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MorphoSys AG Investor Presentation 2010

Nov 25, 2010

291_ip_2010-11-25_70b02055-1aec-49ca-8afa-7d00dce583a1.pdf

Investor Presentation

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R&D Day 2010

London – November 25, 2010

Agenda

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This presentation includes forward forward-looking statements. looking

Actual results could differ materially from those included in the forward-looking statements due to various risk factors and uncertainties including changes in business, economic competitive conditions regulatory reforms foreign exchange rate fluctuations and the conditions, reforms, the availability of financing.

These and other risks and uncertainties are detailed in the Company's Annual Report.

Morpy q y hoSys has Grown into a Unique Antibody Discovery & Development Company

  • A technology platform that continues to set new standards for antibody generation
  • Deep antibody expertise spanning discovery & development
  • Promising proprietary product portfolio with best-in-class potential
  • A strong partnership roster creating multiple future product opportunities
  • Well financed and independent from capital markets as a source of financing

Strategy y g and How it Relates to Today's Agenda

PROPRIETARY DEVELOPMENT

  • C f ll l t d i & i fl ti Carefully selected programs in cancer inflammation
  • …taken by MorphoSys to clinical proof-of-concept
  • …promise a lucrative upside

PARTNERED DISCOVERY

  • A growing number of projects against partners' targets partners
  • …promises to result in multiple marketed drugs
  • …delivering a strong flow of milestone and royalty payments

Innovative, Proprietary Antibody Technology & Know-how

  • Fulfilling a growing demand for technologies which can deliver superior antibodies
  • …more efficacious, against new target types, better producible
  • …extending the therapeutic reach and performance of antibodies

Broadest Antibodyp y Pi eline in the Industry: 76 Programs Ongoing

Agenda

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The Morp y hoS s Platform Delivers Highly Optimized Therapeutic Antibodies

Basis for successful antibody drug development:

  • Reliable human antibody source of high quality & diversity
  • RapCLONE Robust high-throughput platform to expression & functional profiling
  • On-demand optimization technologies to i f tdengineer perfect drugs

Develop drugs not just antibodies drugs,

Excellence in Every p Ste of Antibody Generation

Human Combinatorial Antibody y Librar y HuCAL – An Industry Standard

Phag py g e Display Enables Accurate Tuning of Selection Against Various Antigen Classes

RapSODY: Direct Selection in IgG Format Unmasks Novel Epitopes

Surface Display

FACS-based Selection

Antibody Sequence Recovery

Rapid Selection of Displayed IgG's (RapSODY) on surfaceof mammalian cells allows: Target o su ace o a a a ce s a o s

  • FACS-based selection of large IgG libraries
  • Presentation of antigen in natural cell-surface configuration Library Reformating &
  • Selection of IgGs showing simultaneously high expression and affinity to target
  • Selection for additional and novel epitopes since alternative antibody presentation unmasks epitopes under-represented in phage display process
  • Add-on to and fully compatible with modular HuCAL system

RapSODY facilitates direct selection in final IgG format and opens up novel epitope spaces

RapCLONE: Hig gp h Throughput Conversion of Fab to IgG

  • MorphoSys starts with Fab fragments for efficient antibody characterizationTarget
  • IgG is most usual drug format
  • RapCLONE converts thousands of Fabs to IgG, in a single step, early in discovery

RapCLONE introduced a paradigm shift to high-throughput screening Drug Candidate directly in the drug relevant IgG format drug-relevant

Introducing – A Combination of Unique Technologies & Capabilities

HuCAL –"One-Size-Fits-All" Optimization

Beyond HuCAL - The Individually Optimized Antibody Drug

Higher Probabilities of Success & Faster Development

Today

Expectations:

  • Shorten time to generate antibody drug did t b 30%candidate by
  • Increase proportion of programs reaching clinical development to 50%

*Metrics for antibody therapeutics development, Janice M. Reichert

Technolog g ical Progress Exploiting New Opportunities

Agenda

  • 09:30 Simon Moroney Welcome and Introduction 09:35 Marlies Sproll Latest Technology Developments Developments

  • Update Partnered Pipeline

  • 10:05 Q&A

  • 10:20 Arndt Schottelius Introduction Proprietary Portfolio
  • 10:25 John Hamilton GM-CSF Central Mediator in Inflammation
  • 10:55 Arndt Schottelius MOR103 in RA & MS
  • 11:10 Q&A
  • 11:25 Lisa Rojkjaer MOR202 in Multiple Myeloma (MM) in MOR208 in Chronic Lymphocytic Leukemia (CLL)
  • 11:55 Q&A
  • 12:15 Simon Moroney Closing Remarks

Novartis AllianceOne of the Largest Technology Alliances

Discovery Pre-clinic Phase 1 Phase 2

  • 20 discovery programs steady state steady-state ti
  • ~75 employees (FTEs) at MorphoSys
  • Currently two joint predevelopment programs

Currently two tiCurrently two tiCurrently ten active programs active programs active programs

  • Novartis's biologics pipeline of antibodies is growing
  • Number of published joint patent applications so far: 13
  • Antibody development programs across various indications various
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Increasing Number of Partnered Programs in g g Clinical Development

New in 2010

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BHQ880: DKK-1 Sp y ecific Antibody in Multiple Myeloma Associated Osteolysis

Target DKK-1

  • Soluble factor, y py , secreted by multiple myeloma cells, inhibits differentiation of osteoblasts (bone formation) and causes increase in bone resorption which weakens the bones
  • Inhibition of DKK-1 is expected to release suppression of bone formation and to prevent the development of osteolytic disease

Antibody BHQ880

  • HuCAL IgG1 antibody, blocks DKK-1 binding to LRP5/6
  • High specificity and affinity for human and mouse DKK High DKK-1

Active Clinical Trial

  • Phase 1/2 (USA and Australia): BHQ880 in combination with standard chemotherapy and zoledronic acid in relapsed or refractory myeloma patients
  • Assessment of maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of escalating doses of BHQ880 (up to a maximum dose of 20 mg/kg); 9 months minimum treatment period
  • Study closed to enrollment, treatment and bone marker follow up continuing. Early results presented at ASH 2009.
  • Initiation of Phase 2 studies in multiple myeloma patients with renal insufficiency in combination with standard chemotherapy (without bisphosphonates) and as single agent in high risk smoldering agent myeloma is scheduled for Q1 2011

CNTO888: MCP-1 Sp y ecific Antibody in Cancer and Idiopathic Pulmonary Fibrosis

Target MCP-1

  • Monocyte chemoattractant protein 1 (or CCL2)
  • Produced by cancer cells as well as the tumor and bone micro-environment
  • Role in fibroblast activation

Antibody CNTO888

  • HuCAL IgG1 antibody targeting human MCP-1 with high specificity and affinity (~22pM)
  • Inhibition of tumor growth in multiple models

Completed Clinical Trials

Phase 1: Study of the safety and efficacy of single agent CNTO888 in patients with solid tumors

Active Clinical Trials

  • Phase 1b: Study of the safety and efficacy of CNTO888 in combination with Standard of Care chemotherapy in patients with solid tumors
  • Phase 2: Study of the safety and efficacy of single-agent CNTO888 in patients with metastatic castrate resistant prostate cancer
  • Phase 2 (USA, Canada, Belgium, Germany, Netherlands): Study to evaluate the safety and effectiveness of CNTO888 administered i.v. in subjects with Idiopathic Pulmonary Fibrosis (IPF)
  • Patients will be treated for up to 48 weeks (and followed by 72 weeks)
  • E ti t d t d l ti d t J 2012 (E ti t d ll t 120) Estimated study completion date: June (Estimated enrollment: MorphoSys AG – R&D Day – November 2010 Page 25

Gantenerumab: Amyloid Plaq p ue S ecific Antibody for Alzheimer's Disease

Target Amyloid β

  • Aβ peptide appears to be the main constituent of amyloid plaques deposited in the brains of Alzheimer's diseases patients
  • Inhibition of Aβ production and aggregation or increased Aβ-clearance might result in diseasemodifying treatments of AD

Antibody Gantenerumab

  • Human IgG, high affinity (sub-nM) and specificity, targeting aggregated Aβ
  • Chronic treatment in transgenic mouse model led to a significant reduction in amyloid load

Active Clinical Trial

  • Phase 2: Multi-center, randomized, double-blind, placebo-controlled parallel-group study
  • Evaluate the effect of Gantenerumab on cognition and functioning and the safety and pharmacokinetics in patients with prodromal Alzheimer's Disease
  • Subcutaneous doses every 4 weeks for 104 weeks (3 groups: placebo, 105mg or 225mg)
  • Study completion date: May 2015 (Estimated Enrollment: 360)

Pre-clinical and Clinical Data

  • Two Phase 1 studies in AD patients completed
  • Pre-clinical data presented at ICAD meeting in July 2010

BAY 79-4620: Anti-CA IX Immunoconjugate in Solid Tumors

Target CA IX (carbonic anhydrase IX; MN)

  • Overexpressed in a wide rang g e of human solid tumors, such as gastric cancer, non-small cell lung cancer, pancreatic cancer, and colorectal cancer
  • Highest expression in areas of tumor hypoxia
  • Expression is associated with increased malignancy and is predictive of prognosis in several cancers

Antibody Drug Conjugate BAY 79-4620

  • A novel antibody-drug conjugate (ADC) targeting CA IX-positive tumors
  • HuCAL IgG antibody coupled to cytotoxic MMAE (monomethyl auristatin E, Seattle Genetics)
  • Conjugate potently inhibits proliferation and induces cell death of human CA IX-expressing tumor cells by inhibition of tubulin polymerization (EC50 low nM)

Clinical Trial Design

  • Two phase 1 studies initiated (Europe/USA)
  • Determination of the safety and tolerability of the drug, pharmacokinetics profile of BAY79-4620 and its key metabolites, and the maximum tolerated dose (MTD)
  • Estimated St d Completion Date Jan ar 2012 (USA)/Febr ar 2013 (E rope) Estimated Study Date: January (USA)/February (Europe); Estimated enrollment: 55 (USA)/55 (Europe)

Pre-clinical Data

Pre clinical data ere presented at AACR in April 2010 Pre-clinicalwere

Agenda

  • 09:30 Simon Moroney Welcome and Introduction 09:35 Marlies Sproll Latest Technology Developments Update Partnered Pipeline
  • 10:05 Q&A
  • 10:20 Arndt Schottelius Introduction Proprietary Portfolio
  • 10:25 John Hamilton GM-CSF Central Mediator in Inflammation
  • 10:55 Arndt Schottelius MOR103 in RA & MS
  • 11:10 Q&A
  • 11:25 Lisa Rojkjaer MOR202 in Multiple Myeloma (MM) MOR208 in Chronic Lymphocytic Leukemia (CLL)
  • 11:55 Q&A
  • 12:15 Simon Moroney Closing Remarks

Focus of Prop y rietary Portfolio in Inflammation and Oncology

Focus built on core competencies (scientific and medical expertise) Leveraging network of leading KOLs

Creatingyg Value by Building a Sustainable Proprietary Pipeline

Growingp y Pro rietary Portfolio: Ten Active Programs

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Genesis of the MOR103 anti-GM-CSF Program

Agenda

  • 09:30 Simon Moroney Welcome and Introduction 09:35 Marlies Sproll Latest Technology Developments Update Partnered Pipeline 10:05 Q&A
  • 10:20 Arndt Schottelius Introduction Proprietary Portfolio
  • 10:25 John Hamilton GM-CSF – Central Mediator in Inflammation
  • 10:55 Arndt Schottelius MOR103 in RA & MS
  • 11:25 Lisa Rojkjaer MOR202 in Multiple Myeloma (MM) MOR208 in Chronic Lymphocytic Leukemia (CLL)
  • 11:55 Q&A

11:10 Q&A

12:15 Simon Moroney Closing Remarks

GM-CSF as a target in CSF as inflammation

John A Hamilton

Arthritis and Inflammation Research Centre, The University of Melbourne, Department of Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia

Topics

  • •Biology of GM GM-CSF
  • •GM-CSF as a proinflammatory cytokine CSF
  • •Indications for anti-GM-CSF therapy
  • •Advantages vs caveats

GM-CSF

  • •Glycoprotein: MW≈15kDa
  • • Binds GM-CSF-receptor (GM-CSF-R) • GM-CSF-R is a transmembrane glycoprotein Structure and is (α- and β-subunits) a dActivity
  • •Initiates Stat-5 signalling

GM-CSF producing and CSF responding cells

Topics

  • •Biology of GM GM-CSF
  • •GM-CSF as a proinflammatory cytokine CSF
  • •Indications for anti-GM-CSF therapy
  • •Advantages vs caveats

The main functions of GM main functions of GM-CSF

Adapted from: Hamilton JA, (2008) Nat Rev Immunol. 8:533-44

GM-CSF controls inflammatory cell numbers, activation CSF controls cell numbers, and is part of a cytokine network & feedback loop

Adapted from Hamilton JA, The Lancet (1993) 342: 536 - 539

Novel role for GM Novel GM-CSF in the generation and maintenance CSF of Th17 cells by regulation of IL-6 and IL-23

adapted from Sonderegger I et al. J Exp Med (2008), 205:2281-2294

41

Biologic actions of GM Biologic actions of GM -CSF in the CSF in pathogenesis of inflammatory diseases

Topics

  • •Biology of GM GM-CSF
  • •GM-CSF as a proinflammatory cytokine CSF
  • •Indications for anti-GM-CSF therapy
  • •Advantages vs caveats

In vivo validation of GM of GM-CSF as target for CSF inflammation

  • •Exacerbation of disease by GM-CSF
  • • Suppression of disease in GM-CSF-knockout mice
  • • S i f di b t li i tib di Suppression of disease by neutralizing antibodies to GM-CSF

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GM-CSF is a promising target for the CSF a for treatment of rheumatoid arthritis

  • •Elevated levels of GM GM-CSF found in RA synovial fluid CSF fluid
  • • GM-CSF treatment led to flares of RA in patients with F lt ey syndrome
  • • Macrophage numbers in RA synovial tissue
  • –increased numbers correlate with disease severity
  • –decreased numbers numbersobserved after treatment of RA

(Hamilton JA & Tak PP.Arthritis Rheum. 2009 May;60(5):1210-21)

• A ti n -GM-CSF mAb i ff ti t t t i RA is an effective treatment in disease models

GM-CSF depletion suppresses collagen induced arthritis

Campbell IK, Rich MJ, Bischof RJ, Dunn AR, Grail D, Hamilton JA. J. Immunol. (1998) 161: 3639 Cook AD, Braine EL, Campbell IK, Rich MJ, Hamilton JA. Arthritis Res. (2001) 3: 293

48

GM-CSF is strongly implicated in the CSF pathogenesis of rheumatoid arthritis

Inflammation & Synovitis Structural Damage – Bone Erosion

GM-CSF is a promising target for the CSF a for treatment of multiple sclerosis

  • • Elevated levels of GM-CSF correlate with the active phase of MS (Carrieri et al., 1998)
  • • Recombinant GM-CSF exacerbates EAE in GM-CSFwt mice (McQualter et al., 2001)
  • • Anti-GM-CSF mAb is an effective treatment in MS disease models

GM-CSF depletion suppresses experimental CSF depletion suppresses experimental autoimmune encephalomyelitis (EAE)

McQualter JL, Darwiche R, Ewing C, Onuki M, Kay TW, Hamilton JA, Reid HH, Bernard CC. J Exp Med. (2001) 194:873-82

GM-CSF is strongly implicated in the CSF pathogenesis of multiple sclerosis

Periphery CNS

King et al., (2009) Blood 113:3190-7 Ifergan et al. (2008) Brain 131:785-99 Hesske et al., (2010) Brain 133:1637-54 Ponomarev et al., (2007) J Immunol 178:39-48 1234

Topics

  • •Biology of GM GM-CSF
  • •GM-CSF as a proinflammatory cytokine CSF
  • •Indications for anti-GM-CSF therapy
  • •Advantages vs Caveats

GM-CSF targeting caveats

GM-CSF-/- mouse phenotype

  • •Steady state hematopoiesis – unimpaired
  • • Accumulation of phospholipids and surfactant proteins in the lung: resembling pulmonary alveolar proteinosis (Stanley et al 1994; Dranoff et al 1994)
  • • GM-CSF -/- mice are more susceptible to infections, when experimentally challenged with hig pg h doses of pathogens

Pulmonary Alveolar Proteinosis (PAP)

  • •Clinical features: dyspnea, dry cough
  • • In the largest cohort of PAP patients investigated (n=248) intercurrent illnesses, including infections, q( ) were infrequent (Inoue et al 2008)
  • • Manifestation of clinical PAP seems to require long-term GM-CSF deficiency caused by high levels of GM-CSF autoantibodies; clinically manageable

Pulmonary function and infection risk should be monitored in clinical trials

GM-CSF targeting advantages CSF

  • •"Upstream" mediator Upstream"
  • dramatic therapeutic effect in disease models of RA and MS
  • central player in inflammatory processes
  • links o t TNFα, IL-1, IL-23 / b o ogy / Th17 biology
  • • Unlikely a steady state hematopoietic growth factor
  • no i t mpac on h t ii ematopoiesis expect d f ti ted for anti-GM-CSF mAb
  • • Control of myeloid numbers and activation at sites of inflammation
  • therapeutic effect expected at site of pathology (e.g. RA joints)

Agenda

  • 09:30 Simon Moroney Welcome and Introduction 09:35 Marlies Sproll Latest Technology Developments Update Partnered Pipeline
  • 10:05 Q&A
  • 10:20 Arndt Schottelius Introduction Proprietary Portfolio
  • 10:25 John Hamilton GM-CSF Central Mediator in Inflammation
  • 10:55 Arndt Schottelius MOR103 in RA & MS
  • 11:10 Q&A
  • 11:25 Lisa Rojkjaer MOR202 in Multiple Myeloma (MM) MOR208 in Chronic Lymphocytic Leukemia (CLL)
  • 11:55 Q&A
  • 12:15 Simon Moroney Closing Remarks
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MOR103 Potently Neutralizes GM-CSF

IC50: 48 pM - human GM-CSF (E.coli) 11 pM - human GM-CSF (HEK293) 15 pM - rhesus GM-CSF (HEK293) Blocking of STAT5 phosphorylation: TF

MOR103 inhibits proliferation of TF-1 cells MOR103 inhibits downstream signaling of GM-CSF-Receptor GMCSF Receptor

with GM-CSF

w/o GM-CSF

with GM-CSF + MOR103

1 cells were stained with a phospho specific STAT5 antibody (red) TF-1 phospho-specific antibody Nuclei were stained with Hoechst33342 (blue)

GM-CSF is Strongy p l Im licated in the Pathogenesis of Rheumatoid Arthritis

Inflammation & Synovitis Structural Damage – Bone Erosion

Expected Therapeutic Effects of Treatment with MOR103 in Rheumatoid Arthritis

Results From SCW InducedArthritis Rat Model

Error bars show: ±SD; n=5 rats/group; *P<0.03 and **P<0.008 compared to IgG1 control (Mann Whitney)

Treatment: MOR103 dosed at 10 20 and 50 mg/kg once i p 2h before intra-articular administration of SCW fragments to male Wistar rats (right knee) MOR103 10, i.p. intra articular RA Parameters: Knee joint swelling (right/left knee ratio assessed by Technetium uptake) and histopathology (PMN cell influx)

Significantly decreased knee joint swelling and synovium cell influx following treatment with MOR103 compared to IgG1 control (at 50mg/kg)

Rationale for Selecting Rheumatoid Arthritis as Lead Indication for MOR103

  • Strong scientific rationale based on literature and in-house data
  • Suppression of GM-CSF shows therapeutic effect in established RA animal models
  • GM-CSF-mediated flares in RA patients
  • Elevated presence of GM-CSF in synovium of arthritic joints
  • Suppression of base level GM-CSF in humans does not lead to changes in hematopoiesis
  • MOR103 ameliorates sig y ns & symptoms of RA in established animal models
  • Novel mode of action, different from existing therapies
  • Links between GM-CSF and IL-23/Th17 biology
  • Unmet medical need in RA
  • Fewer than 25% of RA patients adequately treated
  • 50% of TNF TNF-responders stop responding within 2 years responders years
  • Commercial opportunity
  • RA Market >\$13bn and growing
  • Interest from potential licensees

© MorphoSys AG MorphoSys

MOR103 – Phase 1b/2a (MSC-1001) in Rheumatoid Arthritis – Clinical Trial Update

  • Objectives: assess safety, signs of efficacy and immunogenicity of MOR103 in patients with active RA
  • Trial design
  • Randomized, double-blind, placebo controlled
  • 135 patients with active RA
  • Four ascending doses i.v. 0.3, 1.0 and 1.5 mg/kg or placebo
  • Primary outcome measures: Adverse event rate and safety profile
  • Secondary outcome measures: DAS28 ACR core set measures and DAS28, EULAR28 response criteria, cytokines, MRI (synovitis & bone edema), pharmacokinetics, immunogenicity and patient reported outcomes up to 16 weeks
  • Stable regimen of concomitant RA therapy
  • Trial approved in Germany, Bulgaria, The Netherlands and Poland
  • Geographic mix provides access to full spectrum from biologicspretreated to biologics-naïve RA patients

The Path to Bone Erosions in RA Pre-erosive Changes Are Detectable by MRI

MRI is the only imaging tool for early detection of synovitis & osteitis as risk factors for progressive destructive disease risk

High Sensitivity Imaging Biomarker in RA

MRI in RA is well validated:

MRI –

  • MRI can detect reduction in synovitis and bone edema as early as 4-6 weeks after therapy
  • (Lisbona MP et al. J Rheum 2008;35:394-397, Q i MA t l Quinn MA et al. A thr r Rh 2005 52 27 Rheum 2005;52:27-35)
  • MRI is more sensitive than X-ray for bone erosions
  • A validated MRI scoring system exists thus exists, thusMRI is suitable for clinical trials
  • MRI imag g in included in MSC-1001 protocol

Synovitis (MRI)

Same hand of RA patient

X-ray: bone erosion MRI: Bone X ray: not visible (obscured)

erosion visible

MRI – High Sensitivity Biomarker Capable of Demonstrating Early Responses to Therapy Enabling Early Proof of Concept

GM-CSF is Strongy p l Im licated in the Pathogenesis of Multiple Sclerosis

King et al., (2009) Blood 113:3190-7 Ifergan et al. (2008) Brain 131:785-99 Hesske et al (2010) Brain 133:1637-54 123 al., Ponomarev et al., (2007) J Immunol 178:39-48 4

Exp p ected Therapeutic Effects of Treatment with MOR103 in Multiple Sclerosis

King et al., (2009) Blood 113:3190-7 Ifergan et al. (2008) Brain 131:785-99 Hesske et al (2010) Brain 133:1637-54 123 al., Ponomarev et al., (2007) J Immunol 178:39-48 4

Results from MOG Induced Rat Model for Multiple Sclerosis

  • Rats were injected with MOG1 peptide on day 0 y
  • MOR103 treatment after MOG immunization
  • Disease onset around da y 10
  • Significant decrease in EAE score after preventive treatment on day 7
  • Thera peutic treatment commencin g p on day 14 resulted in a trend of disease amelioration

*ANOVA LSD posthoc analyses vs. isotype ( p <0.05); SEM is shown

12

Significantly decreased cumulative EAE score following treatment with MOR103 cf IgG1 control (at 50mg/kg) cf.

Rationale for Selecting p Multi le Sclerosis as Second Indication for MOR103

  • Strong scientific rationale based on literature and in-house data
  • Elevated levels of GM-CSF correlate with active phase of MS
  • GM-CSF-/- mice do not develop EAE
  • Anti-GM-CSF ameliorates EAE in GM-CSF wt mice
  • MOR103 reduces cumulative EAE score in GMGM-CSF wt rats CSF
  • Unmet medical need in MS
  • None of currently marketed MS drugs fully control and alleviate symptoms
  • S ifi ll hi h t di l d i i f f MSSpecifically high unmet medical need in progressive forms of
  • Commercial opportunity
  • High-price and g g rowin market
  • Drugs in MS with blockbuster potential
  • Interest from potential Licensees
  • Next steps
  • Prepare protocol and CTA application for Phase 1b safety study
  • Initiate Phase 1b safety study in Q4/2011

MOR103 – Phase 1b/2a (MSC-1001) in Rheumatoid Arthritis – Clinical Trial Update

  • Phase 1b/2a in patients with active rheumatoid arthritis ongoing
  • Final Phase 1b/2a RA data expected in H1 2012
  • Start Phase 1b safety study in multiple sclerosis planned in Q4 2011
  • Subcutaneous administration development ongoing (SQ PK study in healthy volunteers p ) lanned in 2011)
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MOR103 Has a Strong p Com etitive Profile

  • MOR103 is a HuCAL antibody
  • Fully human, high affinity to GM-CSF, may lead to low cost of goods
  • Fully human antibodies have a lower risk of immunogenicity
  • Subcutaneous administration
  • N t li i l bl GM Neutralizing soluble GM-CSF i t d f th t CSF instead of the receptor seen as an advantage
  • Morp y p p pg hoSys has a solid patent position around the program
  • Exclusive access to a US patent from the University of Melbourne: Patent generically covers the treatment of chronic inflammatory disorders via GM-CSF antibodies
  • Worldwide patents and patent applications covering the antibody specifically

Blockbuster potential in multiple indications supported by a broad preclinical data package

Agenda

  • 09:30 Simon Moroney Welcome and Introduction 09:35 Marlies Sproll Latest Technology Developments Update Partnered Pipeline
  • 10:05 Q&A
  • 10:20 Arndt Schottelius: Introduction Proprietary Portfolio
  • 10:25 John Hamilton GM-CSF Central Mediator in Inflammation
  • 10:55 Arndt Schottelius MOR103 in RA & MS
  • 11:10 Q&A

11:25 Lisa Rojkjaer MOR202 in Multiple Myeloma (MM) MOR208 in Chronic Lymphocytic Leukemia (CLL)

  • 11:55 Q&A
  • 12:15 Simon Moroney Closing Remarks
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Multipy gy le Myeloma: Plasma Cell Malignancy With High Unmet Medical Need

  • Second most common hematological malignancy after NHL
  • Estimated 5 -year survival of 38%1 year survival 38%
  • Key disease features: anemia, kidney failure, bony lesions
  • Characterized by disease relapses and increasing drug resistance
  • Sales of leading therapies are combined €2.5 billion+ worldwide and are growing
  • Malignant plasma cells highly express CD38, making MOR202 (anti-CD38) an ideal candidate to evaluate
  • Competition: Two human CD38 molecules are in phase 1 development

CD38 is a Keyg y Tar et in Myeloma

What is CD38?

  • ype a s e ba eg ycop o e
  • Belongs to family of ectoenzymes/receptors involved in catabolism of extracellular nucleotides

Function

  • ADP-Ribosyl-cyclase/cADPR-hydrolase

  • Receptor for CD31

  • Plasma cells, B/T lymphocytes

Highly expressed on MM cells

Utilized to induce ADCC

CD38 Expression in Hematologic Disorders

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Monocytes/macrophages, thymocytes, NK cells * considered CD38-positive when 20 or 30% of cells exhibit CD38- expression (Meta analysis; CLL: 13 publications; ALL; AML; CML: 2 publications; NHL: 1 publication) p ;p )**

PTLD = post-transplant lymphoproliferative disorders

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MOR202 Increases Survival in a Mouse Xenograft Model of Lymphoma

Ramos cells inoculated i v on day 0; 8 mice per group i.v. Treatment started 3 days post inoculation

MOR202 Binds to CD38 and Induces ADCC-Mediated Lysis of Myeloma Cells

40g PBMC Donor A. PBMC Donor BMarlies Sproll 0 001 0 01 0 1 1 10 100 0100.0010.010.1Antibody [nM]

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MM patient cells

MOR202 Inhibits Bone Lysis in an Orthoto pic Mouse Model of Multiple Myeloma

Use of targeted therapy in combination with standard regimens in myeloma can:

Cy y totoxicityof MOR202 is Enhanced by

  • Minimize adverse events while increasing efficacy through different mechanisms
  • Add flexibility to treatment regimens (e.g. in elderly patients)
  • Preclinical investigations are on-going to identify potential combination partners for MOR202

10µg/ml MOR202 and 4nM Bortezomib

Velcade

In vitroADCC assay

MOR202 Well Tolerated in 12-week Repeated Dose Toxicity Study in Non-Human Primates

  • Versatility of HuCAL technology enables generation of antibodies that are cross-reactive, allowing safety assessment in animals to optimize development
  • Marmoset monkey identified as relevant NHP species
  • High target sequence identity
  • Similar binding of MOR202 to human and marmoset CD38 (shown)
  • MOR202 mode of action (ADCC) present in marmoset with similar activity ex vivo
  • Tox study conclusions
  • Safety profile supports entry into clinical trials Safety supports
  • Dose-proportionality of PK parameters observed

MOR202– Phase 1/2a Trial

Design

Multicentre, open-label, dose-escalation study (EU)

Population

Patients with relapsed/refractory multiple myeloma; failure of at least 2 relapsed/refractory prior therapies

Objectives:

  • Investigate maximum tolerated dose, safety and tolerability
  • Pharmacokinetics and immunogenicity
  • Assess preliminary activity

Enrollment of first patient expected in H1 2011

Agenda

  • 09:30 Simon Moroney Welcome and Introduction 09:35 Marlies Sproll Latest Technology Developments Update Partnered Pipeline
  • 10:05 Q&A
  • 10:20 Arndt Schottelius Introduction Proprietary Portfolio
  • 10:25 John Hamilton GM-CSF Central Mediator in Inflammation
  • 10:55 Arndt Schottelius MOR103 in RA & MS
  • 11:10 Q&A
  • 11:25Lisa Rojkjaer MOR202 in Multiple Myeloma (MM) Myeloma

MOR208 in Chronic Lymphocytic Leukemia (CLL)

  • 11:55 Q&A
  • 12:15 Simon Moroney Closing Remarks

Anti-CD19 Antibodies Hold Promise for the Treatment of B-cell Malignancies

  • Broader expression of CD19 in B-cell tumors compared to CD20
  • Potential for use in patients with use rituximab resistance
  • Encouraging clinical data with CD19 bispecific antibody in NHL and ALL validates CD19 as a new target

Success of B-cell depletion in lymphoma opens many possibilities for novel regimens cell novel

Antitumor Mechanisms are Mediated by Ig GFc Receptor Interactions

Two interactions are key for mAb activity:

  • 1 mAb binding to the tumor -associated associated antigen
  • Binding of Fc receptor (FcR) on effector cell (e. g. NK cell) to the Fc portion of the 2(g ) mAb

Immune effector-mediated mechanisms are important for mAb-mediated cytotoxicity:

Fc receptors on leucocytes (Fc R) mediate several effector functions (e.g. phagocytosis, ADCC) against Ab-bound targets

MOR208/XmAb5574: Fc Optimization for Increased Tumor Killing Increased

Higher FcR Affinity Correlates with Better Clinical Response to Rituximab

  • NK cell FcRIIIa receptors are important for rituximab-dependent cytotoxicity Progression Free Survival Cartronagainst lymphoma cells
  • Two polymorphisms in the FcRIIIa gene exist: position 158, valine (V) or phenylalanine (F)
  • Affinity for IgG1: V = 5x F
  • Rituxan were assessed in 49 previouslyuntreated patients with follicular NHL
  • Data demonstrates that stronger IgG bi di t th F RIII t i binding to the FcRIIIa receptor improves ADCC

Higher FcRIIIa affinity Improved clinical efficacy

MOR208/XmAb5574 Has a Humanized, Affinit y Optimized Fv Domain and Enhanced ADCC

MOR208/XmAb5574 Has a High ADCC Fc Domain: Enhanced Binding to Fc RIIa and Fc RIIIa

Fc variantV90 239D/332E–

Human validation in XmAb2513 (anti-CD30) 7

  • Well-tolerated (very few adverse events, no maximum tolerated dose)
  • Low immunogenicity 5.5
  • Objective responses in Hodgkin's disease IgG1 V90 IgG1 V90

MOR208/XmAb5574 Has Superior Cytotoxicity

Highly cytotoxic against a panel of phoma and leukemia cell lines

Higher ADCC than rituximab & alemtuzumab

Hi gher ADCC than I gG1 anti-CD19 g (unmodified)

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MOR208/XmAb5574AntiCD19

rituximab (CD20) alemtuzumab (CD52) ( )XmAb (-) control

MOR208/XmAb5574 Induces Potent ADCC Against Patient-Derived B-CLL Cells

NK-mediated ADCC against patient CLL cells

Awan et al., Blood 2010

MOR208/XmAb5574 Prevents the Growth of Subcutaneous Lymphoma Tumors

Human tumor xenograft in SCID mice; Horton HM et al. Cancer Res 2008;68:8049-57 Tumor inoculation points = 0; 10 mice per group

Efficacy g A ainst Established Tumors is FcR-Dependent and Enhanced by Fc Engineering

  • Human tumor xenograft in
  • 40-120 mm3 Ramos tumors at start of Ab treatment
  • 10 mg/kg Ab, 2x/week for 3 weeks, 10 mice/group

anti-CD19 Fc KO: full length anti-CD19 with two mutations that remove FcR binding

Page 91

MOR208/XmAb5574 Depletes B cells in Cynomolgus Monkeys

Single 10 mg/kg dose; N=6

Zalevsky J et al. Blood 2009;113:3735-3743

MOR208/XmAb5574 showed efficient B cell depletion in peripheral blood and lymph nodes, while not decreasing serum IgG levels

Lenalidomide Sig y nificantly Enhances ADCC Activity of MOR208/XmAb5574

  • Lenalidomide is an immunomodulating agent, approved for relapsed myeloma
  • Reported to enhance T cell and NK cell activity
  • Active in relapsed/refractory CLL

Potential for novel combination regimens with MOR208/XmAb5574 in CLL therapy

Potential Benefits of Targ g etin g CD19

In CLL: CD19 antigen density per cell is significantly higher than CD20

(D'Arena G et al, Leuk Lymphoma 2001;42:649-654)

  • Ability to target and deplete pre-B and immature B cells in the bone marrow, as well as peripheral mature B as -cells(Yazawa N, 2005)
  • May translate into more durable peripheral B cell depletion
  • B-cell depletion in lymph nodes demonstrated cell in lymph in vivo (Schroeder, 2003; Cioc, 2008, Cavallo, 2008)
  • Loss of CD20 expression following Rituxan treatment is reported i t 50% ith i t f CD19 iti it in up to 50%, with persistence o f CD19 positi vity (Chu, 2002; Seliem, 2006)
  • Anti-CD19 antibodies have efficacy against Rituxan-resistant cell lines in vitro(Gerber, 2009)
  • CD19 antibodies in develo pment show preliminar y efficac y in p p yy rituximab refractory/resistant patients

MOR208/XmAb5574 is Competitive in the CD19 Antibody Space

  • Expected half life favoring convenient dosing schedule
  • i v. . administration
  • Straightforward manufacturing
  • Potential for g yp ood safet y profile
  • Embraces a number of effector mechanisms
  • Significantly increased ADCC compared to rituximab in vitro
  • Enhanced FcRIIa affinity may enhance macrophage function, and result in improved tissue B-cell depletion

Fc domain modification of MOR208/XmAb5574 b bd f ff t h i embraces a broader range o f effector mechanisms

MOR208/XmAb5574– Phase 1 Trial

Design

Multicentre, open-label, multi-dose, single-arm phase 1, dose-escalation study (USA)

Population

Patients with CLL/SLL who have not responded to or have become CLL/SLL, to refractory to previous therapies

Objectives

  • I ti t i t l t d d f t d t l bilit Investigate maximum tolerated dose, safety and tolerability
  • Pharmacokinetics and immunogenicity
  • Assess preliminary anti-tumor activity

Clinical Data

Final data will become available in 2012

Agenda

  • 09:30 Simon Moroney Welcome and Introduction 09:35 Marlies Sproll Latest Technology Developments Developments Update Partnered Pipeline
  • 10:05 Q&A
  • 10:20 Arndt Schottelius Introduction Proprietary Portfolio
  • 10:25 John Hamilton GM-CSF Central Mediator in Inflammation
  • 10:55 Arndt Schottelius MOR103 in RA & MS
  • 11:10 Q&A
  • 11:25 Lisa Rojkjaer MOR202 in Multiple Myeloma (MM) in MOR208 in Chronic Lymphocytic Leukemia (CLL)
  • 11:55 Q&A
  • 12:15 Simon Moroney Closing Remarks

Therap g eutic Antibodies: A Star Still Rising

  • Opportunity for therapeutic antibodies continues to grow
  • Increasing understanding is guiding us to new ways of making superior therapeutic antibodies
  • The future will see
  • Antibodies with much greater efficacy
  • …against new target classes
  • …being adopted in new indications
  • …with much lower cost-of-goods
  • and more…

MorphoSys aims to command and apply a range of technologies to deliver innovative new antibody based drugs antibody-based

Strategy y g and How it Relates to Today's Agenda

PROPRIETARY DEVELOPMENT

  • C f &f arefully selected programs in cancer & inflammation
  • …taken by MorphoSys to clinical proof-of-concept
  • …promise even greater upside

PARTNERED DISCOVERY

  • A growing number of projects against partners' targets g g pj g p g
  • …promises to result in multiple marketed drugs
  • …delivering a lucrative flow of milestone and royalty payments

Innovative, Proprietary Antibody Technology & Know-how

  • Fulfilling a growing demand for technologies which can deliver superior antibodies
  • …more efficacious, against new target types, better producible
  • …extending the therapeutic reach and performance of antibodies

A Strategy for Substantial Value Creation

Great Prog p ress of Clinical Pipeline

Clinical Antibody Pipeline is a Key Value Driver Antibody * assuming no attrition

Thank You

www.morphosys.com

HuCAL®, HuCAL GOLD®, HuCAL PLATINUM®, CysDisplay®, RapMAT® and AutoCAL® are registered trademarks of MorphoSys AG

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