Verrica Pharmaceuticals Inc.

Matthew Gene Davidson

Jayson Michael Rieger

Steven R Schow

Eugene R Scavola

Paul Daly

Howard Welgus

Garry Southan

Robert Moore

Peter Wuts

Brian Matthew Eklov

Brad Melvin Loertscher

Eugene Scavola

Applicator devices (), kits, systems, and methods of using such devices for treating one or more body surface conditions (e.g., warts, Molluscum contagiosum, conjunctivitis, otitis) are provided. The applicator device facilitates topical administration of a controllable amount of a pharmaceutical composition to a desired area of an affected body surface (e.g., skin, eye, ear, nose, mouth, anus, vagina). The applicator device includes an ampule () containing the pharmaceutical composition, the ampule being positioned within a tube (). Squeezing the tube breaks the ampule, releasing the pharmaceutical composition. The applicator device includes a filter () that permits passage of fluid and inhibits passage of broken ampule shards. The applicator device includes a dispensing tip () through which the pharmaceutical composition passes.

Devices and methods for the treatment of body surface disorders

Methods of treating one or more skin lesions using cantharidin as well as associated compositions, treatment regimens, kits, devices, and systems are provided. A method of treating a subject having one or more skin lesions may involve administering a composition comprising cantharidin to one or more skin lesions. The method may allow for the efficacious treatment of the skin lesion(s) with minimal or no adverse side effects (e.g., severe adverse side effects, permanent damage of the dermal tissue, scarring, excessive blistering of skin surrounding the lesion, elevated plasma cantharidin concentration, systemic exposure to cantharidin). The efficacy and/or safety of the treatment may be due, to certain features of the composition and/or prolonged exposure of the skin lesion(s) to cantharidin. The methods described herein may be used for a wide variety of cutaneous disorders, including skin disorders that primarily affect the epidermis of skin.

Treatment of cutaneous disorders

The invention provides synthetic methods for the preparation of cantharidin and analogs thereof. In one aspect, the invention provides an improved Diels-Alder cycloaddition to generate a key intermediate en route to cantharidin and analogs thereof. In certain embodiments, the new Diels-Alder reaction involves reacting Compound (2) in the presence of furan, and in the absence of acid or increased pressure, in an aprotic polar solvent with slight warming, to yield Compound (1) in favorable yield and exo-endo ratio. In another aspect, the invention also provides a new Diels-Alder reaction between compounds of Formula (III) and furan to yield compounds of Formula (IV), which can then be transformed into cantharidin or analogs thereof. In yet another aspect, the invention describes a new palladium-mediated carbonylation providing another key intermediate en route to cantharidin and analogs thereof. In addition to synthetic methods, present invention also provides compounds (i.e., intermediates) useful in the synthesis of cantharidin and analogs thereof. Compounds provided herein may have biological activity, and therefore may be used in the treatment of diseases or conditions (e.g., infectious diseases and skin conditions).

Synthesis of cantharidin

Applicator

The present disclosure provides methods for purifying a solution comprising cantharidin and cantharidin-associated impurities. A method to purify the solution can comprise recrystallization or sublimation, for example. The purified cantharidin can be analyzed using a detection method comprising a stationary phase and one or more mobile phases.

Quantification and preparation of pharmaceutical grade cantharidin

Devices, systems, methods, and kits for treating cutaneous diseases, such as warts, with a cantharidin formulation are generally described. The cantharidin formulations, described herein, may have many advantages over traditional cantharidin formulations, including removal of highly volatile and corrosive solvents, improved safety, and improved compatibility with common plastics for ease of delivery. The devices, systems, methods, and kits can be used for the precise application of the cantharidin formulation for the treatment of cutaneous diseases and other topical indications. Treatment of cutaneous diseases with cantharidin, using the devices, systems, methods, and/or kits may have many advantages over traditional therapies, including high single application efficacy, lack of scaring, and a mild pain profile.

Compositions, methods and systems for the treatment of cutaneous disorders

The present disclosure provides methods for synthesizing cantharidin and cantharidin derivatives.

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Venice, CA, United States of America

Matthew Gene Davidson