PowerPoint Presentation • Treatment-related AEs were few: 16% of tirbanibulin-treated patients and 10% of vehicle- treated patients had ≥1 treatment-related AE (mostly transient mild-to-moderate application-site pain and pruritus that did not require treatment). No deaths, discontinuations, or serious AEs related to tirbanibulin occurred. • Incidence and severity of LSRs greater than baseline were higher with tirbanibulin vs. vehicle (Table 2): o For tirbanibulin, the most commonly occurring LSRs were mild to moderate erythema (22% and 63%) and flaking/scaling (26% and 47%), followed by mild crusting (30%) and mild swelling (29%). • 702 subjects were included in the pooled safety population (tirbanibulin n=353; vehicle n=349). Treatment compliance was >99%. Demographics were similar between treatment groups; most were Caucasian males, Fitzpatrick skin type II and median of 6 baseline AK lesions. Baseline characteristics are shown in Table 1. RESULTS Todd Schlesinger1, Neal Bhatia2, Brian Berman3, Ayman Grada4, Albert Torra5, David Cutler6, Mark Lebwohl7 1Dermatology and Laser Centre of Charleston, Charleston, SC, USA; 2Therapeutics Clinical Research, San Diego, CA, USA; 3Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 4Almirall, Exton, PA, USA; 5Almirall, Barcelona, Spain;6Athenex, Inc., Buffalo, NY, USA; 7Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAVORABLE SAFETY PROFILE OF TIRBANIBULIN OINTMENT 1% FOR ACTINIC KERATOSIS: POOLED RESULTS FROM TWO PHASE III STUDIES Table 1. Baseline characteristics • The objective was to report pooled safety data in adults with AK on the face/scalp from two pivotal phase III randomized, double-blinded, vehicle-controlled, parallel-group studies (KX01-AK-003/KX01-AK-004). OBJECTIVE • Safety assessments included local skin reactions (LSRs: erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, erosion/ulceration; scale of 0-3 [absent- severe]) and adverse events (AEs) up to Day (D) 57. • Incidence of maximal post-baseline LSR grades greater than baseline was described by treatment and LSR sign. Pooled LSR composite scores (the sum of all 6 LSRs) by visit and treatment were analyzed. 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-VI 16 (5) 8 (2) Median Baseline AK lesion count (min - max) 6.0 (4 - 8) 6.0 (4 - 8) • Writing support was provided by TFS S.L. • This study was sponsored by Athenex, Inc.. ACKNOWLEDGEMENTS CONCLUSIONS • Pooled data from phase III studies showed a favorable safety and tolerability profile of tirbanibulin ointment 1% once daily for 5 consecutive days in the treatment of AK on the face or scalp. Table 2. Maximal post-baseline LSRs by severity (Safety Population) METHODS • Eligible adult patients with 4-8 clinically visible AK lesions in a 25 cm2 area were randomized 1:1 to receive tirbanibulin ointment 1% or vehicle (5-day once-daily self- application). The study design is shown in Figure 1. • ITT Population: included all randomized patients. Safety Population included all subjects who received at least one dose of tirbanibulin ointment 1% Figure 1. Design of both studies • Regarding composite LSR scores, LSR peaked on D8 with tirbanibulin with a maximum mean composite LSR score of 4.1, decreased significantly by D15, and resolved by D29- D57. By D29 and D57, mean composite LSR scores were similar between tirbanibulin (0.6 and 0.4, respectively) and vehicle groups (0.6 and 0.5) (Figure 2 and Figure 3). • No significant difference was observed in mean composite LSR score in patients less and above 65 year old (maximum mean LSR: 4) 40th Annual Fall Clinical Dermatology Conference, October 29 - November 1, 2020 • Tirbanibulin is a first-in-class, novel inhibitor of tubulin polymerization and associated with disruption of Src kinase signaling for actinic keratosis (AK). • No cases of contact sensitization or phototoxicity were observed in two phase I studies (KX01-AK-006/KX01-AK-008). SYNOPSIS Table 3. Treatment-Related Adverse Events Up to Day 57 of Incidence ≥2% by Treatment Location Subgroups (face/scalp) Figure 2. LSR Composite Score from Baseline to Day 57 (Tirbanibulin, ITT population) Once Daily for 5 days Day 57 1 year Day 57 1 year Tirbanibulin N=175 350 patients per trial Vehicle N=175 1-year follow-up phase (only for patients with complete clearance at Day 57) 57-day phase Once Daily for 5 days • There were no differences in treatment-related AEs according to age, gender, and baseline AK lesions. Overall incidence of treatment-related AEs was slightly higher for face (17% and 11%) than scalp subjects (13% and 7%) in the tirbanibulin and vehicle groups, respectively (Table 3). AK, actinic keratosis; SD, standard deviation Safety population (n=702) n (%) Tirbanibulin (n=353) Vehicle (n=349) Erythema Mild 76 (22) 98 (28) Moderate 223 (63) 20 (6) Severe 22 (6) 0 Flaking/scaling Mild 92 (26) 86 (25) Moderate 166 (47) 33 (9) Severe 31 (9) 1 (<1) Crusting Mild 107 (30) 31 (9) Moderate 50 (14) 8 (2) Severe 7 (2) 0 Swelling Mild 102 (29) 15 (4) Moderate 32 (9) 1 (<1) Severe 2 (<1) 0 Vesicles/pustules Mild 25 (7) 3 (<1) Moderate 2 (<1) 0 Severe 2 (<1) 0 Erosions/ulcers Mild 32 (9) 10 (3) Moderate 9 (3) 0 Severe 0 0 The length of the box represents the interquartile range (the distance between the 25th and 75th percentiles). The symbol in the box interior represents the group mean. The horizontal line in the box interior represents the group median. Safety population (n=702) n (%) Tirbanibulin (n=353) Vehicle (n=349) Face Scalp Face Scalp Number of subjects with any treatment- related AEs 41 (17) 15 (13) 27 (11) 8 (7) Application site pain 26 (11) 9 (8) 9 (4) 2 (2) Application site pruritus 23 (10) 9 (8) 18 (8) 3 (3) Figure 3. Evolution of moderate and severe LSR from baseline to Day 57 Moderate LSR Severe LSR M e a n C o m p o s it e L S R S c o re 12 11 10 9 8 7 6 5 4 3 2 1 0 Day 1 Day 5 Day 8 Day 15 Day 29 Day 57 Visit day