METIS’ Pipeline
METIS platform allow the Company to unlock complex targets and develop antibody-based drugs designed for greater efficacy and longer duration.
Expanding the target
The MET family of oncogenes
MET is not the only responsible gene for the control of invasive growth. Paolo Comoglio’s research group and others, have identified a superfamily of genes – all originating from a sole ancestral sequence – which encodes proteins sharing similar structural motifs and that are endowed with functionally related biological properties. Among these molecules are:
The sibling receptor Ron
- The distant relatives Axl and Mer
- The orphan receptor Ror1
Acquisition of the invasive/metastatic phenotype requires the aberrant execution of genetic programs that physiologically sustain ‘invasive growth’ during embryogenesis, tissue repair and organ regeneration.
Agonist MET antibodies
In addition to antibodies that inhibit MET, the METIS’ portfolio includes antibodies engineered to activate the MET receptor and downstream signals (i.e. DO24 and other chimeric antibodies, MetamAbs).
These antibodies are exploited for regenerative medicine and organ-protective treatments. These include protection from ischaemia-induced apoptotic and autophagic cell death (stroke) and chemotherapy-induced oxidative stress (cardiac and skeletal muscles).
Acquisition of the invasive/metastatic phenotype requires the aberrant execution of genetic programs that physiologically sustain ‘invasive growth’ during embryogenesis, tissue repair and organ regeneration.
Preventing drug-induced toxicity
Hepatocyte growth factor (HGF) and macrophage-stimulating protein (MSP) have an intrinsic dual nature: they are trophic cytokines preventing apoptosis on one side and scatter factors promoting invasion on the other.
For therapeutic use, their anti-apoptotic activity must be separated from their pro-invasive activity. To this end, Paolo Comoglio’s research group engineered chimeric factors containing selected functional domains of HGF and/or MSP, generating chimeric cytokines concomitantly activating the HGF (MET) and MSP receptor (Ron).
The recombinant cytokines prevent apoptosis and stimulates cell proliferation, but are devoid of any pro-invasive activity. In murine models of drug-induced nephrotoxicity, intravenous injection of the chimeric cytokines prevented renal damage and preserved tubular integrity. These molecules are leads for development of drugs preventing chemotherapy-induced cytotoxicity (Nat Biotechnol. 2002; 20(5):488-95).