SGX943 is an Innate Defense Regulator, containing the same active ingredient as SGX942 (dusquetide). Dusquetide is a fully synthetic, 5-amino acid peptide with high aqueous solubility and stability. Extensive in vivo preclinical studies have demonstrated enhanced clearance of bacterial infection with SGX943 administration. SGX943 has shown efficacy against both gram-negative and gram-positive bacterial infections in preclinical models, independent of whether the bacteria is antibiotic resistant or antibiotic sensitive. Melioidosis is caused by the gram-negative bacterium Burkholderia pseudomallei (Bps), which has high intrinsic resistance to antibiotic treatment. Bps can cause an acute disease characterized by a fulminant pneumonia and a chronic condition that can recrudesce. There is no preventive vaccine or effective immunotherapy for melioidosis. Therefore, there is a significant medical need for improved prevention and treatment.

The IDR technology platform (also referred to by its research name SGX94) represents a novel and innovative approach to therapeutically modulating immune defenses by targeting the innate immune system. Preclinical data indicate that SGX94 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.

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

A publication describing the activity of SGX94 (dusquetide) in infectious disease, including melioidosis, is available at the ScienceDirect Website.

About Melioidosis

Melioidosis is a potentially fatal infection caused by the Gram-negative bacillus, Burkholderia pseudomallei (Bps). Highly resistant to many antibiotics, Bps and the closely-related Burkholderia mallei (Bm) are considered possible biological warfare agents by the Department of Health and Human Services (DHHS) because of the potential for widespread dissemination through aerosol. Bps is classified as a Tier 1 biothreat and a category B priority pathogen by the National Institute of Allergy and Infectious Diseases (NIAID) and is a top five priority in the most recent Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) Strategy document.

Bps is intrinsically resistant to antibiotics normally used for first line treatment of Gram-negative bacteria, including first, second and third generation cephalosporins, aminoglycosides, penicillins and polymyxin, highlighting the need for recognition of melioidosis when presumptive antimicrobial therapy is commenced. Lengthy courses of treatment are required, including a prolonged eradication phase. Despite these treatment courses, mortality still ranges from 15-40%.

Melioidosis is a disease of the rainy season in endemic areas. Bps is a saprophytic organism found widely in soil and is associated with high mortality. It can be transmitted from the soil to humans by inhalation, through cuts in the skin and by ingestion. It mainly affects people who have direct contact with wet soils and/or have an underlying predisposition to infection, i.e., individuals with diabetes mellitus, renal disease, cirrhosis, thalassaemia, alcoholism, or those who are immunosuppressed, as well as individuals who are immunologically naive.

Bps infection (melioidosis) is a major public health concern in the endemic regions of Southeast Asia and Northern Australia. Moreover, the organism has a worldwide distribution and the full extent of global spread is likely underestimated. Bps activity is seen in Southeast Asia, South America, Africa, the Middle East, India, and Northern Australia. The highest pockets of disease activity occur in Northern Australia and Northeast Thailand, Burma and Vietnam, and is likely under-reported in China. In Northeast Thailand, the mortality rate associated with Bps infection is over 40%, making it the third most common cause of death from infectious disease in that region after HIV/AIDS and tuberculosis.

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.