BEVENOPRAN FACT SHEET

Bevenopran (formerly known as CB-5945) Bevenopran is a small-molecule mu-opioid Stimulation of these GI mu-opioid receptors receptor antagonist intended to block the by morphine, or other opioid pain medica- adverse effects of opioid pain medications tions, disrupts normal gut function causing on the GI tract without affecting pain relief. constipation. This is the primary mechanism Bevenopran is currently being investigated underlying OIC. in a Phase 3 program for the treatment of opioid-induced constipation (OIC) in patients with chronic non-cancer pain. HOW OIC AFFECTS PEOPLE WITH CHRONIC PAIN ABOUT OIC OIC affects up to 80 percent of patients who Opioid pain medications, such as morphine, are prescribed opioids to manage their pain. are commonly prescribed for treatment It is the most common adverse effect occur- of moderate to severe pain, which could ring with chronic opioid use and unlike other include pain associated with or as a result side effects of opioids, it can persist the of back pain, arthritis, cancer and other entire time people take these medicines. chronic pain conditions.

Chronic non-cancer pain affects one in five adults, with back pain by far the most common form. It is one of the most disabling types of pain and is costly to the health care system.

• 70 percent of patients with chronic non- cancer pain have had their pain condition for more than five years.

• In the U.S., 6.4 million people are on chronic opioid therapy for 90 or more days.

Opioids work by binding to opioid receptors in the central nervous system. However, opioids can also bind to opioid receptors in the gastrointestinal (GI) tract. These type of opioid receptors, known as mu-opioid receptors, regulate GI tract functions, such as motility, secretion and absorption.

Date last updated 07-19-13 Bevenopran FACT SHEET

OIC can be distressing, causing a significant burden Bevenopran is being evaluated to treat OIC in patients and impact on someone’s quality of life. Surveys have with chronic non-cancer pain. Until recently, there were suggested that some people on long-term opioid treat- no FDA-approved drugs to treat OIC specifically in this ment for pain would rather endure their pain than the patient population and approved treatment options constipation that opioids may cause. remain very limited.

Effective management of OIC remains a significant challenge to both physicians and patients due to the CLINICAL STUDIES OF BEVENOPRAN limited and often ineffective treatment options Two Phase 2 studies measuring change from baseline currently available. in the weekly average number of spontaneous bowel movement (SBM) over a four-week treatment period Laxatives are the most commonly prescribed treatment were completed in 2011, and results showed: to reduce constipation for patients with OIC; however, they are largely ineffective. The failure of laxativesto • Statistically significant increases (over baseline) in weekly average number of SBMs as compared with manage OIC often leads to patients modifying their placebo in patients with OIC (P <0.001). opioid therapies, compromising pain management and increasing the risk for systemic opioid withdrawal. • 56 percent of patients treated with bevenopran had a SBM response, as compared to 26 percent SBM response in patients treated with placebo. HOW BEVENOPRAN IS DIFFERENT Bevenopran is a peripherally-acting mu-opioid receptor • In patients with chronic non-cancer pain, suffering antagonist and not a laxative. It works by blocking the from OIC, once-daily dosing resulted in statistically effect of opioids on the GI tract without compromising significant and clinically meaningful efficacy. pain relief caused by opioid action in the central nervous system. • Fewer than 5 percent of patients who received bevenopran reported one or more GI-related adverse events.

• There was no evidence of drug-related central opioid withdrawal or reversal of analgesia in any of the bevenopran treatment groups across both studies.

In late 2012, Cubist initiated a Phase 3 registrational program with bevenopran to evaluate treatment of OIC in patients with chronic non-cancer pain.

Date last updated 07-19-13