Infinity Pharmaceuticals (NASDAQ: INFI) Overview for investor presentations January 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 September 30, 2006, as filed with the Securities and Exchange Commission on November 9, 2006. • 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 • Focus on emerging targets in oncology • Lead clinical product: IPI-504, a novel Hsp90 inhibitor – Biologically active, well-tolerated in disease-focused Phase I trial (GIST) – Expansion of clinical development expected in 2007 • Pipeline of internally-discovered cancer drug candidates – Hedgehog pathway, Bcl-2/Bcl-xL, additional programs • 5 Pharma/Biotech corporate alliances – MedImmune, Novartis (2), Amgen, and J & J • Significant cash position – Projected cash runway through at least the end of 2009 • Proven biotech leadership team Profile of Infinity Pharmaceuticals (NASDAQ: INFI) |
4 IPI-504 (Combinations) IPI-504 (Oral) Additional tumors (solid & hem.) IPI-504 (IV) NSCLC IPI-504 (IV) GIST 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 Lead clinical product: IPI-504 (Hsp90 inhibitor) • Novel chemical entity with strong intellectual property position • Preclinical evidence of broad therapeutic potential • Biologically active and well-tolerated in Phase I (patients with metastatic Gleevec ® -refractory GIST) • Clinical expansion expected in 2007 – Phase I/II trial in non-small cell lung cancer (NSCLC) – Phase II trial(s) – Combination with standards of care • Clinical trial for oral IPI-504 planned for 2007 |
7 Phase I trial in refractory GIST 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) |
8 Preliminary results from GIST trial (November 2006) • 20 GIST patients treated with IPI-504 – 20/20 prior Gleevec ® therapy – 19/20 prior Sutent ® therapy • IPI-504 well-tolerated up to 400 mg/m 2 – MTD not reached • Biological activity observed via qualitative assessment of PET images (“PET response”) in 7 of 17 evaluated patients (41%) • 6 of 15 evaluated patients (40%) received 5 or more cycles of therapy |
9 Background on PET imaging • Positron emission tomography (PET) is an imaging technology – Labelled 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 • 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 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 |
11 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Weeks Post First Dose 0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240 252 264 PROGRESSION On Imatinib Median 36 wks Overall Survival by Best Response Achieved (Kaplan Meier Estimate) STABLE DISEASE Median not reached PARTIAL RESPONSE GIST Patients Benefit Regardless of Tumor Shrinkage (Gleevec) 1 Blanke, CD, et al. J Clin Onc 2006 (ASCO Proceedings) Part I, Vol 24; No. 18S: 9528. 1 |
12 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 |
13 IPI-504 PET response (at 400 mg/m 2 ) Baseline Cycle 1 Day 12 24 hours after 4 th dose of IPI-504 Courtesy of Van den Abbeele, Wagner & Demetri: Dana-Farber Cancer Institute Harvard Medical School (Other spots are anatomical features: kidney, Tumor |
14 PET images suggest biological activity and inform schedule • Modulation of PET signal in response to drug administration and holiday suggests a pharmacological effect of IPI-504 – Similar pattern of response seen with Sutent on a 4-weeks on, 2-weeks off schedule¹ • New schedule to evaluate removal of drug holiday Days 1, 4, 8, 11 of 21-day cycle (with drug holiday) 90 mg/m 2 400 mg/m 2 No MTD reached Twice-weekly, no drug holiday 150 mg/m 2 Dose-escalate through MTD and/or Phase II dose 1 Van den Abbeele AD, et al. Abstract 714, ECCO 13, 2005 |
15 Next Indication: Phase I/II NSCLC trial • Patient population – Stage IIIb/IV NSCLC patients • Rationale from preclinical data – Mutant EGFR is highly sensitive to treatment with IPI-504 – Kinase inhibitor (Tarceva, Iressa) resistance mutations are equally sensitive to treatment with IPI-504 • Trial design – Dose escalate to determine MTD followed by expansion – Assess response by RECIST, correlate with EGFR mutation status (+/-) – Additional assessment with PET • Lead investigator – Dr. Thomas Lynch, Massachusetts General Hospital • Expect to treat first patient in 1H07 |
16 0 500 1000 1500 2000 2500 3000 3500 4000 12 15 19 22 26 27 32 Days Post-Implant IPI-504 Vehicle Gefitinib Vehicle 100mpk Gefitinib, oral (daily for 3 weeks) 100mpk IPI-504, IP (2x weekly) 69% difference in tumor volume (p=0.009) IPI-504 is active preclinically against Tarceva/Iressa- resistant NSCLC |
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 Apoptosis 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 Potential advantages of IPI-504 1. Equally potent to targeted therapies (e.g., Gleevec) 2. Overcome resistance to kinase inhibitors in refractory settings 3. Active against multiple resistance mutations 4. Synergistic in combination with kinase inhibitors Front-line use Refractory settings where TKI has failed Fast path to market due to high unmet medical need Less reliant on genotyping or patient subpopulations Earlier lines of therapy Expanded market potential Potential opportunity Preclinical evidence |
20 0% 20% 40% 60% 80% 100% 15 35 55 75 95 Days post BMT Placebo Gleevec IPI-504 (50 mpk/d) IPI-504 (100 mpk/d) Overcomes resistance to kinase inhibitors in preclinical models of refractory settings Oral IPI-504 prolongs survival in Bcr-Abl T315I mice (Gleevec-resistant) Collaboration: Shauguang Li, Jackson Labs |
21 0% 20% 40% 60% 80% 100% 15 35 55 75 95 Days post BMT Overcomes resistance to kinase inhibitors in preclinical models of refractory settings Placebo Gleevec IPI-504 (50 mpk/d) IPI-504 (100 mpk/d) Oral IPI-504 prolongs survival in Bcr-Abl T315I mice (Gleevec-resistant) Collaboration: Shauguang Li, Jackson Labs |
22 0% 20% 40% 60% 80% 100% 15 35 55 75 95 Days post BMT Overcomes resistance to kinase inhibitors in preclinical models of refractory settings Placebo Gleevec IPI-504 (50 mpk/d) IPI-504 (100 mpk/d) Oral IPI-504 prolongs survival in Bcr-Abl T315I mice (Gleevec-resistant) Collaboration: Shauguang Li, Jackson Labs |
23 Collaboration: Shauguang Li, Jackson Labs 0% 20% 40% 60% 80% 100% 15 35 55 75 95 Days post BMT Overcomes resistance to kinase inhibitors in preclinical models of refractory settings Placebo Gleevec IPI-504 (50 mpk/d) IPI-504 (100 mpk/d) Oral IPI-504 prolongs survival in Bcr-Abl T315I mice (Gleevec-resistant) |
24 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 mpk/d Collaboration: Shauguang Li, Jackson Labs Oral IPI-504 in Bcr-Abl mice with various resistance mutations |
25 0 20 40 60 80 100 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 Days post BMT Placebo Gleevec IPI-504 Gleevec+IPI-504 Oral IPI-504 in Bcr-Abl mice with mixed-population tumors (both “wild-type”-and T315I Bcr-Abl tumor cells) Synergistic in combination with kinase inhibitors in preclinical studies IPI-504 at 50 mpk/d Collaboration: Shauguang Li, Jackson Labs |
26 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 |
27 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 |
28 • Focus on most rapid path to registration – Single-agent activity in refractory setting (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 IPI-504 clinical development strategy |
29 Preclinical programs Hedgehog, Bcl-2 * * * * * |
30 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 in 2007 – MedImmune alliance – Opportunity for best-in-class product |
31 Overview of Bcl-2 program • Role of Bcl-2 in cancer – Central molecule 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; potential for clinical candidate selection in 2007 – Novartis alliance – Opportunity for best-in-class product |
32 Corporate Alliances and Financials Strong validation, significant value retention * * * * * |
33 Chemistry platform 2004-2006 Core technology 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 |
34 3 rd generation alliance Ensure near-term financial strength and long-term value Multi-program partnership; R&D and commercial jointly led Hsp90/Hedgehog August 2006 Preclinical/Phase I • $70M upfront • $430M milestones • 50/50 R&D cost share • 50/50 WW profit split • Co-promotion right in US • Leverage Infinity’s strengths in chemistry and oncology • Add MedImmune’s worldwide registration and commercialization reach • Align with MedImmune’s strategic expansion in oncology |
35 Strong balance sheet and cash runway • January 2007 cash and equivalents (unaudited) : ~$135M – Includes $35M payment from MedImmune received on January 5, 2007 (second half of upfront fee from collaboration) • 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 |
36 Corporate Summary Proven team, track record of success * * * * * |
37 Leadership Steven Holtzman, CEO Millennium, DNX Julian Adams, Ph.D., President & CSO Millennium, ProScript, Boehringer Ingelheim, Merck Adelene Perkins, EVP & CBO Transform, Genetics Institute, Bain, GE David Grayzel, M.D., VP Clinical Development & Medical Affairs Dyax, Mass General Hospital Steven Kafka, Ph.D., VP Strategic Product Planning & Finance Millennium, Strategic Decisions Group 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 |
38 • Advance product pipeline 2006 Infinity goals and achievements AMGN extension Novartis on track J&J complete NVS (Bcl) Reverse merger with DPI (3+ years of cash) + + MEDI (Hsp90, HH) IPI-504: Well-tolerated in Phase I Biological activity in resistant GIST + • Successful execution of technology access alliances • At least one new corporate alliance • Financing event – Year-end cash runway: 12-24 months |
39 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 (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 |
40 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 to strategically to create shareholder value – Evaluate business development and other value-adding opportunities |
Infinity Pharmaceuticals (NASDAQ: INFI) Overview for investor presentations January 2007 |