Merck Sharp + Dohme Corp.

Cerecor, Inc.

Johns Hopkins University

Avalo Therapeutics, Inc.

James Vornov

Blake Paterson

Reza Mazhari

Todd D Nelson

Djelila Mezaache

Rachel M Garner

Barbara S Slusher

Rana Rais

Blake M Paterson

The disclosed subject matter provides certain polymorphic forms of Compound (I) as well as pharmaceutical compositions comprising Compound (I) or such polymorphic forms, and methods of using or making such compounds and pharmaceutical compositions. It has now been discovered that Compound (I) can exist in multiple crystalline forms (polymorphs). One particular crystalline form, Form II, has been found to be more thermodynamically stable and, thus, likely more suitable for bulk preparation and handling than other polymorphic forms. Efficient and economic methods have been developed to prepare Compound (I) and Form II in high purity on a large scale. In animal studies, Form II has demonstrated safety and efficacy in treating depressive disorders and, when micronized, improved absorption compared to non-micronized Form II.

Compounds, compositions and methods

The disclosed subject matter provides certain polymorphic forms of Compound (I) as well as pharmaceutical compositions comprising Compound (I) or such polymorphic forms, and methods of using or making such compounds and pharmaceutical compositions. It has now been discovered that Compound (I) can exist in multiple crystalline forms (polymorphs). One particular crystalline form, Form II, has been found to be more thermodynamically stable and, thus, likely more suitable for bulk preparation and handling than other polymorphic forms. Efficient and economic methods have been developed to prepare Compound (I) and Form II in high purity on a large scale. In animal studies, Form II has demonstrated safety and efficacy in treating depressive disorders and, when micronized, improved absorption compared to non-micronized Form II. 

Methods for buccally, sublingually, or intranasally administering a prodrug of propofol to a subject in need of treatment thereof in an amount sufficient to deliver a therapeutically effective amount of propofol to the subject are disclosed.

Buccal, sublingual and intranasal delivery of fospropofol

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Pikesville, MD, United States of America

James Vornov