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 Merger and Where to Find It

In connection with the proposed merger transaction between Infinity Pharmaceuticals, Inc. (“Infinity”) and Discovery Partners International, Inc. (“Discovery Partners”), on August 7, 2006, Discovery Partners filed with the Securities and Exchange Commission (the “SEC”) an amended registration statement that contains a proxy statement/prospectus, which registration statement has been declared effective by the Securities and Exchange Commission. Investors and securityholders of Discovery Partners and Infinity are urged to read the proxy statement/prospectus (including any amendments or supplements to the proxy statement/prospectus) regarding the proposed transaction because it contains important information about Discovery Partners, Infinity and the proposed transaction. Discovery Partners’ stockholders can obtain a free copy of the proxy statement/prospectus, as well as other filings containing information about Discovery Partners 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

Discovery Partners 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 Discovery Partners in connection with the proposed transaction. 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 Discovery Partners is also included in Discovery Partners’ 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 (http://www.sec.gov) and from Discovery Partners’ Investor Relations at the address listed above.

On August 16, 2006, Infinity made the presentation set forth below to a limited group of investors.

Introduction to Infinity

August 16, 2006

Forward-Looking Statements

•

Various statements in this presentation concerning our future expectations, plans and prospects

constitute forward-looking statements for the purposes of the safe harbor provisions under The

Private

Securities

Litigation

Reform

Act

1995.

Such

forward-looking

statements

include

statements regarding the proposed transaction with Discovery Partner International (DPI), DPI

and

the

combined

company's

net

cash

closing,

anticipated

cash

post-closing

and

projected period in which such cash will be available, the trading of the combined company's

shares on the

NASDAQ

National

Market,

the

potential

value

created

the

proposed

merger

for

DPI's

and Infinity's stockholders, the efficacy, safety, and intended utilization of

Infinity's product candidates, the results of discovery efforts and clinical trials, and plans

regarding regulatory filings, future research and clinical trials and current and future

collaborative activities. Actual results may differ materially from those indicated by such

forward-looking

statement

result

various

important

factors,

including

risks

to:

the

ability

DPI

and

Infinity

complete

the

proposed

transaction;

the

amount

DPI's

net

cash

closing;

the

availability

funds

to continue research and development

activities; the results of future clinical trials with respect to Infinity's product candidates and

compounds and Infinity's ability to successfully develop and commercialize product candidates;

the success of Infinity's collaborations and its ability to enter into additional collaborations;; the

timing and success of regulatory filings;; the scope of Infinity's patents and the patents of others;

competitive

factors

and

other

risks

and

uncertainties

fully

described

DPI's

filings

with

the

Securities

and

Exchange

Commission,

including

its

Registration

Statement

Form

S-4,

filed

May

24,

2006

and

subsequently

amended.

The

proposed

transaction

subject

customary

closing

conditions,

including

approval

DPI's

and

Infinity's

stock

holders.

•

Any forward-looking statements speak only as of the date made. Infinity undertakes no obligation

to publicly 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

•

4 Pharma/Biotech corporate alliances

–

Amgen, J & J and Novartis (2)

•

Proven biotech leadership team

•

Expected cash runway post-DPI merger

–

~ $90+ million

–

Sufficient funds through 2007

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

–

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

–

Bcl-2 product alliance with 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. Michael Foley, VP Chemistry

Harvard ICCB, Glaxo, BMS

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

–

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

–

Bcl-2 product alliance with 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

R²

R³

SR2

•

Diversity Oriented Synthesis (DOS)

•

2004 –

2006: > $65 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-2 alliance with Novartis

•

Joint discovery of novel Bcl-2

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

Discovery

Preclinical

Start Clinical

Trials

Hsp90

(IPI-504)

Bcl2/Bcl-xL

2005

2007/2008*

100% owned

Novartis

Non-exclusive

–

Amgen

–

Novartis

–

J&J

Small molecule drug technologies

Alliance and financing strategy: value retention

Hedgehog

Pathway

(IPI-609)

2007*

*Planned

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

•

A financing event only –

programs, employees, partnerships,

or 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

•

Expected reverse stock split at closing to lower share number and

increase share price

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

•

4 Pharma/Biotech corporate alliances

–

Amgen, J & J and Novartis (2)

•

Proven biotech leadership team

•

Estimated approximately $90 million cash

•

Projected cash runway through 2007 and 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

–

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

–

Bcl-2 product alliance with 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

*Reference: Kamal

et al, Nature,

2003, 425,.407-410

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

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

•

Novel chemical entity

•

Patient-friendly formulations

–

IV in two Phase I trials

–

Oral under development

•

Broad therapeutic potential

•

Strong intellectual property position

•

Phase II planned for 2007

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

IPI-504

IPI-504

IPI-504 competitive landscape for IV formulation

POTENCY

DELIVERY

CHEMICAL

PROPERTIES

MTD

COMPOUND

COMPANY

17-DMAG

KOS-1022

~25-50 nM

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

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

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

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

•

Gleevec

2x daily, 100 mg/kg

•

IPI-504 oral MWF, 100 mg/kg (p=0.001)

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

•

Gleevec

2x daily, 100 mg/kg

•

IPI-504 oral MWF, 100 mg/kg (p=0.001)

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

•

Gleevec

2x daily, 100 mg/kg

•

IPI-504 oral MWF, 100 mg/kg (p=0.001)

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 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

–

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

–

Bcl-2 product alliance with 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 (Novartis, J&J, Amgen)

•

At least one new corporate alliance

•

Financing event

–

Year-end

cash

runway:

12-24

months

2006/Early 2007 Goals, Achievements and Anticipated News Flow

NVS -

Bcl

Pending

DPII merger

AMGN

extension

Expected

at EORTC

11/7/06