Soligenix Announces FDA Clearance of Phase 3 Clinical Protocol of SGX301 in Cutaneous T-Cell Lymphoma

Pivotal Phase 3 Clinical Trial Targeted to Begin in First Half of 2015

PRINCETON, N.J., Sept. 17, 2014 -- Soligenix, Inc. (SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company developing products that address unmet medical needs in the areas of inflammation, oncology and biodefense, announced today that agreement has been reached with the US Food and Drug Administration (FDA) on the design of a pivotal, Phase 3 clinical trial evaluating its product SGX301 (synthetic hypericin) for the treatment of cutaneous T-cell lymphoma (CTCL).

SGX301 is a novel, first-in-class, photodynamic therapy utilizing safe visible light for activation.  The active ingredient, synthetic hypericin, is a potent photosensitizer which is topically applied to skin lesions and activated by visible fluorescent light. This treatment approach 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) exposure. Topical hypericin has demonstrated safety in a Phase 1 clinical study in healthy volunteers. In a Phase 2, double-blind, placebo-controlled clinical study in CTCL patients, the drug was safe and well tolerated, with 58.3% of the CTCL patients responding to SGX301 treatment compared to only 8.3% receiving placebo (p  0.04). 

"I enthusiastically support Soligenix in their efforts to improve outcomes for patients with CTCL, affecting up to 50,000 patients in the US," stated Alain Rook, MD, Director, Cutaneous Lymphoma Program, Hospital of the University of Pennsylvania. "I have had a lengthy scientific and clinical interest in hypericin and am pleased that the Soligenix team is advancing this product to a Phase 3 clinical study. I believe that SGX301 has the potential to be a major step forward in the treatment of CTCL by providing a safer alternative therapy over the course of the patients' disease than is currently available."

Based on the positive results demonstrated in the Phase 2 study of SGX301, the upcoming Phase 3 protocol will be a highly powered, double-blind, randomized, placebo-controlled, multicenter trial and will seek to enroll approximately 120 patients. The trial will consist of three treatment cycles, each of 8 weeks duration. Treatments will be administered twice weekly for the first 6 weeks and treatment response will be determined at the end of Week 8. In the first treatment cycle, approximately 80 patients will receive SGX301 and 40 will receive placebo treatment of their index lesions. In the second cycle, all patients will receive SGX301 treatment of their index lesions and in the third (open-label) cycle all patients will receive SGX301 treatment of all their lesions.  Subjects will be followed for an additional 6 months after the completion of treatment. The primary clinical efficacy endpoint is treatment response assessed using the CAILS (Composite Assessment of Index Lesion Severity) score evaluating the three worst index lesions at the end of Cycle 1 (Week 8). The trial is anticipated to begin in the first half of 2015 with primary data available in the second half of 2016. 

"We are pleased to have FDA agreement on our Phase 3 protocol design in CTCL," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "We are excited to move forward with this pivotal trial in an effort to address the significant unmet medical need in this orphan disease."

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. A relatively uncommon sub-group of CTCL patients present with extensive skin involvement and circulating malignant cerebriform T-cells, referred to as Sezary syndrome. These patients have substantially graver prognoses than those with MF. 

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 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; therefore, 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. 

About SGX301

SGX301 is a novel, first-in-class, photodynamic therapy utilizing safe visible light for activation.  The active ingredient in SGX301 is synthetic hypericin, a potent photosensitizer which is topically applied to skin lesions and then activated by fluorescent light 16 to 24 hours later.  Hypericin is also found in several species of Hypericum plants, although the drug used in SGX301 is chemically synthesized by a proprietary manufacturing process and not extracted from plants. Importantly, hypericin is optimally activated with visible light thereby avoiding the negative consequences of ultraviolet light.

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 as well as a light dose-dependent fashion. These effects appear to result, in part, from the generation of singlet oxygen during photoactivation of hypericin. 

Hypericin is one of the most efficient known generators of singlet oxygen, the key intermediate for phototherapy. The generation of singlet oxygen induces necrosis and apoptosis in adjacent cells.  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, patients experienced a significant response with topical hypericin treatment as compared to placebo: 58.3% compared to 8.3% (p 0.04), respectively.   

SGX301 has received orphan drug designation from the US FDA. The US Orphan Drug Act is intended to assist and encourage companies to develop safe and effective therapies for the treatment of rare diseases and disorders. In addition to providing a seven year term of market exclusivity for SGX301 upon final FDA approval, orphan drug designation also positions Soligenix to be able to leverage a wide range of financial and regulatory benefits, including government grants for conducting clinical trials, waiver of expensive FDA user fees for the potential submission of a New Drug Application for SGX301, and certain tax credits.

About Soligenix, Inc.

Soligenix is a late-stage biopharmaceutical company developing products that address unmet medical needs in the areas of inflammation, oncology and biodefense. Soligenix is developing proprietary formulations of oral BDP (beclomethasone 17,21-dipropionate) for the prevention/treatment of gastrointestinal disorders characterized by severe inflammation, including pediatric Crohn's disease (SGX203) and acute radiation enteritis (SGX201). Soligenix is also advancing its novel innate defense regulator (IDR) technology SGX942 for the treatment of oral mucositis and SGX301, its novel first-in-class photodynamic technology utilizing synthetic hypericin with safe visible light, for the treatment of cutaneous T-cell lymphoma.  

Through its BioDefense Division, Soligenix is developing countermeasures pursuant to the Biomedical Advanced Research and Development Authority (BARDA) Strategic Plan of 2011-2016 for inclusion in the US government's Strategic National Stockpile. Soligenix's biodefense products in development are a recombinant subunit vaccine called RiVax™, which is designed to protect against the lethal effects of exposure to ricin toxin and VeloThrax™, a vaccine against anthrax exposure. RiVax™ has demonstrated statistically significant survival results in a lethal aerosol exposure non-human primate model and has also been shown to be well tolerated and immunogenic in two Phase 1 clinical trials in healthy volunteers. Both RiVax™ and VeloThrax™ are currently the subject of a $9.4 million National Institute of Allergy and Infectious Diseases (NIAID) grant supporting development of Soligenix's new vaccine heat stabilization technology known as ThermoVax™. Soligenix is also developing OrbeShield™ for the treatment of gastrointestinal acute radiation syndrome (GI ARS) under a BARDA contract award valued up to $26.3 million and a NIAID contract award valued up to $6.4 million. OrbeShield™ has previously demonstrated statistically significant preclinical survival results in a canine model of GI ARS funded by the NIAID. Additionally, Soligenix has an exclusive worldwide collaboration with Intrexon Corporation (XON) focused on the joint development of a treatment for Melioidosis, a high priority biothreat and an area of unmet medical need.

For further information regarding Soligenix, Inc., please visit the Company's website at www.soligenix.com.

This press release contains forward-looking statements that reflect Soligenix, Inc.'s current expectations about its future results, performance, prospects and opportunities, including but not limited to, potential market sizes, patient populations and clinical trial enrollment.  Statements that are not historical facts, such as "anticipates," "estimates," "believes," "intends," "potential," or similar expressions, are forward-looking statements.  These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements.  Soligenix cannot assure you that it will be able to successfully develop, achieve regulatory approval for or commercialize products based on its technologies, particularly in light of the significant uncertainty inherent in developing vaccines against bioterror threats conducting preclinical and clinical trials of vaccines, obtaining regulatory approvals and manufacturing vaccines, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that it will be able to successfully obtain any further funding to support product development and commercialization efforts, including grants and awards, maintain its existing grants which are subject to performance requirements, enter into any biodefense procurement contracts with the US Government or other countries, that it will be able to compete with larger and better financed competitors in the biotechnology industry, that changes in health care practice, third party reimbursement limitations and Federal and/or state health care reform initiatives will not negatively affect its business, or that the US Congress may not pass any legislation that would provide additional funding for the Project BioShield program.  These and other risk factors are described from time to time in filings with the Securities and Exchange Commission, including, but not limited to, Soligenix's reports on Forms 10-Q and 10-K.  Unless required by law, Soligenix assumes no obligation to update or revise any forward-looking statements as a result of new information or future events.