DISRUPTING

THE DRUG DISCOVERY

LIFECYCLE

DRUG DISCOVERY IS A LONG CYCLE

ALMOST UNCHANGED FOR THE

LAST 50 YEARS

DISCOVERY PROCESS

Laboratory – design, biotech

Upscaling (GMP)

Testing (in vitro, in situ, non clinical, clinical)

Laboratory – design, biotech

Upscaling (GMP)

Testing (in vitro, in situ, non clinical, clinical)

LABORATORY

1. SYNTHESIS – TEST FOR ACTIVITY

2. TARGETED DRUG DISCOVERY

3. BIOTECHNOLOGY

1 – RAISING COSTS / FINANCIAL

CAPABILITY

80s-90s

MACROMOLECULAR CRYSTALLOGRAPHY

ALLOWED

RECEPTOR IDENTIFICATION

CELLS PRODUCE WHAT WE INTEND

EXTRACTION / PURIFICATION

(20-30,000 Da – 2-300,000 Da)

Laboratory – design, biotech

Upscaling (GMP)

Testing (in vitro, in situ, non clinical, clinical)

500-700 Kg protein

USD 1 bn, 25,000L, very large

area

USD 450 million, 15-20,000L,

large area

2010

2013

very large and expensive (USD 1 bn) production facility to supply the

global market

Old paradigm

Centralized manufacturing for development economies (e.g. USA,

EU, Japan)

500-700 Kg protein

USD 25 million, 2-2,500L,

7,000m2

2015

Process

Development

Quality Control

Administration

Upstream

Warehouse/

Dispense

Utilities + 6F & Roof

Downstream

| Centre of Excellence

500-700 Kg protein

USD 2-5 million, continuous or

50-200L, 3-5 m2

2017-8

New paradigm Distributed manufacturing for local markets

(e.g. Africa, Asia, Latin America)

No large storage tanks No large filtration equipment No large chromatography column, no

large TFF system No large pumps

Single use process

Media Preparation

INTEGRATION INTO A CONTINUOUS PROCESS

ALL IN ONE

Viral Clearence

Capturing Concentration Cell

harvest Culture

Smaller Equipment

Smaller Footprint

Reduction of utilities

comsumption

Simplified operations

Reduced OPEX

& CAPEX

- Proprietary systems -

New paradigm

1

3

2

CAPEX

intensive

Prohibitive

OPERATIONAL

COSTS

Lack of KNOW

HOW

AFFORDABLE

facility

RE- INVENT

manufacturing

strategy

Consortium for

GLOBAL SUPPORT

in project management

CoGS

50 kg / 5 m doses 500 kg / 50 m doses

Investment

USD m ] [

Production capacity / year

≈

200

20

Stainless Steel facility

SINGULARIS FACILITY

PRICE OF PROTEIN

Eur 30,000/g

to Eur 1,000/g and even less

PRODUCTIVITY

Less than 1g/L – 7g/L

Formulation / analytics

Upscaling (GMP)

Testing (in vitro, in situ, non clinical, clinical)

MODELS

• Models to measure a specific

response

• Reproducible, reliable

BIOSIMILARITY

• Finger-print like similarity

• Analytical data sufficient

• CPMP/EWP/4151/00 REV 1:

• „...ONLY COMPARATIVE IN VITRO DATA,

• OBTAINED WITH AN ACCEPTED METHOD MAY BE

CONSIDERED ACCEPTABLE

• IF THE PRODUCT SATISFIES ALL OF THE

FOLLOWING 9 CRITERIA

RESPIRATORY MODEL

REGISTRATION PATH …

8. The inhalation device has the same resistance to airflow (within+/-15%)

6

0 5

E 4

2

app I i cants in haler

2 Seretaide inalador

a

0

0 2 0 3 0 4 0 5 0 6 0 7 0 2 0 9 0 1 0 0 1 1 0

Caudal [Lim in]

9. The delivered dose is the same (within +/- 15% of labelled claim)

Nível1 (P,O) Nível2 11,21 Leven. Nível4

OAS l 6,7;0

Ltve 1 (P,O) Le ve 2 (1,2) Level Level 4 (5,4,5)

Salmeterol / 50 lig

Flow rate 60 L/min

0

SOO •

Mea

n m

ass

[R,g

]

400 •

300 •

200 •

100 •

Fluticasone propionate

Flow rate 60 L/min 2

I n

C ra

2

200

0

120

0

160

0

140

0

120

0

100

0

SOO

SOO

400

200

0

· 4—Mean mass rug] Reference product (R) —0—Mean mass (lag] Reference product lR)

· 0—Mean mass (pgj Reference product (A) —a—Mean mass (pg] Reference produtct (A)

WOUND MODEL (burns, cuts, diabetic

foot, post-surgery)

IN VITRO - no standard test

ANIMAL- ethical concerns

HUMAN – ethical concerns

How to measure

wound healing?

WOUND HEALING

Diameter

Doctor’s eye Blood flow

COMPARING COST EFFICACY OF

DIFFERENT TREATMENTS

INFRARED

DATA TREATMENT

TWO CRITICAL CONDITIONS

1 – VALIDATION OF DATA

REPRODUCIBILITY

2 – REGULATORY APPROVAL

COMMERCIALIZATION

Highly regulated industry

Paper industry

Medical devices

3m-3 years

Pharmaceutical

6m-7 years

Biolotus Biotech

Av Evandro Lins e Silva 840, Sl 319

Barra da Tijuca, 22631-470

Rio de Janeiro

Brazil

Tel +5521-24802405, -30793451, -982069998

biolotus@biolotus.com

www.biolotus.com