Multi-Mechanism Drugs for Oncology and Inflammation. September 2007

Transcription

1 Multi-Mechanism Drugs for Oncology and Inflammation September

2 Forward-Looking Statements Statements that are not descriptions of historical facts are forward-looking and subject to risk and uncertainties. Actual results may differ materially from those currently anticipated due to a number of factors, including risks relating to additional financing, earlystage product development, clinical trials, and those set forth in the Company s Securities and Exchange Commission filings. 2

3 EntreMed: A Clinical-Stage Oncology Company Public Company Therapeutic Focus NASDAQ: ENMD Established: 1991 IPO: 1996 Cancer & Inflammation Development Stage Phase 2 Oncology Technology Expertise Facilities Angiogenesis, Cell Cycle Regulation, Apoptosis, Kinase Signaling Rockville, Maryland and Toronto, Ontario Employees Financials (June 30, 2007) 57 Total; 42 in R&D 18 Ph.D. and M.D. Cash & Short-Term Investments: $38 MM 3

4 Our Strategy: Build a Leading Clinical Oncology Company Pursue a Focused Strategy Broad-based oncology pipeline Multiple clinical candidates Apoptosis Oral, small molecule drugs Multiple mechanisms/pathways Tumor Growth Multiple signalling pathways Target tumor cells and vasculature Limit drug resistance Angiogenesis Multiple clinical trials Consistent execution 4

5 Focus on Execution Experienced Management Team Research and clinical management experience Commercial and business development expertise Consistent execution meet guidance Build broad pipeline Three clinical programs in three years Multiple opportunities for success Mitigate development risk Strong resource management Tight cash management Celgene relationship 5

6 Investment Highlights Robust clinical pipeline Panzem NCD Multiple Phase 2 MKC-1 Multiple Phase 2 ENMD-1198 Phase IND Candidates Panzem in Rheumatoid Arthritis ENMD-2076 (Aurora/Angiogenesis Inhibitor) Strong IP, retained commercial rights to all compounds Selective partnering discussions initiated Strengths Experienced management team focused on execution Expertise in angiogenesis and cell proliferation Celgene Corporation, largest shareholder Cash and short-term investments into

7 Deep Mid-Stage Clinical Pipeline 7

8 Panzem NCD: Novel Phase 2 Anticancer Agent Oral, liquid formulation Novel antiproliferative agent Promotes both pro-apoptotic and antiangiogenic effects Combines well with other anticancer agents in preclinical models Well-tolerated with an acceptable safety profile in over 250 patients Bioavailable formulation (NCD) inlicensed from Elan Broad IP position; composition-ofmatter through

9 Panzem NCD Preclinical Activity Alone and in Combination Potent inhibitor of HIF-1α Single agent activity in NSCLC, MBC, and ovarian models Demonstrated additive and synergistic effects in combination with other agents and conventional cytotoxics Tarceva, Velcade, Camptosar, Temodar, Taxol, Cisplatin, and 5-FU Safety profile lends itself to a variety of drug combinations Apoptosis (caspase activation) Tumor Growth (G2M-specific arrest) Oncogenic Pathways ( HIF-1α, VEGF) 9

10 2ME2 in Combination with Temodar Causes Tumor Regression in a Preclinical Glioblastoma Model n=2 studies, 10 mice/group Vehicle Control 2ME2 400mg/kg p.o., qd Temodar 42 mg/kg p.o., qd x 5 Temodar 42 mg/kg p.o., qd x 5 + 2ME2 400 mg/kg p.o., qd Rx initiated % change in tumor growth Days following tumor challenge 10

11 Panzem NCD: Clinical Development Program INDICATION TRIAL TYPE SITE(S) N= STATUS NEXT EVENT Glioblastoma Multiforme Phase 2 Duke University 27 Closed Report additional results (GBM) Glioblastoma Multiforme (GBM) Phase 2 (w/temodar ) Duke University 32 Enrolling Complete enrollment Metastatic Breast Cancer Phase 1b (w/taxol ) Duke University 15 Enrolling Report additional results Carcinoid Tumors Phase 2 (w/avastin ) Dana-Farber MGH 31 Closed Interim results Hormone-Refractory Prostate Cancer Phase 2 Univ. of Wisconsin (lead, multicenter) 50 Enrolling Complete enrollment Ovarian Cancer Phase 2 Indiana University (lead, multicenter) 17 Closed Interim results Renal Cell Carcinoma Phase 2 (w/sutent ) Univ. of Wisconsin (lead, multicenter) 82 Enrolling Complete enrollment 11

12 Panzem NCD: Recent Clinical Results Phase 2: Panzem NCD in glioblastoma multiforme (ASCO) Twenty-seven patients with recurrent GBM; well-tolerated One partial response (PR) and seven stable diseases (SD) Supported rationale for combination study (initiated May 07) Phase 1b: Panzem NCD/Taxol in metastatic breast cancer (ASCO) Ten patients with stage IV or III inoperable breast cancer; well-tolerated One complete response (CR), one partial response (PR), and one patient with a 30% reduction in tumor volume Phase 2: Panzem Capsules in multiple myeloma (ASCO) Sixty patients with relapsed or plateau phase multiple myeloma Progression free survival rates were 24%, 17% and 11% at 1, 2, and 3 years Five patients remain on study, including three patients who have been on study for over four years without disease progression 12

13 MKC-1: Novel Phase 2 Cell Cycle Inhibitor Oral, antiproliferative, cell-cycle inhibitor acting through multiple mechanisms: PI3 Kinase mtor pathways Importin β Microtubules Extensive preclinical and clinical package from Roche (including durable responses in breast and NSCLC) Extensive IP through 2019, including composition-of-matter and formulation Exclusive world-wide license 13

14 MKC-1: Clinical Activity Demonstrated Prior Phase 1 & 2 trials in 269 patients Efficacy demonstrated even with suboptimal doses PRs and MRs in NSCLC and metastatic breast cancer Stable disease in pancreatic and ovarian cancer Toxicity included neutropenia, GI effects; no neuropathy, no abnormal cardiovascular findings 125 mg/m 2 bid, 14d, q4wks (Phase 1 recommended dose) Apoptosis (caspase activation) Tumor Growth (G2M-specific arrest) Oncogenic Pathways (PI3k, mtor) 14

15 MKC-1: Three Clinical Trials Initiated in 2006 INDICATION TRIAL TYPE SITE(S) N= STATUS NEXT EVENT Metastatic Breast Cancer Phase 2 Multicenter Up to 60 Enrolling Report final data Hematological Cancers Phase 1 Princess Margaret Hospital 30 Enrolling Report data Non-Small Cell Lung Cancer Phase 1/2 (w/alimta ) Multicenter Up to 60 Enrolling Report Phase 1 results 15

16 MKC-1: Recent Clinical Results Phase 2: MKC-1 in metastatic breast cancer (ASCO Breast Cancer Symposium) 35 patients with anthracycline/taxane refractory metastatic breast cancer; well-tolerated Durable single-agent responses One complete response (CR) Two partial responses (PR) Three stable diseases (SD) of greater than four months No protocol modifications per 2 nd DSMB Study currently in second stage up to 53 evaluable patients 16

17 MKC-1: Additional Phase 2 Studies Being Planned Phase 2 pancreatic cancer Single center Single agent Patients with unresectable or metastatic pancreatic cancer who have failed at least one prior therapy Phase 2 ovarian/endometrial cancer Multi-center Single agent Patients with advanced ovarian or endometrial cancer 17

18 MKC-1: Potential Commercial Advantages Over Taxanes Multiple MOAs Durable responses in MBC and NSCLC Orally available No neuropathy No abnormal CV findings 1,800 1,500 1, DOCETAXEL PACLITAXEL US Sales ($MM) Source: Wolters Kluwer Health Source Prescription Pharmaceutical Audit 18

19 ENMD-1198: Novel, Multi-Mechanism Antimitotic Agent in Clinical Development for Oncology Novel antiproliferative and antiangiogenic mechanisms Oral, stable, liquid dispersion Strong IP position; new chemical entity (NCE); multiple patents pending Broad applicability: many different tumor types inhibited preclinically Phase 1b clinical trial in advanced cancer patients ongoing Report results 4Q07/1Q08 19

20 ENMD-1198: Excellent Preclinical Antitumor Activity In vivo antitumor activity in both hematological and solid tumor models Decreases HIF-1α, pnf-κb, pstat3, and angiogenesis in multiple in vivo tumor models Activity against MDR overexpressing cells as well as cells resistant to taxanes and vinca alkaloids Competitive advantages to today s marketed products Apoptosis Tumor Growth (mitotic arrest) Oncogenic Pathways ( HIF-1α, VEGF) 20

21 ENMD-1198: Potential Commercial Advantages Broad spectrum of activity Multiple MOAs Orally available Competitive advantages compared to today s marketed products TAXOIDS DNA TOPO INHIBITORS VINCA ALKALOIDS 2,500 2,000 1,500 1, US Sales ($MM) Source: Wolters Kluwer Health Source Prescription Pharmaceutical Audit 21

22 Dual-Acting Aurora/Angiogenesis Inhibitor Aurora kinase overexpression leads to tumor cell formation Inhibition of Auroras leads to growth arrest and cell death ENMD is a novel, oral, AK inhibitor with apoptotic and antiangiogenic activity Unique pattern of kinase inhibition Proliferation: Aurora A, Flt3, Src Angiogenesis: VEGFR2, FGFR, PDGFR 22

23 ENMD : Promising Pre-IND Candidate Inhibits multiple proangiogenic kinases Induces regression in multiple models colon breast leukemia Well-tolerated Multiple patents pending IND filing expected 4Q07 Tumor volume (mm 3 ) Response of MV4;11 Xenograft to ENMD Treatment Rx initiate d Endpoint Rx altered Days following tumor challenge mg/kg, po qd No treatment Vehicle Control ENMD ENMD ENMD ENMD

24 Antitumor Activity of ENMD on HCT-116 Tumor Growth Tumor volume (mm 3 ) Mice: NCR nude, female N : 10/group Rx initiated Vehicle Control ENMD mg/kg po, bid ENMD mg/kg po, bid 5 x 2 ENMD mg/kg po, bid 5-FU 30 mg/kg ip, qd x5 VX mg/kg ip, bid x % change in tumor size from Rx initiation Tumor type: human CRC Tumor site: sc, day 0 Rx initiated: day 10 Days following tumor challenge 24

25 Antitumor Activity of ENMD on MDA-MB-231 Tumor Growth Tumor volume ( mm 3 ) Mice: CB17 SCID, female N : 9/group Tumor type: human breast Tumor site: sc, day 0 Rx initiated: day Vehicle Control ENMD mg/kg po, qd ENMD mg/kg po, qd ENMD mg/kg po, qd CTX 150 mg/kg ip qod X 3 repeat cycle every 21 days Rx initiated Days following tumor challenge % change in tumor size from Rx initiation

26 ENMD-2076 is the Form of ENMD Selected for Clinical Use ENMD-2076 is the tartrate salt of ENMD ENMD-2076 and ENMD have identical properties in preclinical models in vivo ENMD-2076 has significant manufacturing advantages relative to the free base ENMD IND submission planned for 4Q07 26

27 Panzem : Potential Utility Beyond Oncology Direct, dose-dependent inhibition in preclinical RA models (DMARD) cellular infiltration, pannus formation, cartilage lesions, bone resorption histologic & radiographic measures Near complete disease inhibition in combination with methotrexate in preclinical arthritis model Comparable activity to Enbrel in preclinical RA model Medical need for alternative, oral, well-tolerated DMARDs IND submission scheduled for 2H07 Vehicle Control 2ME2 Radiograph source: Dr. Ernest Brahn, UCLA 27

28 Inhibition of Synovial Inflammation in the Arthrogen- CIA Model by 2ME2 Vehicle 2ME2 28

29 2ME2 Inhibits Severity of Disease Progression 16 Severity Score Bone resorption Cartilage lesion Pannus Cellular Infiltration Articular histology equivalent to normal joint ME2 (mg/kg) 29

30 Potential First-in-Class Oral DMARD for RA Major cross-over opportunity More than 300 million cases in 7 biggest markets, growing rapidly due to aging populations $18 billion market Need for alternative DMARDs Oral; small molecule Unique mechanism Potential to compete against DMARDs (Trexall, Plaquenil ) and Biological Response Modifiers (Enbrel, Remicade, Humira ) 20,000 16,000 12,000 8,000 4,000 0 ENBREL REMICADE HUMIRA Worldwide Sales ($MM) Source: EvaluatePharma 30

31 Financial Performance: 2Q07 vs. 2Q06 Six Months Ended June 30, Total revenues $ 0 $ 0 Research & development 12,979,983 8,269,306 General & administrative 3,701,137 3,759,346 Operating loss (15,608,279) (11,254,533) Acquired in-process R&D 0 29,481,894 Net Loss (15,608,279) (40,736,427) Net loss per share attributable to common shareholders (ongoing) $ (0.19) $ (0.18) Net loss per share attributable to common shareholders (basic) $ (0.19) $ (0.59) Weighted avg. number of shares outstanding (basic) 84,015,999 69,765,434 Cash & short term investments $38,062,570 $ 45,091,175 31

32 2007 Milestones: Clinical Trial Progress and Data Clinical Data Flow Panzem NCD Capsule Phase 2 multiple myeloma trial Panzem NCD Phase 2 single agent GBM trial (interim) Panzem NCD + Taxol Phase 1b metastatic breast cancer trial (interim) Panzem Phase 1b food effect, scheduling studies MKC-1 Phase 2 metastatic breast cancer trial (interim) MKC-1 + Alimta Phase 1/2 NSCLC trial (Phase 1 results) MKC-1 Phase 1 leukemia trial (1H08) ENMD-1198 Phase 1b dose-escalation trial (interim) Clinical Trial Initiation Panzem NCD + Temodar combination GBM trial Panzem NCD + Sutent renal cell cancer trial MKC-1 Phase 2 pancreatic or ovarian cancer trial IND Filings Aurora/angiogenesis inhibitor (ENMD-2076) for use in oncology Panzem for the treatment of rheumatoid arthritis Collaborations/Partnerships Aurora/angiogenesis inhibitor co-development alliance 32

33 Investment Highlights Robust clinical pipeline Panzem NCD Multiple Phase 2 MKC-1 Multiple Phase 2 ENMD-1198 Phase IND Candidates Panzem in Rheumatoid Arthritis ENMD-2076 (Aurora/Angiogenesis Inhibitor) Strong IP, retained commercial rights to all compounds Selective partnering discussions initiated Strengths Experienced management team focused on execution Expertise in angiogenesis and cell proliferation Celgene Corporation, largest shareholder Cash and short-term investments into

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