GW Pharmaceuticals plc. June 2016

Transcription

1 GW Pharmaceuticals plc June 2016

2 Disclaimers FORWARD-LOOKING STATEMENTS This presentation contains forward-looking statements that are based on our management s beliefs and assumptions and on information currently available to management. Forward-looking statements include information about our current expectations for future events, including potential results of operations, the timing of clinical trials, demand for our commercially available products and products in development and the clinical benefits, safety profile and commercial potential of Sativex and Epidiolex. These forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that could cause our actual results, performance or achievements to be materially different than any future results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking statements represent our management s beliefs and assumptions only as of the date of this presentation. You should read our most recent Annual Report, as filed on Form 20-F with the Securities and Exchange Commission, including the Risk Factors set forth therein and the exhibits thereto, completely and with the understanding that our actual future results may be materially different from what we expect. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. EXPANDED ACCESS STUDIES Expanded access studies are uncontrolled, carried out by individual investigators independent from us, and not typically conducted in strict compliance with Good Clinical Practices, all of which can lead to a treatment effect which may differ from that in placebo-controlled trials. Data from these studies provide only anecdotal evidence of efficacy for regulatory review, contain no control or comparator group for reference and are not designed to be aggregated or reported as study results. Moreover, data from such small numbers of patients may be highly variable. Information obtained from these studies, including the statistical principles that the independent investigators have chosen to apply to the data, may not reliably predict data collected via systematic evaluation of efficacy in company-sponsored clinical trials or evaluated via other statistical principles that may be applied in those trials. Reliance on such information may lead to Phase 2 and 3 clinical trials that are not adequately designed to demonstrate efficacy and could delay or prevent our ability to seek approval of Epidiolex. Expanded access programs may provide supportive safety information for regulatory review. Physicians conducting these studies may use Epidiolex in a manner inconsistent with the protocol, including in children with conditions different from those being studied in our own sponsored trials. Any adverse events or reactions experienced by subjects in the expanded access program may be attributed to Epidiolex and may limit our ability to obtain regulatory approval with labeling that we consider desirable, or at all. 2

3 GW Pharma Overview World leading position in development of cannabinoid therapeutics Proprietary cannabinoid product platform targeting broad range of disease areas Founded in 1998 in UK; Significant U.S. clinical and regulatory activity since 2005 Epidiolex (CBD) orphan program in pediatric epilepsy Initial Target Indications Dravet syndrome: Positive Phase 3 data Lennox-Gastaut syndrome: Phase 3 trials to report June 2016 and Q Tuberous Sclerosis Complex : Phase 3 study underway GW retains global commercial rights NDA submission expected H US commercial operation established Promising clinical stage cannabinoid product pipeline CBDV in epilepsy and autism spectrum disorders Orphan programs in NHIE and glioma 3

4 Our Pipeline Unpartnered GW owns global rights Partnered 4

5 Treatment-Resistant Childhood Epilepsy: Significant Unmet Need 466,000 US CHILDREN WITH EPILEPSY Response to AEDs in patients with newly diagnosed epilepsy 3 little change to this statistic over last 15 years 30% PHARMACORESISTANT EPILEPTICS 1,4 SEIZURES THAT PERSIST, DESPITE MULTIPLE AED TREATMENT 2 140,000 TARGET US POPULATION REFRACTORY EPILEPSY COMPOSED OF MULTIPLE SYNDROMES 36% 47% 4% 13% Seizure-free with 1st drug Seizure-free with 2nd drug Seizure-free with 3rd or multiple drugs Pharmacoresistant epilepsy [1] Sander JW, Epilepsia. 1993;34(6):1007. [2] Picot et al, 2008 ; (3) Kwan P, Brodie MJ. N Engl J Med. 2000;342: (4) Kwan P, Brodie MJ, CNS Spectr. 2004;9(2):110 5

6 Treatment-Resistant Childhood Epilepsy: Spectrum of Rare Disorders Many different types of epilepsy syndromes, seizures and causes, including FIRES LENNOX-GASTAUT SYNDROME 3 TO 4% OF CHILDHOOD EPILEPSY 1 DRAVET SYNDROME UP TO 5% OF ALL CHILDHOOD EPILEPSIES IN FIRST YEAR OF LIFE 2 CDKL5 TUBEROUS SCLEROSIS COMPLEX DOOSE SYNDROME ANGELMAN S SYNDROME STXBP1/OHTAHARA SYNDROME DUP15q SYNDROME RASMUSSEN SYNDROME GLUT 1 TRANSPORTER DEFICIENCY AICARDI SYNDROME WEST SYNDROME (INFANTILE SPASM) 68% of patients being treated with Epidiolex in latest expanded access data have conditions other than Dravet and LGS [1] Trevathan et al, 1997; [2] Dravet et al,

7 Cannabinoids May Offer a New Class of Anti-Epileptic Drug Cannabinoids may act on both endocannabinoid system (ECS) and non-ecs targets, including cannabinoid, serotonin, melatonin and orphan receptors, and inhibition of adenosine reuptake [1] Possible CBD targets: Role for inflammation in epilepsy [2] Current treatments may not modulate inflammation Preclinical CBD actions: CBD has anti-inflammatory and anti-oxidant properties Have a protective effect during neuroinflammation inhibit release of cytokines Many different ion channels influence epileptogenesis [3] These include both voltage-gated and ligandgated cation channels (e.g. TRPs) CBD has cation channel modulatory actions Alter intracellular levels of calcium ions via several mechanisms [1] Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and Epilepsy. Neurotherapeutics. 2015;12(4): [2] Vezzani A.. Epilepsy Curr 2005;5:1 6 [3] Armijo JA et al. Pharm Des. 2005;11(15):

8 CBD Epilepsy Pre-Clinical Evidence IN VITRO EFFICACY Antiepileptiform activity demonstrated in brain slices IN VIVO EFFICACY Successful within multiple acute seizure models Anticonvulsant activity confirmed in chronic model Additive in combination with standard AEDs Orally effective in both acute and chronic models IN VIVO TOLERABILITY Comparator AED: Valproic acid (VPA), ethosuximide (ESM), phenobarbital (PBL) CBD does not cause any notable deficits at therapeutic doses Mg2+ free induced burst wave No Cannabinoid With Cannabinoid Mortality in PTZ model of generalized seizures Static Beam Test: % Fail Jones et al., JPET 332: ; Jones et al., Seizure 21: ; Hill et al., BPS 170: ; Amada et al., PeerJ 1: e214 doi: /bph

9 Epilepsy Clinical Program Overview Dravet Syndrome Phase 3 (n=120) positive Phase 3 (n=150) recruiting NDA EPIDIOLEX GW Sponsored Lennox-Gastaut Syndrome Tuberous Sclerosis Complex Phase 3 (n=171) fully enrolled Phase 3 (n=225) fully enrolled NDA Phase 3 (n=~200) recruiting Physician Sponsored Childhood Epilepsy Syndromes Physician and State INDs (>900 patients) Ongoing Treatment Data - Other epilepsies CBDV GW Refractory Epilepsies Part A (n=30) complete Phase 2 Part B (n=100) recruiting 9

10 Dravet Syndrome 1 st Phase 3 Trial Design 4 weeks Baseline Observation Period 2 weeks Titration Phase 14 week analysis period 12 weeks Treatment Phase Up to 10 days Taper Period Part A Complete Dose Selection Screening Randomization Epidiolex 20 mg/kg (n=61) Placebo (n=59) Open Label Extension Primary Endpoint: % change from baseline in monthly convulsive seizure frequency during the 14 week treatment period compared with the 4 week baseline period Measures taken to ensure quality, reduce noise include: -Choice of primary endpoint -Daily IVRS -Diagnosis verification -Investigator selection of responsible -Seizure count and description training and familiar parents 10

11 Dravet Syndrome Phase 3 Trial Results Patient demographics 120 patients (average age: 10, 30% <6 years old) On average, Epidiolex administered as 8 th AED in treatment regime Median baseline convulsive seizure frequency was 13 per month Efficacy Primary endpoint achieved with high statistical significance (p=0.01) Convulsive seizures: Epidiolex (n=61): -39%, placebo (n=59): -13% Secondary efficacy endpoints reinforced overall effectiveness Safety Epidiolex was generally well tolerated in this study 84% of patients on Epidiolex reported AEs as mild or moderate SAEs: 10 on Epidiolex, 3 on placebo Only 8 Epidiolex patients discontinued treatment due to AEs vs 1 on placebo Regulatory Pre-NDA meeting expected to be held with the FDA in mid

12 Principal Investigator for Dravet 1 Trial The results of this Epidiolex pivotal trial are important and exciting as they represent the first placebo-controlled evidence to support the safety and efficacy of pharmaceutical cannabidiol in children with Dravet syndrome, one of the most severe and difficult-to-treat types of epilepsy. These data demonstrate that Epidiolex delivers clinically important reductions in seizure frequency together with an acceptable safety and tolerability profile, providing the epilepsy community with the prospect of an appropriately standardized and tested pharmaceutical formulation of cannabidiol being made available by prescription in the future. Orrin Devinsky, M.D. Principal Investigator, Dravet 1 Phase 3 study New York University Langone Medical Center s Comprehensive Epilepsy Center 12

13 Lennox-Gastaut Syndrome 1 st Phase 3 Trial Design 4 weeks Baseline Observation Period 2 weeks Titration Phase 14 week analysis period 12 weeks Treatment Phase Up to 10 days Taper Period Part A Complete Dose Selection Screening Randomization Epidiolex20mg/kg (n=50) 171 patients Randomized 1:1 Placebo (n=50) Open Label Extension Primary Endpoint: % change from baseline in monthly drop seizure frequency during the 14 week treatment period compared with the 4 week baseline period Measures taken to ensure quality, reduce noise include: -Choice of primary endpoint -Daily IVRS -Diagnosis verification -Investigator selection of responsible -Seizure count and description training and familiar parents 13

14 Lennox-Gastaut Syndrome Phase 3 Trial Design Considerations Sample size Increase in patients randomized in both trials First LGS trial: from 100 to % power to detect 25% difference assuming 50% standard deviation Second LGS trial: from 150 to 225 Primary endpoint - drop seizures Sum of reported atonic, tonic and tonic-clonic seizures that were also deemed drop seizures (involving entire body, trunk or head that led or could have led to a fall, injury, slumping in a chair or hitting the patient s head on a surface) Dose EAP mean doses: Week mg/kg, Week mg/kg EAP data 40 LGS patients - 2 nd largest group 71.1% reduction in atonic seizures (n=14) Placebo effect in previous LGS trials Purcarin et al, 2014: from -5% to 12% (total seizures) 14

15 2 nd Dravet and 2 nd LGS Phase 3 Trials Dose Ranging Design 4 weeks Baseline Observation Period 2 weeks Titration Phase 14 week analysis period 12 weeks Treatment Phase Up to 10 days Taper Period Part A Complete Dose Selection Screening Randomization Epidiolex 20 mg/kg (n=50) -LGS 2: 225 patients randomized Epidiolex 10 mg/kg (n=50) -Dravet 2: enrollment ongoing Placebo (n=50) Open Label Extension Dravet Primary Endpoint: % change from baseline in monthly convulsive seizure frequency during the 14 week treatment period compared with the 4 week baseline period LGS Primary Endpoint: % change from baseline in monthly drop seizure frequency during the 14 week treatment period compared with the 4 week baseline period 15

16 US Commercialization Approx. 140,000 children in U.S. with treatment-resistant epilepsy Incidence of Dravet and LGS: 25-35K Epidiolex represents a new class of Anti-Epileptic Drug Experienced US commercial leadership team in place Implementation of high efficiency commercial deployment model 4-5,000 US specialists, expected to require sales force of approx Establish high touch patient, payor and physician communication, education and distribution model Importance of medical affairs organization Strong relations with patient organizations U.S. physician enthusiasm for a new therapeutic alternative is very high 16

17 Third Epidiolex Target Indication: Tuberous Sclerosis Complex Single Phase 3 pivotal trial commenced TSC is a genetic disorder that results from a mutation in tumor suppression genes TSC1 or TSC2 TSC causes non-malignant tumors to form in different organs primarily the brain, eyes, heart, kidney, skin and lungs Of TSC patients with epilepsy, 70% experience seizure onset in their first year of life Co-morbidities include Cognitive impairment (50%) Autism spectrum disorders (up to 40%) Neurobehavioral disorders (over 60%) 50,000 U.S. patients 75-90% Epilepsy 60% Treatment-resistant seizures Target population: ~25,000 US patients 17

18 TSC Expanded Access Data (AES 2015 Geffrey et al) Safety and efficacy data on 10 patients diagnosed with TSC Month 2 Month 3 Month 6 Month 9 Month 12 50% Responders 50% 50% 40% 60% 66% Improvements in alertness, verbal capacity/communication, vocalizations, cognitive availability, and initiation of emotional and physical connections, as well as heightened expression of emotion Diarrhea was the only side effect directly attributed to CBD Other AEs were result of drug-drug interactions, which occurred in five patients. These AEs were alleviated by AED dose adjustments without loss of seizure control Although additional studies are needed, the data in this small population suggests that CBD is safe, well-tolerated, and effective 18

19 GWP42006 (CBDV) CBDV is similar in chemical structure to CBD CBDV has shown anti-epileptic properties across a range of in vitro and in vivo models of epilepsy CBDV strongly suppressed seizures in six different experimental models CBDV exhibits few of the side effects caused by many existing AEDs Phase 1 trial completed in 66 healthy subjects CBDV well tolerated even at the highest tested dose No serious or severe adverse events, nor any withdrawals due to AEs Phase 2 trial (n=130) in patients with epilepsy underway CBDV evaluated in pre-clinical models of autism spectrum disorders Promising signals on cognitive/social endpoints as well as repetitive behavior Open-label clinical experience to commence H2 2016; Phase 2 trials expected to commence Q

20 Other Pipeline Candidates: Significant Clinical Programs NHIE FDA Orphan and Fast Track designation: Phase 1 expected to commence Q Glioma FDA Orphan designation: Phase 2a THC:CBD trial (in recurrent glioblastoma)- data due Q Type 2 Diabetes GWP42004 Phase 2 dose ranging trial fully enrolled data due Q2/Q Sativex Phase 2 study in spasticity due to cerebral palsy ongoing - data due Q Schizophrenia GWP42003 Phase 2a trial complete, data shows positive proof-of-concept 20

21 Key Financial Data $M Cash at 31 Mar Projected cash spend for H Capex (11-14) Opex (60-65) Share Capital Current Options Fully Diluted ADS/m Ordinary shares/m

22 Anticipated Newsflow Timing LGS Phase 3 data 1 st Phase 3 LGS data June nd Phase 3 LGS data Q Dravet Phase 3 data publication Q American Epilepsy Society data presentations Dec 2016 NDA submission with FDA H Epidiolex Phase 3 trials Start of 4 th indication H nd Dravet trial data 2017 TSC trial data H GWP42006 (CBDV) Phase 2 epilepsy trial data Q Phase 2a autism spectrum disorders trial start Q Pipeline Phase 1 NHIE trial start Q Phase 2a glioma data Q Phase 2b diabetes data Q2/Q Sativex Phase 2 cerebral palsy spasticity data Q

23 GW Pharmaceuticals plc NASDAQ: GWPH AIM: GWP Stephen Schultz, VP Investor Relations