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Corporate Presentation Immune
Responses, On Cue Nasdaq: CUE November 2021 Exhibit 99.1
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forward-looking statements include, among others, statements we make regarding our development plans for CUE-101, CUE-102 and the continued buildout of our pipeline, the sufficiency of our cash, cash equivalents and marketable securities to support
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Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, our limited operating history, limited cash and a history of losses; our
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Leading the next wave of disruptive,
breakthrough immunotherapies addressing the specificity and diversity of the human immune system to cure complex human disease. 2021 CUE BIOPHARMA Cue Biopharma's Vision Harnessing natural signals ("Nature's Cues") for
tailored immune activation against cancers to enhance efficacy and tolerability Exploit evolutionary selectivity of the immune system enabled by rational protein engineering to design therapeutics with potentially enhanced activity Emerging clinical
data, including clinical response and patient benefit, provides potential for de-risking and validation of the entire platform Platform modularity and scalability expected to support broad clinical applications
Asia Rights, with option for China
sub-license: CUE-101 CUE-102 NEXT ANTICIPATED MILESTONE PARTNER TARGET SELECTION PRE-CLINICAL PHASE 1 CUE-101 (HLA:A02) Monotherapy 2L+ (HPV) CUE-101 + Keytruda 1L (HPV) CUE-102 (HLA:A02-WT1) CUE-302 CUE-103(HLA:A11-KRAS G12V) CUE-101 Neoadjuvant
(HPV) Neo-STAT-HLA: A02 Cancer: CUE-100 series and derivatives IL-2 RDI-STAT 1H 22: Top-line Phase 1b data 2Q 22: Initiate Dose Expansion 2H 2021: Trial Initiated 1Q 2022: IND Filing 2022: IND Enabling Studies 2022: IND Enabling
Studies CUE-100 Series: Changing the Therapeutic Landscape Neo-STAT-HLA: A11 & 24 Infectious disease: CUE-200 series CD80 & 4-1BBL CUE-201 Autoimmune disease: CUE-300 series PD-L1 & Undisclosed CUE-301 (Proins / DR4) CUE-302 Autoimmune
disease: CUE-400 series IL-2/TGF- CUE-401 (iTregs) 2021 CUE BIOPHARMA
Checkpoint inhibitors provided early
insights that immunotherapy has the potential to eradicate cancer, however many challenges remain Overall response rates for checkpoints are 15-25%, depending on tumor type Many tumors show an absence of T cell infiltration i.e., many tumors are
"cold" How do we make immunotherapy more effective? Increasing and activating tumor targeted T cells is key to enhancing therapeutic benefit IL-2 was the first cytokine to be successfully used in the treatment of cancer because it
promotes expansion, function and survival of effector T cells IL-2 was approved for therapy of metastatic melanoma and metastatic renal cell carcinoma Overall response rates have remained low due to narrow therapeutic window and poor tolerability A
significant challenge in the development of IL-2 as a therapeutic anti-tumor agent is the indiscriminate activation of numerous immune cells - leading to severe toxicity and narrow therapeutic window 2021 CUE BIOPHARMA Immunotherapy Has
Transformed Oncology Treatment
IL-2 Therapy Challenges: Non-selective
Immune Activation = Poor Tolerability and Poor Therapeutic Performance CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+
CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ Wild Type IL-2 or IL-2 Variants Lack of Selectivity for
Tumor-specific CD8+ T cells Non-specific Activation of ALL CD8+ T cells NON TUMOR-SPECIFIC CD8+ T CELL TUMOR-SPECIFIC CD8+ T CELL CD8+ CD8+ Considerations and Challenges Vast majority of T cells are NOT tumor-specific Need for IL-2 selectivity for
tumor-specific T cells Activation of Tregs Toxicities (VLS, CRS etc.) 2021 CUE BIOPHARMA Examples Wt IL-2 (aldesleukin) "Not-alpha" IL-2 variants Tumor-localized IL-2 variants (e.g., FAP-targeted) "Masked" IL-2 for
conditional activation Lineage-biased IL-2 variants (e.g. CD8+ T cells, or PD-1+ T cells) CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+
2021 CUE BIOPHARMA CUE-100
Series: Designing an IL-2 Variant in Context of T Cell Receptor (TCR) Engagement TUMOR-SPECIFIC T CELLS +++ IL-2R IL-2 TCR p-HLA IL-2R IL-2 TCR p-HLA +/- NON TUMOR-SPECIFIC T CELLS >>> Fc Fc CUE-100 series Immuno-STAT Engineered
IL-2 favors activation of TCR-engaged T cells Abrogate binding to IL-2R Attenuate binding to IL-2R Selective engagement tumor-specific T cells p-HLA p-HLA (2X) IL-2 variant (4X) IL-2 variant IgG-Fc CUE-100 series Immuno-STAT Fc backbone
for stability, manufacturing, and half-life Molecular structure exploits concurrent TCR and IL-2R engagement to activate tumor-specific CD8+ T cells
LEGEND IL-2 IL-2R peptide-HLA TCR IL-2
Immuno-STAT IL-2 p-HLA Fc +++ +++ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+ CD8+
Focused Activity on Tumor-specific T cells Biased Activation and Expansion of Tumor-specific T cells (or "TCR-engaged" T cells) ADVANTAGES Selective activity of IL-2 on tumor-specific T cells (cis-interaction) Potential for activation of
TCR-engaged anti-tumor T cells (trans-interaction of IL-2) Demonstrated expansion of NK cells (IL-2-mediated) Minimize Treg activation Generally well-tolerated to date lead candidate CUE-101 dosed up to 8.0 mg/kg with no MTD CUE-100 series CUE-100
Series: Directing IL-2 Activity to Tumor-specific T cells and Enhancing Tolerability and Efficacy 2021 CUE BIOPHARMA NON TUMOR-SPECIFIC CD8+ T CELL TUMOR-SPECIFIC CD8+ T CELL CD8+ CD8+
CUE-100 Series: Opportunity to Maximize
the Fullest Potential of IL-2 2021 CUE BIOPHARMA Wild Type IL-2 or IL-2 Variants NON TUMOR-SPECIFIC T CELLS TUMOR SPECIFIC T CELLS EQUAL ENGAGEMENT OF ALL T CELLS +++ +++ CUE-100 Series TUMOR-SPECIFIC T CELLS NON TUMOR-SPECIFIC T CELLS
BIASED ACTIVATION OF TUMOR-SPECIFIC T CELLS +/- +++ IL-2 IL-2R p-HLA TCR The CUE-100 series has the potential of enabling a broad therapeutic window to enhance IL-2's clinical effectiveness TOLERATED CLINICAL DOSES 0.037 mg/kg (approved dose)
0.006 mg/kg (RP2D) 0.006 to 0.024 mg/kg Proleukin (aldesleukin) Bempegaldesleukin (NKTR-214) and nemvaleukin alfa (ALKS-4230) SAR444245 (formerly THOR-707) CUE-101 dosed up to 8.0 mg/kg NO MTD identified LEGEND
Platform Validation CUE-100 Series:
Validate, Expand, and Accelerate CUE-100 Series Immuno-STATs CUE-101 (A02): HPV E7 Phase 1 Mono in 2L+ R/M HNSCC Phase 1 CPI Combo in 1L R/M HNSCC Phase 1 Neo-Adj in locally/advanced HNSCC CUE-101 Clinical Data Validates the Immuno-STAT Platform:
Clinical and mechanistic PoC for selective IL-2-targeting to tumor-relevant T cells and NK cells Generally well tolerated at efficacious doses PD and PK (lack of evidence of drug-clearing ADAs) Anti-tumor efficacy in monoTx based on RECIST1.1
De-risks CUE-101 as well as the IL-2-based CUE-100 series Currently in RP2D dose expansion Currently in dose escalation Initiated 4Q 2021 Signal 1 HLA-A*02:01 + HPV-16 E711-20 Signal 2 Engineered IL-2 variant 2021 CUE BIOPHARMA
CUE-101: Lead Clinical-stage Asset
from IL-2 based CUE-100 Series 2021 CUE BIOPHARMA Overview of CUE-101 Phase 1 Monotherapy Part A Dose Escalation Study Overview of CUE-101 Phase 1 Monotherapy Dose Escalation and Expansion Study Phase 1 Part A Dose Escalation Completed and
Part B Expansion Enrolling 38 patients with recurrent/metastatic H&N cancer across 7 dose escalation cohorts 15 patients treated at the RP2D (4 mg/kg) PK Dose proportional exposure, sustained exposure with repeat dosing No evidence of
anti-drug antibodies (ADAs) PD Expansion of disease-relevant CD8+ T cells and NK cells, with evidence of tumor T cell infiltration Tolerability Patients given CUE-101 doses ranging from 0.06 mg/kg - 8 mg/kg Generally well-tolerated with no MTD
identified Efficacy Clinical activity observed across several dose cohorts (partial response/stable disease) PR and durable SD observed at RP2D (4.0mg/kg Q3W)
Data extracted from EDC 03-Nov-2021
(7 patients remain on study) *To qualify as Durable Stable Disease requires SD at 2 consecutive post-treatment scans through week 12. Preliminary Tumor Responses for CUE-101 Monotherapy at the RP2D (4 mg/kg) 2021 CUE BIOPHARMA
CUE-101: Confirmed PR with ~ 54%
Reduction in Target Lesions Increase in HPV E7-specific CD8+ T cells with minimal change in total T cells Confirmed PR Duration of Response 30 weeks Patient remains on treatment *Data updated 28OCT21 2021 CUE BIOPHARMA Case History Prior
therapy: 1L cetuximab 2L pembrolizumab Progressive disease prior to enrollment Treated in metastatic 3L setting with 4.0 mg/kg CUE-101 Q3W (Cohort 6) Patient completed 13 cycles of CUE-101 and remains on study with PR ongoing
CUE-101: Tumor Necrosis and T Cell
Infiltrates in Target Lesions 2021 CUE BIOPHARMA Case History Prior therapy: 1L chemotherapy 2L pembrolizumab Progressive disease prior to enrollment Treated in metastatic 3L setting with 1.0 mg/kg CUE-101 Q3W (Cohort 4) Confirmed and
sustained SD through 18 weeks Target lesion resected at 18 weeks due to proximity to an artery Patient remains disease free post resection Immunostaining (CD8+ T cells = rose; PD-LI = brown) Hematoxylin and Eosin Stain
CUE-101: Increase in Tumor
Infiltrating T Cells (TILs) 20x Pre-dose Cycle 3 Day 1 CD3 GZMB Cytokeratin CD3 GZMB Cytokeratin IHC staining indicates increase in TILs (CD3+) and granzyme (GZMB) within a target tumor lesion following CUE-101 monotherapy 2021 CUE BIOPHARMA
Case History Prior therapy: 1L chemotherapy 2L pembrolizumab Progressive disease prior to enrollment Treated in metastatic 3L setting with 2.0 mg/kg CUE-101 Q3W (Cohort 5)
Part C: Pembrolizumab Combination
Dose Escalation Pembrolizumab 200 mg, Q3W CUE-101 Dose (mg/kg) 4.0 Dose (mg/kg) 2.0 1.0 Abbreviations: PD, pharmacodynamics; PK, pharmacokinetics; RP2D, Recommended Phase 2 Dose Dosing complete, no DLTs Cohort 1 Cohort 3 Cohort 2 Enrolling Dosing
complete, no DLTs Part C: Dose Escalation of CUE-101 in Combination with Pembrolizumab Preliminary results: 3 of 3 patients from cohort 2, 2 mg/kg, demonstrated tumor reductions in their target lesions on their first scan after two cycles of therapy
All 3 remain on treatment 1st patient has confirmed SD 2nd patient unconfirmed PR 3rd patient has had 1 scan to date Cohort 2 (2mg/kg) 2021 CUE BIOPHARMA
CUE-101: Potential for Multiple
Registration Paths 2021 CUE BIOPHARMA Monotherapy 2nd line+ therapy for HPV+ head and neck cancer Combination therapy First line HPV+ Head and Neck cancer in combination with pembrolizumab Neoadjuvant therapy Early treatment in neoadjuvant
setting (study launched in 2H 21)
Phase 1 Adj in recurrent HNSCC
Platform Validation and Expansion CUE-100 Series Immuno-STATs CUE-102 (WT-1) IND filing 1Q 2022 CUE-103 (KRASG12V) IND enabling activities initiated Platform Expansion via CUE-102 and CUE-103: Demonstration of platform modularity Expansion of tumor
antigens (WT-1, KRAS) Expansion of HLA allelic coverage (A02, A11) Expansion into major disease indications with significant patient reach Exploits clinical de-risking of IL-2-based CUE-100 series by CUE-101 Safety and tolerability of IL-2 dosing
Well defined regulatory strategy Potential for expedited clinical development path CUE-100 Series: Validate, Expand, and Accelerate CUE-101 (HPV E7) Phase 1 Mono in 2L+ R/M HNSCC Phase 1 CPI Combo in 1L R/M HNSCC Phase 1 Neo-Adj in locally/advanced
HNSCC 2021 CUE BIOPHARMA
Top-ranked onco-fetal tumor antigen
by the NCI with restricted tissue-expression Broad therapeutic opportunity in numerous solid cancers and hematological cancers Core IL-2 framework is de-risked by the clinical experience of CUE-101 IL-2 Variant (same as CUE-101) Fc Backbone (same as
CUE-101) HLA A:02 (same as CUE-101) WT137-45 CUE-102: Targeting Wilms Tumor 1 (WT1) - IND Filing 1Q 2022 Molecular Design 2021 CUE BIOPHARMA CUE-102 Selectively Expands WT-1-specific T Cells CUE-102 Expands WT-1-specific T Cells that
are Cytolytic WT137-45-specific CD8+ T cells (Fold-change over background) WT137-45-specific CD8+ T cells (Fold-change over background) % Specific Lysis
2021 CUE BIOPHARMA Broad
therapeutic opportunity for targeting of multiple cancers with KRAS driver mutations (NSCLC, CRC, PC, etc.) KRAS G12V is a key driver mutation in highly prevalent solid tumors KRASG12V is a validated epitope that is recognized by anti-tumor T cells
KRASG12V A11 asset serves as a beachhead for targeting multiple KRAS mutations (G12D, G12R) and global alleles (i.e., A03, B07) - Source (UPenn PMID 34272369) CUE-103: KRAS G12V - Proof of Concept for Targeting KRAS Mutations Molecular Design
IL-2 Variant (same as CUE-101) Fc Backbone (same as CUE-101) KRAS7-16 G12V HLA A:11 Molecular Design CUE-103 Selectively Expands KRASG12V-specific T Cells
Expansion of Modular CUE-100 Series