Therapeutics and methods of treating COVID-19 in a patient in need thereof comprising administering a pharmaceutically effective dose of a therapeutic, wherein the therapeutic contains an ACE2 externalizer, and the ACE2 externalizer is one of diminazene, diminazene aceturate, or a pharmaceutically acceptable salt, solvate, ester, amide, clathrate, stereoisomer, enantiomer, or prodrug thereof.

This invention relates to a hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethy-l-benzyl)-azetidine-3-carboxylic acid (Compound I), to pharmaceutical compositions comprising this salt, to processes for forming this salt and to its use in medical treatment. In addition, the present invention also relates to new polymorphic forms of the hemifumarate salt form of Compound I, as well as to pharmaceutical compositions comprising these polymorphic forms, to processes for obtaining them, and their use in medical treatment.

This invention relates to a hemifumarate salt of 1-(4-{1-[(E)-4-cyclohexyl-3-trifluoromethyl-benzyloxyimino]-ethyl}-2-ethy-l-benzyl)-azetidine-3-carboxylic acid (Compound I), to pharmaceutical compositions comprising this salt, to processes for forming this salt and to its use in medical treatment. In addition, the present invention also relates to new polymorphic forms of the hemifumarate salt form of Compound I, as well as to pharmaceutical compositions comprising these polymorphic forms, to processes for obtaining them, and their use in medical treatment.

Provided herein are compositions and methods for treating, inhibiting and/or reducing the severity of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) in subjects in need thereof. The methods include providing an agent that inhibits expression or activity of ONECUT2 and administering a therapeutically effective amount of the agent so as to treat, inhibit and/or reduce the severity of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) in the subject.

Provided herein are compositions and methods for treating, inhibiting and/or reducing the severity of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) in subjects in need thereof. The methods include providing an agent that inhibits expression or activity of ONECUT2 and administering a therapeutically effective amount of the agent so as to treat, inhibit and/or reduce the severity of neuroblastoma, small cell lung cancer (SCLC), large cell neuroendocrine cancer (LCNEC), large-cell carcinoma (LCC), squamous cell carcinoma (SqCC), and/or adenocarcinoma (AC) in the subject.

The compounds of Formula I is described herein along with their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof. The compounds described herein, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof are bicyclic compounds that are inhibitors of PD-1/PD-L1 interaction/activation. ##STR00001##

The compounds of Formula I is described herein along with their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof. The compounds described herein, their polymorphs, stereoisomers, tautomers, prodrugs, solvates, and pharmaceutically acceptable salts thereof are bicyclic compounds that are inhibitors of PD-1/PD-L1 interaction/activation. ##STR00001##

The invention is directed at use of ezetimibe or a pharmaceutically acceptable salt or derivative thereof in the manufacture of a pharmaceutical composition for treatment of an Mdm2-overexpressing cancer. It is also directed at use of ezetimibe, or a pharmaceutically acceptable salt or derivative thereof, in combination with curcumin in the manufacture of a pharmaceutical composition for treatment of an Mdm2-overexpressing colon cancer. The invention is further directed at a pharmaceutical composition comprising ezetimibe, or a pharmaceutically acceptable salt or derivative thereof, and curcumin for use in a method of treating an Mdm2-overexpressing cancer.

The invention is directed at use of ezetimibe or a pharmaceutically acceptable salt or derivative thereof in the manufacture of a pharmaceutical composition for treatment of an Mdm2-overexpressing cancer. It is also directed at use of ezetimibe, or a pharmaceutically acceptable salt or derivative thereof, in combination with curcumin in the manufacture of a pharmaceutical composition for treatment of an Mdm2-overexpressing colon cancer. The invention is further directed at a pharmaceutical composition comprising ezetimibe, or a pharmaceutically acceptable salt or derivative thereof, and curcumin for use in a method of treating an Mdm2-overexpressing cancer.

The invention is directed at use of ezetimibe or a pharmaceutically acceptable salt or derivative thereof in the manufacture of a pharmaceutical composition for treatment of an Mdm2-overexpressing cancer. It is also directed at use of ezetimibe, or a pharmaceutically acceptable salt or derivative thereof, in combination with curcumin in the manufacture of a pharmaceutical composition for treatment of an Mdm2-overexpressing colon cancer. The invention is further directed at a pharmaceutical composition comprising ezetimibe, or a pharmaceutically acceptable salt or derivative thereof, and curcumin for use in a method of treating an Mdm2-overexpressing cancer.