 Infinity Pharmaceuticals (NASDAQ: INFI) Company Update August 2007 Exhibit 99.1 |
 2 Forward-Looking Statements • This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements 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. • Such forward-looking statements include statements regarding future preclinical and clinical trial activity for IPI- 504, IPI-493, and IPI-926; the timing of IND submissions for IPI-504, IPI-493, and IPI-926; the collection of additional clinical information on IPI-504; the intended utilization and commercial potential of IPI-504; the ability to name clinical candidates in the company’s research programs; estimates of 2007 financial performance and year-end cash balance; and the expectation that Infinity 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 company's current expectations. For example, there can be no guarantee that any product candidate Infinity is developing will successfully complete necessary preclinical and clinical development phases, be approved for sale in any market or that, if approved, revenue 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 content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities and investigational review boards at clinical trial sites; Infinity’s ability to enroll patients in its clinical trials; Infinity's dependence on its collaborations with MedImmune and Novartis; Infinity's ability to obtain additional funding required to conduct its research, development and commercialization activities; unplanned cash requirements and expenditures; and Infinity'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" included Infinity's quarterly report on Form 10-Q for the quarter ended June 30, 2007, as filed with the Securities and Exchange Commission on August 9, 2007. • Further, 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. • All trademarks used in this presentation are the property of their respective owners. |
 3 Profile of Infinity Pharmaceuticals (NASDAQ: INFI) Strategy Management Business Portfolio Emerging targets in oncology, areas of high patient need Build rapid registration paths, broaden market potential Led by proven drug developers and company-builders Premier investor base and strong balance sheet Lead clinical product: IPI-504, a novel Hsp90 inhibitor Hedgehog pathway inhibitor, IPI-926 Pipeline of internally-discovered cancer drug candidates |
 4 Lead clinical program IPI-504 – a novel Hsp90 inhibitor * * * * |
 5 Hsp90 clinical development strategy Focus on most rapid path to registration with IPI-504 i.v. – Evaluate for single-agent activity in refractory setting GIST and NSCLC – Inform Phase II dose and schedule In parallel, initiate additional trials for broader indications – Additional tumors (solid and hematological) in refractory settings – Combination therapy with standards of care to expand market potential Rapid development of oral dosage form – Ease of use for earlier lines of therapy and chronic settings – Two ansamycin-based molecules in preclinical development |
 6 Hsp90 clinical development strategy Focus on most rapid path to registration with IPI-504 i.v. – Evaluate for single-agent activity in refractory setting GIST and NSCLC – Inform Phase II dose and schedule In parallel, initiate additional trials for broader indications – Additional tumors (solid and hematological) in refractory settings – Combination therapy with standards of care to expand market potential Rapid development of oral dosage form – Ease of use for earlier lines of therapy and chronic settings – Two ansamycin-based molecules in preclinical development |
 7 IPI-504 i.v. Phase I trial in refractory GIST/STS Principal Investigator: • Dr. George Demetri, Dana-Farber Cancer Institute Objectives: • Safety, PK, dose-ranging • Establish Phase II dose Surrogate marker of response: • PET scans Schedule A: • Days 1, 4, 8, 11 of 21 day cycle, with a 10-day-off period, or “drug holiday” Schedule B: • Twice weekly in a 3-week cycle (i.e., no drug holiday) Trial description: • Phase I trial in patients with Gleevec-refractory metastatic gastrointestinal stromal tumors (GIST) and advanced soft tissue sarcomas (STS) |
 8 Preliminary results from Phase I trial in GIST/STS* (ASCO, June 2007) • 28 patients treated with IPI-504 – Average 2.6 prior therapies (primarily Gleevec ® and Sutent ® ) • IPI-504 well-tolerated up to 400 mg/m 2 – MTD not yet reached • Biological activity observed – Schedule A (EORTC quantitative PET criteria) • 15 of 18 (83%) Stable Disease or better • 4 of 18 (22%) Partial Response – Schedule B (qualitative PET) • 3 of 4 responses – Histological and CT changes • 16 of 21 (76%) Stable Disease by RECIST (Schedule A) • 7 of 20 (35%) received 5 or more cycles of therapy (Schedule A) *Results published at ASCO, June 2007: George D. Demetri, et al, "Inhibition of the Heat Shock Protein 90 (Hsp90) chaperone with the novel agent IPI-504 to overcome resistance to tyrosine kinase inhibitors (TKIs) in metastatic GIST: Updated results of a phase I trial," (Poster Number 8, Abstract No: 10023) and A.D. Van den Abbeele, et al, "Inhibition and flare patterns of metabolic response to the heat shock protein 90 (Hsp90) inhibitor IPI-504 visualized by FDG-PET in patients (pts) with advanced gastrointestinal stromal tumors (GIST) resistant to tyrosine kinase inhibitor (TKI) therapy," (Poster Number 1, Abstract No: 3530) |
 9 IPI-504 PET response (at 400 mg/m 2 ) Courtesy of Van den Abbeele & Demetri: Dana-Farber Cancer Institute Harvard Medical School • Baseline • Baseline • Cycle 1, Day 22 • 10 days off treatment • Cycle 1, Day 22 • 10 days off treatment • Cycle 1, Day 12 • Cycle 1, Day 12 • 24 hrs post 4 th dose Patient discontinued for personal reasons |
 10 Metabolic Response in patients at Cycle 1 Day 11 Patient with greatest progressive disease did not carry c-Kit mutation Metabolic response to IPI-504 at Cycle 1 Day 11 "ON" (N = 18 patients) -100 -75 -50 -25 0 25 50 75 100 Patients ranked by percent change in SUVmax EORTC PD PR SD |
 11 Histopathology of GIST lesions before and after 3 cycles of IPI-504 treatment (225 mg/m 2 ; Schedule A) Photomicrographs courtesy of Jason Hornick, MD, PhD, Dana-Farber / Brigham and Women’s Cancer Center Pathology Tumor Section 1 post-IPI-504 Viable GIST cells are noted in this section from resection specimen Pre IPI-504 Tumor Section 2 post-IPI-504 Extensive stromal hyalinization with Hemosiderin deposition consistent with treatment effect |
 12 CT scans for patient before and after IPI-504 treatment Patient received 400 mg/m 2 (Schedule A) of IPI-504 Screening End of Cycle 3 |
 13 Initial PET response predicts long-term survival (Gleevec) 1 Kaplan Meier Estimate of Progression-Free Survival 1 Stroobants S, et al. Eur J Cancer 2003;39:2012-20. PET responders PET non-responders |
 14 Overall Survival by Best Response Achieved (Kaplan Meier Estimate) GIST Patients Benefit Regardless of Tumor Shrinkage (Gleevec) 1 1 Blanke, CD, et al. J Clin Onc 2006 (ASCO Proceedings) Part I, Vol 24; No. 18S: 9528. |
 15 Time To Progression (TTP) >6 weeks is meaningful in the refractory setting 1 Results from the Phase 3 Sutent trial in GIST (N=312) TTP on Placebo: 6.4 weeks TTP on Sutent: 27.3 weeks 4x improvement in TTP vs. Placebo 1 Goodman VL, Rock EP, Dagher R, Ramchandani RP, Abraham S, Gobburu JVS, Booth BP, Verbois SL, Morse DL, Liang CY, Chidambaram N, Jiang JX, Tang S, Mahjoob K, Justice R, Pazdur R. Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res (2007) 13:1367-1373. |
 16 Path forward for IPI-504 i.v. in refractory GIST • Expansion at 400 mg/m 2 on Schedule A – 20 patients (10 GIST, 10 STS) – Further characterize safety and response to inform Phase II / III • Phase II / III provides opportunity for rapid approval path – Active consultation with advisors; FDA meetings planned – Ongoing discussions of trial structure (e.g., control arm) |
 17 Hsp90 clinical development strategy Focus on most rapid path to registration with IPI-504 i.v. – Evaluate for single-agent activity in refractory setting GIST and NSCLC – Inform Phase II dose and schedule In parallel, initiate additional trials for broader indications – Additional tumors (solid and hematological) in refractory settings – Combination therapy with standards of care to expand market potential Rapid development of oral dosage form – Ease of use for earlier lines of therapy and chronic settings – Two ansamycin-based molecules in preclinical development |
 18 Cancer cell death Tyrosine kinase inhibitor (e.g., Gleevec, Tarceva) Normal protein Oncogenic protein drives cancer cell survival & growth Resistance mutations evade TKI therapy IPI-504 IPI-504: an alternative to direct inhibition of oncogenic proteins IPI-504 Dependent on Hsp90 for function Still dependent on Hsp90 for function |
 19 Cancer cell death Tyrosine kinase inhibitor (e.g., Gleevec, Tarceva) Normal protein IPI-504 Scientific rationale informs clinical development strategy IPI-504 Single-agent, refractory Combination, earlier lines |
 20 Many critical oncogenic proteins depend on Hsp90… Indication CML AML CLL GIST Breast (HER2+) NSCLC Renal cell Prostate (PTEN-/-) Bcr-Abl Flt3 Zap70 c-Kit HER2 EGFR VEGFR / HIF-1a p-Akt Hsp90 client proteins Broad clinical potential for Hsp90 inhibition |
 21 Gleevec ® /Sprycel ® Investigational Investigational Gleevec ® /Sutent ® Herceptin ® /Tykerb ® Tarceva ® /Erbitux ® Nexavar ® /Sutent ® Investigational Targeted therapy …with well-validated commercial potential Indication CML AML CLL GIST Breast (HER2+) NSCLC Renal cell Prostate (PTEN-/-) Bcr-Abl Flt3 Zap70 c-Kit HER2 EGFR VEGFR / HIF-1a p-Akt Broad clinical and commercial potential for Hsp90 inhibition Hsp90 client proteins |
 22 Phase I/II trial in advanced NSCLC Principal Investigator: • Dr. Thomas Lynch, Massachusetts General Hospital Objectives: • Phase I: Safety, PK, dose-ranging • Phase II: Expand at MTD to further characterize response of patients with mutant or wt EGFR Markers of response: • CT scans (RECIST) • PET scans Schedule : • Twice weekly in a 4-week cycle Trial description: • Phase I/II trial in Stage IIIb/IV NSCLC patients with previous TKI therapy Patient population: • Prior therapy (>12 weeks) on a TKI |
 23 IPI-504 oral is active in Tarceva- / Iressa-resistant NSCLC (T790M mutation) 0 200 400 600 800 1000 1200 1400 1600 1800 2000 15 21 24 28 32 37 Days Post Implant Vehicle IPI-504 at 25mg/kg IPI-504 at 50mg/kg IPI-504 at 100mg/kg 95% difference 25% difference 72% difference IPI-504 Every Other Day oral H1975 (EGFR mut L858R/T790M) tumor model |
 24 H1650 (EGFR del exon 19) tumor model Days post implant 0 100 200 300 400 500 600 700 800 900 20 23 26 30 34 Low dose IPI-504 sensitizes human NSCLC xenografts to Taxol Vehicle IPI-504, 50 mg/kg, 1x/week i.p. Taxol, 20 mg/kg, 1x/week i.p. Combination |
 25 Days post implant IPI-504 + Taxotere inhibits the growth of human PC-3 prostate xenografts |
 26 Hsp90 clinical development strategy Focus on most rapid path to registration with IPI-504 i.v. – Evaluate for single-agent activity in refractory setting GIST and NSCLC – Inform Phase II dose and schedule In parallel, initiate additional trials for broader indications – Additional tumors (solid and hematological) in refractory settings – Combination therapy with standards of care to expand market potential Rapid development of oral dosage form – Ease of use for earlier lines of therapy and chronic settings – Two ansamycin-based molecules in preclinical development |
 27 Hsp90 Oral program progressing rapidly • Key strategic objective: flexibility and breadth • Two molecules in preclinical development, ansamycin class – Infinity expertise in geldanamycin natural product and analogs – IPI-504 PO – IPI-493, named as development candidate 2Q 2007 • Both molecules show potent and selective inhibition of Hsp90 – Good oral bioavailability • Preclinical studies and evaluation of comparative data ongoing – Determine which candidate, or candidates to move into clinic – Anticipate IND filing(s) late 2007 / early 2008 |
 28 0% 20% 40% 60% 80% 100% 15 35 55 75 95 Days post BMT Collaboration: Shauguang Li, Jackson Labs Overcomes resistance to kinase inhibitors in preclinical models of refractory settings Oral IPI-504 prolongs survival in Bcr-Abl T315I mice (Gleevec-resistant) Placebo Gleevec IPI-504 (50 mg/kg, MWF) IPI-504 (100 mg/kg, MWF) |
 29 Active against multiple resistant mutations 0 20 40 60 80 100 15 20 25 30 35 40 45 50 55 60 65 70 Days post BMT Placebo IPI-504 T315I 0 20 40 60 80 100 20 30 40 50 60 70 80 90 Days post BMT Placebo IPI-504 E225K 0 20 40 60 80 100 12 16 20 24 28 32 36 40 44 48 Days post BMT Placebo IPI-504 M351T 0 20 40 60 80 100 13 17 21 25 29 33 Days post BMT Placebo IPI-504 Y253F IPI-504 at 50 mg/kg, MWF Collaboration: Shauguang Li, Jackson Labs Oral IPI-504 in Bcr-Abl mice with various resistance mutations |
 30 Synergistic in combination with kinase inhibitors in preclinical studies IPI-504 at 50 mg/kg, MWF Collaboration: Shauguang Li, Jackson Labs Oral IPI-504 in Bcr-Abl mice with mixed-population tumors (both “wild-type” and T315I Bcr-Abl tumor cells) |
 31 Preclinical programs Hedgehog, Bcl-2 * * * * |
 32 Role of Hedgehog pathway in cancer • Embryonic pathway, typically quiescent in adults • Aberrantly active in a variety of cancers: Genetically-defined tumors Tumors with pathway up-regulation Examples: Childhood medulloblastoma Basal cell carcinoma Rhabdomyosarcoma Examples: Pancreatic Small cell lung Breast Ovarian |
 33 Infinity’s Hedgehog program: IPI-926 • Selected as development candidate Q2 2007 – Clinical studies anticipated in 2008 • Derivative of natural product cyclopamine • Promising preclinical data – Highly potent, selective inhibition of Hedgehog pathway – Oral bioavailability, extended half life – Activity in vivo • Issued composition of matter patent |
 34 Profile of IPI-926 7,230,004 U.S. patent Other High Therapeutic Index Safety ACTIVE PD and efficacy 15 nM In vitro potency Pharmacology Stable Metabolism Extensive Distribution 8-24 hr T1/2 High Oral BA DMPK |
 35 IPI-926 down-regulates Hh signaling to stromal tissue IPI-926 Human Tumor Surrounding murine stromal tissue SHH Gli1 Tumor expresses SHH IPI-926 regulates Gli in stroma Tumor: stromal interactions are critical Gene expression measured 4 hours post last dose |
 36 Broadly collaborating to explore the potential of Hedgehog pathway inhibition in a variety of clinical indications • Orthotopic and primary pancreatic • Primary SCLC with chemo • Primary breast tumors • Mesothelioma • Hematologic tumors • Primary CNS |
 37 Surrogate PD assay: IPI-926 reduces Gli-1 expression in murine skin/fur Vehicle IPI-926 Gli-1 expression measured 8 hours after single dose 0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 |
 38 Hedgehog program milestones 2007 2008 2009 • Select development candidate (IPI-926) • IND-enabling studies • File IND • Initiate Phase I • Expand clinical development |
 39 Overview of Bcl-2 program • Role of Bcl-2 in cancer – Central oncology target in the apoptosis pathway – Promotes cancer cell survival, including drug resistance, by inhibiting apoptosis • Infinity’s program – Novel, highly potent and on-target inhibitors of Bcl-2 and Bcl-2/Bcl-xL – Lead optimization – Partnered with Novartis |
 40 Corporate Alliances and Financials Strong validation, significant value retention * * * * * |
 41 Chemistry platform 2004-2006 Core technology Non-exclusive access to DOS chemistry libraries • $60M upfront & committed • Potential royalties • No downstream rights 1 st and 2 nd generation alliances Build the company Traditional product-based license Bcl-2/Bcl-xL March 2006 Discovery • $30M upfront & committed • >$370M milestones • Significant WW royalty • Co-promotion right in US |
 42 3 rd generation alliance Ensure near-term financial strength and long-term value • Leverage Infinity’s strengths in chemistry and oncology • Align with MedImmune’s strategic expansion in oncology • AstraZeneca acquisition –All rights and obligations survive –Hsp90 cited as key clinical stage program Multi-program partnership; R&D and commercial jointly led • $70M upfront • $430M milestones • 50/50 R&D cost share • 50/50 WW profit split • Co-promotion right in US Hsp90/Hedgehog August 2006 Preclinical/Phase I |
 43 Strong balance sheet and cash runway • June 2007 cash and equivalents (unaudited): $122M • Burn rate well-controlled via alliances – 50% cost-sharing of Hsp90, Hedgehog programs with MedImmune – 100% of Bcl-2 program funded by Novartis • January 2008 cash and equivalents (projected) : >$100M • Cash runway through at least the end of 2009 – Based on current operating plan and assuming no financing or business development activity |
 44 Corporate Summary Proven team, track record of success * * * * |
 45 Infinity Leadership Michael Curtis, Ph.D., Sr Dir Pharmaceutical Development TKT, Syntonix, Genzyme, Bristol-Myers Squibb David Grayzel, M.D., VP Clinical Development & Medical Affairs Dyax, Mass General Hospital Steven Kafka, Ph.D., VP Finance Millennium, Strategic Decisions Group John Keilty, Sr Dir Informatics Millennium, UMass Medical School Jeanette Kohlbrenner, Dir Human Resources Genetics Institute, Syntonix Vito Palombella, Ph.D., VP Drug Discovery Syntonix, Millennium, ProScript Gerald Quirk, Esq., VP & General Counsel Genzyme, Palmer & Dodge Jeffrey Tong, Ph.D., VP Corporate & Product Development McKinsey & Co, Harvard Center for Genomics Research Jim Wright, Ph.D., VP Pharmaceutical Development Millennium, Alkermes, Boehringer Ingelheim, Syntex, U. of Wisconsin Steven Holtzman, CEO Millennium, DNX Julian Adams, Ph.D., President and CSO Millennium, ProScript, Boehringer Ingelheim, Merck Adelene Perkins, EVP & CBO Transform, Genetics Institute, Bain, GE |
 46 Upcoming milestones Hsp90 • Preliminary Phase I/II NSCLC data at EORTC(Q407) • Complete Phase I trial in GIST/STS (Q407) – Additional Schedule A and B data (1H08) • Initiate Phase II single-agent trial(s) (Q407) • Initiate combination trial(s) (Q407) • Oral Hsp90 preclinical comparisons, file IND(s) (late ‘07 / early ‘08) Hedgehog • File IND, initiate clinical studies (2008) |
 47 IPI-504 (Oral) Combinations IPI-504 (IV) IPI-493 (Oral) Additional tumors IPI-504 (IV) NSCLC IPI-504 (IV) GIST/STS IPI-504 (IV) Early discovery Hsp90 Bcl-2/Bcl-xL Hedgehog pathway, IPI-926 Phase II Phase I Preclinical Discovery Programs Product pipeline Current Planned for next 12 months, pending data Phase I/II |
 Infinity Pharmaceuticals (NASDAQ: INFI) Company Update August 2007 |