LAWRENCEVILLE, N.J.–(BUSINESS WIRE)–Asana BioSciences, a clinical stage biopharmaceutical company, announced that it will present positive results from a Phase 2b study evaluating the efficacy and safety of its investigational oral Janus kinase family (JAK) and spleen tyrosine kinase (SYK) inhibitor gusacitinib (ASN002) in adult patients with moderate-to-severe chronic hand eczema (CHE) in a late-breaking news session at the EADV Virtual Congress to be held October 29th-31st, 2020.
According to the International Eczema Council, CHE is an often debilitating condition that affects approximately 10% of the U.S. population and millions of people worldwide. Patients with CHE suffer greatly from this disease, which limits their ability to work and perform activities of daily living. CHE often results from a combination of causes, including genetic and unknown factors (constitutional hand dermatitis), injury (irritant dermatitis) and immune reactions (atopic, allergic dermatitis). Currently there are no approved treatments for CHE in the U.S. and many other major markets.
Gusacitinib achieved rapid, dose-dependent, clinically meaningful, and statistically significant improvement relative to placebo in both the primary and key secondary endpoints of efficacy as early as 2 weeks and the effects were sustained for the duration of the study. Safety results show that both doses of gusacitinib were well-tolerated. The most common treatment-emergent adverse events observed were upper respiratory tract infection, headache, nausea, and nasopharyngitis. The study was a randomized, double-blind, placebo-controlled, parallel-group study evaluating oral gusacitinib (40 mg or 80 mg once daily) for up to 32 weeks, with the primary endpoint of mean modified total lesion severity score (mTLSS) at week 16 (NCT03728504). The physician global assessment (PGA) and pruritus were among the key secondary endpoints studied.
The details of the presentation (Abstract: D1T03.4C) are as follows:
Study Title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Gusacitinib (ASN002) in Subjects with Moderate-to-Severe Chronic Hand Eczema.
Presenter: Howard Sofen, M.D., United States
Session: Late Breaking News
Date/Time: 29th October 2020 /16:15 – 16:30 Central European Time (11:15 AM-11:30 AM US EDT)
In addition to CHE, gusacitinib was also effective in patients with chronic foot eczema and atopic dermatitis (as measured by vIGA in CHE patients who also had AD involvement) in this study. Gusacitinib also demonstrated significant improvement in overall work productivity impairment. These results will be presented at a future date.
About Gusacitinib (ASN002)
Gusacitinib (ASN002) is a potent inhibitor of the Janus kinase (JAK) family (JAK1, JAK2, JAK3 and TYK2) and spleen tyrosine kinase (SYK). Autoimmune, inflammatory and immunological-based diseases, including atopic dermatitis, have complex pathogeneses that involve interactions between multiple cytokines and immune cells. JAK kinases play a significant role in these inflammatory conditions. The JAK kinases family (JAK1, JAK2, JAK3 and TYK2) is involved in signaling pathways of the Th2, Th22, Th1 and Th17 cytokines involved in AD pathogenesis. Hence, JAK kinases play a significant role in inflammatory conditions, particularly those driven by cytokines. SYK is a vital mediator of immunoreceptor signaling in macrophages, neutrophils, mast cells, and B cells. SYK mediated signaling leads to increased release of inflammatory cytokines, lipid mediators, and various proteases. Activated B cells and macrophages also act as antigen presenting cells and potent activators of T cells in inflammatory conditions. SYK also plays a critical role in IL-17R signaling in keratinocytes and in keratinocyte proliferation and terminal differentiation.
In order to effectively treat these complex diseases, gusacitinib simultaneously targets multiple disease-relevant signaling pathways to allow for greater control over those pathways that drive disease pathogenesis. SYK-JAK inhibition with gusacitinib modulates Th2, Th22, Th1 and Th17 cytokines, thereby targeting both the immune cells and epithelial cells responsible for the disease pathogenesis of CHE. This multi-pathway approach holds promise for treating a wide range of dermatological diseases such as CHE, atopic dermatitis, alopecia, psoriasis, hidradenitis suppurative, and inflammatory conditions including systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis and asthma.
Gusacitinib, a potential best-in-class JAK/SYK inhibitor, has been studied in over 400 subjects to date including an earlier Phase 2b study (RADIANT) in 244 adult patients with moderate-to-severe atopic dermatitis and has shown good safety and tolerability. The RADIANT trial was a randomized, double-blind, placebo-controlled, parallel-group study evaluating three doses of gusacitinib (40, 60, and 80 mg once daily) over 12 weeks (NCT03654755). Gusacitinib showed a rapid and statistically significant reduction in pruritus as well as a statistically significant reduction in EASI score from baseline in moderate-to-severe AD patients.
About Asana BioSciences, LLC
Asana BioSciences is a clinical stage biopharmaceutical company based in Lawrenceville, NJ. Asana is focused on discovery and development of novel targeted investigational medicines in immunology/inflammation and oncology.
Asana’s second immunology/dermatology asset ASN008 is a novel, topical Na+-channel blocker with high functional selectivity for itch and pain sensing neurons without affecting motor nerves. In a Phase 1b study in atopic dermatitis patients, topical application of ASN008 showed rapid onset of pruritus relief after a single application, which lasted between 8-12 hours, and no tachyphylaxis to this response was observed after 2 weeks of daily application (NCT03798561). ASN008 also has potential for the treatment of pain, urologic and other chronic conditions.
Asana also has several oncology assets. Asana’s lead oncology asset, ASN007, is a potent inhibitor of the extracellular-signal-regulated kinases ERK1 and ERK2, which are key players in the RAS/RAF/MEK/ERK (MAPK) signaling pathway. ASN007 has completed Phase 1 dose-finding showing encouraging efficacy and is in clinical development in patients with advanced solid tumors, including RAF- and RAS-mutant cancers (NCT03415126).
ASN003 is a selective inhibitor of BRAF and PI3 kinases. Dual targeting of RAF and PI3K pathways has the potential to overcome and/or delay acquired resistance to selective RAF inhibitors. ASN003 is in Phase 1 development in patients with BRAFV600 mutated metastatic melanoma, metastatic colorectal and advanced non-small cell lung cancer (NCT02961283).
ASN004 is an antibody drug conjugate that targets the 5T4 oncofetal antigen, which is expressed in a wide range of malignant tumors but has very limited expression in normal tissues. ASN004 demonstrates robust and durable antitumor activity after single administration in multiple human tumor xenograft models. A First-in-Human Phase 1 trial is being planned.
Asana is also developing ASN009, a highly selective antagonist of the purinergic P2X3 ion channel that is activated by extracellular ATP and involved in various pain, urological and respiratory disease conditions. Preclinical proof-of-concept has been demonstrated with ASN009 in a cough model. ASN009 is currently in preclinical development.