Bolt Biotherapeutics, Inc. · NASDAQ:BOLT
Bolt Biotherapeutics — ESMO Immuno-Oncology 2021
24 slides from Bolt Biotherapeutics's conference presentation, December 2021
Slide 1: BDC-1001 Interim Clinical Data, ESMO Immuno-Oncology 2021
BDC-1001 Interim Clinical Data ESMO Immuno-Oncology 2021 December 2021 1
Slide 2: Today's Agenda
Today’s Agenda Randall Schatzman, Ph.D. David Dornan, Ph.D. Edith A. Perez, M.D. Chief Executive Officer Chief Scientific Officer Chief Medical Officer BDC-1001 Interim Results Introduction & Review of BDC-1001 Presented at Closing Remarks Mechanism & Preclinical Data ESMO Immuno-Oncology 2021 2
Slide 3: Disclaimer
Disclaimer This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding Bolt Biotherapeutics, Inc. (the "Company," "we," "us," or "our")’
Slide 4: Dose Escalation Study Continues
BDC-1001 Dose Escalation Study Continues • Recommended Phase 2 Dose (RP2D) not yet reached Favorable • BDC-1001 has demonstrated favorable safety & tolerability to date Safety Profile • No DLTs at dose levels up to 20 mg/kg q3w or 12 mg/kg q2w PK/PD Insights • Drug half-life shorter than expected: ~
Slide 5: Review of BDC-1001 Mechanism & Preclinical Data
Review of BDC-1001 Mechanism & Preclinical Data 5
Slide 6: Key Features Combine to Deliver Unique MOA
BDC-1001: Key Features Combine to Deliver Unique MOA BDC-1001 Boltbody™ ISAC Trastuzumab (anti-HER2) Key structural features: • Targeting: Trastuzumab (anti-HER2) biosimilar Proprietary • ADCP engagement via antibody Fc domain TLR7/8 Immune • Stable, non-cleavable linker Stimulant • Proprietary TLR
Slide 7: Hallmarks of Boltbody ISAC Platform
Hallmarks of BoltbodyTM ISAC Platform 7
Slide 8: Surrogate Shows Dose-Dependent Efficacy and Pharmacodynamic Responses
BDC-1001 Surrogate Shows Dose-Dependent Efficacy and Pharmacodynamic Responses HCC1954 IHC3+ Xenograft Model (Functional Myeloid Cells Only) MIP-1β Tumor Trastuzumab BDC-1001 Surrogate 5 mg/kg BDC-1001 Surrogate (Dendritic Cells) 1 mg/kg BDC-1001 Surrogate 0.2 mg/kg BDC-1001 Surrogate CD11c Innate I
Slide 9: Surrogate Engages Innate and Adaptive Immune Responses
BDC-1001 Surrogate Engages Innate and Adaptive Immune Responses MMC rHER2 Syngeneic Model (Fully Immune-Competent) rHER2 mAb BDC-1001 Surrogate MIP-1β Tumor (Dendritic Cells) CD11c Innate Immunity Day 1 (Macrophages) MIP-1β Plasma F4/80 Day 1 Immunity Adaptive (T cells) CD8 Pharmacodynamic biomarker
Slide 10: BDC-1001 Interim Results Presented at ESMO Immuno-Oncology 2021
BDC-1001 Interim Results Presented at ESMO Immuno-Oncology 2021 December 2021 10
Slide 11: Monotherapy Dose Escalation Design of Ongoing Phase 1/2
BDC-1001 Monotherapy Dose Escalation Design of Ongoing Phase 1/2 20 mg/kg 12 mg/kg * 8 mg/kg * N = 3-15 5 mg/kg per cohort q3w 2 mg/kg 0.5 mg/kg 20 mg/kg 0.15 mg/kg 12 mg/kg * q2w 8 mg/kg * Future cohorts will * explore weekly dosing NCT04278144 *Cohort open to enrollment as of October 6, 2021 Prima
Slide 12: Ongoing Phase 1/2 Demographics and Baseline Characteristics
BDC-1001 Ongoing Phase 1/2 Demographics and Baseline Characteristics All Subjects (N=57) Median age, years (range) 64 (30, 84) Sex, n (%) Female 33 (58) Male 24 (42) ECOG PS at baseline, n (%) 0 17 (30) 1 40 (70) Number of prior anti-cancer regimens, median (range) 4 (1, 11) Subjects with prior anti
Slide 13: Overall Safety Summary
BDC-1001 Overall Safety Summary • Consistent with BDC-1001’s design, this agent has demonstrated good safety and tolerability at doses tested to date • No DLTs observed to date; MTD has not been reached at up to 20 mg/kg q3w or 12mg/kg q2w dose levels • Two treatment-related SAEs, both of which led
Slide 14: Rapid Clearance; No Evidence of Anti-drug Antibody Formation
BDC-1001 Demonstrates Rapid Clearance; No Evidence of Anti-drug Antibody (ADA) Formation ISAC Cohort Mean – q3w Only • No subjects (0/53) developed antibodies to BDC-1001 after treatment was initiated – 2/53 (3.8%) subjects were found to have pre-existing antibodies reactive to BDC-1001 14 Sharma MR
Slide 15: PK Parameters Show Increase with Ascending Dose Levels
BDC-1001 PK Parameters Show Increase with Ascending Dose Levels Summary of PK Data • Target Cmin levels not yet achieved • (Cmin of ~16 µg/ml for optimal efficacy)1,3 • Clinical PK modeling suggests that higher sustained trough levels >16 µg/mL can be achieved in humans via weekly dosing schedule •
Slide 16: Correlation Between Drug Concentration and Biomarker Levels
Time-matched PK Concentration vs Plasma Biomarker Levels Correlation Between Drug Concentration and Biomarker Levels Biomarker Value, pg/ml Increasing plasma cytokine/ chemokine levels were observed at higher drug concentration levels and Biomarker Value, pg/ml have not reached a plateau BDC-1001 Se
Slide 17: Induces Changes in the Tumor Microenvironment Consistent with MOA
BDC-1001 Induces Changes in the Tumor Microenvironment Consistent with MOA as Seen in Paired Tissue Biopsies from Ongoing Clinical Trial • Representative tissue biomarkers investigated with IHC: • Myeloid cell infiltration: CD11c, CD68, BDCA-2 (pDC), CD163 (M2s) • T cell infiltration and activation:
Slide 18: Evidence of Activated Tumor Immunity in Paired Tissue Biopsies – Example 1
Evidence of Activated Tumor Immunity in Paired Tissue Biopsies – Example 1 Clinical trial subject with cervical cancer on BDC-1001 5 mg/kg q3w Myeloid cells infiltration T cell infiltration & activation H&E • 29-year-old female with recurrent metastatic endocervical cancer, HER2 amplified, MSS, PD-L
Slide 19: Evidence of Activated Tumor Immunity in Paired Tissue Biopsies – Example 2
Evidence of Activated Tumor Immunity in Paired Tissue Biopsies – Example 2 Clinical trial subject with breast cancer on BDC-1001 8 mg/kg q3w Myeloid cells infiltration T cell infiltration & activation • 40-year-old female with metastatic H&E HER2+ (IHC3+) breast cancer • Previously treated with mult
Slide 20: Clinical Activity Seen in 13 of 40 Tumor-evaluable Subjects
BDC-1001 Clinical Activity Seen in 13 of 40 Tumor-evaluable Subjects* Across Tumor Types and Dose Levels (2-20 mg/kg) Duration of Disease Control Tumor Response Site of Primary Tumor Cohort (PR or SD) in Weeks Partial response Colorectal 36§ 5 mg/kg q3w (>36 weeks) Endometrial 24 2 mg/kg q3w Cervix
Slide 21: Subject with Metastatic CRC Confirmed PR at 36 Weeks, Maintained Through 52 Weeks
Subject with Metastatic CRC Confirmed PR at 36 Weeks, Maintained Through 52 Weeks 2014 Chest CT Scans 66-year-old Male with Prior to BDC-1001 Treatment At 12 weeks At 36 weeks Metastatic Adenocarcinoma of the Colon • Tumor HER2+ (IHC3+, amplified; MSS, KRAS wt) • Previous treatments include chemoth
Slide 22: Summary
BIOTHERAPEUTICS Op e011 Summary
Slide 23: Progress in Our Pioneering Journey
Progress in Our Pioneering Journey First-in-class Boltbody™ ISAC: Broadly Enabling Platform Cash on Hand of $295.5 million1 BDC-1001 Technology Achieves Key Milestones Upcoming Milestones for BDC-1001 • 4Q21: Initiate dose-escalation combination trial with anti-PD-1 • Opdivo® anti-PD1 antibody suppl
Slide 24: Thank You
BIOTHERAPEUTICS g BOLT Thank You