Sofpironium Bromide

Sofpironium bromide is a new chemical entity that we are currently developing in the U.S. as a potential best-in-class, self-administered, once-daily, topical therapy for the treatment of primary axillary (underarm) hyperhidrosis. In October 2020, we initiated our U.S. Phase 3 clinical program for sofpironium bromide comprising two pivotal clinical studies, Cardigan I and Cardigan II. Each study is evaluating the safety and efficacy of sofpironium bromide gel, 15% compared to vehicle (placebo) gel in approximately 350 subjects nine years of age and older with primary axillary hyperhidrosis. We expect to announce topline results for the U.S. Phase 3 pivotal Cardigan I and Cardigan II studies concurrently in the fourth quarter of 2021 submit a New Drug Application (NDA) for sofpironium bromide gel, 15% to the U.S. FDA in mid-2022 pending the outcome of these studies.

In addition, in September 2020 our development partner, Kaken Pharmaceutical Co., Ltd., received regulatory approval to manufacture and market sofpironium bromide gel, 5% under the brand name ECCLOCK® for the once-daily treatment of primary axillary hyperhidrosis in Japan. Kaken launched ECCLOCK commercially in November 2020, marking the first commercialization of sofpironium bromide for any indication worldwide.

Sofpironium bromide was designed as a structural analog of a well-known potent anticholinergic, glycopyrrolate, to achieve its therapeutic effect at the application site (skin) similar to glycopyrrolate. However, it differs from glycopyrrolate in that sofpironium bromide was retrometabolically designed.

Key design attributes of a retrometabolic drug include:

• The synthesis of a retrometabolic drug is achieved by starting with a known inactive metabolite of a known active drug (e.g., glycopyrrolate).
• The inactive, or less active, metabolite is then structurally modified to an active form (an analogue of active drug in this case; glycopyrrolate) that will undergo a predictable one-step transformation back into the inactive metabolite in vivo.
• Thus, the retrometabolic drug concept is based upon predictable metabolic deactivation processes by enzymes found predominantly in the systemic circulation.

Sofpironium bromide is delivered as a gel formulation in a metered-dose pump with an applicator that allows patients to avoid direct contact to the hands or other non-axillary body parts. We believe that this will help avoid certain side effects that could be caused by the unintended transference of the drug to unwanted areas, such as the eyes.