A GLOBAL LEADER IN EPIGENETICS

I N V E S T O R P R E S E N TAT I O N

M A D X : O R Y

S a n F r a n c i s c o - J a n u a r y 2 0 1 6

L E G A L N O T I C E

DISCLAMER

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any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise

2

COMPANY HIGHLIGHTS

MADX: ORY A publicly traded company in the

Madrid Stock Exchange since December 14th 2015

Trading started at €3.39 = €96.5M Market Cap

A clinical stage biopharmaceutical company

developing innovative therapies in oncology and

neurodegeneration leading the field of Epigenetics

Two therapeutic programs in clinical development

with multiple indication opportunities & additional

assets in preclinical development

Signed global strategic partnership with ROCHE for

ORY-1001 valued at 500M USD

Strong IP portfolio with technology developed in-

house

Strong financial profile with €+20M cash on balance

sheet with runway till 2018

Experienced management team

3

E P I G E N E T I C S : THE CRITICAL ROLE OF HISTONE CODING

Epigenetics − the study of heritable changes in genome function that occur without a change in DNA

sequence

These changes mainly occur due to variations in the structure of chromatin that silence or activate

whole regions of the chromosome and all the genes that reside in this region

These variations are caused by post-translational modifications on histones, the proteins that serve as

scaffold for the DNA to conform the chromatin

Lysine methylation and demethylation is one of the key epigenetic modifications of the Histone tails

4

EPIGENETICS COMPETITIVE LANDSCAPE

EPIGENETICS is a new Space being explored by the Pharma Industry: Clinical Programs are still in Early Phases.

ORYZON, Epizyme and Constellation are the only Biotechs developing more than one compound.

GSK, Roche, Merck, Pfizer ,Celgene and other Big Pharmas are also entering in the field either through their own programs or through

alliances.

C O M P A N Y C O M P O U N D D E S C R I P T I O N I N D I C A T I O N S T A T U S

Reverlogix RVX-208 BET bromodomain inhibitor Atherosclerosis -Diabetes Phase II b

Acetylon

Pharmaceuticals

(ACY-1215) lic. to

Celgene Oral selective HDAC6 inhibitor Multiple myeloma (MM) Phase I/II

Oryzon Genomics

ORY-1001 lic. to Roche

Lysine-specific demethylase 1

(LSD1) inhibitor

Acute myelogenous leukemia (AML) Phase I/IIa

ORY-2001

LSD1-MAOB dual inhibitor

Alzheimer's Disease

Other Neurodegenerative disorders

CTA filed

Constellation

Pharmaceuticals

CPI-1205 EZH2 inhibitor lymphoma Phase II

CPI-0610 BET bromodomain inhibitor Progressive Lymphoma

AL, MDS, myeloproliferative neoplasms

Multiple myeloma Phase I

Epizyme

EPZ 6438 Tazemetostat EZH2 inhibitor non-Hodgkin B-cell lymphoma

Synovial Sarcoma

Phase I/II

IND / Phase I

EPZ-5676 lic. to Celgene HMT DOT1L inhibitor MLL- AML Phase I/II

Tensha Therapeutics TEN-010 BET bromodomain inhibitor Cancers including NUT midline carcinomas Phase I

5

EXTENSIVE PIPELINE WITH MULTIPLE INDICATIONS

6

L S D 1 P R O G R A M : AN EPIGENETIC “ERASER”

Lysine-specific histone demethylase 1 (LSD1 or KDM1A) is an enzyme that demethylates

histones (removes methyl groups), specifically mono and di-methylated H3K4 and H3K9

LSD1 belongs to the family of flavin adenine dinucleotide, dependent amine oxidases,

which include known drug targets such as MAO-A and MAO-B

LSD1 is located in the nucleus, unlike MAOs

LSD1 expression has a high correlation in many solid tumors

In some aggressive Leukemia, Leukemia Stem Cells are addicted to LSD1 activity

The pan-MAO inhibitor tranylcypromine: a chemical starting point to design covalent LSD1

inhibitors.

Protected by 19 patent families filed globally with 10 granted in US

7

ORYZON’s CLINICAL ONCOLOGY PROGRAM: O R Y- 1 0 0 1

KDM1A is a key effector of the differentiation block in MLL leukemia

KDM1A sustains expression of the MLL-AF9 oncogenic program

Nanomolar KDM1A inhibitor concentrations induce differentiation of human AML cells

KDM1A inhibition in vivo targets MLL-AF9 cells, but spares normal repopulating cells.

Modified from Harris et al., Cancer Cell. 2012: 21(4):473-87)

Oryzon’s LSD1 inhibitor (OG-86) blocks

progression of leukemia cells into the

circulation MLL-AF9 mice model

Oryzon’s LSD1 inhibitor (OG-86) targets

leukemia stem cells but spares normal

hematopoietic stem cells

8

O R Y- 1 0 0 1 : O N C O L O G Y P R O G R A M

ORY-1001 a highly potent and selective LSD1

inhibitor with orphan drug status granted by the

European Medicines Agency (EMA)

Pharmacological Properties

• High druggability

• Optimal ADMET and PK profiles

• Orally bioavailable once daily

• Easy to scale up

• Good pharmaceutical properties

Currently in Phase I/IIA

• Completed Part 1 of the study (Phase I) in acute

leukemia

• Extension Arm (Phase II-A) ongoing

Potential for additional indications, such as solid

tumors (like SCLC) and sickle cell disease

Global strategic collaboration with ROCHE

valued >500M USD

9

O R Y- 1 0 0 1 : ROCHE PARTNERSHIP

Development and sales milestones total >500M USD

Payment at contract signing plus near term milestone total 21M USD

Sales royalty rates tiered up to mid-teens.

10

In April 2014, Oryzon and ROCHE entered into a global collaboration to research,

develop and commercialize LSD1 inhibitors, including ORY-1001, for oncology,

hematology and non-malignant conditions

Licensed compounds are covered by 2 patents in the Oryzon IP portfolio

Remaining LSD1 inhibitors in Oryzon’s LSD1 IP portfolio are not part of the

ROCHE license agreement

Clinical development and all related investments beyond the ongoing Phase I/IIA

trial are the responsibility of ROCHE

Parties will collaborate on R&D through the ROCHE Translation Clinical Research

Center (TCRC)

P H A S E I H I G H L I G H T S : ORY-1001 LEUKEMIA

T R I A L D E S I G N

Refractory & Relapsed

Acute Leukemia Multi-Center (5)

Multiple Ascending Dose (8

Cohorts)

P R I M A R Y E N D P O I N T

Evaluate Safety (hematological and non-hematological toxicities) and Tolerability

S E C O N D A R Y E N D P O I N T S

Characterize PK

Assess Responses

(CR/Cri/PR), particularly for

rMLL gene

Evaluate surrogate PD

markers for target

engagement

P R E L I M I N A R Y R E S U LT S

Excellent safety profile with no SAEs

Demonstrated impact on pharmaceutical target

PD clear readings several biomarkers

Good PK

Established maximum recommended dose

11

PHASE IIA: O R Y- 1 0 0 1 L E U K E M I A

After the MRD , an Expansion arm (Phase II-A) to include patients with target mutations (MLL

and others) to evaluate preliminary signs of efficacy

9 Patients to be included

Status: 3 patients enrolled and actively recruiting

Completion Date: 2Q-2016

C E N T E R S

10 Hospitals in 3 Countries

UK

• Christie Hospital, Manchester

• University College London hospitals NHS, London

FRANCE

• Gustave Roussy, Paris

• CHU Hopitaux, Bordeaux

• Hôpital Purpan - (CHU), Toulouse

SPAIN

• Valle de Hebron, Barcelona

• La Fe, Valencia

• Virgen del Rocío, Sevilla

• 12 de Octubre, Madrid

• Gregorio Marañón, Madrid

12

ORY-1001 CLINICAL & MARKET POTENTIAL

ORY-1001 market capture opportunity above $1.8 billion.

A number of scientific reports point out the potential of LSD1 inhibition as a target in a number of solid

tumors

Non oncological diseases as SCD and others may also be a CDP option

Small Cell Lung Cancer

15% of all Lung Cancers

32.420 new cases in US in

2014 1,3

Global Mk Potential of $684

million in 2017 5

Sickle Cell Disease

SCD Epidemiology

US/EU Prevalence ~150K

US Mk Potential of $200

million in 2017, (Market to grow at 17% CGAR till 2019)

Acute Myeloid Leukemia

12% of all Blood Cancers

18.860 new cases in US in

2014 1,2

Global Mk Potential of $932

million in 2024, CAGR of 10.5% 4

NOTE: ROCHE is the sole responsible for the further clinic development Plan for ORY-1001. The indications and markets

mentioned above are only presented on its likelihood based on the development of competitors or published scientific reports

1. ACS, Cancer Facts & Figures 2014

2. www.hematology.org

3. www.lungcancer.org

4. Global Data 2015

5. Decision Resources 2015

13

R O L E O F E P I G E N E T I C S : NEURODEGENERATIVE DISORDERS

Studies suggest epigenetic modifications

that induce alterations in gene expression

programs contribute to neurodegenerative

disorders:

• Alzheimer’s Disease (AD)

• Parkinson’s Disease (PD)

• Huntington’s Disease (HD)

Epigenetic alterations on related genes

may also result in neurodegeneration,

partially accounting for the etiology

Epigenetic drugs target the proteins

responsible for modifications on DNA or

histone

• HDAC inhibitors (HDACi)

• HAT modulators

• DNA methyltransferase inhibitors

• Histone demethylase inhibitors

Identical twins (monozygotic)

Same DNA with GBA risk

mutation

Disconcordant for symptoms of

Parkinson’s

Up to 20 years difference in

onset

Patient derived iPSCs: difference in MAO-B levels

14

E N V I R O N M E N T

G E N E S E X P E R I E N C E

15

Luca Lovrečić, et al., 2013 The Role of Epigenetics in

Neurodegenerative Diseases

HDACi improves HD symptoms in animal

models

HDAC2 inhibition recovers memory on the

bi-transgenic CK-p25 Tg mouse model

HDAC inhibition improves FTD

However, while pan-HDAC inhibitors have demonstrated

preclinical proof of concept that inhibition of HDACs

improves cognitive function, these drugs have dose limiting

side effects that make them unsuitable for the chronic

settings needed in neurological indications.

Developing more selective HDAC inhibitors is not an

insignificant challenge as HDACs are highly conserved

proteins

HDAC2 selective

inhibitors in AD

HDAC i in Prodromal to Moderate

FTD with Granulin Mutation

Efforts to develop Selective HDACi

R O L E O F E P I G E N E T I C S : NEURODEGENERATIVE DISORDERS

LSD1 IN THE NERVOUS SYSTEM

LSD1 is a key component of the LSD1-REST-

CoREST-HDAC1/2 repressor complex

involved mainly in controlling developmental

programs and modulating neuronal

morphology in the CNS

LSD1 is known to be an important regulator in

the maintenance of pluripotency and in

specification of neuronal commitment of pluri-

or multipotent cells

Different to what happens in HDACs, it has

been proven that it is possible to develop

extremely selective LSD1 inhibitors with

excellent pharmacological properties

Oryzon has the wider IP portfolio in the LSD1

space with drug candidates specially suitable

to be developed in neurological indications

16

O R Y- 2 0 0 1 : CNS PROGRAM

ORY-2001 is a highly selective dual LSD1-MAO-B inhibitor

Preclinical Proof of Concept: LSD1 Against AD and HD

Clinical development

• CTA Filed

• Phase I to start in 1Q2016

Alzheimer’s Disease is lead indication

Potential for additional indications: PD, HD and others

Exclusively owned by Oryzon

Pharmacological Properties

• Optimal ADMET and PK profiles

• Crosses efficiently the BBB

• Once daily oral bioavailable

• Good pharmaceutical properties

• Selectivity against MAO-A demonstrated in-vitro and in-vivo

• High therapeutic window in animals

17

The SAMP8 mouse is an excellent model to examine the pathophysiology of early defects seen in

Alzheimer’s disease. They develop accelerated aging and senescence and show deficits in learning

and memory as well as other similarities to pathology of AD

ORY-2001 cognitive effect tested by NORT in five different studies

After 2 and 4 month of oral treatment, ORY-2001 provides a robust protective effect in the medium and

long-term memory of female mice, compared to age-matched SAMP8 mice

We lowered dose in males (Study #2)

PoC studies in SAMP8 mice

18

2 months treatment

Tested 2 h after training

LSD1+MAOB LSD1 alone MAOB alone

*** ***

***

14/15 3/16 16/16 15/16

SAMPR1 Veh

SAMP8

3.20mpk 0.96mpk

Dis

crim

inat

ion

In

dex

SAMPR1 Veh

SAMP8

3.20mpk 0.96mpk

LSD1+MAOB LSD1 alone MAOB alone

***

***

5/5 0/5 5/5 4/5

***

4 months treatment

Tested 2 h after training

SAMP8 male animals (n=8 per group)

LSD1+MAOB LSD1 alone MAOB alone

LSD1+MAOB LSD1 alone MAOB aloneLSD1+MAOB LSD1 alone MAOB

alone

***

***

***

SAMPR1 Veh

SAMP8

0.96mpk 0.32mpk 3.0mpk

ORY-2001 ORY-2001 Rasag.

MAOB inhibition alone shows a trend

on cognitive improvement on the

SAMP8 animals but it is not

significant

• p=0.12 at 2h

• p=0.22 at 24h

LSD1 inhibition is therefore crucial to

obtain the recovery on cognitive

improvement on the SAMP8 animals

Dissecting the LSD1 and MAOB components

19

PoC studies in SAMP8 mice

SAMP8 female animals (n=8 per group)

ORY-2001 provides a robust

protective effect in the medium and

long-term memory of mice, compared

to age-matched SAMP8 mice

LSD1 inhibition alone is also able to

produce an effect but less

pronounced

Protection is driven by the LSD1

inhibition and not by MAO-B, but the

combination with MAO-B inhibition

(i.e. a dual compound,ORY-2001)

enhances the effect

Dissecting the LSD1 and MAOB components

LSD1+MAOB LSD1 alone MAOB alone

SAMPR1 Veh

SAMP8

0.96 mpk

0.32 mpk

0.1 mpk

ORY 2001

ORY 2001

ORY LSD1

ORY LSD1

0.3 mpk

PoC studies in SAMP8 mice

20

ORY-2001 has a pleiotropic effect on the hippocampal gene expression pattern and increases

memory associated genes and reduces levels of inflammatory genes.

Down-regulation of the pro-inflammatory S100A9 protein by ORY-2001 is particularly interesting,

since S100A9 is emerging as an important contributor to inflammation-related neurodegeneration.

S100A9 was found to be increased in patients with AD, postoperative cognitive dysfunction

(POCD) and traumatic brain injury (TBI). In addition, knockout or knockdown of S100A9 has been

shown to be beneficial to memory in APP/PS1 and Tg2576 models of Alzheimer’s disease

BIOMARKERS : We have identified different biomarkers upon ORY-2001 treatment:

ORY-2001 - PROOF OF CONCEPT IN SAMP8 MICE

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Delta

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*** ***

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SAMPR1 Veh

SAMP8

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***

0

8

10

12

14

2015 2016 2017

3Q2015 4Q2015 1Q2016 2Q2016 3Q2016 4Q2016 1Q2017 2Q2017

CMC / 4W

Reg Tox IB / IMPD

CTA

Phase I

(SAD)

Phase I

(MAD)

6M Reg Tox

Additional Preclinical Work to Broaden CDP

Phase II

Dossier

Phase II AD

Phase II Additional

Indications

ORY-2001 DEVELOPMENT TIMELINE

22

ORY-2001 CLINICAL & MARKET POTENTIAL

ORY-2001 market capture opportunity above $3 billion.

Further development may include Neuro- inflammatory disorders

1. Alzheimer’s association www.alz.org

2. Alzheimer Europe www.alzheimer-europe.org

3. European Parkinson’s Diesease Association http://www.epda.eu.com/

4. American Parkinson Disease Association http://www.apdaparkinson.org/ ,

http://www.ninds.nih.gov/

5. http://www.huntington-assoc.com/

6. http://www.fiercebiotech.com/

7. http://www.strategyr.com

ALZHEIMER’S DISEASE

5.4 M people currently affected in US. By 2025 the number of patients will rise to 7.1 million in USA1

8.7 million Europeans are also affected 2 and in Asia another potential 10 to 12 million people are

diagnosed or suspected to suffer AD.

Drug market projected to reach US $9.5 billion by 2017 6

PARKINSON’S DISEASE

Around 6.3 million people have the condition worldwide3

It affects over 1 million people in the US, with nearly 60,000 people newly diagnosed every year. 4

Drug market projected to reach US $2.6 billion in 2020 in the 7MM

HUNTINGTON’S DISEASE

Worldwide prevalence of HD is 5–10 cases per 100,000 persons. There are around 30,000 symptomatic

Americans and more than 200,000 at-risk of inheriting the disease 5

Up to 71,000 patients in Europe.

Drug market projected to reach US$1.3 billion by 2020 7

23

EXPERIENCED LEADERSHIP TEAM

Respected team in the European biopharmaceutical industry

Experienced in drug discovery and development. Able to bring assets to clinical stages in a cost efficient

manner

Proven track record to promote and close world class deals

Ability to lead and unite teams. Leading international consortia

ANNA BARAN

IR Director

TAMARA MAES

CSO and FOUNDER

CARLOS BUESA

CEO and FOUNDER

ENRIC RELLO

COO and CFO-Spain

NEUS VIRGILI

CIPO

EMILI TORRELL

CBO

CESAR MOLINERO

CMO

24

FINANCIAL HIGHLIGHTS

Strong balance sheet with €+20m in cash

$5 million payment from ROCHE in 2015

Secured €2.6M in public aids in 2015

Unused credit line of €6 M from commercial banks

€10M in debt with low interest rates

• Repayment terms over either 3-4y or 8-10y (commercial loans or Public R&D loans)

• Rates from 0-3% (average cost of debt 1,3%)

Expected cash burn of €10-12M annually for next 2 years

Raised €31 M since inception

Spanish GAAP rules adapted to IFRS

Accounts audited by Grant Thornton since 2003 and through 2014

Audited in 1H 2015

35 employees

25

KEY INVESTMENT HIGHLIGHTS

E P I G E N E T I C S

E X T E N S I V E

P I P E L I N E

P R O V E N

T R A C K

S O L I D I P

L E A D E R S H I P

F I N A N C I A L S

• Global leader in Epigenetics, an emerging field recognized by the pharmaceutical

industry as a novel approach to varying diseases and personalized medicine

• 2 programs in clinical development

• Both clinic programs can expand in multiple indications

• An Epigenetic platform with additional assets

• Collaborative agreement with ROCHE valued at $500 million

• Cutting edge science endorsed by international agencies

• Strong patent portfolio with19 patent families and10 granted in US

• All patented technology developed in-house with no owed royalties

• Highly experienced management team

• €+20M on balance sheet with runway till 2018

• Plan to grow as a public company in Europe and dual list on NASDAQ in the future

26

ORY-1001: LEAD CANCER ASSET

• Conclude Phase I dosing study

• Receive recommended dose milestone payment from Roche

• Phase IIA first patient-in

• Complete Phase IIA and report target efficacy

• Roche execute ongoing clinical development plan

ORY-2001: LEAD CNS ASSET

• Complete preclinical toxicology package

• File CTA/IND

• Begin Phase I patient enrolment

• Complete Phase I dosing safety study

• Layout of a multiple Phase II clinical study

CORPORATE

• €16.5M cross over funding in Spain

• List on the Spanish Main Market

• Prepare to List on the NASDAQ in the future

CATALYSTS 2015 - 2016

27

INTERNATIONAL RESEARCH NETWORK

28

ORYZON IS A TRANSATLANTIC COMPANY

UNITED STATES

ORYZON Corp.

245 First Street

Suite 1800

Cambridge, MA 02142

Investor Relations

US Clinical Operations

Business Development

EUROPE

ORYZON

Sant Ferran, 74

08940 Cornellà de LL.

Barcelona, Spain

Research and Development

European Clinical Trials

Intellectual Property

29

THANK YOU VERY MUCH!

C AR L O S B U ES A

C . E . O . & P r e s i d e n t

c b u e s a @ o r y z o n . c o m

A N N A K . B A R A N

I R D i r e c t o r

a b a r a n @ o r y z o n . c o m

E M I L I T O R R E L L

B D O

e t o r r e l l @ o r y z o n . c o m

T H E R U T H G R O U P

I R f i r m f o r U S A

o r y z o n @ t h e r u t h g r o u p . c o m