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COWEN COLLABORATIVE INSIGHTS February 25, 2019 GW’s platform allows it to produce chemotypes with precise concentrations of various cannabinoids, and the company is testing numerous other cannabinoids. GW’s CBDV drug is in a 10 patient investigator sponsored trial in autism spectrum disorders, and a Phase II 100 patient placebo controlled trial in this indication began in December 2018. GW is also investigating CBDV for use in epilepsy, though the first clinical trial was not successful. Zynerba studied its transdermal CBD gel ZYNOO2 in Fragile X syndrome ina 12 week Phase II open-label study in children and adolescents. In the trial, patients were initiated ona dose of 50mg daily with the option to titrate up to 250mg daily. The primary endpoint was the Anxiety, Depression, and Mood Scale (ADAMS) Total Score. Twenty patients were enrolled, 18 of whom completed the 12 week treatment. At 12 weeks, two patients were on 100mg and 16 were on 250mg. On the primary endpoint, subjects saw an average improvement of 14.1 points (or 45.8%) from baseline (p<0.0001) with the greatest improvements seen in social avoidance (52.9%), general anxiety (54.0%), and manic/hyperactive behavior (p=0.0003). Twelve patients continued in a long-term extension study out to 12 months of follow up. These patients showed statistically significant improvements in mean % change from baseline in ADAMS Total Score, as well. The extension trial also contributed to a more robust safety dataset. The most common treatment-emergent adverse events were gastroenteritis (14%) and upper respiratory tract infection (12%); no serious AEs were reported. A randomized, double- blind, placebo-controlled trial to extend these findings to a larger population is ongoing in Australia, New Zealand, and the U.S. Figure 130 ZYNOO2 Produced Reductions In ADAMS At 12 Weeks... Figure 131 ...And Efficacy Persisted Out To 12 Months In An Extension Study Weak 12 A = [pans] Scale: ADAMS STNG | PROGR 12: | 1 erowemont | F-aeiue 2 20 (n=20) | (n=18) i Group Mean Ee an ve a BO2 582 so" soa" Total Score - -14.1 (45.8) <0.0001 : 7 Tass i Social Avoidance a -§.1 (52.9) 0.0002 : . MamiG GS aCe | a4 61 -27 (35.1) 0.0003 _ hu Behavior e a! Social Avoidance Manic/Hyperactive Depressed Mood General Anxiet; Compute ve Depressed Mood 2.8 2.0 -0.9 (28.6) 0.1417 “e<0.08 Monn 3 in=12) = Monin @ (N12) _etnonth 12 (n=12) Sener General Anxiety 10.0 46 -4.8 (54.0) <0.0001 Compulsive : Behavior 2.8 i4 -1.2 (50.0) 0.0262 Source: Zynerba Source: Zynerba COWEN.COM 93 HOUSE_OVERSIGHT_024909