- Late-breaking abstract on the differences between IL-13Rα1 and IL4R blockade on Type 2 and Type 1 signaling in atopic dermatitis (AD) accepted for oral presentation and late-breaking abstract on role of farudodstat in human model of alopecia areata accepted for poster presentation
- Abstracts of the two additional poster presentations at ISID have been published online in the Journal of Investigative Dermatology
- Subgroup analysis from the previously published proof-of-concept study of eblasakimab in moderate-to-severe AD reveals that patients who received eblasakimab achieved higher improvements in EASI scores across different body regions, including the head and neck, compared to placebo
- Eblasakimab significantly inhibited cytokine-enhanced neuronal sensitization to itch and reduced spontaneous neuronal activity, suggesting a potential to treat conditions characterized by chronic itch and showing promise for broader application to neuropathic symptoms beyond itch
San Mateo, California, and Singapore, April 24, 2023 – ASLAN Pharmaceuticals (NASDAQ: ASLN), a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients, today announced the acceptance of two late-breaker abstracts – one on eblasakimab and one on farudodstat – for presentation at the 1st International Societies for Investigative Dermatology (ISID) Meeting, which will take place from May 10 to 13, 2023, in Tokyo, Japan. Two further abstracts on eblasakimab, which were earlier accepted for presentation at the ISID meeting, have been published online in the Journal of Investigative Dermatology.
“We are excited to be sharing three abstracts on eblasakimab at ISID, including a late-breaking podium presentation, as well as showcasing our new findings on farudodstat in an alopecia areata human ex vivo model,” said Dr Alex Kaoukhov, Chief Medical Officer at ASLAN Pharmaceuticals. “The abstracts published today highlight the potential of eblasakimab to offer important differentiated benefits for AD patients. Chronic itch is one of the most burdensome symptoms for AD patients and our translational data provide a strong mechanistic rationale for blocking IL-13Ra1 to combat cytokine-driven amplification of itch and spontaneous activation of neurons, potentially resulting in rapid itch relief for patients receiving eblasakimab treatment. Furthermore, a sub-analysis from our Phase 1 study indicated substantial improvements in EASI scores of eblasakimab-treated AD patients across all body areas, including sensitive, difficult-to-treat anatomical areas such as the head and neck, compared to placebo. These results suggest that in addition to addressing itch, eblasakimab may have the potential to treat sensitive areas of the skin where steroid-containing topical treatments are often restricted. Both of these attributes could provide substantial psychological relief to patients with AD. We look forward to learning more about the clinical benefits of eblasakimab on EASI and itch in patients from the topline data of our Phase 2 TREK-AD study in early July.”
Late-breaker oral presentation: Downstream effects of IL-13Rα1 blockade on Type 2 inflammation and Th1 immune axis activation in atopic dermatitis
(abstract ID: LB1751)
Pharmacology and Drug Development Mini-Symposium, May 13, 13:15-15:45 JST, Room CM18-04
Late-breaker poster presentation: A novel ex vivo model of human hair follicle immune privilege collapse reveals the potential of farudodstat, a DHODH inhibitor, as a therapeutic for alopecia areata treatment
(abstract ID: LB1777)
Additional details from the late-breaker abstracts will be shared after presentation at the conference and all posters presented at ISID will be made available within the “Publications” section of ASLAN’s website.
2023 ISID published abstracts
Eblasakimab monotherapy improves moderate-to-severe atopic dermatitis symptoms across anatomical regions in a Phase 1 study
(abstract ID: 657)
The clinical presentation of AD varies by anatomical location due to differences in skin area sensitivity and can limit an individual’s long-term treatment options. Current research shows that interleukin-4 (IL-4) and IL-13 signal through a Type 2 receptor complex composed of IL-4Rα1 and IL-13Rα1 to mediate the pathogenesis of AD. Eblasakimab obstructs this signaling cascade by binding to the IL-13Rα1 subunit. The Phase 1b subgroup analysis explored the effects of eblasakimab on Eczema Area and Severity Index (EASI) across different anatomical regions compared to placebo.
Patients treated with 400mg or 600mg subcutaneous eblasakimab once weekly showed notable improvement in percent change from baseline in EASI across all four anatomic regions (head/neck, trunk, upper extremities, lower extremities) compared to placebo. The published abstract is available to view here.
Neuromodulation beyond itch is blocked by targeting IL-13Rα1 with eblasakimab
(abstract ID: 1594)
IL-4 and IL-13, two cytokines that play a pivotal role in the pathogenesis of AD, are associated with high-burden symptoms such as chronic itch. IL-13 signals via the IL-13Rα1 subunit to enhance histaminergic and nonhistaminergic itch. Eblasakimab binds to the IL-13Rα1 subunit to block IL-4 and IL-13 signalling pathways. This study evaluated 1) whether IL-4 and IL-13 exert redundant or distinct functions in human sensory neurons, and whether eblasakimab can 2) attenuate cytokine-enhanced neuronal responses to itch and 3) reduce spontaneous neuronal activity.
Human dorsal root ganglia neurons were treated with IL-4, IL-13, or their combination with or without eblasakimab and subsequently either challenged with pruritogens (BAM8-22 and PAMP-20) or tested for spontaneous neuronal activity. Neuronal responses to pruritogens and spontaneous neuronal activity were measured via live-cell calcium imaging.
When applied to human dorsal root ganglion, IL-4, IL-13, and their combination treatments enhanced neuronal responses to the non-histaminergic pruritogen (BAM-822) and IL-13 treatment increased neuronal responses to the histaminergic pruritogen (PAMP-20) through amplifications of the activity of MRGPRX2, suggesting a novel neuroimmune pathway besides its mast cell specific function. Eblasakimab significantly hampered cytokine-enhanced itch responses to both pruritogens. Compared to vehicle, IL-4 treatment significantly increased spontaneous neuronal activity; this effect was notably reduced by eblasakimab. Spontaneous neuronal activity was not impacted by IL-13 treatment but was increased with IL-4 treatment, which was also effectively reduced by eblasakimab. These results reveal that IL-4 and IL-13 exert nonredundant neuronal function and demonstrate the ability of eblasakimab to block these effects. This indicates that direct impact on neuronal responses may contribute to reduction of chronic itch demonstrated in AD patients treated with eblasakimab. The published abstract is available to view here.
Eblasakimab is a potential first-in-class monoclonal antibody targeting the IL‑13 receptor subunit of the Type 2 receptor, a key pathway driving several allergic inflammatory diseases. Eblasakimab’s unique mechanism of action enables specific blockade of the Type 2 receptor and has the potential to improve upon current biologics used to treat allergic disease. By blocking the Type 2 receptor, eblasakimab prevents signaling through both interleukin 4 (IL‑4) and interleukin 13 (IL‑13) – the key drivers of inflammation in atopic dermatitis (AD). Positive results from a Phase 1b multiple-ascending-dose study established proof-of-concept for eblasakimab and supported its potential as a novel, differentiated treatment for AD. ASLAN is currently conducting TREK‑AD, a Phase 2b trial to evaluate eblasakimab in biologic naïve moderate-to-severe AD patients, with topline readout expected in early July 2023. ASLAN is also investigating eblasakimab in dupilumab experienced, moderate-to-severe AD patients in the Phase 2 trial TREK‑DX, with data expected in the first quarter of 2024.
Farudodstat is a potent, oral DHODH inhibitor that suppresses immune cell proliferation and IFN-γ secretion by blocking de novo production of pyrimidines required for DNA replication. Compared to first-generation DHODH inhibitors, farudodstat has been shown to be approximately 30 times more potent in its inhibition of DHODH and limiting T cell activity and has demonstrated a well-tolerated safety profile. ASLAN has generated data showing that farudodstat can protect against the loss of immune privilege in hair follicles, supporting its potential as a first-in-class treatment option for alopecia areata (AA).
About ASLAN Pharmaceuticals
ASLAN Pharmaceuticals (Nasdaq: ASLN) is a clinical-stage, immunology-focused biopharmaceutical company developing innovative treatments to transform the lives of patients. ASLAN is developing eblasakimab, a potential first-in-class antibody targeting the IL-13 receptor in moderate-to-severe atopic dermatitis (AD) with the potential to improve upon current biologics used to treat allergic disease. Eblasakimab is being investigated in a global Phase 2b trial of moderate-to-severe AD patients with topline readout expected in early July 2023. ASLAN is also developing farudodstat, a potent oral inhibitor of the enzyme DHODH, as a potential first-in-class treatment for alopecia areata (AA) and plans to initiate a proof-of-concept trial in 2Q 2023. ASLAN has teams in San Mateo, California, and in Singapore. For additional information please visit the website or follow ASLAN on LinkedIn.
Forward looking statements
This release contains forward-looking statements. These statements are based on the current beliefs and expectations of the management of ASLAN Pharmaceuticals Limited and/or its affiliates (the “Company”). These forward-looking statements may include, but are not limited to statements regarding the Company’s business strategy and clinical development plans; the Company’s plans to develop and commercialize eblasakimab and farudodstat; the safety and efficacy of eblasakimab and farudodstat; the Company’s plans and expected timing with respect to clinical trials, clinical trial enrolment and clinical trial results for eblasakimab and farudodstat; the potential of eblasakimab as a first-in-class treatment for atopic dermatitis and of farudodstat as a first-in-class treatment for alopecia areata; and the Company’s cash runway. The Company’s estimates, projections and other forward-looking statements are based on management’s current assumptions and expectations of future events and trends, which affect or may affect the Company’s business, strategy, operations, or financial performance, and inherently involve significant known and unknown risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of many risks and uncertainties, which include, unexpected safety or efficacy data observed during preclinical or clinical studies; clinical site activation rates or clinical trial enrolment rates that are lower than expected; the impact of the COVID-19 pandemic or the ongoing conflict between Ukraine and Russia and bank failures on the Company’s business and the global economy; general market conditions; changes in the competitive landscape; and the Company’s ability to obtain sufficient financing to fund its strategic and clinical development plans. Other factors that may cause actual results to differ from those expressed or implied in such forward-looking statements are described in the Company’s US Securities and Exchange Commission filings and reports (Commission File No. 001- 38475), including the Company’s Annual Report on Form 20-F filed with the US Securities and Exchange Commission on March 24, 2023. All statements other than statements of historical fact are forward-looking statements. The words “believe,” “may,” “might,” “could,” “will,” “aim,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “plan,” or the negative of those terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify estimates, projections, and other forward-looking statements. Estimates, projections, and other forward-looking statements speak only as of the date they were made, and, except to the extent required by law, the Company undertakes no obligation to update or review any estimate, projection, or forward-looking statement.
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