Cue Biopharma, Inc. · NASDAQ:CUE
Cue Biopharma — Investor Presentation (November 2025)
26 slides from Cue Biopharma's investor presentation, November 2025
Slide 1: Transforming Patients' Lives Through Precision Immunoengineering in Autoimmune Disease
Transforming Patients’ Lives Through Precision Immunoengineering in Autoimmune Disease November 2025 ©2025 ©2024 Cue 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 1
Slide 2: Cautionary Note Regarding Forward Looking Statements
Cautionary Note Regarding Forward Looking Statements This presentation has been prepared by Cue Biopharma, Inc. (“we,” “us,” “our,” “Cue” or the “Company”) and limited operating history, limited cash and a history of losses; our ability to achieve profitability; potential is made for informational p
Slide 3: The Problem: Immune Imbalance Underlies Autoimmunity
The Problem: Immune Imbalance Underlies Autoimmunity Regulation is Dominated and Suppressed by Inflammatory Players Deficient Regulatory Cells Dominant Pro-Inflammatory Cells ↓ IL-2 ↑ Autoreactive Teffs ↓ Treg frequency ↑ B cells/Autoantibodies ↓ Treg function ↑ Proinflammatory innate immune cells ↓
Slide 4: Stages of Autoimmune Disease
Stages of Autoimmune Disease Distinct Immunological Characterization of Prodromal Disease Documented for over Three Decades in Major Autoimmune Disorders* Specific Asymptomatic Non-disease Full blown symptoms, At risk stage with specific autoimmune uncertain autoimmunity symptoms disease diagnosis G
Slide 5: A 'Master Switch' of Immune Balance?
A ‘Master Switch’ of Immune Balance? Restoring Long-Term Tolerance by Re-Establishing Balance via T Regulatory Cells An Ideal Therapeutic that Expansion of nTregs and Induces Appropriate Reduction and inhibition iTregs to enhance & T Regulatory Populations of pro-inflammatory maintain self-tolerance
Slide 6: Nobel Prize Confirms the Role of IL-2 and TGFβ in Treg Induction
Nobel Prize Confirms the Role of IL-2 and TGFβ in Treg Induction Critical Signaling Agents to Produce Induced T-regulatory Cells via FOXP3 Gene Upregulation TGF-β provides the “GO" signal to turn on the FOXP3 gene • Primary cytokine that activates the SMAD pathway and directs FoxP3 transcription, pr
Slide 7: CUE-401 - A 'Master Switch' of Immune Balance
CUE 401 - A ‘Master Switch’ of Immune Balance Restoring Long-Term Tolerance by Re-Establishing Balance via T regulatory cells Expansion of nTregs and Reduction and inhibition iTregs to enhance & of pro-inflammatory maintain self-tolerance CUE-401 mechanisms nTregs iTregs Granulocytes Macrophages Pro
Slide 8: CUE-401: First in Class, Bifunctional Tolerogenic Mechanism
CUE-401: First in Class, Bifunctional Tolerogenic Mechanism Transformative first-in-class molecule incorporating attenuated components of TGF-β and IL-2 • Unique next generation mechanism tolerizes multiple cell types involved in autoimmunity Pipeline in a Fc Backbone Allows for simultaneous deliver
Slide 9: CUE-401: A 'Master Switch' of Immune Balance
CUE-401: A "Master Switch” of Immune Balance Designed with Goal of Restoring Long-Term Tolerance via Re-Establishing Balance Protein design solves classic challenges of TGF-b Receptor • Engineered mask improves stability and enables clinical Mask scale manufacturing Fc Backbone • Targeted point muta
Slide 10: Optimizing Biological Activity via Protein Engineering
Optimizing Biological Activity via Protein Engineering Attenuating Cytokine Affinities Retains Key Biologic Functions and Reduces Potential for Effects on Non-Immune Cells IL-2 Induced Reporter TGF-β-Induced Signaling Mask 2.0 Luminescence (RLU) mean ± SD rhTGF ± SD± SD 1.5 CUE- >10,000 fold mean A4
Slide 11: CUE-401 Induced FOXP3+ Suppressive iTregs From Naïve Murine CD4+ T Cells
CUE-401 Induced FOXP3+ Suppressive iTregs From Naïve Murine CD4+ T Cells IL-2 and TGF-β are Both Critically Required Cytokines to Produce Sufficient iTregs ©2025 ©2024 Cue 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 Source: Sponsored Research Collaboration with 11 Dr. Richard DiP
Slide 12: CUE-401 Harnesses Multiple Signals to Induce iTregs
CUE-401 Harnesses Multiple Signals to Induce iTregs Provides Both IL-2 and TGF-β activating Signals that are Necessary for iTreg Differentiation Control IL-2 alone TGF-β alone CUE-401 FOXP3 CFSE* Conventional T cells ©2025 ©2024 Cue Biopharma C O N F*carboxyfluorescein I D E N T I A L D O N O T succ
Slide 13: Durable Efficacy in Preclinical Model of Autoimmune Gastritis
CUE-401: Durable Efficacy in Preclinical Model of Autoimmune Gastritis Normalizes Histopathologic Gastritis Scores While Markedly Reducing Pathologic Autoimmune Effector T Cells in Tissue Prevention of Autoimmune Gastritis Frequency of Self-Reactive Effector T Cells in In vivo gastritis histology sc
Slide 14: Durable Benefit in Model of Acute GVHD
CUE-401: Durable Benefit in Model of Acute GVHD Increased Tissue Tregs and Maintenance of Graft 9+ Weeks Post-Treatment after 3 Doses 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-4
Slide 15: Suppression of Inflammation in Diverse Models of Disease
CUE-401: Suppression of Inflammation 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 o
Slide 16: Significant Activity in Non-Human Primates (NHP)
CUE-401: Significant Activity in Non-Human Primates (NHP) Supports Potential Strong Translatability to Humans Dose levels leading to ~2-5-fold increase in 30 Tregs Treg frequency across multiple murine disease models 25 NK Cells Fold Change vs Vehicle CD8+ T cells 20 In NHP, ~25-fold increase in Tre
Slide 17: NHP Data Indicates Significant Fold Increase in Tregs After Single Dose of CUE-401
NHP Data Indicates Significant Fold Increase in Tregs After Single Dose of CUE-401 CUE-401 - Fold change in % of Tregs CUE-401 - Fold change in number of Tregs/ul 30 Fold Change in # Tregs/ul vs vehicle Tregs NK Cells 100 Fold Change in Percent 25 CD8+ T cells 20 80 15 60 10 40 5 20 0 0 Vehicle 0.1
Slide 18: Highly Differentiated Approach to Immune Balance
Highly Differentiated Approach to Immune Balance Treg Expanders Treg Cell Tolerizing Cytokine CUE-401 (E.g. IL-2 muteins) Therapies Vaccines Blockers TGFβ–mediated suppression of inflammatory cell types YES NO NO NO NO Expansion of nTregs YES YES YES NO NO Generation of iTregs YES NO YES / NO NO NO
Slide 19: Differentiated Efficacy and Safety
Differentiated Efficacy and Safety Unique Biology Compared with Isolated Regulatory T cell Approaches Efficacy Profile Safety Profile Increased quantity of Tregs Attenuation of both TGF-b and IL-2 Proliferation of existing Tregs while inducing new self- prevents or limits off target signaling antige
Slide 20: CUE-401: IND Enabling Studies are Ongoing; IND Submission Planned Q2 2026
CUE-401: IND Enabling Studies are Ongoing IND Submission Planned Q2 2026 • Highly manufacturable and stable CMC • Processes and assays established to support release of material for GLP toxicology and clinical studies IND-Enabling • Existing datasets informed GLP study design that will define clinic
Slide 21: CUE-401: Rapid & Efficient Path to Clinical Proof of Concept
CUE-401: Rapid & Efficient Path to Clinical Proof of Concept Healthy Volunteer / Atopic Dermatitis First-in-Human Phase 1 PART A PART B Single Ascending Dose in Healthy Volunteers Multiple Dose in Atopic Dermatitis Patients Phase 1a Study Design: Phase 1b Study Design: • Blinded, randomized, placebo
Slide 22: CUE-401: Leading Disease Indication Options for Phase 2/3
CUE-401: Leading Disease Indication Options for Phase 2 / 3 Phase 1b PoC May Provide Support for Multiple Opportunities Rheumatoid Inflammatory Bowel Graft vs Host Systemic Lupus Primary Biliary Arthritis Disease Disease Erythematosus Cirrhosis Local Treg dysfunction, Biologic Decreased Treg functio
Slide 23: CUE-401: Redefining the Management of Autoimmune Disease
CUE-401: Redefining the Management of Autoimmune Disease With the Potential to Address Disease Control, Maintenance and Restoration* Specific Asymptomatic Non-disease Full blown symptoms, At risk stage with specific autoimmune uncertain autoimmunity symptoms disease diagnosis Genetic risk Environmen
Slide 24: Additional Relevant Publications
Additional Relevant Publications https://www.cuebiopharma.com/cue-401-publications/ Critical Role of TGF-β and IL-2 Receptor Signaling in Foxp3 Induction by an Inhibitor of DNA Methylation Freudenberg K, Lindner N, Dohnke S, Garbe AI, Schallenberg S, Kretschmer K. Critical Role of TGF-β and IL-2 Rec
Slide 25: Thank You
Thank You ©2025 ©2024 Cue 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 25
Slide 26: Nektar ACR 2017
Nektar 385 ACR 2017 ©2025 ©2024 Cue 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 26
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