Combined therapy of clascoterone and minoxidil for use in the treatment of hair loss.

Description

1 / 69 Combined therapy of clascoterone and minoxidil for use in the treatment of hair loss. FUNDAMENTALS

[0001] Alopecia is a group of disorders with multiple and variable etiologies that result in hair loss from the body. The most common form of alopecia is androgenetic alopecia (“AGA”). AGA is also commonly called male pattern baldness or male or female pattern hair loss. AGA has been reported to affect approximately 50% of men over 40 years of age. This form of alopecia could eventually affect up to 80% of white men by around 70 years of age and about half of all women. Hair loss is often a cause of great concern to affected individuals for cosmetic and psychological reasons, but it can also be an important sign of systemic disease.

[0002] The medical management of AGA includes surgical treatment options, including hair transplantation. This procedure has been successfully performed for decades. Hair transplantation involves harvesting intact hair follicles from within a safe donor area (SDA) of a patient's scalp by follicular unit strip harvesting surgery (FUSS) or follicular unit extraction (FUE). Although cosmetic results after surgery are often satisfactory, surgery can only be performed when a sufficient number of donor plugs (or follicles) are available to cover the balding area(s). Additionally, hair transplantation is generally reserved for patients who have experienced massive hair loss and for patients in whom AGA is not yet progressing.In younger patients, for example, hair transplantation is generally not recommended, as androgens, particularly dihydrotestosterone (DHT), can act on the newly transplanted follicles, resulting in the same thinning and eventual hair loss that affected the follicles originally. Petition 870250088666, dated 09 / 30 / 2025, page 18 / 102 2 / 69 present.

[0003] In view of the shortcomings and disadvantages associated with surgical treatment options, there remains a need in the field for pharmacological therapies for the treatment of hair loss, including alopecia and, in particular, AGA. BRIEF SUMMARY

[0004] Minoxidil, also known as 2,4-diamino-6-piperidinopyrimidine 3-oxide, is formulated as a topical pharmaceutical product for the treatment of AGA, typically in two potency levels: 2% (topical solution) and 5% (as a topical solution or foam). See, for example, U.S. Patents Nos. 4,596,812 and 6,946,120, each of which is incorporated into this descriptive report by reference in its entirety. To exert its effect, minoxidil needs to be transformed into its active metabolite, minoxidil sulfate, by the enzyme sulfotransferase. This enzyme is present in the outer root sheath of anagen follicles. Unfortunately, clinical trials have shown that topical application of a 2% minoxidil solution to patients with hair loss results in stimulated dense hair regrowth in less than about 5% of patients and moderate hair regrowth in only about 30% of patients. See, for example, E.A. Olsen et al., "Topical Minoxidil in Early Male Pattern Baldness, J. Amer. Acad. Derm. 13, 185-192 (1985); and J. Roberts, "Androgenetic Alopecia: Treatment with Topical Minoxidil, J. Amer. Academic. Derm. 16 (3) 705-710 (1987).

[0005] Cortexolone-17α-propionate, also known as 17α-propionyloxy-21-hydroxy-pregna-4-ene-3,20-dione and clascoterone, is a topical antiandrogen that displaces androgenic hormones from binding to their receptors. Cortexolone-17α-propionate is known to be suitable for the treatment of acne, alopecia, and other diseases of the skin and cutaneous appendages. See, for example, US Patents Nos. 8,143,240 and 8,865,690. Petition 870250088666, dated 09 / 30 / 2025, page 19 / 102 3 / 69 WO 2009 / 019138 and WO 2016 / 207778. The compound is also known to exist in several distinct crystalline polymorphs, each having unique properties. See, for example, US Patent No. 8,785,427. Each of these patents is incorporated into this descriptive report by reference in its entirety.

[0006] It has been surprisingly discovered that hair loss, including alopecia, can be effectively treated with a combination of cortexolone-17α-propionate and minoxidil. In some embodiments, a synergistic effect can be provided by the combination so that, surprisingly, a smaller effective amount of each active ingredient can be used for effective treatment or the same amount of each active ingredient can be used to obtain greater combined synergy. As a result of this combined therapy, an advantageous clinical outcome can be observed after daily topical administration for an appropriate amount of time, such as a few days, weeks, or months.

[0007] Consequently, the present disclosure provides a method of treating hair loss in an individual in need, comprising the topical administration to the individual of an effective amount of cortexolone-17a-propionate and an effective amount of minoxidil.

[0008] In some embodiments, cortexolone-17α-propionate may be co-administered in an amount of at least 1% of body weight up to about 20% of body weight, together with an effective amount of minoxidil. In some embodiments, minoxidil may be co-administered in an amount of about 0.1% of body weight up to about 20% of body weight, together with an effective amount of cortexolone-17α-propionate.

[0009] In some embodiments, cortexolone-17a-propionate and minoxidil are co-administered sequentially. In these embodiments, cortexolone-17a-propionate and minoxidil may be in separate pharmaceutical formulations. In other embodiments, cortexolone-17a-propionate and minoxidil may be Petition 870250088666, dated 09 / 30 / 2025, page 20 / 102 4 / 69 co-administered simultaneously. In some embodiments, cortexolone-17α-propionate and minoxidil may be combined in the same pharmaceutical formulation.

[0010] In some embodiments, the pharmaceutical formulation may be a liquid or semi-solid formulation. In a further embodiment, the pharmaceutical formulation is a solution, a suspension, an emulsion, a microemulsion, a cream, a paste, a gel, an ointment, or a foam. In further embodiments, the pharmaceutical formulation is a solution. In some embodiments of the solution, the solution may comprise water, saline solution, a buffered saline solution, a polyol, a polyol ether, a C1-C7 alcohol, or a combination thereof.

[0011] In some embodiments of the method, the pharmaceutical formulation may further comprise at least one (for example, 1, 2, 3, 4, 5, 6, 7 or 8) additive(s) selected from the group consisting of an acid, a buffer, an antioxidant, an emulsifier, a penetration enhancer, a moisturizer, a preservative, a chelating agent, and combinations thereof. In some embodiments, cortexolone-17α-propionate is co-administered in a pharmaceutical formulation comprising less than about 5% by weight of water. In some embodiments, cortexolone-17α-propionate and minoxidil are combined in the same pharmaceutical formulation comprising less than about 5% by weight of water. In some embodiments, the pharmaceutical formulation is co-administered topically once or twice daily.

[0012] In some modalities of the method, hair loss is alopecia. In some modalities, the alopecia is androgenetic alopecia, alopecia areata, telogen effluvium, anagen effluvium, traction alopecia, or a combination of any of the aforementioned. In some modalities, alopecia areata is selected from the group consisting of diffuse alopecia areata, monolocular alopecia areata, alopecia areata Petition 870250088666, dated 09 / 30 / 2025, page 21 / 102 5 / 69 multilocular, ophiasis, alopecia totalis, and alopecia universalis. In some particular forms, the alopecia is androgenetic alopecia.

[0013] The present disclosure further provides a topical pharmaceutical formulation comprising cortexolone-17α-propionate, minoxidil, and one or more pharmaceutically acceptable carriers. In some embodiments, the cortexolone-17α-propionate is fully solubilized in the pharmaceutical formulation. In some embodiments, the pharmaceutical formulation comprises cortexolone-17α-propionate at a concentration of about 1% by weight to about 20% by weight, including from about 2% by weight to about 15% by weight, from about 3% by weight to about 10% by weight, or from about 4% by weight to about 7.5% by weight. In some embodiments, the pharmaceutical formulation comprises cortexolone-17α-propionate at a concentration of about 1% by weight, about 2% by weight, about 3% by weight, about 4% by weight, about 5% by weight, about 6% by weight, about 7% by weight, about 7.5% by weight, about 8% by weight, about 9% by weight, or about 10% by weight.In some embodiments, the pharmaceutical formulation comprises minoxidil at a concentration of about 0.1% of weight to about 20% of weight, including from about 2% of weight to about 15% of weight, from about 3% of weight to about 10% of weight, and from about 4% of weight to about 7.5% of weight. In some embodiments, the pharmaceutical formulation comprises minoxidil at a concentration of approximately 1% by weight, approximately 2% by weight, approximately 3% by weight, approximately 4% by weight, approximately 5% by weight, approximately 6% by weight, approximately 7% by weight, approximately 7.5% by weight, approximately 8% by weight, approximately 9% by weight, approximately 10% by weight, approximately 11% by weight, approximately 12% by weight, approximately 13% by weight, approximately 14% by weight, approximately 15% by weight, approximately 16% by weight, approximately 17% by weight, approximately 18% by weight, approximately 19% by weight, or approximately 20% by weight. In some embodiments, the pharmaceutical formulation comprises a... Petition 870250088666, dated 09 / 30 / 2025, page 22 / 102 6 / 69 combination of cortexolone-17α-propionate and minoxidil, each at a concentration of about 0.1% of body weight to about 20% of body weight, including from about 2% of body weight to about 15% of body weight, from about 3% of body weight to about 10% of body weight, or from about 4% of body weight to about 7.5% of body weight.

[0014] In some embodiments, the pharmaceutical formulation is a liquid or semi-solid formulation. In some embodiments, the pharmaceutical formulation is a solution, a suspension, an emulsion, a microemulsion, a cream, a paste, a gel, an ointment, or a foam. In some embodiments, the pharmaceutical formulation is a solution. In some of these embodiments, the solution comprises water, saline solution, a buffered saline solution, or a combination thereof. In some embodiments, the pharmaceutical formulation comprises less than about 5 percent water by weight.

[0015] In some embodiments, the (one or more) pharmaceutically acceptable carriers are selected from the group consisting of a polyol, a polyol ether, and a C1-C7 alcohol. In some embodiments, the C1-C7 alcohol is ethanol, isopropanol, methanol, or a combination thereof. In some embodiments, the C1-C7 alcohol is ethanol. In some embodiments, the polyol is selected from the group consisting of ethylene glycol, propylene glycol, glycerol, hexanotriol, and combinations thereof. In some embodiments, the polyol is propylene glycol. In some embodiments, the polyol ether is selected from the group consisting of polypropylene glycol, polyethylene glycol, polyethylene-polypropylene triblock copolymers, dipropylene glycol, diethylene glycol monoethyl ether (Transcutol®), and combinations thereof. In some embodiments, the polyol ether is diethylene glycol monoethyl ether.In some embodiments, the polyol is propylene glycol, the polyol ether is diethylene glycol monoethyl ether, and the C1-C7 alcohol is ethanol.

[0016] In some forms, the pharmaceutical formulation Petition 870250088666, dated 09 / 30 / 2025, page 23 / 102 7 / 69 further comprises at least one additive (for example, 1, 2, 3, 4, 5, 6, 7 or 8) selected from an acid, a buffer, an antioxidant, an emulsifier, a penetration enhancer, a moisturizer, a preservative, a chelating agent, and combinations thereof. In some embodiments, the buffer is a phosphate buffer, citrate buffer, lactate buffer, or a combination thereof. In some embodiments, the antioxidant is selected from the group consisting of butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbyl palmitate, ascorbic acid, alpha-tocopherol, propyl gallate, 2,4,5-trihydroxybutyrophenone, 4-hydroxymethyl-2,6-di-tert-butylphenol, erythorbic acid, guaiac gum, thiodipropionic acid, dilauryl thiodipropionate, tert-butylhydroquinone, pharmaceutically acceptable salts or esters thereof, and combinations thereof. In some embodiments, the antioxidant is BHT, ascorbyl palmitate, or a combination of BHT and ascorbyl palmitate.In some embodiments, the emulsifier is selected from the group consisting of PEG-15 hydroxystearate (polyoxyl-15-hydroxystearate), PEG-30 stearate, PEG-40 laurate, PEG-40 oleate, a polysorbate (e.g., polysorbate 20, polysorbate 60, polysorbate 80), PEG-20 cetostearyl ether, polyoxyl 25 cetostearyl, cetomacrogol 1000, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monooleate-propylene glycol fatty acid esters, polyglycerol fatty acid esters, polyoxyl 5 castor oil, polyoxyl 15 castor oil, polyoxyl 35 castor oil, hydrogenated polyoxyl 40 castor oil, Caprylocapril polyoxyl-8 glycerides, caprylocaproyl polyoxylglycerides, lauroyl polyoxylglycerides, oleoyl polyoxylglycerides, and combinations thereof. In some embodiments, the emulsifier is a polysorbate such as, for example, polysorbate 60, polysorbate 80, or a combination of polysorbate 60 and polysorbate 80.In some modalities, the penetration enhancer is... Petition 870250088666, dated 09 / 30 / 2025, p. 24 / 102 8 / 69 selected from the group consisting of a diol, a polyol, a fatty acid (for example, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, or a combination thereof), a fatty alcohol, a fatty acid ester, an azone, a surfactant, a pyrrolidone, and combinations thereof. In some embodiments, the moisturizer is selected from the group consisting of a fatty alcohol, a fatty acid, a fatty acid ester, an oil, a polyethylene glycol, glycerin, an alpha hydroxy acid, and combinations thereof. In some formulations, the moisturizer is cetyl alcohol, cetearyl alcohol, stearyl alcohol, stearic acid, isopropyl myristate, isopropyl palmitate, cocoa butter, lanolin, liquid paraffin, shea butter, a silicone oil, castor oil, a polyethylene glycol, glycerin, lactic acid, glycolic acid, malic acid, citric acid, tartaric acid, or a combination thereof.

[0017] In certain embodiments, the present disclosure provides a method of treating alopecia, the method comprising topical administration to an individual in need of the topical pharmaceutical formulation described in this descriptive report, wherein topical administration of the pharmaceutical formulation for at least six months achieves a weighted average Hair Growth Assessment (HGA) score of approximately 0.30 compared to vehicle.

[0018] In certain embodiments, the present disclosure provides a method of treating alopecia, the method comprising topical administration to an individual in need of a topical pharmaceutical formulation described in this descriptive report, wherein topical administration of the pharmaceutical formulation for at least six months achieves a weighted average Investigator Global Assessment (IGA) score of approximately 0.43 compared to vehicle.

[0019] In certain ways, the present disclosure provides a Petition 870250088666, dated 09 / 30 / 2025, page 25 / 102 9 / 69 Alopecia treatment method, the method comprising the topical administration to an individual in need of a topical pharmaceutical formulation described in this descriptive report, wherein topical administration of the pharmaceutical formulation for at least six months is free of systemic antiandrogenic side effects.

[0020] In certain embodiments, the present disclosure provides a method of treating alopecia, the method comprising the topical administration to an individual in need of a topical pharmaceutical formulation described in this descriptive report, wherein the topical administration of the pharmaceutical formulation provides: a) an average change from baseline in the Target Area Hair Count equal to or greater than 9 hairs / cm2 after 6 months of daily or twice-daily (BID) application; or b) an average change from baseline in the Target Area Hair Count equal to or greater than 10 hairs / cm2 after 6 months of daily or BID application; or c) an average change from baseline in the Target Area Hair Count equal to or greater than 11 hairs / cm2 after 6 months of daily or BID application; or d) an average change from baseline in the Target Area Hair Count equal to or greater than 12 hairs / cm2 after 6 months of daily or BID application; or (e) a weighted average HGA score equal to or greater than 0.20 after 6 months of daily or BID application; or f) a weighted average HGA score equal to or greater than 0.30 after 6 months of daily or BID application; or g) a weighted average HGA score equal to or greater than 0.40 after 6 months of daily or BID application; or h) a weighted average IGA score equal to or greater than 0.10 after 6 months of daily or BID application; or i) a weighted average IGA score equal to or greater than Petition 870250088666, dated 09 / 30 / 2025, page 26 / 102 10 / 69 that is 0.20 after 6 months of daily application or BID; or j) a weighted average IGA score equal to or greater than 0.30 after 6 months of daily or BID application; or k) a favorable (positive) HGA score in at least approximately 10% of individuals after 6 months of daily or BID application; or l) a favorable (positive) HGA score in at least approximately 20% of individuals after 6 months of daily or BID application; or m) a favorable (positive) HGA score in at least approximately 30% of individuals after 6 months of daily or BID application; or n) a favorable (positive) IGA score in at least approximately 10% of individuals after 6 months of daily or BID application; or o) a favorable (positive) IGA score in at least approximately 20% of individuals after 6 months of daily or BID application; or p) a favorable (positive) IGA score in at least approximately 30% of individuals after 6 months of daily or BID application; or q) a favorable (positive) IGA score in at least about 40% of individuals after 6 months of daily or BID application.

[0021] In a further embodiment, the topical pharmaceutical formulation of the present invention is for use in the treatment of hair loss in an individual in need. DETAILED DESCRIPTION

[0022] The articles a, the, an, and the are used in this descriptive report to refer to one or more than one (i.e., at least one) of the grammatical objects of the article. Just as an example, an element means one element or more than one element. Petition 870250088666, dated 09 / 30 / 2025, page 27 / 102 11 / 69

[0023] As used in this descriptive report, the term “about” means within an acceptable range of error for the particular value as determined by those skilled in the art, which depends, in part, on how the value is measured or determined, i.e., on the limitations of the measurement system. For example, “about” may mean within 3 or more than 3 standard deviations, by practice in the art. Alternatively, “about” may mean a range of up to 10% (e.g., up to 5%, up to 1%) of a certain value.

[0024] As used in this descriptive report, the phrase “active agent” refers to cortexolone-17α-propionate or minoxidil.

[0025] The term “alopecia, as used in this descriptive report, refers to, collectively or individually as specified, androgenetic alopecia (AGA), alopecia areata (including diffuse alopecia areata, monolocular alopecia areata, multilocular alopecia areata, ophiasis, alopecia totalis and alopecia universalis), telogen effluvium, anagen effluvium and traction alopecia.

[0026] As used in this descriptive report, the term “anhydrous” means substantially free of water, that is, containing less than about 5% of the weight of water and, in certain embodiments as specified in this descriptive report, less than about 3% of the weight of water.

[0027] As used in this descriptive report, the term “at least,” before a number or series of numbers, is understood to include the number associated with the term “at least,” and all subsequent numbers or integers that could logically be included, as evident from the context. When “at least” is present before a series or range of numbers, it is understood that “at least” may modify each of the numbers in the series or range. For example, “at least 3” means at least 3, at least 4, at least 5, etc. When “at least” is present before a component in a step Petition 870250088666, dated 09 / 30 / 2025, page 28 / 102 12 / 69 of a method, so that component is included in the step, while additional components are optional.

[0028] As used in this descriptive report, the terms “Bis In Die” or “BID” mean “twice a day.”

[0029] As used in this descriptive report, the term “buffer” refers to a compound or group of compounds (e.g., a weak acid-base conjugate pair such as, for example, a weak acid and its conjugate base or a weak base and its conjugate acid) that controls the pH of a solution within a desired range. In some embodiments, the conjugate base may be added as a Group I or Group II salt. Examples of a buffer include, for example, a phosphate buffer, citrate buffer, lactate buffer, or a combination thereof.

[0030] As used in this descriptive report, the phrase “C1-C7 alcohol” refers to an alcohol having 1, 2, 3, 4, 5, 6, or 7 carbons that is suitable for use in a topical pharmaceutical formulation. Examples of such C1-C7 alcohols include, without limitation, methanol, ethanol, isopropanol, n-butanol, n-propanol, benzyl alcohol, and the like. Without wishing to be bound to any particular theory, it is believed that C1-C7 alcohols, and particularly short-chain C1-C7 alcohols such as C2-C3 alcohols (e.g., ethanol, n-propanol, or isopropyl alcohol), contribute to the spreadability of the pharmaceutical formulations described in this descriptive report.

[0031] As used in this descriptive report, the term “chelating agent” refers to a compound that can bind to metal ions or metal compounds. In some embodiments, a chelating agent can stabilize the formulation by preventing, for example, oxidation or precipitation. Suitable chelating agents include, for example, citric acid, phytic acid, sodium phytate, clioquinol, ethylenediaminetetraacetic acid (EDTA) (e.g., disodium EDTA, tetrasodium EDTA), etidronic acid, galactaric acid, tetrahydroxypropyl Petition 870250088666, dated 09 / 30 / 2025, p. 29 / 102 13 / 69 ethylenediamine, sodium metasilicate, or a combination thereof.

[0032] As used in this descriptive report, the term co-administration means concomitant or sequential administration of two different active agents, namely, cortexolone-17α-propionate and minoxidil. In some embodiments, the active agents are administered with sufficiently close time to each other that the first and second therapeutic agents are simultaneously present in individuals receiving the co-administration.

[0033] As used in this descriptive report, the term cortexolone (also known as 11-deoxycortisol or Reichstein's substance) refers to the compound that has the following structure: .O ,OH

[0034] As used in this descriptive report, the term cortexolone-17α-propionate refers to the compound 17αpropionyloxy-21-hydroxy-pregna-4-ene-3,20-dione, which is also known as clascoterone and is equivalent to the chemical structure:

[0035] As used in this descriptive report, the term degradation product refers to those compounds that result from the in vitro degradation of cortexolone-17α-propionate. Known exemplary degradation products of cortexolone-17α-propionate include, without limitation, cortexolone-21-propionate and Petition 870250088666, dated 09 / 30 / 2025, page 30 / 102 14 / 69 cortexolone.

[0036] As used in this descriptive report, the term ester refers to esterified organic solvents which include, without limitation, ethyl acetate and ethyl lactate.

[0037] As used in this descriptive report, the term ethanol refers to ethyl alcohol, i.e., CH3CH2OH, and includes pure (absolute) ethanol and 96° ethanol, the latter being ethanol containing water in an amount that typically ranges from about 4% to about 5.1% by volume. In some embodiments, ethanol is denatured alcohol, such as, for example, especially denatured alcohol (SD), which includes a denaturing agent to prevent consumption.

[0038] As used in this descriptive report, the term fatty refers to an aliphatic carbon chain that is either saturated or unsaturated. The chain is of any suitable length, such as C4-C28, including more specifically chain lengths C10-C20, C12-C22 and C12-C18.

[0039] As used in this descriptive report, the term gelling agent refers to a pharmaceutically acceptable compound that can transform an aqueous or oily phase into a gel. A gelling agent acts as a thickening agent, typically without imparting stiffness. The gelling agent may be an inorganic gelling agent, an organic gelling agent, a hydrogel, an organogel, or a combination thereof.

[0040] As used in this descriptive report, the term minoxidil refers to the compound 2,4-diamino-6-piperidinopyrimidine 3-oxide, which is equivalent to the chemical structure: OΟθ Petition 870250088666, dated 09 / 30 / 2025, page 31 / 102 15 / 69

[0041] In some embodiments, minoxidil is present in the form of a salt. The salt may be, for example, acetate, citrate, succinate, benzoate, hydrochloride, sulfate, phosphate, or lactate. In some embodiments, an acetate or lactate salt of minoxidil is used.

[0042] As used in this descriptive report, the term metabolite refers to those compounds that result from the in vivo metabolism or degradation of an active agent such as, for example, cortexolone-17α-propionate or minoxidil. Known exemplary metabolites of cortexolone-17α-propionate include, without limitation, cortexolone and tetrahydrocortexolone. Known exemplary metabolites of minoxidil include, without limitation, minoxidil sulfate.

[0043] As used in this descriptive report, the term moisturizer refers to those compounds that impart moisture to the skin, soften the skin, or both. Exemplary moisturizers are emollients that include, for example, a fatty alcohol, a fatty acid, a fatty acid ester, an oil, a polyethylene glycol, glycerin, an alpha hydroxy acid (e.g., lactic acid, glycolic acid, malic acid, citric acid, or tartaric acid), and combinations thereof. Specific examples of a moisturizer include, for example, cetyl alcohol, cetearyl alcohol, stearyl alcohol, stearic acid, isopropyl myristate, isopropyl palmitate, cocoa butter, lanolin, liquid paraffin, shea butter, a silicone oil, castor oil, a polyethylene glycol, glycerin, lactic acid, glycolic acid, malic acid, citric acid, tartaric acid, or a combination thereof; Preferably, the aforementioned moisturizers are selected from cetyl alcohol and stearyl alcohol.

[0044] As used in this descriptive report, the phrase natural oil refers to those isolable oils from natural sources. Petition 870250088666, dated 09 / 30 / 2025, p. 32 / 102 16 / 69 Exemplary natural oils include, without limitation, olive oil, jojoba oil, coconut oil, almond oil, cottonseed oil, safflower oil, sunflower oil, sesame oil, soybean oil, castor oil, calendula oil, and the like.

[0045] As used in this descriptive report, the phrase “penetration enhancer” refers to those pharmaceutically acceptable compounds that increase the penetration of the active agent through the dermis. Exemplary penetration enhancers include, for example, hydroxypropyl β-cyclodextrin, polyoxyethylene alkyl ethers, polyoxyl glycerides, dimethyl sulfoxide, pyrrolidone, N-methyl-2-pyrrolidone, diethylene glycol monoethyl ether (e.g., TRANSCUTOL™, Gattefossé, France), dimethyl isosorbide, diethyl sebacate, azone, menthol, nerol, camphor, methyl salicylate, polysorbate 80 (e.g., TWEEN™ 80, Sigma-Aldrich, St.Louis, MO), SDS, benzalkonium chloride, polyoxyl 40 hydrogenated castor oil (e.g., CREMOPHOR™ RH40, KOLLIPHOR™ RH40, BASF, Germany), didecyldimethylammonium bromide (DDAB), didecyltrimethylammonium bromide (DTAB), fatty acid esters (e.g., isopropyl myristate, isopropyl palmitate), fatty acids (e.g., oleic acid, palmitic acid, linoleic acid, and salts thereof), fatty alcohols (e.g., oleyl alcohol, myristyl alcohol, stearyl alcohol), medium-chain triglycerides, and combinations of any of the foregoing.

[0046] As used in this descriptive report, and unless it is clear from the context in which it is used that it means otherwise, the term “pH” should be considered an “apparent pH” to acknowledge the fact that the behavior of a pH electrode in a complex multicomponent dermatological vehicle that is not entirely aqueous in nature cannot be considered a “pH” in the strictest sense. Petition 870250088666, dated 09 / 30 / 2025, page 33 / 102 17 / 69

[0047] As used in this descriptive report, the term polyol refers to organic molecules containing two or more hydroxyl groups. Exemplary polyols include, without limitation, ethylene glycol, propylene glycol, glycerol, hexanotriol and the like, preferably propylene glycol.

[0048] As used in this descriptive report, the term polyol ether refers to a polyol ether suitable for use in a topical pharmaceutical formulation. Exemplary polyol ethers include, without limitation, polypropylene glycol, polyethylene glycol, polyethylene-polypropylene triblock copolymers, dipropylene glycol, diethylene glycol monoethyl ether, and the like.

[0049] As used in this descriptive report, the term preservative refers to a compound with antimicrobial activity, such as an antibacterial or antifungal agent. Suitable preservatives include, for example, a paraben (e.g., methylparaben, ethylparaben, propylparaben, butylparaben), a benzoate (e.g., sodium benzoate), a sorbate (e.g., potassium sorbate), a quaternary ammonium compound (e.g., benzalkonium chloride, benzethonium chloride), an alcohol (e.g., chlorobutanol, benzyl alcohol, ethanol, phenol, m-cresol, chlorocresol), sodium metabisulfite, imidazolidinyl urea, glycerin, propylene glycol, or a combination thereof.

[0050] As used in this descriptive report, the term solvent means one or a mixture of more than one pharmaceutically acceptable solvent suitable for topical application, including, without limitation, the scalp, which is used to solubilize cortexolone-17a-propionate and / or minoxidil in a formulation described in this descriptive report.

[0051] As used in this descriptive report, the term tetrahydrocortexolone refers to the compound that has Chemical Abstracts Service (CAS) number 68-60-0. Petition 870250088666, dated 09 / 30 / 2025, page 34 / 102 18 / 69

[0052] As used in this descriptive report, the terms treat, “treating,” and “treatment” refer to any indication of successful treatment or improvement of an injury, illness, or condition, including any objective or subjective parameter such as, for example, reduction; remission; decrease in one or more symptoms or making the injury, illness, or condition more tolerable to the individual; slowing the rate of degeneration or decline; or improving an individual’s physical or mental well-being. Treatment or improvement of symptoms may be based on objective or subjective parameters, including the results of a physical examination, neuropsychiatric tests, or psychiatric evaluation.

[0053] As used in this descriptive report, the term “prevent” refers to preventing the occurrence or existence of, or alternatively, delaying the onset or recurrence of, a disease, disorder, or condition to which this term applies, or one or more symptoms associated with a disease, disorder, or condition. The term “prevent” also refers to reducing the incidence of a disease, disorder, or condition. The term “prevention” refers to the act of preventing.

[0054] As used in this descriptive report, the term “sequentially” means that, to an individual, a first active agent is co-administered to the individual in a first time period, followed by an administration of a second active agent in a second time period. In other words, the term “sequentially” includes a first therapy in a first time period, followed by a second therapy in a second time period. The first and second time periods may be separated in the order of seconds, minutes, hours, or days, as required. In some modalities, the first and second time periods are separated by seconds (e.g., approximately 60 seconds or less, approximately 30 seconds or less).

[0055] As used in this descriptive report, the term Petition 870250088666, dated 09 / 30 / 2025, page 35 / 102 19 / 69 The individual is typically directed at a mammal. In some modalities, the individual being treated is human.

[0056] As used in this descriptive report, the phrase % of weight aims to encompass and reveal modalities in which % of weight is the % of weight by volume (w / v) and the percentage of weight by total weight (w / w) for a given value. Just as an example, a modality comprising 10% of the weight of element X reveals modalities comprising both 10% of the weight of X (w / v) and 10% of the weight of X (w / w). Similarly, and again just as an example, a modality comprising 10% of the weight of X, 20% of the weight of Y, and 60% of the weight of Z, reveals modalities comprising: a) 10% of the weight of X (w / v), 20% of the weight of Y (w / v), and 60% of the weight of Z (w / v); and b) 10% of the weight of X (w / w), 20% of the weight of Y (w / w), and 60% of the weight of Z (w / w). Notwithstanding the above, in some modalities, a value will be specifically marked (p / p) or (p / v). In those cases, the value should be interpreted as revealing only the marked value, that is, only (p / p) or only (p / v) - but not both.

[0057] As used in this descriptive report, the terms comprise, which includes, which contains, which includes, which contains and the like are open-ended terms meaning including, without limitation. To the extent that a certain embodiment disclosed in this descriptive report comprises certain elements, it should be understood that the present disclosure also specifically contemplates and discloses embodiments that consist basically of those elements and that consist of those elements.

[0058] As used in this descriptive report, the terms basically consist of, which basically consists of and similar terms should be considered as semi-closed terms, meaning that no other ingredient that materially affects the basic and novel characteristics of an embodiment is included. Petition 870250088666, dated 09 / 30 / 2025, page 36 / 102 20 / 69

[0059] As used in this descriptive report, the terms “consists of,” “that consists of,” and the like should be considered as closed terms, such that a modality “that consists of” a particular set of elements excludes any element, step, or ingredient not specified in the modality.

[0060] As used in this descriptive report, the terms “Target Area Hair Count” or “TAHC” refer to the change, from baseline, in the number of terminal hairs in a target area of ​​the scalp. The target area may be, for example, 1 cm2 or a circle with a diameter of 2.54 cm (5.1 cm2).

[0061] As used in this descriptive report, the terms “Hair Growth Assessment” or “HGA” refer to a score given by the individual that compares the standardized global photo of the individual’s scalp baseline with a standardized global photo “in real time.”

[0062] As used in this descriptive report, the terms “Investigator Global Assessment” or “IGA” refer to a score given by an assessor who compares the standardized global photo of the individual’s scalp baseline with a standardized global photo “in real time.” The method

[0063] The present disclosure provides a method of treating hair loss, such as alopecia, in an individual in need, comprising the topical administration to the individual of an effective amount of cortexolone-17a-propionate and an effective amount of minoxidil. Topical administration comprises the application of cortexolone-17a-propionate and minoxidil to the skin and / or scalp of the individual, as described in this descriptive report.

[0064] In preferred modalities, the individual can be a mammal such as, for example, a human. Petition 870250088666, dated 09 / 30 / 2025, page 37 / 102 21 / 69

[0065] In some modalities, hair loss may be associated with alopecia. Alopecia may include, for example, androgenetic alopecia (AGA), alopecia areata (including diffuse alopecia areata, monolocular alopecia areata, multilocular alopecia areata, ophiasis, alopecia totalis, and alopecia universalis), telogen effluvium, anagen effluvium, and traction alopecia. In some modalities, the alopecia to be treated may be AGA.

[0066] In some embodiments, cortexolone-17a-propionate and minoxidil are co-administered sequentially, wherein a first active agent may be administered to the individual at a first time period, followed by administration of the second active agent at a second time period. The particular order of administration is not limited. In some embodiments, cortexolone-17a-propionate may be administered first, and minoxidil may be administered afterward. In other embodiments, minoxidil may be administered first, and cortexolone-17a-propionate may be administered afterward. The time period between the two administration steps may be separated on the order of seconds, minutes, hours, or days, as required. In some embodiments, the first and second administration steps may be separated by seconds (e.g., approximately 60 seconds or less, approximately 30 seconds or less).

[0067] In certain embodiments, the present disclosure provides a method of treating alopecia, the method comprising topical administration to an individual in need of a topical pharmaceutical formulation described in this descriptive report, wherein topical administration of the pharmaceutical formulation for at least six months achieves a weighted average Hair Growth Assessment (HGA) score of approximately 0.30 compared to vehicle.

[0068] In certain embodiments, the present disclosure provides a method for treating alopecia, the method comprising Petition 870250088666, dated 09 / 30 / 2025, page 38 / 102 22 / 69 topical administration to an individual in need of a topical pharmaceutical formulation described in this descriptive report, where topical administration of the pharmaceutical formulation for at least six months achieves a weighted average Investigator Global Assessment (IGA) score of approximately 0.43 compared to vehicle.

[0069] In certain embodiments, the present disclosure provides a method of treating alopecia, the method comprising topical administration to an individual in need of a topical pharmaceutical formulation described in this descriptive report, wherein topical administration of the pharmaceutical formulation for at least six months does not result in systemic antiandrogenic side effects in the individual.

[0070] In certain embodiments, the present disclosure provides a method of treating alopecia, the method comprising the topical administration to an individual in need of a topical pharmaceutical formulation described in this descriptive report, wherein the topical administration of the pharmaceutical formulation provides: a) an average change from baseline in the Target Area Hair Count equal to or greater than 9 hairs / cm2 after 6 months of daily or BID application; or b) an average change from baseline in the Target Area Hair Count equal to or greater than 10 hairs / cm2 after 6 months of daily or BID application; or c) an average change from baseline in the Target Area Hair Count equal to or greater than 11 hairs / cm2 after 6 months of daily or BID application; or d) an average change from baseline in the Target Area Hair Count equal to or greater than 12 hairs / cm2 after 6 months of daily or BID application; or (e) a weighted average HGA score equal to or greater than 0.20 after 6 months of daily or BID application; or Petition 870250088666, dated 09 / 30 / 2025, p. 39 / 102 23 / 69 f) a weighted average HGA score equal to or greater than 0.30 after 6 months of daily or BID application; or g) a weighted average HGA score equal to or greater than 0.40 after 6 months of daily or BID application; or h) a weighted average IGA score equal to or greater than 0.10 after 6 months of daily or BID application; or i) a weighted average IGA score equal to or greater than 0.20 after 6 months of daily or BID application; or j) a weighted average IGA score equal to or greater than 0.30 after 6 months of daily or BID application; or k) a favorable (positive) HGA score in at least approximately 10% of individuals after 6 months of daily or BID application; or l) a favorable (positive) HGA score in at least approximately 20% of individuals after 6 months of daily or BID application; or m) a favorable (positive) HGA score in at least approximately 30% of individuals after 6 months of daily or BID application; or n) a favorable (positive) IGA score in at least approximately 10% of individuals after 6 months of daily or BID application; or o) a favorable (positive) IGA score in at least approximately 20% of individuals after 6 months of daily or BID application; or p) a favorable (positive) IGA score in at least approximately 30% of individuals after 6 months of daily or BID application; or q) a favorable (positive) IGA score in at least about 40% of individuals after 6 months of daily or BID application. Pharmaceutical formulations

[0071] In some forms, cortexolone-17α-propionate Petition 870250088666, dated 09 / 30 / 2025, page 40 / 102 24 / 69 and minoxidil can be co-administered sequentially. In these modalities, cortexolone-17α-propionate and minoxidil may be provided in separate pharmaceutical formulations. Each pharmaceutical formulation may be as described in this descriptive report.

[0072] In other embodiments, cortexolone-17a-propionate and minoxidil may be co-administered simultaneously (i.e., concomitantly). In some embodiments, cortexolone-17a-propionate and minoxidil may be provided in the same pharmaceutical formulation (e.g., a combination formulation).

[0073] The pharmaceutical formulation may be in any form suitable for topical administration. In some embodiments, the pharmaceutical formulation may be a liquid or semi-solid formulation, depending on the carriers and excipients that may be present, as described in this descriptive report. Examples of liquid or semi-solid formulations include, for example, a solution, a suspension, an emulsion, a microemulsion, a cream, a paste, a gel, an ointment, or a foam. In preferred embodiments, the pharmaceutical formulation may be a solution.

[0074] In some embodiments, the formulation may be a cream. In some embodiments, the cream may comprise oil and water in equal parts in the form of an emulsion.

[0075] In some embodiments, the formulation may be a paste. In some embodiments, the paste may comprise a fatty acid (for example, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, or a combination thereof), an oil, or a combination thereof.

[0076] In some embodiments, the formulation may be a gel that includes at least one gelling agent. The gelling agent may be, for example, an inorganic gelling agent (e.g., aluminum hydroxide gel, bentonite magma), a Petition 870250088666, dated 09 / 30 / 2025, p. 41 / 102 25 / 69 organic gelling agent (e.g., a carbomer polymer, tragacanth), a hydrogel (e.g., an organic hydrogel, a natural or synthetic gum, or an inorganic hydrogel), an organogel (e.g., a type of hydrocarbon, a vegetable fat, a soap-based fat, or a hydrophilic organogel), or a combination thereof. The organic hydrogel may include, for example, pectin paste and tragacanth jelly. The natural or synthetic gum may include, for example, methylcellulose, sodium carboxymethyl cellulose, and poloxamer. The inorganic hydrogel may include, for example, bentonite gel, smectite (e.g., VEEGUM™, Vanderbilt Minerals, LLC, Norwalk, CT), or silica. The hydrocarbon type of organogel may include, for example, petrolatum and mineral oil / polyethylene gel. Vegetable fat-type organogels may include, for example, cocoa butter.Soap-based fat-type organogels may include, for example, aluminum stearate with heavy mineral oil gel. Hydrophilic organogels may include, for example, Carbowax bases such as, for example, polyethylene glycol (PEG) ointment.

[0077] In some embodiments, the gelling agent may be a carbomer polymer. The term carbomer is a generic name for a high molecular weight polymer of acrylic acid slightly crosslinked with allyl ethers of polyalcohols (e.g., allyl sucrose, allyl pentaerythritol). The term may also be used to describe CARBOPOL™ polymers (Lubrizol Corp., Wickliffe, OH).

[0078] In some embodiments, the formulation may be an ointment. In some embodiments, the ointment may comprise a hydrocarbon (e.g., paraffin, petrolatum), lanolin, beeswax, a macrogol, a polyethylene glycol, an emulsifying wax, an alkyltrimethylammonium bromide (e.g., cetrimide), a vegetable oil (e.g., olive oil, jojoba oil, coconut oil, almond oil, seed oil). Petition 870250088666, dated 09 / 30 / 2025, p. 42 / 102 26 / 69 cottonseed oil, safflower oil, sunflower oil, sesame oil, soybean oil, castor oil, or calendula oil), or a combination thereof. In some embodiments, the ointment may comprise about 20% or less of water by weight.

[0079] In some embodiments, the formulation may be a foam. The foam formulation may be used in combination with one or more acceptable propellants such as, for example, propane, butane, isobutene, nitrogen, P75 propellant and the like. The solvent

[0080] In some embodiments where the pharmaceutical formulation may be a solution, the pharmaceutical formulation may comprise water, saline solution (e.g., a sodium chloride salt solution), a buffered saline solution (e.g., a phosphate-buffered saline solution), or a combination thereof.

[0081] In some embodiments, the pharmaceutical formulation may be considered anhydrous and may contain less than about 5 percent by weight (% of weight) (for example, less than about 4% of weight, less than about 3% of weight, less than about 2% of weight, or less than about 1% of weight) of water.

[0082] In some embodiments, particularly in embodiments containing less than about 5% by weight of water, cortexolone-17α-propionate can be fully solubilized in the pharmaceutical formulation. The topical pharmaceutical formulation may comprise one or more pharmaceutically acceptable carriers (e.g., solvents) in addition to or in place of water, such as, for example, a polyol, a polyol ether, a C1-C7 alcohol, and combinations thereof.

[0083] In some embodiments, the pharmaceutical formulation may comprise a solvent selected from the group comprising or consisting of: water, a C1-C7 alcohol, a polyol ether, a polyol, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), a natural oil, an ester, tricaprilin (2,3 Petition 870250088666, dated 09 / 30 / 2025, p. 43 / 102 27 / 69 di(octanoyloxy)propyl octanoate), a medium-chain triglyceride, caprylocaproyl polyoxyl-8 glycerides, and combinations of any of the aforementioned. In preferred embodiments, the (one or more) pharmaceutically acceptable carriers are selected from the group consisting of a polyol, a polyol ether, a C1-C7 alcohol, and combinations thereof.

[0084] In some embodiments, the pharmaceutical formulation may comprise at least about 50% by weight of solvent (for example, water, saline solution, a buffered saline solution, a polyol, a polyol ether, a C1-C7 alcohol, or a combination thereof). In other embodiments, the pharmaceutical formulation may comprise at least about 60% by weight of solvent. In other embodiments, the pharmaceutical formulation may comprise at least about 70% by weight of solvent. In other embodiments, the pharmaceutical formulation may comprise at least about 80% by weight of solvent. In other embodiments, the pharmaceutical formulation may comprise at least about 85% by weight of solvent, at least about 90% by weight of solvent, at least about 91% by weight of solvent, at least about 92% by weight of solvent; at least about 93% by weight of solvent; at least about 94% by weight of solvent; or at least about 95% by weight of solvent.

[0085] In some embodiments, the solvent may comprise a mixture of a C1-C7 alcohol, a polyol ether, and a polyol. In these embodiments, the pharmaceutical formulation may comprise from about 10 to about 50% by weight of the polyol ether; from about 5% to about 55% by weight of the polyol; and from about 5% to about 50% by weight of the C1-C7 alcohol. In some embodiments, the mixture of the C1-C7 alcohol, the polyol ether, and the polyol may be present in a ratio of approximately 1:1:1 on a w / w / w basis. In some embodiments, each of the C1-C7 alcohol, the polyol ether, and the polyol may be present at about 30% by weight. Petition 870250088666, dated 09 / 30 / 2025, p. 44 / 102 28 / 69

[0086] In some embodiments, the pharmaceutical formulation may comprise from about 15 to about 45% by weight of the polyol ether; from about 20 to about 40% by weight of the polyol ether; from about 25 to about 35% by weight of the polyol ether; or from about 30 to about 35% by weight of the polyol ether. In some embodiments, the pharmaceutical formulation may comprise about 30% by weight of the polyol ether. In other embodiments, the pharmaceutical formulation may comprise about 32% by weight of the polyol ether.

[0087] In some embodiments, the polyol ether may be selected from the group comprising or consisting of: polyethylene glycol, polypropylene glycol, polyethylene-polypropylene triblock copolymers, dipropylene glycol, diethylene glycol monoethyl ether (TRANSCUTOL™, Gattefossé, France), and combinations thereof.

[0088] When the polyol ether can be a polyethylene glycol (PEG), the PEG can have a number average molecular weight (Mn) that can be from about 200 g / mol to about 6,000 g / mol. In some embodiments, the PEG can be selected from the group comprising or the group consisting of: PEG 200, PEG 300, PEG 400, PEG 540 and PEG 600. In some embodiments, the polyol ether can be PEG 200. In other embodiments, the polyol ether can be PEG 400. Still in other embodiments, the polyol ether can be diethylene glycol monoethyl ether.

[0089] In some embodiments, the polyol may be selected from the group comprising or consisting of: propylene glycol, ethylene glycol, glycerol, hexanotriol, and combinations thereof. In some embodiments, the polyol may be glycerol. In preferred embodiments, the polyol may be propylene glycol.

[0090] In some embodiments, the polyol may be present in an amount ranging from about 5% to about 55% of the total formulation weight; from about 10% to about 50% of the total formulation weight; from about 20% of the Petition 870250088666, dated 09 / 30 / 2025, p. 45 / 102 29 / 69 weight up to about 45% of the total formulation weight; and, in some embodiments, from about 25% of the weight up to about 40% of the weight. In one particular embodiment, the polyol may comprise about 30% of the total formulation weight. In a further embodiment, the polyol comprising about 30% of the total formulation weight may be propylene glycol.

[0091] In some embodiments, the pharmaceutical formulation may comprise from about 5 to about 50% by weight of C1-C7 alcohol. In some embodiments, the pharmaceutical formulation may comprise from about 15 to about 45% by weight of C1-C7 alcohol; from about 20 to about 40% by weight of C1-C7 alcohol; or from about 25 to about 35% by weight of C1-C7 alcohol. In some embodiments, the pharmaceutical formulation may comprise about 30% by weight of C1-C7 alcohol. In further embodiments, the pharmaceutical formulation may comprise C1-C7 alcohol in an amount ranging from about 10% by weight to about 40% by weight, or from about 15% by weight to about 35% by weight.

[0092] In some embodiments, the C1-C7 alcohol may be selected from the group comprising or consisting of methanol, ethanol, isopropanol, n-butanol, n-propanol, and benzyl alcohol. In preferred embodiments, the C1-C7 alcohol may be ethanol. In some embodiments, the ethanol comprises about 30% of the weight of the total formulation. In other embodiments, the C1-C7 alcohol may be isopropanol.

[0093] In some embodiments, the C1-C7 alcohol may contain a small fraction of water, generally in the range of about 4 percent to about 5.1 percent by volume. In embodiments where the pharmaceutical formulation may be anhydrous, the C1-C7 alcohol containing about 4 percent to about 5.1 percent water by volume may be present in the pharmaceutical formulation in an amount such that the water content in the finished formulation itself may be less than about 5 percent of the Petition 870250088666, dated 09 / 30 / 2025, p. 46 / 102 30 / 69 weight or less, which is about 3% of the weight.

[0094] In some embodiments, the solvent may comprise a polyol, a polyol ether, and a C1-C7 alcohol. In some embodiments, the solvent may comprise ethanol as the C1-C7 alcohol, diethylene glycol monomethyl ether as the polyol ether, and propylene glycol as the polyol. These solvents may be present in any acceptable proportion, but typically are present such that each is about 25 to about 35% of the weight of the pharmaceutical formulation. Other components

[0095] In some embodiments, the pharmaceutical formulation may further comprise at least one additive selected from an acid, a buffer, an antioxidant, an emulsifier, a penetration enhancer, a moisturizer, a preservative, a chelating agent, and combinations thereof.

[0096] In some embodiments, the pharmaceutical formulation may comprise from about 0.1% to about 50% of the weight of each additive (for example, an acid, a buffer, an antioxidant, an emulsifier, a penetration enhancer, a moisturizer, a preservative, a chelating agent) relative to the total weight of the composition (i.e., constituting up to 100% of the weight).For example, each additive may be present in the pharmaceutical formulation in an amount of approximately 0.1% of the weight up to approximately 45% of the weight, approximately 0.1% of the weight up to approximately 40% of the weight, approximately 0.1% of the weight up to approximately 35% of the weight, approximately 0.1% of the weight up to approximately 30% of the weight, approximately 0.1% of the weight up to approximately 25% of the weight, approximately 0.1% of the weight up to approximately 20% of the weight, approximately 0.1% of the weight up to approximately 15% of the weight, approximately 0.1% of the weight up to approximately 10% of the weight, approximately 0.1% of the weight up to approximately 5% of the weight, approximately 0.1% of the weight up to approximately 2% of the weight, approximately 0.5% of the weight up to approximately 50% of the weight, approximately 0.5% of the weight up to approximately 45% of the weight, approximately 0.5% of body weight up to about 40% of body weight, approximately 0.5% of body weight up to about 35%. Petition 870250088666, dated 09 / 30 / 2025, page 47 / 102 31 / 69 of the weight, approximately 0.5% of the weight up to approximately 30% of the weight, approximately 0.5% of the weight up to approximately 25% of the weight, approximately 0.5% of the weight up to approximately 20% of the weight, approximately 0.5% of the weight up to approximately 15% of the weight, approximately 0.5% of the weight up to approximately 10% of the weight, approximately 0.5% of the weight up to approximately 5% of the weight, approximately 0.5% of the weight up to approximately 2% of the weight, approximately 1% of the weight up to approximately 50% of the weight, approximately 1% of the weight up to approximately 45% of the weight, approximately 1% of the weight up to approximately 40% of the weight, approximately 1% of the weight up to approximately 35% of the weight, approximately 1% of the weight up to approximately 30% of the weight, approximately 1% of the weight up to approximately 25% of the weight, approximately 1% of weight to about 20% of weight, about 1% of weight to about 15% of weight, about 1% of weight to about 10% of weight, about 1% of weight to about 5% of weight, about 1% of weight to about 2% of weight, about 50% of weight, about 48% of weight, about 46% of weight, about 44% of weight, about 42% of weight, about 40% of weight,approximately 38% of the weight, approximately 36% of the weight, approximately 34% of the weight, approximately 2% of the weight, approximately 30% of the weight, approximately 28% of the weight, approximately 26% of the weight, approximately 24% of the weight, approximately 22% of the weight, approximately 20% of the weight, approximately 18% of the weight, approximately 16% of the weight, approximately 14% of the weight, approximately 12% of the weight, approximately 10% of the weight, approximately 8% of the weight, approximately 6% of the weight, approximately 5% of the weight, approximately 4% of the weight, approximately 3% of the weight, approximately 2% of the weight, approximately 1% of the weight, approximately 0.9% of the weight, approximately 0.8% of the weight, approximately 0.7% of the weight, approximately 0.6% of the weight, approximately 0.5% of the weight, approximately 0.4% of the weight, approximately 0.3% of the weight, approximately 0.2% of the weight, or approximately 0.1% of the weight of the total composition.

[0097] In some embodiments, the pharmaceutical formulation may include an acid to help solubilize one or both of the active agents, to maintain a desired pH, or both. Any suitable acid may be used, such as, for example, a mineral acid (e.g., hydrochloric acid, sulfuric acid, nitric acid, or phosphoric acid), an organic acid (e.g., citric acid, Petition 870250088666, dated 09 / 30 / 2025, page 48 / 102 32 / 69 acetic acid, succinic acid or maleic acid), or mixtures thereof. Examples of suitable acidic additives include, for example, 1-hydroxy-2-naphthoic acid; 2,2-dichloroacetic acid; 2-hydroxyethanesulfonic acid; 2-oxoglutaric acid; 4-acetamidobenzoic acid; 4-aminosalicylic acid; acetic acid; adipic acid; L-ascorbic acid; L-aspartic acid; benzenesulfonic acid; benzoic acid; (+)-camphoric acid; (+)-camphor-10-sulfonic acid; capric acid (decanoic acid); caproic acid (hexanoic acid); caprylic acid (octanoic acid); carbonic acid; cinnamic acid; citric acid; cyclamic acid; dodecylsulfuric acid; ethane-1,2-disulfonic acid; ethanesulfonic acid; formic acid; fumaric acid; galactaric acid; gentisic acid; D-glucoheptonic acid; D-gluconic acid; D-glucuronic acid; glutamic acid; glutaric acid; glycerophosphoric acid; glycolic acid; hippuric acid; hydrobromic acid; hydrochloric acid; isobutyric acid; lactic acid;Lactobionic acid; lauric acid; maleic acid; L-malic acid; malonic acid; mandelic acid; methanesulfonic acid; naphthalene-1,5-disulfonic acid; naphthalene-2-sulfonic acid; nicotinic acid; nitric acid; oleic acid; oxalic acid; palmitic acid; pamoic acid; phosphoric acid; propionic acid; L-pyroglutamic acid; salicylic acid; sebacic acid; stearic acid; succinic acid; sulfuric acid; L-tartaric acid; thiocyanic acid; ptoluenesulfonic acid and undecylenic acid. In some embodiments, acetic acid, citric acid or lactic acid may be added to the pharmaceutical formulation.

[0098] In some embodiments, the acid may be added in a sufficient quantity so that the pH of the pharmaceutical formulation may be about 7.0 or less (e.g., about 4 to about 7.0, about 4 to about 6.5, about 4 to about 6, about 4 to about 5.5, about 4 to about 5, about 4.5 to about 7.0, about 4.5 to about Petition 870250088666, dated 09 / 30 / 2025, page 49 / 102 33 / 69 6.5, approximately 4.5 to approximately 6, approximately 4.5 to approximately 5.5, approximately 4.5 to approximately 5, approximately 5 to approximately 7.0, approximately 5 to approximately 6.5, approximately 5 to approximately 6, approximately 5 to approximately 5.5, approximately 5.5 to approximately 7.0, approximately 5.5 to approximately 6.5, approximately 5.5 to approximately 6, approximately 6 to approximately 7.0, or approximately 6 to approximately 6.5).

[0099] In some embodiments, the pharmaceutical formulation may include a buffer to help maintain the pH of the formulation within a desired range. In some embodiments, the buffer may be a phosphate buffer, citrate buffer, lactate buffer, or a combination thereof. In some embodiments, the formulation may comprise phosphoric acid, citric acid, lactic acid, or a combination thereof.

[0100] Because oxidation can result in degradation of the active agent, in some embodiments, the pharmaceutical formulation may include an antioxidant. In some embodiments, the antioxidant may be, for example, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbyl palmitate, ascorbic acid, alpha tocopherol, propyl gallate, 2,4,5-trihydroxybutyrophenone, 4-hydroxymethyl-2,6-di-tert-butylphenol, erythorbic acid, guaiac gum, thiodipropionic acid, dilauryl thiodipropionate, tert-butylhydroquinone, pharmaceutically acceptable salts or esters thereof, and combinations thereof. In some embodiments, the antioxidant may be ascorbyl palmitate, BHA, BHT, or a combination thereof. In some formulations, the antioxidant may be BHT, ascorbyl palmitate, or a combination of BHT and ascorbyl palmitate.

[0101] In some embodiments, the pharmaceutical formulation may include up to about 1% of the weight of an antioxidant. In some embodiments, the pharmaceutical formulation may include up to about 0.5% of the weight of an antioxidant or include about 0.5% of the weight of the antioxidant.

[0102] In some forms, the pharmaceutical formulation may Petition 870250088666, dated 09 / 30 / 2025, p. 50 / 102 34 / 69 include an emulsifier, particularly to provide a solution, a suspension, an emulsion, or a microemulsion. Without wanting to be tied to any particular theory, it is believed that emulsifiers, when present, help or facilitate the dissolution of any solid substances, such as an active agent, in the pharmaceutical formulation. In other embodiments, however, the emulsifier may be present to facilitate the incorporation of two immiscible liquids into each other (for example, to form an emulsion or microemulsion).

[0103] In other embodiments, and without wishing to be bound to any particular theory, an emulsifier may increase the spreadability of the product. For example, and without wishing to be bound to any particular theory, when the pharmaceutical formulation is a liquid solution, it is believed that the presence of an adequate amount of an emulsifier increases the surface tension between the pharmaceutical formulation and the lipid environment of the superficial layer of the skin and / or scalp. This makes it easier to spread the pharmaceutical formulation and is believed to aid in the penetration of the active agent(s) into the skin (including the scalp), hair follicles, or both.

[0104] In some embodiments, the emulsifier may be selected from the group comprising or consisting of: polyethylene glycol (PEG) fatty acid monoesters such as, for example, PEG-15 hydroxystearate (also known as polyoxyl-15-hydroxystearate), PEG-30 stearate, PEG-40 laurate, PEG-40 oleate and the like; polyoxyethylene sorbitan fatty acid esters (polysorbates) such as, for example, polysorbate 20, polysorbate 60, polysorbate 80 and the like; polyoxyethylene alkyl ethers such as, for example, PEG-20 cetostearyl ether, polyoxyl 25 cetostearyl, cetomacrogol 1000 and the like; sorbitan fatty acid esters such as, for example, sorbitan monolaurate, Petition 870250088666, dated 09 / 30 / 2025, page 51 / 102 35 / 69 sorbitan monopalmitate, sorbitan monooleate and the like; propylene glycol fatty acid esters; polyglycerol fatty acid esters; polyoxyethylene castor oil derivatives such as, for example, polyoxyl 5 castor oil, polyoxyl 15 castor oil, polyoxyl 35 castor oil, hydrogenated polyoxyl 40 castor oil and the like; caprylocapril polyoxyl-8 glycerides; polyoxylglycerides such as, for example, caprylocaproyl polyoxylglycerides, lauroyl polyoxylglycerides, oleoyl polyoxylglycerides and the like; polyoxyethylene lauryl alcohol; together with combinations of any of the aforementioned. In some embodiments, the emulsifier may be hydrogenated castor oil polyoxyl 40, polyoxyl-15-hydroxystearate, polysorbate 60, polysorbate 80, or a combination thereof.In preferred embodiments, the emulsifier may be a polysorbate such as, for example, polysorbate 60, polysorbate 80, or a combination of polysorbate 60 and polysorbate 80.

[0105] In some embodiments, the pharmaceutical formulation may include the emulsifier in an amount of up to about 5% of the total formulation weight (e.g., up to about 4% of the weight, up to about 3% of the weight, up to about 2% of the weight). In some embodiments, the emulsifier may be present in an amount ranging from 0.05 to 5% of the weight (e.g., from about 0.05% of the weight to about 4% of the weight, from about 0.05% of the weight to about 3% of the weight, from about 0.05% of the weight to about 2% of the weight). In preferred embodiments, the pharmaceutical formulation may include the emulsifier in an amount of approximately 0.1% by weight, approximately 0.2% by weight, approximately 0.3% by weight, approximately 0.4% by weight, approximately 0.5% by weight, approximately 0.6% by weight, approximately 0.7% by weight, approximately 0.8% by weight, approximately 0.9% by weight, approximately 1% by weight, approximately 1.5% by weight, approximately 2% by weight, approximately 2.5% by weight, approximately 3% by weight, approximately 3.5% by weight, approximately 4% by weight, approximately 4.5% by weight. Petition 870250088666, dated 09 / 30 / 2025, page 52 / 102 36 / 69 by weight or about 5% by weight. In further embodiments, the pharmaceutical formulation may include the emulsifier in an amount up to about 0.1% by weight, or it may include about 0.1% by weight of emulsifier. In further embodiments, the emulsifier may be present in the pharmaceutical formulation at about 0.1% by weight.

[0106] In some embodiments, the pharmaceutical formulation may include one or more penetration enhancers. Without adhering to a specific theory, penetration enhancers are believed to beneficially affect the release of the active agent(s) into the skin (including the scalp) and / or hair follicles. Advantageously, and in some embodiments, the solvent or some component (or components) of the solvent acts as a penetration enhancer. For example, in embodiments where the pharmaceutical formulation comprises ethanol and / or diethylene glycol monoethyl ether, these solvents may also act to increase the penetration of the active agent into the skin (including the scalp), hair follicles, or both. Notwithstanding the presence of ethanol and / or diethylene glycol monoethyl ether, the pharmaceutical formulations described in this descriptive report may still include additional penetration enhancers.

[0107] In some embodiments, the penetration enhancer may be selected from the group consisting of hydroxypropyl β-cyclodextrin, a diol, a polyol, a fatty acid (e.g., myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, or a combination thereof), a fatty alcohol, a fatty acid ester, a surfactant, a pyrrolidone, and combinations thereof. Examples of additional penetration enhancers that may be incorporated into formulations described in this descriptive report include, without limitation, polyoxymethylene alkyl ethers, polyoxyl glycerides, dimethyl sulfoxide, pyrrolidone, N Petition 870250088666, dated 09 / 30 / 2025, page 53 / 102 37 / 69 methyl-2-pyrrolidone, diethylene glycol monoethyl ether (e.g., TRANSCUTOL™, Gattefossé, France), dimethyl isosorbide, diethyl sebacate, azone, menthol, nerol, camphor, methyl salicylate, polysorbate 80 (e.g., TWEEN™ 80, Sigma-Aldrich, St. Louis, MO), SDS, benzalkonium chloride, polyoxyl 40 hydrogenated castor oil (e.g., CREMOPHOR™ RH40, KOLLIPHOR™ RH40, BASF, Germany), didecyldimethylammonium bromide (DDAB), didecyltrimethylammonium bromide (DTAB), fatty acid esters (e.g., isopropyl myristate, isopropyl palmitate), fatty acids (e.g., oleic acid, acid palmitic acid, linoleic acid, and salts thereof), fatty alcohols (e.g., oleyl alcohol, myristyl alcohol, and stearyl alcohol), medium-chain triglycerides, and combinations of any of the foregoing.

[0108] In some embodiments, the penetration enhancer may be dimethyl isosorbide. In other embodiments, the penetration enhancer may be a mixture comprising dimethyl isosorbide and diethylene glycol monoethyl ether. In other embodiments, the penetration enhancer may be dimethyl sulfoxide.

[0109] In some embodiments, the penetration enhancer may be present in an amount ranging from about 1% to about 50% of the weight relative to the total weight of the pharmaceutical formulation. In other embodiments, the penetration enhancer may be present from about 2% to about 40% of the weight relative to the total weight of the pharmaceutical formulation; or from about 5% to about 35% of the weight relative to the total weight of the pharmaceutical formulation. According to some embodiments, the penetration enhancer may be present in the pharmaceutical formulation described in this descriptive report in an amount of about 1%, about 2%, about 5%, or about 35% of the weight relative to the total weight of the pharmaceutical formulation. Petition 870250088666, dated 09 / 30 / 2025, p. 54 / 102 38 / 69 of 10% of the weight, approximately 15% of the weight, approximately 20% of the weight, approximately 25% of the weight, approximately 30% of the weight, approximately 35% of the weight, approximately 40% of the weight, approximately 45% of the weight, or approximately 50% of the weight in relation to the total weight of the pharmaceutical formulation.

[0110] In some embodiments, the pharmaceutical formulation may include one or more moisturizers. Without adhering to a specific theory, a moisturizer is believed to impart moisture and / or softness to the skin (including the scalp), particularly when a component known to dry the skin, such as an alcohol, is also present in the formulation. In some embodiments, the moisturizer may be a fatty alcohol, a fatty acid (e.g., myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, or a combination thereof), a fatty acid ester, an oil, a polyethylene glycol, glycerin, an alpha hydroxy acid, or a combination thereof.In some embodiments, the moisturizer may be cetyl alcohol, cetearyl alcohol, stearyl alcohol, stearic acid, isopropyl myristate, isopropyl palmitate, cocoa butter, lanolin, liquid paraffin, shea butter, a silicone oil, castor oil, a polyethylene glycol, glycerin, lactic acid, glycolic acid, malic acid, citric acid, tartaric acid, or a combination thereof. In some embodiments, the moisturizer may be cetyl alcohol, stearyl alcohol, or a combination of cetyl alcohol and stearyl alcohol.

[0111] In some embodiments, the pharmaceutical formulation may include one or more preservatives (e.g., an antibacterial, an antifungal). Suitable preservatives include, for example, a paraben (e.g., methylparaben, ethylparaben, propylparaben, butylparaben), a benzoate (e.g., sodium benzoate), a sorbate (e.g., potassium sorbate), a quaternary ammonium compound (e.g., benzalkonium chloride, benzethonium chloride), an alcohol (e.g., Petition 870250088666, dated 09 / 30 / 2025, page 55 / 102 39 / 69 chlorobutanol, benzyl alcohol, ethanol, phenol, m-cresol, chlorocresol), sodium metabisulfite, imidazolidinyl urea, glycerin, propylene glycol, or a combination thereof.

[0112] In some embodiments, the pharmaceutical formulation may include one or more chelating agents. Suitable chelating agents include, for example, citric acid, phytic acid, sodium phytate, clioquinol, ethylenediaminetetraacetic acid (EDTA) (e.g., disodium EDTA, tetrasodium EDTA), etidronic acid, galactaric acid, tetrahydroxypropyl ethylenediamine, sodium metasilicate, or a combination thereof. Methods of administration

[0113] The pharmaceutical formulations described in this descriptive report may be co-administered according to varying dosage regimens. In one embodiment, the method of administration of the pharmaceutical formulation may be continuous. For example, the pharmaceutical formulations may be applied topically once daily, twice daily, three times daily, four times daily, or more, as specified by a physician. In some embodiments, a formulation described in this descriptive report may be applied topically once daily or twice daily. According to a particular embodiment, the pharmaceutical formulation described in this descriptive report may be applied topically once daily. According to another embodiment, the pharmaceutical formulation described in this descriptive report may be applied topically twice daily.

[0114] In some embodiments, a dosage regimen can be changed gradually. That is, the pharmaceutical formulation can be applied once a day for an initial period of time, twice a day thereafter for a second period of time, three times a day thereafter for a third period of time, and so on. In one particular embodiment, the Petition 870250088666, dated 09 / 30 / 2025, p. 56 / 102 The 40 / 69 pharmaceutical formulation may be administered once daily on the first day, and twice daily thereafter, with the appropriate treatment duration determined by the individual's physician. Alternatively, gradual changeover of administration may involve administering the pharmaceutical formulation on a tapering schedule, starting with multiple administrations per day for an appropriate period of time and reducing the number of administrations over an appropriate period of time until a maintenance dosage schedule can be achieved. It is within the knowledge of a physician skilled in the art, armed with the present disclosure, to determine the appropriate starting point, rate of tapering, and maintenance dosage schedule.

[0115] In some embodiments, the pharmaceutical formulation may be applied over the duration of a period of days, weeks or months. For example, the pharmaceutical formulation may be applied once, twice, three, four or five times a day for up to: 1, 2, 3, 4, 5, 6 or 7 days (i.e., about 1 week); about 2 weeks, about 3 weeks or about 4 weeks; approximately 2 months, approximately 3 months, approximately 4 months, approximately 5 months, approximately 6 months, approximately 7 months, approximately 8 months, approximately 9 months, approximately 10 months, approximately 11 months, approximately one year (i.e., approximately 12 months), approximately 13 months, approximately 14 months, approximately 15 months, approximately 16 months, approximately 17 months, approximately 18 months, approximately 19 months, approximately 20 months, approximately 21 months, approximately 22 months, approximately 23 months, or approximately 24 months. Depending on the specific dosage, the pharmaceutical formulation may be applied once on the first day and twice daily thereafter for approximately 4 weeks.

[0116] In other modalities, the pharmaceutical formulation can be applied topically to the scalp once a day for 1 month, once a day for 2 months, once a day for 3 months, once a day for 4 months, once a day for 5 months, once a day Petition 870250088666, dated 09 / 30 / 2025, p. 57 / 102 41 / 69 for 6 months, once daily for 8 months, once daily for 12 months, once daily for 14 months, once daily for 16 months, once daily for 18 months, once daily for 20 months, once daily for 22 months, or once daily for 24 months. In some embodiments, the pharmaceutical formulation may be applied topically to the scalp once daily for 6 months. In some embodiments, the pharmaceutical formulation may be applied topically to the scalp once daily for 12 months.

[0117] In other embodiments, the pharmaceutical formulation may be applied topically to the scalp twice daily for: approximately 1 month; approximately 2 months; approximately 3 months; approximately 4 months; approximately 5 months; approximately 6 months; approximately 8 months; approximately 12 months; approximately 14 months; approximately 16 months; approximately 18 months; approximately 20 months; approximately 22 months; or approximately 24 months. In some embodiments, the pharmaceutical formulation may be applied topically to the scalp twice daily for 6 months. In some embodiments, the pharmaceutical formulation may be applied topically to the scalp twice daily for 12 months.

[0118] In other embodiments, the pharmaceutical formulation may be applied more than twice a day (i.e., 3 times a day (TID), 4 times a day (QID), etc.) for: approximately 1 month; for approximately 2 months; for approximately 3 months; for approximately 4 months; for approximately 5 months; for approximately 6 months, for approximately 8 months, for approximately 12 months, for approximately 14 months, for approximately 16 months, for approximately 18 months, for approximately 20 months, for approximately 22 months, or for approximately 24 months. In some embodiments, the pharmaceutical formulation may be applied topically to the scalp more than twice a day (i.e., TID, QID, etc.) for 6 months. In some embodiments, the pharmaceutical formulation may be applied topically to the scalp more than twice a day (i.e., TID, QID, etc.) for 12 months.

[0119] In another modality, the mode of administration of Petition 870250088666, dated 09 / 30 / 2025, p. 58 / 102 42 / 69 pharmaceutical formulations can be cyclical. For example, the pharmaceutical formulation may first be applied continuously as described above for a desired period of time, the application may then be suspended for a period of time such as, for example, a few days, and then the application of the pharmaceutical formulations may be started again, as described above. The treatment period may include one or more cycles which may be the same or different. In some modalities, the treatment period may be as follows: a) the pharmaceutical formulation may be applied topically to the scalp for a period of time such as, for example, 4 months, by continuous administration, b) the application may be suspended for a few days (e.g., 2 to 5 days), and 3) the topical application may be continued for an additional period of time such as, for example, 6 months.

[0120] In some embodiments, the method of administration may be cyclical, in that cortexolone-17α-propionate and minoxidil may be co-administered sequentially. For example, a pharmaceutical formulation comprising cortexolone-17α-propionate may be administered first for a first period of time, and a pharmaceutical composition comprising minoxidil may be administered second for a second period of time. In other embodiments, a pharmaceutical composition comprising minoxidil may be administered first and a pharmaceutical composition comprising cortexolone-17α-propionate may be administered second. The time period between when the first pharmaceutical composition may be administered and the second pharmaceutical composition may be administered may be any suitable time period. For example, the time between each administration may be on the order of seconds, minutes, hours, or days, as required.In some embodiments, the administration of the first and second pharmaceutical compositions may be separated by seconds (for example, approximately 60 seconds or less, approximately. Petition 870250088666, dated 09 / 30 / 2025, p. 59 / 102 43 / 69 seconds or less). In some embodiments, the administration of the first and second pharmaceutical compositions may be separated by hours (e.g., approximately 1 hour or less, approximately 2 hours or less, approximately 3 hours or less, approximately 5 hours or less, approximately 8 hours or less, approximately 12 hours or less, approximately 24 hours or less). In some embodiments, the administration of the first and second pharmaceutical compositions may be separated by days (e.g., approximately 1 day, approximately 2 days, approximately 3 days, approximately 4 days, approximately 5 days, approximately 6 days, or approximately 7 days). In some embodiments, the administration of the first and second pharmaceutical compositions may be separated by weeks (e.g., approximately 1 week, approximately 2 weeks, approximately 3 weeks, or approximately 4 weeks).

[0121] In some embodiments, a first pharmaceutical formulation comprising cortexolone-17α-propionate or minoxidil may be administered for an initial period of time, which may be on the order of days or weeks. During the initial period of time, the first pharmaceutical formulation may be administered multiple times to the skin or scalp, as described in this descriptive report, before a second pharmaceutical formulation comprising the other active agent may be administered for a second period of time. Similar to the initial period of time, the second period of time may be on the order of days or weeks. For example, a first pharmaceutical formulation comprising cortexolone-17α-propionate may be administered for an initial period of time (e.g., about 1 day or more, about 2 days or more, about 7 days or more, about 2 weeks or more, about 3 weeks or more, or about 4 weeks or more).A second pharmaceutical formulation comprising minoxidil may be administered for a second period of time (e.g., about 1 day or more, about 2 days or more, about 7 days or more, about 2 weeks or more). Petition 870250088666, dated 09 / 30 / 2025, pp. 60 / 102 44 / 69 plus, approximately 3 weeks or more or approximately 4 weeks or more). In some modalities, an individual may alternate (e.g., cycle between) administration between the first and second pharmaceutical formulations for a certain period of time to effect treatment.

[0122] The “effective amount of each active agent” is an amount that provides the desired outcome (e.g., to induce hair growth and / or regrowth). In some embodiments, the pharmaceutical formulation may comprise cortexolone-17α-propionate, minoxidil, or both active agents, in a concentration from about 0.1% by weight to about 20% by weight. For example, the pharmaceutical formulation may comprise cortexolone-17α-propionate, minoxidil, or both active agents, in a concentration of about 0.1% by weight or more (e.g., about 0.2% by weight or more, about 0.3% by weight or more, about 0.4% by weight or more, about 0.5% by weight or more, about 0.6% by weight or more, about 0.7% by weight or more, about 0.8% by weight or more, about 0.9% by weight or more, about 1% of body weight or more, approximately 1.2% of body weight or more, approximately 1.4% of body weight or more, approximately 1.6% of body weight or more, approximately 1.8% of body weight or more,approximately 2% of weight or more, approximately 2.2% of weight or more, approximately 2.4% of weight or more, approximately 2.6% of weight or more, approximately 2.8% of weight or more, approximately 3% of weight or more, approximately 3.2% of weight or more, approximately 3.4% of weight or more, approximately 3.6% of weight or more, approximately 3.8% of weight or more, approximately 4% of weight or more, approximately 4.2% of weight or more, approximately 4.4% of weight or more, approximately 4.6% of weight or more, approximately 4.8% of weight or more, approximately 5% of weight or more, approximately 5.2% of weight or more, approximately 5.4% of weight or more, approximately 5.6% of weight or more, approximately 5.8% of weight or more, approximately 6% of weight or more, approximately 6.2% of body weight or more, approximately 6.4% of body weight or more, approximately 6.6% of body weight or more, approximately 6.8% of body weight or more, approximately 7% of body weight or more, Petition 870250088666, dated 09 / 30 / 2025, pp. 61 / 102 45 / 69 approximately 7.2% of the weight or more approximately 7.4% of the weight or more approximately 7.6% of the weight or more, approximately 7.8% of the weight or more approximately 8% of body weight or more, approximately 8.2% of body weight or more, approximately 8.4% of body weight or more, approximately 8.6% of body weight or more, approximately 8.8% of body weight or more, approximately 9% of body weight or more, approximately 9.2% of body weight or more, approximately 9.4% of body weight or more, approximately 9.6 times the weight or more, approximately 9.8 of the weight or more approximately 10% of the weight or more approximately 10.5 of the weight or more approximately of the weight or more approximately 11.5 times the weight or more, approximately 12% of the weight or more approximately 12.5 times the weight or more, approximately 13% of the weight or more approximately 13.5 of the weight or more approximately 14% of the weight or more approximately 14.5 of the weight or more approximately 15% of the weight or more approximately 15.5 of the weight or more approximately of the weight or more approximately 16.5 of the weight or more approximately 17% of the weight or more approximately 17.5 of the weight or more approximately 18% of the weight or more approximately 18.5 of the weight or more approximately of the weight or more or approximately 19.5 of the weight or more) up to about 19.5 of the weight or less (for example about ... 19.5 of the weight or less approximately of the weight or less approximately 18.5 of the weight or less, approximately 18% of the weight or less, approximately 17.5 of the weight or less, approximately 17% of the weight or less, approximately 16.5 of the weight or less approximately of the weight or less approximately 15.5 of the weight or less, approximately 15% of the weight or less, approximately 14.5 of the weight or less, approximately 14% of the weight or less, approximately 13.5 of the weight or less, approximately 13% of the weight or less, approximately 12.5 of the weight or less, approximately 12% of the weight or less, approximately 11.5 times the weight or less, approximately, of the weight or less, approximately. 10.5 of the weight or less, approximately 10% of the weight or less, approximately 9.5 of the weight or less, approximately 9% of the weight or less, approximately 8.5 of the weight or less, approximately 8% of the weight or less, approximately 7.5 of the weight or less, approximately 97% of the weight or less, approximately 6.5 times the weight or less, approximately 6% of the weight or less, approximately 5.8% of the weight or less, approximately 5.6% of the weight or less, approximately 5.4% of body weight or less Petition 870250088666, dated 09 / 30 / 2025, pp. 62 / 102 46 / 69 approximately 5.2% of weight or less, approximately 5% of weight or less, approximately 4.8% of weight or less, approximately 4.6% of weight or less, approximately 4.4% of weight or less, approximately 4.2% of weight or less, approximately 4% of weight or less, approximately 3.8% of weight or less, approximately 3.6% of weight or less, approximately 3.4% of weight or less, approximately 3.2% of weight or less, approximately 3% of weight or less, approximately 2.8% of weight or less, approximately 2.6% of weight or less, approximately 2.4% of weight or less, approximately 2.2% of weight or less, approximately 2% of weight or less, approximately 1.8% of weight or less, approximately 1.6% of weight or less, approximately 1.4% of weight or less, approximately 1.2% of weight or less weight or less, approximately 1% of weight or less, approximately 0.9% of weight or less, approximately 0.8% of weight or less, approximately 0.7% of weight or less, approximately 0.6% of weight or less, approximately 0.5% of weight or less, approximately 0.4% of weight or less, approximately 0.3% of weight or less, or approximately 0.2% of weight or less).In preferred embodiments, the pharmaceutical formulation may comprise cortexolone-17α-propionate, minoxidil, or both active agents, in a concentration ranging from about 0.5% of weight to about 18% of weight or from about 1% of weight to about 15% of weight or from about 1.5% of weight to about 15% of weight or from about 2% of weight to about 12% of weight or from about 2.5% of weight to about 10% of weight or from about 2.5% of weight to about 8% of weight or from about 3% of weight to about 7% of weight.

[0123] In some embodiments, the pharmaceutical formulation may comprise cortexolone-17α-propionate at a concentration of about 1% by weight to about 20% by weight. In some embodiments, the pharmaceutical formulation may comprise minoxidil at a concentration of about 0.1% by weight to about 20% by weight. In some embodiments, the pharmaceutical formulation may be a solution that may comprise cortexolone-17α-propionate at a concentration of about 1% by weight to about 20% by weight and minoxidil at a concentration of about 0.1%. Petition 870250088666, dated 09 / 30 / 2025, pp. 63 / 102 47 / 69 of the weight up to about 20% of the weight. In preferred embodiments, the pharmaceutical formulation may be a solution comprising about 5% of the weight of cortexolone-17α-propionate and about 5% of the weight of minoxidil.

[0124] In some embodiments, the amount of cortexolone-17a-propionate in a single application may vary from about 20 mg to about 400 mg. In other embodiments, the amount of cortexolone-17a-propionate in a single application may vary from about 20 mg to about 350 mg. In other embodiments, the amount of cortexolone-17a-propionate in a single application may vary from about 20 mg to about 300 mg. In other embodiments, the amount of cortexolone-17a-propionate in a single application may vary from about 20 mg to about 250 mg.

[0125] In some embodiments, the amount of cortexolone-17a-propionate in a single application may vary from about 20 mg to about 200 mg. In other embodiments, the amount of cortexolone-17a-propionate in a single application may vary from about 20 mg to about 170 mg. In other embodiments, the amount of cortexolone-17a-propionate in a single application may vary from about 20 mg to about 150 mg. In some embodiments, the amount of cortexolone-17a-propionate in a single application may vary from about 20 mg to about 100 mg. In some embodiments, the amount of cortexolone-17apropionate in a single application may be approximately 20 mg, approximately 25 mg, approximately 30 mg, approximately 35 mg, approximately 40 mg, approximately 45 mg, approximately 50 mg, approximately 55 mg, approximately 60 mg, approximately 75 mg, approximately 80 mg, approximately 85 mg, approximately 90 mg, or approximately 100 mg.In another embodiment, the amount of cortexolone-17a-propionate in a single application may be approximately 25 mg. In another embodiment, the amount of cortexolone-17a-propionate in a single application may be approximately 30 mg. In yet another embodiment, the amount of cortexolone-17a-propionate in a... Petition 870250088666, dated 09 / 30 / 2025, pp. 64 / 102 In a single application of 48 / 69, the amount may be approximately 50 mg. In another embodiment, the amount of cortexolone-17a-propionate in a single application may be approximately 75 mg. In yet another embodiment, the amount of cortexolone-17a-propionate in a single application may be approximately 80 mg. In yet another embodiment, the amount of cortexolone-17a-propionate in a single application may be approximately 100 mg. In other embodiments, the amount of cortexolone-17a-propionate in a single application may be approximately 110 mg, approximately 111 mg, approximately 112 mg, approximately 113 mg, approximately 114 mg, approximately 115 mg, approximately 116 mg, approximately 117 mg, approximately 118 mg, approximately 119 mg, or approximately 200 mg. In yet another form, the amount of cortexolone-17a-propionate in a single application can be around 150 mg.

[0126] In some modalities, the amount of minoxidil in a single application may vary from about 2 mg to about 20 mg. In other modalities, the amount of minoxidil in a single application may vary from about 2 mg to about 15 mg. In other modalities, the amount of minoxidil in a single application may vary from about 2 mg to about 10 mg. In other modalities, the amount of minoxidil in a single application may vary from about 2 mg to about 5 mg.

[0127] In some embodiments, the pharmaceutical formulation can be self-administered by the individual once daily or twice daily. In some embodiments, when the pharmaceutical formulation can be in liquid form that has a concentration of cortexolone-17α-propionate of about 5% by weight and a concentration of minoxidil of about 5% by weight, the pharmaceutical formulation can be self-administered once daily or twice daily in a dose ranging from about 0.2 to about 2.0 ml, from about 0.5 to about 1.5 ml and, in additional embodiments, to about 1 ml or about 1.5 ml.

[0128] In some modalities, when the formulation Petition 870250088666, dated 09 / 30 / 2025, pp. 65 / 102 49 / 69 pharmaceutical formulations may be in liquid form containing a cortexolone-17α-propionate concentration of approximately 2.5% by weight and a minoxidil concentration of approximately 2% by weight. The pharmaceutical formulation may be self-administered once daily or twice daily in doses ranging from approximately 0.2 to approximately 2.0 ml, from approximately 0.5 to approximately 1.5 ml, and in additional embodiments, to approximately 1 ml or approximately 1.5 ml.

[0129] In some embodiments, when the pharmaceutical formulation may be in liquid form having a cortexolone-17α-propionate concentration of about 3% by weight and a minoxidil concentration of about 3% by weight, the pharmaceutical formulation may be self-administered once daily or twice daily in a dose ranging from about 0.2 to about 2.0 ml, from about 0.5 to about 1.5 ml and, in additional embodiments, to about 1 ml or about 1.5 ml.

[0130] In some embodiments, when the pharmaceutical formulation may be in liquid form that has a cortexolone-17α-propionate concentration of about 7.5% by weight and a minoxidil concentration of about 1.5% by weight, the pharmaceutical formulation may be self-administered once daily or twice daily in a dose ranging from about 0.2 to about 2.0 ml, from about 0.5 to about 1.5 ml and, in additional embodiments, to about 1 ml or about 1.5 ml.

[0131] The pharmaceutical formulation described in this descriptive report can be applied to any body surface requiring treatment, such as a skin region susceptible to hair growth induction. Suitable skin regions include, for example, the scalp, face (e.g., eyebrows, eyelashes, upper lip, lower lip, chin, cheeks, beard area, or mustache area), arms, armpits, legs, chest, abdomen, or any combination thereof. In some embodiments, treatment is not permitted on the face. In other embodiments, the formulation Petition 870250088666, dated 09 / 30 / 2025, page 66 / 102 50 / 69 pharmaceutical can be applied to the scalp. Kit

[0132] The present disclosure further provides a kit comprising one or more topical pharmaceutical formulations in various forms, as described in this descriptive report. The kit may contain one or more liquid or semi-solid formulations suitable for administration. The kit may also comprise an administration device such as, for example, a dropper, a pipette or an injection device (e.g., manual or electronically operated), for use by those skilled in the art. The kit may also include instructions for the preparation and administration of the (one or more) pharmaceutical formulations. The instructions may be in various formats such as, for example, printed material, magnetic disk, magnetic tape, compact disc, flash memory, or other suitable means for transmitting the appropriate information.

[0133] In some embodiments, the kit may comprise a pharmaceutical formulation comprising cortexolone-17apropionate as a first component and a pharmaceutical formulation comprising minoxidil as a second component. The kit may further comprise instructions for use of the first and second components. In some embodiments, the first component and the second component may be combined shortly before use (for example, within 1 hour before use, within 45 minutes before use, within 30 minutes before use, within 20 minutes before use, within 15 minutes before use, within 10 minutes before use, or within 5 minutes before use) and applied to the skin or scalp as the single combined formulation. In some embodiments, both the first and second components are solutions. In some embodiments, one or both of the first and second components may be a gel.In some embodiments, one or both of the first and second components may be a cream. In some embodiments, one or... Petition 870250088666, dated 09 / 30 / 2025, pp. 67 / 102 51 / 69 Both the first and second components can be a foam.

[0134] In some embodiments, the kit may comprise cortexolone-17a-propionate in solid form as a first component and a pharmaceutical formulation comprising minoxidil as a second component. The kit may also include instructions for use of the first and second components. In some embodiments, the cortexolone-17a-propionate in solid form may be a powder, a rapidly disintegrating tablet, a granule, a pellet, and the like. Preferably, the cortexolone-17a-propionate is in powder form. In some embodiments, the cortexolone-17a-propionate in solid form may be stored separately from the container containing the pharmaceutical formulation comprising minoxidil. In these embodiments, the cortexolone-17a-propionate in solid form may be stored inside a capped bottle or sealed container.

[0135] In some embodiments, cortexolone-17a-propionate in solid form may be stored within the same container that contains the pharmaceutical formulation comprising minoxidil. According to these embodiments, cortexolone-17a-propionate in solid form may be stored in a constituent part of the container containing the pharmaceutical formulation comprising minoxidil, which is designed to prevent contact between the two active agents. In some embodiments, the constituent part of the container, which is designed to prevent contact between cortexolone-17a-propionate in solid form and the pharmaceutical formulation comprising minoxidil, may be a lid containing a storage chamber for a solid substance (e.g., a reservoir lid), or a chamber separate from the main chamber containing the pharmaceutical formulation comprising minoxidil. In some embodiments, the container containing the pharmaceutical formulation comprising minoxidil may Petition 870250088666, dated 09 / 30 / 2025, pages 68 / 102 52 / 69 is capped with a reservoir cap containing cortexolone-17a-propionate in solid form, which is equipped with a cutting device activated by the individual pushing, twisting, or pulling the cap itself. According to this embodiment, activation of the cutting device on the reservoir cap allows the cortexolone-17a-propionate in solid form to come into contact with the pharmaceutical formulation comprising minoxidil.

[0136] In some embodiments, the first component and the second component may be combined shortly before use (for example, within 1 hour before use, within 45 minutes before use, within 30 minutes before use, within 20 minutes before use, within 15 minutes before use, within 10 minutes before use, or within 5 minutes before use) and applied to the skin or scalp as a single combined formulation. In some embodiments, the first component may be in solid form and the second component may be a solution. In some embodiments, the first component may be in solid form and the second component may be a gel. In some embodiments, the first component may be in solid form and the second component may be a cream. In some embodiments, the first component may be in solid form and the second component may be a foam.

[0137] In some embodiments, the kit may comprise minoxidil in solid form as a first component and a pharmaceutical formulation comprising cortexolone-17apropionate as a second component. The kit may also include instructions for use of the first and second components. In some embodiments, the minoxidil in solid form may be a powder, a rapidly disintegrating tablet, a granule, a pellet, and the like. In some embodiments, the minoxidil in solid form may be stored separately from the container containing the pharmaceutical formulation comprising cortexolone-17a-propionate. In these embodiments, minoxidil in Petition 870250088666, dated 09 / 30 / 2025, pages 69 / 102 53 / 69 solid form can be stored inside a capped jar or sealed bottle.

[0138] In some embodiments, minoxidil in solid form may be stored within the same container that contains the pharmaceutical formulation comprising cortexolone-17a-propionate. According to these embodiments, minoxidil in solid form may be stored in a constituent part of the container that contains the pharmaceutical formulation comprising cortexolone-17a-propionate, which is designed to prevent contact between the two. In some embodiments, the constituent part of the container, which is designed to prevent contact between the minoxidil in solid form and the pharmaceutical formulation comprising cortexolone-17a-propionate, may be a lid containing a storage chamber for a solid substance (e.g., a reservoir lid), or a chamber separate from the main chamber containing the pharmaceutical formulation comprising cortexolone-17a-propionate.In some embodiments, the container holding the pharmaceutical formulation comprising cortexolone-17α-propionate may be capped with a reservoir cap containing minoxidil in solid form, which is equipped with a cutting device activated by pushing, twisting, or pulling the cap itself. According to this embodiment, activation of the cutting device on the reservoir cap allows the minoxidil in solid form to come into contact with the pharmaceutical formulation comprising cortexolone-17α-propionate. In some embodiments, the first component and the second component may be combined shortly before use (e.g., within 1 hour before use, within 45 minutes before use, within 30 minutes before use, within 20 minutes before use, within 15 minutes before use, within 10 minutes before use, or within 5 minutes before use) and applied to the skin or scalp as the single combined formulation.In some modalities, the first component may be in shape. Petition 870250088666, dated 09 / 30 / 2025, pp. 70 / 102 54 / 69 solid and the second component may be a solution. In some embodiments, the first component may be in solid form and the second component may be a gel. In some embodiments, the first component may be in solid form and the second component may be a cream. In some embodiments, the first component may be in solid form and the second component may be a foam. Stability in storage

[0139] Storage stability is an important metric for pharmaceutical products. In general, greater stability means that a given formulation is both easier to transport and store, which increases the likelihood that it will be stocked by pharmacies and that individuals will not have to worry about special storage instructions. In some embodiments, the pharmaceutical formulation described in this descriptive report may have a desirable stability profile allowing the final formulation to be stored for at least about 3 months, at least about 6 months, at least about 9 months, at least about 12 months, at least about 15 months, at least about 18 months, at least about 21 months, or at least about two years – each at room temperature (around 20°C) or at refrigerated temperatures (e.g., around 4°C).

[0140] For example, one of the main degradation pathways of cortexolone-17α-propionate is transesterification to cortexolone-21-propionate (17α-hydroxy-21-propionyloxy-pregna-4-ene-3,20-dione): .0 \θH� Petition 870250088666, dated 09 / 30 / 2025, pp. 71 / 102 55 / 69

[0141] In some embodiments, maintaining the pharmaceutical formulations disclosed in this descriptive report at an acidic pH, including a pH of less than 7.0 (for example, less than about 6.5, less than about 6, less than about 5.5, less than about 5, less than about 4.5, between about 4 and about 7, between about 4 and about 6.5, between about 4 and about 6, between about 4 and 5.5, between about 4 and 5, between about 4 and about 4.5, or at about 6.5, about 6, about 5.5, about 5, about 4.5 or about 4), may slow down this degradation process. In some applications, the pH may be around 4. The appropriate pH can be obtained by adding an adequate amount of a pH modifier, such as the acids described in this descriptive report.

[0142] In some embodiments, the pharmaceutical formulations described in this descriptive report may, at room temperature (around 20°C) or at refrigerated temperatures (e.g., around 4°C), have less than about 5% by weight of cortexolone-21-propionate or other degradation products after storage for a period of about 24 months. FIGURES

[0143] Figure 1: IL-6 concentration in Human Hair Follicle Dermal Papilla (HFDPC) cell cultures after 24 hours of treatment with the drug.

[0144] Figure 2: Side-by-side comparison of IL-6 concentrations for clascoterone + DHT groups vs. clascoterone + DHT + minoxidil groups in HFDPC. EXAMPLES

[0145] The pharmaceutical formulations described in this descriptive report will now be further detailed with reference to the following examples. These examples are provided for illustrative purposes only and the embodiments described in this report Petition 870250088666, dated 09 / 30 / 2025, pp. 72 / 102 56 / 69 descriptive examples should in no way be considered as being limited to these examples. On the contrary, the modalities should be interpreted as encompassing any and all variations that become evident as a result of the teachings provided in this descriptive report. Example 1: 5% w / w anhydrous solution of cortexolone-17αpropionate

[0146] A 5% w / w (w / w) solution of cortexolone-17apropionate having the components shown in Table 1 below was prepared by dissolving the active agent in the solvent mixture, followed by the addition of the emulsifier (Polysorbate 80). Table 1 Component Quantity (g / 100 g) Cortexolone-17apropionate 5.26 Diethylene glycol monoethyl ether 31.75 Alcohol (Ethanol) 31.75 Polysorbate 80 0.11 Propylene glycol 31.12 Citric acid monohydrate 0.04

[0147] This formulation provided the stability profile (40°C and 75% relative humidity (RH)) shown in Table 2. Table 2 Time Point Cortexolone-17αpropionate (% by weight) Cortexolone 21-propionate (% by weight)* Total impurities (% by weight)* 0 5.108 0.07 0.13 1 month 5.046 1.08 1.19 Petition 870250088666, dated 09 / 30 / 2025, pp. 73 / 102 57 / 69 3 months 4, 989 2.78 3. 11 6 months 4.847 4.76 5. 23 * Cortexolone-21-propionate content calculated as (% (w / w) of cortexolone-21-propionate) / (% (w / w) of cortexolone-17-propionate x 100) Example 2: 5% w / w minoxidil foam

[0148] A 5% by weight (w / w) minoxidil foam containing the components shown in Table 3 can be prepared. Table 3 Component Quantity (g / 100 g) Minoxidil 5.0 Cetyl alcohol 2.2 Stearyl alcohol 1 Ethanol 51.8 Polysorbate 60 0.4 Polyoxyethylene lauryl alcohol 1 Propylene glycol 5 Propellant P75 4.3 Acetic alcohol qs pH 6.0 Purified water qs to 100 g qs: quantum satis (sufficient quantity) Example 3: 5% w / w minoxidil solution

[0149] A 5% by weight (w / w) minoxidil solution containing the components shown in Table 4 can be prepared. Table 4 Component Quantity (g / 100 g) Minoxidil 5.0 Propylene glycol 35 Ethanol 48 Water qs to 100 g

[0150] Ethanol and propylene glycol are mixed and heated. Petition 870250088666, dated 09 / 30 / 2025, pp. 74 / 102 58 / 69 up to 60-70°C; when the temperature is within the above range (60-70°C), minoxidil is added and the mixture is kept under stirring until the minoxidil is completely dissolved. Next, water is slowly added to the mixture while stirring and maintaining the temperature in the 60-70°C range, until the final weight is reached. Then, the mixture is slowly cooled to room temperature while stirring. Example 4: Solution of minoxidil (2.5% w / w) and cortexolone 17α-propionate (2.5% w / w)

[0151] A solution of minoxidil (2.5% w / w) and cortexolone-17apropionate (2.5% w / w) having the components shown in Table 5 can be prepared. Table 5 Component Quantity (g / 100 g) Minoxidil 2.5 Cortexolone-17apropionate 2.5 Propylene glycol 35 Ethanol 48 Water qs to 100 g

[0152] Ethanol and propylene glycol are mixed and heated to 60-70°C; when the temperature is within the above range (60-70°C), minoxidil is added and the mixture is kept under Stir until the minoxidil is completely dissolved. Then, cortexolone-17α-propionate is added and the mixture is kept under stirring until the minoxidil is completely dissolved. Next, water is slowly added to the mixture while stirring and maintaining the temperature in the range of 60-70°C, until the final weight is reached. Then, the mixture is slowly cooled to room temperature while stirring. Example 5: Kit containing a solution of minoxidil (5.0% w / w) and cortexolone-17α-propionate in solid form.

[0153] A 5% by weight (w / w) minoxidil solution containing Petition 870250088666, dated 09 / 30 / 2025, pp. 75 / 102 59 / 69 of the components shown in Table 6 can be prepared. Table 6 Component Quantity (g / 100 g) Minoxidil 5.0 Propylene glycol 35 Ethanol 48 Water qs to 100 g

[0154] Ethanol and propylene glycol are mixed and heated to 60-70°C; when the temperature is within the above range (60-70°C), minoxidil is added and the mixture is kept under stirring until the minoxidil is completely dissolved. Next, water is slowly added to the mixture under stirring and maintaining the temperature in the 60-70°C range, until the final weight is reached. Next, the mixture is slowly cooled to room temperature under stirring. The solution containing minoxidil is then filled into 60 ml glass bottles. Cortexolone-17α-propionate powder is filled into the reservoir cap storage container (approximately 3 g per cap). The 60 ml bottles containing the minoxidil solution are then capped with the reservoir caps filled with cortexolone-17α-propionate powder. Example 6: Kit containing a solution of cortexolone-17αpropionate (5.0% w / w) and minoxidil in solid form.

[0155] A 5% by weight (w / w) solution of cortexolone-17apropionate having the components shown in Table 7 can be prepared. Table 7 Component Quantity (g / 100 g) Cortexolone-17apropionate 5.26 Diethylene glycol monoethyl ether 31.75 Alcohol (Ethanol) 31.75 Petition 870250088666, dated 09 / 30 / 2025, pp. 76 / 102 60 / 69 Polysorbate 80 0.11 Propylene glycol 31.12 Citric acid monohydrate 0.04

[0156] A 5% by weight (w / w) solution of cortexolone-17a-propionate having the components shown in Table 7 was prepared by dissolving the active agent in the solvent mixture, followed by the addition of the emulsifier (Polysorbate 80). The solution containing cortexolone-17a-propionate is then filled into 60 ml glass bottles. Minoxidil powder is filled into the reservoir cap storage container (approximately 3 g per cap). The 60 ml bottles containing the cortexolone-17a-propionate solution are then capped with the reservoir caps filled with minoxidil powder. Example 7. The combined treatment of clascoterone and minoxidil synergistically inhibits IL-6 secretion in Human Hair Follicle Dermal Papilla (HFDPC) cells.

[0157] Clascoterone is a potent antiandrogen that blocks the effects of the androgen receptor in human hair follicles. Topical administration demonstrates clinically significant efficacy in AGA. Part of its mechanism of action is to inhibit androgen-induced IL-6 secretion by HFDPC, and this reduces IL-6-induced hair follicle damage. Thus, IL-6 secretion by these cells is a relevant efficacy biomarker that correlates with hair growth.

[0158] Minoxidil is a KATP channel modulator that demonstrates topical efficacy in AGA. There are no reports of its effects on IL-6 secretion in HFDPC.

[0159] In this study, the combination of clascoterone with minoxidil in inhibiting IL-6 secretion by HFDPC was better than expected. That is, the combined efficacy was greater than the simple addition of the efficacy of each agent alone.

[0160] The results suggest that the synergistic combination of Petition 870250088666, dated 09 / 30 / 2025, pp. 77 / 102 61 / 69 topical clascoterone and topical minoxidil should provide significantly increased efficacy when used in patients with AGA. Rationale

[0161] The majority of the hair follicle is composed of keratinocytes, the epithelial cells that comprise the hair shaft itself, as well as the inner and outer root sheaths that surround it. However, a specialized mesenchymal population, the dermal papilla (DP), plays a critical role in directing the activities of these keratinocytes to form the follicle and generate the hair shaft (Greco et al. 2009). Active communication between the DP or its precursors and the epithelial compartment regulates many aspects of follicle biology. The DP influences the size and shape of the hair shaft by generating signals that act on the keratinocytes.

[0162] In androgenetic alopecia, a reduction in hair follicle size associated with progressive thinning and hair loss includes an inability to maintain PD cell function (Elliott et al. 1999). Several observations suggest that this stems from a primary defect in PD. One of the fundamental paracrine factors produced by PD cells in male pattern baldness is the cytokine IL-6.

[0163] IL-6, in response to dihydrotestosterone (DHT), is upregulated in PD cells in baldness compared to PD cells without baldness (Kwack et al. 2012); IL-6 receptors are expressed in follicular keratinocytes, including matrix cells. Recombinant human IL-6 (rhIL-6) inhibited hair shaft elongation and suppressed matrix cell proliferation in cultured human hair follicles. Furthermore, rhIL-6 injection into the hypodermis of mice during anagen (hair growth phase) caused premature onset of catagen (growth inhibition). Thus, DHT-inducible IL-6 inhibits hair growth as a paracrine mediator by PD (Kwack et al. 2012). Petition 870250088666, dated 09 / 30 / 2025, pp. 78 / 102 62 / 69

[0164] There are three classes of drugs that are effective in halting the progression of hair loss: antiandrogens (e.g., Clascoterone), 5-α-reductase type 2 inhibitors (e.g., Finasteride), and KTP channel inhibitors (e.g., Minoxidil). These compounds act on PD cells in cell cultures or isolated hair follicles (Kaufman et al. 1998; Randall 2008; Shorter et al. 2008).

[0165] Clascoterone has been shown to inhibit DHT-induced IL-6 expression in dermal papilla cells (Rosette et al. 2019). However, it is not known whether minoxidil can modulate IL-6 expression in PD cells or whether the combination of clascoterone and minoxidil may demonstrate greater efficacy than either agent alone. Experimental section Cell lines

[0166] Human Hair Follicle Dermal Papilla (HFDPC) cells from the vertex region of the human scalp were obtained from Cell Applications (San Diego, CA). Cells were propagated in Complete Hair Follicle Dermal Papilla Cell Basal Medium (Cell Applications, San Diego, CA) and 10% fetal bovine serum (Gibco, Gaithersburg, MD). All flasks and plates used were coated with collagen. Collagen was obtained from Cell Applications (San Diego, CA) and used according to the manufacturer's instructions. For analysis of IL6 secretion, cells were trypsinized and seeded (2 x 10⁵ cells per well) in 24-well collagen-coated plates containing Dermal Hair Follicle Papilla Cell Basal Medium and 5% charcoal-dextran filtered serum (DCC-FBS) (Omega Scientific, Tarzana, CA) and incubated overnight. Experiments were performed in triplicate in wells.The following day, the medium was removed and fresh Basal medium + DCC-FBS 5% containing the compounds and DHT were added and incubated for 24 hours. All cell incubations were performed at 37°C and 5% CO2. For the... Petition 870250088666, dated 09 / 30 / 2025, pp. 79 / 102 63 / 69 concentrations of compounds used in these experiments were determined to have no significant effect on cell proliferation (data not shown). Compounds

[0167] Clascoterone (CB0301) was custom synthesized for Cosmo Pharmaceuticals (Lainate, Italy). Dihydrotestosterone (DHT) was obtained from Millipore-Sigma (Saint Louis, MO) and Minoxidil was obtained from VWR (San Diego, CA). All compounds were dissolved in 100% DMSO and then diluted in 5% HFDP + DCC-FBS Basal Medium for cell culture experiments. The final DMSO concentrations in each well were 0.1%. Quantification of IL-6 protein expression by ELISA.

[0168] Various concentrations of DHT, clascoterone, and minoxidil were used to treat dermal papilla cells. The compounds were added simultaneously (without pre-incubation) to the wells. After 24 hours of culture, the medium in each well was collected and used immediately for the determination of secreted IL-6. The Human IL-6 ELISA detection kit was from Invitrogen (San Diego, CA) and used according to the manufacturer's instructions. Absorbance was quantified using a ClarioStar microplate reader (Ortenberg, Germany), and the data were analyzed using Prism software version 10.1.1 (GraphPad, La Jolla, CA). Results

[0169] Figure 1 shows that incubation of HFDPC with 100 nM DHT for 24 hours resulted in significantly increased IL-6 secretion, compared with 0.1% DMSO used as a control (47.5 pg / ml vs. 39.2 pg / ml; p < 0.004). Minoxidil at a concentration of 1 mM in the presence of DHT only slightly decreased IL-6 secretion by 7% (47.5 pg / ml to 44.3 pg / ml).

[0170] Clascoterone in the presence of 100 nM DHT inhibited Petition 870250088666, dated 09 / 30 / 2025, pages 80 / 102 64 / 69 dose-dependently affects IL-6 secretion over 24 hours. Importantly, the combination of 1 μM Minoxidil with 15 nM or 30 nM doses of clascoterone showed an unexpected synergism resulting in significantly greater inhibition of IL-6 secretion compared to treatment with clascoterone alone. The 60 nM clascoterone group also showed synergism, but without statistical significance.

[0171] All clascoterone treatment groups showed statistically significant inhibition of IL-6 secretion, relative to 100 nM DHT. Table 8 lists the IL-6 concentrations and their relation to inhibition by the compounds in each treatment condition. Table 8. Mean and standard deviation of IL-6 concentrations in relation to inhibition by the compounds in each experimental treatment group. Condition IL-6 Mean (pg / ml) Standard deviation (pg / ml) % relative inhibition for 100 nM DHT DMSO 39.0 5.8 100 nM DHT 47.5 6.1 Only 1 μM MNX 42.2 5.6 1 μM MNX + DHT 44.3 4.1 7% 15 nM CB0301 + 100 nM DHT 39.7 2.8 16% 30 nM CB0301 + 100 nM DHT 38.4 6.4 19% 60 nM CB0301 + 100 nM DHT 31.3 3.0 34% Petition 870250088666, dated 09 / 30 / 2025, pages 81 / 102 65 / 69 15 nM CB0301 / 1 μM MNX / DHT 31.4 ± 2.6 34%

[0172] As shown in Figure 2, when comparing the effects of clascoterone + DHT vs. clascoterone + DHT + minoxidil, the clascoterone treatment groups containing 1 μM of minoxidil showed more than an additive effect. That is, there was a synergistic inhibition of IL-6 in HFDPC for all concentrations of clascoterone when combined with 1 μM of minoxidil.

[0173] The predictive additive efficacy for the clascoterone and minoxidil combination vs. the actual observed efficacy of the combination is listed in Table 9. This also includes the p-values ​​from the ANOVA statistical analysis comparing the means of the clascoterone + DHT groups vs. the clascoterone + DHT + minoxidil groups. Table 9. Predicted additive effect of (clascoterone + DHT) + (minoxidil + DHT) vs. observed effect of the combination and statistical analysis of the p-value of the mean clascoterone vs. mean of the clascoterone + minoxidil treatment groups. Clascoterone concentration (nM) Predicted additive effect (%) Observed effect of the combination (%) P-value 15 23% 34% P < 0.009 30 26% 36% P < 0.003 Petition 870250088666, dated 09 / 30 / 2025, pages 82 / 102 66 / 69 60 41% 43% P < 0.7

[0174] The 15 nM clascoterone + DHT group showed 16% inhibition compared to DHT alone, and the 1 mM minoxidil + DHT group showed 7% inhibition compared to DHT alone. Therefore, an additive effect should provide 23% (16% + 7%) inhibition. However, the 34% inhibition observed for the clascoterone + DHT + minoxidil combination is greater than 23%, indicating a synergistic inhibition between clascoterone and minoxidil when used in combination. The combined treatment was significantly different compared to clascoterone + DHT (p < 0.009).

[0175] The 30 nM clascoterone group showed 19% inhibition compared to DHT alone, and the 1 mM minoxidil group showed 7% inhibition compared to DHT alone. Therefore, an additive effect should provide 26% (19% + 9%) inhibition. However, the 36% inhibition observed for the combination is higher, indicating synergistic inhibition between clascoterone and minoxidil when used in combination. The combined treatment (clascoterone + DHT + minoxidil) was significantly different compared to clascoterone + DHT (p < 0.003).

[0176] The 60 nM clascoterone group showed 34% inhibition compared to DHT alone, and the 1 mM minoxidil group showed 7% inhibition compared to DHT alone. Therefore, an additive effect should provide 41% (34% + 7%) inhibition. The 43% inhibition observed for the combination is higher, which may indicate synergistic inhibition. However, this difference was not significant (p < 0.7). Conclusion

[0177] Human dermal papilla cells respond to DHT to activate the androgen receptor. IL-6 is a crucial negative regulator of hair growth and has been shown to be elevated. Petition 870250088666, dated 09 / 30 / 2025, pp. 83 / 102 67 / 69 in hair follicles of the scalp with baldness compared to hair follicles of the scalp without baldness. Clascoterone is a potent antiandrogen that has demonstrated clinical efficacy in patients with androgenetic alopecia to increase hair growth. Clascoterone has previously been shown to inhibit DHT-induced IL-6 secretion by human dermal papilla cells. Therefore, IL-6 is an HFDPC biomarker that correlates with hair growth.

[0178] Minoxidil is also approved for the treatment of androgenetic alopecia, but there is no information in the literature regarding its effects on IL-6 secretion by dermal papilla cells. In the experimental data presented, Minoxidil demonstrated a mild, non-significant inhibition of IL-6 secretion by HFDPC. Clascoterone at all concentrations tested demonstrated statistically significant inhibition of IL-6 vs. HFDPC treated with DHT. The comparison of clascoterone + DHT vs. clascoterone + DHT + minoxidil showed that the combination was more than additive. In fact, the combination of clascoterone with minoxidil exhibited synergistic efficacy in inhibiting IL-6 secretion by HFDPC.

[0179] Thus, it is evident that patients with androgenetic alopecia should benefit dramatically from the combined treatment of clascoterone plus minoxidil.

[0180] The phraseology or terminology in this descriptive report is for descriptive purposes only, not for limitation. Therefore, the terminology and / or phraseology in this descriptive report should be interpreted by those skilled in the art in light of the teachings and guidelines in this descriptive report.

[0181] The scope and breadth of the present invention shall not be limited by any of the exemplary embodiments described above, but shall be defined only in accordance with the following claims and their equivalents. Petition 870250088666, dated 09 / 30 / 2025, pp. 84 / 102 68 / 69

[0182] All patents, patent applications and other references noted or cited in this application are incorporated herein by reference in their entirety. References

[0183] Greco V., Chen T., Rendl M., Schober M., Pasolli H.A., Stokes N., Dela Cruz-Racelis J., Fuchs E. A two-step Mechanism for Stem Cell Activation During Hair Regeneration. Cell Stem Cell 4: 155 -169, 2009.

[0184] Elliott K., Stefenson T.J., Messenger A.G. Differences in Hair Follicle Dermal Papilla Volume are due to Extracellular Matrix Volume and Cell Number: Implications for the Control of Hair Follicle Size and Androgen Responses. J. Invest. Dermatol. 113: 873-877, 1999.

[0185] Mi Hee Kwack, Ji Sup Ahn, Moon Kyu Kim, Jung Chui Kim, Young Kwan Sung. Dihydrotestosterone-Inducible IL-6 Inhibits Elongation of Human Hair Shafts by Suppressing Matrix Cell Proliferation and Promotes Regression of Hair Follicle in Mice. J. Invest. Dermatol., janeiro de 2012; 132 (1) : 43-9.

[0186] Kaufman K.D., Olsen E.A., Whiting D., Savin R., DeVillez R., Bergfeld W., Price V.H., Van Neste D., Roberts J.L., Hordinsky M., e cols. Finasteride in the Treatment of Men with Androgenetic Alopecia. Finasteride Male Pattern Hair Loss Study Group. J. Am Acad. Dermatol. 39: 578-589, 1998.

[0187] Randall V.A. 2008. Androgens amd Hair Growth. Dermatol Ther 21: 314-328.

[0188] Shorter K., Farjo N.P., Picksley S.M., Randall V.A. Human Hair Follicles Contain two Forma of ATP-Sensitive Potassium Channels, Only One of which is Sensitive to Minoxidil. EASED J 22: 1.725-1.736, 2008.

[0189] Caridad Rosette, Niccolette Rosette, Alessandro Mazzetti, Luigi Moro, Mara Gerloni. Cortexolona 17a-Propionate (Clascoterone) is an Androgen Receptor Antagonist in Dermal Papilla Cells In Vitro. J. Drugs Dermatol., Iode fevereiro de Petição 870250088666, de 30 / 09 / 2025, pág. 85 / 102 69 / 69 2019; 18 (2): 197-201. Petition 870250088666, dated 09 / 30 / 2025, pp. 86 / 102

Claims

1 / 13 CLAIMS 1. A method for treating hair loss in a needy individual, characterized by comprising the topical co-administration to the individual of an effective amount of cortexolone-17apropionate and an effective amount of minoxidil.

2. Method according to claim 1, characterized in that cortexolone-17α-propionate is co-administered in an amount of at least 1% of body weight up to about 20% of body weight.

3. Method according to claim 1, characterized in that minoxidil is co-administered in an amount of about 0.1% of body weight up to about 20% of body weight.

4. A method, according to any one of claims 13, characterized in that cortexolone-17α-propionate and minoxidil are co-administered sequentially.

5. Method according to claim 4, characterized in that cortexolone-17α-propionate and minoxidil are in separate pharmaceutical formulations.

6. A method, according to any one of claims 13, characterized in that cortexolone-17α-propionate and minoxidil are co-administered simultaneously.

7. Method according to claim 6, characterized in that cortexolone-17α-propionate and minoxidil are in the same pharmaceutical formulation.

8. Method according to claim 7, characterized in that the pharmaceutical formulation is a liquid or semi-solid formulation.

9. Method according to claim 7 or 8, characterized in that the pharmaceutical formulation is a solution, a suspension, an emulsion, a microemulsion, a cream, a paste, a gel, an ointment or a foam.

10. Method, according to any one of claims 7-9, characterized in that the pharmaceutical formulation is a solution. Petition 870250088666, dated 09 / 30 / 2025, page 87 / 102 2 / 13 11. A method according to claim 10, characterized in that the solution comprises water, saline solution, a buffered saline solution, a polyol, a polyol ether, a C1-C7 alcohol, or a combination thereof.

12. A method according to any one of claims 7-11, characterized in that the pharmaceutical formulation further comprises at least one additive selected from an acid, a buffer, an antioxidant, an emulsifier, a penetration enhancer, a moisturizer, a preservative, a chelating agent, and combinations thereof.

13. A method according to any one of claims 1-12, characterized in that cortexolone-17apropionate is co-administered in a pharmaceutical formulation comprising less than about 5% by weight of water.

14. A method according to any one of claims 1-13, characterized in that the pharmaceutical formulation is co-administered topically once or twice daily.

15. A method, according to any one of claims 1-14, characterized in that the hair loss is alopecia.

16. Method, according to claim 15, characterized in that the alopecia is androgenetic alopecia, alopecia areata, telogen effluvium, anagen effluvium, traction alopecia, or a combination of any of the aforementioned.

17. Method, according to claim 16, characterized in that alopecia areata is selected from the group consisting of diffuse alopecia areata, monolocular alopecia areata, multilocular alopecia areata, ophiasis, alopecia totalis and alopecia universalis.

18. Method, according to claim 16, characterized in that the alopecia is androgenetic alopecia.

19. Topical pharmaceutical formulation, characterized by comprising cortexolone-17α-propionate, minoxidil, and one or more pharmaceutically acceptable carriers. Petition 870250088666, dated 09 / 30 / 2025, page 88 / 102 3 / 13 20. Topical pharmaceutical formulation, according to claim 19, characterized in that cortexolone 17α-propionate is fully solubilized in the pharmaceutical formulation.

21. Topical pharmaceutical formulation, according to claim 19 or 20, characterized in that the pharmaceutical formulation comprises cortexolone-17α-propionate in a concentration of about 1% by weight up to about 20% by weight.

22. Topical pharmaceutical formulation, according to any one of claims 19-21, characterized in that the pharmaceutical formulation comprises minoxidil in a concentration of about 0.1% by weight up to about 20% by weight.

23. Topical pharmaceutical formulation, according to any one of claims 19-22, characterized in that the pharmaceutical formulation is a liquid or semi-solid formulation.

24. Topical pharmaceutical formulation, according to claim 23, characterized in that the liquid or semi-solid formulation is a solution, a suspension, an emulsion, a microemulsion, a cream, a paste, a gel, an ointment or a foam.

25. Topical pharmaceutical formulation, according to claim 24, characterized in that the pharmaceutical formulation is a solution.

26. Topical pharmaceutical formulation, according to claim 24 or 25, characterized in that the solution comprises water, saline solution, a buffered saline solution, or a combination thereof.

27. Topical pharmaceutical formulation, according to any one of claims 19-26, characterized in that the pharmaceutical formulation comprises less than about 5 percent water by weight.

28. Topical pharmaceutical formulation, according to any Petition 870250088666, dated 09 / 30 / 2025, page 89 / 102 4 / 13 one of claims 19-27, characterized in that one or more pharmaceutically acceptable carriers are selected from the group consisting of a polyol, a polyol ether and a C1-C7 alcohol.

29. Topical pharmaceutical formulation, according to claim 28, characterized in that the C1-C7 alcohol is ethanol, isopropanol, methanol, or a combination thereof.

30. Topical pharmaceutical formulation, according to claim 29, characterized in that the C1-C7 alcohol is ethanol.

31. Topical pharmaceutical formulation, according to any one of claims 28-30, characterized in that the polyol is selected from the group consisting of ethylene glycol, propylene glycol, glycerol, hexanotriol, and combinations thereof.

32. Topical pharmaceutical formulation, according to claim 31, characterized in that the polyol is propylene glycol.

33. Topical pharmaceutical formulation, according to any one of claims 28-32, characterized in that the polyol ether is selected from the group consisting of polypropylene glycol, polyethylene glycol, polyethylene-polypropylene triblock copolymers, dipropylene glycol, diethylene glycol monoethyl ether, and combinations thereof.

34. Topical pharmaceutical formulation, according to claim 33, characterized in that the polyol ether is diethylene glycol monoethyl ether.

35. Topical pharmaceutical formulation, according to any one of claims 28-34, characterized in that the polyol is propylene glycol, the polyol ether is diethylene glycol monoethyl ether, and the C1-C7 alcohol is ethanol.

36. Topical pharmaceutical formulation, according to any one of claims 19-35, characterized in that the pharmaceutical formulation further comprises at least one additive selected from an acid, a buffer, an antioxidant, an emulsifier, a penetration enhancer, a moisturizer, a preservative, a chelating agent, and combinations thereof.

37. Topical pharmaceutical formulation, according to claim 36, characterized in that the antioxidant is selected from the group consisting of butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), ascorbyl palmitate, ascorbic acid, alpha tocopherol, propyl gallate, 2,4,5-trihydroxybutyrophenone, 4-hydroxymethyl-2,6-di-tert-butylphenol, erythorbic acid, guaiac gum, thiodipropionic acid, dilauryl thiodipropionate, tert-butylhydroquinone, pharmaceutically acceptable salts or esters thereof, and combinations thereof.

38. Topical pharmaceutical formulation, according to claim 37, characterized in that the antioxidant is BHT, ascorbyl palmitate, or a combination of BHT and ascorbyl palmitate.

39. Topical pharmaceutical formulation, according to any one of claims 36-38, characterized in that the emulsifier is selected from the group consisting of PEG-15 hydroxystearate (polyoxyl-15-hydroxystearate), PEG-30 stearate, PEG-40 laurate, PEG-40 oleate, polysorbate 20, polysorbate 60, polysorbate 80, PEG-20 cetostearyl ether, polyoxyl 25 cetostearyl, cetomacrogol 1000, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monooleate-propylene glycol fatty acid esters, polyglycerol fatty acid esters, polyoxyl 5 castor oil, polyoxyl 15 castor oil, polyoxyl 35 castor oil, Polyoxyl 40 hydrogenated castor oil, caprylocapril polyoxyl-8 glycerides, caprylocaproyl polyoxylglycerides, lauroyl polyoxylglycerides, oleoyl polyoxylglycerides, and combinations thereof.

40. Topical pharmaceutical formulation, according to claim 39, characterized in that the emulsifier Petition 870250088666, dated 09 / 30 / 2025, page 91 / 102 6 / 13 is polysorbate 60, polysorbate 80, or a combination of polysorbate 60 and polysorbate 80.

41. Topical pharmaceutical formulation, according to any one of claims 36-40, characterized in that the penetration enhancer is selected from the group consisting of a diol, a polyol, a fatty acid, a fatty alcohol, a fatty acid ester, a surfactant, a pyrrolidone, and combinations thereof.

42. Topical pharmaceutical formulation, according to any one of claims 36-41, characterized in that the moisturizer is selected from the group consisting of a fatty alcohol, a fatty acid, a fatty acid ester, an oil, a polyethylene glycol, glycerin, an alpha hydroxy acid, and combinations thereof.

43. Topical pharmaceutical formulation, according to claim 42, characterized in that the moisturizer is cetyl alcohol, cetearyl alcohol, stearyl alcohol, stearic acid, isopropyl myristate, isopropyl palmitate, cocoa butter, lanolin, liquid paraffin, shea butter, a silicone oil, castor oil, a polyethylene glycol, glycerin, lactic acid, glycolic acid, malic acid, citric acid, tartaric acid, or a combination thereof.

44. Topical pharmaceutical formulation, according to any one of claims 36-43, characterized in that the buffer is a phosphate buffer, citrate buffer, lactate buffer, or a combination thereof.

45. Alopecia treatment method, the method characterized by comprising the topical administration to an individual in need of the topical pharmaceutical formulation, as defined in any of claims 19-44, wherein topical administration of the pharmaceutical formulation for at least six months achieves a weighted average Hair Growth Assessment (HGA) score of approximately 0.30 compared to Petition 870250088666, dated 09 / 30 / 2025, p. 92 / 102 7 / 13 vehicle.

46. ​​Alopecia treatment method, the method characterized by comprising the topical administration to an individual in need of the topical pharmaceutical formulation, as defined in any of claims 19-44, wherein topical administration of the pharmaceutical formulation for at least six months achieves a weighted average Investigator Global Assessment (IGA) score of approximately 0.43 compared to vehicle.

47. Alopecia treatment method, the method characterized by comprising the topical administration to an individual in need of the topical pharmaceutical formulation, as defined in any of claims 19-44, wherein topical administration of the pharmaceutical formulation for at least six months is free of systemic antiandrogenic side effects.

48. Alopecia treatment method, the method characterized by comprising the topical administration to an individual in need of the topical pharmaceutical formulation, as defined in any one of claims 19-44, wherein the topical administration of the pharmaceutical formulation provides a) an average change from baseline in the Target Area Hair Count equal to or greater than 9 hairs / cm2 after 6 months of daily or BID application; or b) an average change from baseline in the Target Area Hair Count equal to or greater than 10 hairs / cm2 after 6 months of daily or BID application; or c) an average change from baseline in the Target Area Hair Count equal to or greater than 11 hairs / cm2 after 6 months of daily or BID application; or d) an average change from baseline in the Target Area Hair Count equal to or greater than 12 hairs / cm2 after 6 months of daily or BID application;or Petition 870250088666, dated 09 / 30 / 2025, pp. 93 / 102 8 / 13 e) an average weighted HGA score equal to or greater than 0.20 after 6 months of daily application or BID; or f) an average weighted HGA score equal to or greater than 0.30 after 6 months of daily application or BID; or g) an average weighted HGA score equal to or greater than 0.40 after 6 months of daily application or BID; or h) an average weighted IGA score equal to or greater than 0.10 after 6 months of daily application or BID; or i) an average weighted IGA score equal to or greater than 0.20 after 6 months of daily application or BID; or j) an average weighted IGA score equal to or greater than 0.30 after 6 months of daily application or BID; or k) a favorable (positive) HGA score in at least about 10% of individuals after 6 months of daily or BID application; or l) a favorable (positive) HGA score in at least about 20% of individuals after 6 months of daily or BID application;or m) a favorable (positive) HGA score in at least about 30% of individuals after 6 months of daily or BID application; or n) a favorable (positive) IGA score in at least about 10% of individuals after 6 months of daily or BID application; or o) a favorable (positive) IGA score in at least about 20% of individuals after 6 months of daily or BID application; or p) a favorable (positive) IGA score in at least about 30% of individuals after 6 months of daily or BID application; or q) a favorable (positive) IGA score in at least about 40% of individuals after 6 months of daily or BID application. Petition 870250088666, dated 09 / 30 / 2025, pp. 94 / 102 9 / 13; 49. Cortexolone-17α-propionate and minoxidil for use in the treatment of hair loss in an individual in need, characterized by the fact that they are co-administered topically to the individual.

50. Cortexolone-17α-propionate and minoxidil for use, according to claim 4 9, characterized in that cortexolone-17α-propionate is co-administered in an amount of at least 1% of body weight up to about 20% of body weight.

51. Cortexolone-17α-propionate and minoxidil for use, according to claim 4 9, characterized in that minoxidil is co-administered in an amount of about 0.1% of body weight up to about 20% of body weight.

52. Cortexolone-17a-propionate and minoxidil for use according to any one of claims 49-51, characterized in that cortexolone-17a-propionate and minoxidil are co-administered sequentially, preferably cortexolone-17a-propionate and minoxidil are in separate pharmaceutical formulations.

53. Cortexolone-17a-propionate and minoxidil for use, according to any of claims 49-51, characterized in that cortexolone-17a-propionate and minoxidil are co-administered simultaneously, preferably cortexolone-17a-propionate and minoxidil are in the same pharmaceutical formulation.

54. Cortexolone-17α-propionate and minoxidil for use according to claim 53, characterized in that the pharmaceutical formulation is a liquid or semi-solid formulation, preferably the pharmaceutical formulation is a solution, a suspension, an emulsion, a microemulsion, a cream, a paste, a gel, an ointment or a foam, more preferably the pharmaceutical formulation is a solution.

55. Cortexolone-17α-propionate and minoxidil for use according to claim 54, characterized in that the solution comprises water, saline solution, a buffered saline solution, a polyol, a polyol ether, a C1-C7 alcohol, or a combination thereof.

56. Cortexolone-17α-propionate and minoxidil for use, according to claim 54 or 55, characterized in that the pharmaceutical formulation further comprises at least one additive selected from an acid, a buffer, an antioxidant, an emulsifier, a penetration enhancer, a moisturizer, a preservative, a chelating agent, and combinations thereof.

57. Cortexolone-17a-propionate and minoxidil for use according to any one of claims 49-56, characterized in that cortexolone-17a-propionate is co-administered in a pharmaceutical formulation comprising less than about 5% by weight of water.

58. Cortexolone-17α-propionate and minoxidil for use according to any one of claims 49-57, characterized in that the pharmaceutical formulation is co-administered topically once or twice daily.

59. Cortexolone-17α-propionate and minoxidil for use according to any of claims 49-58, characterized in that the hair loss is alopecia, preferably the alopecia is androgenetic alopecia, alopecia areata, telogen effluvium, anagen effluvium, traction alopecia, or a combination of any of the aforementioned, most preferably the alopecia is androgenic alopecia.

60. Cortexolone-17α-propionate and minoxidil for use according to claim 59, characterized in that alopecia areata is selected from the group consisting of diffuse alopecia areata, monolocular alopecia areata, multilocular alopecia areata, ophiasis, alopecia totalis and alopecia universalis.

61. Topical pharmaceutical formulation, according to any one of claims 19-44, characterized in that the formulation is for use in the treatment of hair loss in an individual in need. Petition 870250088666, dated 09 / 30 / 2025, pp. 96 / 102 11 / 13 62. Topical pharmaceutical formulation for use, according to claim 61, characterized in that the hair loss is alopecia.

63. Topical pharmaceutical formulation for use, according to claim 62, characterized in that the alopecia is androgenetic alopecia, alopecia areata, telogen effluvium, anagen effluvium, traction alopecia, or a combination of any of the aforementioned.

64. Topical pharmaceutical formulation for use, according to claim 63, characterized in that alopecia areata is selected from the group consisting of diffuse alopecia areata, monolocular alopecia areata, multilocular alopecia areata, ophiasis, alopecia totalis and alopecia universalis.

65. Topical pharmaceutical formulation for use, according to claim 62, characterized in that the alopecia is androgenic alopecia.

66. Topical pharmaceutical formulation for use, according to any one of claims 61-65, characterized in that topical administration of the pharmaceutical formulation for at least six months achieves a weighted average Hair Growth Assessment (HGA) score of approximately 0.30 compared to vehicle.

67. Topical pharmaceutical formulation for use, according to any one of claims 61-65, characterized in that topical administration of the pharmaceutical formulation for at least six months achieves a weighted average Investigator Global Assessment (IGA) score of approximately 0.43 compared to vehicle.

68. Topical pharmaceutical formulation for use, according to any one of claims 61-67, characterized in that topical administration of the pharmaceutical formulation for at least six months is free of systemic antiandrogenic side effects. Petition 870250088666, dated 09 / 30 / 2025, pp. 97 / 102 12 / 13 69. Topical pharmaceutical formulation for use, according to any one of claims 61-67, characterized in that topical administration of the pharmaceutical formulation provides a) an average change from baseline in the Target Area Hair Count equal to or greater than 9 hairs / cm2 after 6 months of daily or BID application; or b) an average change from baseline in the Target Area Hair Count equal to or greater than 10 hairs / cm2 after 6 months of daily or BID application; or c) an average change from baseline in the Target Area Hair Count equal to or greater than 11 hairs / cm2 after 6 months of daily or BID application; or d) an average change from baseline in the Target Area Hair Count equal to or greater than 12 hairs / cm2 after 6 months of daily or BID application; or e) a weighted average HGA score equal to or greater than 0.20 after 6 months of daily or BID application;or f) a weighted average HGA score equal to or greater than 0.30 after 6 months of daily or BID application; or g) a weighted average HGA score equal to or greater than 0.40 after 6 months of daily or BID application; or h) a weighted average IGA score equal to or greater than 0.10 after 6 months of daily or BID application; or i) a weighted average IGA score equal to or greater than 0.20 after 6 months of daily or BID application; or j) a weighted average IGA score equal to or greater than 0.30 after 6 months of daily or BID application; or k) a favorable (positive) HGA score in at least approximately 10% of individuals after 6 months of daily or BID application; or l) a favorable (positive) HGA score in at least approximately 20% of individuals after 6 months of daily or BID application;or Petition 870250088666, dated 09 / 30 / 2025, pp. 98 / 102 13 / 13 m) a favorable (positive) HGA score in at least about 30% of individuals after 6 months of daily or BID application; or n) a favorable (positive) IGA score in at least about 10% of individuals after 6 months of daily or BID application; or o) a favorable (positive) IGA score in at least about 20% of individuals after 6 months of daily or BID application; or p) a favorable (positive) IGA score in at least about 30% of individuals after 6 months of daily or BID application; or q) a favorable (positive) IGA score in at least about 40% of individuals after 6 months of daily or BID application. Petition 870250088666, dated 09 / 30 / 2025, pp. 99 / 102;

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