SCIENCE - In3Bio

Our proprietary platform technology is designed to inhibit cancer cell proliferation by stimulating a natural antibody response against targeted growth factors.

Technology Platform

We design synthetic therapeutics that include immunogenic sequence of growth factors domain that are expressed with a synthetic carrier.

Growth factors are natural occurring proteins that are recognized by the body that will not normally be targeted by the body’s immune system. We have developed a proprietary platform that can create synthetic molecules that stimulate an antibody response targeting specific growth factors proteins active in tumour proliferation.

Our innovative approach allows us to develop novel mono- or bi-specific therapeutics, in order to treat cancers which are often controlled by multiple growth factor-triggered pathways.

Monomeric

Single targeted synthetic molecule

1. We take a part of the targeted growth factor gene

2. Infused with a carrier protein it is then fused onto a plasmid

3. A monomeric synthetic molecule is expressed in a bacteria host

Bi-specific

Multi targeted synthetic molecule

1. Using 2 targeted growth factors genes

2. Both are infused with a carrier protein then fused to a plasmid

3. A bi-specific synthetic molecule is expressed in a bacteria host

Our approach is to involve the patient’s B-cell response using designed biologics. The hereby naturally-raised antibodies neutralise the particular (selected) growth factors that activate known cancer proliferation pathways.

In other words, this active immunisation (vaccination) approach stimulates the patient’s own immune system to recognise, bind and remove specific growth factors, i.e. ligands that are active in the growth-promoting pathways in cancer cells.

Normal vs Cancer cell proliferation

In solid tumour cancers, normal cell activity is de-regulated resulting is an uncontrolled cell proliferation. It follows that, inhibiting cancer cell proliferation can inhibit cancer growth.

Normal Cell Activity

Normal cell replication triggered by growth factors that bind to a receptor on the cell membrane

Cancer Cell Activity

More growth factors bind to more receptors resulting in uncontrolled replication.

Our approach

We apply Extracellular Pathway Targeted Immunisation (EPTI). This approach induces an antibody response, thus diminishing the growth factor supply. This process happens outside of the cells (extracellular).

Monomeric molecule

1. Synthetic molecule administered to stimulate an immune response

3. Antibodies bind to targeted growth factors

4. Neutralised growth factors unable to activate cancer cell division

Bi-specific molecule

Our bispecific molecules stimulate multiple antibodies that can target multiple growth factors.

1. Synthetic molecule produces multiple antibodies

2. Multiple antibodies neutralize multiple growth factors

This approach does not address active pathways that are ligand-Independent

Combination & Resistance

Oncology is currently incorporating combination approaches. Using drugs in parallel makes cancer treatment more effective. We have suitable solutions for such combination strategies.

Evolution of cancer drug resistance

With improved technology platforms and increased knowledge of cancer pathways, precision therapeutics that specifically target active pathways have improved patients’ survival.

Cancer drug resistance remains a major cause of unsuccessful targeted and immunotherapies. Overcoming the challenges of resistance is still one of the major strategies for emerging new treatments.

Our Solution

Preclinical studies on combinations and resistance with approved treatments.

We have done extensive preclinical studies on combinations and observed the delay resistance from the outcomes. Combination studies with 15 different commercially available Small Molecule Inhibitors (SMI) addressing a range of different cancers suggest a significant improvement in efficacy against SMI alone. The targeted therapies (SMI) can address different solid cancers.

The seven classes of SMI tested with our lead molecule in combination are:

Epidermal growth factor receptor (EGFR) gene provides instructions for making a protein on cells that helps them grow. A mutation in the gene for EGFR can make it grow too much and cause cancers. The mutation is found in 10-50% in lung cancer patients.

Click here for more details on the significantly increased antitumor activity of EGFR TKIs and delaying emergence of resistance with our lead molecule.

Click here for the published Phase I clinical data demonstrating 6.5 months progression free survival advantage of combination against single treatment.

We have demonstrated that our lead molecule (IN01) significantly reduces the emergence of resistance with SMIs that target not just one, but many classes. One head-to-head comparison preclinical study using our lead molecule tested against an approved combination therapy in colorectal cell lines showed a 50% improvement in progression free survival.

Clinical study: EPICAL Phase I

A recently concluded investigator-led Phase I EPICAL trial in Spain using combination of first-generation molecule with approved 1st-line EGFR TKI (Tyrosine Kinase Inhibitor). The observed progression free survival for the combination was 6.5 months longer than the EGFR TKI alone. The data from this study replicates the outcomes of the numerus pre-clinical studies and adds to the confidence of the pre-clinical package.

“The Epical trial achieved a significant PFS improvement in sharp contrast with 2 failed clinical trials combining Afatinib with commercially available treatments.”

Dr Erik D’Hondt, CEO / CSO In3Bio

Our solution not only increases the choice of therapies, it prolongs the efficacy of existing therapies without increasing the burden on patient. The toxicity profile of the combination was in the range expected for EGFR TKI single agent, indicating that our approach used in the trial did not increase the risk of adverse events.

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