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1 Phase 2b REZOLVE-AD Topline Results from 16-Week Induction Rezpegaldesleukin in Patients with Moderate-to- Severe Atopic Dermatitis June 24, 2025
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Forward-Looking Statements 2 Safe Harbor Statement This presentation and any accompanying oral discussion contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, express or implied statements regarding Nektar Therapeutics (the “Company” or “Nektar”)’s plans, progress, and timing relating to the Company’s rezpegaldesleukin program in atopic dermatitis, including expectations for the end of Phase 2 Meeting with the U.S. Food and Drug Administration, timing for topline results from the Phase 2b REZOLVE- AA (alopecia areata) trial, timing for the 52-week maintenance data and 52-week off study treatment durability data from the Phase 2b REZOLVE-AD (atopic dermatitis) trial, and the presentation of data, rezpegaldesleukin’s potential to be a first-in-class T regulatory cell therapy, the potential market opportunity in atopic dermatitis and high unmet need for a new mechanism of action, the Company’s current and future research and development plans or expectations, the structure, timing and success of the Company’s planned clinical trials, the potential benefits of any of the Company’s current or future product candidates in treating patients, and the Company’s goals and strategy. Nektar intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by terms such as, but not limited to, “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “anticipate,” “project,” “target,” “design,” “estimate,” “predict,” “potential,” “plan,” “on track,” or similar expressions or the negative of those terms. Such forward-looking statements are based upon current expectations that involve risks, changes in circumstances, assumptions, and uncertainties. The express or implied forward-looking statements included in this presentation are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: risks related to the success, cost, and timing of the Company’s development activities and clinical trials, risks related to the Company’s dependence on the success of rezpegaldesleukin, the outcomes of competitive immunotherapy clinical trials, significant competition for the Company’s product candidates, the risk that preliminary and interim data from the Company’s clinical studies are subject to audit and verification procedures that could result in material changes in the final data and may change as more patient data become available, risks related to delays in clinical trials, risks related to dependence on third parties to conduct clinical trials, risks regarding future capital requirements, risks related to dependence on the Company’s collaboration agreements, risks related to the Company’s reliance on contract manufacturers and suppliers, risks related to obtaining regulatory approval for the Company’s drug candidates, risks related to the Company’s ability to protect and maintain its intellectual property position, risks related to legal proceedings and related litigation costs and liabilities and other risk factors that are described in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of Nektar’s most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and any other filings that Nektar has made or may make with the U.S. Securities and Exchange Commission in the future. Any forward-looking statements contained in this presentation and any accompanying oral discussion represent Nektar’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Nektar explicitly disclaims any obligation to update any forward- looking statements. Certain information contained in this presentation may be derived from information provided by industry sources. The Company believes such information is accurate and that the sources from which it has been obtained are reliable. However, the Company cannot guarantee the accuracy of, and has not independently verified, such information.
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REZOLVE-AD Phase 2b Validates Rezpeg as a First-in-Class Novel T-Regulatory Mechanism in Atopic Dermatitis (AD) Novel T-Reg MOA differentiates from existing and in-development biologics Up to 6-fold increase in T-regs Clear dose-dependent reduction in multiple AD biomarkers: IL-19, TARC/CCL17, Periostin, MDC/CCL22 Safety consistent with previously-reported safety profile with no new safety concerns • No increased risk of conjunctivitis, oral ulcers, or infections, including oral herpes, in study treatment arms • Most frequent AEs were mild injection site reactions (ISRs) that were self-resolving (<1% discontinuations due to ISRs) All 3 Dose Arms Met Primary Endpoint: Highest Dose Met all Six Key Secondaries: Other 2 doses also met multiple secondary endpoints EASI-75 (p<0.001) vIGA-AD 0/1 (p<0.05) Itch-NRS (p<0.01) EASI-90 (p-<0.05) BSA (p<0.001) % improvement in EASI at 16 weeks (p<0.001) Clear dose-dependent response Rapid onset of action (early separation from placebo) Equal efficacy observed in severe patients as in moderate 3
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REZOLVE-AD: Phase 2b Trial Design Patients with Moderate-to-Severe Atopic Dermatitis Induction Period (16 Weeks) Randomize (3:3:3:2) N=~393 (MITT) Maintenance Period (36 Weeks) 1:1 Continue 24 µg/kg at q4W or q12WRezpegaldesleukin 24 µg/kg (q2W) Rezpegaldesleukin 24 µg/kg (q4W) Placebo q4W Key Inclusion Criteria: Age: >18 years Moderate/severe AD diagnosis for < 12 months EASI ≥ 16 vIGA-AD of 3 or 4 BSA ≥ 10% Biologic-naive (no prior biologic systemic therapy) and systemic JAKi-naïve Failure of prior therapy, including TCS of medium or higher potency, within last 6 months Rezpegaldesleukin 18 µg /kg (q2W) Placebo q2W Screening Stratification Geographic region Baseline severity Key Pharmacodynamic Biomarkers: • T regulatory cell • TARC/CC17 • Periostin • MDC/CCL22 • IL-19 N= 581 N=106 N=110 N=73 N=104 1:1 Continue 18 µg/kg at q4W or q12W 1:1 Continue 24 µg/kg at q4W or q12W > EASI-50 opportunity to advance to maintenance < EASI-50 option to advance to escape arm 24 µg/kg (q2W) 4MITT is defined as patients who received at least one dose of study treatment or placebo.
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REZOLVE-AD: Phase 2b Trial Design Primary and Secondary Endpoints, Use of Rescue Therapy and Statistical Design Primary Endpoint: • Mean % EASI improvement at Week 16 Key Secondary Endpoints at Week 16: • vIGA-AD of 0 or 1 with ≥ 2-point reduction from baseline (vIGA-AD 0/1) • EASI-75, -90, -50 • Itch NRS, ≥ 4-point reduction from baseline • Mean % Body Surface Area (BSA) improvement • Primary Estimand analysis: patients who used rescue therapy outside protocol specifications or who discontinue treatment due to lack of efficacy were considered NONRESPONDERS (using baseline observation carry forward (BLOCF) for continuous endpoints, and non responder imputation for binary endpoints), regardless of observed clinical response; data after patients who discontinue due to other reasons set to missing and all missing data are imputed using the multiple imputation method. Statistical Analysis Methods • The Primary Estimand analysis for continuous endpoints of %EASI improvement and %BSA improvement use a mixed model for repeated measures (MMRM) to estimate the treatment difference between dose arms and placebo • The Primary Estimand analysis for binary endpoints (vIGA-AD 0/1, EASI-75, EASI-90, and Itch NRS) use a logistic regression model to estimate the treatment difference between dose arms and placebo • Statistical methodologies most similar to Sanofi STREAM-AD Phase 2b Study 5EASI: Eczema Area and Severity Index; vIGA-AD: Validated Investigators Global Assessment for Atopic Dermatitis; NRS: Numerical Rating Scale
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Baseline Demographics and Disease Characteristics Patient Demographics - Patients were predominantly recruited from Europe, but also from North America and Australia - Stratification Factor: North America (27.5%) vs Rest of World (72.5%) - Majority of patients were under 65 years-old, well balanced among men and women - Majority were White (84.2%) with mean ± SD disease duration of 21.5 ± 14.9 years Baseline Disease Characteristics, mean ± SD: - EASI was 26.0 ± 9.8 • EASI < 21 (40.7%) vs EASI ≥ 21 (59.3%) - Stratification Factor: Baseline vIGA-AD 3 (67.9%) vs vIGA-AD 4 (32.1%) - BSA was 39.5 ± 20% - Itch NRS was 6.8 ± 1.95 - Well-balanced across arms 6
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0 2 4 6 8 10 12 14 16 -80 -60 -40 -20 0 % EASI Reduction From Baseline Study Weeks %, LS Mean (SEM) -61% -58% -53% -31% Placebo REZPEG 24 μg/kg, q2w REZPEG 18 μg/kg, q2w REZPEG 24 μg/kg, q4w Study Weeks Dose Dependent % EASI Reduction, Clear Separation from Placebo at All Timepoints for Study Treatment Arms 0 20 40 60 80 53%58%61% 31% Week 16 % EASI Improvement *** *** *** ***p-value<0.001 % EASI Reduction from Baseline (Primary Estimand) LS Mean At Week 16 Primary Estimand 7 All dose arms met primary endpoint with statistical significance p-value <0.001 N=73, 104, 106, and 110 for the placebo, 24 µg/kg q2w, 18 µg/kg q2w, and 24 µg/kg q4w groups
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***p-value<0.001 **p-value<0.01 *p-value<0.05 EASI-90EASI-50 EASI-75 Placebo REZPEG 24 μg/kg, q2w REZPEG 18 μg/kg, q2w REZPEG 24 μg/kg, q4w 8 High Dose Met all Key Secondary Endpoints Multiple endpoints met for 2 additional dose arms Primary Estimand: N=73, 104, 106, and 110 for the placebo, 24 µg/kg q2w, 18 µg/kg q2w, and 24 µg/kg q4w groups
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vIGA-AD 0/1 Itch NRS BSA % Change ***p-value<0.001 **p-value<0.01 *p-value<0.05 Placebo REZPEG 24 μg/kg, q2w REZPEG 18 μg/kg, q2w REZPEG 24 μg/kg, q4w 9 High Dose Met all Key Secondary Endpoints Multiple endpoints met in 2 additional dose arms Primary Estimand: N=73, 104, 106, and 110 for the placebo, 24 µg/kg q2w, 18 µg/kg q2w, and 24 µg/kg q4w groups) for the vIGA-AD 0/1 and continuous BSA endpoint. The MITT population with baseline itch ≥ 4 (N=63, 95, 92, and 102 for the placebo, 24 µg/kg q2w, 18 µg/kg q2w, and 24 µg/kg q4w groups)
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Fast Onset of Action Across All Key Secondary Endpoints Placebo 24 μg/kg, q2w 18 μg/kg, q2w 24 μg/kg, q4w 0 2 4 6 8 10 12 14 16 0 10 20 30 vIGA-AD 0/1 Study Weeks Response Rate (%) 0 2 4 6 8 10 12 14 16 0 10 20 30 EASI-90 Study Weeks Response Rate (%) 0 2 4 6 8 10 12 14 16 0 10 20 30 40 50 Itch NRS Study Weeks Response Rate (%) 0 2 4 6 8 10 12 14 16 0 10 20 30 40 50 EASI-75 Study Weeks Response Rate (%) EASI-75 EASI-90 vIGA-AD 0/1 Itch NRS 10 Primary Estimand Analysis For EASI-75, vIGA-AD 0/1, and EASI-90: N = 73, 104, 106, and 110 for placebo, 24 µg/kg q2w, 18 µg/kg q2w, and 24 µg/kg q4w For Itch NRS: N=63, 95, 92, and 102 for the placebo, 24 µg/kg q2w, 18 µg/kg q2w, and 24 µg/kg q4w groups
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0 2 4 6 8 10 12 14 16 0 10 20 30 EASI-90 (Baseline vIGA-AD 0/1 = 4) Study Weeks Response Rate (%) Placebo 24 μg/kg, q2w 18 μg/kg, q2w 24 μg/kg, q4w Arm Baseline vIGA-AD =3 Baseline vIGA-AD =4 Placebo 51 22 24 µg/kg, q2w 71 33 18 µg/kg, q2w 70 36 24 µg/kg, q4w 75 35 Sample Size 0 2 4 6 8 10 12 14 16 0 20 40 60 EASI-75 (Baseline vIGA-AD 0/1 = 4) Study Weeks Response Rate (%) 0 2 4 6 8 10 12 14 16 0 20 40 60 EASI-75 (Baseline vIGA-AD 0/1 = 3) Study Weeks Response Rate (%) Primary Estimand Analysis EASI-75 (Baseline vIGA-AD = 4) EASI-75 (Baseline vIGA-AD = 3) EASI-90 (Baseline vIGA-AD = 4) 11 Similar Efficacy Observed in Severe Patients as in Moderate EASI-75 and EASI-90 by baseline vIGA-AD score 0 2 4 6 8 10 12 14 16 0 10 20 30 EASI-90 (Baseline vIGA-AD 0/1 = 3) Study Weeks Response Rate (%) EASI-90 (Baseline vIGA-AD = 3)
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Patients with baseline values >ULN included in the analysis Arm IL-19 (>51 pg/mL) TARC/ CCL17 (>0.94 ng/mL) Periostin (>322 ng/mL) MDC/ CCL22 (>839 pg/mL) Placebo 14 29 21 21 24 µg/kg, q2w 25 35 29 28 18 µg/kg, q2w 23 34 29 28 24 µg/kg, q4w 28 34 32 27 IL-19 TARC/CCL17 Periostin MDC/CCL22 -60 -40 -20 0 20 30 % Difference from Baseline to Week 16 Placebo REZPEG 24 μg/kg, q2w REZPEG 18 μg/kg, q2w REZPEG 24 μg/kg, q4w TARC, CCL22, Periostin – normal range provided by Rules Based Medicine, based on their analysis of 100 NHV IL-19 - Konrad et al, 2019 TARC/CCL17, Periostin, MDC/CCL22, IL-19 are key markers associated with atopic dermatitis* 12 *2021 Renert-Yuval et. al. https://doi.org/10.1016/j.jaci.2021.01.013; 2019 Konrad et. al. https://rdcu.be/eq5C3 Reductions Observed in Four Key Biomarkers of Atopic Dermatitis Sample Size
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Study Weeks 13 0 2 4 6 0 2 4 6 8 12 14 16 Study Weeks Fold change from basline, %CD25bright Tregs (mean+SEM) Up to 6-fold increase in T-reg consistent with prior studies of REZPEG PK/PD Profile Consistent with Prior Studies Strong relationship to dose-dependent clinical responses 0 2 3 4 5 8 12 16 N 95 83 39 85 37 79 75 75 N 102 84 45 84 41 82 74 71 N 107 84 31 78 38 81 83 78Administration q4w dosed on w0, w4, w8, w12, and w16 Treg Analysis: N=9, 14, 19, and 19 for the placebo, 24 µg/kg q2w,18 µg/kg q2w, and 24 µg/kg q4w groups Study Weeks Dose-Dependent Pharmacokinetics 0 2 4 6 8 10 12 14 16 0 50 100 150 200 250Mean Concentration (ng/mL)
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REZOLVE-AD: Safety Summary Safety of rezpeg for 16-week induction period in this Phase 2b study is consistent with previously observed and reported safety profile - Serious and severe AEs were rare (1.6% and 3.1%, respectively) for rezpeg-exposed patients - Discontinuation rate due to AEs was low (5.6%) for rezpeg-exposed patients and was within the range of rates seen in contemporary Phase 2b studies - No imbalance to suggest an increased risk of infection over placebo • No increased risk of conjunctivitis, oral ulcers, or infections, including oral herpes, in study treatment arms The most frequently observed adverse event was injection site reactions (ISRs) - Nearly all were mild-moderate in severity and self-resolving - The treatment discontinuation rate due to ISRs was very low (0.6%) for rezpeg exposed patients - Planning ISR mitigation strategy for commercialization 14
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ISR Severity Breakdown Across All Dose Administrations By Severity Level Over 16-Week Induction % of ISRs in each arm across all dose administrations. N= number of study treatment or placebo administrations in arm (at 24 µg/kg q4w, only rezpeg administrations counted) Mild: Faint erythema, asymptomatic, no or mild itch, no or mild tenderness Moderate: Notable/great erythema, widespread itch, readily apparent induration, moderate pain Severe: Widespread and constant itch limiting daily life, gross deviation of normal anatomic contour for induration, severe pain Majority of ISRs observed were mild with faint erythema and asymptomatic 15 Rezpeg 24 µg/kg q2w N=703 Rezpeg 18 µg/kg q2w N=712 Rezpeg 24 µg/kg q4w N=401 Placebo N=543
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Phase 2b Benchmarks Endpoint Rezpegaldesleukin 18/24 µg/kg q2w Phase 2b 16 Weeks Nektar Amlitelimab 250mg q4w1 Phase 2b 16/24 Weeks Sanofi Rocatinlimab 150/600mg q4w2 Phase 2b 16 Weeks Amgen Nemolizumab 30mg q4w3 Phase 2b 24 Weeks (TCS Combo) Galderma Lebrikizumab 250mg q2w4 Phase 2b 16 Weeks Lilly/Dermira Tralokinumab 300mg q2w5 Phase 2b 12 Weeks (TCS Combo) Leo Pharma Dupilumab 300mg q2w6 Phase 2b 16 Weeks Regeneron MOA IL-2R agonist OX40L OX40 IL-31 IL-13 IL-13 IL-4 & IL-13 Enrollment Completion Trial Size 2025 N=398 2022 N=390 2020 N=274 2018 N=226 2019 N=280 2016 N=204 2014 N=380 EASI LS Mean % reduction from baseline (Placebo) 58/61% (31%) 62% (29%) 62/60% (32%) 69% (52%) 72% (41%) Not Reported 68% (18%) Placebo Adjusted 27/30% 32% 30/28% 17% 31% Not Reported 50% EASI-75 (Placebo) 46/42% (17%) 40% (11%) 44/40% (11%) 46% (26%) 48% (12%)b 43% (16%) 52% (11%)d Placebo Adjusted 29/25% 29% 33/29% 20% 36% 27% 41% vIGA-AD Responders (0/1) (Placebo) 26/20% (8%) 22% (5%) IGA-AD 19/15% (2%) 37% (21%) IGA-AD 45% (15%) IGA-AD 27% (12%) IGA-AD 30% (2%) IGA-AD Placebo Adjusted 18/12% 17% 17/13%% 16% 30% 15% 28% EASI-90 (Placebo) 18/25% (9%) 16% (4%) 19/12% (4%) 30% (11%) 44% (11%) Not Reported 30% (4%)d Placebo Adjusted 9/16% 12% 15/8% 19% 33% Not Reported 26% Itch NRS ≥ 4 pt Responders (Placebo) 35/42% (16%) 25% (5%) 37/46% (19%) 43% (24%) a 67% (39%)c Not Reported 41% (8%)e Placebo Adjusted 19/26% 20% 18/27% 19% 28% Not Reported 33% 1. Weidinger et al. 2025, JACI 155:1264-75 2. Guttman-Yassky et al. 2023, Lancet 401:204-14 5. Wollenberg et al. 2019, JACI 143:135-41 6. Thaci et al. 2016, Lancet 387:40-52 16 3. Silverberg et al. 2020, JACI 145:173-82 4. Guttman-Yassky et al. 2020, JAMA Derm 156:411-20 a: estimated from Fig 4b b: Sensitivity analysis 3, NRI for rescue meds & LOCF for other missing data (eTable 4) c: MCMC imputation (eFig 3b) d: estimated from Fig 3 e: 3pt responder scale
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Benchmark to Phase 2b OX40/OX40L Class Endpoint Rezpegaldesleukin 18/24 µg/kg q2w Phase 2b 16 Weeks Nektar Amlitelimab 250mg q4w1 Phase 2b 16 Weeks Sanofi Rocatinlimab 150/600mg q4w2 Phase 2b 16 Weeks Amgen MOA IL-2R agonist OX40L OX40 Enrollment Completion Trial Size 2025 N=398 2022 N=390 2020 N=274 EASI LS Mean % reduction from baseline (Placebo) 58/61% (31%) 62% (29%) 62/60% (32%) Placebo Adjusted 27/30% 32% 30/28% EASI-75 (Placebo) 46/42% (17%) 40% (11%) 44/40% (11%) Placebo Adjusted 29/25% 29% 33/29% vIGA-AD Responders (0/1) (Placebo) 26/20% (8%) 22% (5%) IGA 19/15% (2%) Placebo Adjusted 18/12% 17% 17/13%% EASI-90 (Placebo) 18/25% (9%) 16% (4%) 19/12% (4%) Placebo Adjusted 9/16% 12% 15/8% Itch NRS ≥ 4 pt Responders (Placebo) 35/42% (16%) 25% (5%) 37/46% (19%) Placebo Adjusted 19/26% 20% 18/27% 1. Weidinger et al. 2025, JACI 155:1264-75 2. Guttman-Yassky et al. 2023, Lancet 401:204-14 17
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Rezpeg q2w Arms Show Similar Responses as OX40/OX40L Class (EASI-75 at Week 16) 0 2 4 6 8 10 12 14 16 0 10 20 30 40 50 EASI-75 Study Weeks Response Rate (%) 42% 46% 34% 17% * ** *: Phase 3 dose level **: Phase 3 dose range (q4w regimen) References: Amlitelimab – Weidinger et al. 5th Inflammatory Skin Disease Summit, November 15-18; Vienna Austria (Fig. 3) Rocatinlimab – Guttman-Yassky et al. 2023 Lancet 401:204-14 (Fig 2c) Week 16 Week 16 18 Amlitelimab Rocatinlimab Rezpegaldesleukin
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Rezpeg q2w Arms Show Similar Responses as OX40/OX40L Class (vIGA-AD 0/1 at Week 16) * *: Phase 3 dose level ** **: Phase 3 dose range (q4w regimen) 20% 26% 19% 8% 0 2 4 6 8 10 12 14 16 0 10 20 30 vIGA-AD 0/1 Study Weeks Response Rate (%) Week 16 Week 16 19 Amlitelimab Rocatinlimab Rezpegaldesleukin References: Amlitelimab – Weidinger et al. 5th Inflammatory Skin Disease Summit, November 15-18; Vienna Austria (Fig. 3) Rocatinlimab – Guttman-Yassky et al. 2023 Lancet 401:204-14 (Fig 2c)
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20 David Rosmarin, MD Chair of the Department of Dermatology at Indiana University School of Medicine Kampen-Norins Scholar in Dermatology Jonathan Silverberg, MD, PhD, MPH Professor of Dermatology at The George Washington University School of Medicine and Health Sciences Director of Clinical Research and Contact Dermatitis Dr. Silverberg is Professor of Dermatology at The George Washington University School of Medicine and Health Sciences in Washington, DC. He is the Director of Clinical Research and Contact Dermatitis. Dr. Silverberg's area of clinical subspecialty is inflammatory skin disease, particularly atopic and contact dermatitis. Dr. Silverberg has also been a local, national and/or international principal investigator for numerous clinical trials for novel treatments in atopic dermatitis and other inflammatory disorders. Dr. Silverberg's research interests include drug development, clinical trial design, biomarkers, dermato- epidemiology, health services research, patient-reported outcomes, comorbidities and burden of itch and inflammatory skin disease and evidence-based dermatology. His publications include more than 1000 peer- reviewed articles, abstracts and book chapters. He is an associate editor for the Journal of the American Academy of Dermatology, British Journal of Dermatology and Current Dermatology Reports. Dr. Rosmarin is Chair of the Department of Dermatology at Indiana University and is Kampen-Norins Scholar in Dermatology. He is nationally recognized and serves as a referral for physicians with difficult to manage inflammatory diseases such as atopic dermatitis. Previously, Dr. Rosmarin served as the Director of the Clinical Trials Unit in the Department of Dermatology at Tufts Medical Center. His research interests focus on development of novel therapeutics and investigating novel uses of established therapies, with a particular focus on chronic skin diseases such as atopic dermatitis, vitiligo, discoid lupus, and hidradenitis suppuritiva. For his training, Dr. Rosmarin went to medical school at NYU, dermatology residency at Boston University-Tufts combined training program, and fellowship at Brigham and Women’s Hospital.
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• Rezpeg has potential for longstanding clinical benefit (remittive effect) • Phase 2b results support advancement of a novel, first-in-class Treg-based immune-balancing mechanism Novel T-Reg MOA differentiates from existing and in-development biologics • Only T-regulatory mechanism to show compelling efficacy data across all endpoints in a large Phase 2b study • Treg fold increase up to 6-fold • Clear reduction in numerous AD markers of IL-19, TARC/CCL17, Periostin, MDC/CCL22 Highest dose arm significant on primary and all key secondary endpoints • Fast onset of clinical benefit, observed within first several doses • Clear dose-dependent efficacy across multiple dose arms • No drop-off in treatment effect in severe AD population Safety consistent with previously reported safety results • No increased risk of conjunctivitis or oral herpes as found with other biologics and JAKis • Most frequent observed AEs were mild injection site reactions (ISRs) that were self-resolving • Less than 1% of discontinuations due to ISRs 21 REZOLVE-AD Phase 2b Validates Rezpeg as a First-in-Class Novel T-Regulatory Mechanism in Atopic Dermatitis
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Rezpeg Program: Next Steps • End of Phase 2 Meeting with FDA to review Phase 3 development plan • Full presentation of data to be submitted for presentation at a medical meeting in 2025 • Topline results from Phase 2b REZOLVE-AA (alopecia areata) in December 2025 • 52-week maintenance data from Phase 2b REZOLVE-AD (atopic dermatitis) in early 2026 • 52-week off-study treatment durability data from Phase 2b REZOLVE-AD in early 2027 22
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Beyond Rezpeg in Atopic Dermatitis, Potential Blockbuster Expansions for Treg MOA Dermatology Alopecia areata (Phase 2b underway, data December 2025) Potential for expansion into vitiligo and other skin- related immune conditions Immunology Type 1 diabetes (Phase 2 starting in 2025) Potential for expansion into systemic lupus and other auto-immune conditions Second T Regulatory Cell Mechanism Entering Clinic in 2026 TNFR2 agonist antibody (planned IND 2026) with novel bispecifics combining TNFR2 agonism (Treg) with validated antibody mechanisms in auto- immune disease Potential for development in Crohn’s Disease, UC, MS 23
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Appendix (data tables, additional materials) 24
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REZOLVE-AD: Baseline Demographics Placebo q2w N = 73 Rezpeg 24 µg/kg q2w N = 104 Rezpeg 18 µg/kg q2w N = 106 Rezpeg 24 µg/kg q4w N = 110 Total N = 393 Age Mean (SD) 37.9 (14.39) 38.0 (13.73) 36.3 (15.41) 36.5 (14.30) 37.1 (14.44) Median 35 36.5 31.5 33.5 34 Min, Max 18, 69 18, 70 18, 73 18, 69 18, 73 Age Category <65 yrs 70 (95.9%) 101 (97.1%) 100 (94.3%) 103 (93.6%) 374 (95.2%) > = 65 yrs 3 (4.1%) 3 (2.9%) 6 (5.7%) 7 (6.4%) 19 (4.8%) Sex Female 35 (47.9%) 49 (47.1%) 56 (52.8%) 63 (57.3%) 203 (51.7%) Male 38 (52.1%) 55 (52.9%) 50 (47.2%) 47 (42.7%) 190 (48.3%) Race White 58 (79.5%) 87 (83.7%) 90 (84.9%) 96 (87.3%) 331 (84.2%) Black or African American 2 (2.7%) 7 (6.7%) 3 (2.8%) 5 (4.5%) 17 (4.3%) Asian 9 (12.3%) 9 (8.7%) 11 (10.4%) 7 (6.4%) 36 (9.2%) Other or not reported or Unknown 4 (5.5%) 1 (1.0%) 2 (1.9%) 2 (1.8%) 9 (2.3%) 25
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REZOLVE-AD: Baseline Demographics Country and Region Distribution Placebo q2w N = 73 Rezpeg 24 µg/kg q2w N = 104 Rezpeg 18 µg/kg q2w N = 106 Rezpeg 24 µg/kg q4w N = 110 Total N = 393 Country Australia 3 (4.1%) 3 (2.9%) 4 (3.8%) 8 (7.3%) 18 (4.6%) Bulgaria 7 (9.6%) 8 (7.7%) 9 (8.5%) 16 (14.5%) 40 (10.2%) Canada 7 (9.6%) 10 (9.6%) 14 (13.2%) 13 (11.8%) 44 (11.2%) Croatia 1 (1.4%) 4 (3.8%) 0 1 (0.9%) 6 (1.5%) Czechia 9 (12.3%) 7 (6.7%) 8 (7.5%) 9 (8.2%) 33 (8.4%) Germany 8 (11.0%) 12 (11.5%) 10 (9.4%) 8 (7.3%) 38 (9.7%) Hungary 0 0 0 1 (0.9%) 1 (0.3%) Poland 21 (28.8%) 41 (39.4%) 42 (39.6%) 36 (32.7%) 140 (35.6%) Spain 3 (4.1%) 2 (1.9%) 4 (3.8%) 0 9 (2.3%) USA 14 (19.2%) 17 (16.3%) 15 (14.2%) 18 (16.4%) 64 (16.3%) STRATA 1 for Region North America (USA, Canada) 21 (28.8%) 27 (26.0%) 29 (27.4%) 31 (28.2%) 108 (27.5%) Rest of the world 52 (71.2%) 77 (74.0%) 77 (72.6%) 79 (71.8%) 285 (72.5%) 26
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REZOLVE-AD: Baseline Disease Levels Balanced Across Arms Placebo q2w N = 73 Rezpeg 24 µg/kg q2w N = 104 Rezpeg 18 µg/kg q2w N = 106 Rezpeg 24 µg/kg q4w N = 110 Total N = 393 STRATA 1 for vIGA-AD 3 51 (69.9%) 71 (68.3%) 70 (66.0%) 75 (68.2%) 267 (67.9%) 4 22 (30.1%) 33 (31.7%) 36 (34.0%) 35 (31.8%) 126 (32.1%) EASI Total Score (0-72) Mean (SD) 25.2 (8.57) 25.4 (9.14) 27.2 (10.40) 26.1 (10.45) 26.0 (9.77) Median 23.5 23 23.8 22.6 23.4 Min, Max 16.0, 59.1 16.2, 59.6 16.3, 62.0 16.1, 66.2 16.0, 66.2 EASI Total Score Category I <18 19 (26.0%) 22 (21.2%) 16 (15.1%) 24 (21.8%) 81 (20.6%) > = 18 54 (74.0%) 82 (78.8%) 90 (84.9%) 86 (78.2%) 312 (79.4%) EASI Total Score Category II <21 29 (39.7%) 44 (42.3%) 43 (40.6%) 44 (40.0%) 160 (40.7%) > = 21 44 (60.3%) 60 (57.7%) 63 (59.4%) 66 (60.0%) 233 (59.3%) 27
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REZOLVE-AD: Majority of Rezpeg-Treated Patients Continued into Maintenance Percentages are calculated using completers at week 16 as denominator W16 EASI < 50%W16 EASI ≥ 50% Placebo REZPEG 24 μg/kg, q2w REZPEG 18 μg/kg, q2w REZPEG 24 μg/kg, q4w 28
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REZOLVE-AD: Patient Populations and Disposition Placebo q2w Rezpeg 24 µg/kg q2w Rezpeg 18 µg/kg q2w Rezpeg 24 µg/kg q4w Total Intent to Treat (ITT) 74 106 107 111 398 Modified Intent to Treat (MITT) 73 104 106 110 393 Discontinued before W16 8 (11.0%) 23 (22.1%) 25 (23.6%) 16 (14.5%) 72 (18.3%) Completed W16 induction 65 (89.0%) 81 (77.9%) 81 (76.4%) 94 (85.5%) 321 (81.7%) Continued to Maintenance (W16) 23 (31.5%) 58 (55.8%) 56 (52.8%) 53 (48.2%) 190 (48.3%) Continue study to Escape (W16) 42 (57.5%) 21 (20.2%) 20 (18.9%) 39 (35.5%) 122 (31.0%) Discontinued at W16 0 2 (1.9%) 5 (4.7%) 2 (1.8%) 9 (2.3%) MITT Population count is used as the denominator to calculate the percentages in this table. Discontinuation rates for all rezpeg arms comparable to treatment arms in Phase 2b studies for approved and late-stage biologics (others range from 3 – 24%)* *Dupilumab Phase 2b (Thaci et al. 2016, Lancet 387:40-52 & supplemental); Tralokinumab Phase 2b (Wollenberg et al. 2019, JACI 143:135-41 & supplemental); Lebrikizumab Phase 2b (Guttman-Yassky et al. 2020, JAMA Derm 156:411- 20 & supplemental); Nemolizumab Phase 2b (Silverberg et al. 2020, JACI 145:173-82 & supplemental); Rocatinlimab Phase 2b (Guttman-Yassky et al. 2023, Lancet 401:204-14); Amlitelimab Phase 2b (Weidinger et al. 2025, JACI 155:1264- 75 & supplemental) 29
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REZOLVE-AD: Treatment Discontinuation Reasons During 16- Week Induction Placebo q2w N = 73 Rezpeg 24 µg/kg q2w N = 104 Rezpeg 18 µg/kg q2w N = 106 Rezpeg 24 µg/kg q4w N = 110 Rezpeg Overall N = 320 Total N = 393 Discontinued before Week 16 8 (11.0%) 23 (22.1%) 25 (23.6%) 16 (14.5%) 64 (20.0%) 72 (18.3%) Adverse Event 0 7 (6.7%) 5 (4.7%) 4 (3.6%) 16 (5.0%) 16 (4.1%) ISR subset 0 1 (1.0%) 0 1 (0.9%) 2 (0.6%) 2 (0.5%) Non-Compliance with Study Procedure 0 0 0 1 (0.9%) 1 (0.3%) 1 (0.3%) Patient Decision 7 (9.6%) 14 (13.5%) 19 (17.9%) 9 (8.2%) 42 (13.1%) 49 (12.5%) Lack of efficacy to study treatment 0 1 (1.0%) 0 1 (0.9%) 2 (0.6%) 2 (0.5%) Other 1 (1.4%) 1 (1.0%) 1 (0.9%) 1 (0.9%)* 3 (0.9%) 4 (1.0%) Discontinued at Week 16 0 2 (1.9%) 5 (4.7%) 2 (1.8%) 9 (2.8%) 9 (2.3%) EASI-50 Responder 0 1 (1.0%) 4 (3.8%) 1 (0.9%) 6 (1.9%) 6 (1.5%) Patient Decision 0 1 (1.0%) 3 (2.8%) 0 4 (1.3%) 4 (1.0%) EASI-50 Non-responder 0 1 (1.0%) 1 (0.9%) 1 (0.9%) 3 (0.9%) 3 (0.8%) Adverse Event 0 1 (1.0%) 0 0 1 (0.3%) 1 (0.3%) Overall discontinuation rates due to AEs for treatment arms across Phase 2b studies for approved and late-stage biologic therapies range from 0 – 15%* *Dupilumab Phase 2b (Thaci et al. 2016, Lancet 387:40-52 & supplemental); Tralokinumab Phase 2b (Wollenberg et al. 2019, JACI 143:135-41 & supplemental); Lebrikizumab Phase 2b (Guttman-Yassky et al. 2020, JAMA Derm 156:411-20 & supplemental); Nemolizumab Phase 2b (Silverberg et al. 2020, JACI 145:173-82 & supplemental); Rocatinlimab Phase 2b (Guttman-Yassky et al. 2023, Lancet 401:204-14); Amlitelimab Phase 2b (Weidinger et al. 2025, JACI 155:1264-75 & supplemental) 30 *One patient cited reason for other specified as AE.
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Overall Summary of Treatment Emergent Adverse Events 16-Week Induction Period Placebo q2w N = 73 Rezpeg 24 µg/kg q2w N = 104 Rezpeg 18 µg/kg q2w N = 106 Rezpeg, 24 µg/kg q4w N = 110 Rezpeg Total N = 320 Patients With at Least One TEAE 42 (57.5%) 89 (85.6%) 78 (73.6%) 90 (81.8%) 257 (80.3%) Patients With at Least One TEAE (Excluding ISRs) 42 (57.5%) 69 (66.3%) 60 (56.6%) 64 (58.2%) 193 (60.3%) Patients With at Least One Serious TEAE 0 1 (1.0%) 4 (3.8%) 0 5 (1.6%) Patients With at Least One Severe TEAE 1 (1.4%) 3 (2.9%) 6 (5.7%) 1 (0.9%) 10 (3.1%) Patients With at Least One TEAE Leading to Death* 0 0 0 0 0 TEAEs by System Organ Class and Preferred Term Over ≥ 5% in Any Arm General disorders and administration site conditions 7 (9.6%) 80 (76.9%) 67 (63.2%) 78 (70.9%) 225 (70.3%) Injection site reaction 3 (4.1%) 79 (76.0%) 66 (62.3%) 78 (70.9%) 223 (69.7%) Proportion of ISR events-mild (%) 100% 65.5% 70.7% 69.9% 68.3% Proportion of ISR events-moderate (%) 0% 33.9% 28.9% 30.1% 31.3% Proportion of ISR events-severe (%) 0% 0.6% 0.4% 0% 0.4% Pyrexia 2 (2.7%) 11 (10.6%) 5 (4.7%) 4 (3.6%) 20 (6.3%) Infections and infestations 25 (34.2%) 29 (27.9%) 39 (36.8%) 32 (29.1%) 100 (31.3%) Nasopharyngitis 10 (13.7%) 10 (9.6%) 14 (13.2%) 14 (12.7%) 38 (11.9%) Upper respiratory tract infection 4 (5.5%) 7 (6.7%) 8 (7.5%) 4 (3.6%) 19 (5.9%) Blood and lymphatic system disorders 3 (4.1%) 29 (27.9%) 6 (5.7%) 11 (10.0%) 46 (14.4%) Eosinophilia 2 (2.7%) 17 (16.3%) 4 (3.8%) 4 (3.6%) 25 (7.8%) Lymphadenopathy 0 7 (6.7%) 1 (0.9%) 3 (2.7%) 11 (3.4%) Musculoskeletal and connective tissue disorders 3 (4.1%) 19 (18.3%) 5 (4.7%) 11 (10.0%) 35 (10.9%) Arthralgia 1 (1.4%) 10 (9.6%) 2 (1.9%) 4 (3.6%) 16 (5.0%) Skin and subcutaneous tissue disorders 8 (11.0%) 12 (11.5%) 10 (9.4%) 13 (11.8%) 35 (10.9%) Worsening atopic dermatitis 7 (9.6%) 2 (1.9%) 5 (4.7%) 6 (5.5%) 13 (4.1%) Nervous system disorders 6 (8.2%) 10 (9.6%) 10 (9.4%) 9 (8.2%) 29 (9.1%) Headache 3 (4.1%) 8 (7.7%) 6 (5.7%) 6 (5.5%) 20 (6.3%) Gastrointestinal disorders 3 (4.1%) 8 (7.7%) 7 (6.6%) 11 (10.0%) 26 (8.1%) Respiratory, thoracic and mediastinal disorders 1 (1.4%) 6 (5.8%) 5 (4.7%) 5 (4.5%) 16 (5.0%) Investigations 1 (1.4%) 6 (5.8%) 4 (3.8%) 3 (2.7%) 13 (4.1%) 31 *Following 16-week induction, one death in a 38 y/o female occurred in the escape arm due to coronary thrombosis/heart failure. Patient had multiple, overlapping pre-existing cardiovascular risk factors. The death was assessed as unrelated to study treatment by the Sponsor Drug Safety Committee and independent external experts.
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REZOLVE-AD: Serious TEAEs and TRAEs (All Cases) 16-Week Induction Period System Organ Class Preferred Term Placebo q2w N = 73 Rezpeg 24 µg/kg q2w N = 104 Rezpeg 18 µg/kg q2w N = 106 Rezpeg 24 µg/kg q4w N = 110 Rezpeg Overall N = 320 TEAE TRAE TEAE TRAE TEAE TRAE TEAE TRAE TEAE TRAE Patients With at Least One Serious AE 0 0 1 (1.0%) 0 4 (3.8%) 2 (1.9%) 0 0 5 (1.6%) 2 (0.6%) Infections and infestations 0 0 1 (1.0%) 0 1 (0.9%) 1 (0.9%) 0 0 2 (0.6%) 1 (0.3%) Gastroenteritis viral 0 0 1 (1.0%) 0 0 0 0 0 1 (0.3%) 0 Tonsillitis 0 0 0 0 1 (0.9%) 1 (0.9%) 0 0 1 (0.3%) 1 (0.3%) Immune system disorders 0 0 0 0 1 (0.9%) 1 (0.9%) 0 0 1 (0.3%) 1 (0.3%) Drug hypersensitivity 0 0 0 0 1 (0.9%) 1 (0.9%) 0 0 1 (0.3%) 1 (0.3%) Nervous system disorders 0 0 0 0 1 (0.9%) 0 0 0 1 (0.3%) 0 Cerebrovascular accident 0 0 0 0 1 (0.9%) 0 0 0 1 (0.3%) 0 Skin and subcutaneous tissue disorders 0 0 0 0 1 (0.9%) 0 0 0 1 (0.3%) 0 Worsening atopic dermatitis 0 0 0 0 1 (0.9%) 0 0 0 1 (0.3%) 0 System organ class and preferred terms are coded based on the MedDRA v26.0. TEAEs in Induction are defined as AEs that start on or after the first dose date after randomization and up to one day before first dose date in maintenance or escape if patients receive at least one dose in maintenance or escape, or 30 days after last dose if patients EOT, otherwise, no ending date. 32
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REZOLVE-AD: Severe TEAEs and TRAEs in ≥ 2 Patients in Any Arm 16-Week Induction Period System Organ Class Preferred Term Placebo q2w N = 73 Rezpeg 24 µg/kg q2w N = 104 Rezpeg 18 µg/kg q2w N = 106 Rezpeg 24 µg/kg q4w N = 110 Rezpeg Overall N = 320 TEAE TRAE TEAE TRAE TEAE TRAE TEAE TRAE TEAE TRAE Patients With at Least One Severe AE 1 (1.4%) 0 3 (2.9%) 3 (2.9%) 6 (5.7%) 3 (2.8%) 1 (0.9%) 0 10 (3.1%) 6 (1.9%) General disorders and administration site conditions 0 0 3 (2.9%) 3 (2.9%) 2 (1.9%) 2 (1.9%) 0 0 5 (1.6%) 5 (1.6%) Injection site reaction 0 0 2 (1.9%) 2 (1.9%) 1 (0.9%) 1 (0.9%) 0 0 3 (0.9%) 3 (0.9%) Chest pain 0 0 0 0 1 (0.9%) 1 (0.9%) 0 0 1 (0.3%) 1 (0.3%) Pyrexia 0 0 1 (1.0%) 1 (1.0%) 0 0 0 0 1 (0.3%) 1 (0.3%) Skin and subcutaneous tissue disorders 1 (1.4%) 0 0 0 2 (1.9%) 0 0 0 2 (0.6%) 0 Worsening atopic dermatitis 1 (1.4%) 0 0 0 2 (1.9%) 0 0 0 2 (0.6%) 0 Immune system disorders 0 0 0 0 1 (0.9%) 1 (0.9%) 0 0 1 (0.3%) 0 Drug hypersensitivity 0 0 0 0 1 (0.9%) 1 (0.9%) 0 0 1 (0.3%) 0 Nervous system disorders 0 0 0 0 1 (0.9%) 0 0 0 1 (0.3%) 0 Cerebrovascular accident 0 0 0 0 1 (0.9%) 0 0 0 1 (0.3%) 0 Respiratory, thoracic and mediastinal disorders 0 0 0 0 0 0 1 (0.9%) 0 1 (0.3%) 0 Rhinitis allergic 0 0 0 0 0 0 1 (0.9%) 0 1 (0.3%) 0 33
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Atopic Dermatitis Presents Potential Multi-Billion Dollar Market Opportunity Still High Unmet Need, Especially For New Therapies With Potential for Remittive Effect ~30 million 1 Adults with AD in U.S. ~220 million 2 Adults with AD globally ~50% 3 Adults with AD have moderate-to-severe disease DUPIXENT® is a registered trademarks of Sanofi Biotechnology. Source: 1Eczema stats. National Eczema Association. (2022, September 27). https://nationaleczema.org/research/eczema-facts/; 2Eczema council. (n.d.). https://www.eczemacouncil.org/assets/docs/global-report-on-atopic-dermatitis-2022.pdf; 3ClarivateTM DRG Mature Markets Data 2023.; 4DRG Epidemiology; 5N Engl J Med 2016; 375:2335-2348 DOI: 10.1056/NEJMoa1610020; 6Evaluate Ltd (accessed: 1/6/2025) Atopic dermatitis (AD) is a chronic autoimmune condition that causes inflammation, redness and irritation of the skin. Moderate-to-severe AD is associated with unbearable itching that can result in significant negative impact to quality of life. Dupixent®: current market leader in atopic dermatitis exceeding $10.5B in annual sales, but 50% of patients fail on therapy5, 6 We believe there is a high unmet need for new mechanism of action with potential to: • Offer dosing schedules without rebound effect • Induce deep and potentially therapy-free remission • Favorable safety and tolerability profile for ease of use~8% 4 Patients with moderate/severe AD are treated with a biologic 34
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Rezpegaldesleukin (Rezpeg) is Potential First-in-Class T-Regulatory Cell Mechanism to Restore Balance in Immune System 35 Increased activity and number of T effector cells shift the balance toward inflammation Treg Treg expansion and activation restores the immunoregulatory balance Treg Teff Many patients with moderate-to-severe atopic dermatitis (AD) do not adequately achieve disease control or have safety/tolerability issues with current therapies Tregs play a central role in controlling AD by dampening inflammatory cytokines and overactive T-cells 1 Rezpegaldesleukin is a potential T-cell balancing therapy that has been shown to2,3: - Enhance Treg numbers - Stimulate Tregs thereby reducing proinflammatory cytokines - Offer potential for long-term control of over-active immune response αβγ 1) Silverberg et al. 2024 Nature Communications, 15:9230 2) Fanton et al. 2022 J. Translational Autoimmunity, 5:100152 3) Dixit et al. 2021 J Translational Autoimmunity, 4:100103 Rezpegaldesleukin acts on IL2 receptors to proliferate T-regulatory cells and restore their functionality