Treatment of acne. There are two possible approaches for the use of Nia-114 for the treatment of acne. A study by a corporate partner
of NPI has demonstrated that the combination of Nia-114 and salicylic was very effective for treating acne including clear benefit
in the resolution of acne scarring. This study was not placebo controlled for Nia-114 but salicylic acid has never been reported
to resolve acne scarring and the known mechanisms of action of Nia-114 would be expected to do so. Consequently, NPI believes
a human study containing a placebo arm related to Nia-114 and examining for the effect of Nia-114 and salicylic acid, alone and
in combination for treatment of acne including examination for effects on acne scarring is warranted. A second approach would
involve conjunctive use with retinoid drugs, which are primarily approved to treat acne. However, because the use of retinoids
impairs the skin barrier patients often discontinue use of such therapy due to irritation. Based on NPI's published study
combining Nia-114 and retinoic acid (Jacobson, et al., Experimental Dermatology, 16, 927-935, 2007), a combination of Nia-114
and retinoic acid should allow longer-term use of retinoic acid for this indication and thus permit improved clinical outcome.
NPI believes that a human study examining the effect of conjunctive use of Nia-114 for treatment of acne is warranted by the
Treatment of facial photodamage. Skin barrier impairment caused by sun exposure is a major consequence of skin photodamage. The use of
retinoids such as retinoic acid, the only drugs approved by the FDA to treat photodamaged skin, further degrade the skin barrier before
therapeutic benefit takes place. As a result, patients often discontinue the use of this therapy due to the irritation caused by and
associated with degrading the skin barrier. NPI has completed a human study to support a claim that using Nia-114 with retinoic acid
drug provides superior tolerability and improved efficacy (Jacobson, et al., Experimental Dermatology, 16, 927-935, 2007). By improving
tolerability, the conjunctive use of Nia-114 should increase patient compliance that will permit extended use of retinoic acid and
thus produce additional therapeutic benefit. NPI believes that the available data indicate that a drug indication for Nia-114 for
conjunctive use with retinoic acid for treatment of facial photodamage could be achieved.
Treatment of atopic dermatitis. Skin barrier impairment is a major cause of atopic skin conditions that in severe cases present as eczema.
The use of mid potency topical steroids, the current treatment of choice for this condition, further impairs the skin barrier. NPI has
completed a pilot study that shows skin barrier repair in atopic skin (Jacobson et al., Experimental Dermatology, 16, 490-499, 2007),
supporting the view that combining Nia-114 with a steroid would provide superior efficacy due to improving the skin barrier and will
likely help prevent some atopic skin conditions from occurring at all. NPI believes that our completed human study dictates a second
study for the use of Nia-114 for treatment of atopic dermatitis.
Treatment of rosacea. Skin barrier impairment is an important factor in the cause of rosacea. Topical antibiotics now used to treat this
condition provide minimal therapeutic benefit. NPI believes that combining Nia-114 with metronidazole to address the skin barrier defect
in this disease would provide longer lasting and more efficacious treatment for rosacea. Moreover, the improvement in skin barrier
associated with the use of Nia-114 is likely to lessen the frequency of reoccurrence and the severity of this condition over time.
Since it is estimated that 14 million people in the U.S. have rosacea, a drug regimen capable of successfully treating this condition
could grow this market. NPI believes that a human study for conjunctive use of Nia-114 with metronidazole is justified by the available data.
Reducing cutaneous side effects of cancer chemotherapy. The side effect of hair loss associated with cancer chemotherapy is well known.
Although less well known, many cancer chemotherapeutic drugs cause a range of skin side effects. These effects are related to the cytotoxic
effects of the drug on epidermal proliferation and differentiation that are exacerbated by the loss of skin barrier integrity. While these
effects are rarely life threatening, they nevertheless increase the fragility of already seriously ill patients. The ability of Nia-114 to
promote epidermal differentiation offers the potential to reduce cutaneous side effects.
Reducing skin cancer in organ transplant patients. Patients that undergo organ transplants have a greatly increased risk of skin cancer as
a result of drugs needed to suppress the immune system to prevent organ rejection. The ability of Nia-114 to promote epidermal differentiation
and normalize immune function raises the likely possibility that it would reduce the skin cancer risk of organ transplant patients.