Theravance Biopharma has announced positive results from a Phase 1 single-ascending dose and multiple-ascending dose trial of its TD-8236 pan-JAK inhibitor DPI for the treatment of inflammatory lung diseases. The company had announced initiation of the study in November 2018.
According to Theravance Biopharma, a single dose of up to 4500 μg of TD-8236 was generally well tolerated in healthy subjects and a once-daily dose of up to 4000 μg over 7 consecutive days was generally well tolerated by patients with mild asthma, with no irritation or bronchoconstriction.
In addition, plasma levels of TD-8236 “were several orders of magnitude below the levels predicted to cause systemic pharmacological activity, which is consistent with data from preclinical studies and the organ-selective design of the compound”; and in the asthma patients who had elevated fractional exhaled nitric oxide (FeNO) levels, doses above 150 μg resulted in reductions of FeNO over the seven day treatment period both pre-dose and 6 hours post-dose compared to placebo.
Theravance Biopharma Chief Medical Officer Brett Haumann said, “There is significant need for new therapies capable of preventing exacerbations and reducing symptoms in asthma patients whose disease remains poorly controlled on inhaled corticosteroids despite being treatment compliant. While those patients with poorly controlled disease who have the Th2-high phenotype of asthma can move on to systemic biological agents, those treatments carry the risk of systemic side effects. Additionally, those with Th2-low asthma do not benefit from biologics and many lack a therapeutic option altogether. We believe that TD-8236 has the potential to serve as the first inhaled nonsteroidal anti-inflammatory for the treatment of patients with more severe asthma regardless of whether their disease is characterized as Th2-high or Th2-low. We look forward to continuing to advance this exciting development program.”
CEO Rick E Winningham added, “TD-8236 builds upon our experience with Yupelri in chronic obstructive pulmonary disease and TD-1473 in inflammatory intestinal diseases. TD-8236 represents our latest internally discovered development candidate to demonstrate evidence of organ selectivity. . . . We are pleased with the progress of our pipeline programs and we look forward to sharing additional data from these programs, as well as introducing additional organ-selective programs into the clinic, over the next 12 to 18 months.”
The company said that it has initiated an extension of the Phase 1 trial to assess additional biomarkers in patients with more severe asthma and that it has plans for a lung allergen challenge Phase 2 study of TD-8236.
Read the Theravance Biopharma press release.
