Dual JAK/SYK inhibitor and anti-IL-33 blockade

First promising data for a dual JAK/SYK inhibitor

“This is the first clinical study with ASN002, a novel JAK/SYK inhibitor” said Dr Robert Bissonnette of Innovaderm Research at the presentation of this Phase 1b trial [3].

According to Dr Bissonnette, ASN002 is an interesting molecule and somewhat different from other JAK inhibitors, because it also affects spleen tyrosine kinase (SYK). This intracellular kinase inhibits IL-17 signalling/CC chemokine ligand 20 production in keratinocytes, increases terminal differentiation of keratinocytes, and inhibits B-cell signalling, which plays a role in skin immunity. AS002 thus diminishes production of Th2 and Th22 cytokines. The dysregulation of Th2 and Th22 cytokine pathways are a hallmark of the pathogenesis of AD.

Although safety was the primary target of this trial there were also several efficacy targets. The 36 study participants represented the typical AD population with moderate-to-severe disease. They were separated into three 12-patient groups. In each group, nine received the active drug every day in a dose of 20, 40 or 80 mg for 28 days, followed by a 14-day safety period. No concomitant administration of topical corticosteroids or other immunosuppressants was permitted during or prior to the study.

ASN002 was well-tolerated: the most common adverse event was headache, which occurred at equal rates among the groups. At Day 29, 100% of patients taking 40 mg ASN002 and 88% taking 80 mg had achieved an EASI50 response, and 63% and 50% an EASI75 response. Itch (assessed in a Numeric Rating Scale) was reduced by 19–51%.

There were no clinically significant changes in chemistry lab parameters. Skin biopsies and microbiome analysis will be also performed in this trial, but these data will be presented later this year. According to Dr Bissonnette, ASN002 shows “…clear efficacy in patients with moderate-to-severe atopic dermatitis, with rapid symptom improvement”.

In addition, a significant reduction in patient-reported itch was observed as early as Day 2 of treatment. The agent allows a convenient once-daily dosing.

After this encouraging data, a Phase 2b trial will be initiated this year.

Proof of concept trial regarding anti-IL-33 blockade

Prof. Graham Ogg of Oxford University presented a small trial with an anti-IL33 antibody that was effective in patients with AD [4]. All 12 patients who received one intravenous infusion of ANB020 achieved at least a 50% reduction in their EASI-Score by Day 29. The agent also displayed a rapid onset of action: most of the improvement occurred in the first two weeks. Pruritus was also reduced.

All effects were largely sustained for two months, then gradually began to fade. IL-33 is produced by keratinocytes and epithelial cells and is highly expressed in AD lesions.

As Dr Ogg pointed out, IL-33 is an alarm molecule predominately produced after damage to keratinocyte—for example, after an allergenic challenge to the skin. The antibody was well-tolerated with no drug-related safety signals.

3. Bissonnette, R. Abstract 6777, AAD Annual Meeting, February 16–20 2018.
4. Ogg, G. Abstract 6658, AAD Annual Meeting, February 16–20 2018.



Posted on 20 December 201825 March 2021