COWEN COLLABORATIVE INSIGHTS February 25, 2019 Additional Applications / Implications (Nadeau & Osborne) a a = Epilepsy & Psychiatric Conditions (Nadeau) For companies willing to invest in research and manufacturing, the development of FDA- approved cannabinoid-based drugs provides another path to market. GW’s Epidiolex (highly potent, pure CBD) was approved by the FDA in 2018, and several other companies are dedicating resources to conducting the pre-clinical and clinical research necessary to follow in GW’s footsteps. These companies are developing cannabinoids that differ by route of administration (oral capsule, oromucosal spray, sublingual pill, aerosol, topical cream, etc), formulation (level of purification, bioavailability, concentration), and dosing strategy (single agent or in combination). Below we summarize the clinical trial data from GW’s Epidiolex in epilepsy and psychiatric indications, and Zynerba’s transdermal CBD gel ZYNOO2 in Fragile X syndrome. GW conducted a broad Phase III program for Epidiolex in epilepsy, consisting of two Phase Ill trials in Dravet, two Phase III trials in Lennox-Gastaut syndrome (LGS), a Phase Ill trial in tuberous sclerosis complex, and a Phase II/III trial in infantile spasms. The first three Phase Ill trials (one in Dravet and two in LGS) supported an NDA submission, leading to FDA approval in June 2018. The Phase III efficacy portion of the first Dravet trial randomized 120 patients to either Epidiolex (20 mg/kg/day, n=61), or placebo (n=59). Epidiolex was added to background anti-epileptic drugs (AEDs). On average, patients were taking ~3 AEDS after previously having failed 4 or more. The average age of trial participants was 10 years and 30% of patients were less than 6 years of age. Patients entered the study with a median baseline convulsive seizure frequency of 13/month. The primary endpoint was the % change in monthly frequency of convulsive seizures during the 14-week treatment period compared with the 4-week b