Slide 1: CUE-221 Phase 2 Chronic Spontaneous Urticaria
CUE-221 Phase 2 Chronic Spontaneous Urticaria September 2026 ©2026 ©2026Cue ©2024 CueBiopharma Biopharma C O N F I D E N T I A L D O N O T D I S T R I B U T E
Slide 2: Forward-Looking Statements & Disclaimer
Forward-Looking Statements & Disclaimer • This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, those regarding the potential of CUE-221, including its potenti
Slide 3: Positive Results from CUE-221 Phase 2 CSU Study Demonstrate Robust and Durable Clinical Benefit
Positive Results from CUE-221 Phase 2 CSU Study Demonstrate Robust and Durable Clinical Benefit • Robust Dose-Responsive Results: Primary endpoint of complete resolution of hives (HSS7=0) vs. placebo at week 12 was met, with treatment effect peaking at Week 22 • Potent Disease Control: Secondary end
Slide 4: IgE Drives Allergic Disease by Engaging Two Critical Receptors
IgE Drives Allergic Disease by Engaging Two Critical Receptors FcεRI and CD23 (FcεRII) regulate the allergic response Cross-linking the FcεRI (high affinity) receptor leads B cell surface CD23 (low affinity receptor) decreases IgE to allergic reaction production when engaged by IgE IgE binds to FcεR
Slide 5: CUE-221 Blocks IgE Binding to FcRI: Potent IgE Neutralization
CUE-221 Blocks IgE Binding to FcRI: Potent IgE Neutralization 4-8-fold higher binding affinity Potent Inhibition of FcRI binding results in 7-fold greater potency than (picomolar range) and slower dissociation omalizumab at blocking basophils degranulation (off-rate) than omalizumab Less CUE-221 d
Slide 6: CUE-221 Preserves IgE Binding to FcRII (CD23): Maintains Regulation of IgE synthesis
CUE-221 Preserves IgE Binding to FcRII (CD23): Maintains Regulation of IgE synthesis CUE-221 OMALIZUMAB CUE-221 Omalizumab Binding site (& RPT904) Binding site CUE-221 binds to IgE (yellow) at a Omalizumab and RPT904 (brown) bind IgE location that is distant from where IgE at a location that substa
Slide 7: CUE-221 Differentiated IgE Binding Enables Distinct Functional Properties
CUE-221 Differentiated IgE Binding Enables Distinct Functional Properties IgE binding to CD23 is Preserved Despite Binding of CUE-221 to IgE CUE-221 UB-221 Omalizumab CUE-221 Free-form Anti-IgE: IgE complex 120 Amount of Complex Bound CUE-221 CUE-221 100 CUE-221 binding to IgE preserves IgE-CD23 int
Slide 8: CD23 Acts as a Natural Brake on IgE Production When IgE is Abundant
CD23 Acts as a Natural Brake on IgE Production When IgE is Abundant CUE-221 leverages the CD23-mediated IgE downregulation pathway, decreasing new IgE mRNA and protein synthesis1 IgE mRNA2 IgE protein synthesis3 200 *** ** *** 150 ** ** * CUE-221-IgE binds CD23 and 175 125 downregulates new IgE synt
Slide 9: CSU P2 Study Design
CSU P2 Study Design Randomized Double-Blind Placebo Controlled Study with Active Comparator CUE-221 4 mg/kg Q4W SC Adults with CSU Randomization ( 2:2:2:1:1) inadequately controlled End of Treatment CUE-221 2 mg/kg Q4W SC with H1 antihistamines 20-Week Post- Screening treatment Moderate-to-Severe CS
Slide 10: Subject Disposition
Subject Disposition Randomized N= 145 1 CUE-221 CUE-221 CUE-221 Omalizumab Placebo 4 mg/kg Q4W 2 mg/kg Q4W 1 mg/kg Q4W 300 mg Q4W Q4W n=36 n=36 n=37 n=18 n=18 33 Completed 33 Completed 32 Completed 15 Completed 18 Completed week 12; week 12; week 12; week 12; week 12; 24 Completed 28 Completed 24 Co
Slide 11: Key Baseline Characteristics
Key Baseline Characteristics1 CUE-221 Q4W Omalizumab Characteristic 4 mg/kg 2 mg/kg 1 mg/kg 300 mg Placebo N=35 N=36 N=37 N=17 N=18 Age (years) 41.7 (11.9) 39.1 (13.6) 42.8 (13.1) 42.3 (13.4) 37.8 (15.6) Female, n (%) 19 (54.3%) 18 (50.0%) 23 (62.2%) 6 (35.3%) 11 (61.1%) Weight (kg) 66.6 (11.5) 68.6
Slide 12: Primary Endpoint Met: Complete Resolution of Hives (HSS7=0) at Week 12
Primary Endpoint Met Complete Resolution of Hives (HSS7=0) at Week 12 Was Significantly Higher Versus Placebo and Dose Responsive Across CUE-221 Dose Groups 70 % Complete Resolution of Hives (HSS7=0) 60 = 43 54 *** 53 *** 50 43 * 41 40 30 20 11 10 0 CUE-221 4 mg/kg Cue-221 2 mg/kg Cue-221 1 mg/kg
Slide 13: Key Secondary Endpoint Met: Complete Response (UAS7=0) at Week 12
Key Secondary Endpoint Met Complete Response (UAS7=0) at Week 12 was Significantly Higher Versus Placebo in the 4 mg/kg CUE-221 Dose Group 60 ∆ = 35 50 46 * % Complete Response ( UAS7=0) 40 39 38 ∆ = 17 29 30 20 11 10 0 CUE-221 4 mg/kg Cue-221 2 mg/kg Cue-221 1 mg/kg Omalizumab 300 mg Placebo Q4W Q4
Slide 14: Profound, Significant, and Clinically Meaningful Change From Baseline in UAS7
Profound, Significant, and Clinically Meaningful Change From Baseline At Week 12 In Disease Activity Score (UAS7) CUE-221 4 mg/kg Cue-221 2 mg/kg Cue-221 1 mg/kg Omalizumab 300 mg Q4W Q4W Q4W Q4W Placebo 0 Change from baseline in UAS7 LS -5 -10 -15 -13 -20 -22 ** -25 -24 **** -24 **** -23 -30 UAS7 c
Slide 15: Percent Mean Reduction From Baseline in UAS7 Across Mechanisms
Percent Mean Reduction From Baseline in UAS7 at Week 12 Across Mechanisms RAPT P2 Barzo P2 CUE-221 P2 1 Dupi P3 Remi P3 (cKIT) (IL4/IL13) (BTK) (Anti-IgE) CUE 4 CUE 2 CUE 1 Oma 300 Placebo Dupi 300 Remi 25 mg RPT904 300 RPT904 300 Barzo 300 Barzo 150 mg/kg Q4W mg/kg Q4W mg/kg Q4W mg Q4W Placebo Rang
Slide 16: Complete Hives Resolution Continued to Increase Beyond Week 12
Complete Hives Resolution (HSS7=0) Continued to Increase Beyond Week 12; Most subjects on CUE-221 responded and achieved complete resolution of hives 80 CUE-221 Peak = 28 70 69 61 60 = 36 * % Resolution of Hives (HSS7=0) 60 = 13 57 54 53 Suggests fundamental biological difference 50 43 between
Slide 17: Rapid and Sustained Complete Resolution of Hives Through Week 28
Rapid and Sustained Complete Resolution of Hives Through 12 Weeks Post Last Dose (Week 28) 80 69 70 63 63 60 60 % Resoluton of Hives (HSS7 =0) 57 57 60 54 53 50 46 43 47 * 40 41 41 41 34 35 29 30 29 29 29 26 29 24 24 24 20 17 17 17 11 11 11 11 11 11 10 6 6 6 0 0 0 0 Week 1 Week 4 Week 8 Week 12 Week
Slide 18: Complete Response (UAS7=0) is Also Sustained Over Weeks Off Drug
Complete Response (UAS7=0) is Also Sustained Over 12 Weeks Off Drug (Week 28) at the Highest Dose HSS7=0 50 UAS7=0 * 43 Suggests fundamental % Complete Responders (UAS7=0) 40 biological difference = 19 between omalizumab and CUE- 30 221, supportive of its 25 24 dual MoA design 19 20 11 10 0 Week 2
Slide 19: Contrasting Features of Targeted IgE Therapies
Contrasting Features of Targeted IgE Therapies 60 60 CUE-221 P2 RPT904 P2 CUE-221 P2 RPT904 P2 RPT904 P2 50 50 46 % Complete Response (UAS7=0) 43 39 39 40 38 37 40 29 30 30 25 24 20 19 20 11 Not 11 Disclosed 10 10 0 0 Week 12 Week 28 • The IgE neutralizers • Impact of RPT904 at timepoints Week 28 &
Slide 20: CUE-221 Was Well Tolerated
CUE-221 Was Well Tolerated No treatment related SAEs No adverse events of anaphylaxis CUE-221 Q4W Omalizumab Q4W Treatment group 4 mg/kg 2 mg/kg 1 mg/kg 300 mg Placebo n (%) N=35 N=36 N=37 N=17 N=18 Any TEAE Treatment Related 15 (42.9%) 17 (47.2%) 12 (32.4%) 4 (23.5%) 11 (61.1%) Treatment-related SA
Slide 21: Risk/Benefit Considerations Across Different MOAs
Risk/Benefit Considerations Across Different MOAs XOLAIR® DUPIXENT® RHAPSIDIO® Barzolvolimab (omalizumab) (dupilumab) (remibrutinib) (investigational) MOA Anti-IgE mAb Anti-IL4/IL13 mAb Oral selective BTK Anti-KIT mAb inhibitor Key Warnings/ Anaphylaxis (boxed Hypersensitivity Risk of bleeding; n/a
Slide 22: Targeting Potential for Functional Cure of IgE-Mediated Disease
Targeting Potential for Functional Cure of IgE-Mediated Disease CUE-221 BINDING SITE CUE-221 DOES NOT PREVENT IgE:CUE-221 MAINTAINED CD23 NEGATIVE FEEDBACK CONTRASTING CLINICAL IMPACT 3-MONTH OFF DRUGS DIFFERS FROM OMALIZUMAB COMPLEXES FROM BINDING CD23 LOOP RESULTS IN REDUCED IgE SYNTHESIS POINTS T
Slide 23: Positive Results from CUE-221 Phase 2 CSU Study Demonstrate Robust and Durable Clinical Benefit
Positive Results from CUE-221 Phase 2 CSU Study Demonstrate Robust and Durable Clinical Benefit • Robust Dose-Responsive Results supported by primary endpoint and key secondary endpoint met with statistical significance • Favorable Safety and Tolerability without hypersensitivity reactions (anaphyla