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WO 2018/102407 Al 07 June 2018 (07.06.2018) W !P O PCT

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WO 2018/102407 Al 07 June 2018 (07.06.2018) W !P O PCT (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/102407 Al 07 June 2018 (07.06.2018) W !P O PCT (51) International Patent Classification: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, C07K 7/60 (2006.01) G01N 33/53 (2006.01) EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, CI2Q 1/18 (2006.01) MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (21) International Application Number: KM, ML, MR, NE, SN, TD, TG). PCT/US2017/063696 (22) International Filing Date: Published: 29 November 201 7 (29. 11.201 7) — with international search report (Art. 21(3)) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/427,507 29 November 2016 (29. 11.2016) US 62/484,696 12 April 2017 (12.04.2017) US 62/53 1,767 12 July 2017 (12.07.2017) US 62/541,474 04 August 2017 (04.08.2017) US 62/566,947 02 October 2017 (02.10.2017) US 62/578,877 30 October 2017 (30.10.2017) US (71) Applicant: CIDARA THERAPEUTICS, INC [US/US]; 63 10 Nancy Ridge Drive, Suite 101, San Diego, CA 92121 (US). (72) Inventors: BARTIZAL, Kenneth; 7520 Draper Avenue, Unit 5, La Jolla, CA 92037 (US). DARUWALA, Paul; 1141 Luneta Drive, Del Mar, CA 92014 (US). FORREST, Kevin; 13864 Boquita Drive, Del Mar, CA 92014 (US). HANNAH, Brendan; 5224 Cardeno Drive, San Diego, CA 92109 (US). ONG, Voon; 13966 Royal Melbourne Square, San Diego, CA 92128 (US). RODEN, Maureen; 13 Luna Lane, Severna Park, MD 2 1146 (US). SANDISON, Tay¬ lor; 1042 Third Street, Encinitas, CA 92024 (US). (74) Agent: BELLFVEAU, Michael, J.; Clark & Elbing LLP, 101 Federal Street, 15th Floor, Boston, MA 021 10 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, o UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, o (54) Title: METHODS FOR PREVENTING FUNGAL INFECTIONS 00 (57) Abstract: Provided herein are methods for preventing or reducing the likelihood of a fungal infection or related conditions thereto o in a human subject in need thereof. The methods include the administration of one or multiple doses of a pharmaceutical composition including CDl 0 1 and any pharmaceutically acceptable excipients, wherein the treatment reduces or eliminates the likelihood of de veloping a fungal infection. METHODS FOR PREVENTING FUNGAL INFECTIONS Background This invention features methods for the prevention of fungal infections and conditions related thereto. Fungal infections, such as those caused by Candida, Pneumocystis, and Aspergillus, can be serious and life-threatening infections that represent a significant public health issue, particularly in highly vulnerable populations including the elderly, post-surgical, critically ill, and other hospitalized patients with serous medical conditions. Because of increasing resistance to existing antifungal drugs, there is an urgent need to develop new and more effective antifungal agents to treat or prevent these serious infections. Echinocandins are members of a leading class of antifungal agents for the treatment of fungal infections. These compounds target the cell wall by preventing the production of 1,3-p-D-glucan through inhibition of the catalytic subunit of 1,3-p-D-glucan synthase enzyme complex. The three echinocandins approved by the U.S. Food and Drug Administration for the treatment of fungal infections (caspofungin, anidulafungin, and micafungin) are available only in intravenous formulations. Further, these antifungal agents must be administered daily over multiple days, making it challenging to transition patients to a home setting. Further, failure to comply with this multi-day regimen may contribute to the rise in reports of drug-resistant fungal infections. Thus, there is a need in the art for improved methods of preventing and treating fungal infections. Summary of the Invention The present invention is directed to methods of reducing the likelihood of a fungal infection in a subject (e.g., an immunocompromised subject) by administering to the subject a pharmaceutical composition that includes CD1 0 1 salt, or a neutral form thereof. The invention features a method of reducing the likelihood of a fungal infection in a subject by administering to the subject a pharmaceutical composition including CD1 0 1 salt, or a neutral form thereof, and one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is administered in an amount and for a duration sufficient to reduce the likelihood of the fungal infection. In some embodiments, the pharmaceutical composition is administered in two or more doses. In some embodiments, the pharmaceutical composition is administered one or more times per year (e.g ., 1, 2 , 3 , 4 , 5 , or 6 times per year), one or more times per month (e.g. , 1, 2 , 3 , or 4 times per month), one or more times per week (e.g. , 1, 2 , 3 , 4 , 5 , 6 , or 7 times per week), or one or more times per day (e.g ., 1, 2 , or 3 times per day). In some embodiments, the pharmaceutical composition is administered on consecutive days (e.g., every day), consecutive weeks (e.g., every week), or consecutive months (e.g., every month). In some embodiments, the pharmaceutical composition is administered on non-consecutive days (e.g. , every other day, every 3 days, every 4 days, every 5 days, or every 6 days), weeks (e.g. , every other week or every 2 or 3 weeks), or months (e.g. , every other month or every 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , or 11 months). In some embodiments, the pharmaceutical composition is administered for a duration of about 1 to 8 weeks (e.g. , 1 to 3 , 2 to 4 , 3 to 5 , 4 to 6 , 5 to 7 , or 6 to 8 weeks). In some embodiments, the pharmaceutical composition is administered for a duration of about 2 to 12 months (e.g. , 2 to 4 , 3 to 5 , 4 to 6 , 5 to 7 , 6 to 8 , 7 to 9 , 8 to 10 , or 9 to 11 months). In some embodiments, the pharmaceutical composition is administered at any frequency for a duration of 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months. In some embodiments, the pharmaceutical composition is administered at any frequency for a duration of 1 to 5 years (e.g., 1 year, 2 years, 3 years, 4 years, or 5 years), from 6 to 10 years (e.g., 6 years, 7 years, 8 years, 9 years, or 10 years), from 11 to 15 years (e.g., 11 years, 12 years, 13 years, 14 years, or 15 years), from 16 to 20 years (e.g., 16 years, 17 years, 18 years, 19 years, or 20 years), from 2 1 to 25 years (e.g., 2 1 years, 22 years, 23 years, 24 years, or 25 years), or from 26 to 30 years (e.g., 26 years, 27 years, 28 years, 29 years or 30 years). In some embodiments, the pharmaceutical composition is administered as a lifetime prophylactic (e.g., administered at any frequency starting from when the subject is identified as at risk of a fungal infection to death). In some embodiments, the method further includes administering a second antifungal agent selected from the group consisting of glucan synthase inhibitors, ergosterol inhibitors, and pharmaceutically acceptable salts thereof. In some embodiments, the second antifungal agent is selected from the group consisting of CD1 0 1 , caspofungin, micafungin, anidulafungin, enfumafungin, clindamycin, trimethoprim, sulfamethoxazole, cotrimoxazole, VT-1 16 1 , VT-1 129, VT-1 598, VL-2397, fluconazole, albaconazole, bifonazole, butoconazole, clotrimazole, econazole, efinaconazole, fenticonazole, isavuconazole, isoconazole, itraconazole, ketoconazole, Miconazole, miconazole, omoconazole, oxiconazole, posaconazole, pramiconazole, ravuconazole, sertaconazole, sulconazole, terconazole, tioconazole, flucocytosine, voriconazole, atovaquone, pentamidine, primaquine, pyrimethamine, 67-1 2 1-A, 67-1 2 1-C, amphotericin B, arenomvcin B, aurenin, aureofungin A , aureotuscin, candidin , chinin, chitin synthesis inhibitors, demethoxyrapamycin , dermostatin A , dermostatin B, DJ-400- B 1 , DJ-400-B2, elizabethin, eurocidin A , eurocidin B, filipin I, filipin II , filipin III, filipin IV, fungichromin, gannibamycin, hamycin, levorin A2, lienomycin, lucensomycin, mycoheptin, mycoticin A , mycoticin B, natamycin, nystatin A , nystatin A3, partricin A , partricin B, perimycin A , pimaricin, polifungin B, rapamycin, rectilavendomvcin, rimocidin, roflamycoin, tetramycin A , tetramycin B, tetrin A , tetrin B, polygodial, benzoic acid, ciclopirox, tolnaftate, undecylenic acid, flucytosine or 5-fluorocytosine, griseofulvin, haloprogin, and pharmaceutically acceptable salts thereof. In some embodiments, the second antifungal agent is administered intraorally, intravenously, intramuscularly, intradermally, intrarterially, subcutaneously, orally, or by inhalation. In some embodiments, the subject is administered a single dose of a pharmaceutical composition including CD1 0 1 salt, or a neutral form thereof, and one or more pharmaceutically acceptable excipients.
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