[Edaily Reporter KIM SUNG-JIN ] Yuhan(000100)Overseas clinical trials for “YH32367” (nesprotamig), a bispecific antibody anticancer drug being developed by the company as a “post-Lecraza” (generic name: lazertinib) candidate, are being withdrawn one after another. Although the trial began as a global study recruiting patients in South Korea, the U.S., and Australia, the number of institutions currently recruiting clinical trial participants overseas has been reduced to one each in the U.S. and Australia. The trial, which was initially designed with global development in mind, appears to be effectively shifting its focus to South Korea.

Since Nesprotamig is being developed with the global market in mind, overseas clinical results and data are considered crucial. However, Yuhan maintains that, as the trials are still in the early stages, it is too early to discuss a strategy for approval by the U.S. Food and Drug Administration (FDA).

Overseas Clinical Sites Drop from 6 to 2… Even U.S. Dana-Farber Withdraws

According to the U.S. clinical trial registry ClinicalTrials.gov on the 30th, the clinical status of the U.S.-based Dana-Farber Cancer Institute—one of the overseas institutions conducting the Phase 1/2 trial for YH32367—has changed from “Recruiting” to “Withdrawn.” The Dana-Farber Cancer Institute is a comprehensive cancer treatment and research center located in Boston, Massachusetts, and is a major educational affiliate of Harvard Medical School.

According to past clinical records, the Dana-Farber Cancer Institute joined the Nesprotamig clinical trial network in September of last year. However, it has ended its participation in the trial without enrolling any patients over the course of approximately one year.

The reason cited for the Dana-Farber Cancer Institute’s withdrawal from the trial was the departure of the clinical trial coordinator. A Yuhan Corporation official explained, “The trial was withdrawn because the professor in charge of the trial moved to another institution.”

The problem is that this is not the first time an overseas clinical trial has been withdrawn. Yuhan Corporation has been conducting clinical trials at a total of 19 sites—13 in Korea and 6 overseas—and it has been revealed that, overseas in particular, trials at as many as four sites have been withdrawn or terminated early.

Previously, the Breast Cancer Research Center (Perth) in Australia, which had been conducting a clinical trial, withdrew the trial in January 2024, and Austin Health in Melbourne had its trial withdrawal registered on ClinicalTrials.gov last July. Another Australian clinical trial site, the Southern Oncology Clinical Research Center (Adelaide), announced in June of this year that the trial had been “terminated.”

As a result, the number of overseas clinical trial sites for Yuhan Corporation’s Nesprotamig has been reduced from the original six (two in the U.S. and four in Australia) to two: the Vanderbilt-Ingram Cancer Center in the U.S. and Blacktown Hospital in Australia.

Yuhan Corporation plans to proceed with overseas clinical trials at the two remaining sites for the time being. A Yuhan Corporation official stated, “Overseas clinical trials will proceed with the number of sites reduced to two,” adding, “We are in ongoing discussions with the research team regarding securing additional clinical trial sites.”

All 13 domestic institutions—including Seoul National University Hospital, Samsung Seoul Hospital, Asan Medical Center, and Severance Hospital—are currently recruiting participants. Including the two overseas sites (one each in the U.S. and Australia), 13 out of the total 15 clinical trial sites are now concentrated in South Korea.

Reduction in

Overseas Clinical Trials… Are There Any Issues with the Approval Strategy

? Nesprotamig is a bispecific antibody anticancer drug candidate that Yuhan Corporation licensed from ABL Bio Inc. in 2018. At the time, Yuhan Corporation acquired Nesprotamig alongside YH32364, an immuno-oncology candidate that simultaneously targets the epidermal growth factor receptor (EGFR) and 4-1BB. Nesprotamig is one of Yuhan’s core pipeline assets, considered a potential “second Lecraza” candidate alongside the new allergy drug Resigercept.

Yuhan Corporation initially planned to conduct clinical trials in South Korea and Australia before expanding to the United States. In fact, the early-phase trials were initially centered on South Korea and Australia before expanding to the United States. However, following the successive withdrawal of Australian clinical trial sites and, most recently, the withdrawal of Dana-Farber—a leading U.S. cancer research institution—the company’s overseas clinical trial infrastructure has been significantly reduced.

The clinical trial completion schedule has also been delayed beyond initial expectations. According to current registration information, the projected completion date is April 30, 2028—a delay of approximately one year and four months compared to the original target date of December 2026.

Consequently, the key question now is whether the reduction in overseas clinical sites will affect future technology transfer or new drug approval strategies. In particular, if U.S. approval is the goal, the decrease in U.S. patient data could pose a challenge. While the FDA accepts overseas clinical data, it carefully examines whether the results are applicable to U.S. patients and the U.S. healthcare environment.

It could also affect patient recruitment and data collection. This is because the greater the number of clinical sites, the easier it is to recruit patients from diverse ethnic backgrounds and healthcare settings, and the faster patient recruitment can proceed. It is understood that Yuhan initially planned to conduct the trial at six overseas sites precisely to quickly secure diverse data.

An industry insider noted, “It is not uncommon for overseas clinical trials to be suspended or for plans to change during the process,” but added, “However, since the number of sites has been significantly reduced from six to two, the key question is whether the desired data can be obtained.”

The changing competitive landscape is another variable. Competitive drugs have already emerged in the market for HER2-positive bile duct cancer treatments. A prime example is zaniditamab (brand name Zheera), developed by the Canadian pharmaceutical company Zymeworks and approved by the FDA in partnership with the U.S.-based Jazz Pharmaceuticals. Zaniditamab received accelerated approval from the FDA in November 2024 for the treatment of HER2-positive bile duct cancer.

Of course, some argue that it is difficult to conclude that new drug development will inevitably be disrupted simply because the number of overseas clinical trial sites has decreased. Lecraza, which Yuhan Corporation developed into a global new drug, was also licensed to Janssen in 2018 based on data from Phase 1/2 clinical trials conducted in South Korea.

A Yuhan official commented on this, stating, “It is still early in the clinical trial process, so it is too soon to discuss approval strategies.”