Soligenix, Inc. announced preliminary top-line results of its ongoing Phase 2a trial of SGX302 (synthetic hypericin) for the treatment of mild-to-moderate psoriasis. In the expanded portion of the trial (Cohort 2), an additional five patients were enrolled and the treatment guidelines for use of light activation were adjusted to allow for a more rapid escalation and higher final dose level of light than in the initial cohort (Cohort 1) of patients, which is expected to more closely mirror the way the drug will eventually be used in a "real world" clinical setting. The Cohort 2 patients were treated more aggressively than the patients enrolled in Cohort 1 during an 18-week treatment period.

SGX302 therapy was well tolerated by all patients with no drug related adverse events identified. In the four evaluable patients from Cohort 2 (one patient withdrew early in the treatment course for personal reasons unrelated to the study), two reached a disease status of "Almost Clear" represented by an Investigator Global Assessment (IGA) score of 1, which is considered the standard clinical measure for treatment success in psoriasis. In addition, the Psoriasis Activity and Severity Index (PASI) score, another well-characterized measure of treatment success, for patients in Cohort 2 had a mean drop of approximately 50% over the 18-week treatment.

Visible light-activated synthetic hypericin is a novel, first-in-class, photodynamic therapy (PDT) that is expected to avoid many of the long-term risks associated with other PDT treatments. Synthetic hypericin is a potent photosensitizer that is topically applied to skin lesions and absorbed by cutaneous T-cells. With subsequent activation by safe, visible light, T-cell apoptosis is induced, addressing the root cause of psoriasis lesions.

Other PDTs have shown efficacy in psoriasis with a similar apoptotic mechanism, albeit using ultraviolet (UV) light associated with more severe potential long-term safety concerns. The use of visible light in the red-yellow spectrum has the advantage of deeper penetration into the skin (much more than UV light) potentially treating deeper skin disease and thicker plaques and lesions, similar to what was observed in the positive Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) study in CTCL. Synthetic hypericin or HyBryte?

(tradename used in CTCL) was demonstrated in this study to be equally effective in treating both plaque (42% treatment response rate after 12 weeks treatment, p<0.0001 relative to placebo treatment) and patch (37%, p=0.0009) lesions in this orphan disease caused by malignant T-cells. In a published Phase 1/2 proof of concept clinical study using synthetic hypericin, efficacy was demonstrated in patients with CTCL (58.3% response, p=0.04) as well as psoriasis (80% response, p<0.02). In an ongoing Phase 2a study in mild-to-moderate psoriasis, patients enrolled in the initial portion of the trial (Part A) have completed treatment.

In Cohort 1, the initial five patients enrolled received twice weekly treatment for 18 weeks with 0.25% hypericin ointment, followed by light activation approximately 24 hours later. Light doses were increased by up to 1 J/cm2 on subsequent visits until mild erythema was observed in the treated lesions. Light doses for all patients were still being intermittently increased when the scheduled treatments ended, and light doses were generally safe and well tolerated.

Evaluation of the initial cohort of five patients demonstrated a clear biological signal, with the majority of patients recording an improvement in the PASI score, providing evidence of biological improvement, but no patient met the definition of treatment success (IGA score of 0 or 1) at the 18-week treatment timepoint. The second cohort of five patients were enrolled once the Cohort 1 patients had completed all treatment visits. Given how well-tolerated light treatments were in the first Cohort, it was determined that the second cohort of patients could safely receive an accelerated light treatment with increases in the light dose by up to 2 J/cm2 at each visit and allowing the maximum light dose (25 J/cm2) to be reached earlier by approximately week 14, allowing more treatments at the maximum light dose to be completed in the 18-week treatment schedule.

Two of the four evaluable patients from Cohort 2 achieved a clinical success score at some point during the 18-week treatment period and all evaluable patients improved, yielding an average reduction of approximately 50% in the PASI score. One patient in Cohort 2 dropped out of the study for personal reasons unrelated to the study. This treatment approach avoids the risk of secondary malignancies (including melanoma) inherent with both the frequently used DNA-damaging drugs and other phototherapies that are dependent on UV A or B exposure.

The use of synthetic hypericin coupled with safe, visible light also avoids the risk of serious infections and cancer associated with the systemic immunosuppressive treatments used in psoriasis.