Analyst Day January 17, Alexis Borisy, President and CEO

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1 Analyst Day January 17, 2007 Alexis Borisy, President and CEO

2 2007 CombinatoRx, Incorporated. All rights reserved. 2 Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 concerning CombinatoRx, its product candidates and their development and commercial potential, its collaborations, its clinical trials, its formulation efforts, its intellectual property, its financial results and its plans for other research and development programs. These forward-looking statements are based on the current estimates and assumptions of the management of CombinatoRx as of the date of this presentation and are subject to risks, uncertainties, assumptions and other factors that may cause the actual results of CombinatoRx to be materially different from those reflected in such forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, the future results of on-going or future clinical trials, the unproven nature of our drug discovery technology, outcomes and timing of the regulatory approval process, our ability to initiate and complete clinical trials, our ability to develop proprietary formulations of our product candidates, the performance under our collaboration agreements and the other risks discussed in this presentation and others that can be found in the "Risk Factors" section of the CombinatoRx Annual Report on Form 10-K on file with the Securities and Exchange Commission, and the other filings made by CombinatoRx with the Securities and Exchange Commission. No forward-looking statement can be guaranteed and actual results may differ materially from those CombinatoRx projects. CombinatoRx is providing this information as of the date of this presentation and does not undertake any obligation to publicly update any forward-looking statements contained in this document as a result of new information, future events or otherwise, except as required by law. Today's presentation is not an offer to sell or the solicitation of an offer to buy CombinatoRx common stock.

3 2007 CombinatoRx, Incorporated. All rights reserved. 3 Building CombinatoRx VALUE Synergy = Selective Action The Idea A new approach to drug discovery

4 2007 CombinatoRx, Incorporated. All rights reserved. 4 Building CombinatoRx VALUE Proprietary Technology Renewable and untapped source of drugs The Idea A new approach to drug discovery

5 2007 CombinatoRx, Incorporated. All rights reserved. 5 Building CombinatoRx VALUE 1000 s of Synergies Proprietary Technology Drug Discovery Machine Renewable and untapped source of drugs The Idea A new approach to drug discovery

6 2007 CombinatoRx, Incorporated. All rights reserved. 6 Building CombinatoRx VALUE Technology Partnerships 1000 s of Synergies Proprietary Technology Leverage the Machine Drug Discovery Machine Renewable and untapped source of drugs The Idea A new approach to drug discovery

7 2007 CombinatoRx, Incorporated. All rights reserved. 7 Building CombinatoRx VALUE Multiple POC Clinical Trials Technology Partnerships 1000 s of Synergies Proprietary Technology The Idea Productive Platform Leverage the Machine Drug Discovery Machine Renewable and untapped source of drugs A new approach to drug discovery Introduction of New CRx Products into Clinical Trials * CRx-026 CRx-102 CRx-139 CRx-191 CRx-170 CRx-150 CRx-197 CRx-140 CRx-119 CRx-401 *Planned

8 70% 60% 50% 40% 30% 20% 10% 0% 30% P l a c e b o p = % C R x CombinatoRx, Incorporated. All rights reserved. 8 Building CombinatoRx VALUE % of Patients A chieving AC R20 R espons Advancing the Pipeline Portfolio of Assets Compound Discovery Preclinical Phase 1/2a Phase 2b CRx-102 RA/OA Multiple POC Clinical Trials Productive Platform CRx-170 CRx-139 CRx-150 Chronic Pain RA Immuno-Inflammatory Technology Partnerships Leverage the Machine CRx-026 CRx-191 Multiple Tumors Topical Dermatology 1000 s of Synergies Drug Discovery Machine CRx-197 CRx-401 Preclinical Programs Topical Dermatology Multiple Candidates Diabetes Proprietary Technology Renewable and untapped source of drugs Research: Hepatitis C Huntington s Ophthalmic Cystic Fibrosis Others Multiple Programs The Idea A new approach to drug discovery

9 2007 CombinatoRx, Incorporated. All rights reserved Goals Advance the pipeline with 2 product candidates moving into later-stage clinical development CRx-102 OA and RA CRx-170 Chronic Pain Refresh the pipeline with 3 new product candidates dosed in humans CRx-191 Topical Dermatology CRx-197 Topical Dermatology CRx-401 Type 2 Diabetes Reload late-preclinical pipeline from research engine Introduce next generation product candidates

10 2007 Goals Maintain Financial Strength: 2007 Financial Guidance: Revenue $ M Net Loss $ M* Year-end Cash $ M Partnering strategy * Excluding FAS123 expense 2007 CombinatoRx, Incorporated. All rights reserved. 10

11 2007 CombinatoRx, Incorporated. All rights reserved. 11 CombinatoRx Pipeline: 2007 Compound Discovery Preclinical Phase 1/2a Phase 2b Phase 3 CRx-102 CRx-170 CRx-139 CRx-150 CRx-026 CRx-191 CRx-197 CRx-401 RA/OA Chronic Pain RA Immuno-Inflammatory Multiple Tumors Topical Dermatology Topical Dermatology Diabetes Preclinical Programs Multiple Candidates Research: Hepatitis C Huntington s Ophthalmic Cystic Fibrosis Others Multiple Programs

12 2007 CombinatoRx, Incorporated. All rights reserved. 12 CRx-102 CRx-102* Prednisolone DR Prednisolone IR Dipyridamole XR Synergistic combination of prednisolone and cardiovascular agent Novel mechanism selectively amplifies steroid s desirable activities A combination sciences dissociated steroid Significant activity from an unconventionally low dose of pred (<3mg) 63% ACR20 vs 30% placebo in RA 31% reduction in pain (AUSCAN) vs 7% placebo in OA Advancing into phase 2b trials in RA and OA *Formulation in development

13 Commercial Product CRx-102* Prednisolone DR Prednisolone IR Drug Level Dipyridamole Prednisolone Dipyridamole XR T 0 6hr 12hr 24hr Synergy through sustained co-exposure of components Improved dipyridamole tolerability Once-daily administration Using validated modified-release bead technologies *Formulation in development 2007 CombinatoRx, Incorporated. All rights reserved. 13

14 2007 CombinatoRx, Incorporated. All rights reserved. 14 Goal: A Dissociated Steroid A rapid improvement set in pains and tenderness in the joints abated or disappeared mobility increased patients who had previously been complete invalids could walk about freely Glucocorticoid therapy is very effective at reducing inflammation but chronic use leads to undesirable side effects

15 CRx-102 Mechanism Of Action Synergistically suppresses pro-inflammatory signaling Co-modulates NFkB, AP-1, and NFAT Selective action on trans-repression 2007 CombinatoRx, Incorporated. All rights reserved. 15

16 2007 CombinatoRx, Incorporated. All rights reserved. 16 CRx-102 Clinical Results to Date Study Indication Trial Description Result CRx (POC) Rheumatoid Arthritis 59 subjects, randomized, blinded, moderate RA, 6 weeks, CRx DMARD vs. Placebo + DMARD Significant ACR 20 response, DAS28 and CRP reduction CRx (POC) Osteoarthritis 83 subjects, randomized, blinded, moderate hand OA, 6 weeks, CRx-102 vs. Placebo Significant reduction in pain and stiffness CRx (POM) Inflammatory Biomarker 57 subjects, randomized, blinded, severe periodontitis, 6 weeks, CRx- 102 vs. Placebo Significant reduction in CRP

17 2007 CombinatoRx, Incorporated. All rights reserved. 17 CRx-102: Statistically Significant ACR20 Phase 2a RA Trial CRx DMARD vs. Placebo + DMARD % of Patients Achieving ACR20 Response 70% 60% 50% 40% 30% 20% 10% 0% p= % CRx % Placebo Day 42 % of Patients Achieving ACR20 Response 70% 60% 50% 40% 30% 20% 10% Day of Study CRx-102 Placebo Day 42: p= % *Per Protocol

18 2007 CombinatoRx, Incorporated. All rights reserved. 18 CRx-102: ACR50 and ACR70 Responses Phase 2a RA Trial CRx DMARD vs. Placebo + DMARD ACR50 ACR70 % of Patients Achieving ACR50 Response 30% 25% 20% 15% 10% 5% 0% 15% Placebo p=0.275 (NSS) Day 42 26% CRx-102 % of Patients Achieving ACR70 Response 12% 10% 8% 6% 4% 2% 0% 4% Placebo p=0.368 (NSS) Day 42 11% CRx-102 *Per Protocol

19 CRx-102: Significant DAS28 Response Phase 2a RA Trial CRx DMARD vs. Placebo + DMARD Day of Study Adjusted mean improvement from baseline DAS Placebo CRx p=0.016 Mean Change from Baseline DAS Score Placebo Day 42: p=0.016 CRx-102 Note: Baseline DAS28 scores were 6.9 (CRx-102) and 7.1 (placebo) *Per Protocol 2007 CombinatoRx, Incorporated. All rights reserved. 19

20 2007 CombinatoRx, Incorporated. All rights reserved. 20 CRx-102 Hand OA: Significant Pain Relief Phase 2a OA Trial CRx-102 vs. Placebo Mean percentage improvement from baseline in AUSCAN pain 35% 30% 25% 20% 15% 10% 5% 0% p= % 7% Placebo CRx-102 Day 42 Mean improvement from baseline in AUSCAN pain (mm) p=0.191 (NSS) p=0.010 p=0.023 p=0.006 CRx-102 Placebo Day of Study *Per Protocol

21 2007 CombinatoRx, Incorporated. All rights reserved. 21 Conclusions: CRx-102 in RA and OA Highly positive studies in both RA and OA Result Efficacy in RA Description CRP (-50% vs -19%) p=0.024 ACR20 (63% vs 30%) p=0.025 DAS28 (-1.6 vs -0.7 mean change; -21% vs -10%) p=0.016 Efficacy in hand OA Pain relief (31% vs. 7%) p=0.007 Rapid onset of action Well tolerated Separation seen between 7-14 days No serious adverse events in CRx-102-treated patients Headache and nausea were most common (>5%) adverse events in OA study Headache, GI symptoms, and dizziness were most common (>5%) adverse events in RA study No increases in blood glucose levels or infection rates associated with CRx-102

22 2007 CombinatoRx, Incorporated. All rights reserved. 22 Commercial Opportunities for CRx-102 Immuno-Inflammatory Diseases Rheumatologic Diseases Orphan/Fast track Polymyalgia Rheumatica Osteoarthritis Rheumatoid Arthritis Fibromyalgia TNFα Driven Diseases (IBD, Pulmonary Fibrosis, Psoriasis) CRP Driven Diseases (CAD) Spondyloarthropathies Systemic Lupus Erythematosus Glucocorticoid Sensitive Disease (Asthma, Multiple Sclerosis)

23 CRx-102 RA Opportunities The efficacy and safety profile of CRx-102 may result in multiple viable commercial positions RA Treatment Approach Inadequate Response Initiate Therapy: NSAID Local or Lowdose Systemic Steroids DMARD Add DMARD Methatrexate Other Monotherapy Combination Inadequate Response First-line alternative to steroids or NSAIDS First-line add-on to DMARD Preferred oral add-on to biologic therapy Add Anti-TNF Monotherapy Combination Inadequate Response Try another anti-tnf product Novel Biologics (abatacept, rituximab) Inadequate Response Salvage Therapy Decision Resources May 2006; ACR guidelines 2007 CombinatoRx, Incorporated. All rights reserved. 23

24 2007 CombinatoRx, Incorporated. All rights reserved. 24 CRx-102 OA Opportunities The efficacy and safety profile of CRx-102 may result in a viable alternative for NSAIDs/COXIBs OA Treatment Approach Weight loss and/or exercise Acetaminophen/ paracetamol NSAIDs/ COX-2 inhib. Opioids Intra-articular injections Surgery; Joint replacement CRx-102 Convert NSAIDs/Coxibs Delay/Spare Opioids

25 2007 CombinatoRx, Incorporated. All rights reserved. 25 CRx-102 RA: Planned Trial Design* Stage: Phase 2b Objective: Demonstrate CRx-102 superior to component doses of prednisolone and dipyridamole Subjects: patients (6 arms) Study Design: Randomized, double-blind, controlled; Add-on design Enrollment Criteria: Moderate to severe RA (>4 swollen and >6 tender joints; CRP > upper limit of normal); Concomitant DMARD therapy Treatment: 12 weeks (+ 12 month extension trial) Primary Endpoints: ACR20 (at Week 12) Secondary Endpoints: DAS28, CRP *subject to regulatory approval

26 2007 CombinatoRx, Incorporated. All rights reserved. 26 CRx-102 RA: Planned Trial Schematic* CRx /360 mg CRx /180 mg Prednisolone 2.7 mg Screening Prednisolone 7.5 mg Safety Extension Dipyridamole 360 mg Placebo Day - 28 Day 0 Day 7 Day 28 Day 56 Day 84 (Baseline visit) *subject to regulatory approval

27 2007 CombinatoRx, Incorporated. All rights reserved. 27 CRx-102 Knee OA: Trial Design* Stage: Phase 2b Objective: Demonstrate efficacy of CRx-102 in additional OA target joint (knee) Subjects: patients (5 arms) Study Design: Randomized, double-blind, controlled; Standard flare design: Screening VAS points; Following 1 week NSAID washout, VAS must increase 10 points Primary Comparison: CRx-102 (all doses) to placebo Enrollment Criteria: Radiographic evidence of knee OA; Functional class I, II, III according to the American Rheumatism Association Treatment: 12 weeks (+ 12 month extension trial) Primary Endpoints: Changes in WOMAC pain (baseline to Week 12) Secondary Endpoints: WOMAC stiffness, WOMAC physical function, patient global assessment (VAS) *subject to regulatory approval

28 2007 CombinatoRx, Incorporated. All rights reserved. 28 CRx-102 Knee OA: Planned Trial Schematic* CRx /360 mg CRx /180 mg Screening (wash out NSAIDs) CRx /90 mg Safety Extension Prednisolone 2.7 mg Placebo Day - 7 Day 0 Day 7 Day 28 Day 56 Day 84 (Baseline visit) *subject to regulatory approval

29 2007 CombinatoRx, Incorporated. All rights reserved. 29 CRx-102 Development Status Initiate knee OA phase 2b trial: Mid 2007 Initiate RA CvP trial: 2H07 QD (1x/day) formulation available: 2H07 Initiate clinical comparability study for QD formulation: 1H08 Data from knee OA trial: 2H08 Data from RA trial: 2H08 Data from clinical comparability study: End 2008 Start Phase 3 trials: 1H09

30 2007 CombinatoRx, Incorporated. All rights reserved. 30 CombinatoRx Pipeline: 2007 Compound Discovery Preclinical Phase 1/2a Phase 2b Phase 3 CRx-102 CRx-170 CRx-139 CRx-150 CRx-026 CRx-191 CRx-197 CRx-401 RA/OA Chronic Pain RA Immuno-Inflammatory Multiple Tumors Topical Dermatology Topical Dermatology Diabetes Preclinical Programs Multiple Candidates Research: Hepatitis C Huntington s Ophthalmic Cystic Fibrosis Others Multiple Programs

31 CRx-170 in Chronic Pain CRx-170* Prednisolone DR Nortriptyline CR Synergistic combination of nortriptyline and ultra-low dose steroid Novel dual-action agent Combines analgesic activity of nortriptyline with anti-inflammatory activity of prednisolone Synergy enables low doses and broad therapeutic window Once-daily, night-time formulation for optimal therapeutic benefit Advancing into phase 2 trials in chronic pain *Formulation in development 2007 CombinatoRx, Incorporated. All rights reserved. 31

32 2007 CombinatoRx, Incorporated. All rights reserved. 32 TC + Steroid: Synergistic Combination Class Pro-inflammatory cytokines Steroid Budesonide (um) 0 1.5e-4 6.2e Inhibition (%) DT N=2-4 Average Joint Diameter (mm) In Vivo RA Control Placebo Steroid 3 mg/kg Steroid 0.3 mg/kg TC 5 mg/kg TC/Steroid Mean % Change in Forced Vital Capacity from Baseline 7% 6% 5% 4% 3% 2% 1% 0% Asthma Clinical Trial Mean% Change in Forced Vital Capacity 0.76% 1.04% 5.73% TC Steroid TC/Steroid In Vivo RA Decreased Bone Destruction CRx TC/Steroid Nortriptyline Hydrochloride (um) TC Adjuvant Eosinophils (10^6) in Lung Fluid Days TC + Steroid In Vivo Asthma * 1.5 * 1 * 0.5 Mean Change from Baseline- Response in Injured Paw % Change from Study BL In Vivo Pain % Change from Tx BL mean change from T0 to T1: p-value = Vehicle Diclofenac Steroid 1 mg/kg TC 3 mg/kg TC/Steroid 0 Unchallenged Vehicle Dex 0.3 mg/kg TC 10 mg/kg Steroid 0.3 mg/kg TC/Steroid -30

33 2007 CombinatoRx, Incorporated. All rights reserved. 33 CRx-170: Preclinical Pain Model Synergistic reduction in pain In Vitro In Vivo Nortriptyline Nortriptyline Prednisolone Prednisolone In Vitro TNFa Isobol at 20% inhibition; Pred (.99 um); Nortrip (3.4 um) In Vivo Pain model Isobol at 30 grams retraction force; Pred (.91 mg/kg) Nortrip ( 2.1 mg/kg)

34 Chronic Low Back Pain (CLBP) Pain and disability with episodes lasting > 3 months Prevalence of 30M in major markets (2005) 1 $15B+ in global sales in Tricyclics widely used to treat CLBP Proven activity in multiple randomized controlled trials 2 Anti-depressant use in 10 35% of CLBP patients 1,3 Majority of anti-depressant use from tricyclics Standard dosages of steroid only used intermittently Clear commercial opportunity Convert existing tricyclic prescriptions Capture market share from alternate classes 1 Decision Resources 2006; 3 CombinatoRx market research Dec Salerno et al. (2002); Atkinson et al. (1998) 2007 CombinatoRx, Incorporated. All rights reserved. 34

35 Novel Pharmacology Required CRx-170* Prednisolone DR Nortriptyline CR Plasma [ ] Prednisolone (4-6 h DR) Nortriptyline (CR) 10 pm 3 am 8 am Time *Formulation in development Synergy through co-exposure and optimized timing Builds on traditional tricyclic analgesic use at night plus CR for improved tolerability Prednisolone nocturnal release for optimal activity Using validated modified-release bead technology 2007 CombinatoRx, Incorporated. All rights reserved. 35

36 CRx-170 Chronic Pain: Planned Trial Design* Stage: Phase 2 Objective: Assess the efficacy of CRx-170 for the treatment of chronic low back pain Subjects: Study Design: Randomized, double-blind, placebo/active controlled Primary Comparison: Reduction in pain comparing CRx-170-treated subjects to patients treated with nortriptyline alone Enrollment Criteria: 3 months of low back pain with flare design Study Duration: 8 weeks Primary Endpoints: Pain reduction as measured through a visual analogue scale Secondary Endpoints: Improvement in back-related disability index, reduction of morning symptoms and quality of life assessments *subject to regulatory approval 2007 CombinatoRx, Incorporated. All rights reserved. 36

37 2007 CombinatoRx, Incorporated. All rights reserved. 37 CRx-170 Development Status Complete formulation development: 2H07 Initiate phase 2 study in CLBP: 2H07 Data from phase 2 study: 2H08

38 2007 CombinatoRx, Incorporated. All rights reserved. 38 CRx-191 Product Candidate Summary CRx-191 Mometasone / Nortriptyline Cream Synergistic combination of mometasone and nortriptyline Novel mechanism amplifies mometasone s desirable activities Target profile is efficacy of high-potency steroid, safety of midpotency steroid Novel topical formulation of nortriptyline Advancing into phase 2a trials

39 CRx-191: Psoriasis Market Opportunity Psoriasis prevalence of M US 1 Challenges to topical steroid use in psoriasis Mid-potency steroids well-tolerated, but have limited efficacy High potency steroids effective, but limited by skin atrophy and HPA-axis suppression Strong demand for topical dissociated steroid profile Efficacy of a high-potency steroid with the safety of a mid-potency steroid Potential to extend treatment duration vs. high potency steroid More rapid onset of action vs. mid-potency steroid Multiple expansion opportunities beyond psoriasis Total topical corticosteroid prescription sales > $1B WW 2 across indications 1 NIH, 2 Per-Se Technologies (formerly NDC Health Corporation) March CombinatoRx, Incorporated. All rights reserved. 39

40 2007 CombinatoRx, Incorporated. All rights reserved. 40 Rapid Proof-Of Of-Concept Goal: Demonstrate efficacy similar to high-potency corticosteroid Psoriasis Microplaque Test Up to six arms tested per subject subjects Two week treatment period Quantifiable, validated endpoints Skin thickness (sonography) Infiltrate erythema (chromametry) Clinical assessment

41 2007 CombinatoRx, Incorporated. All rights reserved. 41 CRx-191 Planned Trial Design* Objective Establish CRx-191 efficacy vs. components Design Psoriasis microplaque test Single-center study Double-blind, randomized Primary endpoint: Skin thickness vs. baseline CRx % Mometasone / High % Nortriptyline CRx % Mometasone / Low % Nortriptyline Screening High % Nortriptyline Low % Nortriptyline 0.1% Mometasone Vehicle Day - 7 Day 0 Day 3 Day 7 Day 10 Day 14 (Baseline visit) *subject to regulatory approval

42 2007 CombinatoRx, Incorporated. All rights reserved. 42 CRx-191: Development Status Preclinical toxicology studies in progress Initiate phase 2a trial in plaque psoriasis: Mid 2007 Initiate phase 2a skin atrophy toxicity study: Mid 2007 Data from both phase 2a trials: 2H07 Potential future clinical development in psoriasis and other steroid-responsive dermatoses (pending data)

43 2007 CombinatoRx, Incorporated. All rights reserved. 43 CRx-197 Product Candidate Summary CRx-197 Loratadine / Nortriptyline Cream Synergistic combination of loratadine and nortriptyline Novel mechanism, topical anti-inflammatory Synergistic action on IL-2 and other key cytokines involved in the pathogenesis of atopic dermatitis Novel topical formulations of loratadine and nortriptyline Advancing into phase 2a

44 CRx-197: Atopic Dermatitis Market Opportunity Prevalence: ~15M Atopic Dermatitis patients in the US 1 Significant unmet need Topical corticosteroids (a treatment mainstay) limited by steroidassociated side effects Rapid uptake of topical calcinueurin inhibitors at launch Elidel sales $348M US 2 (2004) following launch in 2001 Protopic sales $200M WW 3 (2004) following launch in 2000 However, Elidel and Protopic use limited by a 2005 FDA health advisory and 2006 black box warning Greater than 40% drop in sales since Continuing significant opportunity for novel MOA topical immunomodulatory agents Source: 1 National Institute of Arthritis and Muscoloskeletal and Skin Dieases, 2 Verispan 2004, 3 Astellas 2005 annual report, 4 Company reports 2005, CombinatoRx, Incorporated. All rights reserved. 44

45 2007 CombinatoRx, Incorporated. All rights reserved. 45 CRx-197 Planned Trial Design* Objective Establish CRx-197 efficacy vs. components Design Psoriasis microplaque test Single-center study Double-blind, randomized Primary endpoint: Skin thickness vs. baseline CRx-197 Loratadine [Dose 1] / Nortriptyline CRx-197 Loratadine [Dose 2] / Nortriptyline Screening CRx-197 Loratadine [Dose 3] / Nortriptyline CRx-197 Loratadine [Dose 4] / Nortriptyline Loratadine Vehicle Day - 7 Day 0 Day 3 Day 7 Day 10 Day 14 (Baseline visit) *subject to regulatory approval

46 2007 CombinatoRx, Incorporated. All rights reserved. 46 CRx-197: Development Status Initiate non-clinical toxicology program: 1H07 Initiate phase 2a trial in plaque psoriasis: 2H07 Data from phase 2a trial: 1H08 Future clinical development targeting atopic dermatitis (pending positive data)

47 CRx-401: Product Candidate Summary CRx-401* Bezafibrate SR Diflunisal IR Synergistic combination of bezafibrate (ex-us dyslipidemia agent) and low-dose diflunisal (analgesic salicylate derivative) Initial preclinical studies suggest novel mechanism with both PPAR and anti-inflammatory activities Demonstrated efficacy in decreasing fasting glucose and insulin resistance comparable to pioglitazone without promoting weight gain in vivo Improves lipid parameters by increasing HDL and decreasing triglycerides Advancing into phase 2a in Type 2 Diabetes *proposed bi-layered formulation in development 2007 CombinatoRx, Incorporated. All rights reserved. 47

48 CRx-401: Bezafibrate Lipid Benefit Bezafibrate is currently a standard of care drug for elevating HDL and reducing triglycerides HDL Triglycerides 25 Pioglitazone Atorvastatin Niacin (ER) Bezafibrate Change in HDL (%) Change in Tg (%) Pioglitazone Atorvastatin Niacin (ER) Bezafibrate -50 Source: Actos (30 mg/d). Package Insert 2004; Lipitor (20mg/d). Package Insert 2004; Niaspan Package Insert (1000 mg/d); Bezalip. Ogawa S. et al. Metabolism. March 2000, 49(3): CombinatoRx, Incorporated. All rights reserved. 48

49 CRx-401: Bezafibrate & Diabetes Bezafibrate also exhibits anti-diabetic properties Decreases fasting plasma glucose modestly in Type 2 diabetic patients and reduces insulin resistance 1 Reduces the incidence and delays the onset of Type 2 diabetes in high risk patients independent of the use of ACE inhibitors, BMI, LDL cholesterol, and triglyceride levels 2,3 Slows decline of beta cell function and increases insulin sensitivity in diabetics 3 Sources: 1 Matsui (1997), Oron-Herman (2005), Jia et al. (2004), Mori et al. (2004), Yuan et al. (2001), Harmon (2001), Pickavance (2005), Kim et al. (2001), Taniguchi et al (2001), Ogawa (2000), Alberti (1990), Mathur (1990), Rovellini (1992), Smud (1997), 2 Circulation May 11;109(18): , 3 Eur Heart J Oct;26(19): CombinatoRx, Incorporated. All rights reserved. 49

50 CRx-401: Preclinical Efficacy The combination of bezafibrate and diflunisal has demonstrated synergistic anti-diabetic benefits in-vitro and in-vivo In Vitro Isobologram Fasting Blood Glucose Insulin Resistance Fractional [ ] 2 Bezafibrate (35uM) Fractional [ ] 2 Diflunsal (100uM) Median Fasting Blood Glucose (mg/dl) Chow Vehicle Pio 6 mg/kg 196 Bez 30 mg/kg 215 DF 50 mg/kg * 182 CRx-401 Median HOMA Score Chow Vehicle Pio 6 mg/kg 20.0 Bez 30 mg/kg 23.2 DF 50 mg/kg * 8.1 CRx-401 High Fat Fed High Fat Fed Data presented in poster format at the American Diabetes Association 66th Scientific Sessions, June 9-13, 2006, Washington, DC. Values: Mean + SEM; * p< 0.05 vs. HFF (ANOVA). Fractional [ ] is fraction of drug concentration achieving 1.5 fold increase in glucose uptake as a single agent 2007 CombinatoRx, Incorporated. All rights reserved. 50

51 CRx-401: Preclinical Efficacy The anti-diabetic benefits are not associated with weight gain Weight Gain Mean % Change in Body Weight Chow Vehicle Pio 10 mg/kg CRx-401 * High Fat Fed Data presented in poster format at the American Diabetes Association 66th Scientific Sessions, June 9-13, 2006, Washington, DC. Values: Mean + SEM; * p< 0.05 vs. Chow (ANOVA) 2007 CombinatoRx, Incorporated. All rights reserved. 51

52 2007 CombinatoRx, Incorporated. All rights reserved. 52 CRx-401: Metabolic Syndrome Through combined insulin, glucose and lipid actions, CRx-401 may offer a novel metabolic syndrome profile Glucose Insulin Resistance Triglyceride HDL LDL Obesity Blood Pressure CRx-401 Development Pipeline GLP-1 Agonists (Byetta, Januvia) Dual PPAR Agonists Fenofibrate + Metformin CETPi Multiple (Acomplia) Current Treatment TZDs TZD+Metformin Metformin Secretagogues Insulin Fibrates Statin + Niacin Statins Orlistat Sibutramine Multiple

53 2007 CombinatoRx, Incorporated. All rights reserved. 53 CRx-401: Market Opportunity The unmet need is substantial and opportunities exist in first line, second line, and custom market segments Market Segment Diagnosed and treated with oral anti-diabetic agents Poorly controlled on existing therapeutics Poorly controlled plus elevated triglycerides and low HDL Market Size ~ 28 MM ~ 10 MM ~ 2.7 MM CRx-401 Market Opportunity Novel MOA for glycemic control Improve lipid profile Weight-neutral Novel MOA to complement standard agents and improve glycemic control Weight-neutral vs glitazones/dual PPARs Improve lipid profile Novel MOA for glycemic control Lower TG and raise HDL to address key patient need Weight-neutral Source: Decision Resources Type 2 Diabetes September 2004: Estimated patient numbers in 2008.Harrison s Principles of Internal Medicine; Alexander et al., Diabetes, Vol. 52, May, 2003, CombinatoRx analysis

54 CRx-401: Planned Trial Design* Stage: Phase 2a Objective: Demonstrate that CRx-401 is superior to bezafibrate alone in lowering fasting plasma glucose Subjects: 80 patients (2 arms) Study Design: Randomized, controlled Primary Comparison: CRx-401 to bezafibrate Enrollment Criteria: Type-2 diabetics who are poorly controlled on metformin Treatment: 12 weeks Primary Endpoints: Changes in fasting plasma glucose Other Measures: HbA1c, Triglycerides, HDL, HOMA-IR, and Weight *subject to regulatory approval 2007 CombinatoRx, Incorporated. All rights reserved. 54

55 2007 CombinatoRx, Incorporated. All rights reserved. 55 CRx-401: Development Status Initiate phase 2a trial in Type 2 diabetes: Mid 2007 Data from phase 2a trial expected: Mid 2008

56 2007 CombinatoRx, Incorporated. All rights reserved. 56 CombinatoRx Pipeline: 2007 Compound Discovery Preclinical Phase 1/2a Phase 2b Phase 3 CRx-102 CRx-170 CRx-139 CRx-150 CRx-026 CRx-191 CRx-197 CRx-401 RA/OA Chronic Pain RA Immuno-Inflammatory Multiple Tumors Topical Dermatology Topical Dermatology Diabetes Preclinical Programs Multiple Candidates Research: Hepatitis C Huntington s Ophthalmic Cystic Fibrosis Others Multiple Programs

57 2007 CombinatoRx, Incorporated. All rights reserved Milestones Program Activity Target CRx-139 Data: Phase 2a, 210 subject, 3 arm, RA trial CRx-150 Data: Phase 2a, 60+ subject, RA trial 1H07 CRx-191 CRx-401 CRx-102 CRx-102 CRx-191 CRx-170 CRx-197 CRx-102 Initiate: Phase 2a topical dermatology (psoriasis) Initiate: Phase 2a type 2 diabetes Initiate: Phase 2b knee OA Initiate: Phase 2b RA Data: Phase 2a topical dermatology (psoriasis) Initiate: Phase 2 chronic lower back pain Initiate: Phase 2a topical dermatology (psoriasis) Complete: QD formulation Mid07 2H07

58 2007 CombinatoRx, Incorporated. All rights reserved Milestones Program Activity Target CRx-197 Data: Phase 2a topical dermatology (psoriasis) CRx-102 Initiate: Clinical comparability study 1H08 CRx-401 Data: Phase 2a type 2 diabetes Mid08 CRx-170 CRx-102 CRx-102 CRx-102 Data: Phase 2 chronic lower back pain Data: Phase 2b knee OA Data: Phase 2b RA Data: Clinical comparability study 2H08

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