Technoderma Announces FDA Clearance of IND for TDM-180935, a Novel Topical JAK1/Tyk2 Inhibitor for Atopic Dermatitis
Another Chronic, Relapsing Skin Disease Poised for Effective Clinical Management.
On August 9, 2022 (Pacific Time), Jiaxing Technoderma Biotechnology Co., Ltd. (“Technoderma”), a company dedicated to the research and development of novel dermatological therapeutics, officially announced that its investigational candidate TDM-180935 for the treatment of atopic dermatitis (AD) had received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA), along with the official approval letter.
It is understood that TDM-180935, which has recently received approval for clinical trials, is the first small-molecule topical agent from Technoderma’s JAK inhibitor research platform to enter clinical development among several preclinical candidate compounds. It is a dual JAK1/Tyk2 inhibitor.
Preclinical data indicate that TDM-180935 not only inhibits the characteristic Th2 immune response responsible for the pathogenesis of atopic dermatitis, but also suppresses the Th1 and Th17 immune responses involved in the chronic phase of the disease, thereby effectively blocking multiple pathogenic pathways. Topical administration of TDM-180935 demonstrated robust dose-dependent efficacy across three animal models of atopic dermatitis.
Official Approval Letter for the Phase I Clinical Trial Application (IND) of TDM-180935 (STUDY MAY PROCEED letter)
“Intense pruritus, cutaneous inflammation, and impaired skin barrier function”: Atopic dermatitis often causes significant inconvenience to patients’ lives and health.
Data indicate that in China, the prevalence of atopic dermatitis is 4.6% among adults, 12.9% among children aged 1–7 years, and as high as 30.48% among infants aged 1–12 months, with this figure continuing to rise year by year. The growth and development, cognitive function, and attention span of infant and pediatric patients may all be affected. Adult patients not only suffer from debilitating pruritus but may also experience sleep deprivation, dietary restrictions, anxiety, and depression, which severely impair their quality of life and work performance and exert negative effects on their mental and psychological well-being.
More critically, this “bothersome” skin disease remains incurable. Current standard clinical treatments involve skin moisturization and topical glucocorticoids to alleviate symptoms. Additionally, topical calcineurin inhibitors may be used on areas such as the face, neck, vulva, and groin, where long-term use of corticosteroids is not recommended.
“Currently available clinical treatments offer only modest efficacy, and long-term topical use of corticosteroids can lead to skin atrophy, hyperpigmentation or hypopigmentation, infection, and tachyphylaxis.” According to Technoderma Medicines, Inc., there has been an unmet medical need for safe and highly effective topical agents that can replace corticosteroids in the treatment of chronic inflammatory skin diseases such as atopic dermatitis. Over the past two decades, advances in basic research have deepened our understanding of the role of Janus kinases (JAKs) in mediating cytokine-driven immune responses, providing new directions for the development of innovative therapies for atopic dermatitis.
TDM-180935, which has recently received approval for Phase I clinical trials, is the first small-molecule topical agent from Technoderma’s JAK inhibitor development platform to enter clinical testing among several preclinical candidate compounds. It is a dual JAK1/Tyk2 inhibitor.
According to the introduction, TDM-180935 not only inhibits the characteristic Th2 immune response during the acute phase of atopic dermatitis but also suppresses the Th1 and Th17 immune responses involved in pathogenesis during the chronic phase, thereby effectively blocking multiple pathways underlying the development of atopic dermatitis.
Preclinical trial data demonstrate that topical TDM-180935 exhibits excellent dose-dependent efficacy in three animal models of atopic dermatitis, with therapeutic effects comparable to those of topical corticosteroids.
Furthermore, in terms of safety, the physicochemical properties and preclinical metabolic studies of the drug indicate that TDM-180935 exhibits poor systemic absorption following topical administration and has a short plasma clearance half-life. These characteristics are highly advantageous in avoiding unnecessary systemic effects. Preclinical toxicology studies have also confirmed that TDM-180935 demonstrates a favorable safety profile when applied topically to the skin of various experimental animal species.
As planned, following the approval of this clinical trial application, TDM-180935 will initiate Phase I clinical trials in healthy male volunteers in two stages. The first stage involves single ascending dose dermal administration, while the second stage entails 28-day multiple ascending dose dermal administration. The relevant clinical study is designed as a randomized, double-blind, vehicle-controlled, parallel-group, multiple ascending dose trial, aiming to evaluate the safety, tolerability, and pharmacokinetics of TDM-180935 in healthy male subjects. Additionally, Technoderma Medicines, Inc. has disclosed that several U.S. clinical centers are expected to participate in the study.
The U.S. FDA has also paid close attention to TDM-180935, a highly innovative product.
It is reported that Technoderma officially submitted the Investigational New Drug (IND) application for the Phase I clinical trial of TDM-180935 on June 30 this year, and received approval from the U.S. FDA on August 1. The entire process took only 30 days from submission to approval, fully demonstrating the R&D strength of Technoderma’s scientific team.
It is worth noting that this is not the first time Technoderma’s pipeline has received U.S. FDA approval for clinical trials.
Previously, in April 2021, the FDA approved Technoderma’s Investigational New Drug (IND) application for TDM-105795 tincture, a topical treatment for androgenetic alopecia (AGA). This product is a globally protected, internationally leading small-molecule drug for the treatment of androgenetic alopecia, holding promise to provide new therapeutic options and benefit patients with this condition.
According to the latest updates, the Phase I clinical trial of TDM-105795 is nearing completion and will soon advance to the Phase II clinical trial stage.
In February this year, Dr. Wang Zengquan, Founder and CEO of Technoderma Medicines, Inc., stated that TDM-105795, a treatment for androgenetic alopecia, was the company’s first blockbuster clinical candidate in its dermatology pipeline, and that the company was striving to advance its second pipeline product, aimed at treating atopic dermatitis, into clinical studies by mid-year. The recent approval of the investigational new drug application for TDM-180935 undoubtedly fulfills Technoderma’s commitment.
Public information indicates that Technoderma, a small-molecule drug R&D-focused innovative enterprise specializing in dermatology, has successively launched two innovative drugs for skin diseases, both of which have received FDA approval for clinical trials. The company is committed to becoming a world-leading R&D and innovation platform for dermatological therapeutics, developing and launching First-in-Class global novel drugs targeting major skin-related diseases.
Leveraging its strong founding team, Technoderma has built a pipeline of first-in-class or best-in-class candidates in the field of dermatology.
In addition to the two innovative products already approved for clinical trials, Technoderma plans to submit investigational new drug (IND) applications in the second half of 2023 for its novel topical and oral drug candidates targeting psoriasis. The company’s pipeline for systemic lupus erythematosus (SLE) is also advancing rapidly. Furthermore, through collaborative partnerships, Technoderma is conducting biological research on novel targets and early-stage medicinal chemistry exploration for multiple dermatological conditions, thereby further strengthening its new drug development pipeline.