SGX301 is a novel, first-in-class photodynamic therapy using a potent photosensitizer, synthetic hypericin, that is topically applied and activated by safe visible fluorescent light. This treatment avoids the risk of secondary malignancies (including melanoma) inherent with the frequently employed DNA-damaging chemotherapeutic drugs and other photodynamic therapies that are dependent on ultraviolet A (UVA) light exposure. Topical, synthetic hypericin has demonstrated safety in a Phase 1 clinical study in healthy volunteers. In a Phase 2, placebo-controlled, clinical study in patients with cutaneous T-cell lymphoma (CTCL), the drug was safe, well tolerated, and effective in ameliorating the skin lesions. These clinical data fully support advancing this therapy to a pivotal Phase 3 clinical trial in CTCL.

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 both settings, it appears that the mode of action is an induction of cell death in a concentration-dependent as well as a light dose-dependent fashion. Hypericin is one of the most efficient known generators of singlet oxygen, the key intermediate for phototherapy. The generation of singlet oxygen induces localized necrosis and apoptosis. The use of topical hypericin coupled with directed visible light results in generation of singlet oxygen only at the required site. The use of visible light (as opposed to cancer-causing ultraviolet light) is a major advance in photodynamic therapy. In a published Phase 2 clinical study in CTCL, 58.3% of patients receiving SGX301 while only 8.3% of those receiving placebo experienced a significant response, a statistically significant difference (p <0.04).

Preclinical and clinical data with photoactivated hypericin supports other potential indications, including psoriasis that is similarly characterized by cutaneous accumulation of T-cell lymphocytes but without cancerous transformation. Psoriasis affects over 7 million adults in the US. Photodynamic therapy is a frequently employed initial therapy for psoriasis, despite the need for ultraviolet light exposure and its attendant risk of melanoma and non-melanoma skin cancer. The Phase 2 clinical study has shown that hypericin and visible light phototherapy is also effective in treating these lesions.

Soligenix has a strong worldwide intellectual property position on the use of photoactivated hypericin.

SGX301 has received orphan drug designation from the US FDA for the treatment of CTCL.

About CTCL

Cutaneous T-cell lymphoma (CTCL) is a class of non-Hodgkin’s lymphoma (NHL), a type of cancer of the white blood cells that are an integral part of the immune system. Unlike most NHLs which generally involve B-cell lymphocytes (involved in producing antibodies), CTCL is caused by an expansion of malignant T-cell lymphocytes (involved in cell-mediated immunity) normally programmed to migrate to the skin. These skin-trafficking malignant T-cells migrate to the skin, causing various lesions to appear that may change shape as the disease progresses, typically beginning as a rash and eventually forming plaques and tumors. Mycosis fungoides (MF) is the most common form of CTCL. It generally presents with skin involvement only, manifested as scaly, erythematous patches. Advanced disease with diffuse lymph node and visceral organ involvement is usually associated with a poorer response rate to standard therapies.

With CTCL mortality is related to stage of disease, with median survival generally ranging from about 12 years in the early stages to only 2.5 years when the disease has advanced. There is currently no cure for CTCL. Treatment of early-stage disease (the most frequent type of CTCL) generally involves skin-directed therapies. Most MF treatments are not approved by the FDA. One of the most common unapproved therapies used for early-stage disease is oral 5 or 8-methoxypsoralen (Psoralen) given with ultraviolet A (UVA) light, referred to as PUVA. Although having demonstrated a level of efficacy, psoralen is a mutagenic chemical that interferes with DNA causing mutations and other malignancies. Moreover, UVA is a carcinogenic light source that when combined with the psoralen, results in serious adverse effects including secondary skin cancers. As a result, the FDA requires a Black Box warning for PUVA.

CTCL constitutes a rare group of NHLs, occurring in about 4% of the approximate 500,000 individuals living with the disease. It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of CTCL that it affects over 20,000 individuals in the US, with approximately 2,800 new cases seen annually.