Soligenix, Inc. announced that it has received agreement from the European Medicines Agency (EMA) on the key design components of a confirmatory Phase 3 placebo-controlled study evaluating the safety and efficacy of HyBryte? (synthetic hypericin) in the treatment of cutaneous T-cell lymphoma (CTCL) patients with early-stage disease. This confirmatory 18-week study is expected to enroll approximately 80 patients in the United States and Europe and is targeted to begin patient enrollment by the end of 2024 with top-line results anticipated in the second half of 2026.

The confirmatory study, called FLASH2 (Fluorescent Light Activated Synthetic Hypericin 2), replicates the double-blind, placebo-controlled design used in the first successful Phase 3 FLASH study that consisted of three 6-week treatment cycles (18 weeks total), with the primary efficacy assessment occurring at the end of the initial 6 week double-blind, placebo-controlled treatment cycle (Cycle 1). However, the second study extends the double-blind, placebo-controlled assessment to 18 weeks of continuous treatment (no ?between-Cycle? treatment breaks) with the primary endpoint assessment occurring at the end of the 18-week timepoint.

In the first Phase 3 study, a treatment response of 49% (p<0.0001 vs patients receiving placebo in Cycle 1) was observed in patients completing 18 weeks (3 cycles) of therapy. In this second study, all important clinical study design components remain the same as in the first FLASH study, including the primary endpoint and key inclusion-exclusion criteria. The extended treatment for a continuous 18 weeks in a single cycle is expected to statistically demonstrate HyBryte?s? increased effect over a more prolonged, ?real world?

treatment course. The confirmatory Phase 3, randomized, double-blind, placebo-controlled, multicenter study includes approximately 80 subjects with early-stage CTCL. It will evaluate the efficacy and safety of HyBryte?

topically applied to CTCL lesions twice weekly for 18 weeks, with each application followed 21 (±3) hours later by the administration of safe, visible light at a wavelength of 500 to 650 nm. The light will be administered starting at 6 J/cm2 twice weekly. This will be increased upwards by 2 J/cm2 until: 1) the patient experiences a Grade 1 erythema, 2) the patient reaches the maximum dose of 30 J/cm2, or 3) the patient cannot tolerate the treatment time, whichever comes first.

All of the patient?s lesions that are readily available for exposure to the visible light source will be treated and 3 to 5 index lesions in each patient will be prospectively identified and indexed for the modified composite assessment of index lesions severity (mCAILS) evaluation prior to randomization (baseline). The primary efficacy endpoint will be assessed on the percent of patients in each of the two treatment groups (i.e., HyBryte? and placebo) achieving a Partial or Complete Response (yes/no) of the treated lesions defined as a = 50% reduction in the total mCAILS score for the 3-5 index lesions following 18 weeks of treatment compared to the total mCAILS score at baseline.

Other secondary measures will assess treatment response (including duration), degree of improvement, time to relapse and safety. Following treatment, all patients will be followed every 4 weeks for a total of 12 weeks (through Week 30). The Data Monitoring Committee (DMC) will conduct one (1) interim analysis when approximately 60% of the total subjects have completed the primary endpoint evaluation.

The primary efficacy endpoint and the key safety endpoints will be analyzed. A sample size recalculation may be performed after examining the assumptions or the trial halted for either futility, safety concerns, or overwhelming efficacy. Soligenix, participating in clinical investigators, and any personnel involved in trial conduct will remain blinded to study treatment until completion of the trial.