Crystalline PPARδ agonist

Inventors

DEL RIO GANCEDO, Susana • Suleiman, Osama • Sharp, Emma • BALOGH, Cristina • LEE, Rachael • MACRAE, Julie • Feeder, Neil

Assignees

Reneo Pharma Ltd • OnKure Therapeutics Inc

Abstract

Described herein is crystalline sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate, uses of such crystalline material in the preparation of pharmaceutical compositions for the treatment of diseases or conditions that would benefit by administration with a PPARδ agonist compound.

Core Innovation

The patent describes crystalline sodium (E)-2-(4-((3-(4-fluorophenyl)-3-(4-(3-morpholinoprop-1-yn-1-yl)phenyl)allyl)oxy)-2-methylphenoxy)acetate (Compound II) as solid-state forms that include Crystalline Form 1 (unsolvated) and optionally Crystalline Form 2 and/or Crystalline Form 5. The crystalline forms are defined by characteristic X-ray powder diffraction (XRPD) patterns measured using Cu Kα radiation with specified peak positions, and the disclosure also includes an amorphous form of Compound II.

The crystalline forms are further characterized using DSC thermograms and TGA profiles that report endothermic events and weight-loss/degradation onset behavior. Additional solid-form identification features are provided for key forms by FTIR and Raman characteristic peaks, and for Crystalline Form 1, single-crystal X-ray diffraction provides unit-cell parameters and a space group description.

The patent reports solid-form moisture-related behavior and stability, including reversible moisture uptake and stability under defined relative humidity and temperature conditions. For example, Form 2 maintains unchanged XRPD after gravimetric vapor sorption (GVS) and after storage under specified humidity and temperature conditions, while other solvates are reported to show conversions under humidity or handling. The disclosure additionally describes pharmaceutical compositions comprising the crystalline forms with pharmaceutically acceptable excipients and solid oral dosage forms, and it includes a process overview for preparing Compound II from an acid precursor Compound I as well as converting between solid forms.

Claims Coverage

The independent claim set covers three crystalline solid forms of Compound II and related pharmaceutical compositions. Across the independent claims, the inventive features are defined primarily by XRPD peak patterns measured using Cu Kα radiation, with additional characterization for specific forms.

Overall, the claims cover specific crystalline sodium Compound II solid forms defined by Cu Kα XRPD peak patterns for Crystalline Form 1, the Crystalline Form 2 hydrate, and the Crystalline Form 5 acetone solvate, with dependent coverage extending to additional characterization and pharmaceutical compositions.

Stated Advantages

Documented Applications