Izalontamab brengitecan Clinical ADC, Bispecific

Antibody Information

Entry ID	444
INN	Izalontamab brengitecan
Status	Clinical
Drug code(s)	BL-B01D1, BMS-986507
Brand name	None
mAb sequence source	mAb chimeric/human
General Molecular Category	ADC, Bispecific
Format, general category	Appended Ig conjugate
Format details	2+2 symmetric, IgG-(scFv)2
Isotype (Fc)	IgG1
Light chain isotype	kappa/lambda
Linker	Cathepsin B cleavable linker
Ave. DAR	8
Conjugated/fused moiety	Topoisomerase I inhibitor, Ed-04
Discovery method/technology	None

Therapeutic information

Target(s)	EGFR, HER3
Indications of clinical studies	Chordoma, Glioblastoma, Small cell lung cancer, Head and Neck Squamous Cell Carcinoma, Urothelial Carcinoma, Triple-neg breast cancer, Non-small cell lung cancer (EGFR wild-type), Esophageal squamous cell carcinoma, Cervical cancer, Nasopharyngeal Carcinoma, Non-small Cell Lung Cancer With EGFR-sensitive Mutations, Gynecological Malignant Tumor, Urinary tract cancer, Breast cancer, Gastrointestinal Tumors, Solid tumors
Primary therapeutic area	Cancer

Development stage information

Phase lengths*

*The graph represents early-stage clinical development phase lengths. For molecules approved or under evaluation for marketing authorization in the US is provided a complete overview of all clinical development phase lengths. Phase lengths are calculated from the start of the first in human (FIH) study (Start of clinical phase). “Start of Phase 2” bar represents Phase 1 length (Start of clinical phase to start of Phase 2); “Start of Phase 3” bar represents Phase 1+2 length (Start of clinical phase to start of Phase 3); “Date BLA/NDA submitted” bar represents Phase 1+2+3 length (Start of clinical phase to Date BLA/NDA submitted); and “Date of first US approval” bar represents Phase 1 to first US approval length (Start of clinical phase to Date of first US approval).

Most advanced stage of development (global)	Phase 3
Status	Active
Start of clinical phase (IND filing or first Phase 1)	August 15, 2021
Start of Phase 2	April 15, 2023
Start of Phase 3	December 04, 2023
Date BLA/NDA submitted to FDA
Year of first approval (global)	None
Date of first US approval
INN, US product name	None
US or EU approved indications	None

Company information

Company	Sichuan Baili Pharmaceutical Co. Ltd., Systimmune
Licensee/Partner	Bristol Myers Squibb
Comments about company or candidate	NCT06857175 Phase 3 in urothelial carcinoma due to start in March 2025. NCT06787664 Phase 2 in Chordoma started in Jan 2025. Phase 3 studies for Nasopharyngeal carcinoma (NCT06118333 / CTR20233419); Esophageal Squamous Cell Carcinoma (NCT06304974), Small Cell Lung Cancer (NCT06500026), Non-small Cell Lung Cancer (NCT06382129, NCT06382116), Triple-Negative Breast Cancer (NCT06382142), HR+HER2- Breast Cancer (NCT06343948) are recruiting as of May-September 2024 NCT06304974 Phase 3 in esophageal squamous cell carcinoma started in Mar 2024. Dec 2023: BMS gains ex-China rights to the EGFRxHER3 bispecific BL-B01D1. NCT06118333 / CTR20233419 Phase 3 in Nasopharyngeal Carcinoma started in Dec 2023. NCT05990803 Phase 2 in cervical cancer due to start in Sep 2023. NCT05880706 Phase 2 due to start in July 2023. NCT05785039 Phase 2 started in April 2023. NCT05470348 Phase 1 started in July 2022. NCT05461768 Phase 1 recruiting when first posted on July 18, 2022; NCT05393427 Phase 1 started in Feb 2022. Dec 2021: Beacon reports Phase 1 was started; CTR20212923 NCT05194982 Phase 1 started in Nov 2021. On August 10, 2021, the clinical trial application of Bailey Pharmaceuticals BL-B01D1 was accepted by NMPA
Full address of company	1#, Building 1,No.161, Baili Road, Cross-Strait Science and Technology Industrial Development Park, Wenjiang District, Chengdu City Postcode：610041 Asia China http://www.baili-pharm.com/

Description/comment

BL-B01D1 is a bispecific antibody conjugate (ADC) developed by Bailey Pharmaceuticals, which can target EGFR and HER3 at the same time. It is planned to develop BL-B01D1 for the treatment of lung cancer, esophageal cancer, head and neck squamous cell carcinoma and other indications. BL-B01D1 is comprised of a bispecific antibody against EGFR/HER3 (SI-B001), a cathepsin B cleavable linker, and a novel topoisomerase I inhibitor agent (Ed-04), which is a derivative of the alkaloid camptothecin, driving cell cycle arrest at the S phase and subsequent apoptosis. BL-B01D1 achieves a high drug-to-antibody-ratio (DAR=8) with a highly stable linker. Cancer Res (2023) 83 (7_Supplement): 2642. doi.org/10.1158/1538-7445.AM2023-2642.
The Fab arms and Fc domains are derived from cetuximab.
https://www.bms.com/assets/bms/us/en-us/pdf/investor-info/doc_presentations/2024/ESMO-2024-investor-presentation.pdf

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None