Novel peptide-based therapeutics for reprogramming the tumour stroma extracellular matrix using molecular modelling and computational engineering

Introduction

Cancer is the second biggest cause of death worldwide. 90% of cancers are solid tumours, where tumour stromal cells secrete a dense mass of proteins called the extracellular matrix (ECM). This ECM is part of a protective tumour microenvironment that promotes cancer proliferation, invasiveness, and resistance to chemotherapy and biologics.

Current Therapies and Challenges

Several therapies now available or being developed rely on:

1. Monoclonal antibodies aimed at tumour-expressed antigens.
2. Activation of immune cells.

Many promising immunotherapeutic approaches fail because of the stromal barrier and/or toxicity due to off-target effects. Targeting proteins and pathways in the tumour microenvironment is now considered critical by oncology experts and pharmaceutical companies for the success of beating solid tumours. However, no therapies have yet emerged to address this €200+B market.

Our Solution

Our platform uses novel molecular computational simulation models to generate small peptides that bind to highly specific sites on ECM proteins. These peptides block interactions known to promote tumour aggressiveness.

TAX2

The first of these peptides, TAX2, selectively targets a clinically relevant interaction between the ECM signalling protein Thrombospondin-1 and its receptors. This regulation affects:

• Tumour proliferation
• Vascularisation
• Immune cell (T-cell) infiltration of the tumour

TAX2 shows extremely promising results in 15 preclinical models, including:

• Ovarian cancer
• Pancreatic cancer
• Colorectal cancer
• Melanoma

In these models, TAX2 inhibits tumour progression and metastasis. Additionally, it substantially improves the efficacy of antibody therapies when combined.

Focus and Future Plans

Our current focus is on ovarian cancer, a cancer with high unmet need and a very high mortality rate. EIC support will enable:

• Large-scale manufacture
• Regulatory steps
• First-in-human, multi-indication clinical trials (Ph I and Ph IIa)

This preparation is aimed at outlicensing TAX2 to a pharmaceutical partner who would take the therapy through more advanced clinical trial stages.