Saturated Nectin-4 Market: Samsung Bioepis Bets on "Safety"

Zeroing In on Padcev’s Side Effect Limitations
Thirteenfold Dosage Tolerated in Monkey Trials

Amid the saturation of the antibody-drug conjugate (ADC) market, Samsung Bioepis is accelerating its preparations to launch its first ADC new drug, drawing considerable attention. Samsung Bioepis, which recently signed an exclusive contract with INTOCELL and officially entered the competition, has emphasized safety as its key differentiator.

As of July, according to ClinicalTrials.gov, Samsung Bioepis added an Australian institution to its Phase 1 clinical trial sites for SBE303. When initially registered in April, there was only one site in Virginia, USA, but within four months, the number of sites increased to six: two in the United States, two in Australia, and two in Spain. This demonstrates the company's vigorous recruitment efforts for its first in-house new drug candidate.

SBE303 is an ADC candidate targeting a protein called nectin-4, which plays a role in the connection between cells. The protein is found in urothelial carcinoma, as well as certain breast and lung cancers, and appears more frequently in cancer cells than in normal cells, making it an attractive ADC target.

The challenge is the competition, as numerous companies are already pursuing this target. Padcev, developed by Astellas and Pfizer, became the first-line treatment for urothelial carcinoma by the end of 2023, applied in combination with the immuno-oncology drug Keytruda (pembrolizumab). Clinical trials have shown that this regimen nearly doubled patient survival compared to conventional chemotherapy.

As uncertainty over the target faded, more drug developers flocked to the field. Celltrion received fast-track designation from the U.S. Food and Drug Administration (FDA) for CT-P71 in April, and Eli Lilly is also developing related candidates. According to academic reports, there are more than ten ADC candidates targeting nectin-4. Samsung Bioepis, which began dosing its first patient in Phase 1 trials only in March of this year, is a latecomer.

Samsung Bioepis is tackling the dilemma posed by adverse effects that have not been resolved by Padcev. Padcev is associated with significant skin-related side effects, leading to the strictest warning label in the United States. Numbness in hands and feet, elevated blood sugar, and ocular disorders are also common.

Dosage is another limiting factor. While higher doses of anti-cancer treatments tend to be more effective, they also amplify side effects. Ultimately, the dosage is determined not by efficacy but by tolerability of adverse effects. This is why late entrants are focusing on safety rather than potency.

SBE303 has already demonstrated encouraging safety results in animal studies. According to the company, in monkey studies, it could be administered at up to 40mg per kilogram of body weight without severe side effects. This is about 13 times higher than Padcev's 3mg/kg. Celltrion's CT-P71, targeting the same protein, is reportedly tolerable at 30mg/kg, while Eli Lilly's LY4101174 is around 20mg/kg. There were also no signs of interstitial lung disease or other respiratory adverse events, such as fluid buildup in the lungs.

INTOCELL's linker technology has lent significant support to this effort. ADCs are anticancer agents in which cytotoxic drugs are attached to antibodies that home in on cancer cells, and the linker is the component bridging them. If the linker breaks down prematurely in the bloodstream, the payload can damage healthy cells. Therefore, enhancing linker stability is essential to reducing adverse effects. Samsung Bioepis combined its proprietary antibody with INTOCELL's linker to create SBE303, and secured commercialization rights for the compound through a definitive agreement signed on July 22. This contract is the first outcome of a collaborative research initiative launched in December 2023, which aims to discover up to five candidate substances.

The company's choice of cancer indications is also attracting attention. According to the disease category listed for the Phase 1 clinical trial on ClinicalTrials.gov, only "advanced solid tumors" is stipulated. This means any patient with advanced solid cancers unresponsive to standard treatment, regardless of cancer type, may be eligible to participate. A Samsung Bioepis official commented, "At present, we are keeping multiple possibilities open as we proceed with clinical development."

This content was produced with the assistance of AI translation services.