TRANSCENTA-B (06628) announced the presentation of preclinical data for its self-developed LIV1 Antibody-Drug Conjugate (ADC) at the 2026 AACR Annual Meeting. The data demonstrated potent anti-tumor activity, differentiated payload-dependent efficacy, and a favorable tolerability profile, supporting further development in LIV1-positive solid tumors. LIV1 is a member of the zinc transporter family. Its expression is limited in normal tissues but is frequently highly expressed in breast cancer (93%), prostate cancer (72%), and lung cancer (10%), making it a notable cell surface target for ADC therapy development.
The company has developed 48D6, a novel, self-developed, humanized anti-LIV1 monoclonal antibody with high binding affinity, specificity, and internalization capability. Using Retrogenix cell microarray technology, 48D6 showed no non-specific interactions with other human proteins, confirming its high target specificity. Utilizing 48D6, the company subsequently generated two ADC candidates via a glycosyltransferase-mediated site-specific conjugation platform: ADC-2 (conjugated with a topoisomerase I inhibitor payload) and ADC-3 (conjugated with MMAE).
In a LIV1-expressing prostate cancer PDX model, ADC-2 showed limited tumor growth inhibition after two doses. After replacing ADC-2 with the MMAE-based ADC-3 starting from the third dose, ADC-3 significantly suppressed prostate tumor growth. In a high LIV1-expressing prostate cancer PDX model, tumor growth inhibition by ADC-3 persisted for over 70 days after dosing cessation.
In an exploratory toxicity study evaluating safety and tolerability, ADC-2 showed a favorable tolerability profile in mice after multiple administrations at all tested doses. Minor lesions were observed in the 60 mg/kg group during treatment and resolved completely by the end of the recovery period. Based on these results, the maximum tolerated dose (MTD) for ADC-2 in mice was determined to be 60 mg/kg. The safety and tolerability of ADC-3 have not yet been explored.
Overall, these data demonstrate that TRANSCENTA's LIV1 ADC-2 and ADC-3 programs exhibit potent anti-tumor activity as monotherapies in PDX models of ER-positive/HER2-negative breast cancer (which accounts for approximately 60% of all breast cancers) and prostate cancer. ADC-2 and ADC-3 displayed excellent tolerability profiles in mice. Notably, TRANSCENTA's LIV1 ADC also showed potent anti-tumor activity in triple-negative breast cancer (TNBC) tumor models, with related data previously presented at the 2024 SABCS. These results support further investigation into the application of TRANSCENTA's LIV1 ADC in LIV1-positive solid tumors.
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