Unmask cancer, elicit immune response.
Phost’in develops first-in-class Glycocalyx Modifiers for selective treatment of Cancers and other serious diseases.
Our first generation of GnT-V inhibitors aims to unblock immune response and down-modulate invasiveness for the treatment of agressive solid tumors.
Phost’In has focused its R&D on un unmet medical need: creating an anti-tumoral and anti-invasive treatment able to wreck tumor progression by unblocking anti-cancer immune response.
We have choosen to target cancer cell glycosylation, which can lead to profound modifications of the glycocalyx at the cell surface.
Using its unique expertise in phosphorus chemistry, the Phost’In team has synthesized and screened 400 original glycomimetics to select highly potent GnT-V inhibitors, including the Drug Candidate PST3.1a, described in July 2016 as the first selective inhibitor of GnT-V.
Phostine PST3.1a Targets MGAT5 and Inhibits Glioblastoma-Initiating Cell Invasiveness and Proliferation.
Mol Cancer Res. 2017 Oct;15(10):1376-1387. doi: 10.1158/1541-7786.MCR-17-0120.
C-glycoside mimetics inhibit glioma stem cell proliferation, migration, and invasion.
J Med Chem. 2014 Oct 23;57(20):8293-306. doi: 10.1021/jm500522y.
Oxaphosphinanes: new therapeutic perspectives for glioblastoma.
J Med Chem. 2012 Mar 8;55(5):2196-211. doi: 10.1021/jm201428a.
Why glycocalyx modifiers ?
Resistance to treatment and invasive capacities of cancer stem cells (CSCs) rely mainly on the presence at the cell surface of a highly complex glycocalyx. This glycocalyx has the property to strongly bind soluble Galectins, forming a lattice which promotes signalling activities and escape from anti-cancer immune response. A proper glycocalyx modification could lead to the significant reduction of CSC invasiveness associated with a strong reduction of Galectin expression/binding, which opens the way to the restoration of an efficient anti-cancer immunity.
- Phost’In Platform has ability to generate 100 new molecules per year.
Agressive Solid Tumors
Phost’In has demonstrated in vivo the efficacy of its Lead PST3.1a in various cancer models, reaching a strong reduction of tumoral volumes and down regulation of invasiveness (up to 90% in orthotopic glioblastoma model) and metastasis formation. Median survival of treated animals is highly increased. Moreover, decrypting the MoA has highlighted predictive response markers and opened the way to screening for new indications.
First targeted indication, Glioblastoma is a deadly brain cancer affecting around 53,000 people per year worldwide. Despite a heavy standard of care involving chemotherapy, radiotherapy and surgery, only 10% of affected patients may survive 5 years after diagnosis. The highly infiltrative properties of GBM cells constitute a major drawback to the development of efficient therapies and are responsible for current therapeutic failure.
The entirely innovative mechanism of action of Lead PST3.1a involves an enhanced anti-cancer immune response from the host without targeting immune cells directly, unlike the current generation of immunotherapy operates. Treatment with PST 3.1a directly modifies the tumor cell to make it visible by the host’ immune system and thus accessible to the anti-tumor action. PST3.1a has demonstrated strong antitumoral activity associated with an excellent safety profile.
Beyond the specific results with PST3.1a, anti-proliferative, anti-invasive, anti-migratory effects have already been demonstrated in vitro/in vivo with other phostinesTM, confirming the family potential. More than 100 new compounds can now be synthesized per year, based on the PhostineTM scaffold.
CEO / Co-founder
R&D director / Co-founder
Professeur Norbert Bakalara
Biochemistry consultant / Co-founder
Professeur Jean-Luc Pirat
Chemistry consultant / Co-founder
Professeur David Virieux
Chemistry consultant / Co-founder
Professeur Hugues Duffau
Scientific Board Director / Neurosurgeon
Phost’In continues to work in close collaboration with academic teams, which are inventors of the preliminary results.
- Team « Plasticity, stem cells and glioma », Institute of Neurosciences of Montpellier (Inserm Unit 1051) in CHU Saint Eloi (Montpellier-France)
- Team « Molecular Architecture et Nanostructurated materials », Charles Gerhardt institute of Montpellier (UMR 5253 UMII, CNRS, ENSCM, UMI) in Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM) (Montpellier-France)
- Team « Advanced Material for Catalysis and Health», Charles Gerhardt institute of Montpellier (UMR 5253 UMII, CNRS, ENSCM, UMI) in Montpellier University (Montpellier-France)
- Team “Bioorganic and Structural Chemistry” CSPBAT Laboratory (UMR 7244 CNRS - UMR 7244) from Paris13 University (Paris-France)
To implement first clinical trials, Phost’in works closely with clinical teams from CHU of Montpellier and Montpellier Institute of Cancer.
August 2018: PST3.1a quoted in conclusion of Nagae et al, Nature Communication 2018, 9(1):3380
June 2018: Phost'in completes Pre-IND Meeting With FDA on PST3.1a for the treatment of Aggressive Solid Tumors: Clinical Development to Begin in 2019
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Phost’In, « Grand Prix » du Concours National d’Aide à la Création d’Entreprises de Technologie Innovantes 2014
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