ASLAN Expands Collaboration with Zenyaku to Investigate Eblasakimab’s MOA Compared to Other Biologics in AD

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ASLAN Pharmaceuticals recently announced that it will continue its research collaboration with its partner, Zenyaku Kogyo Co, to develop new research projects comparing the mechanism of action of eblasakimab to other biologics for atopic dermatitis, including dupilumab (Dupixent; Sanofi and Regeneron) and lebrikizumab (Ebglyss; Eli Lilly).¹

According to ASLAN, previous translational study data from immune cells and skin biopsies of patients with atopic dermatitis showed that blocking the interleukin (IL)-13 receptor (IL-13R) with eblasakimab was more effective at downregulating inflammatory markers than blocking the IL-4 receptor (IL-4R) as dupilumab does. This data suggests that eblasakimab could be more efficient in the blockade of type 2 receptor signaling than dupilumab. To further understand this possibility, ASLAN and Zenyaku will conduct studies to explore the biology of the IL-13 and IL-4 receptors, including the effects of eblasakimab, dupilumab, and lebrikizumab on each receptor subunit.

“Eblasakimab may indeed find its own unique niche of patients as we see further clinical development and a potential approval, but for now, the results from TREX-DX are especially interesting as we look to position therapies in relation to dupilumab, our first and most commonly used advanced therapy - which works well for many but not all patients. These data show that blocking IL-13R1 may be an effective and novel strategy to drive early and deep clearance in moderate-severe AD patients by targeting a key receptor complex in type 2 inflammation," said Raj Chovatiya, MD, PhD, clinical associate professor at the Rosalind Franklin University Medical School, founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois, and Dermatology Times' Fall Editor in Chief, in a previous interview.

ASLAN and Zenyaku hope that the research from their collaboration will provide additional insights into the differentiated receptor biology of targeting IL-13R compared to IL-4R. According to ASLAN, it’s also possible that their research will explain the long-lasting inhibition of disease severity biomarkers, such as TARC, observed after the end of the eblasakimab treatment period in earlier clinical studies.²

“Eblasakimab could be an important new treatment for the growing number of AD patients and we are pleased to expand our collaboration with ASLAN to learn more about the scientific principles underlying eblasakimab’s differentiation from other biologics by utilizing our cutting-edge research facilities. Based on the strong translational and clinical data that ASLAN has generated to date, we believe that eblasakimab has a unique mechanism of action that could provide patients with a safe, efficacious, and convenient new treatment option for AD,” said Kazuhiko Haruta, the head of the research and development center of Zenyaku Kogyo, in the news release.¹

“Based on our recent positive interim data from TREK-DX, we believe eblasakimab may have the potential to be effective in AD patients with inadequate response to dupilumab and this collaboration may help us to understand the biology underlying why some patients may respond better to eblasakimab than other biologics,” Carl Firth, PhD, chief executive officer of ASLAN Pharmaceuticals, concluded in the news release.¹

Last month, ASLAN also announced new positive interim results from its phase 2 study, TREK-DX, evaluating eblasakimab for the treatment of moderate to severe atopic dermatitis in adult patients previously treated with dupilumab. Overall, 60.0% of dupilumab-treated patients with atopic dermatitis treated with 400mg of eblasakimab weekly achieved a 90% reduction in their Eczema Area Severity Index (EASI) score after 16 weeks, and 66.7% of patients achieved a validated Investigator Global Assessment score of 0 (clear) or 1 (almost clear) after 16 weeks, compared to 14.3% of patients receiving placebo.³

The primary end point of the percent change in EASI score from baseline to week 16 was statistically significant compared to placebo. Out of 15 patients receiving eblasakimab, 11 patients achieved a reduction in EASI score of at least 75% from baseline (EASI-75) compared to 14.3% (1/7) of patients receiving placebo (p=0.0431).³

References

1. ASLAN Pharmaceuticals announces expansion of its collaboration with Zenyaku to investigate the biology underlying differential effects of eblasakimab compared to other biologics. News release. ASLAN Pharmaceuticals. May 2, 2024. Accessed May 2, 2024. https://ir.aslanpharma.com/news-releases/news-release-details/aslan-pharmaceuticals-announces-expansion-its-collaboration
2. Cevikbas F, Simpson E, Ward A, Thng S, Veverka K. Eblasakimab, a monoclonal antibody targeting IL‑13Rα1 reduces serum biomarkers associated with atopy and correlated with disease severity in patients with moderate‑to‑severe atopic dermatitis. Presented at: 25th World Congress of Dermatology; July 3-8, 2022; Singapore.
3. ASLAN Pharmaceuticals announces positive interim results from phase 2 study of eblasakimab in dupilumab-experienced atopic dermatitis patients. News release. ASLAN Pharmaceuticals. April 22, 2024. Accessed May 2, 2024. https://ir.aslanpharma.com/news-releases/news-release-details/aslan-pharmaceuticals-announces-positive-interim-results-phase-2