Analyst & Investor Day February 27, 2009 - IIS …library.corporate-ir.net/library/97/975/97573/items/...Analyst & Investor Day February 27, 2009 Driving a New Era in Anticancer Therapies

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Analyst & Investor DayFebruary 27, 2009

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WelcomeCarol Hausner, Executive Director,

Investor Relations

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Meeting AgendaDriving a New Era Daniel Juniusin Anticancer Therapies President and CEO

Driving Our Technology John Lambert, Ph.D.And Pipeline Executive VP and CSO

Break

Development Strategies James O’Leary, M.D.for Our Clinical Compounds Vice President and CMO

Business Development and Gregory PerryOur Financials: Mutually Supportive Senior Vice President and CFO

Q&A

Closing Remarks Daniel Junius

Being Webcast!

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Terminology

Antibody-Cytotoxic agent Conjugates (ACCs)• Monoclonal antibody (MAb) or other cell-targeting vehicle with

attached small molecule cancer-killing agent (CKA)• We use purpose-developed, ImmunoGen-proprietary CKAs

rather than existing drugs

Tumor-Activated Payload (TAP) Technology = ImmunoGen’sproprietary ACC technology

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Forward-Looking Statements

This presentation includes forward-looking statements based on management’s current expectations. For these statements, ImmunoGen claims the protection of the safe harbor for forward-looking statements provided by the Private Securities LitigationReform Act of 1995. Various factors could cause the Company’s actual results to differ materially from those discussed or implied in the forward-looking statements and you are cautioned not to place undue reliance on these forward-looking statements, which are current only as of the date of this presentation. Factors that could cause future results to differ materially from such expectations include, but are not limited to: uncertainty whether the Company’s TAP technology will produce safe, effective and commercially viable products; the difficulties inherent in the development of novel pharmaceuticals, including uncertainties as to the timing, expense and results of preclinical studies and clinical trials conducted by the Company or its collaborative partners; determination by the Company or by its collaborative partners to alter the resource support for a given product program; the Company’s dependence on collaborative partners; and other factors more fully described in ImmunoGen’s Annual Report on Form 10-K for the fiscal year ended June 30, 2008 and other reports filed with the Securities and Exchange Commission.

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Driving a New Era in Anticancer TherapiesDaniel Junius, President and

Chief Executive Officer

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ACCs are opening a new era in cancer treatments.

ImmunoGen is well positioned for success…through our technology and throughour product programs.

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ACCs: Potential for Better Anticancer Products

Example: Trastuzumab-DM1 (T-DM1)

Initial findings in patients with HER2+ metastatic breast cancer that progressed on trastuzumab (Herceptin) + chemotherapy. Some also had received lapatinib(Tykerb) + chemotherapy.

Favorable tolerability

38.2%43.4%Overall

Objective Response RateConfirmed

• Interim findings from Phase II trial, San Antonio Breast Cancer Symposium, 12/08• Data from patients (n=76) who either had ≥ 6 months follow up or were off study at data cut-off• Objective response rate is Complete + Partial Responses; Stable Disease not included• 2 discontinuations due to possibly drug-related side effects. Most side effects were ≤ Grade 2

and manageable

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Phase I Start 4/06

1st LinePhase II Trial

T-DM1 (alone) vs Herceptin + TaxotereStarted 7/08 NCT00679341

With PertuzumabPhase Ib Trial

Patients progressing on Herceptin* To start 1H09

*Administered with chemotherapy. All studies outlined to date are in patients with HER2+ metastatic breast cancer

Genentech and Roche: Implementing a Broad, Aggressive T-DM1 Clinical Development Plan

3rd Line: After Herceptin,* after Tykerb* Phase II Trial

May enable discussion of accelerated pathway with FDA

Started 7/08 NCT00679211

2nd Line: After Herceptin*Phase III Trial (EMILIA)

T-DM1 vs Tykerb + XelodaTo start 1H09 NCT00829166

Additional Studies

PotentialRoutes to

Registration

Phase II (2nd-Line+) Start 7/07Concurrent evaluation ofalternative dosing schedule

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ACCs – Potential for More Anticancer Products

CD19

CD22 CD30

CD33

CD56

CD70

CD79b

Integrin

B7-H4CanAg

Cripto

DS6

EphA2

GPNMB

CD138

PTK7 RG-1

TIM-1

PSMA

ACC TargetsDisclosed

by ≥1 Company

Many ACC targetsare undisclosed

VEGFEGFRCD52CD20

Targets with Anticancer MAbs

Today

Had ~$18Bin sales in 2008

HER2

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Multiple Major Companies Are Now Pursuing MAb-Based Therapeutics

Ones with ACC collaborationsalready include:

• AstraZeneca (Medimmune)• Amgen• Bayer HealthCare• Biogen Idec• Daiichi Sankyo• Genentech/Roche• Sanofi-aventis

Others with MAb programsinclude:

• Boehringer Ingelheim• Eli Lilly (Imclone) • Genzyme• GlaxoSmithKline • Merck • Novartis • Pfizer

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ImmunoGen: Positioned Well in ACC Field

• Technology used in trastuzumab-DM1

• Expected to be first significant ACC product on market

• Activity in patients whose cancer progressed on trastuzumab (Herceptin) + chemotherapy

• Continually expanding platform technology

• Greatest number of proprietary ACC compounds in clinic and most partnered ACC compounds in clinic

• Expanding portfolio of increasingly more attractive partnerships

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ImmunoGenACC

Leadership

Efficacy• Demonstrated with T-DM1• Expected for additional

compounds in 2009

Tolerability• Highest MTDs in field


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ImmunoGen Technology: Impressive Tolerability

<<12 in clinicDNAHydrolysableNon-IMGN

<22 in clinicTubulinCleavableNon-IMGN

IMGN242

T-DM1

IMGN901

Compound

IMGN

IMGN

IMGN

Design

3.4**TubulinCleavable (SPDB)

3.6TubulinNon-cleavable (SMCC)

≥ 6.0 TubulinCleavable (SPP)

MTD(mg/kg)

Site of Actionof Killing AgentLinker

* Dosed at 3 week intervals** ≥4.5 mg/kg in certain patient populations

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ImmunoGenACC

Leadership

Efficacy• Demonstrated with T-DM1• Expected for additional

compounds in 2009

Tolerability• Highest MTDs in field

Manufacturability• Commercial-scale DM1/

DM4 manufacturer in place• ImmunoGen, other

conjugation capacity in place


Design Flexibility• Linker, CKA portfolios• Modular approach

facilitates testing alternative existing and new designs

Continued TechnologyEnhancements• New linkers and CKAs

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ImmunoGen: Expanding Technology Platform

Stage IDeveloped a highly potent maytansinoid CKA and stable, controlled-release linker• One design in clinic“One Size Fits Some”

• We/our partners select optimum design using modular components

• Multiple designs in clinic“Customized Design”

Stage IIDeveloped alternative MAY CKAs and linkers

Stage IIIExpanding portfolio of alternative CKAs, linkers, and designs to continually broaden potential uses

• Linkers appropriate for more-challenging situations (e.g., MDR cancers)

• CKAs with alternative mechanisms of action

“Customized Functionality”

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IMGN388*

SAR3419AVE1642+

Others+

SAR650984+, others+

IMGN901

Target licensed 4Q08

Developer Compound Phase I Phase II Phase III

IMGN242

T-DM14 more targets licensed

SAR566658

BIIB015BT-062**

Multiple

ImmunoGen + Partners: Deep, Advancing Pipeline

*Centocor has opt-in rights **ImmunoGen has opt-in rights

+Is or includes naked antibodies

Phase III to start 1H09

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ImmunoGen + Partners: Deep, Advancing PipelineIncreasing Number of Clinical-Stage Compounds

0

2

4

6

8

6/30/05 6/30/06 6/30/07 6/30/08 Today

We expect 2-4 more compounds in the clinic in 2010

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ImmunoGen + Partners: Deep, Advancing PipelineExpanding, More Advanced Clinical Programs

Completed trials not included

0

2

4

6

8

10

12

14

16

6/30/05 6/30/06 6/30/07 6/30/08 Today

# Trials - Total

# Trials - Ph II

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Partnering ConsiderationsControl of Target• If critical IP held by another company, must collaborate

to achieve product (e.g., trastuzumab-DM1)

Magnitude of BenefitE.g., sanofi-aventis collaboration:• Significant committed research funding – minimized our burn

while our compounds advanced – plus milestones, royalties • Global partner for multiple early-stage compounds• Resulted in multiple additional sources of cash

Expertise• Expansion into other applications for our technology

likely to include collaborations

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ACC: Partner MAb/Our Technology

ACC: Our MAb/Our Technology

“Naked” MAb:Our MAb

Partner Compounds:T-DM1, BIIB015

Partner Compound/IMGN Opt-in Rights:

BT-062

IMGN Compound/Partner Opt-in Rights:

IMGN388

Our Compounds:IMGN901, IMGN242

Only clinical-stage partner compounds are listed

Partner Compound:AVE1642

Our Compounds(preclinical)

Compounds with ImmunoGen marketing and development rights

Judicious Use of Partnerships to Expand Pipeline, Reduce Dependence on Capital Markets


Partner CompoundSAR3419

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ACC: Partner MAb/Our Technology

ACC: Our MAb/Our Technology

“Naked” MAb:Our MAb

Partner Compounds:T-DM1, BIIB015

Partner Compound/IMGN Opt-in Rights:

BT-062

IMGN Compound/Partner Opt-in Rights:

IMGN388

Our Compounds:IMGN901, IMGN242

Only clinical-stage partner compounds are listed

Partner Compound:AVE1642


Compounds with ImmunoGen marketing and development rights

Judicious Use of Partnerships to Expand Pipeline, Reduce Dependence on Capital Markets


Partner CompoundSAR3419

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After IMGN242

(First dose)

Baseline

FDG-PET Scan Images

• Target – CanAg – found on many types of solid tumors

• In Phase II for CanAg+ gastric cancer• Gastric cancer – a leading cause of death globally,

sensitive to IMGN242 in preclinical testing

• Plan – evaluate in 23 patients• ≥ 1 durable objective response → study expansion to 39• Otherwise, discontinuation

• Go/no go decision expected in 2009; minimal $ to achieve

IMGN242Wholly Owned by ImmunoGen

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• Target – CD56 – found on multiple myeloma (MM) and numerous solid tumors

• In Phase I testing for CD56+ MM and solid tumors• Encouraging activity in both areas

• Next steps• MM: continued assessment as monotherapy• MM: initiation of Ph I/II trial in combination• Solid tumors: additional insights from current study

• Looking for signal in 2009; minimal incremental $ to achieve

IMGN901Wholly Owned by ImmunoGen

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IMGN388*

SAR3419AVE1642+

Others+

SAR650984+, others+

IMGN901

Target licensed 4Q08

Developer Compound Phase I Phase II Phase III

IMGN242

T-DM14 more targets licensed

SAR566658

BIIB015BT-062**

Multiple

ImmunoGen + Partners: Deep, Advancing Pipeline

*Centocor has opt-in rights **ImmunoGen has opt-in rights

+Is or includes naked antibodies

Phase III to start 1H09

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IMGN388 – A Broadened Use of Our Technology

• Targets an integrin found on array of solid tumors

• IMGN388 activity by direct killing of cancer cells

• Standard mechanism of action of TAP compounds

• Integrin target also plays role in new blood vessel formation(angiogenesis)

• Potential activity via disruption of a process critical to the growth of any solid tumor

• Expands potential utility of IMGN388, our technology

• First clinical data expected in 4Q09

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ImmunoGenACC

Powerhouse

ImmunoGenProduct

DevelopmentCompany

Strong Product Development Capabilities

MAb development,including• Target evaluation• Candidate generation• Humanization• Candidate evaluation • Cell line development

Full lab-to-clinic capabilities(Preclinical, IND prep, manufacturing, etc.)

Contributed extensivelyto sanofi-aventis’

oncology pipeline over 5-year collaboration

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• IGF-1R-binding antibody – developed, humanized by ImmunoGen

• Blocks pathway used by cancer cells to survive chemotherapy

• In development by sanofi-aventis – leader in chemotherapy

• Currently evaluating for:

• Advanced solid tumors used with Taxotere (75 mg/m2

or 100 mg/m2), Gemzar + Tarceva, or doxorubicin (Ph I)

• Liver carcinoma used with Nexavar or Tarceva (Ph I/II)

• Hormone-dependent breast cancer used with fulvestrantvs. fulvestrant alone (Ph II)

Lead Compound in sanofi-aventis Collaboration:AVE1642

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ImmunoGen’s Contribution to sanofi-aventis’ Oncology Pipeline

Reproduced from sanofi-aventis’ website in June 2008. ImmunoGen has since regained AVE9633 (IMGN633)

ImmunoGen-derived conjugate

ImmunoGen-derived naked antibody

Not shown: undisclosed, earlier-stage compounds

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ImmunoGen Research: Now Rebuilding Our Proprietary Pipeline

sanofi-aventis Pipeline5-year R&D Collaboration

ImmunoGenPipeline

Post-sanofi

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ImmunoGen: A Major Anticancer Company?

• Highly effective ACC compounds are achievable with our technology

• Well-tolerated ACC compoundsare achievable with our technology

• Does our TAP technology work with MAbs that lack their own anticancer activity?

• Does IMGN242 have meaningful anticancer activity?

• Does IMGN901 have meaningfulanticancer activity?

• What should we expect in terms ofImmunoGen’s internal pipeline

What’s Been Established What’s Coming

In 2009

In 2009

By late 2009/early 2010

“Under construction”

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Anticipated Events – ImmunoGen

Clinical Events/Presentations

1Q09 2Q09 3Q09 4Q09EORTC data:IMGN901IMGN242IMGN388

Other DataPresentations

AACR data: New linkersPreclinical data(multiple compounds)

ASCO data: IMGN242

ASH data:IMGN901

IMGN901+ RevlimidPh I/II start

IMGN242Ph II expandor end

EORTC data:New cell-killing agentsPreclinical data(multiple compounds)

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Anticipated Events – ImmunoGen + Partners

Clinical Events/Presentations

1Q09 2Q09 3Q09 4Q09T-DM1 Ph IIIstart

T-DM1 + pertuzumabPh Ib start

EORTC data:IMGN901IMGN242IMGN388AVE1642

Other DataPresentations

Data presentations by partners are ImmunoGen estimates

ASCO data: T-DM1IMGN242AVE1642

ASH data:IMGN901SAR3419BT-062

ASCO Breast and/or SABC data:T-DM1

BusinessDevelopment

EORTC data:New cell-killing agentsPreclinical data(multiple compounds)

AACR data: New linkersPreclinical data(multiple compounds)

IMGN901+ RevlimidPh I/II start

IMGN242Ph II expandor end

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Driving Our Technology and PipelineJohn Lambert, Ph.D.,

Executive Vice President and Chief Scientific Officer

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Further Enhancing OurTAP Technology Portfolio• Additional linkers• Additional

cancer-killing agents

Building Our Product Pipeline• Specific goals,

advancement criteria• Reflect findings in

clinic with our/our partners’ compoundsImmunoGen

Research

Process Development• Commercial-scale

manufacturing processes• T-DM1, SAR3419, IMGN901

Clinical Support• Target expression,

pharmacokinetics, etc.

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• Our current CKAs, linkers performas intended• CKAs – highly active in clinic

(e.g., trastuzumab-DM1)• Linkers – achieve high doses without toxicities

associated with free CKA

• Our modular approach – separate linkers and CKAs –facilitates development, testing of new designs

• Why expand our CKA portfolio? Some cancers respond to one type of agent better than another

• Why expand our linker portfolio? More complex

Further Enhancing Our TAP Technology Portfolio

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Bind to antigenon cell surface

Cancer Cell

InitialInsights

◄ = Highly Cytotoxic

Internalizationvia endocytosis

Traffic toLysosome

Tubulin

Degradation ofMAb in lysosome

Lysine- ۞-DMxDisulfideCleavage

DMx

Cancer Cell

Tubulin

Driving our Leadership in Linkers: Our Expertise in ACC Intra-Cellular Processing

◄ = With either cleavable or non-cleavable linker

◄ = Only with cleavable linker

ImmunoGen:Non-cleavableand cleavable(inside cell) linkers

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Cancer Cell


FurtherInsights


TubulinDMx

DMx

Traffic toLysosome


Lysine- ۞-DMxDisulfideCleavage

Cancer Cell

Tubulin

Disulfide cleavage

◄ = Highly Cytotoxic◄ = With either cleavable or

non-cleavable linker◄ = Only with cleavable linker

For some ACCs,need cleavablelinker for activity

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Cancer Cell


Our ExpandingKnowledge




Traffic toLysosome


Lysine- ۞-DMx

Tubulin

MDR Efflux Pump

DMx

Disulfide cleavage

DisulfideCleavage

DMx

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Cancer Cell


Our New POLFamily of Linkers• Cleavable• Non-Cleavable




Traffic toLysosome


Lysine- ۞-DMx

Tubulin

MDR Efflux Pump

DMx

Disulfide cleavage

DisulfideCleavage

DMx

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New Family: Our Hydrophilic (“POL”) Linkers

• Both cleavable and non-cleavable designs

• Allows increased retention of CKA inside cancer cells

→Expands utility for multi-drug resistant (MDR) cancers

• Allows attachment of more CKA/antibody

→Expands utility for cancer cells with low expressionof the target antigen

• Can use with our maytansinoid CKAs (e.g., DM1, DM4)

• Patents filed

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AbN

O

OO

HN

O OO

NH

O

O

NCl

MeO

HOMeO

NO

CH3 OS

SO3-

Our New Hydrophilic Linkers: Non-Cleavable Designs

POL-1 LinkerPEG4 group

Antibody-Sulfo-Mal-DM4

Antibody-PEG4-Mal-DM4 Antibody-SMCC-DM1

Standard Non-Cleavable Linker

Negatively-charged sulfonate groupPOL-2 Linker

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POL-3 Linker

Ab-Sulfo-SPDB-DM4Ab-SPDB-DM4

Standard Disulfide Linker(More Hindered Design)Negatively-charged sulfonate group

Our New Hydrophilic Linkers: Cleavable Designs

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Example: POL-1 Anti-EpCAM ACC More Active Against MDR Tumors In Vivo

COLO205-MDR(pgp transfected)

xenografts

COLO205(pgp negative)

xenografts

~3.5 DMx/MAb anti-EpCAM conjugates; single injection, i.v.; 170, 340 μg/kg DMx dose (MAb dose ~10, 20 mg/kg)

340 μg/kg

5 15 25 35 45 55 650

200

400

600

800

1000

1200

1400

PBSAb-SMCC-DM1

Ab-PEG4-Mal-DMxAb-SPDB-DM4

Days (post inoculation)

Med

ian

Tum

or V

olum

e (m

m3 )

340 μg/kg

5 15 25 35 45 55 65 750

200

400

600

800

1000

1200


Med

ian

Tum

or V

olum

e (m

m3 )

170 μg/kg

5 15 25 35 45 55 65 750

200

400

600

800

1000

1200


Med

ian

Tum

or V

olum

e (m

m3 )

170 μg/kg

5 15 25 35 45 55 650

200

400

600

800

1000

1200

1400


Med

ian

Tum

or V

olum

e (m

m3 )

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~3.5 DMx/MAb anti-EpCAM conjugates; single injection, i.v.; 340 μg/kg DMx dose (20 mg/kg MAb dose)

0 10 20 30 40 50 600

500

1000

1500 Vehicle Control

Ab-SMCC-DM1

Ab-PEG4-Mal-DMx

Ab-SPDB-DM4

Days after cell inoculation

Mea

n Tu

mor

Vol

ume

(mm

3 )

Naturallypgp-expressing

HCT-15xenografts

Example: POL-1 Anti-EpCAM ACC More Active Against MDR Tumors In Vivo

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Pgp-inhibitor Cyclosporin A restores SPDB-DM4 and SMCC-DM1 conjugate activity; does not affect PEG4-Mal-DMx activity

~3.5 DMx/MAb anti-EpCAM conjugates; 5 day continuous incubation; WST-8 assay

10-11 10-10 10-9 10-80.0

0.5

1.0

Ab-MCC-DM1

Ab-PEG4-Mal-DMx

Ab-SPDB-DM4

Conjugate Concentration, M

Cel

l Sur

vivi

ng F

ract

ion

10-11 10-10 10-9 10-80.0

0.5

1.0

+ cyclosporin A

Conjugate Concentration, M

Cel

l Sur

vivi

ng F

ract

ion

Naturallypgp-expressing

HCT-15cancer cells

Example: POL-1 Anti-EpCAM ACC More Active Against MDR Tumors In Vitro

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More DMx per Antibody → Increased EfficacyPOL-1 Anti-EpCAM ACC with 7.7 or 3.8 DMx/MAb

10-12 10-11 10 -10 10-9 10-8 10 -7 10-60

20

40

60

80

100Ab-PEG4-Mal-DMx, 7.7 DMx/Ab,IC50 = 2 x 10-11 M

Ab-PEG4-Mal-DMx, 3.8 DMx/Ab,IC50 = 8 x 10-10 M

MOLP-8 cells

[Conjugate], M

% S

urvi

ving

Fra

ctio

n

40-fold

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Research





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Expanding Our Portfolio of Cancer-Killing Agents

ImmunoGenTubulin-Acting CKAs

Two Main Types of CKAs:Tubulin Acting and

DNA Acting

• Family created – DMx

• Alternative agents (DM1, DM4) in clinical-stageTAP compounds

• Issued patents

•Family created – IGNs

•Alternative agents for future compounds

•Patent application filed

ImmunoGenDNA-Acting CKAs

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Our IGN Family of DNA-Acting Agents

• New class of DNA-alkylating agents• Chemical structures to be unveiled

at 2009 scientific conference

• Highly potent and specific

• Can attach in active form• Alternative approach:

attach in inactive form, rely on conversionin body

10-13 10-12 10-11 10-10 10-9 10-80.0

0.2

0.4

0.6

0.8

1.0

1.2

COLO 205

COLO 205w/ Blocking Ab

Concentration,M

Surv

ivin

g fr

actio

n

Test MAb-IGN13

10-13 10-12 10-11 10-10 10-9 10-80.0

0.2

0.4

0.6

0.8

1.0

1.2

RH30/Antigen (+) cells

Namalwa/Antigen (-) cells

Concentration, M

Surv

ivin

g fr

actio

n

Test MAb-IGN07

2 x 10-9Antigen (-)

2 x 10-12Antigen (+)

IC50 MCell Line

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Research





52

ImmunoGen Research: Established Productivity

sanofi-aventis Pipeline5-year R&D Collaboration

Pre-sanofi

IMGN R&D

s-a pipeline benefit• 3 TAP compounds• 2 naked MAbs• Additional undisclosed

compounds

During sanofiImmunoGen Pipeline

Post-sanofi

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SAR3419: TAP Compound for Non-Hodgkin’s Lymphoma

10 20 30 40 50 600

500

1000

1500

2000

2500


Mea

n tu

mor

vol

ume

(mm

3 )

Single dose

SAR3419: pronounced activity against human non-Hodgkin’s lymphoma

tumors in xenograft models

Ramos cell line

ControlSAR34192.3 mg/kgSAR3419 4.6 mg/kg

• Targets CD19• Created by ImmunoGen

• Target identification• MAb development,

humanization• Sanofi-aventis evaluating

in US and EU Ph I trials• First clinical data expected

in 4Q09

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SAR650984: Naked MAb for Multiple Myeloma, Non-Hodgkin’s Lymphoma, Other Cancers

• Binds to CD38 –target identifiedby ImmunoGen

• MAb developed, humanized by ImmunoGen

• Potent ADCC, CDCand apoptotic activities

• Preclinical stage

0

10

20

30

40

50

60

70

% K

illin

g

0

5

10

15

20

25

% K

illin

g

DaudiNHL cells

RajiNHL cells

SAR650984: greater apoptotic activity than rituximab against

non-Hodgkin’s lymphoma cells

ControlSAR650984Rituximab

55

ImmunoGen Research Goal: Advance One New Novel Anticancer Compound Each Year

• Advance 1 new product candidate into Preclinical Development each year, starting in 2009• Initiates preclinical and process development activities

to create an “IND-ready” package for ImmunoGen clinical advancement or licensing

• Dominance of ImmunoGen compounds in sanofi-aventis’portfolio demonstrates:• Our capabilities• Not easy to achieve

56

ImmunoGen Research: Setting a High Barin Performance for New Product Candidates

Example: Dose Levels Needed for Activity in Humans vs Mice• Maximum achievable doses

in humans are ~3.5 - 7.0 mg/kg (130 - 260 mg/m2) for MAb-DMx compounds

• Must have significant anti-tumor activity in mouse xenograft models at 3.5 – 7.0 mg/kg (10.5 – 21 mg/m2), up to 10-fold less than MTDs in mice.

In mice, it’s the absolute dose that matters

Enhanced Knowledge

• Growing body of preclinical and clinical data with TAP compounds – ours + our partners’ – provides us with greater insights on our product profile criteria and the standards critical for success

57

ImmunoGen Research: Setting a High Barfor Quality in New Product Candidates

Enhanced Knowledge

• Growing body of preclinical and clinical data with TAP compounds – ours + our partners’ – provides us with greater insights on our product profile criteria and the standards critical for success

• Expanded understanding ofhow MAb-linker-DMx constructs are metabolized by tumors

Enhanced Tool Kit: Our New Linkers

• Expands potential in hard-to-treat cancers (e.g., multi-drug resistant cancers)

• Expands potential to moretypes of cancer cells (e.g., reduced antigen density)

Further increasing thetherapeutic window

58

7 1

Regeneration of ImmunoGen Pipeline after sanofi-aventis Research Collaboration

4 1

Forvalidation

2Active

Go/no go• Freedom to

operate• Target rationale• Disease indication

Number of candidates as of Feb. 2009

Go/no go• Tissue

distribution• Tumor

prevalence

Go/no go MAbproperties vs criteria• Affinity• Activity• Ability to deliver

CKA

Go/no go Achieves targetproduct profile(conjugate,naked MAb)

0(Went to s-a)

Lead Identification

MAbtarget Exploratory Antibody

GenerationCandidate identification INDPre-clinical

59

ImmunoGen: Full Target-to-Clinic Capabilities

60


BREAK

61


Development Strategiesfor Our Clinical Compounds

James O’Leary, M.D.Vice President and Chief Medical Officer

62

Presentation Content

• Introductory remarks • Devising clinical development strategies • Clinical development strategies for

• IMGN901

• IMGN242

• IMGN388

63


• Devising clinical development strategies

• Clinical development strategies for

• IMGN901

• IMGN242

• IMGN388

64

Devising Clinical Development Strategies

1. Determine potential indications based on:• Preclinical data – antigen expression (tumors, healthy tissue),

in vitro and in vivo activity• Available clinical information – tubulin (in)sensitivity,

findings in our human studies to date

2. Evaluate and prioritize indications on criteria, including:• Market opportunity – size, need …• Time to benefit – outlicense, NDA filing• Clinical costs – site, clinical supplies…• Risks – timing of key findings relative to key decision points,

competitive environment

65

Devising Clinical Development Strategies (cont.)

3. Integrate evaluations into strategy• Scenario 1

Modeled on standard pharma practicesClinical trial schedule balancing NPV and riskServes as benchmark

• Scenarios 2, 3, ….Variations adapted to ImmunoGen’s environment to reflect

Finances, resources, risk toleranceOut-licensing value and timing

66




• IMGN901

• IMGN242

• IMGN388

67

IMGN901 Clinical Development Strategy Background

• CD56-targeting TAP compound

• Clinical trials to date

• Ph I dose-escalation trial in CD56+ solid tumors; Ph II portion in relapsed SCLC – conducted by British Biotech

• Ph I trial in CD56+ solid tumors – ongoing; another dose-escalation expected shortly

• Ph I/II trial in CD56+ multiple myeloma (MM) – ongoing;another dose-escalation expected shortly

• Next step: initiation of Ph I/II combination trial in MM

68

IMGN901 Clinical Development Strategy Identify and Prioritize Indications

1,000tbdtbd

21,65032,00019,920

USIncidence*

100tbdtbd5810070

% CD56+

Yes+/-1,000Merkel CellYesYesNoYesYes

In-house Clinical Data?

+/-tbdCarcinoid+/-tbdNeuroendocrineYes12,560OvarianYes32,000SCLC**Yes13,950Multiple Myeloma

Tubulin-Agent

Sensitive?CD56+

IncidenceIndication

* Not corrected for line of treatment**Small-cell lung cancer

69

IMGN901 Clinical Development Strategy

1,000tbdtbd

21,65032,00019,920

USIncidence*

100tbdtbd5810070

% CD56+

Yes+/-1,000Merkel CellYesYesNoYesYes

In-house Clinical Data?

+/-tbdCarcinoid+/-tbdNeuroendocrineYes12,560OvarianYes32,000SCLC**Yes13,950Multiple Myeloma

Tubulin-Agent

Sensitive?CD56+

IncidenceIndication

* Not corrected for line of treatment**Small-cell lung cancer

70

IMGN901 Clinical Development Strategy MM: Evaluation of Available Clinical Data

• Trial design• Patients with relapsed/refractory CD56+ MM

after treatment with approved agents• Ph I – dose escalation (current stage); Ph II – treat at MTD• Dose weekly for 2 weeks every 3 weeks

• Status at time of ASH (12/08)• N=19 • Dose – 40 to 140 mg/m2

• Average of 6 prior treatments for MM – typically included bortezomide, lenalidomide, thalidomide

71

IMGN901 Treatment DurationInvestigator Assessment

* Treatment ongoing (140 mg/m2/week) at time of ASH 12/08

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

PATI

ENTS

*

Minimal Objective Response

Stable Disease

Progressive Disease

3 Months 6 Months 9 Months 12 MonthsCYCLES

Patient 202: Achieved disappearance of urine M component + marked drop in serum M component

Patient 218: Achieved marked drop in urine M component; had no serum M component at baseline

Patient 212: Withdrew due to broken leg while showing increasing benefit

Patient 212Patient 202

Patient 218

Many patients remained on IMGN901 longer than on agents received earlier in the course of their disease

72

Additional ExperienceMTD Monotherapy(Study 003 Ph II)

Multiple MyelomaCombination Trial

(Study 005)

Clinical Plan for IMGN901 in MM: Next Steps

MTD

Go/No goMM combination

Go/No goMM monotherapy

Multiple MyelomaMonotherapy Trial(Study 003 Ph I)

Will include US and non-US sites

Criteria drafted;Being vetted byexperts in field

IMGN901 + lenalidomide+ dexamethasone

73

IMGN901 Clinical Development Strategy SCLC: Evaluation of Available Clinical Data

• Two trials included SCLC patients – 001 and 002• Different dosing schedules• Heterogeneous populations (e.g., # prior therapies)• MTD established low in 001; not yet established in 002

• SCLC enrolled included was primarily pulmonary, but alsoincluded some non-pulmonary

74

IMGN901 Clinical Development Strategy SCLC: Evaluation of Available Clinical Data

Pulmonary SCLC (n=57)• 2 PRs as 3rd-line treatment – 1 for 24 weeks; 1 for 8 weeks• 19 patients had clinically meaningful stable disease

as ≥ 2nd-line treatment

Supportive data in non-pulmonary SCLC• 1 CR in a patient with rapidly progressive* Merkel Cell Carcinoma

(“primary small cell carcinoma of the skin”) – has been progression free for >3 years

• 1 PR (unconfirmed) as 3rd-line treatment – patient with small cell carcinoma of the cervix

*Developed progressive disease ≈ 3 months after definitive treatment with surgery, radiation, and chemotherapy

75

IMGN901 Clinical Development Strategy SCLC: What Have We Learned?

• Signals of activity in SCLC

• Also signals of activity for other types of solid tumors –Merkel Cell carcinoma, neuroendocrine

• Currently not robust enough to embark on registration trial

• Based on preclinical xenograft studies - additional solid tumor opportunities (e.g., ovarian cancers)

76

IMGN901 – Clinical Development Plan

MTD

MTD

Go/No goMM combination

Go/No goMM monotherapy

“Go” in MM gating to further

solid tumor trials

Multiple MyelomaCombination Trial

(Study 005)

Additional ExperienceMTD Monotherapy

(Study 003 extension)

Additional ExperienceMTD Monotherapy

(Study 002 extension)

Multiple MyelomaMonotherapy Trial

(Study 003)

Solid TumorMonotherapy Trial

(Study 002)

Use to gain experience in additional types of solid tumors

Use to gain experience in additional types of solid tumors

77




• IMGN901

• IMGN242

• IMGN388

78


• Targets CanAg – expressed on many types of solid tumors

• Phase I trial – any CanAg+ solid tumor• Established Phase II dose of 168 mg/m2 (q 3 weeks)

• Phase II trial – CanAg+ gastric cancer

• Gastric cancer• A leading cause of death globally – prevalent in Asia• Agents used – limited efficacy, pronounced toxicity• Highly sensitive to IMGN242 in preclinical models

79

Target for IMGN242 Occurs on Many Tumor Types

• Colon cancer• Pancreatic cancer• Gastric cancer• Non-small cell lung cancer (NSCLC) –

both adenocarcinoma and squamous cell carcinoma• Cholangiocarcinoma and gall bladder carcinoma• Breast cancer• Cervical cancer• Adenocarcinoma of unknown primary

Binding of IMGN242 Antibody to Human Tumor Tissues, Assessed by Immuno-Histochemistry

80

Phase II Gastric Cancer Trial

• 2-step design• Need at least one objective response (RECIST criteria)

in first 23 patients to proceed• If met, enroll to 39 response-evaluable patients

• Patients• CanAg+ metastatic or locally-advanced gastric

or GE junction cancer • Previously treated with front-line therapy• Dose based on level of CanAg in serum (below/above

1000 U/ml receive 126/168 mg/m2, respectively)

• Abstract submitted to ASCO

81

IMGN242: Early Evidence of Activity

After IMGN242(First dose)Baseline

FDG-PET Scan Images• 46 year old patient first diagnosed in 2004

• Was treated with docetaxel, 5-FU, carboplatin, irinotecan, capecitabine, gefitinib; alsowith radiation

• Entered trial with lung, liver, ascites, peritoneal disease, other metastases

• Marked response after 1st dose; unconfirmed PR after 2nd dose

• Did not meet study expansion criteria

82

Clinical Plan for IMGN242: Next Steps

Expand to total of39 response-

evaluable patients

End

Dose 23 patients in gastric cancer

Phase II study

Objectiveresponse(s)by RECIST?

83




• IMGN901

• IMGN242

• IMGN388

84


• Integrin-targeting TAP compound

• Integrin target expressed on:

• Numerous solid tumors

• Vascular endothelial cells in process of makingnew blood vessels (angiogenesis)

• IND filed mid-May 2008; first patient dosed July 2008

85

Numerous carcinomas, including• Basal cell• Bladder• Breast • EsophagealAlso• Head & Neck Tumors • Testicular tumors

Target for IMGN388 Occurs on Many Types of Solid TumorsBinding of IMGN388 Antibody to Human Tumor Tissues, Assessed by Immuno-Histochemistry

• Gastric• Lung• Ovarian• Pancreatic

• Prostate• Renal cell• Thyroid

• Melanomas • Sarcomas

86

Phase I Dose-Escalation Trial of IMGN388 in Patients with Solid Tumors (Study 201)

• Underway at START

• Three dose levels evaluated to date

• No significant toxicities noted

• Accrual and dose escalation will continue

• Expect to report first clinical data in 4Q09

87

ImmunoGen Clinical Program

• 5 clinical studies underway; 6th to start this year

• Patient enrollment has accelerated

• Encouraging findings to date

• Tightening our standards – study purpose, success criteria

88


Business Development and Our Financials:Mutually Supportive

Gregory Perry, Senior Vice Presidentand Chief Financial Officer

89

Financial Overview• Financial resources managed conservatively

• $46 MM in cash/marketable securities at 12/31/08; no debt• Cash use moderated by partnerships

• Balanced business model• Our partnerships have yielded $200+ MM since 2000• Outlicenses of TAP technology provide cash,

expand opportunity• Building portfolio of novel anticancer therapeutics –

three clinical compounds plus earlier programs

• Building shareholder value:• Drive clinical programs to value inflection points• Move high value earlier-stage compound into clinic• Maintain global leadership in ACC technology

90

Net Cash Used for Operating Activities and Number of IMGN/Partner Compounds in Clinic

0

10

20

30

40

2001 2002 2003 2004 2005 2006 2007 20080

2

4

6

8

Cash UsedCompounds in Clinic

$ Millions

Fiscal Year

# Compounds in Clinic on June 30

91

Cash Received from Partnerships

$0

$10

$20

$30

$40

2001 2002 2003 2004 2005 2006 2007 2008

Fiscal Year

$ Millions

92

Our TAP Technology: Increasingly Valuable Source of Non-Dilutive Financing

• Bayer single-target license (10/08) – $4MM upfront

• sanofi-aventis expanded access to platform (8/08) – $3.5 MM upfront

• T-DM1 – $5 MM at Ph II start; milestone due at Ph III start (expected 1H09)

Single-Target TAP Technology Licenses

$4 MM upfront

$170.5 MM milestones

Best royalty rates to date

$1-2 MM upfront

$~40 MM milestones

Royalties

Most Recent DealEarly Deals

93

Generated Therapeutics

TAP Compounds• SAR3419• SAR566658• Other

Naked Antibodies• AVE1642• SAR650984• Other

Right to license TAP technology

for additional targets

Expansion of sanofi-aventis Collaboration

Use of our humanization technology: $4.5 MM milestones, plus royalties

For each, $32 MM milestones,

plus royaltiesAlso payment for any research,

manufacturing done for s-a

For each, $21.5-30 MM milestones,

plus royaltiesAlso payment for any research,

manufacturing done for s-a

Generated Agreements

94

Expansion of Genentech Collaboration

Licensed right to use our TAP technology with MAbs to HER2

• Milestones potentially totaling $44 MM – received $7MM to date

• Milestone due with Phase III start

• Royalties on sales, independentof source (Genentech/Roche)

Option to license rights for additional, undisclosed targets

Licensed 2nd targetT-DM1

Options for other targets

Licensed 3rd target

Licensed 4th target

Licensed 5th target

95

Our TAP Platform: Numerous Additional OpportunitiesAround the target/antibody…• Additional single-target

TAP licenses

• Additional multi-target TAP licenses

• TAP licenses around targetsnot limited to cancer cells

• TAP licenses involving other types of targeting vehicles

For each, can involve• Our new CKAs

• Our new linkers

• Using our linker expertise to attach other types of payloads

96

Product Candidate PartnershipsImmunoGen Today

• We have multiple product candidates, includingIMGN242, IMGN901, IMGN633*, earlier-stage compounds

• We plan to partner our current lead candidates – for financial benefit and to gain a strong marketing presence globally

• MAb-based anticancer compounds have achieved attractive deal terms

*Formerly huMy9-6-DM4/AVE9633

97

First Half FY 2009 Expense Analysis

Partner Support47%

TAP Platform22%

ProprietaryPipeline

31%

R&D$24.8 MM

G&A$7.2 MM

Total Operating Expense

$32.0 MM

Research &Development

ExpenseComponents

Most (¾) reimbursed by partners

98

FY 2008Ended 6/30/08

1H 2009Ended 12/31/08

Guidance*FY 2009

Ending 6/30/09Revenues $40.2 $15.5Operating expenses $74.4 $31.9Net loss ($32.0) ($16.5) ($34-37)

Net cash used for operations $20.1 $0.4 $16-19Capital expenditures $18.0 $1.0 $1-3

Cash/marketable securities $47.9 $45.9 $26-29Shareholders’ equity $55.3 $41.2

Financial Information $ Millions

*As of January 29, 2009

99

Financing: Goal is to Maintain >1 Year of Cash

• Cash in from current collaborations

• Business development – new collaborations• Single-target TAP licenses• Multi-target TAP licenses• Product licenses – clinical, preclinical

• Flexibility around expenses

• Balance business development prospects with financing needs while aggressively managing cash use

100

ImmunoGen Value Drivers• T-DM1

• Genentech and Roche – experienced with HER2 MAbcompounds (Herceptin sales >$4.5 B in 2008, growing)

• Multiple studies, paths to registration

• IMGN242 clarity – strong clinical data or termination

• IMGN901 clarity – strong clinical data or termination

• Current partners – product advancements, additional licenses

• New partnerships

• Multiple pipeline entrants beginning in 2010

101


Question and Answer Session

102

Analyst & Investor DayFebruary 27, 2009Closing Remarks

Daniel Junius, President and Chief Executive Officer

103

Closing Remarks

• T-DM1 is changing perceptions of ImmunoGen – our field, the value of our partnerships, our path to sustained cash flow

• Our read: the Street is giving most of the credit for T-DM1’sactivity and tolerability to Genentech and trastuzumab rather than to ImmunoGen and our TAP technology• View can persist until another TAP compound

demonstrates compelling clinical activity• Near-term candidates – IMGN242, IMGN901, SAR3419,

potentially also IMGN388, BT-062, BIIB015• Multiple data presentations expected in 2009, plus

reporting of expansion or end of IMGN242 Ph II trial

104

Closing Remarks (cont.)• Multiple paths to success

• T-DM1 is the most visible path to sustained cash flow• Significant value across our product portfolio

(ImmunoGen + partner compounds)• Expanding product and license opportunities

around our growing technology portfolio

• Expect increasing benefit from Business Development• Increased milestones as compounds progress• New agreements on richer deal terms• Opportunity to expand into new areas – new types

of targeting vehicles and payloads, outside cancer

105

Closing Remarks (cont.)

ImmunoGen is a product development company

• Multiple IMGN-developed compounds in/near the clinic:• IMGN242, IMGN901, AVE1642, SAR3419 – clinical• SAR566658, SAR650984, others – advancing to clinic

• We have highly promising proprietary compounds –market need, product potential

• Implementing a new level of discipline to our processes• Clinical programs: clear expectations, criteria as to what

constitutes success• Using expertise and clinical experience to define

and tighten standards for earlier-stage compounds

106

Closing Remarks (cont.)

• Recognize the difficult financing environment

• Our business model gives us considerable flexibility

• Multiple levers we can pull

• Building a high caliber management team

• Palpable excitement

• Thank you for your interest in ImmunoGen!

107

Changing the Treatment of Cancer

Documents

Analyst & Investor Day February 27, 2009 - IIS …library.corporate-ir.net/library/97/975/97573/items/...Analyst & Investor Day February 27, 2009 Driving a New Era in Anticancer Therapies