1 August 2003 Elements of a Profitable Biopharmacutical Company Roland E. Dolle September 24, 2003

2 August 2003 Outline Evolution of biotech business models Adolor Corporation

3 August 2003 Business model evolution 1980s: Product-based

4 August 2003 Business model evolution 1980s: Product-based R&D + Sales & Marketing Some big success stories - Amgen, Genentec More companies failed than succeeded Many unfulfilled promises

5 August 2003 Business model evolution Project risks Failure to optimize a lead into a clinical candidate Clinical candidate failure on safety, PK Failure of mechanism to treat disease Failure to differentiate over existing treatments Failure to make a return on investment if launched

6 August 2003 Business model evolution Attrition prior to Phase II Biggest problem as a percent >80% loss prior to NDA Attrition in Phase II and later Biggest problem in cost Target validation issue

7 August 2003 Business model evolution 1980s: Product-based companies 1990s: Technology-based companies

8 August 2003 Business model evolution 1990s: Technology-based Genomic platforms Combinatorial chemistry platforms Miscellaneous drug discovery services Investor rationale Product-based model seen as too risky Enabling technology will accelerate R Instant revenue stream ($$)

9 August 2003 Business model evolution Reality Genomic and combichem platforms did not live up to expectation (over sold) More targets - but not validated More compounds - but not drug-like Drugs to market have been declining while expenditures escalating Profit margins slim Tech-based companies can’t “hit the home-run” Little up-side potential for shareholders

10 August 2003 Business model evolution 1980s: Product-based 1990s: Technology-based 2000s: Product-based

11 August 2003 Business model evolution 2000s: Product-based Pure technology service platforms - out of favor Technology companies transforming themselves into product-based companies Miscellaneous drug discovery services - moving outside of U.S.

12 August 2003 Business model evolution Example: Millennium Pharmaceuticals (Boston, MA) 1993: Genomic screening platform (target validation) 1997: ChemGenics acquired for library screening and lead optimization 1999: LeukoSite acquired for clinical development and product pipeline 2000: Cambridge Discovery acquired for chemistry/screening 2001: CorTherapeutics acquired for clinical product including sales and marketing infrastructure 2003: Restructuring initiative shuttered R&D in San Francisco, Cambridge, England 2004: Plans to cut staff by 26% to focus on drug development and commercialization

13 August 2003 Product-based Business Model of the 2000s Must build profitable business Build the company in stages Corporate alliances/partnerships Technology Management expertise Finance Target ID Validation Drug Discovery Development Sales & Marketing

14 August 2003 Build a profitable pharmaceutical company specializing in the discovery, licensing, acquisition, development and commercialization of prescription pain management products. Mission

15 August 2003 Forward-Looking Statements This presentation and the questions and answers that follow contain forward-looking statements including but not limited to statements about the following: Our forward-looking statements are subject to risks and uncertainties, known and unknown, that could cause actual results and developments to differ materially from those expressed or implied in such statements. Further information about these and other relevant risks and uncertainties may be found in Adolor’s filings with the SEC, available in its EDGAR database at and from Adolor at Given the uncertainties affecting pharmaceutical companies in the development stage, you are cautioned not to place undue reliance on any such forward-looking statements, any of which may turn out to be wrong due to inaccurate assumptions, unknown risks, uncertainties or other factors. Adolor undertakes no obligation to publicly update or revise the statements made herein or the risk factors that may relate thereto. Our ability to submit, if positive confirming results are achieved in our other studies, our alvimopan clinical study 302 in an NDA Our ability to achieve positive confirming results in the other alvimopan Phase 3 clinical studies Our target dates for completing accrual and announcing results in our alvimopan clinical studies 308 and 313 Our target date to submit an NDA for alvimopan in the first half of 2004 Our alvimopan clinical study 304 results and plans for further development of alvimopan in opioid bowel dysfunction Our ability to complete a Phase 2 study for ADL in late 2004 Our ability to submit an NDA for ADL in 2006 Our product development efforts, including results from clinical trials Anticipated dates of clinical trial initiation, completion, and announcement of trial results Anticipated trial results and regulatory filing dates for our product candidates Analysis and interpretation of data by regulatory authorities; the status and anticipated timing of regulatory approval for our product candidates Anticipated operating losses and capital expenditures Our intentions regarding the establishment of collaborations Anticipated efforts of our collaborators, including initiation of clinical studies of alvimopan in opioid bowel dysfunction in 2003 Our intention to rely on third parties for manufacturing Our plans to build a hospital-focused sales force Estimates of the market opportunity and the commercialization plans for our product candidates, including our plans for the establishment of a sales force

16 August 2003 Profile Capabilities  130 employees: from discovery and clinical research to business development, manufacturing and marketing Alvimopan  Peripheral mu opioid receptor antagonist developed to manage negative gastrointestinal (G.I.) side effects of opioid pain products  Positive results in late-stage clinical trials in two distinct indications  Substantial potential market opportunities in both hospital and out-patient settings  GlaxoSmithKline partner for collaborative development and commercialization ADL  Sterile lidocaine impregnated patch being developed for management of postoperative incisional pain in North America  Potential customer synergy with alvimopan Discovery  Research focus on cannabinoid, delta, kappa, mixed mu/kappa, peripheral mu and other receptor targets

17 August 2003 Importance of Pain Management/Treatment Pain costs approximately $100 Billion in treatment and lost productivity  Most common symptom that causes people to seek medical care in the U.S. Recognition and Acceptance  Pain - “The Fifth Vital Sign” as defined by the American Pain Society  The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) developed guidelines in 1999 that mandates hospitals recognize the rights of patients to appropriate assessment and management of pain Market Potential  Total U.S. market for pain pharmaceuticals: $15 billion  Opioids in U.S.: 190 million annual prescriptions; $4.6 billion in sales  Increasing number of surgeries/aging population

18 August 2003 ProgramR & DPhase 1Phase 2Phase 3 Postoperative Ileus Chronic Opioid Induced Bowel Dysfunction Acute Opioid Induced Bowel Dysfunction Pain Postoperative Incisional Pain Post-surgical/Inflammatory/ Visceral Pain Joint Pain Neuropathic Pain Irritable Bowel Syndrome Post-surgical/Inflammatory Pain Alvimopan Kappa Peripheral Mu Delta R & D Pipeline Mixed Mu/Kappa Cannabinoid Agonist ADL Combination Product (alvimopan + opioid)

19 August 2003 Alvimopan Selectively Antagonizes GI Opioid Receptors Opioid Bowel Dysfunction Peripheral Mu Opioid Receptors in Bowel Central Mu Opioid Receptor Postoperative Ileus Mu Opioid Narcotic Analgesics: - morphine - codeine - oxycodone AlvimopanMechanism Of Action

20 August 2003 Postoperative Ileus POI is a temporary impairment of gastrointestinal motility after abdominal or other surgeries Severity / duration is associated with type of intra- abdominal surgery Opioid analgesics used for postoperative pain delay G.I. recovery Patient recovery and recovery of G.I. function is often rate limiting in patient satisfaction and hospital discharge No FDA approved drugs for this indication; current treatments are not adequate

21 August 2003 Alvimopan for the Management of Postoperative Ileus - Studies 302, 308, 313 Design Double-blind, placebo-controlled, multi-center Placebo, 6 mg, 12 mg, equal randomization First dose at least two hours prior to surgery, and then twice a day until hospital discharge or up to 7 days post-surgery Postoperative pain management with intravenous Patient Controlled Analgesia (PCA pump) with opioids Subjects Limited simple hysterectomies  20% max in Study 302 and 308; none in Study 313 Radical hysterectomy; large bowel resection Small bowel resection (Studies 308 and 313)

22 August 2003 Primary Efficacy Endpoint  Time to recovery of gastrointestinal (G.I.) function (composite endpoint is upper AND lower G.I. recovery) Time to upper G.I. recovery: tolerating solid foods Time to lower G.I. recovery: flatus or bowel movement Secondary Efficacy Endpoints  Proportion of Responders  Time to be Ready for Discharge based solely on Recovery of Gastrointestinal Function  Time to First Solid Food  Time to Hospital Discharge Order Written  Time to First Flatus  Time to First Bowel Movement Alvimopan for the Management of Postoperative Ileus - Studies 302, 308, 313

23 August 2003 Alvimopan for the Management of Postoperative Ileus – Study 302 Pre-specified primary analysis method Cox proportional hazard model 6 mg dose vs. placebo Cox hazard ratio = 1.47 P < of 6 secondary endpoints statistically significant (P = for other) 12 mg dose vs. placebo Positive Trend  Cox hazard ratio = 1.23  P = 0.11 Statistically significant P <0.01 in proportion of responders (first order secondary endpoint) Statistical Analysis

24 August 2003 Specified Primary Endpoint Analysis: Time to Recovery of GI Function - Alvimopan Study mg vs. placebo: hazard ratio = 1.47, P<0.01 (Cox Proportional Hazard Model) 6 mg Placebo 16 hour faster average recovery of G.I. function 14 hour earlier average time of hospital discharge order written

25 August 2003 Number of Subjects Who Had Hospital Discharge Order Written- Alvimopan Study Hospital Days:

26 August 2003 Most frequent adverse events were: Placebo6 mg12 mg n = 153n = 150n = 146 Nausea67.3%64.0%56.8% Vomiting32.0%25.3%15.1% Hypotension15.0%12.0%11.6% Discontinuations for adverse events: 14.4%6.7%17.8% Alvimopan for the Management of Postoperative Ileus - Study 302

27 August 2003 Alvimopan for the Management of Postoperative Ileus - Development Targets Studies Accrual Completion TargetsSubjects 302Complete Complete Q3 – Q4Enrolling 313Complete510 »NDA submission will depend on achieving confirmatory clinical trial results; timing of any submission is dependent on timing of accrual completion and other factors. NDA Submission Target First half 2004

28 August 2003 Approximately 50 million Americans suffer from chronic pain  Back Pain - 27 million  Osteoarthritis - 20 million  Other pain syndromes - 3 million 190 million prescriptions for opioids written in the U.S. each year  Approximately 30 million of those prescriptions are for 14 or more days’ medication 40% of patients on long term opioid therapy meet the clinical definition of constipation (< 3 bm / per week) Chronic Pain Market U.S.

29 August 2003 Alvimopan for the Management of Chronic Opioid Bowel Dysfunction (OBD) - Study 304 Double-blind, randomized, placebo control Inclusion Criteria  On chronic opioid therapy for at least one month  Have opioid-induced bowel dysfunction N = 168 in chronic pain or methadone maintenance Alvimopan 0.5 or 1.0 mg or placebo 3 weeks (21 days) consecutive daily dosing Primary Efficacy Endpoint  Average proportion of patients having bowel movement within 8 hours following oral medication, measured each day during the 21- day study

30 August 2003 Average proportion of patients with bowel movement < 8 hours of dose measured each day during the 21-day study 29% 43% 55% P < Alvimopan for the Management of Chronic Opioid Bowel Dysfunction (OBD) - Study 304

31 August 2003 Alvimopan for the Management of Chronic Opioid Bowel Dysfunction (OBD) Long-term preclinical toxicity studies initiated Two clinical studies in OBD targeted for initiation in 2003  Will test dosing regimen and extended duration dosing in: -malignant pain patients -chronic pain patients GlaxoSmithKline is primarily responsible for the completion of the OBD development program

32 August 2003 Acute Care Hospital Products POI, Acute OBD Additional Products (Adolor Products) Chronic Care Outpatient Products Chronic OBD, Additional Products (G.I. Products) ROW GSK Develops & Sells Royalty to Adolor U.S. Co-Development/ Co-Promotion Profit Split Co-Development/ Co-Promotion Profit Split Adolor/GlaxoSmithKline - Alvimopan Collaboration $50 million upfront $220 million in milestones Development expense sharing for POI, Acute & Chronic OBD indications in U.S. Adolor supplies API

33 August 2003 Adolor R & D Strategy Utilize proprietary position in opioid receptors and expertise in combinatorial chemistry to develop novel small-molecule therapeutics Collaborate at appropriate value points with established partners for:  Chronic care in the U.S.  Opportunities outside the U.S. Complement internal development efforts with in-licensing and M & A

34 August 2003 Discovery and Outsourcing Established relationship with CiVentiChem in 2002 Expanded relationship in 2003 Supplied critical intermediates for discovery operations Viewed as an extension of internal research group

35 August 2003 Summary Product platform in pain management Alvimopan:  A potential first-in-class product candidate with substantial potential market opportunities  ADL : Multi-target, pain-focused discovery research program Target ID Validation Drug Discovery Development Sales & Marketing