Février Séphora Laloupe, Hélène Toulotte, Thomas …moodle.univ-lille2.fr/pluginfile.php/51632/mod_resource/content/0/... · SWOT Strengths •Patents •Supplementary segments:

Février

2011 Séphora Laloupe, Hélène Toulotte, Thomas Vignon

This is an independent study performed by students

from the Faculté des Sciences Pharmaceutiques of

Lille.

The opinions expressed are our own and not

necessarily those of Morphosys

Table of content

Part 1: Presentation

Part 2: Antibodies technology

Part 3: Business strategy

Part 4: Business revue

Presentation

A biotechnology company focusing on fully

human antibodies

segments

Field of use

Proprietary

development

Partnered

discovery

Therapeutic antibodies Research &

Diagnostics

Location and subsidiaries

• MorphoSys was founded

by two chemists, Dr. Simon

Moroney and Dr. Andreas

Plückthun in Martinsried

near Munich in 1992.

• MorphoSys’s second largest

site is located in Oxford,

England.

Morphosys group 428 employees

Location and subsidiaries

• Research and diagnostic antibodies unit AbD Serotec expand

its sales organization in Düsseldorf.

• AbD Serotec is currently

represented in the most

important research antibody

market in Raleigh, North

Carolina (Research Triangle

Park).

Antibodies

technology

Antibody structure

Fab

Recognition of the antigen

(bacteria or viruses)

Family protein of Ig (immunoglobulins) joined by disulfide bridges

Fc

Determines isotype and hence the

functional properties of the antibody

Monoclonal antibodies (mAb or moAb) are monospecific antibodies

made by identical immune cells that are all clones of a unique

parent cell.

Development of Antibodies Technologies

immunogenicity

Reduced immunogenicity

expected to:

Efficacy

Safety

Ease of use

Obtaining Mouse Antibodies

•Murine Antibody MOMAB

Hybridoma technology

Drawbacks:

-Requires considerable time

-Expensive

-Require an expertise specialized cell

culture, animal facilities

rejected by the human

immune system=>

unsuitable for use as

therapeutic agents.

Obtaining

Chimeric Ab XIMAB

Fusion of genes encoding variable

regions of murine antibody and

constant region of a human Ig

Humanize Ab ZUMAB

- Contain only the murine variable

part composed by highly regions

(CDR) in contact with the antigen.

- CDR grafted in the variable

region of a human Ig.

Development of Antibody Technologies

Need animals Possible In vitro

production

Morphosys Technologies

arYla™

Hucal GOLD®

Hucal platinium®

HucAL® concept

Cysdisplay™

RapMAT®

AgX®

Morphosys Technologies

arYla™

Hucal GOLD®

Hucal platinium®

HucAL® concept

Cysdisplay™

RapMAT®

AgX®

HuCAL library

More than 45 billion functional

human antibody (Fab format) .

selectable using in vitro methods,

such as phage display.

49 frameworks

CDRs= Complementary Determining Regions

7xVH 7xVL

Highly variable

genetic cassettes

(CDRs)

Phage display Technology

-Select your antibodies from 45 billion candidates


HuCAL


Phagemid

Gene III

P III

Antibody library

cloned into a

phagemid vector

simultaneous

periplasmic

expression of

phage coat

proteins and

antibody fragments


HuCAL

CysDisplay™ over monovalent phage display

•Ensuring that all specific binders are eluted from the

antigen

•Preventing elution of binders sticking non-specifically

•Elution of all binders independent of their affinity

Phage display technology

HuCAL

Phage Display technology

HuCAL


HuCAL


HuCAL


HuCAL

HuCAL Concept

in vitro generation

of highly specific

and fully human

antibodies

Features:

-Rapid generation of fully human antibodies

-Proven success with difficult antigens (e.g. non-immunogenic or toxic

antigens)

-High affinity that can be further increased through targeted optimization

-High expression yields in E.coli

Benefits of HuCAL technology Parameter Conventional Monoclonals HuCAL

Selection Random Guided

Production Complicated Easy

Animal based Yes No

Guaranteed Supply No – source dies with

the cell line

Yes – clones can be

resynthesized

Flexible Formats No

Yes

Engineering and

Optimization

No Yes

Humanness No Yes

Throughput Mostly manual

Automated

Success Rate ~75%

98%

Speed of Delivery 4–9 months

8 weeks

Business strategy

Monoclonal Abs Market

One of the fastest-growing drug classes in

human healthcare

Monoclonal Antibody market 2009, Krishan Maggon, Knol Publishing Guild (KPG)


Source Frost & Sullivan 2008

20,5 billion

56,7 billion


Monoclonal Antibody market 2009, Krishan Maggon, Knol Publishing Guild (KPG)

Company

founded in

Martinsried

1992 1997

First

commercial

partnership

with:

1999

IPO of

Morphosys AG

Start of an

extensive

partnership with:

2000

Presentation of the

HuCAL antibody library

First HuCAL patent

granted

2001

HuCAL GOLD

antibody library

Start of a strategic

partnership with:

2003

Start of a

partnership

with:

Start of a

partnership with:

New research

antibodies

division: AbD

Start of a

strategic

partnership with:

2004 2005

First HuCAL Ab

used in clinics

Acquisition of:

2006

Acquisition of:

Serotec

2007

One of the industry

largest pharma-

biotech R&D

collaborations with:

2008

First proprietary

therapeutic Ab

MOR103 enters

clinical trials

2010

Acquisition of:

Partnerships

In the majority of cases

standard terms of these

agreements are:

•upfront payments at signature,

•annual license payments in

exchange for access to

MorphoSys’s technologies,

•development-dependent

milestone payments,

•royalties on product sales.

Partnerships

The partnership with

• Started in 2004 and will run until 2017

•Total payments could potentially exceed € 1 billion

• Novartis pays : • Approx. €20m p.a. technology license including HuCAL

internalization fees

• Approx. €20m p.a. in research funding

• Over €250m milestones (probability adjusted)

• Royalties on all resulting drugs

•Novartis possess 7% of Morphosys

Pipeline

Partnered programs

• BHQ880:

• Osteolytic bone disease in multiple myeloma • Anti-DKK-1 neutralizing antibody

• First-in-class

• Fully human

• Phase 2

The partnership with:

Partnered programs

• Multiple myeloma

• Prevalence

• US : 45 000 people, 14 600 news cases/years (American Cancer

Society)

• France : 4000

• Osteolytic bone disease in multipe myeloma treatment

• Thalidomide + melphalan/prednisone

• Bortezomib + melphalan/prednisone

• Lenalidomide

• BHQ880 : DKK1 as an important therapeutic target in myeloma and

provide the rationale for clinical evaluation of BHQ880 to improve

bone disease and to inhibit MM growth.

• Possibility of provision in any other form of multiple myeloma

Pipeline

Proprietary development

• MOR 103

• Rheumatoid arthritis

• Target : GM-CSF, which plays a central role in activating

granulocytes and macrophages, essential in the

inflammatory cascade

• Clinical trial :Phase 1b/2a

• In several European country, with 135 patients


• Rheumatoid arthritis:

• Prevalence : 4-6 million people worldwide

• Treatment

• Anti-TNFα

• Humira (Adalimumab)

• Enbrel (Etanercept)

• Remicade (Infliximab)

• Interest of MOR 103

• Non-responders to anti-TNFα : 30%

• Non-responders to anti-TNFα (after 2

years) : 50%

• Long-term safety issues with anti-TNFα


• MOR 103

• Other inflammatory disease

indications

Asthma, Multiple Sclerosis, Chronic

Obstructive Pulmonary Disease

• Start Phase 1 Multiple Sclerosis

Focus on AbD Serotec

• >14,000 antibodies and immunological reagents:

custom monoclonal antibodies developed from the

MorphoSys HuCAL library,

large and small scale antibody production and

conjugation services.

• The AbD Serotec brand was created in

early 2006.

• 25% of Morphosys revenues

Antibodies by Design to provide custom antibody development services to the research and diagnostic markets using its proven HuCAL technology.

Biogenesis group (acquisition) >20 years experience in the Ab industry, a vehicle: • to bring HuCAL antibodies into the catalog antibody market • to bring a large and diverse range of catalog antibodies to the MorphoSys group.

2003 2005 2006

Serotec (acquisition) >20 years experience, strong position in the global market for research antibodies: distributors > 55 countries, and a large portfolio of Abs and custom services.

Oxford Biotechnology OBT (acquisition) internet-based Ab sales company, with customers all over the world. The OBT product portfolio is now also part of the AbD Serotec offering.


Order on line


Order on line

Business revue

Sources of finance

• MorphoSys’ major sources of finance: public offerings,

revenues from its strategic pharma alliances,

profits from access fees for its proprietary technology.

• Grant revenues: 18% of revenues in 1997

<0.1% in 2009

Group revenues 2010

MorphoSys Group: 3rd Interim Report January – September 2010

Group revenues 2010

MorphoSys Group: 3rd Interim Report January – September 2010

Shareholder structure

Total Shares Issued: 22,660,557,

MorphoSys AG MOR 24/02/11: €18,46

MorphoSys finance and revenue recognition/expense, 1997-2009 € thousands

Groupe de Recherche en Economie Théorique et Appliquée –UMR CNRS 5113

http://www.innovation-equity.eu/file_upload/william-lazonick_mustafa-erdem-sakinc_presentation.pdf

R&D/

revenues

>50%

Future according to morphosys

Strategic alliance

with Novartis

Investments in proprietary

coumpounds

First clinical proof of

concept

Out licensing of own

coumpounds

First HuCAL-based drugs

on the market

Proprietary HuCAL-based

drugs on the market

SWOT

Strengths •Patents

•Supplementary segments: different

applications of the technology

•Participation in drug development with

multiple partners.

Weaknesses •70% of total revenues arose from the

Company’s three largest alliances

with Novartis, Daiichi Sankyo and

Pfizer.

•No HuCAL-based drug on the market

yet.

Opportunities •Due to strong competition among

generics companies, almost all

pharmaceutical companies are

increasing their commitment to

biologics such as human Abs.

•Monoclonal Abs: One of the fastest-

growing drug classes in human

healthcare.

Threats •No HuCAL-based drug on the market

yet.

•Competitors:

Microbial surface display: Dyax,

Medimmune, BioInvent.

Transgenic mice: Abgenix, Medarex,

Regeneron.

Thank you for your attention

Competitors

Licensee PipelineDyax provides access to its phage display

libraries in various types of licenses and collaborations

under the Licensing and Funded Research Program

(LFRP). Under the LFRP, we maintain more than 70

licenses and collaborations with various research,

biotechnology and pharmaceutical companies. These

licensees have advanced into clinical development

numerous drug candidates identified using our phage

display libraries.Our licensee pipeline currently consists of

17 clinical-stage drug candidates.

Competitors

At MedImmune, antibody drugs are generated using three core technologies:

Phage display

Ribosome display

VelocImmune® (human monoclonal antibody-producing mice)*

Antibodies generated by these three techniques are currently produced from

a single clone of cells, and are therefore called monoclonal antibodies. The

majority of approved monoclonal antibodies marketed today are humanized

and chimeric monoclonal antibodies. However, human monoclonal antibodies

which are less likely to cause adverse immunological responses in patients

now form the largest group in research and development pipelines and are

expected to be the fastest growing segment of antibody therapeutics in the

future.

Competitors

BioInvent has created a highly functional and diverse library called n-

CoDeR®, which contains 2 x 1010 fully-human antibody genes. This

proprietary antibody library is the cornerstone of BioInvent's antibody

discovery platform, and is used in order to rapidly find therapeutic antibody

candidates with desired properties.

Partnerships: Bayer HealthCare, Daiichi Sankyo Company, Mitsubishi

Tanabe, XOMA.

Competitors

Kenta Biotech is focusing on the discovery and

development of innovative, fully human monoclonal

antibodies for the life-saving treatment of patients with

serious infectious diseases.

Evec specializes its business and technical positions

in developing human monoclonal antibodies, and

licensing pharmaceutical companies to use them.

Partnered product pipeline

• Indications of partnered programs

– Cancer, Alzheimer's disease, infectious

disease, cardiovascular dysfunction and

inflammation, etc.

Partnered product pipeline

• R 1450 : Gantenerumab

– Partner : Roche

– Indication : Alzheimer's disease

• Antibody attacks abnormal build-ups of

the amyloid beta protein in the cerebral

tissue that are characteristic of

Alzheimer's disease

– Phase 2 in a clinical trial


Generic NameTarget

Brand ®

FDA

Approval

Companies Indication Sales

$billion

2007 2008 2009

Infliximab c TNFα

Remicade 1998

J&J,

Merck KGA

CD, UC, AS

RA, Ps, PsA

5.04 6.5 6.91

Bevacizumab VEGF hz

Avastin 2004

Roche mBC, mCRC, NSCLC, mRCC, gliobastoma

3.93 4.7 5.92

Rituximab c CD20

Rituxan 1997

Roche Leukemia, Lymphoma, RA

5.01 5.6 5.8


Documents

Février Séphora Laloupe, Hélène Toulotte, Thomas …moodle.univ-lille2.fr/pluginfile.php/51632/mod_resource/content/0/... · SWOT Strengths •Patents •Supplementary segments: