GW Pharmaceuticals plc Reports Fiscal Third Quarter 2017 Financial Results and Operational Progress

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Aug 07, 2017

- Epidiolex® NDA submission process underway –

- Conference call today at 4:30 p.m. EST -

London, UK, Carlsbad, CA, 7 Aug 2017: GW Pharmaceuticals plc (NASDAQ: GWPH, GW, the Company or the Group), a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform, announces financial results for the third quarter ended 30 June 2017.                                  

“I am pleased to report the NDA submission process for Epidiolex is now underway with the final sections of the submission expected to be completed in October. With a clear view now towards our anticipated approval, we are making excellent progress with preparations to ensure a highly successful launch in 2018,” stated Justin Gover, GW’s Chief Executive Officer. “Following the recent publication of our first Phase 3 trial in the New England Journal of Medicine, we look forward to additional Epidiolex data publications and presentations in the second half of the year. In addition to Epidiolex, we continue to keep focus on our growing and innovative cannabinoid pipeline where we have advanced a number of additional exciting clinical programs.”

OPERATIONAL HIGHLIGHTS

  • Epidiolex (CBD) orphan epilepsy program in Dravet syndrome, Lennox-Gastaut Syndrome (LGS), Tuberous Sclerosis Complex (TSC) and Infantile Spasms (IS)

    • Regulatory progress:

      • NDA rolling submission for both Dravet and LGS indications underway. Pre-clinical module submitted;  Clinical module submission in progress; CMC module submission expected in October
      • EMA pre-submission meetings held. Expected EU regulatory submission in Q4 2017
    • Further clinical progress:
      • Phase 3 Dravet syndrome trial published in The New England Journal of Medicine
      • Quality of Life in Childhood Epilepsy published in Epilepsia
      • Phase 3 trial in Tuberous Sclerosis Complex ongoing
      • Part A of two-part Phase 3 trial in Infantile Spasms ongoing
      • Numerous abstracts submitted to American Epilepsy Society annual meeting
    • Manufacturing scale-up on track to deliver significant projected commercial launch inventory:
      • Preparations on track for FDA GMP inspection anticipated in early 2018
    • Expanded access program and open label extension:
      • Over 1,500 patients now exposed to Epidiolex treatment
      • 97 percent of patients who complete Phase 3 trials have entered long term extension
    • Commercial progress:
      • U.S. pre-launch commercial leadership team in place
      • Full team of epilepsy specialist Medical and Scientific Liaisons (MSLs) in place with significant medical education initiatives underway and major presence at key target congresses
      • EU commercial team build-out underway and increasing presence at European congresses
    • Strengthened Epidiolex exclusivity
      • 14 distinct patent families in prosecution relating to the use of CBD in the treatment of epilepsy; decisions expected for several patents towards end 2017 and H1 2018
      • 6 patents published in the last quarter claiming various methods of treatment using CBD
    • Life-cycle management
      • Several new formulations of CBD in Phase 1 trials
  • Progressed cannabinoid pipeline product candidates:
    • CBDV Phase 2 partial-onset epilepsy study in adults fully enrolled. Data expected end 2017/early 2018
    • CBDV in field of autism spectrum disorders
      • Expanded access IND granted by FDA for 10 patients with autism
      • Open label study in Rett syndrome and Phase 2 placebo-controlled trial in planning for H1 2018 
      • Orphan Drug Designation from FDA for CBDV for the treatment of Rett syndrome
    • CBD:THC in Glioblastoma
      • Positive survival data from Phase 2 study presented recently at ASCO; further follow-up demonstrates continued increased survival in the CBD:THC arm.
    • Neonatal Hypoxic-Ischemic Encephalopathy (NHIE) intravenous CBD program
      • Phase 1 trial complete
      • Orphan Drug and Fast Track Designations granted from FDA and EMA
  • Management appointments:
    • Dr. Volker Knappertz appointed Chief Medical Officer
    • Douglas Snyder appointed Chief Legal Officer
    • Prof. Ben Whalley appointed as Director of Research

FINANCIAL HIGHLIGHTS

  • Cash and cash equivalents at 30 June 2017 of £284.1 million ($369.5 million) compared to £374.4 million as at 30 September 2016
  • Revenue for the nine months ended 30 June 2017 of £6.1 million ($7.9 million) compared to £8.6 million for the nine months ended 30 June 2016
  • Loss for the nine months ended 30 June 2017 of £90.3 million ($117.5 million) compared to £46.7 million for the nine months ended 30 June 2016

    Solely for the convenience of the reader, the above balances have been translated into U.S. dollars at the rate on 30 June 2017 of $1.30081 to £1. These translations should not be considered representations that any such amounts have been, could have been or could be converted into U.S. dollars at that or any other exchange rate as at that or any other date.

    Conference Call and Webcast Information

    GW Pharmaceuticals will host a conference call and webcast to discuss the third quarter 2017 financial results today at 4:30 pm EST. To participate in the conference call, please dial 877-407-8133 (toll free from the U.S. and Canada) or 201-689-8040 (international). Investors may also access a live audio webcast of the call via the investor relations section of the Company’s website at http://www.gwpharm.com. A replay of the call will also be available through the GW website shortly after the call and will remain available for 90 days. Replay Numbers: (toll free):1-877-481-4010. For both dial-in numbers please use conference ID # 13667808 and PIN: 19259.

GW Pharmaceuticals plc

(“GW” or “the Company” or “the Group”)

Financial and Operational Results for the Third Quarter Ended 30 June 2017

GW Overview

GW was founded in 1998 and is a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform in a broad range of disease areas.  GW has established the world leading position in the development of plant-derived cannabinoid therapeutics through its proven drug discovery and development processes, intellectual property portfolio and regulatory and manufacturing expertise. The Company’s lead cannabinoid product candidate is Epidiolex®, a pharmaceutical formulation of cannabidiol, or CBD, for which GW retains global commercial rights, and which is in development for a number of rare childhood-onset epilepsy disorders. GW has received Orphan Drug Designation from the U.S. Food and Drug Administration, or FDA, for Epidiolex for the treatment of Dravet syndrome, Lennox-Gastaut syndrome, or LGS, Tuberous Sclerosis Complex, or TSC, and Infantile Spasms, or IS, each of which are severe infantile-onset, drug-resistant epilepsy syndromes. Additionally, GW has received Fast Track Designation from the FDA for the treatment of Dravet syndrome and conditional grant of rare pediatric disease designation by FDA. GW has also received Orphan Designation from the European Medicines Agency, or EMA, for Epidiolex for the treatment of Dravet syndrome and LGS.

During 2016, GW reported positive results from three pivotal Phase 3 trials of Epidiolex in Dravet syndrome and LGS. The Company has now commenced rolling submission of the New Drug Application, or NDA, to the FDA for Epidiolex in both Dravet syndrome and LGS. This submission is expected to be complete in October 2017. GW is also building experienced commercial teams in the United States and Europe in preparation for the potential future launches of Epidiolex.

GW has a deep pipeline of additional cannabinoid product candidates focusing primarily on orphan pediatric neurologic conditions and oncology. In February 2017, GW reported positive Phase 2 data for its CBD:THC product in the treatment of glioblastoma multiforme. The Company’s pipeline includes cannabidivarin, or CBDV, which is in Phase 2 development in the field of epilepsy and is also being researched within the field of autism spectrum disorders, or ASD. In addition, GW has received Orphan Drug Designation and Fast Track Designation from the FDA for intravenous CBD for the treatment of Neonatal Hypoxic Ischemic Encephalopathy, or NHIE, for which a Phase 1 study has been completed.

Previously, GW developed the world’s first plant-derived cannabinoid prescription drug, Sativex® (nabiximols), which is approved for the treatment of spasticity due to multiple sclerosis in 30 countries outside the United States.

Management Appointments

In August 2016, GW announced that Dr. Stephen Wright would be retiring in May 2017 as Chief Medical Officer and in May, GW announced the appointment of his successor, Dr. Volker Knappertz. Dr. Knappertz has over 25 years of clinical trial experience and 17 years of pharmaceutical drug development experience, holding leadership positions with responsibilities for managing international clinical trial and medical affairs programs. Most recently, as the Vice President of clinical development for multiple sclerosis, oncology and biosimilar products at Teva Pharmaceuticals, Dr. Knappertz oversaw multiple regulatory submissions and approvals in the U.S., Canada, Europe and Japan. Prior to joining Teva in 2012, Dr. Knappertz served in clinical and medical roles in CNS, CV, and biologics at Bayer Pharmaceuticals and AstraZeneca. Dr. Knappertz is a U.S. Board certified neurologist who received his residency training at Yale University, where he served as chief resident and was fellowship trained at Wake Forest University. He received his clinical scientist training and M.D. as well as a doctorate degree in research on glioblastoma from the University at Cologne in Germany.

In addition to the appointment of Dr. Knappertz as CMO, Professor Ben Whalley was also appointed in May to the newly created position of Head of Research. Previously, Prof. Whalley was Professor of Neuropharmacology at the Reading School of Pharmacy at the University of Reading, U.K. Since 2007, he has been GW’s principal academic collaborator in the field of epilepsy pre-clinical research and is the author of key papers related to the pre-clinical studies of CBD and CBDV in the treatment of seizures. In this time, he has become a leading authority on the effects of cannabinoids in the central nervous system.

In July 2017, Douglas Snyder joined GW to the newly created position of Chief Legal Officer. Mr Snyder brings more than 20 years of experience providing counsel in the pharmaceutical industry, at the FDA and in private practice.  Prior to joining GW, he led the legal and compliance teams as Senior Vice President, General Counsel, and Secretary for Actelion U.S.  Prior to that, Mr Snyder held the position of Senior Vice President, General Counsel, Secretary at Eisai Inc. where he led the Legal, Compliance, Legislative Affairs, Internal Audit and Security Group.  From 1999-2005, he was Vice-President, Associate General Counsel for GlaxoSmithKline.  During his tenure at GSK, Mr Snyder managed the legal and communications strategies related to some of the Company’s most high profile matters concerning the New York Attorney General, the U.S. department of Justice and the FDA. Before joining the pharmaceutical industry, he held the role of Associate General Counsel for the FDA where he counseled the Commissioner, appeared before Congress in key initiatives, and led the initial False Claims/Kickback cases against the pharmaceutical industry. 

Epidiolex (cannabidiol) in Dravet syndrome and LGS

GW has been conducting pre-clinical research of CBD in epilepsy since 2007 which has shown that CBD has significant anti-epileptiform and anticonvulsant activity using a variety of in vitro and in vivo models. GW’s strategy for the development of Epidiolex within the field of childhood-onset epilepsy is to initially concentrate formal development efforts on four orphan indications: Dravet syndrome, LGS, TSC, and IS, each of which are severe infantile-onset, drug-resistant epilepsy syndromes. GW expects to further expand the potential market opportunity of Epidiolex by targeting additional orphan seizure disorders for regulatory approval.

Dravet syndrome

Dravet syndrome is a severe infantile-onset, genetic, drug-resistant epilepsy syndrome with a distinctive but complex electroclinical presentation. Onset of Dravet syndrome occurs during the first year of life with clonic seizures (jerking) and tonic-clonic (convulsive) seizures in previously healthy and developmentally normal infants. Prognosis is poor and approximately 14 percent of children die during a seizure or from Sudden Unexpected Death in Epilepsy or SUDEP. Patients develop intellectual disability and life-long ongoing seizures. There are currently no FDA-approved treatments specifically indicated for Dravet syndrome.

In 2016, GW reported positive top-line results from the first Phase 3 pivotal efficacy and safety study in 120 patients, achieving the primary endpoint of a median reduction in monthly convulsive seizures compared with placebo (p=0.012). In this study, Epidiolex was generally well tolerated. The most common adverse events (occurring in greater than ten percent of Epidiolex-treated patients) were: somnolence, diarrhea, decreased appetite, fatigue, pyrexia, vomiting, lethargy, upper respiratory tract infection and convulsion.  Of those patients on Epidiolex that reported an adverse event, 84 percent reported it to be mild or moderate. This trial is the largest known controlled trial in Dravet syndrome ever conducted. In May 2017, this trial was published in The New England Journal of Medicine, accompanied by an editorial.

GW is conducting a second Phase 3 trial of Epidiolex in Dravet syndrome. This placebo-controlled trial differs from the first Phase 3 trial in that it includes two Epidiolex dose arms, at 20 mg/kg per day and at 10 mg/kg per day. GW continues to enroll this trial which is expected to recruit 186 patients.

LGS

LGS is a type of epilepsy with multiple types of seizures, particularly tonic (stiffening) and atonic (drop) seizures. Seizures due to LGS are hard to control and they generally require life-long treatment as LGS usually persists into the adult years. Historically patients with LGS have had few effective treatment options. Intellectual and behavioral problems associated with LGS are common and add to the complexity of this syndrome and the difficulties in managing life with LGS. Drug resistance is one of the main features of LGS.

In 2016, GW reported positive results from two LGS Phase 3 pivotal studies, both achieving the primary endpoint of a median reduction in monthly drop seizures compared with placebo. The first study compared a single Epidiolex 20 mg/kg dose arm to placebo in 171 patients (p=0.0135) and the second compared both a 20 mg/kg and 10 mg/kg Epidiolex dose arm to placebo in 225 patients (p=0.0047 and p=0.0016 respectively). In these studies, Epidiolex was generally well tolerated and the pattern of adverse events was consistent with that reported in the Dravet syndrome Phase 3 study. Additional data from the single dose arm trial was presented in poster form at the American Epilepsy Society’s Annual Meeting in December 2016, and additional data from the two dose arms was presented at the American Academy of Neurology Annual Meeting in April 2017, both showing additional safety and efficacy data associated with these studies. These data are available on the GW Pharmaceuticals corporate website in the Investor section. Additionally, GW is working with the investigators in these studies on manuscripts for peer-review publication, the first of which is expected by the end of 2017.

Open Label Extension

All patients in the randomized controlled clinical trials who complete the treatment period are eligible to enroll in a long term open label extension trial. To date, 97 percent of patients who have completed the pivotal treatment period have elected to enroll in the open label extension.

Epidiolex U.S. and EU Regulatory Submissions

The Company completed clinical and CMC pre-NDA meetings in the second half of 2016. Recently, the Company requested to FDA that it submit the NDA as a rolling submission, a request which the FDA accepted. This submission has now commenced with the pre-clinical module already having been submitted, the clinical module submission now underway and expected to be completed in the coming weeks, and the CMC module expected to be submitted in October 2017. Subject to satisfactory FDA review, GW anticipates a simultaneous decision of both indications.

In addition, GW has received confirmation from the FDA granting rare pediatric disease designation of cannabidiol in the treatment of LGS and Dravet syndrome. This conditional designation is a pre-cursor to the potential award of a rare pediatric disease priority review voucher which, if awarded, would be granted at the time of NDA approval.

In Europe, GW has now completed formal pre-submission meetings with the EMA and the designated ‘rapporteur’ regulatory authority. Following these meetings, in which it was agreed that GW could submit a single application for both the Dravet syndrome and LGS indications, the Company is advancing plans to submit a marketing authorization application in Europe in the fourth quarter of 2017.

Epidiolex Follow-On Target Indications

TSC

TSC is a genetic disorder that causes non-malignant tumors to form in many different organs, primarily in the brain, eyes, heart, kidney, skin and lungs. The most common symptom of TSC is epilepsy, which occurs in 75 to 90 percent of patients, about 70 percent of whom experience seizure onset in their first year of life. There are significant co-morbidities associated with TSC including cognitive impairment, autism spectrum disorders and neurobehavioral disorders.

A number of patients with TSC have been treated with Epidiolex in the expanded access program. Most recent Epidiolex data on TSC patients from the expanded access program was published in Epilepsia on 18 patients at Massachusetts General Hospital for Children (Hess et al - 2016) on Epidiolex treatment of refractory epilepsy in these patients. The findings from this paper, suggest that cannabidiol may be an effective and well-tolerated treatment option for patients with refractory seizures in TSC.

GW has commenced a Phase 3 trial of Epidiolex in patients with TSC. This dose-ranging trial is a 16-week comparison of Epidiolex versus placebo which is expected to recruit a total of approximately 200 patients, aged one to 65 years, to assess the safety and efficacy of Epidiolex as an adjunctive anti-epileptic treatment. The primary measure of this trial is the percentage change from baseline in seizure frequency during the treatment period. Primary endpoint seizures include focal motor seizures with or without impairment of consciousness or awareness and generalized convulsive seizures. Data is expected from this trial in 2018.

Infantile Spasms (IS)

An infantile spasm is a specific type of seizure seen in an epilepsy syndrome of infancy and childhood known as West syndrome. West syndrome is characterized by infantile spasms, developmental regression, and a specific pattern on electroencephalography, testing called hypsarrhythmia (chaotic brain waves). The onset of infantile spasms is usually in the first year of life, typically between 4 to 8 months of age.

In December 2015, at the Annual Meeting of the American Epilepsy Society, open-label safety and efficacy data on nine patients suffering from epileptic spasms from the Epidiolex expanded access program were presented by Massachusetts General Hospital for Children (Abati et al). Epilepsy spasms often remain refractory to standard AEDs. According to this poster, Epidiolex exerted its effects in a short time course, with a response rate of 67 percent after two weeks and 78 percent after one month. Three of nine patients became spasm-free after two weeks of Epidiolex treatment.

GW has commenced a two part Phase 3 trial of Epidiolex in patients with IS. The first part is now underway and the results will determine the Company’s next steps.

Epidiolex Manufacturing

GW manufactures Epidiolex through utilization of in-house and external third party facilities for various steps in the production process. The Company is scaling-up various parts of the production process both in-house and with external third parties in readiness for commercial launch.

In December 2016, GW hosted a GMP inspection from the UK’s regulatory authority, the Medicines and Healthcare products Regulatory Agency (MHRA). This inspection resulted in no critical or major findings.

In November 2016, GW held a CMC pre-NDA meeting. At this meeting, understanding was reached on key questions related to the CMC content of the NDA submission and the Company believes that it is on track to be ready for FDA GMP pre-approval inspection anticipated in the first quarter of 2018.

Epidiolex Commercialization

GW will commercialize Epidiolex, and any other products in the United States, under the name Greenwich Biosciences, Inc. (Greenwich). The U.S. organization continues to build out an experienced leadership team of medical affairs professionals, marketing and managed markets/payor expertise, many of whom have strong epilepsy knowledge and experience. Over 2017, Greenwich is continuing to expand its commercial organization in preparation of an expected 2018 Epidiolex approval and launch. The key near-term objectives for the U.S. commercial team include:

Increased visibility at major U.S. medical congresses

Working with clinicians, the Company expects to continue dissemination of important scientific data from the Epidiolex clinical program and anticipates data presentations at important upcoming medical congresses such as the Child Neurology Society (CNS) Annual Meeting and the American Epilepsy Society (AES) Annual Meeting, which will reinforce awareness of Greenwich Biosciences within the physician community. At the recently held American Academy of Neurology (AAN) Annual Meeting in April of this year clinical data from 3 of its Phase 3 studies had podium presentations.

Specific to the upcoming AES Annual Meeting in December, the Company expects an array of new data to be presented from the placebo-controlled trials, the long-term open-label extension study, and from clinics involved in the Expanded Access Program. Abstracts submitted include pooled analyses, health economic data in Dravet syndrome and LGS, mechanism of action, and additional PK drug interaction data.

Continued Medical Affairs and Medical Science Liaison team build-out

The U.S. Medical Affairs team, which is made up of experienced specialists drawn from leading epilepsy companies, currently numbers 13 with plans to expand to 15 by the end of 2017 has enabled the Company to open scientific and consultative communications with key stakeholders, such as the patient and physician communities in the U.S. This team is developing Dravet/LGS disease state information, rolling out programs in cannabinoid education, and intensifying interaction with key epilepsy opinion leaders to collect their insights related to the science emerging from the Epidiolex program.

Increased payor initiatives

As the Company moves closer to approval of Epidiolex, a major focus is on payor education and readiness. A number of individual one-on-one and advisory board interactions have already taken place with some of the larger commercial and state/federal payors.

Health Economic Outcomes Research and Compendia data initiatives

The Company has an experienced team of professionals focused on the development of a comprehensive pharmaco-economic dossier, including burden of illness and economic cost offset data in addition to clinical data for compendia support to assist and inform payor and formulary access and reimbursement decision making.

Patient advocacy initiatives

GW continues to focus on support for, and outreach to, the major epilepsy patient advocacy groups. These initiatives include relationship building, advocacy and education.

Implementation of a dedicated sales force

As GW approaches the expected U.S. Epidiolex approval, the Company anticipates hiring approximately 60 sales professionals in the U.S. to target approximately 4,000 – 5,000 physicians. This commercial organization will be defined by a “high touch” patient, payor and physician communication, education and distribution model.

Progress in Europe

Outside the United States, GW continues to advance its organizational preparations for Epidiolex commercialization in Europe. This European commercial effort is being led by our Chief Operating Officer, Chris Tovey, who has a wealth of experience commercializing and launching products, including within the field of epilepsy. The Company now has in place key staff in medical affairs, market access and marketing disciplines and is rapidly advancing multiple areas of launch planning including activities to put in place a more comprehensive commercial organization in the major European markets as well as continued development of the market access strategy. Alongside this, GW recently attended the 12th Congress of the European Paediatric Neurology Society (EPNS) in Lyon, including the hosting of a Satellite Symposium which was widely attended. GW’s European team are now in final preparations for the 32nd International Epilepsy Congress in Barcelona in September, at which activities will include two scientific symposia, platform and poster presentations of key Phase 3 data and a range of additional medical affairs activities.

U.S. Expanded Access Program (EAP)

In parallel with GW’s formal clinical trial program, the FDA has authorized access to Epidiolex to over 1,100 patients through a combination of Investigational New Drug Applications (INDs) to independent physician investigators in the U.S and expanded access programs supported by seven U.S. states (plus the District of Columbia which will be starting in August), for which GW is supplying Epidiolex free of charge. These include individual emergency and non-emergency INDs. The longest duration of patient use in the EAP is over 3.5 years. The FDA may authorize expanded access INDs to facilitate access to investigational drugs for treatment use for patients with a serious or immediately life-threatening disease or condition who lack therapeutic alternatives. Multiple IND sponsors have published open-label data from their programs.

In the July 2017 e-publication of Epilepsia (Rosenberg et al), the authors assessed caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in the EAP (n=48). Following 12 weeks of CBD, median percent change in seizure frequency was -39.4%, with a ≥50% responder rate of 41.7%. Patients experienced a mean of 8.1 points improvement in QOLCE (p<0.001). Of the 16 subdomains, those with significant improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. QOLCE improvements were not correlated to changes in seizure frequency or adverse events, suggesting that CBD may have beneficial effects on patient QOL that are distinct from its seizure-reducing effects. As previously reported by Devinsky et al in 2015, the EAP found CBD was generally well-tolerated; common adverse events included somnolence, decreased appetite, diarrhea, fatigue, and convulsions.

Epidiolex Intellectual Property

In addition to orphan exclusivity, GW has been seeking to protect Epidiolex through the expansion of its patent portfolio. GW’s patent portfolio relating to the use of CBD in the treatment of epilepsy includes fourteen distinct patent families which are either granted or filed.  The latest expiry date of these families is February 2037. Most of the patent families in this portfolio claim the use of CBD in the treatment of particular childhood epilepsy syndromes or seizure sub-types. These medical use and method of treatment type patent families are supported by additional patent families claiming CBD formulations.  To date, this has resulted in 3 patents granted by the United States Patent and Trademark Office (USPTO) and numerous patent applications being prosecuted at the USPTO.

Over the last quarter, six patents have been published on the USPTO site claiming various methods of treatment using cannabidiol. All of these applications have been filed as “Track One” applications in March 2017, which means the USPTO should make its final determination as to whether to grant these applications by the end of March 2018.

GW also anticipates filing additional patent applications in 2017, claiming the use of Epidiolex, as new data is generated.

Should the NDA for Epidiolex be approved, GW expects a number of its granted patents to be listed in the Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book). In addition, other patent families provide protection for epilepsy related inventions such as extraction techniques, CBD extracts and highly purified CBD.

Epidiolex Formulation Development

In addition to the initial launch formulation, GW continues to develop additional formulations of CBD as part of its life cycle management plan. As well as developing improved liquid formulations, the Company is developing a solid dose form to provide more convenient administration, particularly for adults and older children across our target indications, while sufficient range of dose sizes will maintain the current flexibility for titrating and amending the total daily dose. An intravenous formulation is also under development which is intended to provide short-term replacement or emergency therapy for patients unable to take the oral solution while hospitalized.

Mechanism of action

There is a significant effort utilizing in vitro, in vivo and other models of epilepsy to identify the mechanisms of action that underpin the clinical effectiveness of Epidiolex (and other cannabinoids) in epilepsy, including investigation of the effect of cannabinoids on epilepsy associated gene expression. As recently reported in Neurotherapeutics (Ibeas et al 2015), CBD is likely to be acting via more than one mechanism of action with the effect of reducing neuronal hyperexcitability. Importantly, the anti-seizure effects of CBD are not dependent on cannabinoid receptors, nor on sodium channels.

CBDV (cannabidivarin) Development Program

In addition to Epidiolex, GW’s product candidates also include the cannabinoid CBDV. CBDV has shown anti-epileptic properties across a range of in vitro and in vivo models of epilepsy. In pre-clinical studies, CBDV was also found to provide additional efficacy when combined with drugs currently used to control epilepsy. Positive results using genetic biomarkers for response have been identified. CBDV looks to be differentiated from CBD in four key ways: efficacy profile in seizure models, metabolic profile, pharmacological profile and has different physico-chemical characteristics.

GW has commenced a double-blind, randomized, placebo-controlled two-part trial to investigate the pharmacokinetics, followed by efficacy and safety of CBDV as add-on therapy in adult patients with inadequately controlled focal seizures. The first part of this trial is completed with enrollment of 32 patients and the dose-ranging pharmacokinetic and safety data has been reviewed by an independent panel. GW has closed recruitment for the placebo-controlled safety and efficacy phase of the study with 162 patients randomized. Data from this part of the trial is expected at the end of 2017 or early 2018.

GW has also evaluated CBDV in both general and syndromic pre-clinical models of autism spectrum disorders (ASD) yielding promising signals on cognitive and social endpoints as well as repetitive behaviors. These animal models include both genetically determined and chemically-induced models of neurobehavioral abnormalities, and include Rett syndrome and Fragile X syndrome among others.

Many of the pediatric intractable epilepsy conditions within the Epidiolex expanded access program share considerable overlap with ASD and these conditions often fall within the orphan disease space. Initial clinical observations from treating physicians suggest a potential role for cannabinoids in addressing problems associated with ASD such as deficits in cognition, behavior and communication.

GW is working on various clinical initiatives for CBDV within the field of ASD. A physician-led expanded access IND to treat seizures associated with autism has been granted by FDA in 10 patients. For patients with Rett Syndrome, a condition in which treatment-resistant seizures are a common problem, CBDV has received Orphan drug Designation from the FDA. An open label study in Rett Syndrome and a Phase 2 placebo-controlled trial in this condition are expected to commence in the first half of 2018. GW has received scientific advice from both the FDA and EMA on the study design.

Oncology

Beginning in 2007, GW has conducted substantial pre-clinical oncologic research on several cannabinoids in various forms of cancer including brain, lung, breast, pancreatic, melanoma, ovarian, gastric, renal, prostate and bladder. Cannabinoids have been shown to promote autophagy (the process of regulated self-degradation by cells) via several distinct mechanisms, including acting on the AKT/mTOR pathway, an important intracellular signaling pathway that is overactive in many cancers.

In glioma, the combination of CBD and THC showed good efficacy in various animal models of glioma, particularly when used in combination with temozolomide. These pre-clinical studies justified the initiation of a Phase 2 clinical study.

Earlier this year, GW completed a placebo-controlled Phase 2 study of a combination of CBD and THC in recurrent glioblastoma multiforme, or GBM, a particularly aggressive brain tumor which is considered a rare disease by the FDA and the EMA. The results from this Phase 2 study were presented in a poster at American Society of Clinical Oncology (ASCO) Annual Meeting in June. This study, which evaluated a number of safety and exploratory efficacy endpoints, showed that patients with documented recurrent glioblastoma treated with CBD:THC as add-on therapy to dose-intense temozolomide, had an 83 percent one year survival compared with 53 percent for patients on placebo (plus dose-intense temozolomide) (p=0.042). Median survival time for the CBD:THC group was greater than 550 days compared with 369 days in the placebo group. Further follow-up demonstrates continued increased survival in the CBD:THC arm. CBD:THC was generally well tolerated with treatment emergent adverse events leading to discontinuation in two patients in each group. The most common adverse events (three patients or more and greater than placebo) were vomiting, dizziness, nausea, headache, and constipation. The Company has received Orphan Drug Designation from both agencies for its product for the treatment of glioma.

GW believes that the signals of efficacy demonstrated in this study further reinforce the potential role of cannabinoids in the field of oncology and provide the Company with the prospect of a new and distinct cannabinoid product candidate in the treatment of additional oncology indications. These data are also a catalyst for the acceleration of GW’s oncology research interests and the Company expects to consult with external experts and regulatory agencies on a pivotal clinical development program for CBD:THC in GBM and to expand its research interests in other cancers.

GW’s portfolio of intellectual property related to the use of cannabinoids in oncology includes a number of issued patents and pending applications in both the U.S. and Europe. This portfolio is designed to protect the use of various cannabinoids individually or in combination, in the treatment of a variety of oncology-specific disorders and product formulations.

Neonatal Hypoxic-Ischemic Encephalopathy (NHIE)

NHIE is acute or sub-acute brain injury resulting from deprivation of oxygen during birth (hypoxia). GW estimates 6,500 to 12,000 cases of NHIE occur in the U.S. each year. Of these, 35 percent are expected to die in early life and 30 percent are expected to develop persistent neurologic disability. There are currently no FDA-approved medicines specifically indicated for NHIE.

GW has received Orphan Drug Designation and Fast Track Designation from the FDA for CBD for the treatment of NHIE. GW has also received Orphan Drug Designation from the EMA for CBD for the treatment of perinatal asphyxia, an alternate term that describes the same condition. Under an IND, GW has completed a Phase 1 trial of GWP42003 in healthy volunteers for an intravenous CBD formulation in the treatment of NHIE. GW plans to consult with FDA on the most appropriate design for an efficacy and safety study in neonates.

Schizophrenia

GW’s product candidate, an oral formulation of CBD, has shown notable anti-psychotic effects in accepted pre-clinical models of schizophrenia and in September 2015, GW announced positive top line results from an exploratory Phase 2a placebo-controlled clinical trial of CBD in 88 patients with schizophrenia who had previously failed to respond adequately to first line anti-psychotic medications. GW is evaluating appropriate next steps regarding product development in schizophrenia with future research likely focused on pediatric orphan neuropsychiatric indications.

About GW Pharmaceuticals plc

Founded in 1998, GW is a biopharmaceutical company focused on discovering, developing and commercializing novel therapeutics from its proprietary cannabinoid product platform in a broad range of disease areas. GW is advancing an orphan drug program in the field of childhood epilepsy with a focus on Epidiolex (cannabidiol), for which GW has commenced a rolling NDA submission with the FDA for the treatment of Dravet syndrome and Lennox-Gastaut syndrome. The Company continues to evaluate Epidiolex in additional epilepsy conditions and currently has ongoing Phase 3 clinical trials in Tuberous Sclerosis Complex and Infantile Spasms. GW commercialized the world’s first plant-derived cannabinoid prescription drug, Sativex®, which is approved for the treatment of spasticity due to multiple sclerosis in 30 countries outside the United States. The Company has a deep pipeline of additional cannabinoid product candidates which includes compounds in Phase 1 and 2 trials for glioma, schizophrenia and epilepsy. For further information, please visit www.gwpharm.com.

Forward-looking statements

This news release contains forward-looking statements that reflect GW's current expectations regarding future events, including statements regarding financial performance, the timing of clinical trials, the timing and outcomes of regulatory or intellectual property decisions, the relevance of GW products commercially available and in development, the clinical benefits of Sativex and Epidiolex and the safety profile and commercial potential of Sativex and Epidiolex. Forward-looking statements involve risks and uncertainties. Actual events could differ materially from those projected herein and depend on a number of factors, including (inter alia), the success of GW’s research strategies, the applicability of the discoveries made therein, the successful and timely completion of uncertainties related to the regulatory process, and the acceptance of Sativex, Epidiolex and other products by consumer and medical professionals. A further list and description of risks and uncertainties associated with an investment in GW can be found in GW’s filings with the U.S. Securities and Exchange Commission including the most recent Form 20-F filed on 5 December 2016. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. GW undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise.

Enquiries:

GW Pharmaceuticals plc

 

Stephen Schultz, VP Investor Relations

401 500 6570

Sam Brown (U.S. Media Enquiries)

 

Christy Curran

615 414 8668

 

 

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