Anbenitamab repodatecan Clinical ADC, Bispecific, Biparatopic

Antibody Information

Entry ID	876
INN	Anbenitamab repodatecan
Status	Clinical
Drug code(s)	JSKN003, JSKN033 (combo of JSKN003 and envafolimab)
Brand name	None
mAb sequence source	mAb humanized
General Molecular Category	ADC, Bispecific, Biparatopic
Format, general category	Full length Ab conjugate
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	Dibenzocyclooctyne tetrapeptide linker (Cleavable)
Ave. DAR	3.8 (range 3 to 4)
Conjugated/fused moiety	Topoisomerase I inhibitor, Camptothecin derivative
Discovery method/technology	None

Therapeutic information

Target(s)	HER2, HER2
Indications of clinical studies	Ovarian cancer, Breast cancer, 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)	May 15, 2022
Start of Phase 2
Start of Phase 3	November 15, 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	Alphamab (Australia) Co Pty Ltd.
Licensee/Partner	CSPC Pharmaceutical Group Co., Ltd.
Comments about company or candidate	NCT06751485 Phase 3 in ovarian cancer due to start in Jan 2025. Sep 2024: Alphamab Oncology announced that Jiangsu Alphamab Biopharmaceuticals Co., Ltd., a wholly-owned subsidiary of Alphamab Oncology, entered into a licensing agreement on anti-HER2 bispecific antibody-drug conjugate JSKN003 with JMT-Bio Technology Co., Ltd., a wholly-owned subsidiary of CSPC Pharmaceutical Group Co., Ltd. According to the terms of the Licensing Agreement, JMT-Bio will obtain the exclusive license and sublicense rights to develop, sell, offer for sale and commercialize JSKN003, for the treatment of tumor-related indications in mainland China (excluding Hong Kong, Macau or Taiwan) (the "Territory") and become the sole marketing authorization holder for JSKN003 for the Field in the Territory. Phase III clinical study JSKN003-302 is NCT06079983. Dec. 4, 2023: Alphamab Oncology announced the first patient has been dosed in the phase III clinical study (JSKN003-302) of anti-HER2 bispecific antibody-drug conjugate JSKN003 for treatment of advanced HER2-low breast cancer. https://www.prnewswire.com/apac/news-releases/first-patient-dosed-in-phase--study-of-jskn003-for-the-treatment-of-advanced-her2-low-breast-cancer-302004249.html NCT05744427 and NCT06226766 are Phase 1/2 studies in solid tumors. JSKN033 is a combination drug product comprised of JSKN003 and envafolimab for subcutaneous injection. NCT05744427 Phase 1 started in March 2023; Mar 16: Alphamab Oncology announced that the first patient has been dosed with 2.1mg/kg in a Phase I clinical study (JSKN003-102) of JSKN003, an Anti-HER2 bispecific ADC. NCT05494918 Phase 1 started in Aug 2022; company announced Sep 19, 2022 that the first patient has been successfully dosed in a phase I clinical trial of JSKN003 (a KN026 (a recombinant humanized anti-human epidermal growth factor receptor 2 (“HER2”) bispecific antibody) antibody-drug conjugate (“KN026-ADC”) independently developed by the Company) in Australia, and that in August 2022, the investigational new drug (“IND”) application of JSKN003 was submitted to the National Medical Products Administration of China (the “NMPA”) and accepted for the treatment of solid tumors. The Company completed the efficacy validation and process development for JSKN-003 in June 2021 and targets to submit IND application in the second quarter of 2022. In May 2021, Jiangsu Alphamab entered into a collaboration agreement with Suzhou Alphamab Co., Ltd. for two technology development projects, namely, JSKN003 and the preparation process development project for mGalt1, a key material of conjugation process.
Full address of company	218 Xinhu St. Building #C23, Suzhou, Jiangsu Asia China https://www.alphamabonc.com/en/contact/index.html

Description/comment

JSKN003 is an antibody-drug conjugate (ADC) comprised of a recombinant, humanized anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody conjugated to a topoisomerase I inhibitor via a dibenzocyclooctyne tetrapeptide linker. The anti-HER2 component, KN026, is a recombinant, humanized bispecific antibody that targets both extra-cellular domains II (pertuzumab binding site) and IV (trastuzumab binding site) of HER2. (doi: 10.1093/abt/tbad014.009)
JSKN003 is an anti-HER2 bispecific antibody-drug conjugate (bis-ADC), developed inhouse with proprietary Glycan-specific conjugation platform; targets domain II and IV of HER2 (https://www.alphamabonc.com/en/uploads/2021/01/210003484816.pdf). See also https://www.alphamabonc.com/en/uploads/2023/08/169286574293454.pdf.
JSKN003 and anti-PD-1 envafolimab combination = JSKN033

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None