Slide 1: ESK-001, a Highly Selective Oral TYK2 Inhibitor: 52-Week Phase 2 Study Results
1 ESK - 001, a Highly S elective O ral TYK2 Inhibitor : 52 - Week Phase 2 Study Results In Moderate - to - Severe Plaque Psoriasis Andrew Blauvelt 1 , Shahram Jacobs 2 , Michael Bukhalo 3 , Howard Sofe n 4 , Elisa Muscianisi 5 , Grace Ma 5 , Gabriel Lau 5 , Michelle Bettinger 5 , Roman G. Rubio 5 ,
Slide 2: Disclosure of relationships with industry
〉 AbbVie: Advisory Board, Investigator 〉 Acelyrin : Investigator 〉 Almirall: Advisory Board, Investigator 〉 Alumis : Advisory Board, Investigator 〉 Amgen: Advisory Board, Investigator 〉 Anaptysbio : Advisory Board 〉 Apogee: Advisory Board 〉 Arcutis : Advisory Board , Investigator 〉 Boehringer Ingelh
Slide 3: ESK-001: a potent and selective oral allosteric TYK2 inhibitor
3 ESK - 001: a potent and selective oral allosteric TYK 2 inhibitor designed to achieve durable maximal target inhibition for 24 hours ESK - 001, a highly selective allosteric TYK2 inhibitor 〉 Intrinsic TYK2 selectivity to JH2 domain allows maximal target engagement and avoids classic JAK inhibitor
Slide 4: STRIDE Study: dose-dependent response with highest response at top dose
4 STRIDE Study: ESK - 001 dose - dependent response, with 40 mg BID demonstrating highest response (also reflected by blood/skin biomarkers) * PASI - 75 0.0 19.4 33.3 56.4 56.4 64.1 0 10 20 30 40 50 60 70 80 90 100 *** *** *** *** ** Proportion of Patients with Response (%) N 39 36 36 39 39 38 Prima
Slide 5: OLE Study: dose selection and study design
5 OLE Study: thorough dose selection to identify maximum benefit/risk for evaluation of long - term safety/efficacy of ESK - 001 OLE Study - Study Design Elements 〉 95% of eligible STRIDE patients rolled over to OLE study 〉 Two highest dose arms from STRIDE , 40 mg QD and 40 mg BID, with QD patients
Slide 6: OLE demographics and baseline disease characteristics well-balanced across arms
6 OLE demographics and baseline disease characteristics were well - balanced across study arms Overall (N=165) ESK - 001 40 mg BID* (N=83**) ESK - 001 40 mg QD (N=82) 49.2 (12.4) 50.8 (12.1) 47.5 (12.7) Age (years), mean (SD) 117 (70.9) 61 (73.5) 56 (68.3) Male, n (%) 133 (80.6) 11 (6.7)
Slide 7: OLE Safety profile: no significant safety findings throughout 52 weeks
7 OLE Safety profile of ESK - 001: no significant safety findings throughout 52 weeks Overall (N=164) ESK - 001 40 mg BID* (N=147) ESK - 001 40 mg QD (N=82) EAIR n (%) EAIR n (%) EAIR n (%) 108.18 108 (66) 102.33 73 (50) 122.76 50 (61) Subjects with ≥ 1 TEAE 3.29 6 (4) 3.39 4 (3) 3.10 2 (2) Subjects
Slide 8: PASI response over 52 weeks of treatment
0 20 40 60 80 100 Baseline STRIDE W12 Day 1 W2 W4 W8 W12 W16 W28 W40 W52 Patients with R esponse (%) PASI-75 (40 mg BID) PASI-90 (40 mg BID) PASI-100 (40 mg BID) 53.7 24.4 11.0 46.3 23.2 6.1 82.7 63.0 30.9 77.5 38.8 61.3 Washout STRIDE OLE 8 ESK - 001 response over 52 weeks of treatment: increasing
Slide 9: PASI response over 52 weeks including 40 mg QD arm
0 20 40 60 80 100 Baseline STRIDE W12 Day 1 W2 W4 W8 W12 W16 W28 W40 W52 Patients with R esponse (%) PASI-75 (40 mg QD) PASI-90 (40 mg QD) PASI-100 (40 mg QD) PASI-75 (40 mg BID) PASI-90 (40 mg BID) PASI-100 (40 mg BID) - - 80 80 81 81 81 79 81 82 82 80 82 81 81 82 82 81 76 82 82 82 1 Patients switc
Slide 10: sPGA response over 52 weeks of treatment
0 20 40 60 80 100 Baseline STRIDE W12 Day 1 W2 W4 W8 W12 W16 W28 W40 W52 Patients with R esponse (%) sPGA 0 (40 mg QD) sPGA 0/1 (40 mg QD) sPGA 0 (40 mg BID) sPGA 0/1 (40 mg BID) 10 ESK - 001 response over 52 weeks of treatment: increasing sPGA 0 and 0/1 responses over time ( mNRI *) Washout STRIDE
Slide 11: 62% of patients showed continued improvement in PASI response at Week 52
11 Of the original OLE 40 mg BID, 62% patients showed continued improvement in PASI response at Week 52 compared to Week 12 *Of the 18 non - responders at Week 52, 11 discontinued study early. mNRI analysis: if patient discontinued due to AE or inadequate response, then imputed as a non - responder;
Slide 12: 80% of PASI-75 responders maintained response at Week 52
n = 38 n = 24 n = 11 n = 9 n = 18 n = 13 n = 18 n = 31 * STRIDE Study Week 12 OLE Study Week 52 Shift of patients from STRIDE at Week 12 who showed IMPROVEMENT in PASI response Of the original OLE 40 mg BID, 80 % of ≥PASI - 75 responders in STRIDE main tain ed their ≥PASI - 75 response at Week 52 12
Slide 13: Patient-reported outcomes throughout Week 52
Based on the modified intention - to - treat analysis population. mNRI analysis: if patient discontinued due to AE or inadequate response, then imputed as a non - responder; if discontinued for other reasons, then imputed using LOCF (i.e., last observation carried forward). DLQI, Dermatology Life Qu
Slide 14: OLE 52-week summary and conclusions
14 ESK - 001 OLE: 52 - week summary and conclusions Safety summary 〉 ESK - 001 (40 mg BID) remained generally safe and well - tolerated over 52 weeks; majority of TEAEs were mild - to - moderate in severity and self - limited; no safety signals to date Efficacy summary 〉 40 mg BID patients showed hi