Axelopran (TD-1211) PuMA for -Induced

Opportunity was administered as a once-daily pill to patients with OIC who were on chronic opioid therapy Theravance is developing axelopran (TD-1211), for non-cancer related pain. a novel, orally administered, peripherally- o The study randomized 217 patients with OIC. selective mu- (PuMA) for o During a 2-week baseline period prior to treating opioid-induced constipation (OIC) initiating therapy, patients had an average of without affecting analgesia in patients on 0.1 to 0.3 complete spontaneous bowel chronic opioid therapy. movements (CSBMs) per week. o All patients treated with axelopran received 5 Theravance is also exploring the development mg for the first 4 days of dosing, and on day 5 of axelopran for use in a fixed-dose either remained at 5 mg or were dose- combination with an opioid agonist for treating escalated to 10 mg or 15 mg for the remainder or preventing OIC. of the 5-week treatment period. o All doses of axelopran achieved the primary

efficacy endpoint of change from baseline in Theravance is seeking strategic partners for the average CSBMs per week compared to placebo, development and commercialization of and the 10 and 15 mg doses met all secondary axelopran as a single-agent OIC therapy and as endpoints of the study. a fixed-dose combination with an opioid.

Medical Need Opioid-Induced constipation (OIC) is a common (up to 90% prevalence) and debilitating adverse effect occurring with chronic opioid use and persists throughout the duration of opioid therapy. Various types of , including stool softeners, stimulants, and osmotic agents, are used by this patient population, often simultaneously. However, over 70% of OIC patients using laxatives report failure to achieve o All doses in the study were generally well relief of constipation, likely due to the lack of a tolerated with rates of adverse events direct effect on the opioid mediated mechanism comparable to placebo, with no abnormal causing OIC. trends in laboratory panels. o There was no evidence of CNS opioid Clinical Development withdrawal or analgesic interference. o There were no serious adverse events Axelopran has completed a Phase 2 program considered to be treatment related. comprised of four studies in over 400 patients with OIC. The positive results from the Phase 2 Compound Overview program support progression of axelopran into Axelopran was discovered by Theravance Phase 3 development for the treatment of OIC. through the application of multivalent design to mu-opioid receptors in a drug discovery The key study in the Phase 2 program was a program focused on discovery peripherally- dose-ranging 5-week study in which axelopran restricted antagonists. For Further Information, Contact: William Martin, Executive Director, Corporate & Business Development T +1.650.808.4061 [email protected]