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Raffaele Colombo: Preclinical development of DB-1419 published on Clinical Cancer Research AACR

Raffaele Colombo/LinkedIn

Jun 19, 2025, 13:42

Raffaele Colombo: Preclinical development of DB-1419 published on Clinical Cancer Research AACR

Raffaele Colombo, Associate Director of Medicinal Chemistry at Zymeworks, posted on X:

“Preclinical development of DB-1419 published on Clinical Cancer Research AACR!

DB-1419 is a bispecific ADC (bsADC)

– B7H3 x PDL1
– P1003 (TOPO1i)
– DAR8

Title: Preclinical evaluation of DB-1419, a novel bifunctional and bispecific anti-B7-H3×PD-L1 antibody-drug conjugate

Authors: Chenggang Li, Jun Yao, Junjie Yang, Yu Zhang, Yang Qiu, Zhongyuan Zhu, Haiqing Hua

Read Full Article.

Raffaele Colombo

The B7H3 x PDL1 bispecific (naked) antibody DB-141902 was previously published

DB-141902 has a IgG1-VHH tetravalent 2+2 format.

Raffaele Colombo: Preclinical development of DB-1419 published on Clinical Cancer Research AACR

Title: Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities

Authors: Hua-ying Li, Yi-li Chen, Xiang-nan Deng, Huan-huan Li, Jie Tan, Guo-jian Liu, Yu-juan Zheng, Min Pei, Kai-ting Peng, Li-li Yue, Xiao-jia Chen, Yu Liu, Yong-shan Zhao & Chun-he Wang

Read Full Article.

Raffaele Colombo: Preclinical development of DB-1419 published on Clinical Cancer Research AACR

P1003 is the same payload used in DB-1303/ BNT323.

Most of the other Duality’s ADCs use P1021 instead.

P1003 was disclosed in INN list #131 (see: pamirtecan).
P1021 is still undisclosed, but likely as below (from patents).

All exatecan derivatives (DXd and Ed-04 as ref.)

Raffaele Colombo: Preclinical development of DB-1419 published on Clinical Cancer Research AACR

The DB-1419 BsADC format is quite similar to BL-B01D1.

Another common characteristic is the very short half-life of these 2 BsADCs!

Across doses, ADC half-life:
0.5-1.3 days for DB-1419 (preclinical)
0.4-1.7 days for BL-B01D1 (clinical)

Note: ≠ payloads (P1003 vs Ed-04)

Raffaele Colombo: Preclinical development of DB-1419 published on Clinical Cancer Research AACR

DB-1419 induced P1003-mediated DNA damage and apoptosis.

Authors speculate that adaptive immune activation and promotion of T-cell proliferation and reinvigoration from B7H3xPDL1 BsAb + ICD induced by the P1003 payload may also contribute to the overall efficacy of DB-1419.”

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