Infinity Overview June 2008 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 those regarding future clinical trial activity for IPI-504, IPI-493 and IPI-926, including the completion of the planned Phase 3 clinical trial of IPI-504 in refractory GIST; the presentation of data for IPI-504 and IPI-926; estimates of 2008 financial performance; and the expectation that Infinity will have cash to support its current operating plan into 2010. • Such statements are subject to numerous factors, risks and uncertainties that may cause actual events or results to differ materially from Infinity'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. In particular, 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, investigational review boards at clinical trial sites, and publication review bodies; Infinity's ability to enroll patients in its clinical trials; Infinity's dependence on its collaboration with MedImmune/AstraZeneca; 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 product candidates it is developing. • These and other risks which may impact Infinity’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, 2008, which was filed with the Securities and Exchange Commission on May 9, 2008. • 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. |
Infinity: Innovative small molecule cancer drug discovery and development Financial highlights • $105M in cash as of 3/31/2008 • Significant pipeline investment, and well- controlled burn NASDAQ: INFI Founded: 2001 Headquarters: Cambridge, MA Employees: ~140 R&D highlights • Lead program to enter Phase 3 registration trial in 3Q08 • Broad internally-discovered pipeline of novel candidates • Major alliance with AstraZeneca |
INFI Investment Thesis • Sustainable pipeline of novel, small molecules for key targets – Hsp90 inhibitors: IPI-504 i.v. and IPI-493 p.o. – Hedgehog pathway inhibitor: IPI-926 • International Ph 3 trial for IPI-504 to commence in 3Q08 under SPA – IPI-504 positioned as potential first-in-class anti-chaperone agent • Broad, near-term potential – Multiple IPI-504 trials underway in major disease categories • Strong balance sheet; well-capitalized – Resources support current operating plan into 2010 • Proven management team – First- and best-in-class NDAs, value-creating business transactions |
5 Solid tumors Hsp90 oral: IPI-493 Discovery Preclinical Phase 1 Phase 2 Phase 3 Hsp90 i.v.: IPI-504 (retaspimycin hydrochloride) GIST/STS NSCLC HRPC Taxotere ® Combo Additional Studies Solid tumors Hedgehog Pathway: IPI-926 Bcl-2/Bcl-xL Discovery Programs FPI mid-2008 In 2008 GIST Ph 3 FPI 3Q08 INFI: Building a sustainable oncology pipeline FPI 2H 2008 |
6 Solid tumors Hsp90 oral: IPI-493 Discovery Preclinical Phase 1 Phase 2 Phase 3 Hsp90 i.v.: IPI-504 (retaspimycin hydrochloride) GIST/STS NSCLC HRPC Taxotere ® Combo Additional Studies Solid tumors Hedgehog Pathway: IPI-926 Bcl-2/Bcl-xL Discovery Programs FPI mid-2008 In 2008 GIST Ph 3 FPI 3Q08 Hsp90: Targeted Anti-Chaperone Therapy FPI 2H 2008 |
Targeting the Hsp90 chaperone: a novel strategy for cancer treatment • Lead product IPI-504 in late-stage clinical development – Water-soluable i.v. formulation – Issued U.S. patent, worldwide patents pending – Currently being evaluated in multiple cancers • IPI-493 expected to enter the clinic in mid-2008 – Novel oral formulation – Strong IP position; patent applications filed worldwide – Phase 1 study to commence mid-2008 7 |
8 Hsp90 Inhibition: How it works Hsp90 is a “chaperone” protein responsible for supporting and stabilizing numerous oncogenic proteins IPI-504 binds at ATP site and inhibits cell stabilization Unstable oncogene degraded; tumor growth inhibited |
9 0.0 1.0 2.0 3.0 Rituxan Herceptin Avastin Eloxatin Taxotere Gleevec Gemzar 0 50,000 100,000 150,000 200,000 250,000 Prostate Lung Breast Colorectal Bladder NHL Melanoma Leukemia Hsp90 Inhibition: A major new target ** Sales in top 7 markets. Source: “Commercial insight: Top 20 cancer therapy brands 2006.” Datamonitor, July 2007 * Source: American Cancer Society: Cancer Facts and Figures 2007. Atlanta, Ga: American Cancer Society, 2007 Top cancers in U.S by incidence* Clinical development underway in the three most common cancers Potential for application in combination with major products 2006 sales cytotoxic/targeted therapies ($B)** |
10 Oncogenic protein drives cancer cell survival & growth Cancer cell death Tyrosine kinase inhibitor (e.g., Gleevec, Tarceva) Normal protein Resistance mutations evade TKI therapy IPI-504 / IPI-493 (oral) IPI-504 Dependent on Hsp90 for function Still depends on Hsp90 for function Rapid registration in refractory setting Expand potential in front-line / combo Hsp90 development paradigm: A new treatment approach |
11 Clinical development strategy • Rapid path to registration with IPI-504 – Single-agent therapy, refractory settings – GIST & NSCLC • Broaden potential through additional indications – Signal-finding trials in additional tumors (HRPC, others) – Combination therapy with standards of care (Taxotere®, others) • Rapid development of oral – Earlier lines of therapy, combinations, chronic therapy – Phase 1 expected to commence mid-2008 |
Phase 1 Trial of IPI-504 • Patients with metastatic GIST refractory to Tyrosine Kinase Inhibitors (TKIs) – Gleevec® and Sutent® • Inter-cohort dose escalation trial – Twice weekly dosing for 2 weeks every 21 days – Twice weekly dosing continuously • Endpoints: – Safety and tolerability – Identify dose and schedule for full clinical development – Assessment of biological activity with anatomic and functional imaging (CT and 18FDG-PET scans) • Amended in May 2007 to include other soft-tissue sarcomas • Expansion at MTD to confirm safety and tolerability No currently-approved therapies in refractory GIST |
Patients in Phase 1 GIST study experienced multiple prior TKI therapies Prior Therapy Patients with refractory GIST treated with IPI-504 (n=45) Imatinib 45 (100%) Imatinib > 400 mg 36 (80%) Sunitinib 42 (93%) Nilotinib 9 (20%) 3 or more treatments 17 (38%) Prior surgery 33 (73%) 38% of patients had 3 or more prior therapies |
Phase 1 results confirm activity and safety of IPI- 504 in refractory GIST • 70% overall disease control after 2 cycles in patients with GIST • Estimated Progression Free Survival (PFS) of 12 weeks • IPI-504 was generally well-tolerated with an acceptable safety profile GIST Other STS Number of patients¹ 36 11 Partial Response (PR)² 1 ( 3%) 1 ( 9%) Stable Disease (SD) 24 (67%) 4 (36%) Progressive Disease (PD) 11 (30%) 6 (55%) 1. 90-400 mg/m² - twice weekly, 2 weeks on 1 week off 2. Both PRs confirmed Wagner et al., ASCO 2008 |
Baseline Cycle 1, Day 21 After 10 days off IPI-504 Cycle 1, Day 11 72 hours post 3 rd dose of IPI-504 Cycle 3, Day 12 After IPI-504 dosing resumed PET imaging demonstrates disease control in refractory GIST 18 FDG-PET of Pt 201-007 following progression on imatinib, sunitinib, and nilotinib (IPI-504 dose - 150 mg/m²) |
Baseline Cycle 3 1 year on imatinib at 400 & 800 mg; 1 year on sunitinib at 37.5 & 50mg Patient remains on study as of cycle 5 (15 weeks) Partial response by RECIST (70% reduction) in metastatic GIST after pretreatment with TKIs |
17 Stable disease for >6 weeks is meaningful in the refractory GIST setting 1 Results from the Phase 3 sunitinib trial in GIST TTP on Placebo: 6.4 weeks TTP on sunitinib: 27.3 weeks 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. |
IPI-504: Rapid Advancement into Phase 3 Phase 3 Registration trial to be initiated in 3Q 2008 under Special Protocol Assessment, and with scientific advice from EMEA • Study designed in consultation with international group of KOLs – Randomized, double-blind, placebo-controlled study • Patients to be randomized 2:1 to either IPI-504 or placebo • Cross-over to treatment with IPI-504 if progression occurs – Approx. 200 patients; >50 sites worldwide – Patients with progressive GIST despite treatment with imatinib & sunitinib • Endpoints – Primary: Progression-free survival (PFS) – Secondary: Disease control rate, time to progression, & overall survival • Expect trial to be completed in ~2 years from first patient enrolled 18 |
19 IPI-504 Phase 1/2 study in NSCLC: Potential rapid path to market Encouraging clinical data • Completed Ph 1 portion – Stage IIIb/IV NSCLC patients with >12 weeks previous TKI therapy • Phase 1 data at EORTC 2007* – 12 patients, dose-escalation – 7 of 9 (78%) Stable Disease – 1 pt with mtEGFR experienced extended SD >6 months (28 weeks) – Correlative PET activity observed Clear path forward • Initiated Phase 2 portion – Evaluate mtEGFR and wild-type – Potential to expand • Combination therapy strategy – Phase 1 single agent drives exploration of mechanistic combinations – Important potential setting for oral No approved therapies in TKI-resistant NSCLC * Sequist, L., Janne, P., Sweeney, J., Walker, J., Grayzel, D., Lynch, T. (2007) Phase 1/ 2 Trial of the Novel Hsp90 Inhibitor, IPI-504, in Patients with Relapsed and/or Refractory Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC) Stratified by EGFR Mutation Status. ACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, B79, 2007. |
20 IPI-504 anti-chaperone therapy: Significant potential beyond GIST & NSCLC • Phase 2 Hormone-resistant prostate cancer (HRPC) – 2 groups: 1 docetaxel-naive, 1 post-docetaxel treatment – Establish potential utility in combination and/or as oral therapy • Phase 1b combo with docetaxel – Patients with advanced solid tumors – Establish safety, MTD, and optimal schedule of administration • Additional trials planned to commence in 2008 – Additional clinical studies of IPI-504 – Phase 1 with IPI-493, oral Hsp90 inhibitor, in mid-2008 |
21 Infinity’s oral inhibitor of Hsp90: IPI-493 • Demonstrated potent and selective Hsp90 inhibition preclinically • Excellent oral exposure: PK and half-life • Only oral geldanamycin analogue in clinical development – Previous class-based liabilities eliminated • IPI-493 on track to enter clinic in mid-2008 – Rapid exploration of dose, schedule, and combinations – Leverage signal-finding efforts from Phase 2 studies with IPI-504 |
22 • Worldwide collaboration: R&D and commercial • Compelling economics: Control INFI cash burn, significant downstream participation – $70M upfront; $215M potential milestones – R&D cost share and 50/50 WW profit split – Co-promotion rights in US • Provides global oncology infrastructure and reach MedImmune/AstraZeneca alliance on Hsp90 |
23 Solid tumors Hsp90 oral: IPI-493 Discovery Preclinical Phase 1 Phase 2 Phase 3 Hsp90 i.v.: IPI-504 (retaspimycin hydrochloride) GIST/STS NSCLC HRPC Taxotere ® Combo Additional Studies Solid tumors Hedgehog Pathway: IPI-926 Bcl-2/Bcl-xL Discovery Programs FPI mid-2008 In 2008 GIST Ph 3 FPI 3Q08 FPI 2H 2008 Hedgehog Pathway Inhibitor Program: IPI-926 |
AACR Meeting Abstracts on Hedgehog Pathway, 2004-2008 10 19 31 43 58 2004 2006 2006 2007 2008 Burgeoning interest in Hedgehog pathway |
*Chen et al., 2002 G&D 16:2743 Cyclopamine The Hedgehog signaling pathway |
Hh in Cancer Genetic mutation medulloblastoma basal cell carcinoma Pathway activation pancreatic, gastric, prostate, glioma Tumor progenitor cells SCLC, glioblastoma, breast, multiple myeloma Hedgehog pathway implicated in variety of solid tumors and heme. malignancies |
Infinity’s Hedgehog inhibitor: IPI-926 HO O NH H H H H H 1 st generation 2 nd generation Solubility Chemical stability Potency (15nM in cell based assay) Selectivity Metabolic stability IPI-926 Oral bioavailability Long half-life In vivo activity + cyclopamine O H H O NH H H H • Issued composition of matter patent • Infinity-discovered & 100% owned royalty-free worldwide |
Daily oral administration of IPI-926 shows dose dependent inhibition of tumor growth -500.00 0.00 500.00 1000.00 1500.00 2000.00 2500.00 3000.00 3500.00 4000.00 4500.00 15 20 25 30 35 40 45 50 55 60 65 Days VEH--30% HPBCD in WFI IPI-926 @ 4mg/kg IPI-926 @ 10mg/kg IPI-926 @ 20mg/kg Treatment phase 4/7 fully regressed B837Tx tumor Ptch/Hic model of medulloblastoma Pink et al., 2008 AACR |
29 IPI-926 improves survival in orthotopic medulloblastoma model 0 1 2 3 4 5 6 7 8 9 10 11 10 14 18 22 26 30 34 38 42 46 50 Days post implant Veh IPI-926 @ 40mg/kg Start of TX End of TX Mouse model, orthotopically implanted B837Tx tumor Pink et al., 2008 AACR |
30 5 weeks total of IPI-926 follow-up treatment; 40 mg/kg, PO QD IPI-926 delays tumor recurrence post-chemo Traviglione et al., 2008 AACR |
31 Business Update |
Infinity Goals 2008 • Strong financial profile • Scientific excellence • Integrated Citizen-Ownership culture • Business and operational excellence • Retaspimycin GIST Phase 3 registration trial • Retaspimycin Phase 2 trials for additional indications • IPI-493 Oral Hsp90: Phase 1 clinical study • IPI-926 Hedgehog: Phase 1 clinical study • Identify strategic opportunities to enhance profile Execute on near-term value-drivers Maintain & enhance foundations for success |
Executing on our R&D and Business Strategy Initiate IPI-493 Phase 1 clinical trial Mid-2008 Initiate Phase 1 clinical study 2H 2008 File IND 2H 2008 Present preclinical data (AACR) IPI-926: Hedgehog pathway inhibitor Present preliminary IPI-504 Phase 2 data in HRPC By end 2008 Present preliminary IPI-504 Phase 2 data in NSCLC By end 2008 Initiate additional IPI-504 clinical studies 2H 2008 Initiate Phase 3 registration trial of IPI-504 in refractory GIST Q3 08 Secure SPA for IPI-504 Phase 3 GIST study Present IPI-504 Phase 1 GIST data (ASCO) IPI-504 & IPI-493: Hsp90 inhibitors |
34 Strong balance sheet; well capitalized • $105M cash and equivalents (3/31/08) • Burn rate well-controlled – 50% cost-sharing of Hsp90 program with MedImmune/AstraZeneca • Projected 2008 net cash burn: $35M - $45M • Cash to support current plan into 2010 – Sufficient capital to achieve key value creation milestones |
Infinity Leadership Michael Curtis, Ph.D., VP Pharm. Devel. TKT, Syntonix, Genzyme, Bristol-Myers Squibb David Grayzel, M.D., VP Clin Dev. & Med. Affairs Dyax, Mass General Hospital John Keilty, Sr Dir Informatics Millennium, UMass Medical School Vito Palombella, Ph.D., VP Drug Discovery Syntonix, Millennium, ProScript Steven Kafka, Ph.D., VP Finance Millennium, Strategic Decisions Group Jeanette Kohlbrenner, Sr Dir Human Resources Genetics Institute, Syntonix Gerald Quirk, Esq., VP & General Counsel Genzyme, Palmer & Dodge Jeffrey Tong, Ph.D., VP Corp. & Product Dev. McKinsey & Co, Harvard Ctr. for Genomics Research Steven Holtzman Chair, President & CEO Millennium, DNX Julian Adams, Ph.D. CSO & President of R&D Millennium, ProScript, Boehringer Ingelheim, Merck Adelene Perkins Chief Business Officer & EVP Transform, Genetics Institute, Bain, GE |
INFI Investment Thesis • Sustainable pipeline of novel, small molecules for key targets – Hsp90 inhibitors: IPI-504 i.v. and IPI-493 p.o. ��� Hedgehog pathway inhibitor: IPI-926 • International Ph 3 trial for IPI-504 to commence in 3Q08 under SPA – IPI-504 positioned as potential first-in-class anti-chaperone agent • Broad, near-term potential – Multiple IPI-504 trials underway in major disease categories • Strong balance sheet; well-capitalized – Resources support current operating plan into 2010 • Proven management team – First- and best-in-class NDAs, value-creating business transactions |