SGX942 Oral Mucositis, Dusquetide, Innate Defense Regulator (IDR) candidate - Soligenix

SGX942 is the lead clinical Innate Defense Regulator (IDR) candidate, containing the active ingredient dusquetide.  The IDR technology platform represents a novel and innovative approach to therapeutically modulating immune defenses by targeting the innate immune system.

Dusquetide (also referred to by its research name SGX94) is a fully synthetic, 5-amino acid peptide with high aqueous solubility and stability. Preclinical data indicate that dusquetide is active in models of a wide range of therapeutic indications including severe side-effects of chemo- and/or radiation-therapy and life-threatening bacterial infections. Please refer to the SGX94 (Dusquetide) Executive Summary (pdf) for more detailed information.

A multi-center, double-blind, placebo-controlled, pivital Phase 3 clinical study in oral mucositis in head and neck cancer patients has been initiated. Oral mucositis in this patient population is an area of unmet medical need where there are currently no approved drug therapies. Results from the completed double-blind, placebo-controlled Phase 2 study have demonstrated that SGX942:

  • reduced the median duration of severe oral mucositis by 50% (from 18 to 9 days) compared to placebo;
  • reduced in the median duration of severe oral mucositis by 67% (from 30 days to 10 days) in patients receiving the most aggressive chemoradiation compared to placebo;
  • reduced the rate of infection and increased the incidence of “complete resolution” tumor status compared to placebo at the 1 month follow-up visit;
  • reduced amount of opiate use compared to placebo; and
  • had a reduced mortality rate compared to placebo over the 12 month follow-up visits.

Results from the Phase 2 study have been published in two papers describing the primary effacy and long-term follow-up results.

SGX942 has previously demonstrated safety and tolerability in a double-blind, placebo-controlled, healthy volunteer Phase 1 clinical trial.

SGX942 has been awarded Fast Track designation from the FDA for the treatment of oral mucositis as a result of radiation and/or chemotherapy treatment in head and neck cancer patients.

Soligenix has a strong worldwide intellectual property position on dusquetide and related analogs including composition of matter.

About Oral Mucositis

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. Mucositis affects approximately 500,000 people in the US per year and occurs in 40% of patients receiving chemotherapy. Mucositis almost always occurs in patients with head and neck cancer treated with radiation therapy (>80% incidence of severe mucositis) and is common (40-100% incidence) in patients undergoing high dose chemotherapy and hematopoietic cell transplantation, where the incidence and severity of mucositis depends greatly on the nature of the conditioning regimen used for myeloablation. Mucositis can be severely debilitating and can lead to infection, sepsis, the need for parenteral nutrition and narcotic analgesia. The gastro-intestinal damage causes severe diarrhea. These symptoms can limit the doses and duration of cancer treatment, leading to sub-optimal treatment outcomes. Direct and indirect consequences of mucositis have been estimated to add approximately $18K per patient to cancer treatment costs.

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.

Please refer to the oral mucositis presentation (pdf) for more detailed information.

About Innate Defense Regulators (IDRs)

Innate Defense Regulators are a family of short, synthetic, proprietary peptide and peptide-like analogs with a dual-mode of efficacy, modulating the innate immune response to both damage and pathogen-associated signals, enhancing resolution of infection and tissue damage while suppressing harmful inflammation. IDRs do not impact the adaptive immune system and do not interfere with chemotherapy, radiation therapy or antibiotic treatments. Soligenix has demonstrated the preclinical efficacy of IDRs in diseases associated with dysregulated innate immune responses and tissue damage, such as oral mucositis subsequent to chemotherapy or radiation therapy. Moreover, IDRs are also efficacious in other diseases associated with both Gram-positive and Gram-negative bacterial infections, as well as infections with antibiotic resistant organisms like methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE).

IDRs bind to a pivotal regulatory protein in the innate defense system, known as p62 or sequestosome-1. IDRs bind specifically to the ZZ domain of p62 and a co-crystal structure of the IDR binding site with SGX94 has been obtained.

About Innate Immunity

The immune system is constantly exposed to pathogenic microorganisms (bacteria, virus, fungi, and parasites) but has evolved a powerful response to deal with these threats to our health. This response has been divided into two general types of reactions: reactions of innate immunity and reactions of adaptive immunity. Innate immunity is the “first responder” component of the immune system that is immediately activated to destroy invading microorganisms and trigger inflammation that contributes to blocking their assault. If microorganisms breach the innate immune system, adaptive immunity is activated. Adaptive immunity uses T and B cells to produce antibodies and killer cells to destroy infected cells. The two components of the immune system provide excellent protection against infections but they also pose a risk. If the activation threshold of either component is too low, or if activation is excessive, inflammatory disease may follow.

The innate immune system is a highly integrated system of cells involving both circulating blood cells and cells in tissues protecting us from pathogens at all body surfaces that interface with the external environment: skin, mouth, gastro-intestinal tract and lung. Innate immunity is dependent on rapidly sensing infection or damage and responding quickly with both inflammation and host repair or anti infective functions. When excessive activation of innate immunity causes inflammation, modulation of the activated innate immune system can re-direct the system to decrease inflammatory responses and increase the anti-infection or healing responses. The innate immune system responds quickly by sensing non-specific molecules released by the process of infection and damage through its Toll-like receptors and associated receptors. The p62 molecule integrates and regulates the signals sensed by these receptors and can re-direct the response of the innate immune system in a benign way without perturbing the function of the adaptive immune system.