NEW GENERATION BIOFACTORIES FOR A GLOBAL ACCESS TO HEALTH

Juan J. Infante, PhD.BIONATURIS CSO

BIOORGANIC RESEARCH AND SERVICES, S.A.

BIOPHARMACEUTICAL PRODUCTION IN INSECTS

1. Mind the gaps!2. How do we see the future.3. A value proposition.4. Bionaturis manufacturing.5. Bionaturis products.6. Conclusions.

MIND THE GAPS!

DRUGS BIOLOGICALDRUGS

90 %

10 %

80 %

20 %

World Investment population budget use

Intolerable GAP #1: USE OF MEDICINES

+ Tech Transfer

Security/Efficacy/RegulatoryMarket

Licensing-outBiologicalsAPIs/ReagentsDiagnostics

Intolerable GAP #2: TECH TRANSFER

R&I+D

IP

INSTITUTIONS

BIOTECHS

BIG PHARMA

HOW DO WE SEE THE FUTURE?

INSTITUTIONS

BIOTECHS

BIG PHARMA

+ Tech Transfer

Licensing-outBiologicalsAPIs/ReagentsDiagnostics

WHERE THE CHALLENGES ARE?

HERE!

A NEW SCENARIO

20086 corporations with only 10 drugs = 50% of

recombinant proteins market (USD 80 billions)

A NEW SCENARIO

#6

Herceptin (mAb α-HER2R) 4384#7

Aranesp (EPO) 3344#8

Lantus (insulina) 3130

#9

#10

Avastin (mAb α-VEGFR) 4484

Neulasta (GCSF-PEG) 3318

2008 (USD billions)

If we add other 9 corporations, we realize that 15 corporations making “only” 83

drugs take 99% of recombinant proteins market.

G. Steven Burrill, CEO of Burrill & Company (San Francisco, CA)

"As the industry migrates away from an era of the one-size-fits all blockbuster, the biotechnology industry's strength at developing innovative therapies that meet unmet medical needs and target the molecular mechanisms of diseases gives it an upper hand in creating value,"

From “Big Biotech Outpaces Big Pharma”. Biopharm International , Apr 17, 2013.

G. Steven Burrill, CEO of Burrill & Company (San Francisco, CA)

“But as pricing pressures become an increasingly challenging prospect for pharmaceutical and biotechnology companies alike, they will need to find new ways to build relationships with payers, providers, and patients to capture value outside of their products"

From “Big Biotech Outpaces Big Pharma”. Biopharm International , Apr 17, 2013.

31 dec 09 31 dec 12 31 dec 09 31 dec 120

200

400

600

800

1000

1200

1400

160261

1070

1257

Big BIO vs Big PHARM Capitalization

USD

bill

ions

From “Big Biotech Outpaces Big Pharma”. Biopharm International , Apr 17, 2013.

∆: 57%

∆: 17%

From 15% to 21% in 3 years

A NEW SCENARIO

distribution

manufactur

ing

AVALUE

PROPOSITION

BIOORGANIC RESEARCH AND SERVICES, S.A.

1. What do we do?

CDMO. Development & Manufacturing of Bioactive Agents.

2. For whom?

Pharmaceutical and Veterinary Companies.

3. What´s our goal?

Be an international reference in NICHE DISEASES.

BIOORGANIC RESEARCH AND SERVICES, S.A.

Cabbage looper Trichoplusia niOral infection

Bionaturis headquarters & 400 sq-mt production plant in Jerez de la

Frontera, Cádiz, Spain.

Less investment for more production in a locally sustainable model of protein production.

• 15x decrease in up-front cost.• 10x less space.• Sustain local production.

VALUE PROPOSITION

Flexibility + speed + security + efficacy + SCALABILITY

VALUE PROPOSITION

LARVAE ARE MASS-REARED FOR PEST CONTROL

Industrial production of biological pesticides

Brazil: velvet bean caterpillar, Anticarsia gemmatalis

Embrapa-Soja.

A laboratory for the large-scale production of AgMNPV was opened in 2004 with the intention of being capable of infecting 600,000 larvae per day.

It yields enough virus to treat up to 1.5 million ha/year.

The infected larvae are processed into a wettable powder that involves milling the infected larvae and formulating them into a mixture that contains kaolin.

Baculoviruses were transformed into expression vectors

Disease Brand name(s) Company Active principleVaccines for human use

Cervical cancer Cervarix® GSK L1 protein (VLP)Prostate cancer Provenge® Dendreon PSAInfluenza FluBlok® Protein

Sciences4x HA

Vaccines for veterinary usePCV2 Porcilis® PCV Merck PCV2 ORF2 proteinPCV2 CircoFLEX® B. Ingelheim PCV2 ORF2 proteinClassical Swine Fever Porcilis Pesti® Merck E2 protein

Biological for veterinary useCanine Parvovirus.Feline leukemia virus, Feline Immunodeficiency Virus.

Virbagen Omega®

Virbac Feline interferon Ƴ

FDA/EMA APPROVED BIOLOGICALS MADE IN INSECTS

BIONATURIS MANUFACTURING

BIONATURIS FLYLIFE STAGES OF THE PRODUCTION PROCESS

1. Master Viral DNA

2. Working Viral Bank

3. Manufacturing Viral Seed

4. Upstream Processing

5. Downstream Processing 1

6. Downstream Processing 2

7. Formulation

8. Larvae population rearing

Stages of the production process

CANINE VISCERAL LEISHMANIASIS (BNT005)

1 595 1274

L. Infantum ANTIGEN T. cruzi Hsp70

Animal Health Vaccine Program

Prediction based on data: 3 million doses/day

Entering Leishmania market in Brazil: 200 K doses/year

USD 100/dose

BIONATURIS PRODUCTS

BIONATURIS HDP PROGRAM

Aquatic Health Program

A

B

C

D

BIONATURIS ORAL DELIVERY

Aquatic Health Program

FLYTE strategy

FLYPIDS strategy

Antigen sequence Lipid Droplet Targeting seq.

Antigen sequence Polyproline amphipatic helix

Formulation, method of preparation, and use for delivery to animals or humans. PCT patent application filed March 2012: FORMULATIONS FOR NON-INVASIVE

DELIVERY OF ACTIVE PROTEINS TO AN ANIMAL OR HUMAN. PCT/EP2012/055069.

1.5h 3h

C

G

FP

FT

BIONATURIS ORAL DELIVERY

Aquatic Health Program

TAKE HOME MESSAGES

1. Permanent creativity and innovation in biotechnology and business must lead to a boost in technology transfer.

2. Bionaturis proposal based on insect larvae biofactories is effectively adding value to active principles for niche diseases and promoting more access to health.

THANKS FOR YOUR ATTENTION!Juan J. Infante, PhD.

Bionaturis Chief Scientific Officer.

juanjose.infante@bionaturis.com

www.bionaturis.com