The Challenge
The challenge to effective therapies in solid tumours
The effective treatment of solid tumours is impacted by the complexity of the tumour microenvironment (TME). In advanced carcinomas, the cancer cells are surrounded and protected by tumour‑supporting stromal cells, and an immune‑suppressed environment, creating a dense, often impenetrable and immunologically ‘cold’ barrier. These features make the access of drugs and immune cells to cancer cells challenging, instead allowing the cancer to thrive, evading the body’s own immune response and evolving drug‑resistance mechanisms. These are key reasons why many targeted therapies and immunotherapies fail to deliver durable benefit for large numbers of patients with solid tumours.
In many solid cancers, a significant percentage of the tumour mass (up to 60‑80% of the TME) can consist of tumour‑supporting stromal cells, particularly cancer‑associated fibroblasts (CAFs).
Cancer-associated fibroblasts play an important role in the tumour microenvironment
Despite their importance in driving tumour progression and resistance to therapy, CAFs are often overlooked as direct targets in cancer drug development.
Theolytics’ approach is designed to address the whole TME – tackling both the cancer cells and their support network – to overcome immune suppression and improve outcomes/responses to therapy.
Suppressing and / or excluding immune cells maintaining an immunologically ‘cold’ TME
Physically hinder the penetration and distribution of therapies. Promoting tumour growth, invasion and metastasis
Breaking the barrier
Theolytics is breaking the barrier to solid tumours
Theolytics seeks to break the barriers to the solid TME - addressing the challenges of tumour drug access, cancer heterogeneity, reversing tumour immune suppression / exclusion and overcoming acquired resistance.
From the outset, our approach is patient‑centric: discovering new therapies by employing real patient tumour samples, and with safety and patient convenience at the forefront. By evolving and training a common cold‑type adenovirus to be selective for targeting tumours and inducing anti‑tumour immunity, we identify immunotherapy candidates that remain active far beyond the initial treatment window. This approach aims to reduce treatment burden compared with continuous, intensive regimens.
Candidate discovery is driven by our proprietary Adenovo platform, including a library of >100 million oncolytic adenoviruses whose best‑in‑class performance is illustrated by the differentiated oncolytic immunotherapy candidates we have already generated.
Platform
The Adenovo platform applies Darwinian selection to our library of >100 million unique and diverse adenovirus variants on patient-derived systems to identify the optimum oncolytic immunotherapy candidate for solid tumour types.
From Library to Life
Adenovo enables rigorous interrogation of a vast drug discovery space for new therapeutic traits. Library diversity is tracked using advanced sequencing and bioinformatics techniques, which shine a spotlight on the optimal adenoviral candidate as it outcompetes 100 million contenders in the overall library. This selection is based on certain properties that we carefully apply.
By exposing the library to patient‑derived primary and metastatic tumours, tissue fluids, bloods, and serums, we capture the true complexity of human cancer, which can be missed by basic human screening systems (e.g. cell lines) or alternative non‑human models. Adenovo closes the translational gap, enabling selection of candidates fit to overcome the challenge of treating solid tumours. In doing so, Adenovo helps to break the defences of solid tumours and unlock the potential of cancer immunotherapy.
It can be tailored to a specific Target Product Profile (TPP), for instance a specific patient population, cellular class, or route of administration. Candidates evolve for efficacy within the real patient tumour microenvironment, for intravenous administration routes to tackle both primary and metastatic disease, ease of large‑scale manufacture and a host of other TPP parameters.
The unique value of Adenovo is showcased by the mechanistically novel and differentiated oncolytic immunotherapy candidates identified by Theolytics. These include the lead oncolytic immunotherapy - THEO‑260 - with intrinsic dual targeting of both patient cancer cells and stromal cells (cancer‑associated fibroblasts or CAFs), which make up a significant proportion of the tumour microenvironment.
Theo-260
Identified using Theolytics’ Adenovo platform, THEO-260 breaks the barriers of the solid tumour microenvironment using a unique dual targeting mechanism with the potential to transform outcomes for patients with stroma‑rich carcinomas such as ovarian cancer.