Bolt Biotherapeutics, Inc. · NASDAQ:BOLT
Bolt Biotherapeutics — Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting 2024
15 slides from Bolt Biotherapeutics's conference presentation, 2024
Slide 1: Society for Immunotherapy of Cancer SITC 2024
Society for Immunotherapy of Cancer Sitc2024 39" Annual Meeting & Pre-Conference Programs Advance the science, discover breakthroughs and educate the world on cancer immunotherapy. #SITC24
Slide 2: Key Learnings From BDC-1001 Phase 1 FIH Dose Escalation Trial Inform Next-Generation ISACs
Key Learnings From BDC-1001 Phase 1 FIH Dose Escalation Trial Inform Next-Generation ISACs Jason Ptacek1, Andrew Luo1, Cecelia I. Pearson1, Ecaterina E. Dumbrava2, Joshua Z. Drago3, Marie Du1, Milan Mangeshkar1, Ming Yin1, Tai Yu1, Han K. Kim1, John Tomaro1, Lindsey Gourley1, Edith A. Perez1, Michae
Slide 3: Author Disclosures and Funding
Author Disclosures and Funding Jason Ptacek is an employee of Bolt Biotherapeutics. Nivolumab was provided by Bristol Myers Squibb. This study is funded by Bolt Biotherapeutics (NCT 04278144).
Slide 4: Boltbody Immune-Stimulating Antibody Conjugate (ISAC)
BoltbodyTM Immune-Stimulating Antibody Conjugate (ISAC) First–Generation ISAC Next–Generation ISAC • Monoclonal antibody geo- • Enhanced tumor-targeting antibody locates ISAC to HER2 antigen with active Fc region triggering on surface of a tumor cell phagocytosis • Non-cleavable, cell- • Enhanced po
Slide 5: Boltbody Immune-Stimulating Antibody Conjugate (ISAC)
BoltbodyTM Immune-Stimulating Antibody Conjugate (ISAC) 27Jun2024 1 Binds tumor antigen 2 Phagocytosis of tumor 3 Immune activation 4 Triggers killing by T cells Myeloid antigen presenting cell Antigen recognition by T cells BoltbodyTM ISAC Fc receptor Target ISAC antigen TLR7/8 Pro-inflammatory cyt
Slide 6: BBI-20201001 Trial Overview and Translational Questions
BBI-20201001 Trial Overview and Translational Questions • Phase 1 dose escalation completed & RP2D selected1 • 18 cohorts with 16 different HER2-expressing2 solid tumor types • doses: 0.5 – 20 mg/kg IV; schedules: q3w, q2w, q1w • BDC-1001 well tolerated up to 20 mg/kg q1w as monotherapy and in combi
Slide 7: BDC-1001 Elicits Proinflammatory Cytokines, Associated With Clinical Benefit
BDC-1001 Elicits Proinflammatory Cytokines, Associated With Clinical Benefit • Fold change in biomarkers significantly correlated to dose • Higher peripheral blood cytokine levels are associated with clinical benefit MIP-1β Fold Change Dose Systemic Cytokine Levels in HER2+ Patients 4 hours Post-inf
Slide 8: BDC-1001 Monotherapy Drives Immune Cell Infiltration in HER2 IHC 3+ Tumors
IHC: 5Oct2023 BDC-1001 Monotherapy Drives Immune Cell Infiltration Slide: 21Jun2024 in HER2 IHC 3+ Tumors • BDC-1001 shows the potential to alter the tumor microenvironment • These changes were statistically significant in HER2 IHC 3+ tumors only CD11c+ Dendritic Cells M1 / M2 Macrophage Ratio CD8+
Slide 9: BDC-1001 Monotherapy Drives Increased Immune Gene Signatures in HER2 IHC 3+ Tumors
BDC-1001 Monotherapy Drives Increased Immune Gene Signatures in HER2 IHC 3+ Tumors Fresh Biopsy HER2 Score Gene Signatures 3+ 2+ 1+/0 ** Log2 Fold Change • Transcriptomic analysis TLR Pathway ** performed by RNAseq of ** -0.75 0.75 baseline and on-treatment * ** Permutation Test tumor biopsies * ∗ p
Slide 10: Boltbody Immune-Stimulating Antibody Conjugate (ISAC)
BoltbodyTM Immune-Stimulating Antibody Conjugate (ISAC) First–Generation ISAC Next–Generation ISAC • Monoclonal antibody geo- • Enhanced tumor-targeting antibody locates ISAC to HER2 antigen with active Fc region triggering on surface of a tumor cell phagocytosis • Non-cleavable, cell- • Enhanced po
Slide 11: Next-Generation ISACs Show Enhanced Immune Activation In Vitro With Lower Antigen Levels
20240215_TSM_CLDN_ISAC Next-Generation ISACs Show Enhanced Immune Activation In Vitro in Preclinical Models With Lower Antigen Levels • Next-gen ISACs outperforms first-gen ISAC in cDC–tumor co-culture with low CLDN18.2 (IHC 1+) expressing PA-TU-8988S tumor cells • Next-generation CLDN18.2 ISAC was
Slide 12: Next-Generation ISACs Show Enhanced Immune Activation In Vivo With Lower Antigen Levels
Next-Generation ISACs Show Enhanced Immune Activation In Vivo in Preclinical Models With Lower Antigen Levels • Next-generation ISAC produced greater levels of proinflammatory cytokines across all tumor models • The advantage of the next-generation ISAC was particularly noticeable in lower-antigen t
Slide 13: Next-Generation ISACs Outperform First-Generation ISACs and Cytotoxic ADC in Lower Antigen Models
Next-Generation ISACs Outperform First-Generation ISACs and Cytotoxic ADC in Models With Lower Tumor Antigen Expression • Multiple tumor antigens with varying expression levels were evaluated with different ISACs • Next-generation ISACs show greater tumor growth inhibition across models compared to
Slide 14: Conclusions
27Jun2024 Conclusions • BDC-1001 drives immune activation, leading to anti-tumor activity • Stimulates the production of chemokines and cytokines, mobilizes immune cells and promote immune cell activation related to TLR signaling, innate immunity, antigen presentation, and IFN and T cell inflamed si
Slide 15: Thank You
Thank You The authors thank all participating patients and their families and all study co-investigators and research coordinators.
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