HyBryte™ Clinical Results Demonstrate Continued Improvement Post-Treatment

Significant Efficacy against Plaque Lesions Also Demonstrated with HyBryte™

PRINCETON, N.J., Dec. 2, 2024 /PRNewswire/ -- Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, announced today that analysis of the post-treatment data from the open-label study (protocol HPN-CTCL-04) comparing HyBryte™ (synthetic hypericin) to Valchlor® (mechlorethamine) has demonstrated continued improvement in HyBryte™ treated patients and their individual lesions even after stopping treatment. The study, which enrolled 10 patients randomized 1:1 with 12 weeks of treatment and 4 weeks of follow-up post-treatment, was previously reported to demonstrate a positive difference in the overall per patient treatment response rate (60% in the HyBryte™ group vs. 20% in the Valchlor® group) at the end of treatment. After the 4-week follow-up period (Week 16), the majority (3 of 5) of HyBryte™ patients continued to demonstrate improvement with at least a further 10% improvement (absolute difference) at Week 16 relative to the primary outcome measure at Week 12, including one of the HyBryte™ patients achieving a "complete response". In contrast, of the four patients that completed the Valchlor® arm of the study, none achieved this level of improvement by Week 16. For patients, a treatment response was defined as a ≥50% improvement in their cumulative mCAILS (modified Composite Assessment of Index Lesion Severity) score over 3 to 5 lesions. Treatment response was also assessed on individual lesions. There was a similar continued improvement in the lesion responses over time, with the plaque lesions of particular interest given their increasing association with risk of overall disease progression and long-term mortality. At the 12-week (end of treatment) timepoint, the HyBryte™ treated plaque lesions were statistically significantly improved compared to the Valchlor® treated plaques (63%, [10/16] treatment success with HyBryte™ vs. 17%, [2/12] with Valchlor®, p=0.02). By Week 16, the response rates in lesions treated with HyBryte™ were statistically significant responses for all lesions (72% HyBryte™ vs 28% Valchlor®, p=0.02) and specifically for plaque lesions (75% responding plaque lesions with HyBryte™ treatment vs. 17% with Valchlor®, p=0.006) relative to the Valchlor® group. No safety concerns with HyBryte™ were raised during the follow-up period.

"Following the positive results from the previous Phase 2 and 3 studies where we previously participated in evaluating HyBryte™, we were excited to support Soligenix's effort to conduct a prospective comparative assessment of HyBryte™ versus Valchlor®," stated Dr. Brian Poligone, Director of the Rochester Skin Lymphoma Medical Group, and Principal Investigator for the comparability study. "Despite the small study sample size and a randomization that resulted in the HyBryte™ group having patients with more extensive disease, HyBryte™ continues to demonstrate its rapid onset of action and benign safety profile, compared to one of the most widely prescribed approved drugs for early-stage CTCL. The potentially enhanced effect on plaque lesions mirrors the promising activity against very difficult to treat lesions, such as refractory folliculotropic lesions, which we also observed in the first Phase 3 study. We look forward to continuing our support of Soligenix in the development of HyBryte™ by participating in the upcoming confirmatory Phase 3 placebo-controlled study."

"These results support the positive HyBryte™ data from the previously completed Phase 3 FLASH study and demonstrates that a relatively short treatment period with the drug can result in clinically meaningful outcomes," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "This relatively rapid response to HyBryte™ therapy fits nicely into the treatment arsenal for CTCL and reinforces the relative safety of HyBryte™ in these patients compared to other therapies currently in use. We look forward to continuing to work with Dr. Poligone and all of our committed clinical investigators to initiate the 80-patient confirmatory Phase 3 replication study (FLASH2) next month."

The purpose of the HPN-CTCL-04 study was to obtain preliminary comparative assessment of the safety and efficacy of Valchlor® versus HyBryte™ following 12 weeks of treatment as measured in 3 to 5 prospectively identified index lesions for each patient. HyBryte™ was administered twice weekly with light exposure approximately 24 hours after drug application, while Valchlor® was applied as often as daily as per the package insert. At the end of the 12-week treatment period, 60% of the HyBryte™ patients met the prospectively defined level of "Treatment Success" (≥50% improvement in their cumulative mCAILS score compared to Baseline) compared to only 20% of the Valchlor® patients; although due to the small sample size the results do not achieve statistical significance. Of the remaining two HyBryte™ patients that did not achieve treatment success, both saw a substantial (≥30%) reduction in their mCAILS score. In contrast, in the Valchlor® group, of the remaining 4 patients that did not achieve treatment success, one worsened and dropped from the study, one improved less than 30% and two improved ≥30%. The average cumulative improvement in mCAILS at 12 weeks was 52.5% in the HyBryte™ patients versus 34.7% in the Valchlor® patients. HyBryte™ was well tolerated in all patients whereas 1 of the 5 patients receiving Valchlor® had to be withdrawn from the trial because of a clinically significant allergic contact dermatitis from Valchlor®.

During the 4-week follow-up period (Week 16) the majority (3 of 5) of HyBryte™ patients continued to demonstrate lesion improvement with at least a further 10% reduction (absolute difference) at Week 16 relative to the primary outcome measure at Week 12, including one of these patients achieving a "complete response". The remaining two HyBryte™ subjects showed either a modest (15% change), one had a modest decrease, one remained static, and one had a modest improvement by Week 16. Analysis of the individual lesion responses showed similar response profiles, with treatment response observed in 61% of HyBryte™ treated lesions vs. 33% response in Valchlor® treated lesions (p=0.18) at Week 12. The lesions responses increased over the 4 weeks following treatment to 72% responding lesions with HyBryte™ treatment and decreased over the 4 weeks following treatment to 28% with Valchlor, p=0.02. Focusing specifically on the plaque lesions, 63% of HyBryte™ treated plaque lesions (10/16) responded to treatment vs. 17% of Valchlor® treated plaque lesions (2/12; p=0.02). Again, the responses of the HyBryte™ treated lesions increased over the 4 weeks following treatment to 75% responding plaque lesions with HyBryte™ treatment and the Valchlor® treated lesions response rate was unchanged at 17%, p=0.006. Plaque lesions have been acknowledged as both more difficult to treat and, more recently, as potentially linked to disease progression. The link with disease progression was most recently reported at the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Tumour Group Annual Meeting in Lausanne, Switzerland on October 9-11, 2024.

When comparing the tolerance of the topical therapies (i.e., reactions where the drug was applied to the skin) in this trial, it is notable that all patients tolerated HyBryte™ well and had no adverse events "Related" to the therapy. In contrast, 60% of the Valchlor® treated patients had at least one adverse event "Related" to the therapy. These adverse events in the Valchlor® group included rashes, application site sensitivity, allergic contact dermatitis, and dermatitis, with one patient requiring steroid treatment, one requiring temporary interruption of Valchlor® treatments, and one requiring permanent discontinuation of Valchlor®. No such instances were reported in the HyBryte™ group.

About 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