitis B + MPLA vaccine For > 50 years old and immunocompromised persons

7 rBCG - Hep B vaccine For neonates

8 Onco rBCG vaccine For bladder cancer treatment

9 Adjuvant BpMPLA BpMPLA derived from LPS of B.pertussis to be combined to different vaccines

10 Bee’s antivenom Treatment against multiple bee stings

11 Sílica (SBA-15) Adjuvant for orally administrated vaccines

12 Amblyomin-X Anticancer medicine, obtained from tick saliva

13 Crotalphine Potent analgesic drug from snake venom. Long-lasting analgesic (2-5 days)

14 Crotamin Cell penetrating peptide - Introduction of genetic materials into the cells, such as DNA and

RNA

15 Lopap Prothrombin Activator, anti-apoptotic activity and other pharmaceutical formulations

16 Monoclonal antibodies Anti-CD3 for transplantion rejection and other monoclonals for other uses

17 Hemoderivatives Production of IgG, factor VIII, IX, Albumin and other products

18 Diagnostic kits For Dengue, zika and leptospirosis diagnostic

Boa Vista

Porto Velho

Manaus

Cuiabá

Campo Grande

Brasília

Belo Horizonte

São José do Rio Preto

São Paulo

Porto Alegre

Fortaleza

Recife

Aracaju

00

- 2 clinical sites (Hospital das Clínicas da

Faculdade de Medicina - Universidade

de São Paulo

- 300 volunteers, 18-59 yo

• phase II clinical trials

step b

50 dengue-naïve participants

200 dengue experienced participants

den

gue –

Bu

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IH v

acc

ine

• phase III clinical trials

started on Jan 2016

- 14 clinical research centers

- 17,000 volunteers, 2-59 yo

- safety, immunogenicity and efficacy

objective: vaccine license by Anvisa

step a

50 dengue-naïve participants

zika

vir

us

pro

gra

m –

Inst

ituto

Bu

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n

1. Diagnostic tests

serology test

- Butantan and Medical School of the University of São Paulo

(Grant Horizon 2020: infrastructure for the Butantan dengue vaccine phase III clinical trials)

- Instituto Butantan and Los Alamos National Laboratory (USA)

2. Therapy

- horse immunization – Butantan R&D program

- neutralizing human anti-zika monoclonal antibodies

Butantan and Rockfeller University (USA)

- small molecules with antiviral action

3. Vaccine development

- inactivated zika vaccine: Butantan R&D program – Barda / WHO support

- live attenuated pentavelent dengue-zika vaccine – Butantan / NIH

- live attenuated zika vaccine – Butantan R&D program

- subunity zika vaccine – Butantan / USP

cen

tres

of exc

elle

nce

INCTtoxInstituto Nacional de Ciência e Tecnologia em Toxinas[National Institute of Science and Technology for Toxins]

Financial support: CNPq

[Center of Toxins, Immune-Response and Cellular Signaling]

10 projects – biochemical, molecular and cellular mechanisms of toxins with therapeutic potential

Financial support: Fapesp

discovery and validation of therapeutic targets

for the development of new drugs for

inflammatory based diseases

Financial support: GSK-Fapesp

Centro de Toxinas,

Resposta-Imune e

Sinalização Celular

Instituto

Butantan

Steering

Committee

inte

rnatio

nal c

olla

bo

ratio

n

Dengue vaccine

Zika vaccine

3-4 Nov 16

Zika Summit

Mar 2017

Workshop Butantan

- United Kingdom

Science

dissemination,

animal biology and

neuroscience

Oct 2017

Workshop Butantan -

CEA/France

Vaccines –

Immunology; Toxin

analysis by in vivo

Imaging; Therapeutic

toxins and Expression

of toxic proteins

Butantan - Myanmar

Agência Brasileira de

Cooperação - MRE

Harvard

natio

nal a

nd

in

tern

atio

nal p

art

ners

hip

s

current occupation

labs

production

cultural

administration areas

considering

- public and restricted circulation

- preserved areas

education

Institut for Innovation in

Biotechnology Butantan - IIBB

masterplan

‘

Butantan

USP

grupo de ação rápida para

doenças emergentes

GARDE

total area : 30,000 sq m

fase 1

fase 2

• center dedicated to research, innovation and generation of

innovative enterprises

• renovated building (30,000 sq m)

• promotion of

- Group of prompt action for emergent diseases (Garde)

- joint ventures with private institutions

- Butantan and partners development projects

Institut for Innovation

in Biotechnology Butantan - IIBB

IIBB

conceptual

project

Jorge KalilDirector

Marcelo De FrancoDeputy diretor

Board of DirectorsJorge Kalil (presidente)

Erney F. Plessmann de Camargo

Fernando de Souza Meirelles

Gonzalo Vecina Neto

Luiz R. Raja Gabaglia Travassos

Luiz Vicente Rizzo

Moisés Goldbaum

Paulo Lee Ho

Yara Cury

Geraldo AlckminGovernor of the State of São Paulo

David UipState Secretary of Health

Sergio Swain MullerCoordinator of Science, Technology

and Strategical Health Products

Erney F. P. De Camargo

President

Board of CuratorsJorge Kalil (president)

Fernando de Souza Meirelles

Gonzalo Vecina Neto

João Fernando Gomes da Oliveira

Luiz R. Raja Gabaglia Travassos

Luiz Vicente Rizzo

Marcelo De Franco

Moisés Goldbaum

Paulo Lee Ho

Yara Cury

Finance CouncilCarlos Alberto Marsal

Joaquim José C. Engler

Hélio Nogueira da Cruz