Theravance Biopharma Announces First Subject Dosed in Phase 1 Clinical Trial of TD-8236, a Novel Inhaled pan-JAK Inhibitor
TD-8236 is an internally-discovered JAK inhibitor that has demonstrated a high affinity and selectivity for each of the JAK family enzymes (JAK1, JAK2, JAK3 and TYK2). Through the inhibition of these kinases, TD-8236 interferes with the JAK/STAT signaling pathway and, in turn, modulates the activity of a wide range of pro-inflammatory cytokines. Importantly, TD-8236 is specifically designed to be an inhaled treatment for delivery to the lungs via a dry-powder inhaler with minimal systemic exposure. With multiple JAK-dependent pathways clinically validated in asthma and chronic obstructive pulmonary disease (COPD),
The Phase 1 trial is a randomized, double-blind, placebo-controlled study consisting of two parts. Part A will evaluate single ascending doses (SAD) of TD-8236 in healthy subjects, with the primary objective of assessing safety, tolerability and pharmacokinetics (PK) in this population. Part B will evaluate multiple ascending doses (MAD) of TD-8236 in patients with mild, stable asthma, with the primary objective of assessing safety, tolerability and PK in this population. Key secondary objectives of the trial will include exploratory pharmacodynamic (PD) endpoints with the goal of establishing preliminary dose response relationships in patients with mild stable asthma.
"The advancement of our lung-selective JAK inhibitor program into first-in-human clinical studies is another key milestone for our research efforts in JAK inhibition and localized medicines for localized diseases. As with TD-1473, our gut-selective pan-JAK inhibitor for inflammatory intestinal diseases, we believe that TD-8236 can address key unmet needs by delivering the proven therapeutic activity of JAK inhibition to targeted tissues without immunosuppressive liabilities associated with systemic exposure," said
Preclinical studies have demonstrated that treatment with TD-8236 results in long residence time and duration of action in the lung and low plasma levels, suggesting a profile suitable for once-daily treatment with minimal systemic exposure. Furthermore, TD-8236 demonstrated broad inhibition of key JAK/STAT cytokines in disease-relevant models, providing support for the biological rationale for the compound's development in asthma patients independent of their Th2, eosinophil or periostin status.
About Lung-Selective Pan-Janus (JAK) Kinase Inhibition
JAK inhibitors function by inhibiting the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2) that play a key role in cytokine signaling. Inhibiting these JAK enzymes interferes with the JAK/STAT signaling pathway and, in turn, modulates the activity of a wide range of pro-inflammatory cytokines. JAK inhibitors are currently approved for the treatment of diseases such as rheumatoid arthritis and myelofibrosis, though none are currently approved for the treatment of respiratory diseases such as asthma. Approved JAK inhibitors are known to have side effects associated with their systemic exposure.
TD-8236 is an internally-discovered JAK inhibitor that has demonstrated a high affinity for each of the JAK family of enzymes. Importantly, TD-8236 is a lung-selective treatment specifically designed to distribute adequately and predominantly to the lung, treating inflammation in those tissues while minimizing its systemic exposure.
In our relentless pursuit of this objective, we strive to apply insight and innovation at each stage of our business, including research, development and commercialization, and utilize both internal capabilities and those of partners around the world. Our research efforts are focused in the areas of inflammation and immunology. Our research goal is to design localized medicines that target diseased tissues, without systemic exposure, in order to maximize patient benefit and minimize risk. These efforts leverage years of experience in developing localized medicines for the lungs to treat respiratory disease. The first potential medicine to emerge from our research focus on immunology and localized treatments is an oral, gut-selective pan-Janus kinase (JAK) inhibitor, currently in development to treat a range of inflammatory intestinal diseases. Our pipeline of internally discovered product candidates will continue to evolve with the goal of creating transformational medicines to address the significant needs of patients.
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1 National Heart, Lung, and
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