Axelopran (TD-1211) is a once-daily, oral peripherally active mu opioid receptor antagonist being developed for the treatment of opiod induced constipation (OIC). Axelopran, which has completed long term toxicology studies, is intended to normalize bowel function without impacting analgesia. As a stand-alone treatment, axelopran has been successfully advanced through Phase 2 studies, demonstrating a rapid restoration of normal bowel function followed by maintenance in OIC patients compared to placebo. Phase 2 study data also shows statistically significant improvements in a range of gastrointestinal symptoms in OIC patients for axelopran as compared to placebo. We are refining the development and commercial strategy for both single agent and a fixed-dose combination of axelopran, as well as speaking with potential collaborators.
Axelopran (TD-1211)/Opioid Fixed-Dose Combination
Axelopran (TD-1211) is an investigational, once-daily, oral peripherally active mu opioid receptor antagonist for opioid-induced constipation (OIC). We believe that pairing axelopran and an opioid in a fixed-dose combination (FDC) could present an important market opportunity, as it has the potential to provide pain relief without constipation in a single abuse-deterrent pill for patients using opioids on a chronic basis. To this end, we have developed a proprietary spray-coating technology and applied it to the creation of a FDC of axelopran and controlled-release oxycodone.
To date, we have successfully conducted a Phase 1 study of our novel axelopran FDC , showing that our proprietary spray-coating formulation allowed oxycodone to be coated with axelopran in a single pill without any modification of oxycodone, its activity or abuse-deterrent characteristics. Based on our work to date, we believe our spray-coating technology is applicable to a broad range of opioids, allowing for a potential FDC platform. We are refining the development and commercial strategy for both single agent and a FDC of axelopran, as well as speaking with potential collaborators.
Velusetrag is an oral, investigational medicine developed for gastrointestinal motility disorders. It is a highly selective agonist with high intrinsic activity at the human 5-HT4 receptor and is being developed in collaboration with Alfa Wassermann in a Phase 2 program to test its efficacy, safety and tolerability in the treatment of patients with gastroparesis. A Phase 2b study is currently underway following positive top-line results from a Phase 2 proof-of-concept trial.
TD-8954 is a selective 5-HT4 receptor agonist being investigated for potential use in the treatment of gastrointestinal motility disorders, including enteral feeding intolerance ("EFI"). Millennium Pharmaceuticals, Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited has a global license, development and commercialization agreement for TD-8954 for potential use in the treatment of gastrointestinal motility disorders, including short-term intravenous use for EFI to achieve early nutritional adequacy in critically ill patients at high nutritional risk, for which TD-8954 received U.S. Food and Drug Administration (FDA) Fast Track Designation.
TD-1473 is an intestinally restricted pan-janus kinase (JAK) inhibitor that has demonstrated a high affinity for each of the JAK family of enzymes (JAK1, JAK2, JAK3 and TYK2). Through the inhibition of these enzymes, TD-1473 interferes with the JAK/STAT signaling pathway and, in turn, modulates the activity of a wide range of pro-inflammatory cytokines. Importantly, as an intestinally restricted treatment, TD-1473 is specifically designed to distribute adequately and exclusively to the tissues of the intestinal tract and to minimize systemic exposure. As such, we believe that this novel approach to JAK inhibition has the potential to treat inflammation in the tissues of the intestinal tract while minimizing the risk of systemic side effects. We are conducting a Phase 1 clinical study of TD-1473.