Current microbial pathogens inevitably end up acquiring resistance to modified or older antibiotics. Only in the EU, around 25,000 patients/year die from multidrug-resistant (MDR) hospital-acquired infections with an estimated cost of €1.5 billion/year (ECDC/EMEA Joint Working Group, 2009). Subsequently, the anti-microbial over MDR approach perpetuates a failing strategy in the long run and requires a transformative perspective to enable future population effective anti-infectious therapies.

Sepsia Therapeutics has focused on the human host scavenger-like lymphocyte surface receptors to develop novel, safe and efficacious non-antibiotic approaches to fight infectious agents including MDR, as well as their deadly systemic inflammation and immunosuppressing consequences. These receptors recognize highly-conserved and widely-distributed structural components of fungi and bacteria which are absent from the host. The development of therapies such as infusion of biologicals (protein/peptide/small entities), adoptive transfer of blood cells cells expressing chimerical antigen receptors (CARs), and medical devices for hemadsorption of microbial toxins, are roads ahead towards fighting a wide spectrum of infectious agents while minimizing the risk of antibiotic resistance. Their prophylactic and/or therapeutic use, sets the basis for Sepsia Therapeutics current clinical trials either alone or in combination with other readily available or forthcoming drugs.

Sepsia Therapeutics non-antibiotic broad-spectrum proprietary biological drugs transforms the antibiotic/resistance historical paradigm at three levels:

1. Growth inhibition of infecting fungal and bacterial pathogens
2. By-pass of antibiotic related MDR generating mechanisms, irrespective of Gram +/- bacterial phenotype
3. Neutralization of pathogen toxins in the blood stream to prevent systemic inflammation and immunosuppression processes leading to death in sepsis related disease.

In brief, Sepsia Therapeutics develops innovative host-derived immunomodulatory agents that specifically target sepsis and alternative to, or in conjunction with, established intervention protocols involving antibiotics, fluid resuscitation and organ-specific support.

The human Scavenger-receptors are naturally occurring proteins on the surface of blood cells. They are known to interact and neutralize core structural components of microbial cell walls. Such components, known as Pathogen-Associated Molecular Patterns (PAMPs), constitute an optimal target for fighting bacteria (including multi-drug resistant strains – MDR) and fungi, responsible for infection and the deadly inflammatory body’s immune response triggered during sepsis. The administration of drugs derived from these human scavenger-receptors recovers sepsis-induced mortality, reduces immune triggered inflammation and lowers microbial load in preclinical sepsis models, providing a novel therapeutic strategy for wide-spectrum sepsis treatment (including MDR strains), and an alternative to current antibiotic approaches of limited success.

Sepsia Therapeutics is developing SIXTIDE, a new anti-sepsis drug, spanning the complete process from active principle Pharma-grade manufacturing to full preclinical and clinical phase III trials, based on:

1. Injectable short peptides or proteins derived from human scavenger-receptors that have been shown to inhibit the pro-inflammatory properties of fungal and bacterial PAMPs.
2. Adoptive cell therapies of lymphocytes transduced with scavenger-based Chimeric Antigen Receptors (CARs) using lentiviral vectors to promote specific fungal and bacterial cell killing.
3. Hemadsorption medical devices suitable for bacteria-induced sepsis, irrespective of their Gram-positive or Gram-positive origin or MDR phenotype.