[Edaily Reporter KIM SAE-MI ] There is speculation that the new drug candidates for immune disorders licensed by AprilBio Co.,Ltd.(397030)will enter a new phase of clinical development next year. Although Denmark’s Lundbeck halted development of “APB-A1” for thyroid-associated ophthalmopathy (TED) this year, analysts suggest that development could continue if the indication is changed to another autoimmune disorder. “EVO301” (APB-R3), a treatment for atopic dermatitis licensed to U.S.-based Evomune, is targeting entry into Phase 2b clinical trials next year.

Hana Securities presented this analysis of AprilBio Co.,Ltd.’s new drug development outlook for next year in its report titled “Immune Diseases: It’s Not Over Until It’s Over,” published on the 3rd. Kim Sun-ah, an analyst at Hana Securities, noted that while AprilBio Co.,Ltd.’s two technology-exported pipelines achieved contrasting development results in the first half of this year, the company is expected to encounter new opportunities next year centered on follow-up indications and clinical expansion.

AprilBio Co.,Ltd. has signed two technology export agreements based on its “SAFA” platform, which extends the half-life of protein therapeutics in the body. In October 2021, it licensed the CD40L-targeted APB-A1 to Lundbeck for up to $448 million (approximately 532 billion won at the time), and and in June 2024, it licensed the IL-18-targeted APB-R3 to Evomune for up to $475 million (approximately 660 billion won at the time). The total value of the two agreements amounts to $923 million (approximately 1.2 trillion won based on the exchange rate at the time of the agreements).

APB-A1’s development strategy was revised after it failed to meet expectations in a clinical trial for thyroid-associated ophthalmopathy this year. Last August, Lundbeck confirmed biological activity—including a reduction in thyroid-stimulating hormone (TSH) receptor autoantibodies—in the Phase 1b clinical trial of APB-A1, but determined that it had not achieved sufficient clinical efficacy. Consequently, the company has halted development for the thyroid eye disease indication and is reviewing its potential for development in other autoimmune diseases.

Researcher Kim analyzed, “It is somewhat premature to immediately attribute the failure in the TED clinical trial to an issue with the candidate compound’s efficacy,” adding, “It seems that therapeutic effects can only be expected if the pathological mechanism of TED can be directly targeted.” He explained that a strategy to directly block the signals that trigger the disease may be more effective for treating thyroid-associated ophthalmopathy than an indirect approach that reduces autoantibodies.

Researcher Kim noted that since the safety and tolerability of APB-A1 have been confirmed, it is likely that the drug will proceed directly to Phase 2 trials for new indications without repeating Phase 1. He particularly highlighted the fact that Amgen secured positive results in a Phase 3 clinical trial for a CD40L-targeted therapy for Sjögren’s syndrome last September.

“Sanofi, UCB, and Amgen remain committed to Phase 3 development, and Amgen announced the success of its Phase 3 trial for Sjögren’s syndrome this past September,” he said. “The CD40/CD40L target itself is considered to have been clinically validated for autoimmune diseases.”

Lundbeck has not yet disclosed follow-up indications or the clinical timeline for APB-A1. Therefore, the company’s third-quarter earnings announcement scheduled for the 11th is expected to provide insight into its future development direction. Analyst Kim emphasized, “We need to consistently monitor Lundbeck’s quarterly earnings announcements and investor relations events to determine which indications they will pursue for APB-A1.”

EVO301, another technology export pipeline, is undergoing further development with a focus on atopic dermatitis. EVO301 is a therapeutic agent that inhibits IL-18, which amplifies inflammatory responses; Evomune has completed a Phase 2a clinical trial in patients with moderate-to-severe atopic dermatitis.

In the Phase 2a trial, EVO301 was administered twice at four-week intervals, resulting in a 33 percentage point (p) improvement in the Eczema Severity Assessment Index (EASI) at the 12-week mark compared to the placebo. This is comparable to the 35–36 percentage point placebo-adjusted EASI improvement rate recorded by Sanofi’s blockbuster atopic dermatitis treatment, “Dupixent,” in clinical trials. One key difference is that EVO301 was evaluated at week 12 following two doses, whereas Dupixent was administered at two-week intervals over a 16-week period.

Researcher Kim analyzed that further improvements in efficacy could be expected if the dosing frequency and dosage of EVO301 are optimized. Evomune aims to begin a Phase 2b clinical trial for atopic dermatitis with EVO301 by the middle of next year. The company also plans to develop a subcutaneous (SC) formulation to enhance dosing convenience and to proceed with a Phase 2 clinical trial for ulcerative colitis.

It is also worth noting that after EvoMune failed to meet the primary endpoint in the Phase 2b clinical trial of its existing atopic dermatitis candidate “EVO756,” the company decided to halt development for that indication and focus on EVO301. This means that EVO301 has taken on a greater role in EvoMune’s atopic dermatitis treatment development strategy.

Hana Securities assessed that EVO301 has the potential to differentiate itself because it acts through a mechanism different from existing IL-4 and IL-13-targeted therapies. Analyst Kim noted that since various inflammatory factors, in addition to IL-13, are involved in atopic dermatitis, EVO301—which blocks the upstream signal IL-18—could serve as a meaningful treatment alternative for patients who do not respond adequately to existing antibody therapies.

He also highlighted the new drug development experience of Evomune’s management team. Evomune CEO Luis Peña is a former co-founder and Chief Development Officer (CDO) of Dumira, the company that developed the atopic dermatitis treatment “Epglis.” Dumira was acquired by Eli Lilly in 2020 for $1.1 billion (approximately 1.275 trillion won), and Epglis received approval from the U.S. Food and Drug Administration (FDA) in 2024.

Researcher Kim believes that, depending on the future clinical results of EVO301, there is potential for additional technology transfers or mergers and acquisitions (M&A). He predicted, “Since EVO301 is likely being developed with sublicensing or a company sale in mind, we can expect a major development based on its clinical results.”