SCIENCE

With patients’ welfare a priority, our primary objective is to develop treatments that are effective and excel in tolerability, in order to ensure a better quality of life.

Our R&D model starts from a pre-clinical platform, followed by a translational/clinical stadium, the latter allowing to validate proof of concept in a clinical setting and eventually bringing our new therapeutics to the patient.

We focus on developing next-generation therapeutics that induce a B-cell immune response towards growth factors that are active in tumorigenesis and metastasis. Our collaboration with several expert R&D and clinical teams allows us to explore different immuno-oncology directions.

Drug resistance is one of the biggest challenges in modern Precision Medicine.

The mild nature of our active immunisation approach greatly reduces toxicity, allowing potential combination therapies to be feasible and more effective without increasing the toxicity burden. Our pre-clinical data shows that combination of our biologics with small-molecule inhibitors (SMI) delays resistance to SMI therapy.

The key drivers of our research and development activities are:

Development

We have advanced pre-clinical and clinical R&D of versatile biologics that facilitate immunotherapy by targeting cancer-dominating growth factors.

Tolerability

We develop therapeutics that create a new standard of tolerability in cancer treatment without increasing toxicity burden.

Combination

We continue to improve our therapeutics with high efficacy, less toxicity and help resistance in combination strategies of market demand

Mode of Action

In3Bio’s 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 cell proliferation (ligand-mediated)

The diagrams shows a normal cell with growth factors (ligands), receptors, the cell membrane and the nucleus

When growth factors (ligands) bind to cell-surface receptors, cells start to replicate for this ligand-mediated signalling pathways. There are many types of growth factors circulating in the body that play different function and can enable the cell divisions

Activation of the signalling pathways causes cell to divide

Cancer cell proliferation

Cancer cells have raised numbers of membrane receptors, making them hyperresponsive to growth factors (ligands).

The upregulated receptors bind to more growth factors (ligands), causing enhanced signalling.

Over-activation of cell signalling leads to uncontrolled cell divisions as seen in cancer cell formation

In3Bio's approach

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

Administration of In3Bio’s molecules triggers the body’s B-cells to produce specific antibodies

These specific antibodies bind with targeted growth factors (ligands) outside of cell structure. These antibodies prevent growth factors (ligands) from binding to and activating receptors

Without activation of ligand-mediated receptor, the ability of cancer cells to proliferate is impaired.

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

Current Immunotherapies

Targeted therapy and immunotherapy have changed the paradigm of cancer treatment. Immunotherapy stimulates the body’s natural defences in different ways to fight cancer cells; No one single approach works for all types of solid tumour cancers.

Monoclonal antibody targets cancer cell specific, proteins or the tumour micro-environment that aid growth and survival. Successful blocker are the checkpoint immune inhibitors, liberating the T cell mediated immune response to attack cancer cells.

Adoptive T cell therapy uses engineered T cells loaded with tumour specific protein receptors to target and destroy cancer cells.

Two types of cancer vaccines exist:

Preventive vaccines protect the body from developing cancer caused by viruses such as HPV and HBV.
Therapeutic vaccines comprise (recombinant) cancer-specific antigen/proteins combined with an immunological adjuvant.

How are we different?

In3Bio’s pipelines work in a different mechanism of action; The molecules do not bind to cell receptors, do not interfere with the tumour micro-environment and do not manipulate cellular immunity mediated by T cells.

In3Bio’s approach works in the extracellular matrix, by triggering B cells response to produce specific antibodies to neutralize the target growth factors. Removal of specific growth factors involved in cancer-cellular signalling prevent uncontrolled proliferation.

Data from studies suggest that this approach is less toxic than other approved treatments, making our therapeutics well tolerated with a mild toxicity profile when compared to other leading immune-therapies approach in the market.

The safety/no-toxicity profile had been demonstrated in an animal model as well as in published clinical studies.

We have advanced pre-clinical and clinical R&D of versatile biologics that facilitate immunotherapy by targeting cancer-dominating growth factors.

Combination Approach

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

After decades of conventional chemotherapy, technological advances have now revolutionized cancer treatment. Precision Medicine aims for pathway/biomarker-targeted therapy, reducing toxicity and thus improving quality of life. Therapeutic breakthroughs have led to the introduction of several modalities into the clinic.

However, these new modalities encounter setbacks; serious adverse events happen while resistance inevitably occurs.

The problem of lack of response is multifaceted. Despite the success of immune checkpoint inhibitors (ICIs) in recent years, still approximately 60% to 70% of cancer patients do not respond to single-agent therapy. Targeted therapy with small-molecule inhibitors (SMIs) suffers from selectivity/potency and resistance issues and this has led to the emergence of the next-generation drugs.

Resistance can be tackled by combining drugs. From multiple chemotherapies, this led to increasingly complex regimes of combined targeted therapies. These are not without limitations. Although successful at addressing multiple pathways, the combined toxicity effect is often intolerable.

In3Bio has a versatile portfolio for combination therapy and focuses on improving the efficacy of small-molecule inhibitors (SMI). Both clinical and pre-clinical studies show that our proprietary molecules combined with approved SMIs impair resistance in multiple pathways and improve efficacy without adding toxicity.

COMBINATION SMI CANDIDATES

EGFR TKI | ALK TKI | CDK4/6 | RET

Studies conducted with established lung cancer cell lines using four different types of SMI in combination with the lead molecule IN01 in combination. Data have been published.

Results indicate opportunities for combination in other indications, such as thyroid, kidney, breast and liver.

COMBINATION SMI CANDIDATES

BRAF | MEK | P13K

Studies conducted with established colorectal cancer cell lines using three different types of SMI in combination with the lead molecule IN01. Data have been accepted for public presentation for AACR Annual Meeting, Spring 2020.

Results indicate opportunities for combination in more indications, such as lung, breast, thyroid and melanoma

In3Bio’s solution not only increases the choice of therapies, it prolongs the efficacy of existing therapies without increasing burden on patients.

Please see selected studies below and obtain further information from our publications and posters.

IN01 + EGFR TKI:

Now in Phase I clinical trial

A combination study conducted with approved 1st line EGFR TKI. The pre-clinical experiment was designed to:

Show that IN01 inhibit EGF/EGFR signalling pathways
Confirm the delay of treatment resistance to TKI with IN01 by inhibiting downstream signalling.

The company conducted additional combination studies with several approved 1st-line EGFR TKI. The strong positive data led to an Investigator-led Phase I clinical trial using the combination in EGFR Mutated NSCLC patients.

IN01 + ALK TKI:

Pre-clinical studies

With the experience from the combinations in EGFR mutated cell lines, further studies were conducted with SMI targeting Anaplastic Large-cell Lymphoma Kinase (ALK) mutations. It has been observed that patients treated with ALK inhibitors develop resistance involving signalling molecules that anti-EGF (IN01) can inhibit.

Data from these experimental studies, with commercially available ALK inhibitors, show that development time to resistance had doubled in the combinations when compared to each ALK TKI alone.