Soligenix Announces NIH Small Business Innovation Research Award

Soligenix announced the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health (NIH), has awarded Soligenix a Phase I Small Business Innovation Research (SBIR) of approximately $150,000 to support the evaluation of SGX942 (dusquetide) in pediatric indications. This award will facilitate the assessment of SGX942 safety in juvenile animals, supporting future studies in pediatric populations, including oral mucositis indications in pediatric patients undergoing stem cell transplants and treatments for head and neck cancer.

Innate Defense Regulators (IDRs) regulate the innate immune system to simultaneously reduce inflammation, eliminate infection and enhance tissue healing. Dusquetide is Soligenix's lead clinical IDR candidate. IDRs have no direct antibiotic activity but modulate host responses, increasing survival after infections with a broad range of bacterial Gram-negative and Gram-positive pathogens including both antibiotic sensitive and resistant strains, as well as accelerating resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- or radiation-therapy. Soligenix has previously reported the results of a Phase 2 clinical study using dusquetide in the treatment of oral mucositis in head and neck cancer (HNC) patients undergoing chemoradiation therapy (CRT). In addition to demonstrating a reduction in the median duration of severe oral mucositis in these patients, dusquetide treatment was also associated with a reduced incidence of reported infections and an increased rate of tumor resolution. A pivotal, Phase 3, multinational study in oral mucositis is currently underway in the US and Europe, with an interim analysis expected in the September 2019 timeframe.

"We are appreciative of the continued support provided by NIDCR for the SGX942 development program," said Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "We believe this SBIR grant award further validates dusquetide's novel mechanism of action, as well as the positive clinical data generated to date. Oral mucositis remains an extremely debilitating side effect of cancer treatment in both adults and children. This funding will allow us to further evaluate the safety of IDRs in juvenile animals, allowing for the conduct of pediatric clinical studies, and the potential to expand future use in the pediatric patient population.

Mucositis is the clinical term for damage done to the mucosa by anticancer therapies. It can occur in any mucosal region, but is most commonly associated with the mouth, followed by the small intestine. It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of mucositis, that mucositis affects approximately 500,000 people in the US per year and occurs in 40% of patients receiving chemotherapy. Mucositis can be severely debilitating and can lead to infection, sepsis, the need for parenteral nutrition and narcotic analgesia. The gastrointestinal damage causes severe diarrhea. These symptoms can limit the doses and duration of cancer treatment, leading to sub-optimal treatment outcomes.

The mechanisms of mucositis have been extensively studied and have been recently linked to the interaction of chemotherapy and/or radiation therapy with the innate defense system. Bacterial infection of the ulcerative lesions is now regarded as a secondary consequence of dysregulated local inflammation triggered by therapy-induced cell death, rather than as the primary cause of the lesions.

It is estimated, based upon review of historic published studies and reports and an interpolation of data on the incidence of oral mucositis, that oral mucositis in HNC is a subpopulation of approximately 90,000 patients in the US, with a comparable number in Europe. Oral mucositis almost always occurs in patients with HNC treated with CRT and is severe, causing inability to eat and/or drink, in >80% of patients. It is common (40-100% incidence) in patients undergoing high dose chemotherapy and hematopoietic cell transplantation, where the incidence and severity of oral mucositis depends greatly on the nature of the conditioning regimen used for myeloablation.

In the pediatric population, head and neck cancer is a rarer occurrence and is caused by different underlying pathologies. The major types of HNC in children are lymphoma, sarcomas (including rhabdomyosarcomas), and neuroblastoma rather than squamous cell carcinoma, the major type of adult HNC cancers. Hematopoietic stem cell transplantation (HSCT), especially allogeneic transplantation with higher risk of oral mucositis, is more frequently used in the pediatric population than in adults when treating a number of primary tumor types, as seen in leukemia and lymphoma. Both treatment of HNC and HSCT are associated with high risk of oral mucositis in the pediatric population.

Oral mucositis remains an area of unmet medical need where there are currently no approved drug therapies in the context of any solid tissue tumors.

IDRs are a new class of short, synthetic peptides. They have a novel mechanism of action whereby they modulate the body's reaction to both injury and infection towards an anti-inflammatory, anti-infective and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host's innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. They also accelerate resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy. Preclinical efficacy and safety has been demonstrated in numerous animal disease models including mucositis, colitis, macrophage activation syndrome (MAS) as well as bacterial infections, including melioidosis.

SGX942 (the lead clinical IDR candidate containing the active ingredient dusquetide) has demonstrated safety in a Phase 1 clinical study in 84 healthy human volunteers. Positive efficacy results were demonstrated in a Phase 2 clinical study in 111 patients with oral mucositis due to chemoradiation therapy for head and neck cancer. Soligenix is working with leading oncology centers in the US and Europe to advance SGX942 in oral mucositis with the conduct of a pivotal Phase 3 clinical trial referred to as the "DOM–INNATE" study (Dusquetide treatment in Oral Mucositis – by modulating INNATE immunity).

Soligenix has a strong intellectual property position in the IDR technology platform, including composition of matter for dusquetide and related analogs. IDRs were developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada. Soligenix has received partial funding from NIH for its oral mucositis clinical studies.

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