Infinity Pharmaceuticals (NASDAQ: INFI) Company Overview June 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 clinical trial activity for IPI-504 in both intravenous and oral form; 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 March 31, 2007, as filed with the Securities and Exchange Commission on May 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 Pipeline of internally-discovered cancer drug candidates |
4 Combinations IPI-504 (IV) IPI-504 (Oral) Additional tumors (solid & hem.) IPI-504 (IV) NSCLC IPI-504 (IV) GIST/STS IPI-504 (IV) Early discovery Hsp90 Bcl-2/Bcl-xL Hedgehog pathway Phase II Phase I Preclinical Discovery Programs Product pipeline Current Planned for next 12 months, pending data Phase I/II |
5 Lead clinical program IPI-504 – a novel Hsp90 inhibitor |
6 • Focus on most rapid path to registration – Single-agent activity in refractory setting – Greatest unmet medical need = potential for accelerated approval • In parallel, initiate additional trials for broader indications – Additional solid and hematological tumors 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 IPI-504 clinical development strategy |
7 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* • 28 patients treated with IPI-504 – Average 2.6 prior therapies (primarily Gleevec ® and Sutent ® ) • IPI-504 well-tolerated up to 400 mg/m² – 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 • Duration of clinical benefit – 7 of 20 (35%) 5 or more cycles (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 Background on PET imaging • Positron emission tomography (PET) is an imaging technology – Labeled glucose is visible on PET scan – Glucose concentrates in most metabolically-active tissues – Cancer cells appear as bright spots on PET images • PET used as a surrogate marker of response in oncology trials – PET responses also seen in Gleevec and Sutent GIST trials – FDA Critical Path evaluation of PET in several lethal cancers • PET response correlated with enhanced survival in many cancers, including GIST 1 1 Kelloff GJ, et al. Clin Cancer Res 2005;11(8) April 15, 2005: 2785. |
10 Evaluation of PET Images as marker of biological activity • Standards emerging for methodology of use and measurement of impact • SUV (standardized uptake value) quantifies the ratio of uptake of 18-FDG* for any given point in the body to the expected level – SUV max measures the single point within a tumor with the highest SUV value • Tracking SUV max for a single tumor lesion over time provides a standardized approach for assessing the change in metabolic activity of the cancer during and after treatment by a cancer therapy • European Organization for Research and Treatment of Cancer (EORTC) criteria determines a quantitative measurement using SUV max – Stable Disease as a change in SUV max of +/-25% or less – Partial Response as a greater than 25% decrease in SUV max *18-fluorodeoxyglucose, or 18-FDG, is the most common tracer molecule used in oncology for PET imaging. |
11 Initial PET response predicts long-term survival (Gleevec) 1 Kaplan Meier Estimate of Overall Survival 1 Stroobants S, et al. Eur J Cancer 2003;39:2012-20. PET responders PET non-responders |
12 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. |
13 IPI-504 PET response (at 150 mg/m 2 ) Baseline Cycle 1, Day 21 After 10 days off treatment Cycle 1, Day 11 72 hours post 2 nd dose of IPI-504 Cycle 3, Day 12 After additional cycles of treatment Courtesy of Van den Abbeele & Demetri: Dana-Farber Cancer Institute Harvard Medical School |
14 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 • 24 hrs post 4 • Cycle 1, Day 12 • 24 hrs post 4 th dose |
15 Histopathology of GIST lesions Before and After IPI-504 Treatment Photomicrographs courtesy of Jason Hornick, MD, PhD, Photomicrographs courtesy of Jason Hornick, MD, PhD, Dana-Farber / Brigham and Women’s Cancer Center Pathology Dana-Farber / Brigham and Women’s Cancer Center Pathology -Farber / Brigham and Women’s Cancer Center Pathology Farber / Brigham and Women’s Cancer Center Pathology ’s Cancer Center Pathology s Cancer Center Pathology Viable GIST cells are noted in this section from resection specimen Extensive stromal hyalinization with Hemosiderin deposition (brown spots) consistent with treatment effect Tumor Section 1 post-IPI-504 Tumor Section 2 Post-IPI-504 Pre-IPI-504 Pre-IPI-504 Staining indicative of c-Kit mutation Absence of staining indicative of lack of c-Kit mutation |
16 CT scans for patient before and after IPI-504 treatment Patient received 400 mg/m2 (Schedule A) of IPI-504 Screening End of Cycle 3 |
17 Heat shock protein 90 (Hsp90) is an emerging cancer target Function of Hsp90 • “Chaperone” protein responsible for proper folding and function of some proteins Function of Hsp90 in cancer cells • Many oncogenic proteins rely on Hsp90 to function • Inhibiting Hsp90 is another way to inhibit the oncogenic proteins themselves |
18 Long list of 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 |
19 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 |
20 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 |
21 0 500 1000 1500 2000 2500 3000 3500 4000 12 15 19 22 26 27 32 Days Post-Implant 69% difference in tumor volume (p=0.009) IPI-504 Vehicle Gefitinib Vehicle 100mpk Gefitinib, oral (daily for 3 weeks) 100mpk IPI-504, IP (2x weekly) IPI-504 is active in animal models of Tarceva- / Iressa- resistant NSCLC |
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 Potential advantages of IPI-504 Potential opportunity Preclinical evidence Overcomes resistance to kinase inhibitors in refractory settings Refractory settings where TKIs have failed Fast path to market due to high unmet medical need Active against multiple resistance mutations Less reliant on genotyping or patient subpopulations Synergistic in combination with kinase inhibitors Earlier lines of therapy Expanded market potential Orally available and active Earlier lines of therapy Expanded market potential |
24 Preclinical programs Hedgehog, Bcl-2 |
25 Overview of Hedgehog program • Role of Hedgehog pathway in cancer (emerging rationale) – Aberrantly up-regulated in a variety of lethal cancers – May be implicated in cancer stem cell signaling • Cancer stem cells suspected to be progenitor cells primarily responsible for tumor growth, survival, and metastasis • Infinity’s program – Highly potent, systemic inhibitors of Hedgehog pathway – Clinical candidate to be selected, IND-enabling studies to begin in 2007 – Opportunity for best-in-class product |
26 Overview of Bcl-2 program • Role of Bcl-2 in cancer – Central oncology target in the apoptosis pathway (along with XIAP) – 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 – Opportunity for best-in-class product |
27 Corporate Alliances and Financials Strong validation, significant value retention |
28 Chemistry platform 2004-2006 Non-exclusive access to DOS chemistry libraries • $60M upfront & committed • Potential royalties • No downstream rights 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 |
29 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 |
30 Strong balance sheet and cash runway • March 2007 cash and equivalents (unaudited): ~$127M • 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 projected operating plan |
31 Corporate Summary Proven team, track record of success |
32 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 |
33 2007 Infinity goals and milestones: R&D • Initiate Phase I/II trial of IPI-504 in NSCLC (1H07) • Complete Phase I trial of IPI-504 in GIST/STS (2H07) • Progress IPI-504 to one or more Phase II trials (2H07) • Initiate IPI-504 combination study (2H07) • Enter clinic with oral formulation of IPI-504 (2H07) • Select clinical candidate for Hedgehog program • Continue progress with Novartis on Bcl-2 program • Advance early discovery programs |
34 2007 Infinity goals and milestones: Business • Maintain a strong balance sheet – End 2007 with >$100M cash and runway through at least the end of 2009 (based on current operating plan) • Sustain excellence in strategic alliances with MedImmune and Novartis • Employ position of strength strategically to create shareholder value – Evaluate business development and other value-adding opportunities • Maintain values-driven entrepreneurial culture of citizen-ownership |
35 Combinations IPI-504 (IV) IPI-504 (Oral) Additional tumors (solid & hem.) IPI-504 (IV) NSCLC IPI-504 (IV) GIST/STS IPI-504 (IV) Early discovery Hsp90 Bcl-2/Bcl-xL Hedgehog pathway 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 Overview June 2007 |