Lebrikizumab, a high affinity IL-13 inhibitor, improves moderate-to-severe atopic dermatitis across racial groups: Post hoc efficacy and safety analyses from a randomized, double-blind, placebo‑controlled, dose-ranging, phase 2b study April Armstrong,1 Todd Schlesinger,2 Ramanan Gopalan,3 Janice Drew,3 Jamie Weisman,4 Emma Guttman-Yassky5 1Department of Dermatology, Keck School of Medicine at University of Southern California, Los Angeles, CA; 2Clinical Research Center of the Carolinas, Charleston, SC; 3Dermira, Inc., Menlo Park, CA; 4Atlanta Medical Dermatology Specialists, Atlanta, GA; 5Icahn School of Medicine at Mount Sinai, New York, NY

• Similar rates of TEAEs were reported across race subgroups; most were mild or moderate in severity and INTRODUCTION & OBJECTIVES infrequently lead to discontinuation (Table 3) • Interleukin (IL)-13 is a central pathogenic mediator driving multiple features of atopic dermatitis (AD) Figure 2. Proportion of EASI and IGA Responders by Race Subgroups at pathophysiology1-3 Week 16 • Across subgroups, TEAEs reported in ≥5% in the combined LEB group were nasopharyngitis and upper • IL-13 plays important roles in the inflammation, skin barrier dysfunction, infections, pruritus, lichenification, and respiratory tract infection; cough (6.3%) and oropharyngeal pain (6.3%) were reported in ≥5% in the combined allergic responses characterizing AD1-2,4-10 5 verall LEB group for the Other race subgroup (Table 3) 100 5. hite 1.0 3.1 0. • Lebrikizumab (LEB) is a novel, high-affinity monoclonal antibody targeting IL-13 that selectively prevents .3 .0 5.2 . n10 n40 .4 • Low rates of conjunctivitis were reported in LEB-treated patients across race subgroups (Table 3) n3 4.2 n5 n12 lack formation of the IL‑13Rα1/IL-4Rα heterodimer receptor signaling complex while leaving endogenous regulation of .4 n10 n0 n42 n2 n23 0 ther IL-13 intact n3 • Low rates of herpesvirus infections were reported in LEB-treated patients across race subgroups (Table 3) 50.2 0 4.5 45. 11-12 n2 43. • Although the presentation of AD may differ between racial subgroups, Th2 cell activation occurs regardless of n2 n52 n1 3.3 13 n10 race in patients with AD ; therefore, it is expected that LEB will improve AD symptoms across race subgroups 40 Table 3. TEAEs by Race Subgroup a • Post hoc analyses were performed to assess the potential impact of patient race on LEB efficacy and safety 20 from a randomized, double-blinded, placebo-controlled, dose‑ranging, phase 2b study in moderate‑to‑severe AD 14 LEB Overall Placebo Q2W (NCT03443024) 0 n=228 n=52 L 125 mg 4 L 250 mg 4 L 250 mg 2 Placeo 2 5 White Black Other White Black Other n=119 n=77 n=32 n=26 n=16 n=10 MATERIALS & METHODS 100 • Eligible patients were ≥18 years, with Eczema Area Severity Index (EASI) ≥16, Investigator’s Global Assessment Subjects reporting at least one TEAE, n (%) 68 (57.1) 40 (51.9) 19 (59.4) 15 (57.7) 5 (31.3) 4 (40.0) 0 (IGA) ≥3 (5-point scale), ≥10% body surface area (BSA) affected, and chronic AD for ≥1 year for which topical 2. 0. 3.2 0.0 5.1 5.3 n10 n5 n40 Subjects who discontinued study drug due to treatment provided inadequate control or was medically inadvisable 50.5 n0 52. n2 n23 53.5 7 (5.9) 1 (1.3) 1 (3.1) 0 1 (6.3) 0 0 n42 n12 TEAE, n (%) 43.4 n3 40.2 • Patients were randomized 3:3:3:2 to subcutaneous LEB 125mg every 4 weeks (Q4W; 250mg loading dose n3 34.4 n10 2. Other TEAEs of note, n (%) 40 n2 24.3 2. [LD]), 250mg Q4W (500mg LD), 250mg every 2 weeks (Q2W; 500mg LD at Week 0 and 2), or placebo Q2W for n2 n10 a n52 1.5 16 weeks, with a 16-week safety follow-up Nasopharyngitis 8 (6.7) 4 (5.2) 3 (9.4) 1 (3.8) 1 (6.3) 0 20 n1 • Endpoints were assessed post hoc by race subgroup (White, Black/African American, Other [American Indian/ Upper respiratory tract infection 11 (9.2) 4 (5.2) 2 (6.3) 2 (7.7) 1 (6.3) 0 Alaska Native, Asian, Multiple/Other; races were combined due to low number of patients]); the study design did 0 L 125 mg 4 L 250 mg 4 L 250 mg 2 Placeo 2 a not control for subgroups Conjunctivitis 3 (2.5) 2 (2.6) 1 (3.1) 0 0 0 Herpesvirus infectionb 4 (3.4) 4 (5.2) 0 1 (3.8) 0 1 (10.0) • The primary endpoint was percent change in EASI from Baseline to Week 16 100

aIncludes MedDRA Version 20.1 preferred terms: conjunctivitis, conjunctivitis bacterial, and conjunctivitis allergic • Secondary endpoints included proportion of patients achieving EASI50, EASI75, EASI90 (≥50%/75%/90% b 0 Includes MedDRA Version 20.1 preferred terms: oral herpes, herpes zoster, genital herpes, herpes simplex, and eczema herpeticum improvement from Baseline in EASI), Investigator’s Global Assessment score of 0 or 1 (IGA 0/1 response), and TEAE, treatment emergent adverse event 51.4 pruritus numeric rating scale (NRS) improvement ≥4 points and percent change from Baseline at Week 16 4. 0 42.3 44.0 n12 3.5 3.1 n5 n40 33.2 n2 35. • Other assessments analyzed included sleep loss NRS (sleep loss due to itch), Dermatology Life Quality Index n3 n0 31.2 n23 40 2.1 n42 n10 n3 (DLQI), Patient-Oriented Eczema Measure (POEM), and the Global Assessment of Change-AD a 1.2 11.4 13.0 15.0 n2 10.1 . n10 • Missing data at Week 16 were imputed using Markov chain Monte Carlo multiple imputation for EASI and IGA 20 n10 n52 n2 n1 data CONCLUSIONS 0 • In the overall population of this phase 2b study, the primary endpoint was met by all • Statistical comparisons were only performed for the overall population, not for subgroups L 125 mg 4 L 250 mg 4 L 250 mg 2 Placeo 2 LEB groups, with marked improvement at both 250mg Q2W and Q4W doses • Safety assessments included treatment‑emergent adverse events (TEAEs) ≥ 100 • In these post hoc analyses by race subgroup, similar results to the overall findings RESULTS 0 were observed and were generally consistent across racial groups 53.0 • A total of 73, 80, 75, and 52 patients were randomized to LEB 125mg Q4W, 250mg Q4W, 250mg Q2W, and 0 44. 4.4 n12 – 40.5 n5 n40 LEB improved skin lesion measures versus placebo over 16 weeks of treatment in placebo, respectively 33.0 33. n2 33. 2.5 32.0 40 2. n3 n0 n10 n23 patients with moderate‑to‑severe AD across racial groups 20.1 20.0 n42 20. • Race distribution for each treatment group is shown in Table 1 a n3 n2 n10 15.3 n2 15.0 n52 .5 n10 – • Baseline EASI and IGA scores were similar between race subgroups and the overall population 20 n1 Measures of itch generally improved compared to placebo across racial groups with LEB treatment 0 L 125 mg 4 L 250 mg 4 L 250 mg 2 Placeo 2 – LEB was well tolerated across subgroups, consistent with previous studies Table 1. Baseline Disease Characteristics *P<0.05, **P<0.01, and ***P<0.001 versus placebo from pairwise Cochran-Mantel-Haenszel tests; values have been adjusted for multiple imputation Missing data were imputed using Markov chain Monte Carlo (MCMC) multiple imputation; for the overall group, patients with a missing Baseline value were not included in the analyses No statistical comparisons were performed for the subgroups • These data highlight that selective blockade of IL-13 with LEB leads to improvements in EASI50, ≥50% improvement from Baseline in Eczema Area and Severity Index; EASI75, ≥75% improvement from Baseline in EASI; EASI90, ≥90% improvement from Baseline in EASI; IGA 0/1, LEB 125 mg Q4W LEB 250 mg Q4W LEB 250 mg Q2W Placebo Q2W score of 0 ‘clear’ or 1 ‘almost clear’ and ≥2-point reduction in Investigator Global Assessment (5‐point scale) from Baseline; Q2W, every 2 weeks; Q4W, every 4 weeks n=73 n=80 n=75 n=52 skin and itch symptoms while maintaining a favorable safety profile across a broad AD patient population White Black Other White Black Other White Black Other White Black Other n=37 n=26 n=10 n=42 n=28 n=10 n=40 n=23 n=12 n=26 n=16 n=10 • Similarly, measurements related to itch, including pruritus NRS (Figure 3) and sleep loss NRS (Table 2), generally 50.7% 35.6% 13.7% 52.5% 35.0% 12.5% 53.3% 30.7% 16.0% 50.0% 30.8% 19.2% improved compared to placebo across race subgroups with LEB treatment; no statistical comparisons were EASI, mean 28.6 33.5 25.0 26.4 24.9 28.6 28.8 20.8 23.3 30.1 26.4 29.6 performed for the subgroups References IGA, % patients 1. Moyle M, Cevikbas F, Harden JL, Guttman-Yassky E. Exp Dermatol. 2019;28(7):756-68. 2. Bieber T. Allergy. 3, moderate 56.8 57.7 70.0 66.7 71.4 60.0 62.5 78.3 83.3 53.8 62.5 80.0 Figure 3. Pruritus NRS Percent Change From Baseline and ≥4-Point 2020;75(1):54-62. 3. Tsoi LC, Rodriguez E, Degenhardt F, et al. J Invest Dermatol. 2019; 139(7):1480-89. 4. Kim J, Kim 4, severe 43.2 42.3 30.0 33.3 28.6 40.0 37.5 21.7 16.7 46.2 37.5 20.0 Improvement by Race Subgroups at Week 16 BE, Leung DYM. Allergy Asthma Proc. 2019;40(2):84-92. 5. Brunner PM, Guttman-Yassky E, Leung DY. J Allergy Clin Immunol. 2017;139(4S):S65-S76. 6. Raap U, Weissmantel S, Gehring M, et al. Pediatr Allergy Immunol. 2012;23(3):285- BSA involvement, 39.6 54.9 38.2 42.2 43.0 43.7 40.0 38.6 36.7 43.7 53.5 43.3 mean verall 288. 7. Raap U, Wichmann K, Bruder M, et al. J Allergy Clin Immunol. 2008;122(2):421-423. 8. Ezzat MH, Hasan Pruritus NRS, hite ZE, Shaheen KY. J Eur Acad Dermatol Venereol. 2011;25(3):334-339. 9. Trier AM, Kim BS. Curr Opin Immunol. 7.4 8.1 7.4 6.8 7.2 8.3 7.9 7.3 7.2 7.1 7.7 7.9 mean lack 2018;54:7-12. 10. Czarnowicki T, He H, Krueger JG, Guttman-Yassky E. J Allergy Clin Immunol. 2019;143(1):1-11. 11. a a ther Kaufman BP, Guttman-Yassky E, Alexis AF. Exp Dermatol. 2018;27(4):340-357. 12. Yew YW, Thyssen JP, Silverberg Sleep Loss NRS 100 (related to itch), 2.1 2.3 2.1 2.1 1.7 2.6 2.3 1.9 2.4 1.6 1.9 2.1 L 125 mg 4 L 250 mg 4 L 250 mg 2 Placeo 2 JI. J Am Acad Dermatol. 2019;80(2):390-401. 13. Noda S, Suárez-Fariñas M, Ungar B, et al. J Allergy Clin Immunol. meana 0 0 40.4 2015;136(5):1254-64. 14. Guttman-Yassky E, Blauvelt A, Eichenfield LF, et al.JAMA Dermatol. 2020 Feb 26. doi: 10.1001/ n12 DLQI, mean 13.4 16.5 13.5 14.8 11.5 19.5 14.6 13.4 13.5 12.9 13.4 18.2 40 jamadermatol.2020.0079. [Epub ahead of print] . POEM, mean 21.1 22.3 21.1 20.7 18.0 22.0 21.7 19.0 18.7 18.7 18.6 22.4 20 n22 0 aAssessed by asking subjects: “To what extent did your itching interfere with your sleep last night?” Available ratings were 0 (Not at all), 1 (A little), 2 (Moderately), 3 (Quite a bit) or 4 (Unable to sleep at all) Acknowledgments BSA, body surface area; DLQI, dermatology life quality index; EASI, Eczema Area and Severity Index; IGA, Investigator Global Assessment; NRS, numerical rating scale; POEM, patient-oriented -20 n3 eczema measure; Q2W, every 2 weeks; Q4W, every 4 weeks; SD, standard deviation -13. This study was funded by Dermira, Inc., a wholly-owned subsidiary of Eli Lilly and Company. Medical writing support was -40 n55 n1 n2 n n2 n -0 -3. -3. -32.3 n5 n21 provided by Prescott Medical Communications Group (Chicago, IL). All costs associated with development of this poster a a -41. -44.0 -4. -43. n n50 n2 n1 n -0 -50.3 were funded by Dermira, Inc., a wholly-owned subsidiary of Eli Lilly and Company. • All LEB groups showed dose-dependent, statistically significant improvements in the primary endpoint vs. -2.3 -1. -3.5 -0.2 -5.3 placebo at Week 16 (least squares mean percent change in EASI: LEB 125mg Q4W [-62.3%; P<0.05], 250mg ≥4 Q4W [-69.2%, P<0.01], 250mg Q2W [‑72.1%, P<0.001] vs. placebo [‑41.1%]) 100 1.4 3.1 5.0 Disclosure of any conflicts of interest 0.0 n1 0 n n50 n2 • Similar results for the primary endpoint were observed across race subgroups (Figure 1; no statistical 5.1 April Armstrong: Research, investigator, and/or consultant for AbbVie, Bristol-Myers Squibb, Dermavant, Dermira, Janssen, 50.0 n comparisons were performed for the subgroups) 0 4.4 44.4 4.4 4. KHK, Leo, Lilly, Novartis, Ortho Dermatologics, Regeneron, Sanofi, and UCB. 41. n2 n5 41.4 n21 n n55 33.3 n n2 40 n1 2.3 Todd Schlesinger: Consultants for AbbVie (Honoraria), Aclaris (Honoraria), Allergan (Honoraria), Bristol-Myers Squibb n22 1. a (Honoraria), EPI Health (Honoraria), Galderma (Honoraria), Lilly (Fees), Med Learning Group, Merz (Honoraria), Novartis Figure 1. Percent Change in EASI at Week 16 By Race Subgroup 20 n12 0.0 (Honoraria), Ortho Dermatologics, Pfizer, Pharmatecture, Prolacta Bioscience, Regeneron (Fees), and Sun Pharma, and n3 0 L 125 mg 4 L 250 mg 4 L 250 mg 2 Placeo 2 L 125 mg 4 L 250 mg 4 L 250 mg 2 Placeo 2 has received research funds from AbbVie, Aclaris, Akros, Allergan, Arcutis Premier Research, Astellas Pharma US, Inc, 0 **P<0.01, and ***P<0.001 versus placebo from pairwise Cochran-Mantel-Haenszel tests Biofrontera, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle BioScience, Celgene, Centocor Ortho No statistical comparisons were performed for the subgroups NRS, numerical rating scale; Q2W, every 2 weeks; Q4W, every 4 weeks Biotech, Inc, ChemoCentryx, Coherus Biosciences, Corrona, Cutanea Life Sciences, Dermavant, Dermira, DT Collagen, Lilly, Galderma (Nestle Skin Health), Genentech, Inc, Janssen Pharmaceuticals, Inc, Kinex, Kiniksa, Leo, Merz, Novartis, -20 Pfizer, Regeneron, Sanofi, Sienna Biopharmaceuticals, Sisaf, and Tetros. TS was also involved with speakers bureaus for Aclaris, Almirall, Dermira (Honoraria), Regeneron (Honoraria), Sanofi, Sun Pharma (Honoraria), and Suneva (Honoraria), n10 -40 n1 -32.3 Table 2. Patient Reported and Quality of Life Outcomes at Week 16 by and advisory boards for Almirall (Honoraria), Bioderma (Honoraria), Biofrontera AG (Honoraria), Greenway Therapeutix (No -34. n52 Compensation Received), Remedly, Inc (Stock Options), and Suneva Medical, Inc (Honoraria). - 41.1 n2 Race Subgroup

a n2 a -4.4 - 4.4 -0 Ramanan Gopalan: Employee of Dermira, Inc., a wholly-owned subsidiary of Eli Lilly and Company. n3 n10 LEB 125 mg Q4W LEB 250 mg Q4W LEB 250 mg Q2W Placebo Q2W -2.3 n42 n=73 n=80 n=75 n=52 Janice Drew: Employee of Dermira, Inc., a wholly-owned subsidiary of Eli Lilly and Company. n3 -5.2 n0 n2 n12 verall Change From -. -.2 -. -.3 n5 n40 n23 -.4 -0 n10 -2.1 hite Baseline at Week 16, White Black Other White Black Other White Black Other White Black Other -4. -3. -3.0 Jamie Weisman: Research grants: Abbvie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Eli Lilly,

a a lack mean n=37 n=26 n=10 n=42 n=28 n=10 n=40 n=23 n=12 n=26 n=16 n=10 Galderma, Janssen, Kiniksa, Novartis, Pfizer, Regeneron, Sanofi, UCB. Speaker/advisory boards: Abbvie, Eli Lilly, Sleep Loss NRS ther -55.0 -46.2 -30.0 -52.5 -50.0 -66.7 -63.3 -75.0 -56.0 -33.3 0.0 -25.0 -100 (related to itch) %a Novartis, Regeneron, Sanofi, UCB.

*P<0.05, **P<0.01, and ***P<0.001 versus placebo from pairwise Cochran-Mantel-Haenszel tests; values have been adjusted for multiple imputation Global Assessment of b 2.4 2.6 1.9 2.5 2.0 1.6 1.7 1.6 1.7 2.6 2.5 2.7 Emma Guttman-Yassky: Employee of Mount Sinai and has received research funds (grants paid to the institution) from aFor the overall group, LS mean values are shown Change-AD Missing data were imputed using Markov chain Monte Carlo (MCMC) multiple imputation; for the overall group, patients with a missing Baseline value were not included in the analyses AbbVie, Almirall, Amgen, AnaptysBio, Asana Biosciences, Boehringer-Ingelheim, Celgene, Dermavant, DS Biopharma, No statistical comparisons were performed for the subgroups DLQI -7.3 -9.7 -6.6 -9.4 -7.9 -11.8 -9.5 -10.3 -9.4 -3.9 -6.4 -13.0 EASI, Eczema Area and Severity Index; LS, least squares; Q2W, every 2 weeks; Q4W, every 4 week Eli Lilly, Glenmark, Galderma, Innovaderm, Janssen, Kiniksa, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, POEM -9.2 -7.8 -10.1 -10.9 -11.5 -12.6 -12.8 -12.2 -11.8 -4.3 -6.9 -9.7 Regeneron, Sienna Biopharma, UCB, and Union Therapeutics. EGY is also a consultant for AbbVie, Almirall, Amgen, aAssessed by asking subjects: “To what extent did your itching interfere with your sleep last night?” Available ratings were 0 (Not at all), 1 (A little), 2 (Moderately), 3 (Quite a bit) or 4 (Unable to sleep at all) • Comparable efficacy and dose-dependent response trends were observed across race subgroups in EASI50, bGlobal Assessment of Change-AD presented as mean score at Week 16 Asana Biosciences, Boehringer-Ingelheim, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Eli Lilly, No statistical comparisons were performed for the subgroups EASI75, EASI90, and IGA response of 0/1 from Baseline to Week 16 (Figure 2; no statistical comparisons were AD, atopic dermatitis, DLQI, dermatology life quality index; NRS, numerical rating scale; POEM, patient-oriented eczema measure; Q2W, every 2 weeks; Q4W, every 4 weeks EMD Serono, Escalier, Galderma, Glenmark, Kyowa Kirin, Leo Pharma, Mitsubishi Tanabe, Pfizer, RAPT Therapeutics, performed for the subgroups) Regeneron, Sanofi, Sienna Biopharma, and Union Therapeutics.

Poster presented at Revolutionizing Atopic Dermatitis | Chicago IL | April 2020