[Madrid, Spain = E-Daily Reporter Kim Jinsoo ] “LCB02A uses exatecan as its payload. Drugs in the exatecan class have a bystander effect that allows them to attack surrounding cancer cells, and this effect is expected to be further enhanced through integration with our unique linker technology.”

Ok Chan-young, Director of the Translational Research Center at LigaChem Biosciences(141080), met with PharmDaily on the 23rd (local time) at the European Society for Medical Oncology (ESMO) 2026 and stated, “The key achievement of this study is that we confirmed the tolerability of the claudin 18.2 (CLDN18.2)-targeting antibody-drug conjugate (ADC) LCB02A in preclinical trials.”

LCB02A is an ADC developed using LigaChem Biosciences’ proprietary “Conjuol” ADC platform, in which the topoisomerase 1 (Topo1i) inhibitor exatecan is site-specifically conjugated to an anti-CLDN18.2 antibody.

According to the preclinical data on LCB02A presented by LigaChem Biosciences at this year’s ESMO, excellent tolerability was confirmed in repeated-dose toxicity studies in monkeys when the dose was escalated from 40 mg to 60 mg. Furthermore, linker stability was confirmed, as evidenced by the fact that the concentration of free payload in the blood remained very low. The free payload refers to the anticancer component that has detached from the antibody. A low free payload indicates that the premature dissociation of the drug from the antibody in the bloodstream was limited.

In terms of efficacy, in CLDN18.2-overexpressing gastric cancer and pancreatic cancer xenograft models, tumors were observed for 53 days following a single dose. In the gastric cancer model, a single 2 mg dose resulted in near-complete tumor regression, which was maintained throughout the observation period. Tumor growth was also inhibited at the 1 mg dose, and in the pancreatic cancer model, a single 4 mg dose demonstrated efficacy.

To develop LCB02A, LigaChem Biosciences reviewed various combinations and, after balancing efficacy and safety, set the drug-antibody ratio (DAR)—the number of drug molecules bound to a single antibody—at 4.

He stated, “Given that CLDN18.2 is also expressed in normal gastric mucosa, managing toxicity is crucial.” Conjuol is a platform that combines site-specific conjugation technology—which attaches a payload to a specific location on the antibody—with a beta (β)-glucuronide-based linker. It is designed to maintain the bond between the antibody and the drug in the bloodstream while releasing the payload in tumors through enzymatic action,” he explained.

Center Director Ok stated, “The key to LigaChem Biosciences securing such promising data this time was its proprietary linker and conjugation technology, ‘Conjuol.’ By stably delivering Exatecan to cancer cells and then releasing it within the tumor, the ‘bystander effect’—where the payload attacks surrounding cancer cells—can be utilized even more effectively. It is also significant that we have reconfirmed Conjuol’s stability in the bloodstream,” he stated.

Linker Technology: Maximizing the Bystander Effect Beyond Safety

The benefits that LigaChem Biosciences gains through Conjuol extend beyond the safety of delivering the payload exclusively to cancer cells. If the linker accurately transports the anticancer agent to the tumor and releases it only where needed, the bystander effect can be maximized, which ultimately translates into therapeutic efficacy.

He explained, “Cancer tissue contains a mix of cells that highly express CLDN18.2 and those that express it at low levels. Cancer cells with low target expression are difficult for ADCs to bind to directly and may therefore survive. In such cases, the ADC that enters cells with high target expression releases its payload, and this substance spreads to and attacks surrounding cancer cells—this is the bystander effect.”

Center Director Ok stated, “The exatecan-based payload incorporated into LCB02A is a therapeutic agent that holds promise for the bystander effect. However, even with a potent payload, if it is released into the bloodstream first, the amount of drug reaching the cancer cells decreases, and the toxicity burden may increase. Therefore, if the drug is stably delivered to the tumor using Conjuol technology, the bystander effect can be maximized.”

The effectiveness of LigaChem Biosciences’ Conjuol becomes even more evident when compared to its competitor, the Innovent-Takeda ADC “IBI343.” IBI343, developed by Innovent and Takeda, also uses an exatecan-based payload. The Phase 3 “G-HOPE-001” clinical trial, presented at ESMO on the 23rd, demonstrated improvements in overall survival and progression-free survival. The study was conducted only on patients with CLDN18.2 expression rates of 75% or higher.

LigaChem Biosciences is also selecting patients based on a CLDN18.2 expression rate of 75% or higher during the early phase of the Phase 1 clinical trial for LCB02A. However, the company anticipates the possibility of expanding the patient population to include those with a CLDN18.2 expression rate as low as 40% during the upcoming dose escalation process, while monitoring safety and initial anticancer efficacy.

The company believes that even when using a payload from the same class, if the bystander effect is sufficiently harnessed through Conjuol’s stable drug delivery and intratumoral release, the treatment could be effective even in patients with relatively low target expression.

Center Director Ok emphasized, “To demonstrate differentiation from competing ADCs, it is crucial to show superior efficacy compared to competing drugs in patients with similar CLDN18.2 expression levels,” adding, “I believe it is important for LCB02A to demonstrate efficacy even in the low-expression patient group where the effects of competing drugs are limited.”

Meanwhile, LCB02A began administering the first doses to patients in a Phase 1/2 clinical trial in North America this month.