111

Multi-Target Drugs for Cancer and Inflammation

November 2008NASDAQ: ENMD

222

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.

3

Our Mission: Multi-Target Oncology Drugs

EntreMed is a clinical-stage pharmaceutical company developing

next generation multi-mechanism drugs to treat cancer and

inflammatory disorders by targeting disease cells directly and the

blood vessels that nourish them.

Rockville, Maryland and Toronto, OntarioResearch Facilities

Angiogenesis, Cell Cycle Regulation, Cell Signaling, and Inflammation

Technology Expertise

Phase 2 Oncology Development Stage

Oncology & InflammationTherapeutic Focus

444

Business Model – Targeted, Multi-Mechanism Drugs

• Multiple Shots on Goal– Multiple drug candidates with multiple mechanisms of action – Risk mitigation via multiple early-stage clinical programs– Strong IP, retained commercial rights to all compounds

• Focused on important pathways and targets that can inhibit disease progression– Small molecule, orally-active, antiproliferative, antiangiogenic drugs– Expertise in angiogenesis, cell cycle regulation, cell signaling

• Create Value– Multi-product clinical pipeline – Execute partnering strategy

5

Multiple Phase 1 and Phase 2 Partnering Opportunities

ClinicalCandidate Development

HypothesisGeneration

Risk

Cumulative InvestmentRisk

CumulativeInvestment

Pre‐ClinicalDevelopment

PhaseI

PhaseII

PhaseIII

Regis‐tration

GlobalLaunch

GlobalOptimization

Commercialization

LeadOptimization

Target Identificationand Validation

AssayDevelopment

LeadGeneration

Original Source: James Doroshaw, MD, National Cancer Institute Modified: ENMD November 2008

6

Targeted Agents Will Drive the Growth in Oncology

Source: Oncology Market Size, Competition and Pricing, September 21, 2007

Oncology Market: Share Of Targeted Agents, 2000A-2015 (%)

37%27% 20% 16% 11%

22%

14%11%

8%6%

34%

27%

18%19%

18%

7%

33%51% 57% 65%

0%10%20%30%40%50%60%70%80%90%

100%

2000 2006 2010 2012 2015

Cytotoxics Hormonal Agents

Supportive Care Targeted Agents

7

Focus on Tumor Cell and Angiogenic Inhibition

88

Substantial Progress: All Programs in Clinical Development

• Multi-program clinical development pipeline

• MKC-1 Ph 2 Oncology• ENMD-1198 Ph 1 Oncology• ENMD-2076 Ph 1 Oncology• Panzem® Ph 1 Rheumatoid Arthritis (RA)

• Programs address high unmet medical needs

• Strong IP, retained commercial rights to all compounds

• Partnering discussions underway for ENMD-2076 and Panzem®

for RA

• Cash & short-term investments through 2009

99

Target Interdiction is Key to Cancer Cell Inhibition

ProteinSynthesis

Akt

MKC-1

TORC2Complex

mTOR

GβL Rictor

TORC1ComplexmTOR

GβL Raptor

X

Angiogenesis, Proliferation,Metabolism

Translation

HIF-1α, STAT3, NFκB

Cell Kill, Apoptosis, Metabolic & Antiangiogenic Effects

Importin β

TFREs TFs

X

X

MKC-1

X

CellCycle

ENMD-2076

ENMD-2076

ENMD-1198

Mitosis

m&tRNA

SM/TFs

RTKs

TKs

XX

X

X

10101010

Solid Clinical Pipeline: Multiple Product Opportunities

1111

MKC-1: Novel Phase 2 Cell Cycle Inhibitor

• Oral, antiproliferative, cell-cycle inhibitor; mTOR inhibitor, Importin β, HIF-1α targets

• Broad antitumor activity, alone and in combination

• Predictable toxicity (neutropenia, GI effects); no neuropathy, no abnormal cardiovascular effects

• Exclusive world-wide license from Roche

• Broad IP coverage through 2021, including composition-of-matter & formulation; substantial API inventory

1212

MKC-1 is a 2nd Generation mTOR Drug Candidate that Blocks the TORC2 Complex & Inhibits Akt Function

Cell Metabolism

Angiogenesis

VEGFsGrowth FactorSignaling

ProteinSynthesis

Cell Proliferation

EGFIGF

PI-3K

TSC2/1

RHEB

PTEN

TORC1Complex

mTORGβL

TORC2Complex

Raptor

mTOR

GβL Rictor

Nutrients

HIF-1α

Hypoxia

Akt

MKC-1

RapamycinRAD001

1313

MKC-1: Clinical Trials in Solid Tumors and Leukemia

INDICATION TRIAL TYPE SITE(S) N= Dosing

Metastatic Breast Cancer Phase 2 Multicenter Up to 60 Intermittent

Non-Small Cell Lung CancerPhase 1/2

(w/Alimta®)Multicenter Up to 60 Intermittent

Hematological Cancers Phase 1 Princess Margaret Hospital 30 Intermittent/

Continuous

Pancreatic Cancer Phase 2 Multicenter Up to 33 Intermittent/ Continuous

Ovarian/Endometrial Cancers Phase 2 Multicenter Up to 84 Intermittent

Solid Tumors Phase 1 University of Wisconsin Up to 24 Continuous

141414

MKC-1 Progress in Non-Small Cell Lung Cancer

• Trial Design: Phase 1/2, open label, in combination with pemetrexed(Alimta®) (Phase 1 dose escalation advanced solid tumors, Phase 2 non-small cell lung cancer)

• Dosing: Phase 1 escalating dose started with 75 mg/m2 BID for 14 days on, 7 days off, in combination with pemetrexed at standard dose

• Study Endpoints– Safety occurrence of treatment-emergent AEs– Efficacy (Phase 2) tumor response (according to RECIST)– Median progression free survival– Duration of response and time to response– Time to treatment failure– Median survival

• Primary endpoint (response) has been met

• Randomized Phase 2 in NSCLC (and RCC) under consideration

1515

ENMD-2076: Aurora A and Angiogenesis Inhibitor

• Orally active, selective-kinase inhibitor

• Unique combination of target activities: Aurora A & Angiogenic Kinases (VEGFR, FGFR, PDGFR); Growth Factor Kinases (Flt-3, Src, c-Kit)

• Tumor regression observed in multiple preclinical models

• Excellent efficacy as a single agent

• Combines well with other cancer drugs

• Excellent pharmaceutical properties

• Patents pending; > 600 analogs coveredAurora A

Key Regulator of Cell Division;Expression Linked to Decreased Survival

Aurora A

1616

Significant Tumor Regression Demonstrated with ENMD-2076 in Preclinical Leukemia Model

no treatment

vehicle alone

15 mg/kg

30 mg/kg

75 mg/kg

150 mg/kg

Tum

or V

olum

e (m

m3 )

Endpoint

0

200

400

600

800

1000

1200

1400

1600

20 25 30 35 40 45 50 55 60 65 70 75 80 85 90

Days following Tumor Challenge

Rx initiated

Rx changed

Free base

• MV4;11 Leukemia Tumor Model• Dose escalated to 150 mg/kg in 15 & 30 mg/kg cohorts

1717

Tumor Regression and Antiangiogenic Effects of ENMD-2076 in Preclinical Colon Carcinoma Models

Vehicle Control Day 28

ENMD-2076 po, qd (200 mg/kg) Day 28

HT29 Colon Carcinoma Xenograft

1818

• Ph 1 clinical study initiated 1Q08 – Dana-Farber and University of Colorado

• Ph 1 design and endpoints– 3 + 3 dose escalation with safety, PK

and clinical benefit endpoints– Daily dosing

• PD evaluation of soluble VEGFR2

• Cardiovascular monitoring

• Goal: determine MTD in solid tumor patients

• Clinical trial in hematological cancer planned for 2H08

Multicenter Clinical Trial Underway with ENMD-2076 in Advanced Cancer Patients

ENMD-2076 – Initial Phase 1 Comments & Observations

• Phase 1 clinical trial in patients with advanced solid tumors– Currently enrolling patients in 3rd cohort– Longest patient on study at 6 months of daily dosing

• Initial PK data suggest that T1/2 is higher than what was observed in animal studies

• Longer half life might lead to less than daily dosing/lower doses needed in humans

• Phase 1 results anticipated by mid-2009

2020

ENMD-1198: Oral, Multi-Mechanism Antimitotic Agent

• Novel drug targeting key transcription factors – HIF-1, STAT3 & NFκB

– HIF-1 has a central role in cell survival & proliferation; regulates > 80 genes

– Over-expression associated with tumor aggression & increased angiogenesis

• Antiproliferative & antiangiogenic activity against multiple tumor types, including resistant tumors

• Phase 1 study in advanced cancer patients nearing completion

– Reached dose-limiting toxicity– Cohort expansion to identify combination

therapies and target indications

• MOA indicates prostate cancer may be key indication; clinical development plan pending

2121

Joint in Rheumatoid Arthritis – Effects of 2ME2

Normal Joint

RheumatoidArthritis

2ME2

Pannus Formation

Cellular Infiltration

Cartilage Degradation

Bone Erosion

2222

Panzem® (2ME2) – An Oral, Small Molecule DMARD with Antiangiogenic Activity

• Dose-dependent inhibition in preclinical RA models (DMARD)– Cellular Infiltration– Pannus Formation– Cartilage Lesions– Bone Resorption

• Additive activity in combination with MTX

• Comparable activity to Enbrel® in preclinical RA models

• Orally-active, unique inhibition of targets distinguishes 2ME2 from other RA agents

• Broad IP position; composition-of-matter coverage through 2022

• $14 billion global market; >300 million cases worldwide– Oral, small molecule, unique mechanism– Potentially competitive with BRMs and other DMARDs

CH3

HO

H3CO

OH

2ME2

2323

Healthy Volunteer Study Complete: Clear Path Forward

• Study goals achieved

– Cross-over from oral liquid to dry powder formulation with equivalent PK

– Study used higher oncology dose

– Lower dose anticipated for RA indication

– Substantial safety history

• FDA review of results completed

• Clear development path forward– Drug-drug interaction (DDI) clinical study with methotrexate– Phase 2 following chronic animal toxicity study

• Active partnering effort underway

24

Nine Months Ended September 30,

Year-End2008 2007 2007

Total revenues $ 3,501,307 $ 3,520,259 $ 7,395,651Research & development 16,629,127 18,089,240 23,739,392General & administrative 5,274,585 5,407,588 7,386,570Operating loss (19,314,476) (18,643,625) (22,411,121)

Acquired in-process R&D 2,000,000 0 0Net Loss (21,314,476) (18,643,625) (22,411,121)

Net loss per share attributable to common shareholders (basic) $ (0.26) $ (0.23) $ (0.28)

Weighted avg. number of shares outstanding (basic) 86,060,438 84,015,999 84,166,552Cash & short term investments $27,871,889 $ 50,644,261 $ 47,748,191

Good Financial Position: Emphasis on Tight Cash Management and Execution Against Milestones

252525

Key 2H08 & 1H09 Milestones: Moving Our Clinical Pipeline Forward

Initiate Phase 2 study in ovarian/endometrial cancers 1Q08Report results (Phase 2 metastatic breast cancer) 2Q08Initiate Phase 1 continuous dosing trial 2Q08Report Phase 1 and interim Phase 2 data (non-small cell lung cancer) 4Q08Initiate Phase 1 trial in solid tumors 1Q08Initiate Phase 1 trial in hematological tumors 4Q08Co-development alliance 1H09

Panzem® (2ME2) Complete healthy volunteer trial in rheumatoid arthritis 2H08Complete Phase 1 enrollment 4Q08Initiate expanded Phase 1 or Phase 2 trial 1H09Report interim data for Phase 1 1Q09

Status

MKC-1

ENMD-1198

ENMD-2076

Compound Goal Target

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Multi-Target Drugs for Cancer and Inflammation