Samsung Bioepis and Celltrion(068270), among Korea's bio corporations, are jumping into the race to develop nectin-4–targeted antibody-drug conjugates (ADC), cited as a next-generation anticancer platform. Their strategy is to improve on the limits of "Padcev" (ingredient name enfortumab vedotin) from U.S. Pfizer, which has seized the market, and aim for the "post-Padcev" spot.
According to the industry on the 24th, in Korea, Celltrion, Samsung Epis Holdings(0126Z0) subsidiary Samsung Bioepis, LigaChem Biosciences(141080), and IntoCell(287840) are accelerating the development of nectin-4 ADC candidate substances.
Nectin-4 is a protein that is rarely expressed in normal tissue but is overexpressed in certain solid tumors such as bladder cancer (urothelial carcinoma), breast cancer, and lung cancer. Because it can selectively attack cancer cells, it is drawing attention as a key target for ADC development.
Currently, the nectin-4 ADC market is led by "Padcev," co-developed by Japan's Astellas and U.S. Pfizer. The U.S. Food and Drug Administration (FDA) first approved Padcev in Dec. 2019 as a second-line therapy for patients with metastatic urothelial carcinoma, and in Korea, the Ministery of Food and Drug Safety granted marketing authorization in Mar. this year for treatment of locally advanced or metastatic urothelial carcinoma. This is Korea's first approval case of an ADC for urothelial carcinoma.
However, Padcev is assessed to have limits in increasing the dosing amount due to side effects such as skin toxicity, hyperglycemia, and peripheral neuropathy.
In response, latecomers are attempting to differentiate by lowering toxicity and improving tolerability while maintaining anticancer efficacy. U.S. Eli Lilly and Company has also joined the competition by conducting phase 1 trials on two nectin-4 ADC candidates.
The company progressing development the fastest in Korea is Celltrion. In July last year, Celltrion began global phase 1 trials in Korea, the United States, and elsewhere for its nectin-4 ADC candidate "CT-P71" in patients with solid tumors. CT-P71 is a substance co-developed with Korea's bio corporations Pinotbio.
In preclinical studies, it demonstrated superior anticancer efficacy and safety compared with existing therapies. In particular, the company said that in organoid (mini organ) and xenograft models, it showed stable anticancer effects even in cancers resistant to Padcev.
CT-P71 features a differentiated payload (drug) that causes damage during the DNA replication process of cancer cells. In April, it received priority review (fast track) designation from the U.S. Food and Drug Administration (FDA) for patients with locally advanced or metastatic urothelial carcinoma who had prior treatment experience, accelerating its development.
Celltrion plans to identify the appropriate dose in the phase 1a trial of CT-P71 this year and to select solid tumor indications with expected efficacy in the phase 1b trial next year. It will then continue development in phase 2 for major indications, including urothelial carcinoma.
Samsung Bioepis has also fully entered the ADC race. The day before, Samsung Bioepis signed a definitive agreement with its joint research partner IntoCell for the development and commercialization of the ADC candidate "SBE303."
SBE303 applies IntoCell's linker platform "OPAS" technology and a payload (drug) from China's Frontline. Samsung Bioepis and IntoCell signed a research agreement in Dec. 2023 to jointly discover up to five ADC candidates, and this agreement is a follow-up collaboration targeting the first candidate discovered at that time.
The company said it confirmed 13 times higher tolerability compared with the original therapy Padcev through preclinical results disclosed at the American Association for Cancer Research (AACR) last month. In the United States and Korea, dosing for phase 1 began this month, and the company plans to conduct the global phase 1 through July 2031.
LigaChem Biosciences is also cited as a major developer in the nectin-4 ADC field. LigaChem Biosciences is jointly developing two candidates in partnership with the antibody development corporations Nectin Therapeutics. The approach combines its own ADC platform "ConjuALL" with Nectin Therapeutics' antibody technology.
The two candidates were first unveiled at the European Society for Medical Oncology (ESMO) in Oct. last year. According to the company, preclinical results confirmed the potential for significant antitumor efficacy and safety improvement compared with Padcev. In particular, efficacy and safety were confirmed even at high doses, drawing attention to whether it can improve the skin toxicity and neurotoxicity issues cited as Padcev's limitations.
An industry official said, "The nectin-4 ADC market is already established by Padcev, but if a follow-up candidate emerges that proves improved side effects and differentiated efficacy, the market leadership could change."