Positive clinical results from compatibility study of HyBryte in the treatment of cutaneous T-cell lymphoma.- Soligenix, Inc.

The open-label study (protocol HPN-CTCL-02) 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 Composite Assessment of Index Lesion Severity (CAILS) score. All subjects were enrolled by Brian Poligone, MD, PhD, at the Rochester Skin Lymphoma Medical Group.

The purpose of the study was to establish that any light device capable of producing visible light of an appropriate and consistent wavelength (500 to 650 nm) was suitable for use with HyBryte and extend the pharmacokinetic profile using a recently developed, more sensitive hypericin assay. In addition to meeting these objectives, the efficacy demonstrated strongly substantiates the results of the Phase III FLASH (Fluorescent Light Activated Synthetic Hypericin) study. The treatment response data of 22% following 8 weeks of twice weekly HyBryte therapy recapitulates the results of the FLASH trial, despite the fact that patients in the current study 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 CAILS 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 CAILS 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 cardiac output, which yielded extremely low and limited levels of systemic hypericin (plateau concentration of approximately 0.00013 ug/mL) detected in the blood and no observable impact to normal sinus rhythm, reinforcing the safety of HyBryte.

"We were excited for the opportunity to work with Soligenix and make HyBryte available to our patients," stated Brian Poligone, MD, PhD, Director of the Rochester Skin Lymphoma Medical Group, Fairport, NY, and Principal Investigator for the compatibility study and Leading Enrolling Investigator in the FLASH study. "Since the completion of the Phase III FLASH study, I have had a number of patients asking about possible access to this promising therapy. Fortunately, we were chosen to conduct this study and the patients' enthusiasm for the product was evident by their willingness to participate in the trial, allowing for its rapid completion. I look forward to continuing to work with Soligenix to further advance the HyBryte program so my patients can have this much needed treatment option available to them."

"These results reinforce the positive HyBryte data from the FLASH study. Important corporate objectives for the study were to replicate results previously observed in the FLASH study, while using finished drug product manufactured by our proposed commercial contract manufacturer and activated using a commercially viable light device," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "We look forward to continuing to work with Dr. Poligone and all of our committed clinical investigators to make HyBryte™ available to this underserved orphan patient population."

The recently published Phase III 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, 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 the first 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.></0.0001></0.0001)></0.0001>

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. Of the subset of patients that received HyBryte throughout all 3 cycles of treatment, 49% of them demonstrated a positive treatment response (p<0.0001 vs patients receiving placebo in cycle 1). 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.></0.0001>

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. Within this landscape, treatment of CTCL is strongly motivated by the safety risk of each product. HyBryte potentially represents the safest available efficacious treatment for CTCL. 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.

The Phase III CTCL clinical study was partially funded by the National Cancer Institute via a Phase II SBIR grant (#1R44CA210848-01A1) awarded to Soligenix, Inc. In addition, the FDA awarded an Orphan Products Development grant to support the evaluation of HyBryte for expanded treatment in patients with early-stage CTCL, including in the home use setting. The grant, totaling $2.6 million over 4 years, was awarded to a prestigious academic institution that was a leading enroller in the Phase III FLASH study.

See- "Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides)-The FLASH Phase III Randomized Clinical Trial. Ellen J. Kim, MD; Aaron R. Mangold, MD; Jennifer A. DeSimone, MD; et al JAMA Dermatol. 2022;158(9):1031-1039. doi:10.1001/jamadermatol.2022.2749.