Bolt Biotherapeutics : BDC-4182 AACR Poster (BBI-4182-101 TiP AACR 2026 Final)

Published: 2026-04-17 15:20:06 ET BOLT

Published on 04/17/2026 at 03:20 pm EDT

Study Design: Dose Escalation with Cycle 1 Step-Up Dosing

Backfill at dose levels cleared for safety

Gastric and gastroesophageal cancer patients

Open for enrollment in Australia, South Korea, and Taiwan (NCT06921837)

Target Dose 1

Target Dose 2

Target Dose 3

Target Dose 4

Target Dose

Step-Up Dosing

Target Dose 5

Target Dose 6

Backfill

(≤ 20 patients)

Target Dose 7

Dose Escalation with Step-Up Dosing

Monotherapy, 3 + 3 Design

(21 - 42 patients)

Key Eligibility and Exclusion Criteria

Key Eligibility

Histologically or cytologically confirmed metastatic or unresectable gastric or gastroesophageal cancer

Measurable disease by RECIST v1.1

Received ≥ 1 prior lines of locally available standard therapies or intolerant of standard therapies

CLDN18.2 expression of ≥ 1% of tumor cells scored as ≥ IHC 2+ if prior CLDN18.2 expression is known (may be enrolled if prior expression is unknown)

Adequate organ function suitable for Phase 1 therapy

Willingness to provide tumor biopsy prior to enrollment if clinically feasible

Key Exclusions

Uncontrolled or symptomatic CNS metastases

Clinically significant or uncontrolled cardiac, pulmonary, or hepatic disease

Active infection or residual toxicity from a previous treatment

Recent use of investigational agent or standard anti-cancer therapies

INNATE IMMUNITY

ADAPTIVE IMMUNITY

Biological Rationale

BDC-4182 promotes tumor killing by several mechanisms, including:

Antibody-dependent cellular phagocytosis by tumor-associated myeloid cells

Activation and expansion of tumor-specific T cells

Cytotoxic T cell-mediated tumor cell killing with potential for durable anti-tumor immune memory

A CLDN18.2-targeting ISAC surrogate (BDC-4182.S) elicited complete tumor regression in xenograft and syngeneic models with low levels of CLDN18.2 expression (IHC1+) & generated T cell-dependent immune memory that prevented outgrowth CLDN18.2-negative tumors

Compared with cytotoxic ADCs, BDC-4182.S demonstrated superior anti-tumor efficacy at lower doses in CLDN18.2-high tumors and in tumors with low levels of CLDN18.2 expression1

NCI-N87-hCLDN18.2 (IHC 1+)

PA-TU-8988S (IHC 1+)

MC38-mCLDN18.2 (IHC 1+)

CLDN18.2-targeting ISAC surrogates demonstrated tumor growth inhibition and improved activity relative to cytotoxic ADC controls in models with low CLDN18 expression. Data are shown as mean and SEM with dashed lines indicating the day of dosing.

Summary

BDC-4182 is a first-in-class CLDN18.2 immune-stimulating antibody conjugate (ISAC) being investigated in a Phase 1/2 study in patients with previously treated metastatic gastric or gastroesophageal cancer

Preclinical studies demonstrate robust immune activation, including complete tumor regression, in low-CLDN18.2-expressing models and superior anti-tumor activity compared to cytotoxic ADCs in the same low-expression setting

This study incorporates step-up dose escalation to enable assessment of biologically active exposures while maintaining tolerability

Dose-escalation cohorts are open for enrollment in Australia, South Korea, and Taiwan (NCT06921837)

Acknowledgements

The authors are grateful to the patients and their caregivers for their support as well as the investigators and their study teams for their contributions.

Presenting author has no conflicts of interest to declare.

This presentation is the intellectual property of Bolt Biotherapeutics, Inc. and can be found online at boltbio.com

Sponsor:[email protected]

Biomarker Assessment

Serial blood collection will enable longitudinal analyses of circulating pharmacodynamic biomarkers, including cytokines and chemokines

Baseline tumor tissue will be evaluated to assess CLDN18 expression and support exploratory biomarker analyses

Exploratory blood- and tissue-based analyses may investigate relationships among:

Target expression

Pharmacodynamic activity

Safety

Anti-tumor activity

These analyses aim to inform exposure-response relationships and potential patient selection strategies

References

1. Fu et al. Preclinical Investigation of BDC-4182, a Claudin 18.2-Targeting ISAC to Support Clinical Development. SITC 2025.https://doi.org/10.1136/jitc-2025-SITC2025.0950

CT094

A phase 1/2 study of BDC-4182, a claudin18.2-targeting next-generation immune-stimulating antibody conjugate (ISAC), in patients with advanced gastric and gastroesophageal cancer

Sophia Frentzas1, Michelle Morris2, Megan Barnet3, Niall Tebbutt4, Mark Wong5, Michael Michael6, Hyung-Don Kim7, Keun-Wook Lee8, Sun Young Rha9, Sang Cheul Oh10, I-Chen Wu11, Li-Yuan Bai12, Wen-Chi Chou13, Ming-Huang Chen14, Yen-Yang Chen15, Chia-Chi Lin16, Anthony Rodrigues3, Jason Ptacek17, Michael N. Alonso17, Tariq Arshad17, Jakob Dupont17, Kristi Balacy17, Sung Hee Lim18

1. Monash Medical Centre, Clayton, Australia, 2. Sunshine Coast University Private Hospital, Birtinya, Australia, 3. St Vincent Hospital Sydney (The Kinghorn Cancer Centre), Darlinghurst, Australia, 4. Austin Health, Heidelberg, Australia, 5. Westmead Hospital, Westmead, Australia, 6. Peter MacCallum Cancer Centre, Melbourne, Australia, 7. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,

8. Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea, 9. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea, 10. Korea University Guro Hospital, Seoul, Republic of Korea, 11. Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung City, Taiwan, 12. China Medical University Hospital, China Medical University, Taichung City, Taiwan, 13. Linkou Chang Gung Memorial Hospital, Taoyuan City, Taiwan, 14. Taipei Veterans General Hospital, Taipei City, Taiwan, 15. Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan, 16. National Taiwan University Hospital, Taipei, Taiwan, 17. Bolt Biotherapeutics, Redwood City, CA, USA, 18. Samsung Medical Center, Seoul, Republic of Korea

Binds tumor antigen

Phagocytosis of tumor

Immune activation

4 Triggers killing by T cells

Mechanism of Action

BDC-4182 is a next-generation ISAC with significantly enhanced immune activating capability

Tumor recognition → Innate activation → T cell priming → Tumor regression

Antigen recognition by T cells

BDC-4182

Myeloid antigen presenting cell

Fc receptor

BDC-4182

CLDN18.2

TLR7/8

Cellular activation & inflammatory cytokines

T cells killing tumor cells

Primary Objective

Objective:

Define safety, tolerability, and recommended Phase 2 dose (RP2D)

Endpoints:

Incidence of AEs/SAEs (CTCAE v5.0)

Dose-limiting toxicities

Secondary Objectives

Objectives:

Evaluate preliminary anti-tumor activity

Characterize pharmacokinetics and evaluate immunogenicity of BDC-4182

Endpoints:

Evaluate according to RECIST v1.1 ORR, DOR, DCR, PFS, BOR, and OS

PK parameters (Cmax, Cmin, AUC, CL, V, t1/2)

Incidence of anti-drug antibodies

Exploratory Objectives

Objectives:

Investigate relationship between CLDN18 expression and clinical activity

Explore potential blood and tumor biomarkers associated with exposure, efficacy, or safety

Endpoints:

Correlation of CLDN18 expression and efficacy

Biomarker associations (gene expression, protein, and tissue image analysis)

Disclaimer

Bolt Biotherapeutics Inc. published this content on April 17, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 17, 2026 at 19:19 UTC.