The present invention relates to glycerophosphoinositols (GPIs) and derivatives thereof for use in the treatment of pathologies related to a Lipopolysaccharide (LPS)-activated tissue-factor (TF) activity, as pathologies induced by high bacteremia, i.e. septic shock.

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Information of the volume of the present and expected market in the diagnosis and treatment of sepsis and septic shock has been presented in several studies as reported in the table beside (from “Sepsis Diagnostic Market Size, Share & Trends Analysis Report By Product (Instruments, Blood Culture Media, Assay Kits & Reagents, Software), By Technology, By Pathogen, By Testing Type, By Region, And Segment Forecasts, 2020 – 2027” Published Date: Feb, 2020; Base Year for Estimate: 2019; Historical Data: 2016 – 2018; Report ID: GVR-1-68038-352-2). The top players in the global sepsis diagnostics market include:
T2 Biosystems, Inc. (US), EKF Diagnostics (UK), bioMérieux, Inc. (US), Sandstone Diagnostics, Inc. (US), Becton, Dickinson and Company (US), Immunexpress (US), Cube Dx GmbH (Austria), and Axis-Shield Diagnostics Ltd. (Scotland), are some of the major players operating in the sepsis diagnostics market.
The patented natural compound is thought to prevent the transition from sepsis to septic shock reducing the risk of death.


Sepsis is a life-threatening organ dysfunction that results from the body’s response to infection, and includes systemic inflammation. A progressive severity of the infection leads from sepsis to septic shock.
Several studies led to compilations of guidelines for this syndrome that remains life-threatening and unresolved. As cited on Sepsis and septic shock: guideline-based management (Siddharth Dugar et al., Cleveland Clinic Journal of Medicine. January 2020, 87 (1) 53-64; DOI: :
“ Sepsis affects 750,000 patients each year in the United States and is the leading cause of death in critically ill patients, killing more than 210,000 people every year. About 15% of patients with sepsis go into septic shock, which accounts for about 10% of admissions to intensive care units (ICUs) and has a death rate of more than 50%. The incidence of sepsis doubled in the United States between 2000 and 2008, possibly owing to more chronic diseases in our aging population, along with the rise of antibiotic resistance and the increased use of invasive procedures, immunosuppressive drugs, and chemotherapy.
The cost associated with sepsis-related care in the United States is more than $20.3 billion annually.

The patented natural compound presented here may ameliorate the treatment of septic shock at its onset.

Current Technology Limitations

As stated in “Prospects for the Management of Sepsis in an Era of Personalised Medicine by Jonathan Cohen (Dep. of Medicine, Brighton and Sussex Medical School, Brighton, UK ): “Sepsis remains an unmet medical need, and sustained attempts by intensivists have indeed yielded an incremental improvement in outcomes. However, despite many attempts to introduce novel therapeutic molecules, there has been no step change in survival rates”
It follows that compounds able to intervene on the onset of sepsis are of great value to the market. Glycerophosphoinositol is the compound object of the patent presented here (see below). It has already been object of a patent for its properties as anti-inflammatory, non-steroidal compound; as such it is already in the market as medical device, and several reports from both pharma and academia reported on the efficacy of glycerophsphoinositol treatment even in various forms of dermatitis and psoriasis.
Our recent studies reporting on the mechanism of action and properties of this compound make of it a promising candidate for the treatment of septic shock, and for other inflammatory syndromes that act on the specific signaling and targets modulated by the glycerophosphoinositol (Varone et al., Cell Commun Signal. 2019)

Killer Application

As stated, the invention is ready for further studies of efficacy.

Thus, due to the unmet medical need associated to the sepsis and septic shock manifestations, a compassionate use of the glycerophosphoinositol infusion could be proposed and designed in those cases of severe untreatable disease.

This approach can be considered feasible due to the natural origin of glycerophosphoinositol. However toxicity studies so far performed only in rodents (showing no toxicity at the applied doses) should be extended for the use in humans.

In parallel, the knowledge gathered in the last years on the diverse mechanisms of action of this compound and on the effects of the glycerophosphoinositol on different signalling pathways, is leading us to investigate new applications also in the immune-inflammatory response (acting in this case as a resolvin) and in the inflammation related to cancer.

Our Technology and solutions

Glycerophosphoinositol is a metabolite derived from the phosphoinositide. It is a natural compound, present in virtually all cells, abundant in those of ematopoietic origin.
Exogenously added glycerophosphoinositol shows pharmacological activities due to the fact that it can easily cross the plasma membrane via a permease, it is diffusible being hydrosoluble, and it acts on a specific intracellular target/receptor which initiates a signalling cascade controlling the transcription of proinflammatory factors (e.g., cytokines and coagulation factors).
When exogenously administered to monocytes, this compound inhibits the activity of tissue factor, thus reducing the inflammatory response.
Here below the anti-inflammatory and anti thrombotic activity of the glycerophosphoinositol in a model
of endotoxic shock in mice.


Based on the data reported in the in vitro and in vivo studies performed by the lab of the inventors, the advantages of using this compound in the resolution of inflammation are severalfold.
Because of its chemical nature, glycerophosphoinositol is easily manageable: it is water-soluble, and it crosses the plasma membrane, rapidly reaching its intracellular targets. As it is a natural compound that is present in virtually all cell types, it could be administered (e.g. intravenously) in cases of manifestations of sepsis, such as the disseminated intravascular coagulation, that do not respond to therapy (i.e. septic shock).
Moreover, glycerophosphoinositol, is already commercialized as the main component of a number of medical devices dedicated to the topical treatment of inflammation, including different forms of dermatitis and psoriasis.
Patent WO2000IT00447/EP1332149 “Glycerophosphoinositol derivatives as modulators of cytosolic phospholipase A2”
Glycerophosphoinositol is shown to act by different mechanisms in the resolution of inflammation; it is therefore expected to be active in all those diseases that show also an inflammatory phenotype (such as the immuno-inflammatory response; the inflammation accompanying tumor invasion etc.).


The team of the main inventor has developed virtually all the knowledge today available on this class of compounds, including its metabolism, catabolism, distribution, biological functions, also with reference to the differently phosphorylated glycerophosphoinositols.

This knowledge has to be complemented with expertises in developing preclinical and clinical studies on the proposed application, as described before.

At the same time, collaborations with a pharma ready to invest in this topic and with synthesis expertise could help in obtaining pure compound for proceeding with the studies in humans.

We believe that ideal partners are colleagues interested in the development of a non-steroidal antiinflammatory compound for which the efficacy of the topical application is already demonstrated (and the compound is commercialized for that), but it is in the need of the step forward, to exploit all its possible applications, starting from the septic shock described in this patent, and moving then to other applications that we already have in our pipeline (preliminary data).

We believe that this will be a winning partnership, beneficial for all, patients included (and most important).

Development stage

Glycerophosphoinositol is commercially available in several formulations (lysine, choline, Na +, K+ salts) either after extraction, usually from plants, or chemical synthesis.

We have also synthesized stable forms of glycerophosphoinositol (undisclosed) and proven that they maintain the pharmacological activities of the natural compound.

The patent here proposed is focused on the application in the early phases of the septic shock: the exploitation of this activity of the glycerophosphoinositol requires a clinical study that should be easily approachable due to the unmet medical need of this syndrome.

Based on the data collected the invention can be classified as TRL 4-5

The patent has been already granted in USA and Europe.
USA Patent No US9351983 B2 “Use of glycerophosphoinositols for the treatment of septic shock”
EP 13 773 253.3 “Use of glycerophosphoinositols for the treatment of septic shock”

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