Edgar Filing: INFINITY PHARMACEUTICALS INC

Rule 425

Filed by Discovery Partners International, Inc. Pursuant to Rule 425

Under the Securities Act of 1933

and Deemed Filed Pursuant to Rule 14a-12

Under the Securities Exchange Act of 1934

Subject Company: Infinity Pharmaceuticals, Inc.

Commission File No. 333-134438

Additional Information about the DPI-Infinity Merger and Where to Find It

In connection with the proposed merger between Discovery Partners International, Inc. (DPI) and Infinity, on August 7, 2006, DPI filed an amended registration statement on Form S-4 that contains a proxy statement/prospectus, which registration statement has been declared effective by the SEC. Investors and security holders of DPI and Infinity are urged to read the proxy statement/prospectus (including any amendments or supplements to the proxy statement/prospectus) regarding the proposed merger because it contains important information about DPI, Infinity and the proposed merger. Security holders will be able to obtain a copy of the proxy statement/prospectus, as well as other filings containing information about DPI and Infinity, without charge, at the SEC’s Internet site (http://www.sec.gov). Copies of the proxy statement/prospectus can also be obtained, without charge, by directing a request to Discovery Partners International, Inc., 9640 Towne Centre Drive, San Diego, CA 92121, Attention: Investor Relations, Telephone: (858) 455-8600.

Participants in the solicitation

DPI and its directors and executive officers and Infinity and its directors and executive officers may be deemed to be participants in the solicitation of proxies from the stockholders of DPI in connection with the proposed merger of DPI with Infinity. Information regarding the special interests of these directors and executive officers in the merger transaction is included in the proxy statement/prospectus referred to above. Additional information regarding the directors and executive officers of DPI is also included in DPI’s proxy statement for its 2006 Annual Meeting of Stockholders, which was filed with the SEC on April 6, 2006. This document is available free of charge at the SEC’s web site (www.sec.gov) and from Investor Relations at DPI at the address described above.

Infinity gave the following presentation on September 8, 2006.

Introduction to Infinity

September 8, 2006

Forward-Looking Statements

•

This presentation contains forward-looking statements within the meaning of The Private Securities Litigation

Reform Act of 1995 that involve risks and uncertainties that could cause actual results to be materially different

from historical results or from any future results expressed or implied by such forward-looking statements. You

are urged to consider statements that include the words “may,”

“will,”

“would,”

“could,”

“should,”

“believes,”

“estimates,”

“projects,”

“potential,”

“expects,”

“plans,”

“anticipates,”

“intends,”

“continues,”

“forecast,”

“designed,”

“goal,”

or the negative of those words or other comparable words to be uncertain and forward-

looking. Such forward-looking statements include statements regarding the expected benefits of the merger of

Infinity and DPI for stockholders of the combined company, the expectation that the merger will enable the

combined company to be well positioned to drive forward its pipeline of anti-cancer agents and create

substantial value for patients and stockholders, and the expectation that the combined company will have cash

to support its current operating plan through at least December 31, 2009. Such statements are subject to

numerous factors, risks and uncertainties that may cause actual events or results to differ materially from the

combined company's current expectations. For example, there can be no guarantee that any product candidate

the combined company is developing will successfully complete necessary preclinical and clinical development

phases, be approved for sale in any market or that, if approved,

revenues from sales of such product will reach

any specific level. In particular, management's expectations could be affected by risks and uncertainties relating

to: results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data

received from ongoing and future studies; the combined company's

dependence on its collaborations with

MedImmune

and Novartis; the combined company's ability to obtain additional funding required to conduct its

research, development and commercialization activities; unplanned cash requirements and expenditures; and

the company's ability to obtain, maintain and enforce patent and

other intellectual property protection for any

products it is developing. These and other risks which may impact management's expectations are described in

greater detail under the caption "Risk Factors" in DPI's

registration statement on Form S-4, as amended, as filed

with the Securities and Exchange Commission and DPI’s

other SEC reports.

•

Any forward-looking statements contained in this presentation speak only as of the date hereof and Infinity

expressly disclaims any obligation to update any forward-looking statements, whether as a result of new

information, future events or otherwise.

Mission

To develop targeted therapies for the treatment

of cancer and related conditions discovered

through the use of our innovative small

molecule drug technologies

•

Lead product candidate: IPI-504, a novel Hsp90 inhibitor

–

Two ongoing Phase I cancer studies in GIST and multiple myeloma

–

Phase II expected 2007

•

Pipeline of preclinical cancer drug candidates

–

Internally discovered and developed, chemistry platform

•

5 Pharma/Biotech corporate alliances

–

MedImmune, Novartis

(2), Amgen, and J & J

•

Proven biotech leadership team

•

Significant cash position after MEDI alliance and DPI merger

–

Funds sufficient for projected operating expenses through end of

2009

Infinity Snapshot

Strategy

•

Drugs

–

Internally discovered, novel small molecules

•

Targets

–

“Well-credentialed, but not well-trodden”

•

Products

–

Opportunity for first-in class or fast follower best-in-class

Overview

•

Founded in late 2001 (~5 years old)

•

Team

–

Recognized biotechnology investor, business and R&D leaders

–

~115 employees (~55 PhD / MDs)

•

Alliance and Financing Strategy

–

Hsp90 and Hedgehog pathway product alliance with MedImmune

–

Bcl

family product alliance with Novartis

–

Small molecule technology access alliances with Amgen, J&J and Novartis

–

Public financing via Reverse Merger with Discovery Partners

•

IPI-504 –

lead proprietary oncology drug candidate (Hsp90)

–

Phase I in GIST and multiple myeloma commenced 2005

–

Phase II anticipated in 2007

•

Hedgehog pathway –

preclinical oncology candidate

Our Team: ~115 full-time employees

Infinity headcount

Biology/Clinical/Regulatory

Chemistry

Management & other

(~55 MD or PhDs)

R&D Total

Total

115

G&A

•

Well-balanced

•

Moderate near-term growth

anticipated

–

Primarily in “downstream”

disciplines (i.e. clinical,

regulatory, CMC/ADME/tox)

Leadership

Mr. Steven Holtzman, CEO

Millennium, DNX

Dr. Julian Adams, President & CSO

Millennium, ProScript

Boehringer

Ingelheim, Merck

Ms. Adelene Perkins, CBO

Transform, Genetics Institute,

Bain, GE

Dr. David Grayzel, VP Clinical

Development & Medical Affairs

Dyax, Mass General Hospital

Dr. Vito Palombella, VP Discovery Biology

Syntonix, Millennium, ProScript

Dr. Jeffrey Tong, VP Corp & Prod Dev

McKinsey & Co, Harvard Center for

Genomics Research

Dr. Jim Wright, VP Pharm

Dev

Millennium, Alkermes, Boehringer

Ingelheim, Syntex, U. of Wisconsin

SAB –

Oncology & Chemistry

•

Co-chair: Stuart Schreiber, PhD -

Co-Director Broad Institute, Prof. of Chemistry and

Chemical Biology Harvard University

•

Co-chair: Rick Klausner, MD –

Column Group, former Head of the NCI

•

Arnie

Levine, PhD -

Institute for Advanced Study

•

Eric Lander, PhD -

Co-Director Broad Institute, Whitehead, MIT, Harvard

•

Todd Golub, MD -

DFCI, Broad Institute, Harvard, MIT

•

David Livingston, MD –

Professor of Medicine, Harvard Medical School, DFCI

•

Ken Anderson, MD -

Robert Kraft Prof. of Medicine Harvard Medical School, DFCI

•

Matthew Shair, PhD –

Professor of Chemistry, Harvard University

•

Vicki Sato, PhD –

former President Vertex Pharmaceuticals

•

Phil Needleman, PhD -

former Head of R&D Searle, Pharmacia

Investors

Venture Capitalists

•

Prospect Venture Partners

•

Venrock Associates

•

Advent Venture Partners

•

HBM BioVentures

•

Vulcan Ventures

•

Novartis BioVentures

•

Wellcome

Trust

•

POSCO BioVentures

•

Tallwood

•

Alexandria Equities

•

Lotus BioScience

Pharmaceutical Companies

•

Amgen

•

Novartis

•

J&J

Overview

•

Founded in late 2001 (~5 years old)

•

Team

–

Recognized biotechnology investor, business and R&D leaders

–

~115 employees (~55 PhD / MDs)

•

Alliance and Financing Strategy

–

Hsp90 and Hedgehog pathway product alliance with MedImmune

–

Bcl

family product alliance with Novartis

–

Small molecule technology access alliances with Amgen, J&J and Novartis

–

Public financing via Reverse Merger with Discovery Partners

•

IPI-504 –

lead proprietary oncology drug candidate (Hsp90)

–

Phase I in GIST and multiple myeloma commenced 2005

–

Phase II anticipated in 2007

•

Hedgehog pathway –

preclinical oncology candidate

DOS Small Molecule Technology: Discovery and Alliance Engine

•

Innovative small molecule platform, diversity oriented synthesis

(DOS), enables the creation of novel, “natural product-like”

synthetic drug candidates

•

Potential

access

previously

“undruggable”

drug

targets

•

Unique asset for:

–

Internal drug discovery

–

Value-accretive technology access alliances

•

Diversity Oriented Synthesis (DOS)

•

2004 –

2006: > $60 million upfront/committed cash

•

Additional milestone and royalty potential

•

No license of proprietary Infinity product rights

Small Molecule Technology Access Alliances

•

Total payments >$400M

Early product pipeline: Bcl

family alliance with Novartis

•

Joint discovery of novel Bcl

family (Bcl-2, Bcl-xL) targeted

cancer drugs

•

Infinity participation in clinical

development (at NVS expense)

COLLABORATION

•

Infinity participation in US sales

effort (at NVS expense)

$30M

•

Upfront &

committed funds

FINANCIALS

•

Royalties on WW sales

•

Clinical and

commercial

milestones

Lead products: Hsp90 and Hedgehog alliance with MedImmune

•

Infinity leads early translational

development through proof of concept

•

MedImmune

leads later clinical

development, worldwide registration and

sales and marketing, with Infinity

participation

COLLABORATION

•

Infinity has right to provide up to 35% of

US promotional activity (cost shared by

alliance)

$70M

•

Upfront funds

FINANCIALS

•

50% R&D cost sharing

$430M

•

50% worldwide profit split

Discovery

Preclinical

Start Clinical

Trials

Hsp90

(IPI-504)

Bcl-2/Bcl-xL

2005

2007/2008

50% WW profit

share with MEDI

50% WW profit

share with MEDI

Royalty from

Novartis

Non-exclusive

–

Amgen

–

Novartis

–

J&J

Small molecule drug technologies

Alliance and financing strategy: value retention

Hedgehog

Pathway

(IPI-609)

2007

Reverse Merger

with

Discovery Partners International, Inc.

(NASDAQ: DPII)

DPI reverse merger opportunity

•

Discovery Partners International

–

Publicly traded company on NASDAQ (DPII)

–

Cash position 1/1/06: > $83M

–

Board mandate (Q1, 2006):

•

Shut down existing business

•

Seek alternative, high-value biotech investment opportunity

•

DPI undertakes extensive evaluation of merger candidates

•

DPI selects Infinity as preferred partner

•

financing

event

only

–

programs,

employees,

partnerships,

obligations of DPI transferred to Infinity

–

DPI “invests”

cash and divests operating units

–

7/7/06: Sale of all DPI operating assets to Galapagos

•

If DPI cash between $70M and $75M, ownership:

–

DPII stockholders = 31%

–

Infinity stockholders = 69%

•

If cash above $75M or below $70M, adjustment applied

•

4:1 reverse stock split approved by DPI board to lower share

number and bring share price >$10

The reverse merger: a creative financing and access to

public markets

•

Lead clinical product in two ongoing Phase I cancer studies

–

Phase II expected 2007

•

Pipeline of preclinical cancer drug candidates

–

Internally discovered and developed, chemistry platform

•

5 Pharma/Biotech corporate alliances

–

MedImmune, Novartis

(2), Amgen, and J & J

•

Proven biotech leadership team

•

Significant cash position

–

Projected cash runway through end of 2009

–

Enough cash to reach key value-driving events before any additional

alliances or financing

Snapshot of Post-Merger Infinity (NASDAQ: INFI)

Status of Reverse Merger

Announce merger

File Initial S4

S-4 is Declared Effective

S-4 mailed to DPI and IPI Stockholders

Stockholder meeting/vote scheduled

Deal Closes, INFI publicly traded

April 12, 2006

July 11, 2006

August 7, 2006

August 9-10, 2006

September 12, 2006

Following successful vote

Overview

•

Founded in late 2001 (~5 years old)

•

Team

–

Recognized biotechnology investor, business and R&D leaders

–

~115 employees (~55 PhD / MDs)

•

Alliance and Financing Strategy

–

Hsp90 and Hedgehog pathway product alliance with MedImmune

–

Bcl

family product alliance with Novartis

–

Small molecule technology access alliances with Amgen, J&J and Novartis

–

Public financing via Reverse Merger with Discovery Partners

•

IPI-504 –

lead proprietary oncology drug candidate (Hsp90)

–

Phase I in GIST and multiple myeloma commenced 2005

–

Phase II anticipated in 2007

•

Hedgehog pathway –

preclinical oncology candidate

•

Novel Hsp90 inhibitor

•

Currently in 2 phase I clinical trials:

•

GIST

•

Multiple myeloma

•

Ready for Phase II in 2007

•

Both IV (water-soluble) and oral

formulations

Infinity’s lead clinical product: IPI-504 (Hsp90 inhibitor)

IPI-504

Heat Shock Protein 90 (Hsp90) is an emerging cancer

target

Hsp90 in cancer cells differs from

Hsp90 in normal cells

Function of Hsp90 in cancer cells

•

General chaperone function

–

essential for protein homeostasis

•

Specific chaperone function

–

stabilization of oncogenic

proteins in key cell signaling

pathways

•

Preferential targeting to cancer

Dependence

on Hsp90

Apoptosis

Tyrosine kinase

inhibitor

(e.g

Gleevec, Tarceva)

Oncogene

Cancer cell

survival &

proliferation

Resistance

mutations

Hsp90

inhibitor

Targeting specific oncogenic Hsp90 client proteins

Hsp90

inhibitor

Velcade

Gleevec / dasatinib

Investigational

Gleevec / Sutent

Herceptin

Tarceva

/ Erbitux

Sorafenib

/ Sutent

Sorafenib

Investigational

Targeted therapy

The emerging world of targeted cancer therapies

Indication

Myeloma

CML

AML

GIST

Breast (HER2+)

NSCLC

Renal cell

Melanoma

Prostate (PTEN -/-)

NF-

Bcr-Abl

Flt3

c-Kit

HER2

EGFR

VEGFR / HIF-1a

b-Raf

p-Akt

Molecular Target

The emerging world of targeted cancer therapies

NF-

Bcr-Abl

Flt3

c-Kit

HER2

EGFR

VEGFR / HIF-1a

b-Raf

p-Akt

Molecular Target

•

All are clients of Hsp90

•

Inhibiting Hsp90 affects the

stability of these targets

•

Attractive alternative to

chasing tumor-specific

resistance mutations

History of Geldanamycin

analogs

•

17-AAG is a semi-synthetic natural

product, derived from Geldanamycin

•

17-AAG activity:

–

Potent & selective inhibitor of

Hsp90

–

Well-tolerated in humans (>400

patients tested in multiple

Phase I trials)

–

Removed chemical reactivity of

geldanamycin

•

Problems:

–

Highly insoluble

–

Sub-optimal DMSO-and

Cremophor

based formulations

–

Off-patent

17-AAG

*Reference: Kamal

et al, Nature,

2003, 425,.407-410

•

Novel chemical entity

•

Patient-friendly formulations

–

IV in two Phase 1 trials

–

Oral under development

•

Broad therapeutic potential

–

Large therapeutic window

consistent with targeted therapies

–

Activity in resistant settings

•

Strong intellectual property position

•

Ready for Phase 2 in 2007

Infinity’s lead clinical product: IPI-504 (HSP90 inhibitor)

IPI-504

IPI-504

IPI-504 competitive landscape for IV formulation

POTENCY

NCE

PATENT?

DELIVERY

CHEMICAL

PROPERTIES

MTD

COMPOUND

COMPANY

17-DMAG

KOS-1022

~25-50 nM

Yes

IV 60–120

min

Chemically

reactive

alkylating

agent

<24 mg/m²

Kosan

17-AAG

KOS-953

~25-50 nM

IV 60-120 min

in Cremophor

Special tubing

Steroid

pretreatment

Emulsion

changes

distribution

and PK

Dose escalation

ongoing;

340 mg/m²

Kosan

Emulsion

changes

distribution

and PK

17-AAG

CNF-1010

~25-50 nM

IV 60 min

in lipid

emulsion

175 mg/m²

Biogen/

Conforma

Emulsion

changes

distribution

and PK

17-AAG

~25-50 nM

IV 60 min in

DMSO/Egg

220 mg/m²

Kosan

IPI-504

~25-50 nM

IV 30 min

Diffusion

controlled

distribution

Dose escalation

ongoing at

400 mg/m²

Yes

Infinity

IPI-504 competitive landscape for PO formulations

IPI-504 (same

molecule as IV)

17-DMAG

CNF-2024

Small Molecule

Compound

Company

Phase of Development

Infinity

Kosan

Biogen

Idec

Serenex

Novartis /

Vernalis

Synta

Pre-clinical

Phase I

Preclinical

No competitive oral product is significantly more advanced

Novel small

molecules not

derived from

geldanamycin

Intellectual property protection for IPI-504

•

Composition of matter

•

Formulations (IV and PO)

•

Methods of making

•

Methods of using

Infinity has broad patent applications pending for IPI-504

IPI-504 Preclinical Data

Highly

responsive to

Hsp90 inhibition

T315I

T790M

T670I

Preclinical evidence of potential as salvage therapy

BCR-ABL

EGFR

KIT

Hsp90 Client

Disease

Drug

CML

NSCLC

GIST

Gleevec,

Dasatinib

Tarceva,

Iressa

Gleevec,

Sutent

Kinase

Inhibitor

Resistance

Mutation

CML / Bcr-Abl

Wild-type protein

Bcr

Abl

Non-cancer related

Protein status

Entity

Function

Hsp90-

dependent

Gain-of-function

mutant

Bcr-Abl

fusion

Constitutively

activated signaling

Drug-resistant

mutant

Bcr-Abl

(T315I)

TKI-resistant

kinase

Gleevec-refractory primary CML cells sensitive to IPI-504

Pt 1

Pt 2 (T315I)

Pt 3

Control

0.5 uM IPI-504

2.0 uM IPI-504

Collaboration:

Kapil Bhalla, Moffitt Cancer Center

Placebo

Gleevec

IPI-504

Collaboration:

Shauguang

Li, Jackson Labs

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

Days

Oral IPI-504: survival benefit in Gleevec-resistant T315I

CML transplantation model

Placebo

Gleevec

IPI-504

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

Days

Oral IPI-504: survival benefit in Gleevec-resistant T315I

CML transplantation model

Collaboration:

Shauguang

Li, Jackson Labs

Placebo

Gleevec

IPI-504

0.0%

20.0%

40.0%

60.0%

80.0%

100.0%

Days

Oral IPI-504: survival benefit in Gleevec-resistant T315I

CML transplantation model

Collaboration:

Shauguang

Li, Jackson Labs

NSCLC / EGFR

Wild-type protein

EGFR

Ligand-dependent

RTK

Protein status

Entity

Function

Hsp90-

dependent

Gain-of-function

mutant

EGFR

(

exon19 or

L858R)

Ligand-

hypersensitive RTK

Drug-resistant

mutant

EGFR

(

exon19 or

L858R + T790M)

TKI-resistant,

ligand

hypersensitive RTK

500

1000

1500

2000

2500

3000

3500

4000

Days Post-Implant

IPI-504 Vehicle, IP

Gefitinib Vehicle, PO

100mpk Gefitinib, PO

100mpk IPI-504, IP

•

100mpk

IPI-504

weekly

IP;

100mpk

Gefitinib

daily

for

weeks

•

21%

difference

tumor

volumes

between

vehicle

and

Gefitinib

treated

groups

(p=0.54)

•

69% difference in tumor volumes between vehicle and IPI-504 treated groups (p=0.009)

69%

Non small cell lung cancer xenograft with T790M EGFR

Tarceva/Iressa-resistance mutation

GIST / Kit

Wild-type protein

Kit

Ligand-dependent

RTK

Protein status

Entity

Function

Hsp90-

dependent

Gain-of-function

mutant

c-Kit

Ligand-independent

RTK

Drug-resistant

mutant

c-Kit (T670I)

TKI-resistant,

ligand-independent

RTK

GIST: Gleevec-resistant cells more sensitive to IPI-504

GIST 882*

Gleevec-Sensitive

(primary: exon

13, K642E)

100

1000

10000

Compounds concentrations (nM)

100

1000

10000

Compounds concentrations (nM)

IPI-504 : EC50 = 121 +/-

21 nM

IM : EC50 = 147 +/-

42 nM

Gleevec-

Resistant

(primary: exon

11, V560D +

Gleevec resistance: exon

17, D820A)

100

1000

Compounds concentrations (nM)

IPI-504

Imatinib

GIST 48*

IPI-504 : EC50 = 54 +/-

7 nM

IM : 25% inhibition @ 10uM

Collaboration:

Fletcher, Demetri, DFCI

IPI-504 Clinical Development Strategy

•

Development and registration of IPI-504 in hematologic

malignancies and solid tumors

–

Preclinical support for broad role of Hsp90

•

Early human proof-of-concept with most rapid path to registration

–

Strong scientific rationale

–

Trials targeted to homogenous patient population (disease-focused)

–

Surrogate marker

–

Rapid patient accrual

–

Single-agent activity in refractory setting (potential for expedited

approval)

•

In parallel, initiate broader development for larger indications

(additional diseases, combination therapy, front-line therapy)

IPI-504 Clinical Development Strategy

Principal Investigator:

•

Dr. George Demetri, DFCI

Objectives:

•

Safety, PK, dose-ranging

•

Establish Phase II dose

Surrogate marker of response:

•

PET scans

Solid Tumor

Gastrointestinal Stromal Tumors

(Gleevec-resistant)

Schedule / status:

•

Days 1, 4, 8, 11 of 21 day

•

Continuing dose escalation

Current ongoing phase I clinical trials

Principal Investigator:

•

Dr. Paul Richardson, DFCI

•

Dr. Sundar Jagannath, SVCCC

•

Dr. David Siegel, HUMED

Objectives:

•

Safety, PK, dose-ranging

•

Establish Phase II dose

Surrogate marker of response:

•

M protein levels

Hematologic

Multiple Myeloma

(relapsed, refractory)

Schedule / status:

•

Days 1, 4, 8, 11 of 21 day

•

Continuing dose escalation

Phase I dose escalation for IPI-504 (GIST)

•

1 cycle = 21 days

•

4 doses (days 1, 4, 8, 11 followed by 10 days off)

Phase I schedule

25%

500

33%

400

33%

300

50%

225

66%

150

100%

Escalation over

previous dose

Dose (mg/m2)

Group

Near-term sequence of additional clinical indications

(2006/2007)

Resistance

Mutation

Disease

T. Lynch

T. Kipp, CLL

consortium

Matsui, Smith /

Bhalla

NSCLC

CLL

CML

Tarceva-R

(T790M )

Zap-70

T315I

•

Focused trials would determine IPI-504 activity in patients with known resistance to

targeted therapy

•

If positive, trials provide opportunity to rapidly advance to market

•

Additional indications to follow

Site

MGH

UCSD

JHU, Moffitt

Overview

•

Founded in late 2001 (~5 years old)

•

Team

–

Recognized biotechnology investor, business and R&D leaders

–

~115 employees (~55 PhD / MDs)

•

Alliance and Financing Strategy

–

Hsp90 and Hedgehog pathway product alliance with MedImmune

–

Bcl

family product alliance with Novartis

–

Small molecule technology access alliances with Amgen, J&J and Novartis

–

Public financing via Reverse Merger with Discovery Partners

•

IPI-504 –

lead proprietary oncology drug candidate (Hsp90)

–

Phase I in GIST and multiple myeloma commenced 2005

–

Phase II anticipated in 2007

•

Hedgehog pathway –

preclinical oncology candidate

•

Potential for first-in-class systemic hedgehog inhibitor

•

Proprietary NCE’s

•

Systemic (sub-cu and oral) products

•

Lead molecule (IPI-609) in advanced preclinical development

•

First in man expected in 2007

•

Broad anti-cancer potential

•

Strong data supporting pancreatic, metastatic prostate,

SCLC, others

•

Single agent activity

•

Potential for synergy with standards of care

Infinity’s Hedgehog program

History of cyclopamine –

chemical discovery

1950’s

•

Lambs born in Idaho with cyclopic

features (defect in development of

left-right asymmetry)

•

USDA determines that pregnant

ewes grazed on the plant Veratrum

californicum

•

Cyclopamine

identified as the

teratogenic substance in V.

californicum

•

Purified cyclopamine given to

animals recapitulates cyclopic

features and other birth defects

V. californicum

cyclopamine

History of hedgehog –

genetics

40 years later (1980’s to today)

•

Genes are discovered that control

embryonic development and pattern

formation

•

One such gene is called “hedgehog”

•

Hedgehog mutations in the Drosophila

fruit fly result in cyclopia

•

Hedgehog function in humans related

to development of the pancreas, gut,

and other elements of GI tract

Cyclopamine chemistry meets hedgehog genetics

Chemistry

The chemical cyclopamine

results in cyclopic animals

Genetics

Mutation of hedgehog pathway

results in cyclopic animals

Might the chemical cyclopamine interact

with genes in the hedgehog pathway?

YES

Cyclopamine is a smoothened antagonist

*Chen et al., 2002 G&D

16:2743

Cyclopamine

Normal

Cancer

Cancers have hijacked components of the hedgehog

pathway

ON = active repressor of Smo

* Mutation in Patched

Hahn et al., 1996, Cell

85: 841

Bale & Yu, 2001, Human Molec. Genetic. 10: 757 (review)

Berman et al., 2002 Science

297: 1559

Berman et al., 2003 Nature

425: 846

Kayed et al., 2004 Int. J. Cancer

110: 668

Thayer et al., 2003 Nature

425: 851

Karhadkar et al., 2004 Nature, 431: 707

Fan et al., 2004 Endocrinology

145: 3961

Watkins et al., 2003, Nature

422: 313

Sicklick 2005 ASCO; Mohini, 2005 AACR

Kubo et al., 2004 Cancer Res. 64

:6071

State

Normal

Basal cell carcinoma*

1,2

Medulloblastoma*³

Pancreatic cancer

4,5,6

Prostate cancer

7,8

Small cell lung cancer

Hepatocellular cancer

Breast Cancer

Smoothened

OFF

Patched

Mutant -

OFF

Mutant -

OFF

Hedgehog

OFF

Turned ON

Frequency

---

95%

30-40%

100%

50%

n/a

100%

Cyclopamine validates Hedgehog as a cancer target

•

Cyclopamine is a plant natural

product produced by Veratrum

californicum

Cyclopamine activity:

•

Potent inhibitor of

Smoothened

•

Highly active in pancreatic,

prostate, small cell lung

cancer animal models

Drawbacks:

•

Insoluble

•

Caustic formulations

•

Off-patent

Infinity’s lead Hedgehog pathway inhibitors

•

Novel candidates based on cyclopamine

•

On mechanism

•

Superior to cyclopamine:

–

More chemically stable

–

More potent

–

More soluble

•

Most advanced candidate (IPI-609) in late-preclinical development

–

First in man 2007

–

i.v., s.c., or oral formulations

–

Better oral bioavailability

–

Better tumor PK

IPI-609 competitive landscape

•

CUR-61414 –

Curis and Genentech Hedgehog antagonist

–

Highly insoluble: not suitable for systemic administration

–

Topical formulation failed in Phase 1 Basal Cell Carcinoma trial; failure

attributed to formulation, not pathway

•

Curis and Genentech-have-expressed continued interest in the

Hedgehog pathway for systemic agents

Intellectual property protection for IPI-609

•

Novel scaffold for IPI-609 and analogs with patent applications

pending

•

We believe there are no patents preventing us from marketing IPI-

609 or its analogs

200

400

600

800

1000

1200

1400

1600

Days

Vehicle

IPI-609 10 mpk/day

IPI-609 efficacious in PC-3 prostate xenograft

IPI-609 slows tumor growth rates

200

400

600

800

1000

1200

Day

Linear Fit

Bivariate Fit of P 10 By Day

200

400

600

800

1000

1200

Day

Linear Fit

Bivariate Fit of VP 6 By Day

Median vehicle-treated

animals

Median IPI-609 treated

animals

Clinical development strategy of hedgehog pathway

inhibitors

•

Strong scientific rationale supports targeting of cancers dependent

on the Hedgehog pathway

–

Pancreatic

–

Small cell lung

–

Metastatic prostate

–

Metastatic breast

–

Ovarian

–

Others (medulloblastoma, glioma, basal cell carcinoma, etc.)

•

Identify a rapid path to registration

–

Potential for sole agent activity or

–

Combination with a single Standard of Care

Key Principal Investigator relationships established

•

Pancreatic cancer

Manuel Hidalgo, MD Johns Hopkins

(PCRT –

Dan Van Hoff, MD)

•

Small cell lung cancer

Charles Rudin, MD Johns Hopkins

•

Prostate cancer

Phil Kantoff, MD DFCI

Howard Scher, MD MSKCC

Chris Logothetis, MD MD Anderson

Prostate Consortium

•

Breast

Max Wicha, MD U of Michigan

•

Heme malignancies

Doug Smith, MD Johns Hopkins

Bill Matsui, MD Johns Hopkins

Kapil Bhalla, MD Moffitt Cancer Ctr

Infinity Pharmaceuticals

Summary

•

Product Pipeline

–

IPI-504: Complete Phase I trials

•

Publish First Clinical Data

–

IPI-504: Expect to initiate Phase II in 2007

–

Hedgehog Pathway: Expect to initiate

Phase I in 2007

•

Successful alliance execution

•

At least one new corporate alliance

•

Financing event

–

Year-end cash runway:

12-24 months

2006/Early 2007 Goals, Achievements and Anticipated News Flow

Pending

DPII merger

AMGN

extension

Expected

at EORTC

11/7/06

NVS (Bcl)

MEDI (Hsp90, HH)