CellCeutix pharmaceutical company

KM-133 is a small molecule, acting on the principles of immune stimulation and PRINS reduction, that has been found to be effective against psoriasis in animal models, both in induced psoriasis as well as a xenograft model with human psoriatic tissue.  It is easily synthesized and has the potential for oral dosing.

Chemistry/PK
KM-133 is a small molecule with a molecular weight of less than 500 MW.  It is synthesized through a five-step process using commercially available starting materials.  It is 25% orally bioavailable allowing the potential for oral administration.  KM-133 acts through immune stimulation and PRINS reduction.

Patent Protection
A patent application covering KM-133 is being prepared and should be filed shortly

KM-133 Animal Studies
KM-133 was studied in mice that were irradiated then engrafted with human psoriatic tissue.  Groups of ten mice were treated orally for 14 days with either 10 mg/kg KM-133 once/day, 10 mg/kg KM-133 twice/day, 7.5 mg/kg methotrexate once/day or acted as controls.  The mice were followed for 180 days.  Endpoints were skin appearance, histological observations, and blood levels of PRINS, IL-20 and 12-R lipoxygenase. For these parameters, KM-133 was compared to controls and methotrexate.  CD4+ and CD8+ lymphocyte counts were also measured and compared to efalizumab.

KM-133 significantly reduced all psoriatic endpoints measured relative to controls (p<0.01).  The higher dose of KM-133 reduced psoriatic endpoints more than methotrexate (p<0.01).  In addition, there was no recurrence of psoriasis in animals treated with KM-133, whereas psoriasis recurred after an average of 61 days in animals treated with methotrexate.  Immunosuppression in animals treated with KM-133 was less severe than in those treated with efalizumab.  For a more detailed summary of this study please click here.   

A variation of KM-133 in human xenograft model. The top row animals show a relatively clean coat with limited discernibility of psoriasis. The bottom row are the untreated control animals.

By SAR, the lead candidate KM-133 is selected. KM-133 in human xenograft model. The top row animals show a clean coat with no evidence of psoriasis, essentially showing that KM-133 cured the psoriasis in the mice. The bottom row are the untreated control animals..