The market for developing Antibody-Drug Conjugate (ADC) cancer therapies, dubbed missiles that strike cancer cells, has now entered a phase of "toxicity management competition." While stronger payloads (cytotoxic drugs that kill cancer cells) and new target discovery had been the pillars of competition, the core task lately is how widely to expand the therapeutic window between efficacy and toxicity.
LigaChem Biosciences is no exception. It faces a test this year to prove both efficacy and safety as it releases key clinical data from its pipelines one after another. ADCs work by having an antibody bind to a cancer cell and then release the payload inside the cell to kill it. If the payload is released early in the bloodstream or delivered to normal cells, it can lead to serious adverse events.
A domestic ADC researcher said, "Because of tumor heterogeneity, the bystander effect, which allows ADCs to attack surrounding cancer cells, is essential. But for this effect to work, the payload must freely pass through the cell membrane," and noted, "Good membrane permeability means it does not distinguish the cell membranes of normal tissues."
The researcher added, "Typically, less than 1% of the administered ADC reaches the tumor," and said, "The very structure in which the remaining 99% ends up where it is not intended is the fundamental reason toxicity is so hard to solve."
◇ LCB14 and 71 proved efficacy… next comes toxicity data
The market is watching for follow-up data on "LCB14" and "LCB71." LCB14 is a HER2-targeting ADC and is the most advanced in development among LigaChem Biosciences' pipelines.
In China, partner Fosun Pharma is conducting a phase 3 trial targeting second-line therapy for metastatic HER2-positive breast cancer. It is a head-to-head study directly comparing with Roche's "Kadcyla," and depending on results after completion this year, a new drug application in China could be possible next year.
Global rights are held by U.K. partner Exelixis. Exelixis recently became a subsidiary through an equity investment by LigaChem Biosciences and is conducting a phase 1b trial of LCB14 with the goal of entering the "post-Enhertu" space. It is targeting treatment demand among patients with increased resistance after Enhertu.
There is potential. In phase 1a results released at the European Society for Medical Oncology (ESMO 2025) last year, the objective response rate (ORR) was 64% in cohorts dosed at 90 mg/㎡ or higher. Partial responses (PR) were also confirmed in 3 out of 4 breast cancer patients with prior Enhertu exposure.
LCB71 is a ROR1-targeting ADC whose technology was transferred to China's CStone in 2020. A phase 1b trial is underway with diffuse large B-cell lymphoma (DLBCL) as the main indication. DLBCL is a representative hematologic cancer accounting for 30% to 40% of all non-Hodgkin lymphomas, and the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen has monopolized standard treatment for decades.
In the R-CHOP combination study released by CStone in Mar., the ORR was 100% and the complete response rate (CR) was 95.5%. Observers called the figures unusual for a blood cancer. However, there is also caution that the trial is a small, early-stage study and the results are from a combination with the standard regimen, making it hard to isolate the drug's standalone contribution.
◇ LigaChem tries to break through with its own platform
As clinical progress of candidates transferred to partners becomes visible, the possibility of third-party technology transfer (sub-licensing out) is also being raised. If a partner signs a license deal, LigaChem Biosciences would receive a share of the revenue.
The issue is toxicity. A paper by Professor Dario Trapani's team at the European Institute of Oncology in Milan, published last month in the international journal The Lancet Regional Health – Europe, noted, "While the design of next-generation anticancer therapies, including ADCs, is becoming more sophisticated, toxicity, resistance, and constraints in clinical application remain structural limitations."
In fact, Merck (MSD) and Daiichi Sankyo's "ifinatamab deruxtecan (I-DXd)" had development temporarily halted after grade 5 interstitial lung disease (ILD), meaning deaths, occurred in a phase 3 trial. BioNTech and Medilink's HER3-targeting ADC "BNT326" appeared safe in preclinical studies, but in the clinic, severe toxicity emerged at lower-than-expected doses, leading the FDA to impose a partial clinical hold.
Another domestic ADC researcher said, "Antigen expression, linker (the chemical bond that connects the antibody and payload) stability, payload metabolism, and tissue uptake differ between animals and humans, so preclinical safety may not be reproduced as is in the clinic."
LigaChem Biosciences' LCB14 and LCB71 use, respectively, MMAF (a microtubule inhibitor) with challenging ocular toxicity management and a PBD-class payload with a heavy systemic toxicity burden.
The company's strategy is to control toxicity through its proprietary platform technologies. For LCB14, it applied the "ConjuAll" technology, which enhances linker stability in the bloodstream, and for LCB71, it added a "prodrug" design so the payload is activated only in the intracellular environment of cancer cells.
The company said, "We are confident in our linker technology," and added, "LCB71 has a structure with added safeguards. In the first eight dose cohorts (7–125 μg/kg) of the phase 1a study, no dose-limiting toxicity (DLT) was observed, and the maximum tolerated dose (MTD) was not reached." It continued, "This year, we plan to release a range of toxicity data along with ORR, and internally we view those data as important."