Urovant Sciences Ltd., a clinical-stage biopharmaceutical company, focuses on developing and commercializing therapies for urologic conditions.
The company’s lead product candidate, vibegron, is an oral, once-daily, small molecule that was observed to be a selective agonist of the human beta-3 adrenergic receptor in in vitro assays. Vibegron is being developed for three potential indications: overactive bladder (OAB), the treatment of OAB in men with benign prostatic hyperplasia (BPH), and the...
Urovant Sciences Ltd., a clinical-stage biopharmaceutical company, focuses on developing and commercializing therapies for urologic conditions.
The company’s lead product candidate, vibegron, is an oral, once-daily, small molecule that was observed to be a selective agonist of the human beta-3 adrenergic receptor in in vitro assays. Vibegron is being developed for three potential indications: overactive bladder (OAB), the treatment of OAB in men with benign prostatic hyperplasia (BPH), and the treatment of abdominal pain due to irritable bowel syndrome (IBS).
The company’s second product candidate, URO-902, is a novel gene therapy that it is developing for patients with OAB who have failed oral pharmacological therapy.
In various randomized, placebo-controlled, international Phase 2b and Japanese Phase 3 clinical trials conducted by third parties with various OAB patients, vibegron 50 mg and 100 mg met various primary and secondary efficacy endpoints compared to placebo at week 8 and week 12, respectively.
In March 2018, the company initiated an international pivotal Phase 3 EMPOWUR trial evaluating vibegron for the treatment of OAB.
Its Phase 3 clinical trial had a design in line with the international Phase 2b and Japanese Phase 3 clinical trials. In March 2019, the company reported positive top-line results from this pivotal Phase 3 clinical trial with various patients, with vibegron 75 mg meeting both co-primary efficacy endpoints and all seven key secondary endpoints. Onset of action for the co-primary endpoints was observed as early as week two, the first timepoint measured, and statistically significant efficacy was maintained at all timepoints measured through the end of the study. In September 2019, the company reported positive long-term data from the double-blind extension of its pivotal Phase 3 EMPOWUR trial of vibegron in adults with OAB. In this double-blind extension of the Phase 3 EMPOWUR trial with various patients, vibegron 75 mg further improved the treatment benefit on key OAB symptoms, such as acts of urination, or micturitions, urge urinary incontinence (UUI) urgency and total incontinence through the 40-week extension period. The company submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) in December 2019. The FDA accepted the company’s NDA submission in March 2020 and its NDA submission has been assigned a Prescription Drug User Fee Act goal date of December 26, 2020. Vibegron has been tolerated in all clinical trials to date, has not been associated with clinically relevant drug-drug interactions, such as the inhibition of CYP2D6, and has not demonstrated a clinically relevant QTc signal at any of the human doses tested.
In March 2019, the company initiated the Phase 3 COURAGE randomized, double blind, placebo-controlled trial for OAB in men with BPH who are also taking BPH medications but continue experiencing OAB symptoms. The Phase 3 COURAGE trial would enroll various patients. The study is being conducted in two phases, with the first phase focusing on safety and the second phase, which began enrollment in October 2019, assessing efficacy and safety, and is testing vibegron 75 mg versus placebo, the same dose studied in its Phase 3 EMPOWUR trial. The primary efficacy analysis for the co-primary efficacy endpoints would be measured at 12 weeks and include change from baseline in the average number of micturitions per 24 hours and change from baseline in the average number of urgency episodes per 24 hours. Secondary endpoints include change from baseline in the average number of nocturia episodes per night, which is awakening at night to use the bathroom to urinate. The duration for the double-blind study is 24 weeks. In addition, a 28-week open-label extension study would evaluate the long-term safety and efficacy of vibegron in men with OAB symptoms and on another therapy for BPH. The company completed the first part of the Phase 3 COURAGE trial and began the second part of the trial in October 2019. The company intends to receive top-line data from the Phase 3 COURAGE trial in the second half of 2021.
In December 2018, the company enrolled its first patient in a 200 patient Phase 2a randomized, double blind, placebo-controlled trial with vibegron 75 mg for abdominal pain in women due to IBS with predominant diarrhea or mixed episodes of diarrhea and constipation. The primary endpoint is a 30% reduction in abdominal pain intensity, while secondary endpoints would include Global Improvement Scale ratings, stool symptoms and safety. The company intends to complete enrollment in the summer of 2020 and receive top-line data from the Phase 2a clinical trial in 2020.
The company received an exclusive license to develop, manufacture and commercialize vibegron worldwide, excluding Japan, China, and certain other Asian territories, pursuant to its license agreement with Merck Sharp & Dohme Corp. (Merck), which the company entered into in February 2017. The licensed patents and patent applications under this license agreement cover composition of matter, methods of use and manufacture of vibegron, and the company expects to maintain patent exclusivity until approximately 2034, including through grant of patent term extension on a composition of matter patent. Vibegron is also being developed and marketed by Kyorin Pharmaceutical Co., Ltd. (Kyorin) for the treatment of OAB in Japan and certain other Asian territories. Kyorin received marketing approval from Japan’s Ministry of Health, Labour and Welfare for vibegron for the treatment of adults with OAB in September 2018.
URO-902 Development
The company’s second product candidate, URO-902, is a novel gene therapy that it is developing for patients with OAB who have failed oral pharmacological therapy. In December 2019, the company enrolled its first patient in the placebo-controlled, randomized, multicenter proof-of-concept Phase 2a clinical trial to evaluate the safety and efficacy of URO-902 for the treatment of OAB in various female patients who have not responded to oral pharmacological therapies. The Phase 2a trial is expected to enroll patients in two cohorts: the first cohort would receive either a single administration of 24 mg of URO-902 or matching placebo, and the second cohort would receive 48 mg of URO-902 or matching placebo into the bladder wall. An unblinded review of safety data through an independent Data Safety Monitoring Board would be performed after all subjects in the first cohort reach week 6. Study treatment for the second cohort would begin only after the Data Safety Monitoring Board has agreed that the company could proceed with the second cohort. Patients are followed for approximately 48 weeks after initial administration. The key efficacy endpoints for this Phase 2a clinical trial include reductions per day in micturitions, urgency episodes and UUI episodes. The company intends to receive the week 12 primary efficacy and safety top-line data from both cohorts in the Phase 2a clinical trial in the second half of 2021 and full trial data after the completion of the 48-week post-treatment period in 2022.
The company received an exclusive license to develop, manufacture and commercialize URO-902 worldwide, pursuant to its license agreement with Ion Channel Innovations, LLC (ICI), which it entered into in August 2018. Pursuant to this agreement, the company is the exclusive licensee of an international patent application relating to URO-902 gene therapy, covering the use of URO-902 gene therapy to treat signs or symptoms of OAB or detrusor overactivity. This patent application, if issued, would naturally expire in 2038, subject to any adjustment or extension of patent term that might be available in a particular country. In addition, the company intends that URO-902 would receive 12 years of marketing exclusivity if approved by the FDA given its status as a biological product.
Strategy
The key elements of the company’s strategy are to complete the development and obtain FDA approval of vibegron for the treatment of OAB; expand and complete the clinical development of vibegron for additional indications; improve the commercial potential of vibegron; advance the clinical development of URO-902 as a novel treatment for OAB patients who have not responded to oral pharmacological therapies; and acquire or in-license additional clinical- or commercial-stage product candidates for the treatment of urologic conditions.
Enzyme Supply Agreement with Codexis, Inc. (Codexis)
In September 2017, the company entered into an enzyme supply agreement with Codexis pursuant to which Codexis agreed to supply its proprietary enzyme, used in the production of vibegron, to the company on a non-exclusive basis, or the Codexis Agreement. Pursuant to the Codexis Agreement, the company agreed to purchase from Codexis all of its requirements for such enzyme for use in the clinical and commercial production of vibegron worldwide (other than the Excluded Asian Territories) for the first six years after the first approved product in any of the United States, Europe or Canada. Under the Codexis Agreement, Codexis granted the company a non-exclusive, non-transferrable, non-sublicenseable worldwide license to use and import its proprietary enzyme to make, have made, use, import, sell and have sold vibegron worldwide (other than the Excluded Asian Territories).
License Agreement with ICI
In August 2018, the company entered into a license agreement with ICI, or the ICI Agreement, pursuant to which ICI granted the company an exclusive, royalty-bearing, sublicenseable license under certain patent rights and know-how controlled by ICI, to develop, manufacture and commercialize the gene therapy that it refers to as URO-902 and any and all products containing this gene therapy for use in any human or animal disease or condition. The exclusive license under the ICI Agreement extends to all countries and territories worldwide.
The company is obligated to use commercially reasonable efforts to develop and seek regulatory approval of approximately one licensed product. Under the ICI Agreement, the company controls prosecution, defense and enforcement of the licensed patents, and ICI has backup rights to prosecution, defense and enforcement with respect to any licensed patents for which it elects not to exercise such rights.
Sales and Distribution
To commercialize vibegron, if approved for commercial sale, the company must develop a sales infrastructure. It intends to build an initial sales force of approximately 160 persons in the United States, targeting urologists and other specialists that treat various patients with urologic conditions and prescribers in long-term care facilities.
The company relies on a single supplier, Codexis, for its proprietary enzyme, which it uses in the production of vibegron, and it has agreed to purchase from Codexis all of its requirements for such enzyme for use in its clinical and commercial production of vibegron for the first six years after the first approval of vibegron in any of the United States, Europe or Canada. The company is exploring alternative options for the synthesis of vibegron to enable it to identify and utilize a second source supplier.
URO-902 is a naked DNA plasmid vector containing a cDNA encoding the pore-forming component of the human smooth muscle Maxi-K ion channel. The company intends its existing supply of URO-902, which was transferred to it under the ICI license agreement, to be sufficient for it to complete its ongoing Phase 2a study if materials continue to meet all specifications. The company has contracted with a third-party vendor for the manufacturing of URO-902 for future preclinical studies and clinical trials, but the vendor has not yet manufactured any URO-902. The company intends to contract with third-party vendors for commercialization if and when URO-902 receives marketing approval.
Intellectual Property
Following its execution of the Merck Agreement, as of February 3, 2017, by virtue of the license of patent rights under the Merck Agreement, the company is the exclusive licensee of multiple granted U.S. patents and pending patent applications, as well as patents and patent applications in various foreign jurisdictions (including the United Kingdom, France, Germany, and Canada, but excluding China and the Excluded Asian Territories) relating to beta-3 agonists, including vibegron. As they relate to vibegron, these patents and patent applications cover the vibegron molecule and salts and stereoisomers thereof as a composition of matter, the use of vibegron to treat OAB with symptoms of urinary frequency, UUI and urinary urgency, as well as methods of manufacturing. The patent family directed to the vibegron composition of matter and methods of use naturally expires in 2029 in the United States and in foreign jurisdictions, subject to any adjustment or extension of patent term that might be available in a particular jurisdiction.
The patents and patent applications (if issued) directed to methods of manufacturing beta-3 agonists (including vibegron) and related synthetic intermediates naturally expire between 2032 and 2034, subject to any adjustment or extension of patent term that might be available in a particular country. For example, the term of certain of the composition of matter patents for vibegron in the United States might be extended up to approximately five years under the patent term extension provisions of the Hatch-Waxman Act. In addition to the patent rights licensed from Merck, the company also has three international patent applications directed to use of vibegron at certain dosages to treat OAB. Two of these international patent applications have entered national examination in the U.S. and in various foreign jurisdictions and, if issued, would naturally expire in 2038, subject to any adjustment or extension of patent term that might be available in a particular country. The company also has two international patent applications directed to use of vibegron to treat OAB in men with BPH and use of vibegron to treat abdominal pain due to IBS.
Following its execution of the ICI Agreement, as of August 24, 2018, by virtue of the license of patent rights under the ICI Agreement, the company is the exclusive licensee of an international patent application directed to the use of URO-902 gene therapy to treat signs or symptoms of OAB or detrusor overactivity. This international patent application has entered national examination in the U.S. and in various foreign jurisdictions. Any patents issuing from this application would naturally expire in 2038, subject to any adjustment or extension of patent term that might be available in a particular country. In addition to the patent rights licensed from ICI, the company also has an international patent application directed to the use of URO-902 gene therapy to treat signs or symptoms of OAB or detrusor overactivity.
The company has trademark registrations in the United States for UROVANT and for UROVANT SCIENCES. Under the Merck Agreement, it has the right to market vibegron worldwide (other than the Excluded Asian Territories) under the trademark(s) of its choice, subject to regulatory approval.
Research and Development
The company’s research and development expenses totaled $92.4 million for the year ended March 31, 2020.
Government Regulation
The company and its subsidiaries are subject to the Foreign Corrupt Practices Act of 1977, as amended.
The company is subject to various financial disclosure and securities trading regulations, both in the United States and in other jurisdictions in which it operates, as a public company in the U.S., including laws relating to the oversight activities of the Securities and Exchange Commission and the regulations of the Nasdaq Stock Market LLC, on which its common shares are traded.
In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect the company’s business.
History
The company was founded in 2016. It was incorporated under the laws of Bermuda in January 2016. The company was formerly known as Roivant PPS Holdings Ltd. and changed its name to Thalavant Sciences Ltd. in November 2016. Further, the company changed its name to Urovant Sciences Ltd. in 2017.
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