Multi-Mechanism Drugs for Oncology and Inflammation. Jesup & Lamont Emerging Growth Conference February 28, 2008

Transcription

1 Multi-Mechanism Drugs for Oncology and Inflammation Jesup & Lamont Emerging Growth Conference February 28,

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, early-stage 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 NASDAQ: ENMD Therapeutic Focus Cancer & Inflammation Development Stage Phase 2 Oncology Technology Expertise Facilities Angiogenesis, Cell Cycle Regulation, Apoptosis, Kinase Signaling Rockville, Maryland and Toronto, Ontario Employees 57 Total; 43 in R&D Financials Cash & Short-Term Investments: $50.6 MM (Sept 30, 2007) 3

4 Mission: Discover, Acquire and Develop Multi-Mechanism Cancer and Anti-inflammatory Drugs that Block Cell Proliferation and Angiogenesis Deep clinical pipeline MKC-1 Multiple Phase 2 Panzem NCD Multiple Phase 2 ENMD-1198 Phase 1 Panzem in Rheumatoid Arthritis IND Accepted ENMD-2076 (Aurora/Angiogenesis Inhibitor) IND Accepted Strong IP, retained commercial rights to all compounds Experienced management team focused on execution Celgene Corporation, largest shareholder Cash and short-term investments into

5 Deep Mid-Stage Clinical Pipeline 5

6 MKC-1: Novel Phase 2 Cell Cycle Inhibitor Oral, antiproliferative, cell-cycle inhibitor acting through multiple mechanisms: Akt mtor pathway 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 6

7 MKC-1 Activity is Consistent With Inhibition of mtor at the Level of the mtorc2 Complex mtor LST8/GBL Rictor mtorc2 MKC-1?? Rapamycin FOXO3A elf4g Ser473 GROWTH FACTORS LST8/GBL P13K Akt TSC1 mtor Raptor mtorc1 4E-BP1 elf4e Thr308 MDM2 Thr246 PRAS40 Ser183 elf4b PDK1 S6K1 S6 7

8 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 Activity seen in pancreatic and ovarian cancer Toxicity included neutropenia, GI effects; no neuropathy, no abnormal cardiovascular findings Apoptosis Tumor Growth (G2/M cell cycle arrest) Oncogenic Pathways (PI3k, mtor) 125 mg/m2 bid, 14d, q4wks (Phase 1 recommended dose) 8

9 MKC-1: Clinical Trials in Solid Tumors and Leukemia INDICATION TRIAL TYPE SITE(S) N= STATUS Metastatic Breast Cancer Phase 2 Multicenter Up to 60 Enrolling Hematological Cancers Phase 1 Princess Margaret Hospital 30 Enrolling Non-Small Cell Lung Cancer Phase 1/2 (w/alimta ) Multicenter Up to 60 Enrolling Pancreatic Cancer Phase 2 Multicenter Up to 33 Enrolling Ovarian/Endometrial Cancers Phase 2 Multicenter Up to 84 Enrolling 9

10 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

11 Panzem NCD: Clinical Development Program INDICATION TRIAL TYPE SITE(S) N= STATUS Glioblastoma Multiforme Phase 2 Duke University 27 Closed (GBM) Glioblastoma Multiforme (GBM) Phase 2 (w/temodar ) Duke University 32 Closed Metastatic Breast Cancer Phase 1b (w/taxol ) Duke University 20 Enrolling Carcinoid Tumors Phase 2 (w/avastin ) Dana-Farber MGH Ovarian Cancer Phase 2 Indiana University (lead, multicenter) Renal Cell Carcinoma Phase 2 (w/sutent ) Univ. of Wisconsin (lead, multicenter) 31 Closed 17 Closed 82 Enrolling Final data analysis pending; presentations/publications in

12 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 Extended survival in lung and ovarian cancer Synergistic benefit with vincristine in leukemia Phase 1b clinical trial in advanced cancer patients ongoing 12

13 ENMD-1198 Significantly Increases the Survival of NSCLC (H2122) Tumor Bearing Mice 100 Survival (%) 50 No therapy ENMD-1198 Cisplatin Treatment No therapy Cisplatin ENMD-1198 MST (Days) >53 P-value (control vs. treated) - NS R x Days after cell injection 13

14 ENMD-2076: Dual-Acting Aurora/Angiogenesis Inhibitor Aurora kinase overexpression leads to tumor cell formation Inhibition of Auroras leads to growth arrest and cell death ENMD-2076 is a novel, oral, AK inhibitor with apoptotic and antiangiogenic activity Potent Aurora A activity Unique pattern of kinase inhibition Proliferation: Aurora A, Flt3, Src Angiogenesis: VEGFR2, FGFR, PDGFR 14

15 ENMD-2076 (981693): Promising MTKI Causes Tumor Regression in Multiple Preclinical Models Inhibits multiple proangiogenic kinases Induces regression in multiple models colon breast leukemia Well-tolerated Multiple patents pending IND accepted; Phase 1 trial initiation in 1Q08 Response of MV4;11 Xenograft to ENMD Treatment mg/kg, po qd 1600 Endpoint No treatment Tumor volume (mm3) Rx initiated Rx altered ENMD Days following tumor challenge Vehicle Control ENMD ENMD ENMD

16 ENMD-2076 (981693): Causes Regression in Colon Cancer (HCT-116) and Breast Cancer (MDA-MB-231) Models 1600 Vehicle Control Tumor volume (mm3) 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 13 Rx initiated Days following tumor challenge Tumor volume ( mm3) 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 16

17 Panzem : Crossover Opportunity in Rheumatoid Arthritis Direct, dose-dependent inhibition in preclinical RA models (DMARD) cellular infiltration pannus formation cartilage lesions bone resorption 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 17

18 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) 18

19 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 19

20 Experienced Management Team Kenneth W. Bair, PhD Mark R. Bray, PhD James S. Burns Dane R. Saglio Carolyn F. Sidor, MD Anthony R. Treston, PhD Cynthia Wong Hu, JD SVP, Research & Development Chiron, Pharmacia, Novartis, Sandoz, Burroughs-Wellcome VP, Research Miikana Therapeutics, Amgen President & CEO MedPointe Pharmaceuticals, Osiris Therapeutics, Healthcare Ventures, Becton Dickinson, Booz Allen Hamilton CFO Public Communications Associates VP & CMO UNC Healthcare System, Cato Research, DuPont VP, Product Development & Manufacturing National Cancer Institute VP, General Counsel & Secretary Powell Goldstein, Golden American Life 20

21 Financial Performance: 3Q07 vs. 3Q06 Nine Months Ended September 30, Total revenues $ 3,520,259 $ 3,023,185 Research & development 18,089,240 13,813,440 General & administrative 5,407,588 5,256,958 Operating loss (18,643,625) (14,779,931) Acquired in-process R&D - 29,481,894 Net Loss (18,643,625) (44,261,425) Net loss per share attributable to common shareholders (ongoing) $ (0.23) $ (0.21) Net loss per share attributable to common shareholders (basic) $ (0.23) $ (0.63) Weighted avg. number of shares outstanding (basic) 84,015,999 70,952,694 Cash & short term investments $50,644,261 $39,428,618 21

22 2008 Clinical and Non-Clinical Milestones Compound Goal Target Status Initiate Phase 2 study in ovarian/endometrial cancers 1Q08 Report results (Phase 2 metastatic breast cancer) 2Q08 MKC-1 Initiate Phase 2 continuous dosing trial 2Q08 Report Phase 1 and interim Phase 2 data (non-small cell lung cancer) 2Q08 Report interim results for Phase 1 leukemia 2H08 Report interim results for Phase 2 pancreatic 4Q08 Panzem NCD Report interim data for Phase 2 Avastin trial in carcinoid tumors 1Q08 Report interim results for ongoing studies 2Q/3Q08 Complete Phase 1b enrollment 2Q/3Q08 ENMD-1198 Initiate expanded Phase 1 or Phase 2 trial 3Q/4Q08 Report interim data for Phase 1b 4Q08 Initiate Phase 1 trial in solid tumors 1Q08 ENMD-2076 Initiate Phase 1 trial in hematological tumors 3Q08 Co-development alliance 2H08/1H09 Panzem RA Initiate normal volunteer trial 1H08 22

23 Investment Highlights: Advancing Clinical Pipeline Deep clinical pipeline MKC-1 Oncology Phase 2 Panzem NCD Oncology Phase 2 ENMD-1198 Oncology Phase 1 ENMD-2076 Oncology IND Accepted Panzem Rheumatoid Arthritis IND Accepted Multiple opportunities to succeed and mitigate risk Focus resources on premium opportunities Strong IP; multiple partnering opportunities Cash resources to advance programs into 2H09 23

24 24