Slide 1: Transforming Patients' Lives Through Precision Immunoengineering in Autoimmune Disease
Transforming Patients’ Lives Through Precision Immunoengineering in Autoimmune Disease April 7, 2026 ©2026 ©2024 Cue Biopharma C ON FI D E NT I A L D O NO T D I ST R I B U T E 1
Slide 2: Cautionary Note Regarding Forward Looking Statements
Cautionary Note Regarding Forward Looking Statements This presentation and accompanying oral presentation have been prepared by Cue Biopharma, Inc. (“we,” limited operating history, limited cash and a history of losses; our ability to obtain adequate financing to “us,” “our,” “Cue” or the “Company”)
Slide 3: Agenda and Speakers
Agenda and Speakers Welcome to CUE’s R&D Day Event to Discuss CUE-401, the Company’s Lead Asset for the Treatment of Autoimmune & Inflammatory Diseases Lucinda Warren, Interim Welcome President and CEO Dan Baker, MD, Interim Lucinda Warren Dan Baker, MD CUE-401 Chief Development Interim President an
Slide 4: Pipeline to Maximize Value Creation
Pipeline to Maximize Value Creation Focus on CUE-401 and Autoimmunity Enhances Near-Term Value with Disruptive Potential CUE-401 Drive to Clinic Manufacture and IND enabling activities completed • IND to be filed 2Q 2026 CUE-501 Precision Approach to B Cell Depletion Licensed to Boehringer Ingelheim
Slide 5: The Problem: Autoimmunity Arises When the Regulatory Function of T cells Becomes Deficient
The Problem: Autoimmunity Arises When the Regulatory Function of T cells Becomes Deficient The Resulting Inflammation Further Compromises Regulatory T cell Function INFLAMMATION REGULATION Antigen Loss of Tolerance to Self- presenting cells Reduction in antigens leads to Treg frequency (APC) Autoimm
Slide 6: CUE-401: A Highly Differentiated Bifunctional Cytokine Therapeutic
CUE-401: A Highly Differentiated Bifunctional Cytokine Therapeutic Delivering via the Unique Pleiotropic Combination of IL-2 and TGF-β Proprietary Mutein IL-2 Mask has been clinically derisked Fc Backbone in close to 150 patients via CUE-100 series TGF-β ↓↓↓Proinflammatory IL-2 Breathing Mask enable
Slide 7: CUE-401: Potential Breakthrough Protein Design Solves Classic TGF-β Challenges
CUE-401: Potential Breakthrough Protein Design Solves Classic TGF-β Challenges of Safety and Manufacturability • Attenuating Cytokine Affinities Retain Key Biologic Functions and Reduce Potential for Effects on Non-Immune Cells • Mask Prevents Producer Cell Toxicity and Allows High Yields IL-2 Varia
Slide 8: CUE-401: Highly Differentiated and Potentially Best-in-Class Expanding Tregs
CUE-401: Highly Differentiated and Potentially Best-in-Class Expanding Tregs and T cells to Promote Tolerance Mechanism CUE-401 confirmed by Mask Natural recent article PEG-IL-2 Tregs from Stanford TGF-β University* Reduced affinity Fc Backbone IL-2 Natural Tregs to IL2Rβ IL-2 Alone Attenuated IL-2R
Slide 9: CUE-401: Durable Benefit in Model of Acute GVHD
CUE-401: Durable Benefit in Model of Acute GVHD Increased Tissue Tregs & Maintenance of Graft 9+ Weeks Post-Treatment Delayed GVHD & Increased Overall Survival Increased Treg Persistence of Human Numbers in GVHD T Cell Graft Provides Target Tissue Evidence of Tolerance P<0.0001 CUE-401 Vehicle 8×105
Slide 10: CUE-401: Efficacy in Diverse Models of Disease
CUE-401: Efficacy in Diverse Models of Disease Functional Suppression of Inflammation in Multiple Disease Models Supports Broad Applicability in the Clinic EAE Model of Multiple Sclerosis Delayed Type Hypersensitivity – T Cell Mediated Significant inhibition and delay of disease onset Significant in
Slide 11: Dr. Richard DiPaolo: Coordinated Delivery of IL-2 and TGF-β
Dr. Richard DiPaolo Coordinated Delivery of IL-2 and TGF-β Professor and Chair, Department of Molecular Microbiology & Immunology, Saint Louis University ©2026 ©2025 ©2024 Cue Cue Biopharma C ON FI D E NT I A L D O NO T D I ST R I B U T E 11
Slide 12: Rich DiPaolo, Ph.D.
Rich DiPaolo, Ph.D. Professor and Chair Department of Molecular Microbiology & Immunology Saint Louis University School of Medicine
Slide 13: The Challenge: Achieving Immune Tolerance to Treat Autoimmunity
The Challenge: Achieving Immune Tolerance to Treat Autoimmunity Autoimmune diseases arise when peripheral tolerance breaks down. Regulatory T cells are essential for preventing this but selectively activating them in vivo is challenging. IL-2 and TGF-β are both required for Treg biology, yet coordin
Slide 14: In Vitro: Three Key Outcomes
In Vitro: Three Key Outcomes CUE-401 First, CUE-401 induces Foxp3⁺ iTregs from naïve CD4+Foxp3- T cells at very high efficiency. Second, it expands endogenous CD4+Foxp3+ Tregs while maintaining Foxp3 expression. Third, it reprograms CD4+CD44hi effector/memory T cells toward a less inflammatory state
Slide 15: Robust Treg Expansion after a Single Dose of CUE-401
Robust Treg Expansion after a Single Dose of CUE-401 CUE-401 Flow cytometry Day 6 Vehicle CUE-401 % Tregs 10% 60% 100 ✱✱✱✱ 80 60 % Foxp3 CD4 CD4 40 20 0 PBS CUE Vehicle CUE-401 Foxp3
Slide 16: CUE-401 Expanded Tregs are Stable
CUE-401 Expanded Tregs are Stable CUE-401 Sort Tregs Assess Methylation of Foxp3 TSDR Vehicle CUE-401 TSDR Methylation 100 % De-methylated 80 60 CD4 CD4 40 20 0 Vehicle Vehicle CUE-401 CUE-401 Foxp3-EGFP
Slide 17: CUE-401 Expanded Tregs are Activated
CUE-401 Expanded Tregs are Activated CUE-401 Flow cytometry RNA Seq Flow Cytometry RNA Seq Vehicle CUE-401 Itgae (CD103), GITRhi Nrp1, CD25hi Il2ra, CTLA-4hi Il2rb, UMAP_2 UMAP_2 CD103hi Lag3, Ki67 Tnfrsf18 (GITR), Icosl, Klrg1 UMAP_1
Slide 18: CUE-401 is Distinct from IL-2 and More Specific for Tregs
CUE-401 is Distinct from IL-2 and More Specific for Tregs CUE-401ΔTGFβ3 CUE-401 RNA Seq Sort Tregs Sort Tconv Sorted Tregs Sort Tconv PBS CUE-401ΔTGFβ3 CUE-401 PBS CUE-401ΔTGFβ3 CUE-401 Ctla4 Ctla4 Induced by Foxp3 both Il2ra Foxp3 Lag3 Il2ra Areg Lag3 Ccl4 Ccl4 Only IL-2 Ccl5 Eomes induced Gzma Fut
Slide 19: CUE-401 Suppresses Autoreactive T cells
CUE-401 Suppresses Autoreactive T cells BALB/c nude CUE-401 CD25 (Treg) Depleted Splenocytes Assess Autoimmunity Vehicle Treated CUE-401 Treated ✱✱✱ 100 80 Thy1.2 Thy1.2 60 40 20 0 PBS CUE-401 Vehicle CUE-401 Thy1.1 Thy1.1
Slide 20: CUE-401 Provides Durable Protection from Autoimmunity
CUE-401 Provides Durable Protection from Autoimmunity BALB/c nude CUE-401 CD25 (Treg) Depleted Splenocytes Assess Autoimmunity Vehicle Treated CUE-401 Treated ✱✱ 12 10 8 Score 6 4 2 0 Vehicle CUE-401 1 S 40 PB E- U C
Slide 21: CUE-401 Expands/Activates Tregs During Autoimmunity
CUE-401 Expands/Activates Tregs During Autoimmunity BALB/c nude CUE-401 CD25 (Treg) Depleted Splenocytes scRNA Seq Tregs from Vehicle Tregs from CUE-401 Vehicle PBS CUE-401 Ecm1 Cd81 5.0 5.0 Odc1 IL-2/STAT-5 Slc2a3 Socs2 Il1rl1 (ST 2) Signature Ccnd2 Socs1 Penk 2.5 2.5 Nfkbiz St3gal4 Lrrc8c 0.6 umap
Slide 22: Key Takeaways
Key Takeaways To Summarize: Coordinated IL-2 and TGF-β3 signaling delivered by CUE-401 induces, expands, and stabilizes Tregs; specifically targets Tregs and avoids effector activation; and produces durable immune tolerance. This represents a pharmacologic strategy for in vivo Treg programming in au
Slide 23: Dr. Jonathan Kay: Effective Immunomodulating Capabilities
Dr. Jonathan Kay Effective Immunomodulating Capabilities Timothy S. & Elaine L. Peterson Chair in Rheumatology at UMass Chan Medical School, Professor of Medicine & Population & Quantitative Health Sciences ©2026 ©2025 ©2024 Cue Cue Biopharma C ON FI D E NT I A L D O NO T D I ST R I B U T E 23
Slide 24: CUE-401 Harnesses Complementary Methods of Immunoregulation
CUE-401 Harnesses Complementary Methods of Immunoregulation TGF-β Dampens Inflammatory CUE-401 CUE-401 Drives Regulatory T Cell Responses that Drive Autoimmune Responses that Restore Immune Disease Balance ↓ Proinflammatory nTregs iTregs Cytokines Proliferation Conversion ↓ B cell activation/ differ
Slide 25: Method to Measure Effects of CUE-401 on Effector T cell Cytokine Production
Method to Measure Effects of CUE-401 on Effector T cell Cytokine Production Hypothesis CUE-401 suppresses production of proinflammatory cytokines by human CD4+ Teff/memory cells in a Analyte dose-dependent manner GM-CSF IFN-γ Collect IL-4 Stimulate Anti-CD3/CD28 supernatant IL-5 on day 3 CUE-401 (14
Slide 26: CUE-401 Inhibits Proinflammatory Cytokine Production by Teff/mem Cells
CUE-401 Inhibits Proinflammatory Cytokine Production by Teff/mem Cells Th1 Th2 Th17 IFNg IL-4 IL-13 IL-17 IL-21 IL-22 GM-CSF IL-6 ▼ Proinflammatory Th1 cytokines associated with Th2 Th1, Th2, and Th17 Th17 CUE-401 responses Teff/Memory Cells ©2026 ©2024 Cue Biopharma C ON FI D E NT I A L D O NO T D
Slide 27: CUE-401 Restrains NK Cell Activity Induced by IL-2
CUE-401 Restrains NK Cell Activity Induced by IL-2 ↓ IL-2 Induced NK Cell Proliferation ↓NK Cell Granzyme B Expression ↓Cytokine Producing NK Cells 80 60000 25 1X Fc-IL-2 % CD107a+, IFNg+ TNFa+ NK Cells CUE-401 60 20 % Granzyme B gMFI % Proliferating NK Cells 40000 15 40 10 20000 20 5 0 0 0 0.01 0.1
Slide 28: CUE-401 Suppresses Plasma Cell Differentiation and Antibody Production
CUE-401 Suppresses Plasma Cell Differentiation and Antibody Production CUE-401 does not alter the Mature B cell Differentiated B cell / Plasmablast mature B cell population, but Activation CD20 suppresses differentiation in vitro of plasma cells and antibody Untreated +CUE-401 production +Fc-IL-2 Ga
Slide 29: CUE-401 Harnesses Complementary Methods of Immunoregulation
CUE-401 Harnesses Complementary Methods of Immunoregulation TGF-β Dampens Inflammatory CUE-401 CUE-401 Drives Regulatory T Cell Responses that Drive Autoimmune Responses that Restore Immune Disease Balance ↓ Proinflammatory nTregs iTregs Cytokines Proliferation Conversion ↓ B cell activation/ differ
Slide 30: Phase 1 Single and Multiple Ascending Dose Study
Phase 1 Single and Multiple Ascending Dose Study Study Initiation Planned Q3 2026 with SAD Readout by Q4 2026 and MAD Readout Complete Q2 2027 PART 1 PART 2 Total Study Period: 12 months Single Ascending Dose (SAD) in Multiple Ascending Dose (MAD) in with data readouts within Healthy Volunteers Heal
Slide 31: Unique Mechanism of Action
Unique Mechanism of Action Robust Restoration of Immune Regulatory Control is the Key to Accessing Expansive Treatment Opportunities Neuroinflammation Ocular • MS • ALS • Uveitis • NMO • AD & FTD • Neuromyelitis optica • PD • NMDA encephalitis Endocrine Pulmonary • Type 1 Diabetes • Asthma • Addison
Slide 32: KOLs & Cue Management Discussion and Q&A Session
KOLs & Cue Management Discussion and Q&A Session ©2026 ©2025 ©2024 Cue Cue Biopharma C ON FI D E NT I A L D O NO T D I ST R I B U T E 32
Slide 33: Thank you
Thank you About Cue Biopharma The innate sophistication of the immune system inspires us to engineer precision immunotherapies that transform patients’ lives. ©2026 ©2025 ©2024 Cue Cue Biopharma C ON FI D E NT I A L D O NO T D I ST R I B U T E 33