[Edaily KIM SAE-MI Reporter NA EUN-KYUNG ] AprilBio Co.,Ltd.(397030)has decided to explore other indications for “APB-A1” (Lu AG22515), a technology it licensed to Lundbeck, after the compound failed to demonstrate the expected clinical efficacy in thyroid-associated ophthalmopathy (TED). The biotech industry views this as a negative sign, noting that while development of the candidate compound itself has not been halted, follow-up development for the originally planned indication has been scrapped.

On the 19th, an executive at a biotech venture who previously handled business development (BD) at a global pharmaceutical company told E-Daily in a phone interview, “The fact that development has not been completely halted is a separate issue from whether the program met internal expectations.” He added, “The decision not to proceed with follow-up development for the originally planned indication can be interpreted as meaning the drug failed to meet internal standards for that indication, at the very least, which is a fairly negative signal.”

In its first-half earnings report released that day, Lundbeck stated, “TED is a complex and heterogeneous autoimmune disease, and this biological activity did not translate into the expected clinical effect on disease outcomes.”

According to Lundbeck, the APB-A1 Phase 1b clinical trial for TED confirmed a reduction in thyroid-stimulating hormone (TSH) receptor autoantibodies. This confirmed “Proof of Mechanism” (PoM), demonstrating that the CD40-CD40L pathway is indeed active.

The issue, however, is that this biological activity did not sufficiently translate into actual clinical improvement for patients. An interim analysis presented last June at the Endocrine Society’s Annual Meeting (ENDO 2026) showed positive signs, including an average reduction of 2.06 mm in exophthalmos and a 45% decrease in TSH receptor autoantibodies among the six patients who completed the 24-week treatment.

However, as Lundbeck officially assessed in its first-half report that it had not achieved the expected clinical efficacy, it is interpreted that further development of TED has effectively lost momentum.

This marks a distinct shift from the development strategy Lundbeck had outlined through the first quarter of this year. In its first-quarter earnings report released last May, Lundbeck classified Lu AG22515 as a Phase 1b clinical pipeline candidate for “CD40L inhibitor/thyroid eye disease.” At the time, investor materials explicitly designated TED as the “first indication.”

Lundbeck had previously left open the possibility of expanding the indications for APB-A1. Noting that the CD40-CD40L pathway may be involved in various immune and neurological disorders, the company identified multiple sclerosis (MS), myasthenia gravis (MG), neuromyelitis optica (NMO), and Friedreich’s ataxia as potential areas for development.

However, the strategy at that time was to develop TED as the first indication and then expand into other diseases. This time, Lundbeck stated, “We are utilizing these results to determine the next development steps, including the exploration of other indications where CD40-CD40L biology is more directly involved,” shifting the focus toward exploring new indications rather than the follow-up development of TED. This amounts to a shift in development strategy rather than a simple expansion of indications.

Among the previously proposed candidates, myasthenia gravis and neuromyelitis optica spectrum disorders (NMOSD) could be considered candidates for validating the CD40-CD40L blockade mechanism, given that autoantibodies are directly involved in the onset of these diseases. However, since neither Lundbeck nor AprilBio Co.,Ltd. has disclosed new indications, it is difficult to specify particular diseases at this stage.

Lundbeck gave a positive assessment of the safety and tolerability of APB-A1. The company left open the possibility of developing the candidate compound itself, stating that the safety and tolerability profile confirmed to date supports the continued evaluation of Lu AG22515.

AprilBio Co.,Ltd. also maintains that this issue does not signify the discontinuation or return of APB-A1 and that it plans to continue development for other indications. AprilBio Co.,Ltd. explained, “As we understand it, since the TED trial did not confirm the distinct clinical efficacy we had expected, we are shifting follow-up development to a different indication,” adding, “Since we have confirmed the safety, tolerability, and potential mechanism of action of APB-A1 in autoimmune diseases, we do not plan to return the candidate or halt development; rather, we intend to continue development in another indication that is more suitable for the CD40L mechanism.”

AprilBio Co.,Ltd. explained that even if the indication is changed, there is no need to repeat the Phase 1 clinical trial. Since safety and tolerability were confirmed in the TED Phase 1b trial, the company can proceed directly to Phase 2 development for the new indication without conducting a separate Phase 1 trial. Accordingly, the company anticipates that any delays in the development schedule resulting from the indication change will be minimal.

Changes to the Development Timeline Are Inevitable; Clinical Development May Become More Challenging Due to the Indication Change

Nevertheless, changes to the existing development schedule are expected to be inevitable. Lundbeck had planned to begin the APB-A1 TED Phase 2 clinical trial within this year, but shifting focus to a new indication has necessitated additional procedures, such as selecting the indication, designing the clinical trial, and consulting with regulatory authorities. Since the new indication and the trial start date have not yet been disclosed, there is now significant uncertainty regarding whether the company will be able to enter Phase 2 within the year as originally planned.

Some observers have raised the possibility that the clinical development process could become more challenging due to the change in indication. A clinical development expert noted, “TED is a condition with objective, quantifiable endpoints, such as the degree of exophthalmos,” adding, “If the new indication requires the use of subjective endpoints or metrics that are difficult to validate, it may become harder to demonstrate efficacy in clinical trials—even if the drug is actually effective.”

Lundbeck will hold an investor conference call today at 8:00 p.m. KST (1:00 p.m. local time) to discuss its first-half 2026 financial results. Attention is focused on whether the company will provide further details regarding APB-A1’s future development strategy, new indications, and Phase 2 clinical trial schedule during the call.