[Edaily Reporter Kim Jinsoo ] LigaChem Biosciences(141080)has outlined plans to develop “LCB02A,” an antibody-drug conjugate (ADC) targeting Claudin 18.2 (CLDN18.2), as a first-line treatment. Given LCB02A’s high safety profile, the strategy involves transitioning it from a follow-up treatment to a first-line treatment through combination therapy with existing chemotherapy or immuno-oncology drugs.

According to recent reports from the pharmaceutical and biotech industry, LigaChem Biosciences has recently begun Phase 1 clinical trials for LCB02A in earnest, setting out to thoroughly verify the safety and efficacy of this CLDN18.2-targeting compound—a target distinct from HER2 and TROP2, which have been the focus of existing ADCs.

Preclinical data show that LCB02A effectively eliminated gastric and pancreatic cancer cells expressing CLDN18.2 even at low doses. Notably, it demonstrated high safety by having virtually no effect on cells that do not express CLDN18.2. In particular, while normal blood cells were damaged when the anticancer drug was administered alone, they were unaffected when administered in the form of LCB02A. This confirms the high tumor selectivity of ADCs, in which the antibody targets only cancer cells to deliver the drug, and the compound is expected to be highly competitive in terms of side effects.

In terms of efficacy, tumor growth was suppressed for approximately two months with just a single dose, and in a gastric cancer model, the tumor remained smaller than before administration even at low doses.

Low Side Effects, Potential for “Combination Therapy”

LigaChem Biosciences is currently conducting a clinical trial of LCB02A in “patients with CLDN18.2-positive advanced solid tumors who are refractory to standard therapy or for whom no standard therapy is available.” The drug is being developed as a second-line or later treatment.

However, to target a larger market, LigaChem Biosciences is pursuing a strategy to expand the scope of development to include first-line therapy based on LCB02A’s safety and efficacy data. Since LCB02A has demonstrated tolerability in preclinical studies, the company plans to use this as a basis to evaluate its potential for combination therapy.

LigaChem Biosciences official stated, “We are also planning to develop LCB02A as a first-line treatment for gastric cancer. Once data from the ongoing clinical trials is secured, we plan to begin full-scale studies on its use in combination with immunotherapy or chemotherapy.”

Currently, Astellas’ “Vilo” is used as a first-line treatment for CLDN18.2-targeted gastric cancer. Vilo is an antibody therapy that binds to CLDN18.2 on the surface of cancer cells and attacks the target cells through immune responses and other mechanisms.

In contrast, LigaChem Biosciences’ LCB02A is an ADC that delivers a cytotoxic drug to the tumor via a linker attached to an antibody. Using LigaChem Biosciences’ “Conjuol” platform technology, the drug remains bound in the bloodstream but is released once it reaches the tumor, where an enzyme cleaves the linker. This ensures an adequate drug dose is delivered to the tumor while minimizing unnecessary drug exposure to healthy tissue.

In fact, the existing drug “Vilo” exhibits a high incidence of side effects when used in combination therapy. In Vilo’s Phase 3 clinical trial, the incidence of nausea and vomiting among patients receiving it in combination with chemotherapy was 82% and 67%, respectively—higher than the 61% and 36% rates observed in the control group. Grade 3 or higher nausea and vomiting occurred in 16% of patients, respectively.

A representative from LigaChem Biosciences stated, “LCB02A has been confirmed to deliver a greater payload to the tumor due to its high stability in the bloodstream. This means that not only does it demonstrate higher efficacy when administered at the same dose, but it also allows for a lower dose while achieving the same level of effectiveness as existing treatments,” the representative said. “While a direct comparison of efficacy and side effects with Bilroy under identical conditions is not available, so we cannot claim an exact comparison, we believe it will prove its utility in combination with existing treatments given its lower risk of side effects.”

LigaChem Biosciences expects that LCB02A, by targeting CLDN18.2 to deliver the payload, will enhance the therapeutic efficacy of immunotherapy or chemotherapy. The combination of LCB02A and immunotherapy is expected to produce a synergistic effect that enhances treatment efficacy by directly killing cancer cells while simultaneously activating the patient’s anti-cancer immune response. When LCB02A is used in combination with chemotherapy, the two therapies attack cancer cells through different mechanisms, thereby enhancing the antitumor effect; this approach also has the advantage of targeting even cancer cells with low or no CLDN18.2 expression.

First-Line Treatment Target Market More Than Doubles Compared to Second-Line Treatment

If LCB02A is reclassified from

a second-line

to a first-line treatment

,

the target market size is expected to more

than

double.

According to market analysis released by Astellas this year, the number of patients receiving first-line treatment for gastric and gastroesophageal junction cancer in the U.S., five major European countries, and Japan totals approximately 119,000—2.4 times the number of patients receiving second-line treatment (approximately 50,000). Astellas projected in August that Biloy’s maximum global annual sales could reach 1.7 trillion won.

If LCB02A demonstrates efficacy and tolerability through combination therapy, it will be able to continue competing in the 1.7 trillion won market that Vilo is currently expected to capture.

In particular, if efficacy is confirmed even in first-line treatment, the potential value assessed during technology export negotiations will increase, making it possible to secure a contract on more favorable terms.

An official from LigaChem Biosciences stated, “The most important indications in the LCB02A clinical trials are gastric cancer, gastroesophageal junction cancer, and pancreatic cancer. To demonstrate our differentiation from competing therapies, we plan to focus primarily on proving efficacy, as superior efficacy is paramount.”