PowerPoint Presentation • AK lesion count to Day 57 is shown in Figure 2. Reduction in AK lesion count to Day 57 was significantly greater than vehicle for all post-Baseline visits until Day 57 (Table 2). • Eligible subjects, predominantly Caucasian males with mean age of 70, skin type I- II and had median of 6 AK in the treatment area, were randomized to receive tirbanibulin (n=353) or vehicle ointment (n=349). Over 99% completed treatment. Baseline characteristics are shown in Table 1. RESULTS Andrew Blauvelt1, Steven Kempers2, Todd Schlesinger3, Edward Lain4, Hui Wang5, David Cutler5, Mark Lebwohl6, Jane Fang5, Rudolf Kwan5 1Oregon Medical Research Center, Portland, OR, USA;2Minnesota Clinical Study Center, New Brighton, MN, USA;3Clinical Research Center of the Carolinas, Charleston, SC, USA;4Austin Institute for Clinical Research, Pflugerville, TX, USA;5Athenex, Inc., Buffalo, NY, USA;6Icahn School of Medicine at Mount Sinai, New York, NY, USA. TIRBANIBULIN OINTMENT 1% FOR ACTINIC KERATOSIS (AK): POOLED DATA FROM TWO PHASE 3 STUDIES • Here we present pooled data analyses on efficacy, safety and 1-year follow-up. OBJECTIVE • Writing support was provided by TFS S.L. • This study was sponsored by Athenex, Inc.. ACKNOWLEDGEMENTS CONCLUSIONS • Tirbanibulin ointment 1% applied for 5 days was well tolerated, safe and effective, potentially making it a valuable new addition to AK treatment. Figure 1. Complete and partial clearance rates of AK lesions (ITT population) • Primary and secondary endpoints were complete (100%) and partial (≥75%) clearance of AK lesions at Day (D) 57. • Safety including adverse events (AEs) and local skin reactions (LSRs; Grade 0[none]-3[severe]) was assessed up to D57. Composite LSR scores represents the grades sum of all 6 LSR categories with a possible range from 0 to 18. • Subjects with complete AK clearance at D57 were followed for 1-year to assess safety and clearance durability. METHODS • Two identical Phase 3 randomized, double-blinded, vehicle-controlled studies evaluated efficacy and safety of tirbanibulin ointment 1% vs. vehicle in adults with AK on face/scalp. • Eligible subjects with 4‒8 clinically visible AK lesions in a 25 cm2 area were randomized 1:1 to receive tirbanibulin or vehicle (5-day once-daily self- application). • LSR signs were present at baseline, increased after treatment, peaked on D8 with tirbanibulin, decreased significantly by D15, and mostly resolved by D29. • Maximum mean±SD composite LSR scores were 4.1±2.32 and 1.0±1.14 for tirbanibulin and vehicle group, respectively. • LSRs were mostly transient mild or moderate erythema and flaking/scaling. Severe LSRs were few. All LSRs resolved or returned to baseline and did not require intervention. • No deaths, discontinuations, or serious AEs related to tirbanibulin occurred. • No treatment-related AEs throughout 1-year follow-up were reported. • Tirbanibulin is a novel inhibitor of tubulin polymerization, also associated with disruption of Src kinase signaling, developed as a topical formulation for AK. We have previously shown that 5 days of tirbanibulin ointment is safe and superior to vehicle in AK clearance at 2 months post-treatment in two Phase 3 studies (FCD 2019). SYNOPSIS • Treatment-related AEs were few and mostly mild transient application-site pruritus (tirbanibulin vs. vehicle: 9% vs 6%) and pain (tirbanibulin vs vehicle: 10% vs 3%) (Table 3). Table 1. Baseline characteristics Tirbanibulin (n=353) Vehicle (n=349) Mean Age (SD), years 69.3 (8.61) 70.2 (9.13) Gender: Male, n (%) 305 (86) 304 (87) Race: White, n (%) 352 (>99) 348 (>99) Fitzpatrick Skin Type, n (%) Type I 49 (14) 38 (11) Type II 200 (57) 224 (64) Type III 88 (25) 79 (23) Type IV 15 (4) 7 (2) Type V 0 1 (<1) Type VI 1 (<1) 0 Median Baseline AK lesion count (min - max) 6.0 (4 - 8) 6.0 (4 - 8) AK, actinic keratosis; SD, standard deviation 40th Annual Fall Clinical Dermatology Conference, October 29 - November 1, 2020 Safety population (n=702) n (%) Tirbanibulin (n=353) Vehicle (n=349) Number of subjects with any treatment-related AEs 56 (16%) 35 (10%) Application site pain 35 (10%) 11 (3%) Application site pruritus 32 (9%) 21 (6%) Table 3. Treatment-Related Adverse Events Up to Day 57 (Safety Population) Partial clearanceComplete clearance 9 18 49 72 0 10 20 30 40 50 60 70 80 % p a ti e n ts Vehicle Tirbanibulin Vehicle Tirbanibulin P<0.0001 Δ =54 P<0.0001 Δ =40 Vehicle (N=349) Tirbanibulin (N=353) 0 1 2 3 4 5 6 Baseline Day 8 Day 15 Day 29 Day 57 Tirbanibulin Vehicle Day 8Baseline Day 15 Day 29 Day 57 N u m b e r o f A K l e s io n s ( M e a n ± S E ) Figure 2. Number of lesions by visit and treatment group up to Day 57 AK, actinic keratosis; SE, standard error • At 1-year post-D57 follow-up, Kaplan-Meier estimate of proportion of tirbanibulin- treated patients (n=174) with at least one recurrent lesion present at baseline in the treated area recurring during follow-up was 47% and estimated rate of subjects with any AK lesion (recurred or new) was 73% (Figure 3). A total of 27% of patients had sustained AK clearance at 1-year. Tirbanibulin (n=353) Vehicle (n=349) Baseline Mean (±SE) 5.90 (0.07) 5.85 (0.07) Day 8 Mean (±SE) 3.87 (0.15) 4.75 (0.11) Change from baseline, mean (%) -2.05 (-35%) -1.10 (-19%) p-value <0.0001 Day 15 Mean (±SE) 2.51 (0.13) 4.52 (0.12) Change from baseline -3.38 (-58%) -1.33 (-24%) p-value <0.0001 Day 29 Mean (±SE) 1.68 (0.10) 4.37 (0.12) Change from baseline -4.23 (-72%) -1.48 (-26%) p-value <0.0001 Day 57 Mean (±SE) 1.29 (0.10) 4.14 (0.13) Change from baseline -4.61 (-79%) -1.72 (-31%) p-value <0.0001 Table 2. Summary of AK Lesion Counts Up to Day 57 AK, actinic keratosis; SE, standard error • At D57, complete clearance rates were significantly higher with tirbanibulin vs. vehicle, 49% vs. 9% (P<0.0001); partial clearance rates were 72% vs.18%, respectively (P<0.0001) (Figure 1). Median reduction in AK lesion count at D57 was greater with tirbanibulin vs. vehicle (87.5% vs. 20%). Figure 3. Proportion of patients with any recurrence by number of lesions at baseline 26,5 45,9 44,7 52,6 31,8 40,8 17,6 14,8 18,4 21,1 45,5 20,7 2,9 8,2 7,9 10,5 13,6 8,0 2,9 5,3 1,1 4,5 0,6 0,0 20,0 40,0 60,0 80,0 100,0 1 lesion 2 lesions 3 lesions 4 lesions 6 lesions 89.5 At Recurrence 4 lesions 5 lesions 6 lesions 7 lesions 8 lesions TOTAL 50.0 68.9 71.1 (n=34) (n=61) (n=38) (n=19) (n=22) (n=174) 71.3 P ro p o rt io n o f p a ti e n ts 95.5 Proportion of patients with x lesions at baseline