Evotec SE — Investor Presentation 2016

Dec 16, 2016

Shifting the drug discovery paradigm Evotec and Celgene in exclusive drug discovery collaboration for neurodegenerative diseases

Forward-looking statement

Information set forth in this presentation contains forward-looking statements, which involve ^a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of Evotec as of the date of this presentation. Such forward-looking statements are neither promises nor guarantees, but are subject to ^a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

iPS cells – A paradigm shift in drug discovery

Evotec's industrialised iPSC infrastructure represents one of the largest and most sophisticated iPSC platforms in the industry

Agenda

Rationale for next generation drug discovery

Paradigm shift with iPS cells ("iPSC")

Evotec and Celgene: Alliance in neurodegeneration

Next Steps

Improving R&D productivity in the pharmaceutical industry is imperative

Development costs increase while average peak sales decrease

Patient centric approaches improve success rates

Human genetics and biomarkers are improving the odds of success

Fully integrated iPSC-based drug discovery platform

The Evotec iPSC accelerator platform

i P S C
l t c r e u u

• Access to iPSC lines
• Expansion & banking
• Quality control standards
• Scale up

Patient-derived disease models

• SC-derived disease-relevant cell types
• Optimisation
• Scale up

Hitidentification

• High-content screening
• Electrophysiology
• Gene expression profiling

H2L/LO

• Cellular assays
• Medicinal chemistry
• Target deconvolution
• In vitro toxicity

In vivo pharmacology

• PK/PD
• Biomarker driven in vivo disease models
• Biomarkers

Latest stage technologies open new horizons

Combining human genetics with disease relevant read-outs

Combination of breakthrough technologies enable a new era in drug discovery

• Patient derived cellbased assay systems (e.g. iPSC)
• Gene editing (e.g. CRISPR)
• Cellular molecular analysis (e.g. NGS)
• Automated high-content screening and image analysis (e.g. Opera Phenix)

Agenda

Rationale for next generation drug discovery

Paradigm shift with iPS cells ("iPSC")

Evotec and Celgene: Alliance in neurodegeneration

Next Steps

Only few moments in science are undisputed as genuine and elegant in creativity and simplicity

Shinya Yamanaka – Discovered iPSC in 2007 – Nobel prize in Medicine 2012

"The induced pluripotent stem cells created by Shinya Yamanaka will allow us to interrogate and understand the full extent and variation of human disease, will enable us to develop new medicines and will forever change the way science and medicine will be conducted for the benefit of mankind."1)

iPSC technology shifts the drug discovery paradigm in drug discovery as well as cell-based therapy

Advantages & hurdles with iPSC

	i D d r u g s c o v e r y	C l l h t e e r a p y
K e y d t a v a n a g e s	F h d i l o c s o n m a n s e a s e r e e a n c e u u v  l d i t t a r e a a s c r e e n n g s a g e y R l f d l l & i i t t e p a c e m e n o r o e n c e n o v v  d l m o e s f f N l i i i i t t t t t t t o v e s r a e g y o r p a e n s r a c a o n  / I i l i i l i l i i d i i t t n v r o c n c a r a s p r e c s o n m e c n e  N l l i l b i k t t o v e r a n s a o n a o m a r e r s  E l l b i f l i i t t c e e n a s s o r m o r e c o m p e n r o x x v  d l m o e s C / l i d t o -c r e s o r g a n o s u u 	A l l l h i t t t o o g o s c e e r a p c a n c r c m e n u u y u v  i j i t m m n e r e e c o n u I b i i i h d i i t t t n c o m n a o n w g e n e e n g  h l i d i l t t t e c n o o g y p r o v e s p o e n a c u r e s
K e y h l l c a e n g e s	S d d i i t t a n a r s a o n  I d i l i i t t n u s r a s a o n 	F i l i i i i t t t t n c o n a n e g r a o n n s s e s u u  R l h l l t e g u a o r y c a e n g e s 

iPSC-based drug discovery platform has been established over the last 5 years

Key elements of drug discovery process with iPSC

Focus on human disease relevance from the start

iPSC will shift the drug discovery paradigm

	D i s e a s e r	l e e a n c e v
	O L D	N E W i h i P S C t w	K A d t e a n a g e y v
i f I d l d t n r o m o e s o r r g v u i / f i l i s c r e e n n g p r o n g	L o w	H i h g	P i d i d d i d l f t t- a e n e r e s e a s e m o e s o r v d i d f i l i f r g s c r e e n n g a n p r o n g c o n e r s u d i l l s e a s e r e e a n c e e a r o n v y
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P l i i l i t t r e -c n c a p a e n i f i i t t t s r a c a o n	N i b l t o p o s s e	P i b l o s s e	E l i i f i i b l t t t t t a r p a e n s r a c a o n e n a e s y b f d l i i l d l t t t e e r o c s e c n c a e e o p m e n u v
S i l i i l t c c e s s r a e n c n c a u i i l l d t t e s n g e v e n n w e e f i d i l i t t t n e p a e n p o p u a o n s	L o w	H i h g	W i h i d t t t n c r e a s e s c c e s s r a e s c o s u , f d l f d i f t o r e e o p m e n o a n p r c e s o r v d i i i l l d t m e c a o n e c r e a s e w

Initial focus on key neuronal cell types

From prototype protocol to industrial process

Patient derived functional neurons

Manufacturing process adapted to 384-well format suitable for HCS

Industrialised process to generate patient neurons in 384 well format suitable for HCS

Highly robust, semi-automated human neuron manufacturing process

Unprecedented performance indicators in iPSCderived human neuron assays

Excellent screening performance indicators throughout screening campaign

Highly robust manufacturing process works for all lines tested so far

General applicability of human neuron manufacturing process

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Images obtained with Phenix at 20x magnification

Early patient stratification via 'clinical trial in a dish'

Patient-derived iPSC-lines available for multiple genotypes (e.g. ALS)

Focus on genetically defined subpopulations of widespread diseases

Many opportunities beyond neurodegeneration focus

Neurodegenerative diseases

• Alzheimer's disease
• Parkinson's disease
• Amyotrophic lateral sclerosis
• Huntington disease
• Frontotemporal dementia
• …
• …

Neurodevelopmental diseases

• Autism related spectrum disorders
• Spinal muscular atrophy
• Bipolar disorders
• Epilepsy

Lysosomal storage diseases

• Gaucher, Fabry
• Batten, MLIV1)

Myopathies

• FSHD2)
• Duchenne

Diabetes

• Drug discovery
• Cell therapy

Diabetic complications

• Nephropathy
• Retinopathy

²⁾ FSHD = Facioscapulohumeral Muscular Dystrophy

Agenda

Rationale for next generation drug discovery

Paradigm shift with iPS cells ("iPSC")

Evotec and Celgene: Alliance in neurodegeneration

Next Steps

Clear strategy towards global leadership in iPSC- based drug discovery

From scientific discovery to strategy

Neurological diseases will remain a serious threat to public health

Societal burden of CNS related diseases is daunting1)

Why CNS diseases?

Constitute the biggest health care challenge

• Dementia accounted for 46 Mio. patients in 2015
• Cost of care globally exceeded USD >650 billion in 20153)
• No effective treatments for most CNS diseases as of today

Why neurodegenerative diseases (ND)?

ND cause progressive loss of neurons in the brain

• Genetically inherited or of unknown etiology
• Severe debilitating effects causing ataxia and dementia
• Dementia is expected to account for >131 million patients by 20503)

Why patient derived ?

iPSC technology is uniquely suited to approach ND

• Patient derived disease models are expected to be more predictive than traditional animal models
• Allow systematic screening and profiling of compounds
• Allow early patient stratification

1) Source: 2006 WHO – Global burden of neurological disorders

Global neurodegenerative disease market

in mio USD35,000 15,000 20,000 25,000 30,000 6.5%1.5%2.0%2.5%3.0%3.5%4.0%4.5%5.0%5.5%6.0%10,000 5,000 0201629,553.94 201731,143.58 6.10201533,042.95 2018 20195.382.561.934.714.0828,225.42 27,118.93 201426,177.20 Revenue Growth rate

Market overview

Major exclusive alliance in Neurodegeneration

Celgene & Evotec

Mission

Develop novel therapies for a broad range of neurodegenerative diseases, based on Evotec's unique patient-derived drug screening platform ("iPSCs")

Strategic alliance Celgene & Evotec

• Upfront payment of \$ 45 m
• Potential milestones up to \$ 250 m and up to low double-digit royalties on all in-licensed programmes
• Initial term of the collaboration is five years
• Focus on Amyotrophic lateral sclerosis ("ALS"), Alzheimer's disease ("AD"), Parkinson's disease ("PD"), and multiple other neurodegenerative diseases
• Celgene holds exclusive options to in-license worldwide rights to Evotec programmes developed from the company's compound library

evotec	#RESEARCHNEVERSTOPS
NEWS RELEASE, 15 DECEMBER 2016

Agenda

Rationale for next generation drug discovery

Paradigm shift with iPS cells ("iPSC")

Evotec and Celgene: Alliance in neurodegeneration

Next Steps

Last tick for 2016 done – A strong 2017 ahead of us

EVT Execute & EVT Innovate – Expected key milestones 2016

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