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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
KM133 was studied in SCID mice that were irradiated then engrafted with human psoriatic tissue by
inserting human psoriatic tissue under the skin using a trocar. Groups of ten mice were treated with KM
133 orally for 21 days with either 10 mg/kg KM 133 once/day or 10 mg/kg KM 133 twice/day, or with
7.5 mg/kg methotrexate IP once/day for 5 days. The mice were followed for 180 days. Endpoints were
skin appearance, histological observations, PRINS expression, and blood levels of IL-20. For these
parameters, KM 133 was compared to controls and methotrexate. In a second experiment, groups of 10
immunocompetent CD-1 mice were treated with one or two doses of 10 mg/kg Prurisol daily or 3 mg/kg
efalizumab SC once per week for 3 weeks. 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 KM133 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..
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