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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma ©2026 Cue Biopharma CUE-221 Phase 2 Chronic Spontaneous Urticaria September 2026
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma 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 potential future benefit to patients, the company's plans with respect to CUE-221, including the initiation of a Phase 2b/3 clinical trial in chronic spontaneous urticaria and a Phase 2 clinical trial in food allergy and the timings thereof, the company's expectations regarding the presentation of full clinical data from the Phase 2 CUE-221 trial, and the company's expectations regarding the company's growth, and the company's business strategies, plans, and prospects. Forward-looking statements, which are based on certain assumptions and describe the company's future plans, strategies and expectations, can generally be identified by the use of forward-looking terms such as “believe,” “expect,” “may,” “will,” “should,” “would,” “could,” “seek,” “intend,” “plan,” “goal,” “project,” “estimate,” “anticipate,” “strategy,” “future,” “likely,” “promise,” “potential” or other comparable terms, although not all forward-looking statements contain these identifying words. All statements other than statements of historical facts included in this presentation regarding the company's strategies, prospects, financial condition, operations, costs, plans, and objectives are forward-looking statements. Important factors that could cause the company's actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the company's ability to maintain and establish collaboration, licensing and other arrangements; the company's limited operating history, limited cash and a history of losses; the company's ability to obtain adequate financing to fund its business operations in the future; the company's ability to achieve profitability; potential setbacks in the company's research and development efforts for its current and future drug product candidates, including negative or inconclusive results from its preclinical studies or clinical trials or the company's ability to replicate in later clinical trials positive results found in preclinical studies and early-stage clinical trials of its product candidates; serious and unexpected drug-related side effects or other safety issues experienced by participants in clinical trials; potential challenges associated with clinical trials conducted in China and the company's access to, and acceptability of, the data therefrom; its ability to secure required U.S. Food and Drug Administration (FDA) or other governmental approvals for its product candidates and the breadth of any approved indication; delays and changes in regulatory requirements, policy and guidelines including potential delays in submitting required regulatory applications to the FDA; the company's reliance on licensors, collaborators, contract research organizations, suppliers and other business partners; the company's ability to maintain and enforce necessary patent and other intellectual property protection; competitive factors; general economic and market conditions and the other risks and uncertainties described in the Risk Factors and Management's Discussion and Analysis of Financial Condition and Results of Operations sections of the company's most recently filed Annual Report on Form 10-K and any subsequently filed Quarterly Report(s) on Form 10-Q. Any forward-looking statement made by the company in this presentation is based only on information currently available to the company and speaks only as of the date on which it is made. The company undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. • This presentation also contains estimates, projections and other statistical data made by independent parties and by the company relating to market size and growth and other data about the company’s industry and business. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. The company has not independently verified the accuracy and completeness of the information obtained by third parties included in this presentation. In addition, projections, assumptions and estimates of the company’s future performance and the future performance of the markets in which the company operates are necessarily subject to a high degree of uncertainty and risk. CONFIDENTIAL CONFIDENTIAL 2
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma 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 endpoint of complete response (UAS7=0) was statistically significant in the high-dose group, further supporting clinically meaningful impact • Favorable Safety and Tolerability: including no hypersensitivity reactions (i.e. anaphylaxis) • Durable Benefit: both observations of complete hives resolution and complete response persisted for 12 weeks off-drug for the high-dose group, but not for omalizumab, pointing to fundamental biological differences • Potential as Disease Modifier: We believe the stark contrast observed off-drug at week 28 against a sole IgE neutralizer provides clinical evidence supportive of CUE-221 engineered dual MOA with both neutralization and down-regulation of IgE synthesis • Next Steps: Based on demonstrated potential for differentiated efficacy in CSU and clinical evidence of relevance for the dual MOA, we will plan both P2b/3 in CSU and P2 in food allergy 3
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma IgE Drives Allergic Disease by Engaging Two Critical Receptors FcεRI and CD23 (FcεRII) regulate the allergic response CD23 receptor down-regulates IgE synthesis2IgE binds to FcεRI receptor on the surface of mast cells FcεRI (red): IgE receptor 1 Source: 1 Wright et al 2015 Nature Scientific Reports; 2 Conrad et al. 2007 Curr Allergy & Asthma Reports B cell surface CD23 (low affinity receptor) decreases IgE production when engaged by IgE Cross-linking the FcεRI (high affinity) receptor leads to allergic reaction 4
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma CUE-221 Blocks IgE Binding to FcRI: Potent IgE Neutralization 4-8-fold higher binding affinity (picomolar range) and slower dissociation (off-rate) than omalizumab Source: Kuo et al. J Clin Invest. 2022 and data on file. CUE-221 Potent Inhibition of FcRI binding results in 7-fold greater potency than omalizumab at blocking basophils degranulation Allergen CUE-221 FcRI expressing cells CUE-221 Intensity of degranulation (%) Less CUE-221 drug required to prevent allergen-induced degranulation 5
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma CUE-221 binds to IgE (yellow) at a location that is distant from where IgE (grey) and CD23 interact (green) Omalizumab and RPT904 (brown) bind IgE at a location that substantially overlaps the sites where IgE and CD23 interact (cyan) Source: Kuo et al. J Clin Invest. 2022 CUE-221 OMALIZUMA B CUE-221 Binding site Omalizumab (& RPT904) Binding site CUE-221 was engineered to provide greater control of IgE than that achieved by solely blocking the high affinity receptor CUE-221 Preserves IgE Binding to FcRII (CD23): Maintains Regulation of IgE synthesis 6
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma CUE-221 Differentiated IgE Binding Enables Distinct Functional Properties IgE binding to CD23 is Preserved Despite Binding of CUE-221 to IgE Anti-IgE: IgE complex Source: Kuo et al. J Clin Invest. 2022 0 20 40 60 80 100 120 1 10 100 1000 UB-221 Omalizumab Binding of mAb-IgE complexes to immobilized CD23 mAb (ng/mL) Amount of Complex Bound (% Max. OD450) CUE-221 CUE-221 Free-form CUE-221 CUE-221 CUE-221 binding to IgE preserves IgE-CD23 interaction (total IgE binds to CD23) Omalizumab binding to IgE blocks IgE- CD23 interaction (omalizumab-IgE does not bind CD23) 7
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma Source: Adapted from Kuo et al. J Clin Invest. 2022 Note: 1 Human PBMCs were stimulated with IL-4 and anti-CD40 to induce IgE production, treated with mAbs for 11 days; Total IgE (by ELISA) and IgE mRNA levels (by real-time PCR; data not shown) measured relative to untreated controls; The unstimulated group corresponds PBMCs in which NO IL-4 and NO anti-CD40 was added, and thus is the background IgE (low/undetectable); The untreated group corresponds to a group that was stimulated with IL-4 + anti-CD40 but NO anti-IgE antibody added. This group produces a full IgE response andis used as the reference/baseline (100%). 2 1 µg/mL; 3 10 µg/mL 0 25 50 75 100 125 150 Unstimulated Untreated CUE-221 Omalizumab *** ** *** 0 25 50 75 100 125 150 175 200 Unstimulated Untreated CUE-221 Omalizumab Relative IgE mRNA expression Total IgE (%) ** ** * IgE protein synthesis3IgE mRNA2 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 Omalizumab-IgE cannot bind CD23 and does not impact new IgE synthesis CUE-221-IgE binds CD23 and downregulates new IgE synthesis 8
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma CSU P2 Study Design Randomized Double-Blind Placebo Controlled Study with Active Comparator Screening CUE-221 2 mg/kg Q4W SC Randomization ( 2:2:2:1:1) CUE-221 1 mg/kg Q4W SC Omalizumab 300 mg Q4W SC D1 CUE-221 4 mg/kg Q4W SC Placebo SC Q4W W16W12W4 W8 End of Treatment 20-Week Post- treatment Follow-up (off drug) W36 Adults with CSU inadequately controlled with H1 antihistamines Moderate-to-Severe CSU: UAS7 score ≥ 16 and HSS7 ≥ 8 during 7 days prior to Day 1 Primary Endpoint HSS7=0 Dosing 9
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma Subject Disposition Randomized N= 145 1 CUE-221 4 mg/kg Q4W n=36 CUE-221 2 mg/kg Q4W n=36 CUE-221 1 mg/kg Q4W n=37 Omalizumab 300 mg Q4W n=18 Placebo Q4W n=18 33 Completed week 12; 24 Completed Study 33 Completed week 12; 28 Completed Study 32 Completed week 12; 24 Completed Study 15 Completed week 12; 13 Completed Study 18 Completed week 12; 14 Completed Study 1 The study was analyzed using a modified ITT approach. Twosubjects were randomized but not dosed: one in the 4 mg/kg group and one in the omalizumab group. These two subjects were not part of the analysis, but all other subjects were included in the mITT analysis. 10
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma Key Baseline Characteristics1 CUE-221 Q4W Characteristic 4 mg/kg N=35 2 mg/kg N=36 1 mg/kg N=37 Omalizumab 300 mg N=17 Placebo 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 (14.8) 69.5 (13.9) 77.2 (16.0) 65.3 (15.3) CSU duration (years) 4.1 (3.3) 6.1 (6.6) 4.0 (6.3) 3.3 (3.9) 4.5 (5.1) UAS7 28.5 (7.1) 31.0 (6.8) 29.5 (6.9) 30.6 (7.3) 31.7 (8.5) HSS7 13.8 (4.1) 15.3 (4.0) 14.4 (3.6) 15.0 (3.8) 15.2 (4.6) ISS7 14.7 (3.5) 15.7 (4.3) 15.1 (3.8) 15.6 (3.6) 16.6 (4.1) Previous experience with omalizumab (Yes; n [%]) 2 (5.7%) 2 (5.6%) 0 (0%) 0 (0%) 2 (11.1%) 1 Data shown are mean (SD), unless otherwise specified; UAS7≥28 defines severe disease activity 11
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma 54 53 43 41 11 CUE-221 4 mg/kg Q4W Cue-221 2 mg/kg Q4W Cue-221 1 mg/kg Q4W Omalizumab 300 mg Q4W Placebo 0 10 20 30 40 50 60 70 % Complete Resolution of Hives (HSS7=0) 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 Statistical significance vs placebo: ***p <0.005; * p<0.05; The study was designed to test superiority over placebo. Omalizumab was included to enable comparative efficacy without planned statistical testing. = 43 *** * *** 12
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma 46 39 38 29 11 CUE-221 4 mg/kg Q4W Cue-221 2 mg/kg Q4W Cue-221 1 mg/kg Q4W Omalizumab 300 mg Q4W Placebo 0 10 20 30 40 50 60% Complete Response ( UAS7=0) 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 Statistical significance vs placebo: * p<0.05; ∆ = 35 ∆ = 17 * 13
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma -24 -24 -22 -23 -13 -30 -25 -20 -15 -10 -5 0 CUE-221 4 mg/kg Q4W Cue-221 2 mg/kg Q4W Cue-221 1 mg/kg Q4W Omalizumab 300 mg Q4W Placebo Profound, Significant, and Clinically Meaningful Change From Baseline At Week 12 In Disease Activity Score (UAS7) Change from baseline in UAS7 Level of UAS7 reduction well in excess of Minimal Clinically Important Difference of 9.5-10.5 points (Mathias et al., Ann. Allergy Asthma Immunol., 2012) Statistical significance vs placebo: **** p <0.001; , ** p<0.01 **** ** **** 14
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma -84 -77 -75 -75 -41 -53 -65 -76 -77 -77 -75 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 CUE 4 mg/kg Q4W CUE 2 mg/kg Q4W CUE 1 mg/kg Q4W Oma 300 mg Q4W Placebo Placebo Range Dupi 300 mg Q2W Remi 25 mg BID RPT904 300 mg Q12W RPT904 300 mg Q8W Barzo 300 mg Q8W Barzo 150 mg Q4W Percent Mean Reduction From Baseline in UAS7 at Week 12 Across Mechanisms Sources: CUE-221 Data on File; Dupilumab: Mathur et al. J Allergy Clin Immunol 2024; Remibrutinib REMIX-1: Metz et al. NEJM 2025 and US Prescribing Information; RPT904: RAPT therapeutics PR 20Oct2025; Barzolvolimab: Metz et al. Allergy Clin Immunol 2026. Omalizumab ASTERIA I: Baseline UAS7 = 31.3 and change from baseline at week 12 = 21: Saini et al. J of Investigative Dermatol 2015 and US Prescribing Information. Placebo (-37 to -39) is range across Dupilumab, Remibrutinib and Barzolvolimab trials; RPT904 P2 did not include placebo. • Across published trials, CUE-221 comes closest to providing full control of disease activity • Residual disease activity estimated of minimal clinical relevance Remi P3 (BTK) RAPT P2 (Anti-IgE) CUE-221 P2 1 Dupi P3 (IL4/IL13) Barzo P2 (cKIT) Percent Reduction from Baseline in UAS7 -37 to -39 15
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma Complete Hives Resolution (HSS7=0) Continued to Increase Beyond Week 12; Most subjects on CUE-221 responded and achieved complete resolution of hives 54 69 60 53 61 31 43 57 24 41 41 24 11 11 11 0 10 20 30 40 50 60 70 80 Week 12 Week 22 Week 28 % Resolution of Hives (HSS7=0) CUE-221 4 mg/kg Q4W Cue-221 2 mg/kg Q4W Cue-221 1 mg/kg Q4W Omalizumab 300 mg Q4W Placebo CUE-221 Peak = 36 * Suggests fundamental biological difference between omalizumab and CUE- 221, supportive of its dual MoA design • Completed resolution of hives peaked at week 22, which is 6 weeks after last dose • Meaningful benefit persisted for the 4 mg/kg dose at week 28, which is 12 weeks off drug • Week 28 rate of complete resolution of hives at the 4 mg/kg QW dose significantly higher than with omalizumab (*; p<0.05, Fisher’s exact test, post-hoc analysis) = 28 = 13 16
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma Rapid and Sustained Complete Resolution of Hives Through 12 Weeks Post Last Dose (Week 28) 0 29 43 54 63 63 60 69 57 57 60 46 34 26 0 24 41 41 53 47 35 41 29 29 24 24 29 29 0 0 6 11 11 17 6 11 17 6 11 11 17 11 Week 1 Week 4 Week 8 Week 12 Week 16 Week 18 Week 20 Week 22 Week 24 Week 26 Week 28 Week 30 Week 32 Week 36 0 10 20 30 40 50 60 70 80 % Resoluton of Hives (HSS7 =0) CUE-221 4 mg/kg Q4W Omalizumab 300 mg Q4W Placebo (* p<0.05, Fisher’s exact test, post-hoc analysis) * 17 12 weeks post last dose End of Study Monthly SC dosing period 20-week Follow-up period off-drug20-week Follow-up period off-drug
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma 43 25 19 24 11 0 10 20 30 40 50 Week 28 % Complete Responders (UAS7=0) CUE-221 4 mg/kg Q4W Cue-221 2 mg/kg Q4W Cue-221 1 mg/kg Q4W Omalizumab 300 mg Q4W Placebo Complete Response (UAS7=0) is Also Sustained Over 12 Weeks Off Drug (Week 28) at the Highest Dose = 19 Over 90% of CUE-221 complete response by week 12 was maintained after 12 weeks off-drug at week 28 18 * UAS7=0HSS7=0 18 Suggests fundamental biological difference between omalizumab and CUE- 221, supportive of its dual MoA design *; p<0.05, Fisher’s exact test, post-hoc analysis
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma Contrasting Features of Targeted IgE Therapies • The IgE neutralizers (omalizumab/RPT904) share binding epitopes and MOA and appear to perform closer to CUE-221 low doses rather than high dose • Impact of RPT904 at timepoints Week 28 & beyond has not been disclosed • Week 28 data for CUE-221 support fundamental biological difference with therapeutics that are only blocking IgE 46 39 38 29 11 0 10 20 30 40 50 60 43 25 19 24 11 0 10 20 30 40 50 60 Week 12 Week 28 % Complete Response (UAS7=0) Not Disclosed CUE-221 P2 CUE-221 P2 RPT904 P2 RPT904 P2 Source: CUE-221 Data on File; RPT904: RAPT therapeutics PR 20Oct2025; RPT904 P2 CSU study did not include a placebo group. 37 39 19 RPT904 P2
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma 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 SAE 0(0) 0(0) 0(0) 0(0) 0(0) Treatment-related AESI Anaphylaxis 0(0) 0(0) 0(0) 0(0) 0(0) Serum Sickness 0(0) 0(0) 0(0) 0(0) 0(0) Injection Site Reactions 0(0) 1 (2.8%)1 0(0) 0(0) 0(0) Treatment-related AE leading to study discontinuation 0(0) 1 (2.8%)2 1 (2.7%)3 0(0) 0(0) TEAE leading to death 0(0) 0(0) 0(0) 0(0) 0(0) TEAE: treatment-emergent adverse event; SAE = Serious adverse event; AESI: Adverse event of special interest. 1 ISR > Grade 1; 2 Worsening of urticaria; 3 Insomnia 20
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma Risk/Benefit Considerations Across Different MOAs XOLAIR® (omalizumab) DUPIXENT® (dupilumab) RHAPSIDIO® (remibrutinib) Barzolvolimab (investigational) MOA Anti-IgE mAb Anti-IL4/IL13 mAb Oral selective BTK inhibitor Anti-KIT mAb Key Warnings/ Precautions Anaphylaxis (boxed warning) Malignancy Hypersensitivity reactions Risk of bleeding; Avoid live attenuated vaccines n/a Notable mechanism related safety -- Conjunctivitis/keratitis, eosinophilic conditions; helminth infection Bleeding risk; CYP3A4 drug interactions Hair and skin hypopigmentation ; Decrease in sperm count (preclinical studies) Sources: Omalizumab: US Prescribing Information; Dupilumab US Prescribing Information; Remibrutinib US Prescribing Information; Barzolvolimab: Metz et al. Allergy Clin Immunol 2026. Broad Interest For the Field of Allergy and IgE-Mediated Disease Additional MOAs in Earlier Stage Development without Validated Safety and Efficacy Profiles 21 *All registered trademarks are the property of their respective owners
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma Targeting Potential for Functional Cure of IgE-Mediated Disease CONTRASTING CLINICAL IMPACT 3-MONTH OFF DRUGS POINTS TO FUNDAMENTAL BIOLOGICAL DIFFERENCE CUE-221 BINDING SITE DIFFERS FROM OMALIZUMAB CUE-221 DOES NOT PREVENT IgE:CUE-221 COMPLEXES FROM BINDING CD23 MAINTAINED CD23 NEGATIVE FEEDBACK LOOP RESULTS IN REDUCED IgE SYNTHESIS • The P2 CSU trial results provide the first clinical evidence supportive of CUE-221’s engineered dual MOA and indicates mechanism(s) beyond IgE neutralization • If reduced IgE synthesis is demonstrated, disease modification and functional cure could follow IgE eradication • Active investigation of PK/PD relationships is ongoing with plans to present complete results at future medical conferences * Primary Endpoint: HSS7=0 22
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©2024 Cue Biopharma CONFIDENTIAL DO NOT DISTRIBUTE ©2026 Cue Biopharma 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 (anaphylaxis) • Clinical evidence Supportive of Dual MOA indicative of both IgE blocking and prevention of new IgE production • Path to IgE Eradication can be envisioned which could result in functional cure for IgE- mediated disease • Demonstrated Differentiated Clinical Effects supports implementing a broad approach to IgE mediated disease, starting with registration-enabling trials in CSU and P2 in food allergy 23