METIS' Pipeline

METIS platform allow the Company to unlock complex targets and develop antibody-based drugs designed for greater efficacy and longer duration.

  • Target Identification
  • Hit Identification
  • Hit to Lead
  • Lead Optimization
  • Pre-clinical Development

hOA-DN30

Preclinical Development  - 98%

MET DecAb#

Lead Optimization  - 69%

DO-24

Hit Identification  - 30%

DN30 + radiotherapy

Lead Optimization  - 68%

The lead candidate

hOA-DN30 is a Humanized-one-armed antibody developed in subsequent steps - from 2006 to 2018 - increasing stability, in vivo half-life and therapeutic efficacy.

  • DN30-mAb

  • MvDN30

  • MvDN30
    Pegylated
    (20KD)

  • Dual
    Constant
    Domain

  • hOA-DN30
1
2
3
4
5

half-life 100%

Stability and in vivo half-life

hOA-DN30 is a potent, selective, and irreversible inhibitor of ligand-dependent and ligand-independent MET activation, devoid of any agonistic activity.

hOA-DN30 exerts its therapeutic effect via a unique mechanism whereby the MET receptor is physically removed from the cancer cell surface (‘shedding’).

Expanding the target

MET-family3

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:

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.

MET-antibodies3

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).