Methods of treating and / or preventing psoriasis

Abstract

To provide methods for the treatment and / or prevention of psoriasis, and compounds for use in treatment or prevention.SOLUTION: The present invention provides a method comprising administering a therapeutically effective amount of KX-01, or a pharmaceutically acceptable salt thereof, to a subject in need thereof.SELECTED DRAWING: None

Description

[Technical field]

[0001] Related Applications This application claims priority to and benefit of U.S. Provisional Application No. 62 / 857,796, filed June 5, 2019, the contents of which are incorporated herein in their entirety. [Background technology]

[0002] background Psoriasis is a chronic autoimmune skin disease that speeds up the growth cycle of skin cells. It causes localized or generalized patches of itchy red papules and plaques covered with white or silvery scales, and psoriasis may affect 100 million people worldwide. Psoriasis is most commonly found on the scalp, elbows, knees, and lower back. Psoriasis can develop at any time, including early adulthood (e.g., ages 15-35). Treatments for psoriasis include steroid creams, dressings, phototherapy, and oral medications. Psoriasis has been associated with other serious health conditions, including but not limited to diabetes, heart disease, and depression. There are five types of psoriasis: plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, and erythroderma. Psoriasis affects approximately 1-3% of the population worldwide, with chronic plaque psoriasis accounting for approximately 85-90% of all cases. Plaque-type psoriasis, or psoriasis vulgaris, is primarily characterized by the formation of raised, inflamed plaques that continually peel off scales resulting from excessive growth of skin epithelial cells.

[0003] Conventional systemic therapies for psoriasis (e.g., methotrexate, cyclosporine A, retinoids, or photochemotherapy with psoralens and ultraviolet A [PUVA]) can have long-term toxicity and do not always result in sufficient disease improvement. There remains a need for new therapies that are effective in treating psoriasis and have fewer side effects. The present disclosure addresses this need. Summary of the Invention

[0004] overview In one aspect, the present disclosure provides a method for treating and / or preventing psoriasis, comprising administering to a subject in need thereof a therapeutically effective amount of KX-01: [ka] The present invention relates at least in part to a method comprising administering

[0005] In one aspect, KX-01 is administered to the subject at a dose of about 0.01 mg to about 10 mg to the affected area.

[0006] In one aspect, KX-01 is administered to the subject at a dose of about 0.1 mg to about 10 mg to the affected area.

[0007] In one aspect, KX-01 is administered to the subject at a dose of about 0.2 mg to about 5 mg to the affected area.

[0008] In one aspect, KX-01 is administered to the subject at a dose of about 0.5 mg to about 2.5 mg to the affected area.

[0009] In one aspect, KX-01 is administered to the subject at a dose of about 0.01 mg, about 0.02 mg, about 0.03 mg, about 0.04 mg, about 0.05 mg, about 0.06 mg, about 0.07 mg, about 0.08 mg, about 0.09 mg, about 0.1 mg, about 0.11 mg, about 0.12 mg, about 0.13 mg, about 0.14 mg, about 0.15 mg, about 0.16 mg, about 0.17 mg, about 0.18 mg, about 0.19 mg, about 0.20 mg, about 0.21 mg, about 0.22 mg, about 0.23 mg, about 0.24 mg, about 0.25 mg, about 0.26 mg, about 0.27 mg, about 0.28 mg, about 0.29 mg, about 0.3 mg, about 0.4 mg, or about 0.5 mg to the affected area.

[0010] In one aspect, KX-01 is administered to the subject at a dose of about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.1 mg, about 2.2 mg, about 2.3 mg, about 2.4 mg, about 2.5 mg, about 2.6 mg, about 2.7 mg, about 2.8 mg, about 2.9 mg, about 3 mg, about 4 mg, or about 5 mg to the affected area.

[0011] In one aspect, KX-01 is administered to the subject at a dose of about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.1 mg, about 2.2 mg, about 2.3 mg, about 2.4 mg or about 2.5 mg to the affected area.

[0012] In one aspect, KX-01 is administered to the subject at a dose of about 0.1 mg / g to about 20 mg / g to the affected area.

[0013] In one aspect, KX-01 is administered to the subject at a dose of about 0.01 mg / g to about 10 mg / g to the affected area.

[0014] In one aspect, KX-01 is administered to the subject at a dose of about 0.1 mg / g to the affected area.

[0015] In one aspect, KX-01 is administered to the subject at a dose of about 1.0 mg / g to the affected area.

[0016] In one aspect, KX-01 is administered to the affected area of ​​the subject at a dose of about 10 mg / g.

[0017] In one aspect, KX-01 has a concentration of about 0.0001 mg / cm 2 ~about 5mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0018] In one aspect, KX-01 has a concentration of about 0.0003 mg / cm 2 ~about 10mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0019] In one aspect, KX-01 has a concentration of about 0.001 mg / cm 2 ~about 0.4mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0020] In one aspect, KX-01 has a concentration of about 0.005 mg / cm 2 ~about 0.1mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0021] In one aspect, KX-01 has a concentration of about 0.005 mg / cm 2 ~ approx. 0.02 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0022] In one aspect, KX-01 has a concentration of about 0.025 mg / cm 2 ~about 0.1mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0023] In one aspect, KX-01 has a concentration of about 0.0001 mg / cm 2 , about 0.0002mg / cm 2 , about 0.0003mg / cm 2 , about 0.0004mg / cm 2 , about 0.0005mg / cm 2 , about 0.0006mg / cm 2 , about 0.0007mg / cm 2 , about 0.0008mg / cm 2 , about 0.0009mg / cm 2 , about 0.001mg / cm 2 , about 0.002mg / cm 2 , about 0.003mg / cm 2 , about 0.004mg / cm 2 , about 0.005mg / cm 2 , about 0.006mg / cm2 , about 0.007mg / cm 2 , about 0.008mg / cm 2 , about 0.009 mg / cm 2 , about 0.01mg / cm 2 , about 0.015mg / cm 2 , about 0.02 mg / cm 2 , about 0.025mg / cm 2 , about 0.03mg / cm 2 , about 0.035mg / cm 2 or about 0.04 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0024] In one aspect, KX-01 has a concentration of about 0.001 mg / cm 2 , about 0.002mg / cm 2 , about 0.003mg / cm 2 , about 0.004mg / cm 2 , about 0.005mg / cm 2 , about 0.006mg / cm 2 , about 0.007mg / cm 2 , about 0.008mg / cm 2 , about 0.009 mg / cm 2 , about 0.01mg / cm 2 , about 0.02 mg / cm 2 , about 0.03mg / cm 2 , about 0.04 mg / cm 2 , about 0.05mg / cm 2 , about 0.06mg / cm 2 , about 0.07mg / cm 2 , about 0.08 mg / cm 2 , about 0.09mg / cm 2 , about 0.1mg / cm 2 , about 0.15mg / cm 2 , about 0.2mg / cm 2 , about 0.25mg / cm 2 , about 0.3mg / cm 2 , about 0.35mg / cm 2 or about 0.4 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0025] In one aspect, KX-01 has a concentration of about 0.005 mg / cm 2 , about 0.006mg / cm 2 , about 0.007mg / cm 2 , about 0.008mg / cm 2 , about 0.009 mg / cm 2 , about 0.01mg / cm 2 , about 0.015mg / cm 2 , about 0.02 mg / cm 2 , about 0.025mg / cm 2 , about 0.03mg / cm 2 , about 0.035mg / cm 2 , about 0.04 mg / cm 2 , about 0.045mg / cm 2 , about 0.05mg / cm 2 , about 0.055mg / cm 2 , about 0.06mg / cm 2 , about 0.065mg / cm 2 , about 0.07mg / cm 2 , about 0.075mg / cm 2 , about 0.08 mg / cm 2 , about 0.085mg / cm 2 , about 0.09mg / cm 2 , about 0.095mg / cm 2 or about 0.1 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0026] In one aspect, the affected area of ​​the subject is approximately 0.01 cm 2 ~about 300cm 2 It is.

[0027] In one aspect, the affected area of ​​the subject is about 1 cm 2 ~about 200cm 2 , about 1cm 2 ~Approx. 100cm 2 , about 1cm 2 ~Approx. 75cm 2 , about 1cm 2 ~about 50cm 2 or about 1 cm 2 ~about 25cm 2 It is.

[0028] In one aspect, the affected area of ​​the subject is about 10 cm 2 ~about 200cm 2 , about 10cm 2 ~Approx. 100cm 2 , about 10cm 2 ~Approx. 75cm 2 , about 10cm 2 ~about 50cm 2 or about 10cm 2 ~about 25cm 2 It is.

[0029] In one aspect, the affected area of ​​the subject is approximately 25 cm 2 ~about 200cm 2 , about 25cm 2 ~Approx. 100cm 2 , about 25cm 2 ~Approx. 75cm 2 or about 25cm 2 ~about 50cm 2 It is.

[0030] In one aspect, the affected area of ​​the subject is approximately 25 cm 2 ~Approx. 100cm 2 , about 25cm 2 ~about 90cm 2 , about 25cm 2 ~about 80cm 2 or about 25cm 2 ~about 70cm 2 , about 25cm 2 ~about 60cm 2 , about 25cm 2 ~about 50cm 2 , about 25cm 2 ~about 40cm 2 or about 25cm 2 ~about 30cm 2 It is.

[0031] In one aspect, the affected area of ​​the subject is approximately 25 cm 2 , about 30cm 2 , about 35cm 2 , about 40cm 2 , about 45cm 2 , about 50cm 2 , approx. 55cm 2 , about 60cm 2, approx. 65cm 2 , about 70cm 2 , about 75cm 2 , about 80cm 2 , approx. 85cm 2 , about 90cm 2 , about 95cm 2 Or about 100cm 2 It is.

[0032] In one aspect, the affected area of ​​the subject is the skin.

[0033] In one aspect, the affected areas of the subject are located at one or more locations independently selected from the scalp, forehead, forearms, face, nose, ears, eyelids, lips, neck, arms, elbows, hands, trunk, legs, knees and feet.

[0034] In one aspect, a subject has more than one affected area.

[0035] In one aspect, the affected area is contiguous.

[0036] In one aspect, the affected area is discontinuous.

[0037] In one aspect, KX-01 is administered once a week, once every 3 days, once every 2 days, once a day, twice a day, three times a day, or four times a day.

[0038] In one aspect, KX-01 is administered once daily or twice daily.

[0039] In one aspect, KX-01 is administered once daily.

[0040] In one aspect, KX-01 is administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 days.

[0041] In one aspect, KX-01 is administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days.

[0042] In one aspect, KX-01 is administered for 8, 9, 10, 11, 12, 13 or 14 days.

[0043] In one aspect, KX-01 is administered for 1, 2, 3, 4, 5, 6 or 7 days.

[0044] In one aspect, KX-01 is administered for 1, 2, 3, 4 or 5 days.

[0045] In one aspect, KX-01 is administered for 5 days.

[0046] In one aspect, KX-01 is administered for 5 consecutive days.

[0047] In one aspect, KX-01 is administered 1, 2, 3, 4, 5, or 6 days per week.

[0048] In one aspect, KX-01 is administered 2, 3, 4, 5, or 6 days per week.

[0049] In one aspect, KX-01 is administered for 1, 2, 3, 4 or more weeks, optionally followed by 1, 2, 3, 4 or more weeks of no KX-01, optionally followed by 1, 2, 3, 4 or more weeks of administration of KX-01.

[0050] In one aspect, KX-01 is administered for two weeks, optionally followed by a period of one week where no KX-01 is administered, optionally followed by one or two weeks where KX-01 is administered.

[0051] In one aspect, KX-01 is administered for two weeks, followed by a period of one week where no KX-01 is administered, followed by two weeks where KX-01 is administered.

[0052] In one aspect, KX-01 is administered for four weeks.

[0053] In one aspect, KX-01 is administered once or twice daily for multiple consecutive days per week, followed by discontinuation of administration for the remainder of the week.

[0054] In one aspect, KX-01 is administered once or twice daily on every other day.

[0055] In one aspect, KX-01 is administered once or twice daily, every 3, 4, 5, 6 or 7 days.

[0056] In one aspect, KX-01 is administered once or twice daily for two consecutive days every 3, 4, 5, 6, or 7 days.

[0057] In one aspect, KX-01 is administered once or twice daily for three consecutive days every 4, 5, 6, or 7 days.

[0058] In one aspect, KX-01 is administered once or twice daily for four consecutive days, every 5, 6, or 7 days.

[0059] In one aspect, KX-01 is administered until the psoriasis is completely treated.

[0060] In one aspect, KX-01 is administered locally.

[0061] In one aspect, administration of KX-01 reduces the number and / or severity of local skin reactions or other adverse side effects in a subject as compared to other treatments for psoriasis.

[0062] In one aspect, administration of KX-01 reduces the number of subjects with local skin reactions or other adverse side effects compared to other treatments for psoriasis.

[0063] In one aspect, the local skin reaction is selected from the group consisting of vesiculation, pustulation, sores, ulcers, redness, swelling, peeling, scaling, hard lumps, dryness, pus, and blistering.

[0064] In one aspect, the other side effects are selected from the group consisting of application site pain, application site pruritus, application site irritation, application site swelling, application site burning, application site infection, periorbital edema, nasopharyngitis, chills, sore throat, ptosis, puffy eyes, hypopigmentation, hyperpigmentation, and headache.

[0065] In one aspect, the present disclosure relates at least in part to KX-01 for use in the treatment and / or prevention of psoriasis (e.g., topical use). In some aspects, KX-01 is for use in a subject in need thereof at the doses, dosing schedules and / or in one or more affected areas described herein.

[0066] In one aspect, the present disclosure relates at least in part to the use (e.g., topical use) of KX-01 in the treatment and / or prevention of psoriasis. In some aspects, KX-01 is used in a subject in need thereof at the doses, dosing schedules and / or in one or more affected areas described herein.

[0067] In one aspect, the present disclosure relates at least in part to the use of KX-01 in the manufacture of a medicament for the treatment and / or prevention of psoriasis.In some aspects, KX-01 is used in a subject in need thereof at the dose, dosing schedule and / or at one or more affected areas described herein. [Brief description of the drawings]

[0068] [Figure 1] Figure 1A shows the stage I and stage II study designs for the treatment of plaque-type psoriasis with KX-01. Figure 1B shows the stage III study design for the treatment of plaque-type psoriasis with KX-01. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0069] Detailed Description Disclosed is a method for treating and / or preventing psoriasis, comprising administering to a subject in need thereof a therapeutically effective amount of KX-01: [ka] or a pharma- ceutically acceptable salt thereof.

[0070] Disclosed is a method for treating and / or preventing psoriasis, comprising administering to a subject in need thereof a therapeutically effective amount of KX-01: [ka] The present invention relates to a method comprising administering

[0071] Disclosed is a method of treating psoriasis, comprising administering to a subject in need thereof a therapeutically effective amount of KX-01: [ka] The present invention relates to a method comprising administering

[0072] Disclosed is a method for preventing psoriasis, comprising administering to a subject in need thereof a therapeutically effective amount of KX-01: [ka] The present invention relates to a method comprising administering

[0073] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.1 mg to about 10 mg to the affected area.

[0074] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.2 mg to about 5 mg to the affected area.

[0075] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.5 mg to about 2.5 mg to the affected area.

[0076] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.01 mg to about 10 mg to the affected area.

[0077] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.025 mg to about 10 mg to the affected area.

[0078] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.25 mg to about 10 mg to the affected area.

[0079] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.01 mg, about 0.02 mg, about 0.03 mg, about 0.04 mg, about 0.05 mg, about 0.06 mg, about 0.07 mg, about 0.08 mg, about 0.09 mg, about 0.1 mg, about 0.11 mg, about 0.12 mg, about 0.13 mg, about 0.14 mg, about 0.15 mg, about 0.16 mg, about 0.17 mg, about 0.18 mg, about 0.19 mg, about 0.20 mg, about 0.21 mg, about 0.22 mg, about 0.23 mg, about 0.24 mg, about 0.25 mg, about 0.26 mg, about 0.27 mg, about 0.28 mg, about 0.29 mg, about 0.3 mg, about 0.4 mg, or about 0.5 mg to the affected area.

[0080] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 9 mg, about 0.1 mg to about 8 mg, about 0.1 mg to about 7 mg, about 0.1 mg to about 6 mg, about 0.1 mg to about 5 mg, about 0.1 mg to about 4 mg, about 0.1 mg to about 3 mg, about 0.1 mg to about 2 mg, about 0.1 mg to about 1 mg, about 0.1 mg to about 0.9 mg, about 0.1 mg to about 0.8 mg, about 0.1 mg to about 0.7 mg, about 0.1 mg to about 0.6 mg, about 0.1 mg to about 0.5 mg, about 0.1 mg to about 0.4 mg, about 0.1 mg to about 0.3 mg, or about 0.1 mg to about 0.2 mg.

[0081] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 10 mg, about 0.2 mg to about 9 mg, about 0.2 mg to about 8 mg, about 0.2 mg to about 7 mg, about 0.2 mg to about 6 mg, about 0.2 mg to about 5 mg, about 0.2 mg to about 4 mg, about 0.2 mg to about 3 mg, about 0.2 mg to about 2 mg, about 0.2 mg to about 1 mg, about 0.2 mg to about 0.9 mg, about 0.2 mg to about 0.8 mg, about 0.2 mg to about 0.7 mg, about 0.2 mg to about 0.6 mg, about 0.2 mg to about 0.5 mg, about 0.2 mg to about 0.4 mg, or about 0.2 mg to about 0.3 mg.

[0082] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.3 mg to about 10 mg, about 0.3 mg to about 9 mg, about 0.3 mg to about 8 mg, about 0.3 mg to about 7 mg, about 0.3 mg to about 6 mg, about 0.3 mg to about 5 mg, about 0.3 mg to about 4 mg, about 0.3 mg to about 3 mg, about 0.3 mg to about 2 mg, about 0.3 mg to about 1 mg, about 0.3 mg to about 0.9 mg, about 0.3 mg to about 0.8 mg, about 0.3 mg to about 0.7 mg, about 0.3 mg to about 0.6 mg, about 0.3 mg to about 0.5 mg, or about 0.3 mg to about 0.4 mg.

[0083] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.4 mg to about 10 mg, about 0.4 mg to about 9 mg, about 0.4 mg to about 8 mg, about 0.4 mg to about 7 mg, about 0.4 mg to about 6 mg, about 0.4 mg to about 5 mg, about 0.4 mg to about 4 mg, about 0.4 mg to about 3 mg, about 0.4 mg to about 2 mg, about 0.4 mg to about 1 mg, about 0.4 mg to about 0.9 mg, about 0.4 mg to about 0.8 mg, about 0.4 mg to about 0.7 mg, about 0.4 mg to about 0.6 mg, or about 0.4 mg to about 0.5 mg.

[0084] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.5 mg to about 10 mg, about 0.5 mg to about 9 mg, about 0.5 mg to about 8 mg, about 0.5 mg to about 7 mg, about 0.5 mg to about 6 mg, about 0.5 mg to about 5 mg, about 0.5 mg to about 4 mg, about 0.5 mg to about 3 mg, about 0.5 mg to about 2 mg, about 0.5 mg to about 1 mg, about 0.5 mg to about 0.9 mg, about 0.5 mg to about 0.8 mg, about 0.5 mg to about 0.7 mg, or about 0.5 mg to about 0.6 mg.

[0085] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.6 mg to about 10 mg, about 0.6 mg to about 9 mg, about 0.6 mg to about 8 mg, about 0.6 mg to about 7 mg, about 0.6 mg to about 6 mg, about 0.6 mg to about 5 mg, about 0.6 mg to about 4 mg, about 0.6 mg to about 3 mg, about 0.6 mg to about 2 mg, about 0.6 mg to about 1 mg, about 0.6 mg to about 0.9 mg, about 0.6 mg to about 0.8 mg, or about 0.6 mg to about 0.7 mg.

[0086] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.7 mg to about 10 mg, about 0.7 mg to about 9 mg, about 0.7 mg to about 8 mg, about 0.7 mg to about 7 mg, about 0.7 mg to about 6 mg, about 0.7 mg to about 5 mg, about 0.7 mg to about 4 mg, about 0.7 mg to about 3 mg, about 0.7 mg to about 2 mg, about 0.7 mg to about 1 mg, about 0.7 mg to about 0.9 mg, or about 0.7 mg to about 0.8 mg.

[0087] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.8 mg to about 10 mg, about 0.8 mg to about 9 mg, about 0.8 mg to about 8 mg, about 0.8 mg to about 7 mg, about 0.8 mg to about 6 mg, about 0.8 mg to about 5 mg, about 0.8 mg to about 4 mg, about 0.8 mg to about 3 mg, about 0.8 mg to about 2 mg, about 0.8 mg to about 1 mg, or about 0.8 mg to about 0.9 mg.

[0088] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.9 mg to about 10 mg, about 0.9 mg to about 9 mg, about 0.9 mg to about 8 mg, about 0.9 mg to about 7 mg, about 0.9 mg to about 6 mg, about 0.9 mg to about 5 mg, about 0.9 mg to about 4 mg, about 0.9 mg to about 3 mg, about 0.9 mg to about 2 mg, or about 0.9 mg to about 1 mg.

[0089] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 1 mg to about 10 mg, about 1 mg to about 9 mg, about 1 mg to about 8 mg, about 1 mg to about 7 mg, about 1 mg to about 6 mg, about 1 mg to about 5 mg, about 1 mg to about 4 mg, about 1 mg to about 3 mg, or about 1 mg to about 2 mg.

[0090] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 2 mg to about 10 mg, about 2 mg to about 9 mg, about 2 mg to about 8 mg, about 2 mg to about 7 mg, about 2 mg to about 6 mg, about 2 mg to about 5 mg, about 2 mg to about 4 mg, or about 2 mg to about 3 mg.

[0091] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 10 mg, about 0.3 mg to about 10 mg, about 0.4 mg to about 10 mg, about 0.5 mg to about 10 mg, about 0.6 mg to about 10 mg, about 0.7 mg to about 10 mg, about 0.8 mg to about 10 mg, about 0.9 mg to about 10 mg, about 1 mg to about 10 mg, about 2 mg to about 10 mg, about 3 mg to about 10 mg, about 4 mg to about 10 mg, about 5 mg to about 10 mg, about 6 mg to about 10 mg, about 7 mg to about 10 mg, about 8 mg to about 10 mg, or about 9 mg to about 10 mg.

[0092] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 9 mg, about 0.2 mg to about 9 mg, about 0.3 mg to about 9 mg, about 0.4 mg to about 9 mg, about 0.5 mg to about 9 mg, about 0.6 mg to about 9 mg, about 0.7 mg to about 9 mg, about 0.8 mg to about 9 mg, about 0.9 mg to about 9 mg, about 1 mg to about 9 mg, about 2 mg to about 9 mg, about 3 mg to about 9 mg, about 4 mg to about 9 mg, about 5 mg to about 9 mg, about 6 mg to about 9 mg, about 7 mg to about 9 mg, or about 8 mg to about 9 mg.

[0093] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 8 mg, about 0.2 mg to about 8 mg, about 0.3 mg to about 8 mg, about 0.4 mg to about 8 mg, about 0.5 mg to about 8 mg, about 0.6 mg to about 8 mg, about 0.7 mg to about 8 mg, about 0.8 mg to about 8 mg, about 0.9 mg to about 8 mg, about 1 mg to about 8 mg, about 2 mg to about 8 mg, about 3 mg to about 8 mg, about 4 mg to about 8 mg, about 5 mg to about 8 mg, about 6 mg to about 8 mg, or about 7 mg to about 8 mg.

[0094] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 7 mg, about 0.2 mg to about 7 mg, about 0.3 mg to about 7 mg, about 0.4 mg to about 7 mg, about 0.5 mg to about 7 mg, about 0.6 mg to about 7 mg, about 0.7 mg to about 7 mg, about 0.8 mg to about 7 mg, about 0.9 mg to about 7 mg, about 1 mg to about 7 mg, about 2 mg to about 7 mg, about 3 mg to about 7 mg, about 4 mg to about 7 mg, about 5 mg to about 7 mg, or about 6 mg to about 7 mg.

[0095] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 6 mg, about 0.2 mg to about 6 mg, about 0.3 mg to about 6 mg, about 0.4 mg to about 6 mg, about 0.5 mg to about 6 mg, about 0.6 mg to about 6 mg, about 0.7 mg to about 6 mg, about 0.8 mg to about 6 mg, about 0.9 mg to about 6 mg, about 1 mg to about 6 mg, about 2 mg to about 6 mg, about 3 mg to about 6 mg, about 4 mg to about 6 mg, or about 5 mg to about 6 mg.

[0096] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 5 mg, about 0.2 mg to about 5 mg, about 0.3 mg to about 5 mg, about 0.4 mg to about 5 mg, about 0.5 mg to about 5 mg, about 0.6 mg to about 5 mg, about 0.7 mg to about 5 mg, about 0.8 mg to about 5 mg, about 0.9 mg to about 5 mg, about 1 mg to about 5 mg, about 2 mg to about 5 mg, about 3 mg to about 5 mg, or about 4 mg to about 5 mg.

[0097] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 4 mg, about 0.2 mg to about 4 mg, about 0.3 mg to about 4 mg, about 0.4 mg to about 4 mg, about 0.5 mg to about 4 mg, about 0.6 mg to about 4 mg, about 0.7 mg to about 4 mg, about 0.8 mg to about 4 mg, about 0.9 mg to about 4 mg, about 1 mg to about 4 mg, about 2 mg to about 4 mg, or about 3 mg to about 4 mg.

[0098] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 3 mg, about 0.2 mg to about 3 mg, about 0.3 mg to about 3 mg, about 0.4 mg to about 3 mg, about 0.5 mg to about 3 mg, about 0.6 mg to about 3 mg, about 0.7 mg to about 3 mg, about 0.8 mg to about 3 mg, about 0.9 mg to about 3 mg, about 1 mg to about 3 mg, or about 2 mg to about 3 mg.

[0099] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 2 mg, about 0.2 mg to about 2 mg, about 0.3 mg to about 2 mg, about 0.4 mg to about 2 mg, about 0.5 mg to about 2 mg, about 0.6 mg to about 2 mg, about 0.7 mg to about 2 mg, about 0.8 mg to about 2 mg, about 0.9 mg to about 2 mg, or about 1 mg to about 2 mg.

[0100] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.1 mg to about 1 mg, about 0.2 mg to about 1 mg, about 0.3 mg to about 1 mg, about 0.4 mg to about 1 mg, about 0.5 mg to about 1 mg, about 0.6 mg to about 1 mg, about 0.7 mg to about 1 mg, about 0.8 mg to about 1 mg, or about 0.9 mg to about 1 mg.

[0101] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 3 mg, about 0.2 mg to about 2.9 mg, about 0.2 mg to about 2.8 mg, about 0.2 mg to about 2.7 mg, about 0.2 mg to about 2.6 mg, about 0.2 mg to about 2.5 mg, about 0.2 mg to about 2.4 mg, about 0.2 mg to about 2.3 mg, about 0.2 mg to about 2.2 mg, about 0.2 mg to about 2.1 mg, or about 0.2 mg to about 2.0 mg.

[0102] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.3 mg to about 3 mg, about 0.3 mg to about 2.9 mg, about 0.3 mg to about 2.8 mg, about 0.3 mg to about 2.7 mg, about 0.3 mg to about 2.6 mg, about 0.3 mg to about 2.5 mg, about 0.3 mg to about 2.4 mg, about 0.3 mg to about 2.3 mg, about 0.3 mg to about 2.2 mg, about 0.3 mg to about 2.1 mg, or about 0.3 mg to about 2.0 mg.

[0103] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.4 mg to about 3 mg, about 0.4 mg to about 2.9 mg, about 0.4 mg to about 2.8 mg, about 0.4 mg to about 2.7 mg, about 0.4 mg to about 2.6 mg, about 0.4 mg to about 2.5 mg, about 0.4 mg to about 2.4 mg, about 0.4 mg to about 2.3 mg, about 0.4 mg to about 2.2 mg, about 0.4 mg to about 2.1 mg, or about 0.4 mg to about 2.0 mg.

[0104] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.5 mg to about 3 mg, about 0.5 mg to about 2.9 mg, about 0.5 mg to about 2.8 mg, about 0.5 mg to about 2.7 mg, about 0.5 mg to about 2.6 mg, about 0.5 mg to about 2.5 mg, about 0.5 mg to about 2.4 mg, about 0.5 mg to about 2.3 mg, about 0.5 mg to about 2.2 mg, about 0.5 mg to about 2.1 mg, or about 0.5 mg to about 2.0 mg.

[0105] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 3 mg, about 0.3 mg to about 3 mg, about 0.4 mg to about 3 mg, about 0.5 mg to about 3 mg, about 0.6 mg to about 3 mg, about 0.7 mg to about 3 mg, about 0.8 mg to about 3 mg, about 0.9 mg to about 3 mg, or about 1 mg to about 3 mg.

[0106] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.9 mg, about 0.3 mg to about 2.9 mg, about 0.4 mg to about 2.9 mg, about 0.5 mg to about 2.9 mg, about 0.6 mg to about 2.9 mg, about 0.7 mg to about 2.9 mg, about 0.8 mg to about 2.9 mg, about 0.9 mg to about 2.9 mg, or about 1 mg to about 2.9 mg.

[0107] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.8 mg, about 0.3 mg to about 2.8 mg, about 0.4 mg to about 2.8 mg, about 0.5 mg to about 2.8 mg, about 0.6 mg to about 2.8 mg, about 0.7 mg to about 2.8 mg, about 0.8 mg to about 2.8 mg, about 0.9 mg to about 2.8 mg, or about 1 mg to about 2.8 mg.

[0108] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.7 mg, about 0.3 mg to about 2.7 mg, about 0.4 mg to about 2.7 mg, about 0.5 mg to about 2.7 mg, about 0.6 mg to about 2.7 mg, about 0.7 mg to about 2.7 mg, about 0.8 mg to about 2.7 mg, about 0.9 mg to about 2.7 mg, or about 1 mg to about 2.7 mg.

[0109] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.6 mg, about 0.3 mg to about 2.6 mg, about 0.4 mg to about 2.6 mg, about 0.5 mg to about 2.6 mg, about 0.6 mg to about 2.6 mg, about 0.7 mg to about 2.6 mg, about 0.8 mg to about 2.6 mg, about 0.9 mg to about 2.6 mg, or about 1 mg to about 2.6 mg.

[0110] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.5 mg, about 0.3 mg to about 2.5 mg, about 0.4 mg to about 2.5 mg, about 0.5 mg to about 2.5 mg, about 0.6 mg to about 2.5 mg, about 0.7 mg to about 2.5 mg, about 0.8 mg to about 2.5 mg, about 0.9 mg to about 2.5 mg, or about 1 mg to about 2.5 mg.

[0111] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.4 mg, about 0.3 mg to about 2.4 mg, about 0.4 mg to about 2.4 mg, about 0.5 mg to about 2.4 mg, about 0.6 mg to about 2.4 mg, about 0.7 mg to about 2.4 mg, about 0.8 mg to about 2.4 mg, about 0.9 mg to about 2.4 mg, or about 1 mg to about 2.4 mg.

[0112] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.3 mg, about 0.3 mg to about 2.3 mg, about 0.4 mg to about 2.3 mg, about 0.5 mg to about 2.3 mg, about 0.6 mg to about 2.3 mg, about 0.7 mg to about 2.3 mg, about 0.8 mg to about 2.3 mg, about 0.9 mg to about 2.3 mg, or about 1 mg to about 2.3 mg.

[0113] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.2 mg, about 0.3 mg to about 2.2 mg, about 0.4 mg to about 2.2 mg, about 0.5 mg to about 2.2 mg, about 0.6 mg to about 2.2 mg, about 0.7 mg to about 2.2 mg, about 0.8 mg to about 2.2 mg, about 0.9 mg to about 2.2 mg, or about 1 mg to about 2.2 mg.

[0114] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2.1 mg, about 0.3 mg to about 2.1 mg, about 0.4 mg to about 2.1 mg, about 0.5 mg to about 2.1 mg, about 0.6 mg to about 2.1 mg, about 0.7 mg to about 2.1 mg, about 0.8 mg to about 2.1 mg, about 0.9 mg to about 2.1 mg, or about 1 mg to about 2.1 mg.

[0115] In some embodiments of the methods disclosed herein, KX-01 is administered to the affected area of ​​the subject at a dose of about 0.2 mg to about 2 mg, about 0.3 mg to about 2 mg, about 0.4 mg to about 2 mg, about 0.5 mg to about 2 mg, about 0.6 mg to about 2 mg, about 0.7 mg to about 2 mg, about 0.8 mg to about 2 mg, about 0.9 mg to about 2 mg, or about 1 mg to about 2 mg.

[0116] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.1 mg, about 2.2 mg, about 2.3 mg, about 2.4 mg, about 2.5 mg, about 2.6 mg, about 2.7 mg, about 2.8 mg, about 2.9 mg, about 3 mg, about 4 mg, or about 5 mg to the affected area.

[0117] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.1 mg, about 2.2 mg, about 2.3 mg, about 2.4 mg or about 2.5 mg to the affected area.

[0118] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.1 mg, about 2.2 mg, about 2.3 mg, about 2.4 mg or about 2.5 mg to the affected area.

[0119] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.1 mg / g to about 20 mg / g to the affected area.

[0120] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.5 mg / g to about 20 mg / g to the affected area.

[0121] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 1 mg / g to about 20 mg / g to the affected area.

[0122] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 1 mg / g to about 15 mg / g to the affected area.

[0123] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 5 mg / g to about 15 mg / g to the affected area.

[0124] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 7.5 mg / g to about 12.5 mg / g to the affected area.

[0125] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 8 mg / g to about 12 mg / g to the affected area.

[0126] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.01 mg / g to about 10 mg / g to the affected area.

[0127] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.05 mg / g to about 10 mg / g to the affected area.

[0128] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.05 mg / g to about 5 mg / g to the affected area.

[0129] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.05 mg / g to about 2.5 mg / g to the affected area.

[0130] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.05 mg / g to about 0.25 mg / g to the affected area.

[0131] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.1 mg / g to about 10 mg / g to the affected area.

[0132] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.2 mg / g to about 5 mg / g to the affected area.

[0133] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.5 mg / g to about 2.5 mg / g to the affected area.

[0134] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.1 mg / g to the affected area.

[0135] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 1.0 mg / g to the affected area.

[0136] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 10 mg / g to the affected area.

[0137] In some embodiments of the methods disclosed herein, KX-01 is administered to the subject at a dose of about 0.005 mg / g, about 0.01 mg / g, about 0.05 mg / g, about 0.1 mg / g, about 0.5 mg / g, about 1.0 mg / g, about 2.0 mg / g, about 3.0 mg / g, about 4.0 mg / g, about 5.0 mg / g, about 6.0 mg / g, about 7.0 mg / g, about 8.0 mg / g, about 9.0 mg / g, about 10.0 mg / g, about 11.0 mg / g, about 12.0 mg / g, about 13.0 mg / g, about 14.0 mg / g, about 15.0 mg / g, about 16.0 mg / g, about 17.0 mg / g, about 18.0 mg / g, about 19.0 mg / g, or about 20.0 mg / g.

[0138] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.0001 mg / cm 2 ~about 5mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0139] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.0001 mg / cm 2 ~about 2.5mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0140] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.0001 mg / cm 2 ~About 1mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0141] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.0001 mg / cm 2 ~about 0.5mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0142] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.0001 mg / cm 2 ~about 0.1mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0143] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.0001 mg / cm 2 ~about 0.01mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0144] In some embodiments of the methods disclosed herein, KX-01 is about 0.0002 mg / cm 2 ~about 10mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0145] In some embodiments of the methods disclosed herein, KX-01 is about 0.0002 mg / cm 2 ~about 5mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0146] In some embodiments of the methods disclosed herein, KX-01 is about 0.0002 mg / cm 2 ~about 2.5mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0147] In some embodiments of the methods disclosed herein, KX-01 is about 0.0002 mg / cm 2 ~About 1mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0148] In some embodiments of the methods disclosed herein, KX-01 is about 0.0002 mg / cm 2 ~about 0.1mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0149] In some embodiments of the methods disclosed herein, KX-01 is about 0.0002 mg / cm 2 ~about 0.01mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0150] In some embodiments of the methods disclosed herein, KX-01 is about 0.0003 mg / cm 2 ~about 10mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0151] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.001 mg / cm 2 ~about 0.4mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0152] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.005 mg / cm. 2 ~about 0.1mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0153] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.005 mg / cm. 2 ~ approx. 0.02 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0154] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.025 mg / cm 2 ~about 0.1mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0155] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.0001 mg / cm 2 , about 0.0002mg / cm 2 , about 0.0003mg / cm 2 , about 0.0004mg / cm 2 , about 0.0005mg / cm 2 , about 0.0006mg / cm 2 , about 0.0007mg / cm 2 , about 0.0008mg / cm 2 , about 0.0009mg / cm 2 , about 0.001mg / cm 2 , about 0.002mg / cm 2, about 0.003mg / cm 2 , about 0.004mg / cm 2 , about 0.005mg / cm 2 , about 0.006mg / cm 2 , about 0.007mg / cm 2 , about 0.008mg / cm 2 , about 0.009 mg / cm 2 , about 0.01mg / cm 2 , about 0.015mg / cm 2 , about 0.02 mg / cm 2 , about 0.025mg / cm 2 , about 0.03mg / cm 2 , about 0.035mg / cm 2 or about 0.04 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0156] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.001 mg / cm 2 , about 0.002mg / cm 2 , about 0.003mg / cm 2 , about 0.004mg / cm 2 , about 0.005mg / cm 2 , about 0.006mg / cm 2 , about 0.007mg / cm 2 , about 0.008mg / cm 2 , about 0.009 mg / cm 2 , about 0.01mg / cm 2 , about 0.02 mg / cm 2 , about 0.03mg / cm 2 , about 0.04 mg / cm 2 , about 0.05mg / cm 2 , about 0.06mg / cm 2 , about 0.07mg / cm 2 , about 0.08 mg / cm 2 , about 0.09mg / cm 2 , about 0.1mg / cm 2 , about 0.15mg / cm 2 , about 0.2mg / cm 2 , about 0.25mg / cm 2 , about 0.3mg / cm 2, about 0.35mg / cm 2 or about 0.4 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0157] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.005 mg / cm. 2 , about 0.006mg / cm 2 , about 0.007mg / cm 2 , about 0.008mg / cm 2 , about 0.009 mg / cm 2 , about 0.01mg / cm 2 , about 0.015mg / cm 2 , about 0.02 mg / cm 2 , about 0.025mg / cm 2 , about 0.03mg / cm 2 , about 0.035mg / cm 2 , about 0.04 mg / cm 2 , about 0.045mg / cm 2 , about 0.05mg / cm 2 , about 0.055mg / cm 2 , about 0.06mg / cm 2 , about 0.065mg / cm 2 , about 0.07mg / cm 2 , about 0.075mg / cm 2 , about 0.08 mg / cm 2 , about 0.085mg / cm 2 , about 0.09mg / cm 2 , about 0.095mg / cm 2 or about 0.1 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0158] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.025 mg / cm 2 , about 0.02 mg / cm 2 , about 0.015mg / cm 2 , about 0.01mg / cm 2 , about 0.005mg / cm 2 , about 0.002mg / cm 2 , about 0.001mg / cm 2 , about 0.0005mg / cm2 , about 0.0002mg / cm 2 or about 0.0001 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0159] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.025 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0160] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.02 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0161] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.015 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0162] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.01 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0163] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.005 mg / cm. 2 is administered to the affected area of ​​the subject at a dose of

[0164] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.002 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0165] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.001 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0166] In some embodiments of the methods disclosed herein, KX-01 is present at about 0.0005 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0167] In some embodiments of the methods disclosed herein, KX-01 is about 0.0002 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0168] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.0001 mg / cm 2 is administered to the affected area of ​​the subject at a dose of

[0169] In some embodiments of the methods disclosed herein, the KX-01 is about 0.01 cm 2 ~about 300cm 2 The compound is administered to the affected area of ​​a subject.

[0170] In some embodiments of the methods disclosed herein, the KX-01 is about 0.01 cm 2 ~about 200cm 2 , about 0.01 cm 2 ~Approx. 100cm 2 , about 0.01 cm 2 ~Approx. 75cm 2 , about 0.01 cm 2 ~about 50cm 2 or about 0.01 cm 2 ~about 25cm 2 The compound is administered to the affected area of ​​a subject.

[0171] In some embodiments of the methods disclosed herein, KX-01 is administered in an amount of about 0.1 cm 2 ~Approx. 625cm 2 , about 0.1cm 2 ~about 300cm 2 , about 0.1cm 2 ~Approx. 150cm 2 , about 0.1cm 2 ~Approx. 100cm 2 , about 0.1cm 2 ~Approx. 75cm 2 or about 0.1 cm 2 ~about 50cm 2 The compound is administered to the affected area of ​​a subject.

[0172] In some embodiments of the methods disclosed herein, KX-01 is administered in an amount of about 0.1 cm 2 ~about 300cm 2 , about 0.1cm 2 ~about 200cm 2 , about 0.1cm 2 ~Approx. 100cm 2 , about 0.1cm 2 ~Approx. 75cm 2 , about 0.1cm 2 ~about 50cm 2 or about 0.1 cm 2 ~about 25cm 2 The compound is administered to the affected area of ​​a subject.

[0173] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 10 cm 2 ~Approx. 625cm 2 , about 10cm 2 ~about 300cm 2 , about 10cm 2 ~about 200cm 2 , about 10cm 2 ~Approx. 100cm 2 , about 10cm 2 ~Approx. 75cm 2 , about 10cm 2 ~about 50cm 2 or about 10cm 2 ~about 25cm 2 The compound is administered to the affected area of ​​a subject.

[0174] In some embodiments of the methods disclosed herein, KX-01 is about 16 cm 2 ~Approx. 625cm 2 , about 16cm 2 ~about 300cm 2 , about 16cm 2 ~about 200cm 2 , about 16cm 2 ~Approx. 100cm 2 , about 16cm 2 ~Approx. 75cm 2 , about 16cm 2 ~about 50cm 2 or about 16cm 2 ~about 25cm 2The compound is administered to the affected area of ​​a subject.

[0175] In some embodiments of the methods disclosed herein, KX-01 is administered in an amount of about 1 cm 2 ~about 300cm 2 , about 1cm 2 ~about 200cm 2 , about 1cm 2 ~Approx. 100cm 2 , about 1cm 2 ~Approx. 75cm 2 , about 1cm 2 ~about 50cm 2 or about 1 cm 2 ~about 25cm 2 The compound is administered to the affected area of ​​a subject.

[0176] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 10 cm 2 ~about 300cm 2 , about 10cm 2 ~about 200cm 2 , about 10cm 2 ~Approx. 100cm 2 , about 10cm 2 ~Approx. 75cm 2 , about 10cm 2 ~about 50cm 2 or about 10cm 2 ~about 25cm 2 The compound is administered to the affected area of ​​a subject.

[0177] In some embodiments of the methods disclosed herein, KX-01 is about 25 cm 2 ~about 300cm 2 , about 25cm 2 ~about 200cm 2 , about 25cm 2 ~Approx. 100cm 2 , about 25cm 2 ~Approx. 75cm 2 Or about 25cm 2 ~about 50cm 2 The compound is administered to the affected area of ​​a subject.

[0178] In some embodiments of the methods disclosed herein, KX-01 is administered to a patient at a site approximately 25 cm 2 ~Approx. 100cm 2 , about 25cm 2 ~about 90cm 2 , about 25cm 2 ~about 80cm 2 or about 25cm 2 ~about 70cm 2 , about 25cm 2 ~about 60cm 2 , about 25cm 2 ~about 50cm 2 , about 25cm 2 ~about 40cm 2 or about 25cm 2 ~about 30cm 2 The compound is administered to the affected area of ​​a subject.

[0179] In some embodiments of the methods disclosed herein, the KX-01 has a thickness of about 0.01 cm 2 , 0.1cm 2 , 1cm 2 , 2cm 2 , 3cm 2 , 4cm 2 , 5cm 2 , 6cm 2 , 7cm 2 , 8cm 2 , 9cm 2 , 10cm 2 , 15cm 2 , 20cm 2 , 25cm 2 , 30cm 2 , 35cm 2 , 40cm 2 , 45cm 2 , 50cm 2 , 55cm 2 , 60cm 2 , 65cm 2 , 70cm 2 , 75cm 2 , 80cm 2 , 85cm 2 , 90cm 2 , 95cm 2 or 100cm 2 The compound is administered to the affected area of ​​a subject.

[0180] In some embodiments of the methods disclosed herein, KX-01 is about 25 cm 2 , about 30cm 2 , about 35cm 2 , about 40cm 2 , about 45cm 2 , about 50cm 2 , approx. 55cm 2 , about 60cm 2 , approx. 65cm 2 , about 70cm 2 , about 75cm 2 , about 80cm 2 , approx. 85cm 2 , about 90cm 2 , about 95cm 2 Or about 100cm 2 The compound is administered to the affected area of ​​a subject.

[0181] In some embodiments of the methods disclosed herein, KX-01 is administered to an affected area of ​​the subject, and the affected area is the skin.

[0182] In some embodiments of the methods disclosed herein, KX-01 is administered to an affected area of ​​the subject, the affected area of ​​skin being located in one or more locations independently selected from the scalp, forehead, forearm, face, nose, ear, eyelid, lip, neck, arm, elbow, hand, trunk, leg, knee and foot.

[0183] In some embodiments of the methods disclosed herein, the subject has more than one affected area.

[0184] In some aspects of the methods disclosed herein, the affected area is contiguous. In some aspects of the methods disclosed herein, the affected area is discontinuous.

[0185] In some embodiments of the methods disclosed herein, the subject has more than one affected area located in one or more locations independently selected from the scalp, forehead, forearm, face, nose, ears, eyelids, lips, neck, arms, elbows, hands, trunk, legs, knees and feet.

[0186] In some embodiments of the methods disclosed herein, KX-01 is administered once a week, once every three days, once every two days, once a day, twice a day, three times a day, or four times a day.

[0187] In some embodiments of the methods disclosed herein, KX-01 is administered once daily or twice daily.

[0188] In some embodiments of the methods disclosed herein, KX-01 is administered once daily.

[0189] In some embodiments of the methods disclosed herein, KX-01 is administered on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 8th, 9th, 10th, 11th, 12th, 13th, 14th, 15th, 16th, 17th, 18th, 19th, 20th, 21st, 22nd, 23rd, 24th, 25th, 26th, 27th, 28th, The vaccine is administered for 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59 or 60 days.

[0190] In some embodiments of the methods disclosed herein, KX-01 is administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 days.

[0191] In some embodiments of the methods disclosed herein, KX-01 is administered for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days.

[0192] In some embodiments of the methods disclosed herein, KX-01 is administered for 1, 2, 3, 4, 5, 6, or 7 days.

[0193] In some embodiments of the methods disclosed herein, KX-01 is administered for 1 day, 2 days, 3 days, 4 days, or 5 days.

[0194] In some embodiments of the methods disclosed herein, KX-01 is administered for 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 28 days.

[0195] In some embodiments of the methods disclosed herein, KX-01 is administered for 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 28 days.

[0196] In some embodiments of the methods disclosed herein, KX-01 is administered for 6, 7, 8, 9, 10, 11, 12, 13, 14 or 28 days.

[0197] In some embodiments of the methods disclosed herein, KX-01 is administered for 8, 9, 10, 11, 12, 13, 14 or 28 days.

[0198] In some embodiments of the methods disclosed herein, KX-01 is administered for 10, 11, 12, 13, 14 or 28 days.

[0199] In some embodiments of the methods disclosed herein, KX-01 is administered for one day.

[0200] In some embodiments of the methods disclosed herein, KX-01 is administered for two days.

[0201] In some embodiments of the methods disclosed herein, KX-01 is administered for three days.

[0202] In some embodiments of the methods disclosed herein, KX-01 is administered for four days.

[0203] In some embodiments of the methods disclosed herein, KX-01 is administered for 5 days.

[0204] In some embodiments of the methods disclosed herein, KX-01 is administered for 6 days.

[0205] In some embodiments of the methods disclosed herein, KX-01 is administered for 7 days.

[0206] In some embodiments of the methods disclosed herein, KX-01 is administered for 8 days.

[0207] In some embodiments of the methods disclosed herein, KX-01 is administered for 9 days.

[0208] In some embodiments of the methods disclosed herein, KX-01 is administered for 10 days.

[0209] In some embodiments of the methods disclosed herein, KX-01 is administered for 11 days.

[0210] In some embodiments of the methods disclosed herein, KX-01 is administered for 12 days.

[0211] In some embodiments of the methods disclosed herein, KX-01 is administered for 14 days.

[0212] In some embodiments of the methods disclosed herein, KX-01 is administered for 28 days.

[0213] In some embodiments of the methods disclosed herein, KX-01 is administered 1, 2, 3, 4, 5, 6, or 7 days per week.

[0214] In some embodiments of the methods disclosed herein, KX-01 is administered 2, 3, 4, 5, 6, or 7 days per week.

[0215] In some embodiments of the methods disclosed herein, KX-01 is administered 3, 4, 5, 6, or 7 days per week.

[0216] In some embodiments of the methods disclosed herein, KX-01 is administered 4, 5, 6, or 7 days per week.

[0217] In some embodiments of the methods disclosed herein, KX-01 is administered 5, 6, or 7 days per week.

[0218] In some embodiments of the methods disclosed herein, KX-01 is administered 6 or 7 days per week.

[0219] In some embodiments of the methods disclosed herein, KX-01 is administered 7 days per week.

[0220] In some embodiments of the methods disclosed herein, KX-01 is administered six days per week.

[0221] In some embodiments of the methods disclosed herein, KX-01 is administered five days per week.

[0222] In some embodiments of the methods disclosed herein, KX-01 is administered 1, 2, 3, 4, 5, or 6 days per week.

[0223] In some embodiments of the methods disclosed herein, KX-01 is administered 2, 3, 4, 5, or 6 days per week.

[0224] In some embodiments of the methods disclosed herein, KX-01 is administered once or twice daily for multiple consecutive days per week, followed by discontinuation of administration for the remainder of the week.

[0225] In some embodiments of the methods disclosed herein, KX-01 is administered once or twice daily on every other day.

[0226] In some embodiments of the methods disclosed herein, KX-01 is administered once or twice daily, every 3, 4, 5, 6 or 7 days.

[0227] In some embodiments of the methods disclosed herein, KX-01 is administered once or twice daily for two consecutive days every 3, 4, 5, 6, or 7 days.

[0228] In some embodiments of the methods disclosed herein, KX-01 is administered once or twice daily for three consecutive days every 4, 5, 6, or 7 days.

[0229] In some embodiments of the methods disclosed herein, KX-01 is administered once or twice daily for four consecutive days, every 5, 6, or 7 days.

[0230] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for seven days.

[0231] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for 14 consecutive days.

[0232] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for 21 consecutive days.

[0233] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for 28 consecutive days.

[0234] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for 14 consecutive days, followed by 7 days of not being administered.

[0235] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for 14 consecutive days, followed by 7 days of no administration, followed by 7 days of administration of KX-01 once daily.

[0236] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for 14 consecutive days, followed by 7 days of no administration, followed by 14 days of administration of KX-01 once daily.

[0237] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for 14 consecutive days, followed by 7 days of no administration, followed by 7 days of twice daily administration of KX-01.

[0238] In some embodiments of the methods disclosed herein, KX-01 is administered once daily for 14 consecutive days, followed by 7 days of no administration, followed by 14 days of administration of KX-01 twice daily.

[0239] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for seven days.

[0240] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for 14 consecutive days.

[0241] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for 21 consecutive days.

[0242] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for 28 consecutive days.

[0243] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for 14 consecutive days, followed by 7 days without administration.

[0244] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for 14 consecutive days, followed by 7 days of no administration, followed by 7 days of administration of KX-01 twice daily.

[0245] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for 14 consecutive days, followed by 7 days of no administration, followed by 14 days of administration of KX-01 twice daily.

[0246] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for 14 consecutive days, followed by 7 days of no administration, followed by 7 days of KX-01 administered once daily.

[0247] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily for 14 consecutive days, followed by 7 days of no administration, followed by 14 days of administration of KX-01 once daily.

[0248] In some embodiments of the methods disclosed herein, KX-01 is administered until psoriasis is completely treated.

[0249] In some embodiments of the methods disclosed herein, KX-01 is administered until psoriasis is completely treated, ie, until the psoriasis is no longer present in the subject.

[0250] In some embodiments of the methods disclosed herein, KX-01 is administered locally.

[0251] In some embodiments of the methods disclosed herein, KX-01 is administered once daily at a concentration of about 0.1 mg / g.

[0252] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.1 mg / g once daily for 12 days.

[0253] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.1 mg / g once daily for 14 days.

[0254] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.1 mg / g once daily for 28 days.

[0255] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.1 mg / g once daily for five days.

[0256] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily at a concentration of about 0.1 mg / g.

[0257] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.1 mg / g twice daily for 12 days.

[0258] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.1 mg / g twice daily for 14 days.

[0259] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.1 mg / g twice daily for 28 days.

[0260] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 0.1 mg / g twice daily for five days.

[0261] In some embodiments of the methods disclosed herein, KX-01 is administered once daily at a concentration of about 1.0 mg / g.

[0262] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 1.0 mg / g once daily for 12 days.

[0263] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 1.0 mg / g once daily for 14 days.

[0264] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 1.0 mg / g once daily for 28 days.

[0265] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 1.0 mg / g once daily for five days.

[0266] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily at a concentration of about 1.0 mg / g.

[0267] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 1.0 mg / g twice daily for 12 days.

[0268] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 1.0 mg / g twice daily for 14 days.

[0269] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 1.0 mg / g twice daily for 28 days.

[0270] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 1.0 mg / g twice daily for five days.

[0271] In some embodiments of the methods disclosed herein, KX-01 is administered once daily at a concentration of about 10 mg / g.

[0272] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 10 mg / g once daily for 12 days.

[0273] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 10 mg / g once daily for 14 days.

[0274] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 10 mg / g once daily for five days.

[0275] In some embodiments of the methods disclosed herein, KX-01 is administered twice daily at a concentration of about 10 mg / g.

[0276] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 10 mg / g twice daily for 12 days.

[0277] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 10 mg / g once daily for 14 days.

[0278] In some embodiments of the methods disclosed herein, KX-01 is administered at a concentration of about 10 mg / g twice daily for five days.

[0279] In some aspects of the methods disclosed herein, KX-01 is administered as described in the preceding paragraph, followed by a first period during which KX-01 is not administered, followed by a second period during which KX-01 is administered.

[0280] In some embodiments, the first period is 1 week, 2 weeks, 3 weeks, or 4 weeks. In some embodiments, the first period is 2 weeks. In some embodiments, the second period is 1 week, 2 weeks, 3 weeks, or 4 weeks. In some embodiments, the second period is 2 weeks. In some embodiments, KX-01 is administered in the second period at the same dose as KX-01 was administered prior to the first period. In some embodiments, KX-01 is administered in the second period at a different dose than KX-01 was administered prior to the first period.

[0281] In some embodiments of the methods disclosed herein, administration of KX-01 reduces the number and / or severity of local skin reactions or other adverse side effects in a subject compared to other treatments for psoriasis, such as those described herein.

[0282] In some embodiments of the methods disclosed herein, administration of KX-01 reduces the number of subjects with local skin reactions or other adverse side effects compared to other treatments for psoriasis, such as those described herein.

[0283] In some aspects of the methods disclosed herein, the local skin reaction is selected from the group consisting of vesiculation, pustulation, sores, ulcers, redness, swelling, peeling, scaling, hard lumps, dryness, pus, and blistering.

[0284] In some embodiments of the methods disclosed herein, the other side effects are selected from the group consisting of application site pain, application site pruritus, application site irritation, application site swelling, application site burning, application site infection, periorbital swelling, nasopharyngitis, chills, sore throat, ptosis, puffy eyes, hypopigmentation, hyperpigmentation, and headache.

[0285] In some embodiments, the disclosure relates to KX-01 for use in the treatment and / or prevention of psoriasis (e.g., topical use). In some embodiments, KX-01 is for use in a subject in need thereof at the dose, dosage schedule, and / or at one or more affected areas described herein. In some embodiments, KX-01 is for use in a subject in need thereof at the dose, dosage schedule, and at one or more affected areas described herein. In some embodiments, KX-01 is for use in a subject in need thereof at the dose, dosage schedule, and at one or more affected areas described herein.

[0286] In some embodiments, KX-01 is for use in the dosages described herein.In some embodiments, KX-01 is for use in the dosing schedules described herein.In some embodiments, KX-01 is for use in subjects in need thereof in one or more affected areas described herein.

[0287] In some embodiments, the disclosure relates to the use of KX-01 (e.g., topical use) in the treatment and / or prevention of psoriasis. In some embodiments, KX-01 is used in a dose, dosage schedule, and / or in a subject in need thereof at one or more affected sites as described herein. In some embodiments, KX-01 is used in a dose, dosage schedule, and in a subject in need thereof at one or more affected sites as described herein. In some embodiments, KX-01 is used in a dose, dosage schedule, and in a subject in need thereof at one or more affected sites as described herein.

[0288] In some embodiments, KX-01 is used in the dosage described herein.In some embodiments, KX-01 is used in the dosing schedule described herein.In some embodiments, KX-01 is used in the subject in need thereof in one or more of the affected areas described herein.

[0289] In some embodiments, the disclosure relates to the use of KX-01 in the manufacture of a medicament for the treatment and / or prevention of psoriasis.In some embodiments, KX-01 is used in the dose, dosage schedule and / or in one or more affected areas of a subject in need thereof as described herein.In some embodiments, KX-01 is used in the dose, dosage schedule and in one or more affected areas of a subject in need thereof as described herein.In some embodiments, KX-01 is used in the dose, dosage schedule and in one or more affected areas of a subject in need thereof as described herein.

[0290] In some embodiments, KX-01 is used in the dosage described herein.In some embodiments, KX-01 is used in the dosing schedule described herein.In some embodiments, KX-01 is used in the subject in need thereof in one or more of the affected areas described herein.

[0291] Unless otherwise stated, the terms "KX-01" and "KX2-391" refer to the following structures: [ka] The basic form, or "free base," of a compound having the formula:

[0292] The term "KX-01 MSA" refers to the mesylate salt of KX-01, i.e., the salt compound produced by reacting KX-01 with methanesulfonic acid.

[0293] As used herein, "KX-01" may also be referred to as "KX01," "KX2-391," or "KX-2-391."

[0294] KX-01 and its salts, such as KX-01 MSA, and their preparation are disclosed in PCT Application Publication Nos. WO2008 / 082637, WO2008 / 144045, and WO2010 / 135429, which are incorporated by reference herein in their entireties.

[0295] Psoriasis is a chronic autoimmune skin disease that accelerates the growth cycle of skin cells. Psoriasis causes localized or generalized patches of red, itchy papules and plaques covered with white or silvery scales on the scalp, face, elbows, knees and lower back. Psoriasis can also appear on other body parts, such as the hands, feet, and other areas of the trunk and legs.

[0296] As used herein, the term "trunk" refers to a part of a subject that is not an arm, leg, or head.

[0297] Psoriasis is most commonly seen in subjects in early adulthood, for example, between about 15 and 35 years of age. Psoriasis may occur in children under the age of 10. A subject with psoriasis may have a single lesion or multiple lesions. In some embodiments of the methods disclosed herein, KX-01 is administered to a subject with psoriasis between about 0 and about 110 years of age. In some embodiments, the subject is between about 0 and about 10 years of age. In some embodiments, the subject is between about 10 and about 20 years of age. In some embodiments, the subject is between about 20 and about 30 years of age. In some embodiments, the subject is between about 30 and about 40 years of age. In some embodiments, the subject is between about 40 and about 50 years of age. In some embodiments, the subject is between about 50 and about 60 years of age. In some embodiments, the subject is between about 60 and about 70 years of age. In some embodiments, the subject is between about 70 and about 80 years of age. In some embodiments, the subject is between about 80 and about 90 years of age. In some embodiments, the subject is about 90 to about 100 years old. In some embodiments, the subject is about 90 to about 110 years old. In some embodiments, the subject is about 10 to about 40 years old. In some embodiments, the subject is about 15 to about 40 years old. In some embodiments, the subject is about 15 to about 35 years old. In some embodiments, the subject is about 15 to about 30 years old. In some embodiments, the subject is about 15 to about 25 years old. In some embodiments, the subject is about 60 to about 110 years old. In some embodiments, the subject is about 60 to about 100 years old. In some embodiments, the subject is about 60 to about 90 years old. In some embodiments, the subject is about 60 to about 80 years old. In some embodiments, the subject is about 60 to about 70 years old.

[0298] In some embodiments, psoriasis may increase the risk of developing certain cancers. In some embodiments, the cancer is squamous cell carcinoma. In some embodiments, the cancer is lymphoma.

[0299] Psoriasis includes five types: psoriasis vulgaris (most common), guttate psoriasis, intertriginous psoriasis, pustular psoriasis and erythroderma.Unless otherwise stated, the methods described herein are applicable to all clinical variants, including those listed herein.Psoriasis has been associated with other serious health conditions, including but not limited to diabetes, heart disease and depression.

[0300] In some embodiments, the psoriasis is plaque psoriasis, guttate psoriasis, intertriginous psoriasis, pustular psoriasis, or erythroderma. In some embodiments, the psoriasis is plaque psoriasis. In some embodiments, the psoriasis is guttate psoriasis. In some embodiments, the psoriasis is intertriginous psoriasis. In some embodiments, the psoriasis is pustular psoriasis. In some embodiments, the psoriasis is erythrodermic.

[0301] Treatments for psoriasis include both topical treatments, such as, but not limited to, steroid creams, dressings, phototherapy, oral medications, and injectables. Topical treatments include topical corticosteroids, vitamin D analogs (Dovonex, Vectical), anthralin (Dorito-Scalp), topical retinoids (Tazorac, Avage), calcineurin inhibitors (Prograf and Elidel), salicylic acid, coal tar, and moisturizers. Phototherapy (light therapy) treatments include exposure to ultraviolet light in sunlight or artificial light, UVB phototherapy, narrowband UVB phototherapy, Geckerman therapy, psoralen ultraviolet A (PUVA), and excimer laser. Treatments for psoriasis may also include kinase inhibitors, anti-immunotherapy agents, or anti-inflammatory agents (e.g., inhibitors of phosphodiesterase 4 or inhibitors of TNFα). Examples of psoriasis treatments include apremilast, methotrexate, tofacitinib, alefacept, etanercept, certolizumab-pegol, guselkumab, tildrakizumab, risankizumab, secukinumab, ixekizumab, brodalumab, efalizumab, adalimumab, ustekinumab, and infliximab. Oral or injectable treatments include retinoids, methotrexate (Rheumatrex), cyclosporine (Gengraf, Neoral), and biopharmaceuticals such as etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), ustekinumab (Stelara), golimumab (Simpony), apremilast (Otezla), secukinumab (Cosentyx), and ixekizumab (Taltz). Other treatments include thioguanine (Tabloid) and hydroxyurea (Droxithia, Hydrea). Alternative treatments include aloe vera, fish oil and Oregon grape.

[0302] The phrase "until psoriasis is eliminated", as used herein, refers to an instance in which a subject suffering from psoriasis has had lesions substantially or completely eliminated from the treatment area of ​​the subject. In some embodiments, "substantially" in this context refers to more than 50% of the psoriasis lesions eliminated from the treatment area of ​​the subject. In some embodiments, "substantially" refers to more than 60% of the psoriasis lesions eliminated from the treatment area of ​​the subject. In some embodiments, "substantially" refers to more than 70% of the psoriasis lesions eliminated from the treatment area of ​​the subject. In some embodiments, "substantially" refers to more than 80% of the psoriasis lesions eliminated from the treatment area of ​​the subject. In some embodiments, "substantially" refers to more than 90% of the psoriasis lesions eliminated from the treatment area of ​​the subject. In some embodiments, "substantially" refers to more than 95% of the psoriasis lesions eliminated from the treatment area of ​​the subject. In some embodiments, "substantially" refers to more than 99% of the psoriasis lesions eliminated from the treatment area of ​​the subject.

[0303] As used throughout the disclosure, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a method" includes a plurality of such methods, and reference to "a dosage" includes reference to one or more dosages and equivalents thereof known to those skilled in the art.

[0304] The term "comprising" is intended to mean that the method includes the recited elements, but does not exclude other elements. "Consisting essentially of," when used to define a method, is intended to mean excluding other elements that are of some essential importance to the combination when used for the intended purpose. Thus, a method consisting essentially of the elements defined herein does not exclude substantial method steps. "Consisting of" is intended to mean excluding more than substantial method steps. Embodiments defined by each of these transition terms are within the scope of this disclosure.

[0305] Unless otherwise specified, the terms "approximately" and "about" are synonymous. In some embodiments, "approximately" and "about" refer to ±5%, ±4.5%, ±4%, ±3.5%, ±3%, ±2.5%, ±2%, ±1.75%, ±1.5%, ±1.25%, ±1%, ±0.9%, ±0.8%, ±0.7%, ±0.6%, ±0.5% ±0.4%, ±0.3%, ±0.2%, ±0.1%, ±0.09%, ±0.08%, ±0.07%, ±0.06%, ±0.05%, ±0.04%, ±0.03%, ±0.02%, or ±0.01% of a stated amount, value, or duration. In some embodiments, "approximately" and "about" refer to ±2.5%, ±2%, ±1.75%, ±1.5%, ±1.25%, ±1%, ±0.9%, ±0.8%, ±0.7%, ±0.6%, ±0.5% of the recited amount, value, or duration. In some embodiments, "approximately" and "about" refer to ±1% of the recited amount, value, or duration. In some embodiments, "approximately" and "about" refer to ±0.5% of the recited amount, value, or duration. In some embodiments, "approximately" and "about" refer to ±0.1% of the recited amount, value, or duration.

[0306] The term "subject" includes any organism having or at risk of developing psoriasis. In some embodiments, the term "subject" refers to a mammal having or at risk of developing psoriasis. In some embodiments, the term subject refers to a human having or at risk of developing psoriasis. The term "patient" is meant to be synonymous with "subject" unless otherwise specified, and may be used interchangeably.

[0307] The term "therapeutically effective amount" as used herein refers to the amount of a preparation, e.g., KX-01, to treat, improve, or prevent an identified disease or condition, e.g., psoriasis, or to exert a detectable therapeutic or suppressive effect. The effect can be detected by any analytical method known in the art. The exact effective amount for each subject will vary depending on the subject's weight, size, and health condition; the nature and extent of symptoms; and the therapeutic agent or combination of therapeutic agents selected for administration. The therapeutically effective amount for each given situation can be determined by routine experimentation, which is within the skill and judgment of the clinician.

[0308] For any compound, the therapeutically effective amount can be estimated in an animal model, usually rats, mice, rabbits, dogs or pigs. Animal models may also be used to determine appropriate concentration ranges and routes of administration. Such information can then be used to determine useful doses and routes of administration in humans. Therapeutic / prophylactic efficacy and toxicity can be determined using standard pharmaceutical procedures in cell cultures or experimental animals, e.g., ED 50 (therapeutically effective dose in 50% of the population) and LD 50 (the dose lethal to 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index, and the LD 50 / ED 50 The dosage may vary within this range depending on the dosage form employed and the sensitivity of the subject.

[0309] Dosage and administration are adjusted to provide sufficient level of active ingredient or maintain desired effect.Factors that can be considered include severity of disease, location of disease in subject, general health condition of subject, age, weight and sex of subject, diet, time and frequency of administration, drug combination, reaction sensitivity, and resistance / response to treatment.KX-01 may be administered daily, every other day, every 3rd day, every 4th day, every 5th day, every 6th day, weekly, every other week, or once every 2 weeks, depending on half-life and clearance rate.

[0310] For any of the methods described herein, KX-01 may be administered topically, intradermally, interepidermally, intragingivally, intraocularly, intranasally, intraocularly, transdermally, periodontally, subconjunctivally, sublingually, transmucosally, or auricularly. In some embodiments, KX-01 may be administered topically.

[0311] All percentages and ratios used herein are by weight unless otherwise specified.

[0312] All documents cited herein, including any cross-referenced or related patents or applications, are incorporated herein by reference in their entirety unless expressly excluded or limited. The citation of any document is not an admission that it is prior art with respect to any subject matter disclosed or claimed herein or that it alone, or in combination with any other reference, teaches, suggests or discloses such subject matter. Furthermore, if a meaning or definition of a term in this document conflicts with a meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall control.

[0313] While particular embodiments of the present disclosure have been illustrated and described, various other changes and modifications can be made without departing from the spirit and scope of the disclosure, and the appended claims include within their scope all such changes and modifications within the scope of the disclosure.

[0314] Other features and advantages of the present disclosure are apparent from the various examples, which are provided to illustrate various elements and methodologies useful in practicing the present disclosure.

[0315] The examples do not limit the claimed disclosure: based on this disclosure, one of ordinary skill in the art will be able to identify and employ other elements and methodologies useful in practicing the present disclosure. EXAMPLES

[0316] Example 1. Clinical Activity in Subjects with Psoriasis: Treatment with KX-01 A signal of clinical activity was observed in the first cohort of subjects with psoriasis treated with KX-01 (tirbanibulin) 1% ointment daily for 5 days in a Phase I clinical trial.

[0317] Six subjects with psoriasis with a total area score (TAS) of 4-8 (based on the sum of the erythema, elevation, and scaling scores) were evaluated. All subjects showed improvement in their TAS scores. One subject experienced complete resolution of skin scaling and another subject experienced improvement in the thickness of psoriatic plaques. Treatment was found to be well tolerated. Mild (grade 1) skin burning and irritation were observed in only one subject each. There was no significant absorption of KX-01 systemically. A good safety profile of KX-01 ointment in the treatment of psoriasis was observed in the study.

[0318] Subjects in the clinical study of KX-01 ointment were administered up to 250 mg of KX-01 ointment (5 mg / cm 2 [Dosage] x 25cm 2 [area administered] x 2 [safety factor for larger application areas]). This amount of 0.01% or 0.1% concentration ointment contains 0.025 mg or 0.25 mg of KX-01. Thus, the amount of KX-01 delivered to the skin of an average 60 kg subject is 0.025 or 0.25 mg / 60 kg / dose, or 0.00042 or 0.0042 mg / kg / dose. This dose is approximately 29700 or 2970 times lower than the 12.4 mg / kg / dose of KX-01, which caused mild to moderate skin irritation but no systemic adverse effects in rats after 6 days of twice-daily dermal administration. The safety margin at the administered dermal KX-01 dose indicates that, based on non-clinical studies in animals, there is little risk of systemic adverse effects in humans under clinical study conditions for KX-01 ointment.

[0319] Example 2. KX01 treatment of rats, rabbits and minipigs Administration of KX-01 ointment to rats (for 6 days) and rabbits (twice daily for 7 days, with a single dose on day 8) twice daily at concentrations and amounts delivering up to 12.4 (rats) or 2.0667 (rabbits) mg / kg KX-01 in the ointment caused mild to moderate skin irritation but no signs of systemic adverse effects. Plasma concentrations of KX-01 were very low after a single dose of KX-01 ointment, but after 6 days of repeated dermal administration, plasma concentrations reached or exceeded those seen at the no-observed-effect level in a 28-day oral toxicity study in rats.

[0320] KX-01 1% administered once daily as KX-01 ointment was studied in minipigs with skin covering 10% of the body surface area for 28 consecutive days. Results showed very minimal to mild edema, very minimal to severe erythema and crusting, and / or scaling, fissures, scabs, ulcers, weight loss, and changes in liver, kidney, and blood profiles at the drug application sites. Most of these findings resolved by the final week of recovery.

[0321] Example 3. Phase I dose escalation study A Phase I dose escalation study will be conducted to evaluate the safety, tolerability, and activity of three different strengths of topical KX-01 in treating subjects with plaque-type psoriasis. In Stage I, each subject will be randomly assigned to KX-01 (0.01%, n=6) or placebo (n=2) prior to the first dose of study drug (KX-01 or placebo). Twenty-two subjects will be recruited into three stages.

[0322] Each subject in Stage I will undergo 2 weeks of treatment followed by 1 week off, another 2 weeks of treatment, and then 2 weeks of follow-up. At the end of each subject's follow-up, after satisfactory collaborative review of the lower intensity (0.01%) safety data, if there are no significant safety concerns (significant safety concerns defined as 2 or more subjects in the KX-01 arm having CTCAE grade ≥ 3 or severe adverse drug reaction) and with unanimous consent of the sponsor and principal investigator, a Stage II study will begin in which each subject will be randomly assigned to receive KX-01 (0.1%, n=6) or placebo (n=2) prior to the first dose.

[0323] Each subject in Stage II will undergo 4 weeks of treatment followed by 2 weeks of follow-up. At the end of each subject's follow-up, after a satisfactory collaborative review of the lower strength (0.1%) safety data, Stage III will follow if there are no significant safety concerns. Stage III will involve a single-arm study (n=6) in which each subject will receive 1% KX-01 once daily for 5 consecutive days, followed by post-treatment follow-up on days 6, 15, and 29. ●Stage I: 6 subjects (KX-01 0.01% [0.1 mg / g]) + 2 subjects (placebo) ●Stage II: 6 subjects (KX-01 0.1% [1.0 mg / g]) + 2 subjects (placebo) ●Stage III: 6 subjects (KX-01 1% [10mg / g])

[0324] Subjects will present to the study center for a clinic visit. Stage I (see Tables 1A and 1B) Visit 1: Screening within 28 days prior to the first application of IMP Visit 2: Week 1 (Day 1 / Baseline) Visit 3: Week 2 (Day 8 ± 3 / After 1 week of continuous treatment) Visit 4: Week 3 (Day 15 ± 3 / After 2 consecutive weeks of treatment) Visit 5: Week 4 (Day 22 ± 3 / 1 week after drug holiday) Visit 6: Week 6 (Day 36 ± 3 / After 2 more consecutive weeks of treatment) Visit 7: Week 8 (Day 50 ± 3 / 2 weeks post-treatment follow-up) Stage II (see Tables 2A and 2B) Visit 1: Screening within 28 days prior to the first application of IMP Visit 2: Week 1 (Day 1 / Baseline) Telephone interview (day 8 ± 3, after one consecutive week of treatment) Visit 3: Week 3 (Day 15 ± 3 / After 2 consecutive weeks of treatment) Visit 4: Week 5 (Day 29 ± 3 / After 4 consecutive weeks of treatment) Visit 5: Week 7 (Day 43 ± 3 / 2 weeks post-treatment follow-up) Stage III (see Table 3) Visit 1: Screening within 28 days prior to the first application of IMP Visit 2: Day 1, baseline Visit 3: Day 6 ± 1, after 5 consecutive days of treatment Visit 4: Day 15 ± 2, 10 days post-treatment follow-up Visit 5: Day 29 ± 2, after 24 days of follow-up after treatment

[0325] IMP (treatment or placebo) is applied to a single lesion. For stages I and II, subjects apply IMP topically twice daily (at least 4 hours apart, approximately 8-12 hours apart is recommended) to the selected treatment lesion, regardless of lesion improvement. For stage I, each subject receives IMP for 14 consecutive days, followed by a one-week washout period, then receives IMP for another 14 consecutive days. For stage II, each subject receives IMP for 28 consecutive days. For stage III, each subject receives IMP once daily for 5 consecutive days. For stages I and II, blood samples for determination of KX-01 concentrations are taken before the morning dose on designated visit days to the study center (stage I: days 1, 8 ± 3, 15 ± 3, 22 ± 3; stage II: days 1, 15 ± 3, 29 ± 3) (see Table 4). For Stage III, blood samples for drug concentrations will be taken pre-dose on Day 1, and on Days 6±1 and 15±2. The duration of the study is approximately 3 months for each subject (see Table 4).

[0326] Inclusion criteria Subjects who meet the following inclusion criteria will be considered eligible to participate in the study: 1. Male and female subjects aged 20 years or older with plaque-type psoriasis. 2. Subject had a confirmed diagnosis of chronic plaque-type psoriasis for at least 6 months (no newly confirmed flares within 30 days prior to screening). 3. At least 16cm in size for stages I and II 2 And 625cm 2 Less than (≧16cm 2 And ≦625cm 2 ) and for stage III, size is at least 16 cm 2 And 100cm 2 Less than (≧16cm 2 And ≦100cm 2 A single lesion of 0.01 mm or less in size (0.01 mm or less) will be selected as the target lesion (assessed at screening and on Day 1). The lesion should be in an area sufficient for application of IMP and should meet the following criteria: Lesions located on the trunk and / or extremities, e.g., on the head, palms or soles. Intertriginous or genito-anal areas are not suitable. • No evidence of atrophy in the area selected for treatment. 4. Medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG), and laboratory investigations should be clinically insignificant or within the laboratory reference ranges for relevant laboratory tests, unless the investigator considers the deviations to be irrelevant to the study objectives. 5. There are no other obstacles that, in the opinion of the Investigator, might prevent the subject from participating safely in the study or interfere with the evaluation of the subject's psoriasis. 6. Subject is able to discontinue use of any systemic medications or treatments for psoriasis (e.g., oral or injectable psoriasis medications, psoralens long wave ultraviolet light [PUVA] therapy, herbal remedies, etc.). 7. For women, one of the following conditions must be met: If there is no possibility of pregnancy: - Having been surgically sterilized, having had a hysterectomy, or having amenorrhea for the following period: - ≥ 12 months and considered postmenopausal. Postmenopausal status is confirmed by evaluation of follicle-stimulating hormone (FSH) (supported by FSH > 40 mIU / mL and estradiol < 40 pg / mL [< 147 pmol / L]). If you think you might be pregnant: * Negative serum pregnancy test at screening and not breastfeeding. If this test is positive the subject will be removed from the study. In the rare situation in which a subject is found to be pregnant after receiving IMP, every effort should be made to follow her to term. * Must agree to abstain from sexual activity (if this is the subject's usual lifestyle) or use an accepted method of contraception and agree to continue the same method throughout the study. Examples of reliable methods of contraception include oral contraceptives (ensuring stable dose for at least 4 weeks prior to the first dose of IMP), injectable or implantable contraceptives, intrauterine devices, and barrier methods in combination with another method of contraception. o Other methods are acceptable if the researcher determines they are reliable. 8. Male subjects with fertile partners must be willing to use contraception throughout the study and for 3 months after treatment and must not donate sperm during the study and for 3 months thereafter. 9. Subject must be able to provide written informed consent prior to the initiation of any study-related procedures and be able to comply with all requirements of the study, including study visits and restrictions.

[0327] Exclusion criteria Subjects meeting one or more of the exclusion criteria will not be considered eligible to participate in the study. 1. History of hypersensitivity to IMP or to medicines with a similar chemical structure. 2. The presence of skin disorders other than psoriasis in the areas to be evaluated, including any form of inflammatory or non-inflammatory skin disorder that may interfere with the determination of efficacy or tolerability of IMP. 3. Severe psoriasis or any form of psoriasis other than plaque psoriasis. 4. All systemic psoriasis medications, including PUVA radiation therapy or other systemic immunosuppressants, are not permitted within 5 half-lives or 4 weeks (whichever is longer) prior to the first dose of IMP, i.e. methotrexate, cyclosporine, PUVA and corticosteroids (topical and oral) are not permitted within 4 weeks prior to the first dose of IMP. 5. Use of topical therapy for psoriasis, including ultraviolet B, on study target lesions within 2 weeks prior to the first dose of IMP. Use of topical calcipotriol or ultraviolet B for psoriasis at doses up to 30 g per week or other nonsystemically absorbed topical agents on untreated lesions is permitted during the study. 6. Prior treatment with anti-TNF / IL-12 / IL-23 or any other monoclonal antibody within 3 months prior to the first dose of IMP. 7. Presence or history of any clinically significant acute or chronic illness and at the investigator's discretion that may interfere with subject participation or study results. 8. Subject with drug-induced psoriasis and unable to discontinue the causative agent. 9. Subject is using prescription or non-prescription systemic medications that may affect psoriasis (e.g., vitamins and dietary herbal supplements, paracetamol, aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs)) and is unable to maintain a stable dose or discontinue the dose for the duration of the study. 10. Participation in another study with an experimental drug (where the last dose of prior IMP was within 4 weeks (or 5 elimination half-lives for chemicals or 2 elimination half-lives for antibodies or insulin, whichever is longer) prior to administration of IMP in this study), at the investigator's discretion. 11. Positive serum pregnancy test (beta-human chorionic gonadotropin [β-HCG]) or breastfeeding. 12. Vulnerable subjects, e.g. people in custody.

[0328] Duration of treatment On day 1, for each subject, tumors measuring at least 16 cm in size for stages I and II were 2 The upper limit is 625cm 2 and for stage III, at least 16 cm in size 2 At 100cm 2 Less than (≧16cm 2 And ≦100cm 2 A single treatment lesion consisting of active psoriatic skin lesions of 0.1 mm or less will be selected. Skin areas for IMP application will be marked and checked at each visit.

[0329] For stages I and II, subjects will receive 0.01% KX-01 (stage I) or 0.1% KX-01 (stage II) or placebo at twice daily strengths during the treatment period. For stage III, subjects will receive 1% KX-01 ointment at once daily strength for five consecutive days.

[0330] Follow-up survey For stages I and II, subjects will visit the study center 2 weeks after the last dose of IMP to evaluate any new or ongoing AEs and skin lesions. For stage III, subjects will undergo post-treatment follow-up on days 6, 15, and 29.

[0331] Target Area Score Changes in target area scores (TAS) between baseline and EOT will be measured for each target lesion. TAS will be administered by the investigator or a qualified individual, and when possible, the TAS for each individual subject will be completed by the same assessor at all time points.

[0332] At baseline and at specific time points, investigators rate individual signs of lesions, including erythema, plaque elevation, and scaling, on a 5-point scale: 0 (absent), 1 (mild), 2 (moderate), 3 (severe), and 4 (very severe). The TAS, which can range from 0 to 12, corresponds to the sum of the three variables above, including erythema, plaque elevation, and scaling.

[0333] Table 1A. Stage I evaluation schedule [Table 1] [Table 2] ECG = electrocardiogram; IMP = investigational drug; TAS = target area score

[0334] Table 1B. Stage I Evaluation Schedule [Table 3]

[0335] Table 2A. Stage II Evaluation Schedule [Table 4] [Table 5]

[0336] Table 2B. Stage II Evaluation Schedule [Table 6] ECG = electrocardiogram; IMP = investigational drug; TAS = target area score

[0337] Table 3: Stage III evaluation schedule [Table 7] [Table 8] ECG = electrocardiogram; IMP = investigational drug; TAS = target area score 1. Recorded medical history will be updated on Day 1 as necessary. 2. Includes height and weight at screening. 3. Systolic and diastolic blood pressure, pulse and temperature, and respiratory rate are recorded. 4. Perform a standard 12-lead electrocardiogram. 5. Hematology (Ethylenediaminetetraacetic acid [EDTA tubes]): WBC, RBC, hemoglobin, hematocrit, platelets, neutrophils, eosinophils, basophils, monocytes and lymphocytes (differential, absolute and percentage), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC). Clinical Chemistry (Serum Separator Tubes [SST]): Potassium, Sodium, Urea, Creatinine, Uric Acid, Calcium, Protein, Albumin, Total Bilirubin, Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and AC Glucose, Triglycerides, Bilirubin, Cholesterol. Urinalysis (dipstick): PH, protein, glucose, ketones, bilirubin, urobilinogen, blood, nitrites, white blood cells and specific gravity. Light microscopy as required - red blood cells, white blood cells, hyaline casts, cellular casts, granular casts and epithelial cells. 6. Serum pregnancy test (quantitative β-HCG [beta-human chorionic gonadotropin] method) at screening. Urine pregnancy test at all other visits. Postmenopausal status confirmed by follicle-stimulating hormone (FSH) assessment (supported by FSH >40 mIU / mL and estradiol <40 pg / mL [<147 pmol / L]). 7. See Section 7.2.10. 8. Collect approximately 10 mL of blood sample for drug concentration measurement. 9. A telephone interview will be conducted by the study coordinator on Day 8 ± 3 to assess compliance and any adverse drug reactions. If any severe (>Grade 2) adverse drug reaction is suspected, an unscheduled early visit will be arranged if possible. 10. For stage III, the treatment period is very short and the window allowance makes a big difference in the treatment period. Therefore, subjects need to apply the KX01 dose accurately for 5 consecutive days. There is no window allowance. For subjects attending the Day 11.5 visit, blood samples for PK will be collected prior to the final dose.

[0338] (Table 4) Blood volume [Table 9] * A screening serum pregnancy test (females only) will be performed on samples collected for clinical chemistry.

[0339] Example 4. Results of KX01 administration The KX-01 ointment 0.01% twice-daily regimen was demonstrated to be excellent and well tolerated by most subjects. Grade 1 drug-related tenderness was the only adverse event arising from treatment. No serious adverse events (SAEs) were reported.

[0340] Equivalent The present disclosure may be embodied in other specific forms without departing from its spirit or essential characteristics. The foregoing embodiments are therefore considered in all respects to be illustrative rather than limiting on the disclosure described herein. The scope of the present disclosure is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalence of the claims are intended to be embraced therein.

Claims

1. A method for treating and / or preventing psoriasis comprising administering to a subject in need thereof a therapeutically effective amount of KX-01: 【Chemistry 1】 or a pharma- ceutically acceptable salt thereof.

2. 2. The method of claim 1, wherein KX-01 is administered to the subject at a dose of about 0.1 mg to about 10 mg, about 0.2 mg to about 5 mg, or about 0.5 mg to about 2.5 mg to the affected area.

3. 2. The method of claim 1, wherein KX-01 is administered to the subject at a dose of about 0.2 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1 mg, about 1.1 mg, about 1.2 mg, about 1.3 mg, about 1.4 mg, about 1.5 mg, about 1.6 mg, about 1.7 mg, about 1.8 mg, about 1.9 mg, about 2.0 mg, about 2.1 mg, about 2.2 mg, about 2.3 mg, about 2.4 mg, about 2.5 mg, about 2.6 mg, about 2.7 mg, about 2.8 mg, about 2.9 mg, about 3 mg, about 4 mg or about 5 mg to the affected area.

4. KX-01 is approximately 0.0003 mg / cm 2 ~About 10mg / cm 2 , about 0.001mg / cm 2 ~Approx. 0.4mg / cm 2 , about 0.005mg / cm 2 ~Approx. 0.1mg / cm 2 , about 0.005mg / cm 2 ~ approx. 0.02 mg / cm 2 or about 0.025 mg / cm 2 ~Approx. 0.1mg / cm 2 The method of claim 1, wherein the subject is administered to the affected area at a dose of

5. KX-01 is approximately 0.001 mg / cm 2 , about 0.002mg / cm 2 , about 0.003mg / cm 2 , about 0.004mg / cm 2 , about 0.005mg / cm 2 , about 0.006mg / cm 2 , about 0.007mg / cm 2 , about 0.008mg / cm 2 , about 0.009 mg / cm 2 , about 0.01mg / cm 2 , about 0.02 mg / cm 2 , about 0.03mg / cm 2 , about 0.04 mg / cm 2 , about 0.05mg / cm 2 , about 0.06mg / cm 2 , about 0.07mg / cm 2 , about 0.08 mg / cm 2 , about 0.09mg / cm 2 , about 0.1mg / cm 2 , about 0.15mg / cm 2 , about 0.2mg / cm 2 , about 0.25mg / cm 2 , about 0.3mg / cm 2 , about 0.35mg / cm 2 or about 0.4 mg / cm 2 The method of claim 1, wherein the subject is administered to the affected area at a dose of

6. The affected area is approximately 0.01 cm 2 ~Approx. 300cm 2 , about 1cm 2 ~About 200cm 2 , about 1cm 2 ~Approx. 100cm 2 , about 1cm 2 ~Approx. 75cm 2 , about 1cm 2 ~Approx. 50cm 2 , about 1cm 2 ~Approx. 25cm 2 , about 10cm 2 ~About 200cm 2 , about 10cm 2 ~Approx. 100cm 2 , about 10cm 2 ~Approx. 75cm 2 , about 10cm 2 ~Approx. 50cm 2 , about 10cm 2 ~Approx. 25cm 2 , about 25cm 2 ~About 200cm 2 , about 25cm 2 ~Approx. 100cm 2 , about 25cm 2 ~Approx. 75cm 2 Or about 25cm 2 ~Approx. 50cm 2 , about 25cm 2 ~Approx. 90cm 2 , about 25cm 2 ~Approx. 80cm 2 Or about 25cm 2 ~Approx. 70cm 2 , about 25cm 2 ~Approx. 60cm 2 , about 25cm 2 ~Approx. 40cm 2 Or about 25cm 2 ~Approx. 30cm 2 3. The method of claim 2, wherein

7. The affected area is approximately 25 cm 2 , about 30cm 2 , about 35cm 2 , about 40cm 2 , about 45cm 2 , about 50cm 2 , approx. 55cm 2 , about 60cm 2 , approx. 65cm 2 , about 70cm 2 , about 75cm 2 , about 80cm 2 , approx. 85cm 2 , about 90cm 2 , about 95cm 2 Or about 100cm 2 3. The method of claim 2, wherein

8. 3. The method of claim 2, wherein the affected area is skin.

9. 2. The method of claim 1, wherein KX-01 is administered once a week, once every 3 days, once every 2 days, once a day, twice a day, three times a day, or four times a day.

10. 2. The method of claim 1, wherein KX-01 is administered for 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days or 21 days.

11. 2. The method of claim 1, wherein KX-01 is administered for 1 day, 2 days, 3 days, 4 days or 5 days.

12. 2. The method of claim 1, wherein KX-01 is administered for 1, 2, 3, 4, 5 or 6 days per week.

13. 2. The method of claim 1, wherein KX-01 is administered once or twice daily for multiple consecutive days per week, followed by discontinuation of administration for the remainder of the week.

14. 2. The method of claim 1, wherein KX-01 is administered once or twice daily, every other day, every 3, 4, 5, 6 or 7 days.

15. 2. The method of claim 1, wherein KX-01 is administered once or twice daily for two consecutive days every 3, 4, 5, 6 or 7 days.

16. 2. The method of claim 1, wherein KX-01 is administered once or twice daily for three consecutive days every 4, 5, 6 or 7 days.

17. 2. The method of claim 1, wherein KX-01 is administered once or twice daily for four consecutive days every 5, 6 or 7 days.

18. 13. The method of claim 1, wherein KX-01 is administered until the psoriasis is completely treated.

19. 2. The method of claim 1, wherein KX-01 is administered locally.

20. The method of claim 1, wherein administration of KX-01 reduces the number and / or severity of local skin reactions or other adverse side effects in a subject or the number of subjects having the same compared to other treatments for psoriasis.

21. administering to a subject in need thereof a therapeutically effective amount of KX-01: 【Chemistry 2】 or a pharma- ceutically acceptable salt thereof for use in the treatment or prophylaxis of psoriasis.

22. administering to a subject in need thereof a therapeutically effective amount of KX-01: 【Chemistry 3】 20. Use of a compound in the manufacture of a medicament for use in the treatment or prevention of psoriasis comprising administering to a patient a compound comprising the compound of formula (I) or a pharma- ceutically acceptable salt thereof.

23. administering to a subject in need thereof a therapeutically effective amount of KX-01: 【Chemistry 4】 20. Use of a compound in the treatment or prevention of psoriasis comprising administering to a patient in need thereof a compound comprising the steps of:

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