1. Dr. Geoffrey W. Guy Executive Chairman GW Pharmaceuticals plc, UK NIH, 21 April 2005

2. GW Pharmaceuticals plc Founded in 1998 by Dr Geoffrey Guy and Dr Brian Whittle All research carried out under UK Government licences. Strong support from UK Home Office (Drugs Branch). Total investment raised - £60 million (US $110m) Publicly traded on London Stock Exchange Located on 4 UK sites 110 staff –Integrated R&D infrastructure (CMC, clinical, regulatory) Marketing partnership with Bayer HealthCare in UK and Canada Lead product, Sativex ® buccal spray, approved in Canada April 2005 Neuropathic Pain in Multiple Sclerosis

3. Sativex ® emphasises the importance of pharmaceutical solution –Required to meet standards of modern medicine: quality, safety, efficacy –Standardized for composition and dosage –Non-smoked; delivered like other pharmaceutical products –Maintains integrity of physician-patient relationship –Clinical studies ensure physicians have appropriate prescribing information –Prescription only; patients obtain only through monitored health care sources, i.e., pharmacy –Reimbursed by health insurance –Eliminates physician liability for recommending unapproved drug –Legal; no patient stigma –Remove patients from the broader controversy over marijuana Sativex: Public Health Rationale

4. Cannabinoid System CB1 and CB2 receptors Pain, movement, neuromodulation, smooth muscle, inflammation, cytoprotection, feeding, perception, reward, cognition Pre-synaptic at Dopamine, GABA, Glutamate, 5HT, NA, ACH… Cross-talk – endorphine, vanilloid - organs Effects – TNF, ILs, NO, oxygen radicals, anti-oxidant Endocannabinoids: –Anandamide (AEA), 2-Arachidonoylglycerol (2-AG), Noladin ether, Virodhamine, N ‑ arachidonoyl ‑ dopamine (NADA), Arachidonoyl ‑ serine (ARA ‑ S) Homeostatic super-modulatory system

5. Phyto-Cannabinoids Cannabinoids - molecules unique to the cannabis plant Initial focus on two principal cannabinoids: THC (Tetrahydrocannabinol) and CBD (Cannabidiol) THCAnalgesic, Anti-spasmodic, Anti-tremor, Anti-inflammatory, Appetite stimulant, Anti-emetic CBDAnti-inflammatory, Anti-convulsant, Anti-psychotic Anti-oxidant, Neuroprotective, Immunomodulator Other Cannabinoids CBC(Cannabichromene) CBG(Cannabigerol) CBN(Cannabinol) THC-V / CBC-V (Propyl derivatives)

6. Cannabinoid Therapeutic Window Objective: To provide and maintain therapeutic blood and tissue levels of key cannabinoid components without incurring unacceptable side effects Challenges –Inter-subject pharmacokinetic variability –Minimise Side Effects (psychoactivity) caused by rapid rate of rise of plasma levels –Limitations to oral route –Poor aqueous solubility Predictable Maintenance of acceptable risk / benefit

7. THC plasma levels following administration of 6.65mg* of vaporised THC

8. Cannabinoid Therapeutic Window - Solutions Cannabinoid ratios widen window –CBD counters some of the side effects –CBD delays and reduces intensity of intoxication Route and method of delivery (DDS) –Mucosal route far less variable than Oral (GI) –Mucosal absorption decreases first pass Rate of absorption controlled and matches rate of redistribution in to lipid compartment Formulation and dosage form –Oromucosal spray Self-titration –Predictability Predictable Maintenance Within Therapeutic Window Is Achieved

10. THC Plasma levels following administration of 4 sprays of Sativex ® (10.8mg THC & 10mg CBD # )

11. Comparison of THC plasma levels following administration of 6.65mg* of vaporised THC or 4 sprays of Sativex ® (10.8mg THC & 10mg CBD # )

12. Cannabinoid Botanical Medicines Breeding and cultivation of cannabis plant varieties –Varieties bred for content of selected cannabinoid molecules –Strict control of growing environment Controlled breeding of cloned plants Computer-controlled glasshouses Strict quality control procedures Standardised whole plant extracts (GMP extraction) Formulation into non-smoked drug delivery systems Full commercial pharmaceutical development programme including pre-clinical and clinical research Submission and approval from regulatory authorities Data must provide robust evidence for Quality, Safety, Efficacy Data must provide robust evidence for Quality, Safety, Efficacy

13. Quality

14. Control of Starting Materials: Chemovar Consistency Extracts produced from specially bred plants (“chemovars”) Result of a 15 Year Breeding Programme Each plant selectively bred for: –High rate of cannabinoid production –High yield of cannabinoid per unit area –High level of purity of the desired cannabinoid (purity as used here defines the consistency of cannabinoid content as a ratio) –High inflorescence to leaf ratio (the ‘harvest index’) –Natural resistance to pests and diseases –Sturdy growth capable of bulk plant handling –Ease of harvesting –Minimal production of anthers on female plants –Plant height –Optimal time to flowering (critical day length)

15. Propagation from ‘mother plants’ Grow plants under controlled conditions (light, water, growth medium, heat, humidity, pest control) Harvest plants Dry plants under controlled conditions (temperature, humidity, light exclusion) Mill dried plant to defined particle size QC & Release Botanical Raw Material (BRM; contains: THCA + CBDA) Strip dried plants from stems Apply BRM specification Control of Starting Materials: GAP Cultivation

17. GMP Extraction Storage of BRM under appropriate conditions Selection of batch of stored BRM for extraction Controlled decarboxylation of BRM Primary Extraction of BRM under controlled conditions Secondary Extract – Botanical Drug Substance (BDS) QC & Release BDS (contains: THC + CBD) Apply BDS specification QC sampling / Release QC / In process control Further processing of Primary Extract under controlled conditions Apply macro / micro appearance

18. GMP Manufacture Storage of BDS under appropriate conditions Selection of batch of stored BDS for formulation Dissolve BDS in Solvent 1 Dissolved BDS in vehicle Filter & fill final bulk Solution – Botanical Drug Product (BDP) QC & Release BDP (contains: THC + CBD) Apply BDP specification QC sampling / Release Add Solvent 2 Mix final bulk solution Add Flavouring QC / In process control

19. Sativex ® Characterisation Principal Cannabinoids –THC*27 mg/ml –CBD*25 mg/ml Minor Cannabinoids –CBC*, CBG*, CBN*, THC-V*, CBD-V*, THCA*, CBDA*, CBO #, CBE #, CBC-V, CBL Terpenes –trans-caryophyllene #, α-caryophyllene #, caryophyllene oxide, –α-pinene, β-pinene, terpinolene, myrcene, limonene, linalool –cis-nerolidol, trans-nerolidol, phytol, squalene Carotenoids –β-carotene # Fatty Acids –Linoleic acid, Palmitoleic acid, Linolenic acid, Palmitic acid, Oleic acid, Stearic acid, Myristic acid, Arachidic acid and Behenic acid Sterols –Β-sitosterol, campesterol, stigmasterol Vitamins –Vitamin E Triglycerides –Trilinolenin, Trilinolein……. *Items controlled in the BDP specification # Items controlled in the BDS specification

20. THCV Results Summary –THCV (e.g. 10 nM) antagonized WIN55212-2- & anandamide-induced inhibition of electrically-evoked contractions of the mouse vas deferens in a competitive, surmountable manner. – THCV (100 nM) did not antagonize clonidine-induced inhibition of electrically-evoked contractions of the mouse vas deferens. – A concentration of THCV that markedly antagonized WIN55212-2 and anandamide did not modulate contractile responses to bg-methylene-ATP or phenylephrine. – THCV was significantly less potent in displacing [3H]CP55940 from specific binding sites on mouse brain membranes (Ki = 80 nM) than as an antagonist of WIN55212-2 (KB = 1.5 nM) or anandamide (KB = 1.4 nM) in the mouse vas deferens. – Hence, the target for which THCV apparently competes with WIN55212-2 & anandamide may not be a CB1 receptor.

21. THCV Pharmacology Modulates / modifies CNS effects of THC Had been considered as less potent agonist at CB1 THCV (e.g. 10 nM) antagonized WIN55212-2- & anandamide-induced inhibition of electrically-evoked contractions of the mouse vas deferens in a competitive, surmountable manner. This it does as potently as the established CB1 agonist, SR141716A (Rimonabant- Sanofi) Two targets for THCV seem to be present in the vas deferens The CB1 receptor A second non-CB1 target Further experiments are required to investigate the location of this putative non-CB1 target in the vas deferens the distribution of this putative non-CB1 outside the vas deferens the nature of this putative non-CB1 target SAR of ligands that interact with this putative non-CB1 target Further experiments are also required to investigate –if & how THCV modulates activity of the endocannabinoid system –the clinical consequences of any such modulation

22. THCV Implications THCV may therefore have therapeutic use as: Appetite suppressant Cessation of addictive behaviour (e.g. smoking) Treatment for disorders which are abnormalities of CB1 mediated processes: –movement and postural control, pain and sensory perception, memory, cognition, emotion, autonomic and endocrine functions –obesity, schizophrenia, epilepsy or cognitive disorders such as Alzheimers, bone disorders, bulimia, obesity associated with type II diabetes (non-insulin dependant diabetes) –the treatment of drug, alcohol or nicotine abuse or dependency

23. PRODUCTINDICATIONPre-clinPhase IPhase IIPhase III Submit Approval Sativex Multiple Sclerosis THC:CBD MS Pain (1:1 ratio)MS Spasticity MS Bladder Peripheral Neuropathic Pain Allodynia Diabetic Neuropathy Central Neuropathic Pain MS Brachial Plexus Spinal Cord Injury Cancer Pain High CBDRheumatoid Arthritis ratiosInflammatory Bowel Diseases Neurogenic Symptoms Psychotic Disorders CNS (Epilepsy / Neuroprotection) High THCPost-operative Pain Chronic Pain THC-VNeurotherapeutics MethadoneDrug Dependency DiamorphineDrug Dependency Product Portfolio

24. Safety & Efficacy: Clinical Program

25. Over 1500 subjects participated in clinical program to date Approx 1000 patient-years of safety data Substantial body of positive clinical data –7 Phase III trials –5 Phase II trials –13 Phase I trials –Long term extension studies All patients remain on current medication throughout trials, hence improvements seen are over and above that achieved with available medication 2 additional Phase III trials fully recruited and due to report in H1 2005 No evidence of diversion/abuse to date Results presented at scientific meetings and published in peer reviewed journals Clinical Trials Program

26. Positive Findings in Phase II & III Studies StudyKey ResultP-value PHASE III STUDIES MS Spasticity (n=189)Spasticity0.048 MS Symptoms (n=160) Spasticity Sleep 0.001 0.047 MS Neuropathic Pain (n=66) Pain Sleep 0.005 0.003 Neuropathic Pain (allodynia) (n=125) Pain Sleep 0.004 0.001 Cancer Pain (n=177) Pain Constipation 0.014 0.077 Pain in MS / other conditions (n=70) Pain (escape meds) 0.004 Neuropathic Pain (Brachial Plexus) (n=48) Pain, Sleep 0.005 0.017

27. Positive Findings in Phase II & III Studies StudyKey ResultP-value PHASE II STUDIES MS / Spinal Cord Injury (n=34) Pain Sleep<0.0001 MS Symptoms (n=25) Spasticity Sleep 0.042 0.024 MS Bladder (n=21) Incontinence Nocturia Urgency Frequency<0.05 <0.05 Rheumatoid arthritis (n=58) Pain Sleep Disease Activity 0.018 0.027 0.002

28. Multi centre, double-blind, randomised, placebo-controlled parallel group study of Sativex for the treatment of peripheral neuropathic pain characterised by allodynia N=125 (n=63 Sativex, n=62 placebo) Treatment duration: 5 weeks 6 study centres All patients remain on current medication throughout trial Primary endpoint –Change from baseline in average daily pain score after 5 weeks of treatment, evaluated from daily pain diaries and measured on a Numerical Rating Scale (NRS, 0-10) of pain severity Range of secondary endpoints, including sleep disturbance, allodynia, Pain Disability Index Phase III Trial: Peripheral Neuropathic Pain Abstract presented by Dr. M. Serpell at the UK Pain Society Meeting, Edinburgh, Scotland: 08-11 March 2005; Abstract accepted for poster presentation by Dr M Serpell at ENS, Vienna, 18-22 June, Also presented by Prof. T. J. Nurmikko to the American Academy of Neurology (AAN), Miami, FL, USA 09-16 April 2005, and IASP, Sydney, 21-26 August 2005

29. Phase III Trial: Study Design Peripheral Neuropathic Pain Randomised Treatment Period (5 weeks) Titration Period 1 week V1 Day 0 Baseline No Treatment Study Entry SATIVEX ® Placebo Open Label Extension Study GWEXT0102 Randomisation & Dose Introduction Completion / Withdrawal 4 weeks steady state 1 week 4 weeks V2 Day 7 V3 Day 14 V4 Final Day 42

30. Peripheral Neuropathic Pain Study Dosing

31. Peripheral Neuropathic Pain: Improvement in NRS Pain Score from BL

32. Peripheral Neuropathic Pain: NRS Pain Scores: Responder Analysis

33. Peripheral Neuropathic Pain: Total PDI Score - Improvement from BL

34. Phase III Trial: Study Design Central Neuropathic Pain in MS Double blind, randomised, parallel group placebo controlled study of Sativex in central neuropathic pain in MS Single UK Centre Study N = 66 Treatment duration: 5 weeks All patients remain on current medication throughout trial Primary endpoint –Change from baseline in pain score averaged over last 7 days, evaluated from daily pain diaries and measured on a Numerical Rating Scale (NRS, 0-10) of pain severity Range of secondary endpoints, including neuropathic pain scale, sleep disturbance Abstract presented by Dr. D. Rog at ECTRIMS 2003, September 17–20, 2003, Milan, Italy Abstract presented by Dr D Rog at the American Pain Society, Boston, MA, USA, 30 March – 02 April 2005 Abstract submitted by Dr D Rog to CAPM&R Conference, Ottowa, June 15-18 2005 Abstract submitted by Dr. C.A. Young to IASP, Sydney, 21-26 August 2005

35. Phase III Trial: Central Neuropathic Pain in MS: Dosing SATIVEX ®

36. Central Neuropathic Pain in MS Improvement in NRS Pain Scores from BL p-value obtained using ANCOVA, ITT Scale = BS11 Scale 0-10

37. Central Neuropathic Pain in MS Neuropathic Pain Scale Scores Mean Change from Baseline Scale = 0-100 0=No Pain, 100=Worst Possible p-value obtained using ANCOVA, using Adjusted Means, ITT

38. Neuropathic Pain in MS Study Reduction in Sleep Disturbance Week 4 Analysis p=-value obtained using ANCOVA, ITT Scale = 0-10: 0 = did not disrupt 10=completely disrupts

39. Phase III Trial: Cancer Pain Design: –Double blind, randomised, parallel group, placebo controlled, comparative study of Sativex and THC extract in patients with cancer pain –14-20 days treatment period Investigators: –20+ Centres Countries: –UK, Belgium & Romania No. of Patients: –N = 177 (n=60 Sativex ®, n=58 THC extract, n=59 placebo) Patient characteristics: -Pain not wholly relieved by strong opioids (e.g. morphine) -Patients remain on existing opioid treatment during trial Abstract presented by Dr. J. R. Johnson at the UK Pain Society Meeting, Edinburgh, Scotland: 08-11 March 2005. Abstract submitted by Dr J. Johnson to IASP, Sydney 21-26 August 2005.

40. Phase III Trial: Cancer Pain Pain Scores (ITT)

41. Phase III Trial: Cancer Pain Responder Analysis (ITT)

42. Safety: Adverse Event (AE) Type The Adverse Events likely to be present on Product Label are as follows: –Ear & Labyrinth disorders Vertigo –Gastrointestinal disorders Dry mouth, Nausea, Oral discomfort, oral pain, diarrhoea, mouth ulceration –General disorders and administration site conditions Application site pain, fatigue, feeling drunk, weakness, falling, lethargy, thirst. –Metabolism and Nutrition disorders –Appetite increased –Nervous system disorders Disturbance in attention, dizziness, somnolence. –Psychiatric disorders Disorientation, euphoric mood, dissociation. –Respiratory, thoracic and mediastinal disorders Pharyngitis These are AEs most frequently observed in the SATIVEX ® group in Phase III clinical trials and not seen at an equivalent incidence among placebo treated patients (greater than 3% incidence and SATIVEX ® to placebo odds ratio  2)

43. Safety & Efficacy: Long Term Data

44. Tolerance: Definition “Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time.” Consensus from American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine

45. Tolerance: Efficacy v Safety Tolerance: Undesirable: Loss of efficacy / beneficial effects or requirement for increasing dose to achieve same effect Desirable: Loss / reduction in incidence /severity of side effects

46. Multiple Sclerosis Symptoms Long Term Data

47. Multiple Sclerosis Symptoms Long Term Data Dosing Data

48. Pain Long Term Data Dosing Data CBM 1:1

49. Preliminary Long Term Data Intoxication Scores n=137

50. Budney criteria: Suggested definition of syndrome of ≥4 symptoms: anger or aggression, decreased appetite or weight loss, irritability, nervousness or anxiety, restlessness, sleep difficulties or strange dreams, chills, depression, stomach pain, shakiness, sweating plus “evidence that these symptoms produced clinically significant distress or dysfunction” Investigation of A Cannabinoid Withdrawal Syndrome: Experiences with Sativex ® Budney AJ et al. Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry 2004;161(11):1967-77.

51. Effects of Cessation of Treatment with Sativex ® in patients on long-term treatment Aim: –To assess whether abrupt discontinuation of Sativex ® cannabis based oromucosal medicine from long-term multiple sclerosis (MS) patients would result in a consistent withdrawal syndrome Methods –Subjects had completed at least one year of therapy, and had a stable medical regimen for at least 2 weeks –Invited to discontinue Sativex ® suddenly for 2 weeks with option to continue an additional 2 weeks –At end of withdrawal, subjects rated MS symptoms as ‘much worse’, ‘worse’, ‘no change’, ‘better’, or ‘much better’ –New symptoms were monitored –Subjects then opted to resume Sativex ® or discontinue it Sample Size –N= 62 screened (33 declined to participate - i.e. refused to discontinue Sativex ® ) –3 were deemed unsuitable by PI –N= 26 enrolled, n=25 produced evaluable data

52. Effects of Cessation of Treatment with Sativex ® (continued) Results –Efficacy 26 patients (80%) completed 2 weeks of Sativex ® abstinence, 25 with evaluable data A total of 22 patients (88%) returned to treatment with Sativex ® overall –5 patients (20%) resumed Sativex ® during the 2 weeks due to MS symptom recurrence –7 patients (28%) opted for a 2 nd 2-week abstinence - 5 of these (71%) then resumed long-term Sativex ® –2 remained off of Sativex ® due to lack of symptom worsening –1 further withdrawal due to house move out of the area 17 patients (68%) reported that their symptoms were “Worse or “Much Worse” off treatment (Global Assessment) 17 patients (68%) reported that 2 or more symptoms had worsened off treatment (VAS Scores) A total of 22 patients (88%) returned to treatment with Sativex ® overall Mean Sativex ® dose was 13 sprays/day (35.1 mg THC + 32.5 mg CBD) –Safety No consistent withdrawal syndrome with symptom clusters or time of onset and remission was detected 13/24 (54%) patients had no withdrawal-type symptoms Of 11 (46%) patients with some withdrawal symptoms, none met Budney criteria Conclusion Abstinence from Sativex ® was associated with re-emergence of MS-related symptoms in 7-10 days No rebound phenomena were observed

53. Summary Pharmaceutical development program according to internationally recognised standards Therapeutic window achieved through cannabinoid ratios, drug delivery and predictable self-titration Substantial clinical data to confirm safety and efficacy No tolerance to beneficial therapeutic effects Apparent tolerance to side effects –Adverse Events Diminish over time –Mean intoxication scores are low even during dose-titration –Mean intoxication scores diminish over time No identified withdrawal syndrome seen after abrupt cessation No evidence of diversion/abuse to date First regulatory approval granted in Canada

54. Long Term Data MS Symptom VAS Scores

55. Long Term Data Dosing