SUZHOU, China, April 30, 2025 /PRNewswire/ — Alphamab Oncology (stock code: 9966.HK) announced that the preclinical data on two novel bispecific antibody-drug conjugates (ADCs) JSKN021 and JSKN022 were presented as posters at the 2025 American Association for Cancer Research (AACR) Annual Meeting, which is held in Chicago, USA, from April 25 to 30, 2025.
Title: JSKN021, an innovative site-specific dual-payload bispecific antibody drug conjugate targeting EGFR and HER3 exhibits potent preclinical activities
Abstract ID: 5451 / 9
Location: Poster Section 15
Poster release time: April 29, 2025, 2:00 PM- 5:00 PM CDT
EGFR and HER3 are widely overexpressed in human malignancies, rendering them promising targets for cancer treatment. Alphamab has developed JSKN021, a dual payload bispecific ADC targeting EGFR/HER3, utilizing glycan-specific conjugation technology. The novel DNA topoisomerase I inhibitor T01 and the microtubule inhibitor MMAE, are conjugated to glycan on Fc via cleavable linkers, thereby achieving synergistic antitumor effects through the dual-payload strategy.
Preclinical studies have shown that JSKN021 exhibits excellent stability. Its dual-payload design effectively addresses tumor heterogeneity, demonstrating significantly superior tumor inhibition compared to single-payload ADCs, and might be a promising novel antitumor therapeutic agent. Key differentiating features of JSKN021 include:
- Conjugation and Stability: JSKN021 demonstrated excellent stability in serum from rat, mice, monkey, and human, with minimal payload release owing to glycan-based conjugation.
- Binding and Payload Release: JSKN021 successfully bound to both EGFR and HER3, and its payloads (T01 and MMAE) were effectively released without detectable side metabolites.
- In Vitro Efficacy: JSKN021 significantly inhibited cancer cell growth in multiple cell lines expressing EGFR, HER3, or both (e.g., HCC827, MDA-MB-468, A431, NCI-H1975).
- In Vivo Efficacy: In multiple CDX models, JSKN021 showed superior tumor inhibition compared to single-payload ADCs.
Title: JSKN022, a first-in-class multi-specific ADC targeting PD-L1 and ITGB6/8 with an innovative DNA topoisomerase I inhibitor demonstrates encouraging efficacy in preclinical models
Abstract ID: 5450 / 8
Location: Poster Section 15
Poster release time: April 29, 2025, 2:00 PM- 5:00 PM CDT
Monoclonal antibodies targeting PD-1/PD-L1 have significantly transformed cancer therapy. However, the majority of patients still cannot get benefit from this treatment or may develop resistance afterwards. Leveraging the increased expression of PD-L1 in tumors, Alphamab has developed JSKN022, an innovative sdAb (single domain antibody) Fc fusion protein drug conjugate, based on our independently developed Envafolimab. This drug molecule utilizes glycan-specific conjugation technology to site-specifically conjugate the DNA topoisomerase I inhibitor T01 to the Fc glycans. It is designed to simultaneously target PD-L1 and ITGB6/8, enabling a synergistic anti-tumor effect.
This preclinical study suggests JSKN022, as a first-in-class multi-specific PD-L1/ITGB6/8 ADC, might potentially bring in novelty in the therapeutic approach for cancers that are refractory or resistant to PD-1/PD-L1 inhibitors. Preclinical data demonstrate that JSKN022 exhibits the following differentiating features:
- Binding and Specificity: JSKN022 demonstrated specific binding to PD-L1, αvβ6 and αvβ8 protein without cross-reacting with other integrin family members.
- Internalization: JSKN022 exhibited superior internalization capacity in HCC4006 and Capan-2 cancer cells compared to mono-target antibodies.
- Conjugation and Stability: JSKN022 demonstrated excellent stability in serum from rat, mice, monkey, human, with minimal payload (T01) release, attributed to glycan-based conjugation.
- Efficacy: JSKN022 effectively inhibited the proliferation of cancer cells and demonstrated greater tumor suppression than single-target ADCs in preclinical cancer models.
About JSKN021
JSKN021 is a first-in-class dual payload ADC consisting of an EGFR/HER3 bispecific antibody conjugated with novel topoisomerase I inhibitor (T01) and MMAE. Engineered with finely tuned binding avidity in both arms to address tumor heterogeneity while minimizing on-target, off-tumor toxicity, JSKN021 was designed for enhanced stability and improved homogeneity. It combines T01 (DAR 4) and MMAE (DAR 2) payloads to overcome non-response and resistance observed with single-payload treatment strategies.
About JSKN022
JSKN022 is a first-in-class ADC targeting both PD-L1 and ITGB6/8. Based on independently developed Envafolimab, Alphamab integrates immuno-oncology (IO) mechanisms with ADC approaches. This novel drug molecule utilizes glycan-specific conjugation technology to enhance both stability and homogeneity. The topoisomerase I inhibitor T01 is site-specifically conjugates to multi-functional antibody via a cleavable linker, thereby improving therapeutic efficacy. JSKN022 might potentially bring in novelty in the therapeutic approach for cancers that are refractory or resistant to PD-1/PD-L1 inhibitors.
About Alphamab Oncology
Alphamab Oncology is an innovative biopharmaceutical company focusing on oncology therapeutics. By leveraging its proprietary core technology platforms including single-domain antibodies, bispecific antibodies, glycan-specific conjugation, linker-payload, dual-payload antibody conjugation, and subcutaneous high concentration formulation for biologics, the Company has established a differentiated and globally competitive product portfolio, covering cutting-edge areas such as antibody-drug conjugates (ADCs), bispecific antibodies, and single-domain antibodies.
The Company has one product approved for marketing (Envafolimab, the world’s first subcutaneously injectable PD-(L)1 inhibitor), which has made a significant breakthrough in the convenience and accessibility of cancer treatment. Additionally, the Company has multiple bispecific antibodies and bispecific ADCs in clinical stage, while rapidly advancing the preclinical pipeline prioritizing bispecific ADCs and dual-payload ADCs. Multiple strategic collaborations based on innovative products or technology platforms have been established with partners such as CSPC, ArriVent, and Glenmark.
Our overarching mission is to make cancer manageable and curable by addressing unmet clinical needs in oncology. Alphamab Oncology is continuously dedicated to the development of effective, safe, and globally competitive anti-tumor drugs to benefit patients.
