Soligenix, Inc. announced that the results of its compatibility study evaluating HyBryte? (synthetic hypericin) for the treatment of cutaneous T-cell lymphoma (CTCL) have been published in the Journal of the European Academy of Dermatology & Venereology (JEADV) Clinical Practice. The publication highlights the positive clinical results from study, HPN-CTCL-02, evaluating HyBryte?

in the treatment of CTCL. The open-label study enrolled 9 patients to receive 8 weeks of HyBryte? treatment of their cancerous lesions, with an assessment of treatment response conducted at week 10 using the modified Composite Assessment of Index Lesion Severity (mCAILS) score.

The treatment response results of 22% following 8 weeks of twice weekly HyBryte? therapy reinforces and confirms the results of the Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) trial published in the Journal of the American Medical Association (JAMA) Dermatology, despite the fact that patients in Study HPN-CTCL-02 were specifically selected to have more extensive disease consistent with its potential commercial use. Additionally, in this study all patients had improvements in their cumulative mCAILS score (average improvement of 36.4%, range 8 to 100%).

Results in individual lesions showed that 7 of the 27 index lesions (25.9%) had at least a 50% improvement in their mCAILS score and 4 of the 27 index lesions (14.8%) were completely resolved after as little as 8 weeks of treatment. Other key evaluations included measurements of systemic exposure and electrocardiograms, which yielded extremely low and limited levels of systemic hypericin (plateau concentration of approximately 0.00013 µg/mL) detected in the blood and no observable impact to normal sinus rhythm, reinforcing the safety of HyBryte?. HyBryte?

(research name SGX301) is a novel, first-in-class, photodynamic therapy utilizing safe, visible light for activation. The active ingredient in HyBryte? is synthetic hypericin, a potent photosensitizer that is topically applied to skin lesions that is taken up by the malignant T-cells, and then activated by safe, visible light approximately 24 hours later.

The use of visible light in the red-yellow spectrum has the advantage of penetrating more deeply into the skin (much more so than ultraviolet light) and therefore potentially treating deeper skin disease and thicker plaques and lesions. This treatment approach avoids the risk of secondary malignancies (including melanoma) inherent with the frequently employed DNA-damaging drugs and other phototherapy that are dependent on ultraviolet exposure. Combined with photoactivation, hypericin has demonstrated significant anti-proliferative effects on activated normal human lymphoid cells and inhibited growth of malignant T-cells isolated from CTCL patients.

In a published Phase 2 clinical study in CTCL, patients experienced a statistically significant (p=0.04) improvement with topical hypericin treatment whereas the placebo was ineffective. HyBryte? has received orphan drug and fast track designations from the U.S. Food and Drug Administration (FDA), as well as orphan designation from the European Medicines Agency (EMA).

The published Phase 3 FLASH trial enrolled a total of 169 patients (166 evaluable) with Stage IA, IB or IIA CTCL. The trial consisted of three treatment cycles. Treatments were administered twice weekly for the first 6 weeks and treatment response was determined at the end of the 8th week of each cycle.

In the first double-blind treatment cycle (Cycle 1), 116 patients received HyBryte? treatment (0.25% synthetic hypericin) and 50 received placebo treatment of their index lesions. A total of 16% of the patients receiving HyBryte?

achieved at least a 50% reduction in their lesions (graded using a standard measurement of dermatologic lesions, the CAILS score) compared to only 4% of patients in the placebo group at 8 weeks (p=0.04) during the first treatment cycle (primary endpoint). HyBryte? treatment in this cycle was safe and well tolerated.

In the second open-label treatment cycle (Cycle 2), all patients received HyBryte? treatment of their index lesions. Evaluation of 155 patients in this cycle (110 receiving 12 weeks of HyBryte?

treatment and 45 receiving 6 weeks of placebo treatment followed by 6 weeks of HyBryte? treatment), demonstrated that the response rate among the 12-week treatment group was 40% (p<0.0001 vs the placebo treatment rate in Cycle 1). Comparison of the 12-week and 6-week treatment groups also revealed a statistically significant improvement (p<0.0001) between the two groups, indicating that continued treatment results in better outcomes.

HyBryte? continued to be safe and well tolerated. Additional analyses also indicated that HyBryte?

is equally effective in treating both plaque (response 42%, p<0.0001 relative to placebo treatment in Cycle 1) and patch (response 37%, p=0.0009 relative to placebo treatment in Cycle 1) lesions of CTCL, a particularly relevant finding given the historical difficulty in treating plaque lesions in particular. The third (optional) treatment cycle (Cycle 3) was focused on safety and all patients could elect to receive HyBryte? treatment of all their lesions.

Of note, 66% of patients elected to continue with this optional compassionate use /safety cycle of the study. Moreover, in a subset of patients evaluated in this cycle, it was demonstrated that HyBryte? is not systemically available, consistent with the general safety of this topical product observed to date.

At the end of Cycle 3, HyBryte? continued to be well tolerated despite extended and increased use of the product to treat multiple lesions. Overall safety of HyBryte?

is a critical attribute of this treatment and was monitored throughout the three treatment cycles (Cycles 1, 2 and 3) and the 6-month follow-up period. HyBryte's? mechanism of action is not associated with DNA damage, making it a safer alternative than currently available therapies, all of which are associated with significant and sometimes fatal, side effects. Predominantly these include the risk of melanoma and other malignancies, as well as the risk of significant skin damage and premature skin aging.

Currently available treatments are only approved in the context of previous treatment failure with other modalities and there is no approved front-line therapy available. With very limited systemic absorption, a compound that is not mutagenic and a light source that is not carcinogenic, there is no evidence to date of any potential safety issues. Following the first Phase 3 study of HyBryte?

for the treatment of CTCL, the FDA and the EMA indicated that they would require a second successful Phase 3 trial to support marketing approval. With agreement from the EMA on the key design components, the second, confirmatory study, called FLASH2, is expected to be initiated before the end of 2024.