CRx-191

A topical dissociated steroid providing the efficacy of a high-potency topical steroid with a mid-potency steriod safety profile.

• Description: Synergistic combination of the tricyclic antidepressant nortriptyline and the glucocorticoid steroid mometasone for the treatment of psoriasis and other steroid-responsive dermatoses.
• CRx-191 is a selective steroid amplifier containing a mid-potency steroid, mometasone, and the anti-depressant, nortriptyline. We believe CRx-191 works through a novel mechanism of action in which nortriptyline amplifies mometasone's anti-inflammatory activities without enhancing steroid side effects such as skin atrophy. CRx-191 has demonstrated efficacy in multiple experimental and preclinical models of inflammation, including psoriasis. We have developed a novel topical formulation of CRx-191 for use in planned proof-of-concept clinical trials, as a topical commercial formulation of nortriptyline has not been previously created.
• Data: Positive phase 2a clinical results with CRx-191 in plaque psoriasis.
• Formulation: Novel topical cream co-formulation completed.
• Commercial Opportunity: Psoriasis and potential expansion into other steroid-responsive dermatoses.

There are 6.7 million patients with psoriasis in the U.S.

Status: Completed phase 2a plaque psoriasis study.

Clinical Results: Reported positive Phase 2a clinical data for CRx-191 in plaque psoriasis in which statistically significant reductions in psoriatic infiltrate thickness and erythema (redness) were observed as well as clinically significant improvements in clinical skin assessments. Importantly, when comparing the activity of the CRx-191 combination versus its individual components, CRx-191 demonstrated statistically significant improvements versus its components on the combined clinical index of infiltrate and on erythema. Based on this encouraging data, CombinatoRx has initiated conversations with prospective partners to secure resources focused on maximizing the potential of CRx-191, the first in a series of topical dermatology product candidates within the CombinatoRx portfolio.

CRx-197

A synergistic cytokine modulator for atopic dermatitis and inflammatory dermatoses.

• Description: Combination of the antihistamine loratadine and the antidepressant nortriptyline.
• Data: Demonstrated preclinical efficacy in a number inflammation models, including psoriasis.
• Formulation: Novel topical cream co-formulation completed.
• Commercial Opportunity: Novel class of treatment for atopic dermatitis and other inflammatory dermatoses.

There are 15 million patients treated for atopic dermatitis in the U.S. annually.

Status: Advancied into a phase 2a psoriasis clinical study.

CRx-197 is a selective cytokine modulator containing low concentrations of the allergy drug loratadine and the anti-depressant nortriptyline, neither of which is indicated for the treatment of atopic dermatitis on its own but which have been shown to act synergistically in preclinical models of inflammation. We have developed a novel topical formulation of CRx-197 for use in planned proof-of-concept clinical trials, initially in psoriasis.