ASLAN, Kymera Target Atopic Dermatitis at Dermatology Meeting

Psoriasis Itch_Compressed

Anyone who has dealt with atopic dermatitis, eczema or other inflammatory skin conditions is familiar with what seems like a near-constant itch. That annoying and sometimes unbearable itch could become a thing of the past if ASLAN Pharmaceuticals has something to say about it.

Friday morning, the Singapore-based company unveiled a poster presentation at the Society for Investigative Dermatology meeting highlighting its experimental monoclonal antibody that targets the IL-13 receptor. ASLAN’s eblasakimab is a first-in-class monoclonal antibody under development as a potential therapy for indications driven by type 2 inflammation, including atopic dermatitis and its associated itch. The company believes that eblasakimab has the potential to meet some current unmet needs in atopic dermatitis.

In the poster presentation, ASLAN presented data showing that IL-13 and IL-4 act as neuronal enhancers that amplify the itch associated with type 2 inflammation. That amplification occurs through the IL-13Rα1 subunit of the Type-2 receptor, the company said. Eblasakimab, through its mechanism of action, can inhibit those effects, the company noted. Neuronal responses were captured by live-cell calcium imaging, ASLAN Pharmaceuticals said in its announcement.

ASLAN Chief Medical Officer Alexandre Khaukhov said the data in the poster presentation “paint an encouraging picture” of the role eblasakimab can play in treating patients with chronic itch associated with type 2 inflammation. He said the monoclonal antibody can play a significant role in pruritic neuronal responses through its unique mechanism of action that blocks both IL-4 and IL-13 through the Type 2 receptor.

Khaukhov, who was appointed CMO in March, noted that the chronic itch associated with type 2 inflammation can be debilitating to many patients. Blocking the itch at its source could improve the overall quality of life in these patients, he added.

Last fall, ASLAN announced positive topline data from its multiple-ascending-dose Phase Ib study of eblasakimab. Data from the study conclusively established proof of concept and supports the potential of eblasakimab as a differentiated, novel treatment for atopic dermatitis. Data showed that eblasakimab significantly reduced cytokine-enhanced neuronal responses to IL-4 and IL-13-driven itch by more than 40% compared to control conditions, the company noted at the time.

In January, ASLAN Pharmaceuticals screened its first patient in a Phase IIb dose-ranging study of eblasakimab in adult patients with moderate-to-severe atopic dermatitis. The study is expected to include about 300 patients and top-line data is expected in the first half of 2023.

Also presenting data at the conference was Kymera Therapeutics. The company showcased data that demonstrates its selective IRAK4 degrader KT-474 degrades IRAK4 and inhibits cytokine production in different immune and skin cell types. The company highlighted the broad impact of KT-474 across multiple disease-relevant cell types in the poster presentation.

Watertown, Mass.-based Kymera noted that the data seen so far in its clinical development of KT-474 supports the continued development of IRAK4 degraders in patients with atopic dermatitis and other diseases of the skin that are driven by IL-1R/TLR.

Anthony Slavin, vice president of immunology at Kymera, said KT-474 effectively degrades IRAK4 in both circulating immune cells and resident skin cells such as keratinocytes and fibroblasts.

“These findings are aligned with what we have observed in our Phase I clinical study of KT-474 in healthy volunteers, which showed near-complete IRAK4 degradation in peripheral blood mononuclear cells and skin following multiple daily doses and robust ex vivo inhibition of multiple disease-relevant cytokines,” Slavin said in a statement.

Kymera is collaborating with Sanofi on the development of degrader candidates targeting IRAK4, including KT-474, for indications outside of oncology and immuno-oncology.

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