THEO-260

Table of contents

• What is THEO-260?
• How does THEO-260 work?
• Which conditions is THEO-260 studied for?
• How is THEO-260 given?
• What do the clinical trials show?
• What side effects are known?

What is THEO-260?

THEO-260 is an investigational immunotherapy known as an oncolytic virus.^[3] It is a type of oncolytic adenovirus that has been engineered to selectively enter and kill cancer cells and cancer-associated cells within a tumour.^[4] THEO-260 is not yet an authorised medicine; it is still in clinical development by Theolytics Ltd.^[3] The substance is a biological intervention, specifically an oncolytic virus, and is being developed for the treatment of ovarian cancer.^[2]

How does THEO-260 work?

THEO-260 works by infecting and killing cancer cells and cancer-associated fibroblasts (CAFs), which are supporting cells found in the tumour microenvironment.^[4] Ovarian cancer is considered an immunologically 'cold' tumour, meaning the immune system does not easily recognise and attack it.^[4] By lysing (breaking open) cancer cells and CAFs, THEO-260 triggers a process called immunogenic cell death, which helps to activate the immune system, including T-cells, against the tumour.^[4] Preclinical studies showed that THEO-260 induced T-cell activation and interferon-gamma expression.^[4]

Which conditions is THEO-260 studied for?

• High grade serous ovarian cancer — a common and aggressive form of ovarian cancer, often diagnosed at an advanced stage.^[1]
• Endometrioid ovarian cancer — a less common subtype of ovarian cancer that is being included in the trial.^[1]
• Platinum-resistant ovarian cancer (PROC) — patients whose cancer has returned within 6 to 12 months after platinum-based chemotherapy are described as platinum-resistant.^[3]

How is THEO-260 given?

THEO-260 is given as a solution for infusion, administered intravenously (into a vein).^[1] In the trial, participants receive up to 6 doses of THEO-260 intravenously over a 2-week period.^[3] The trial is investigating different doses of THEO-260 to identify a dose that is safe and well tolerated.^[2]

What do the clinical trials show?

One clinical trial of THEO-260 is registered: the OCTOPOD trial (NCT06618235).^[1] This is a Phase 1/2, open-label, dose-finding, safety, tolerability and exploratory trial in patients with high grade serous or endometrioid ovarian cancer.^[3] The trial is currently authorised and plans to enrol 44 participants.^[1]

The trial is divided into two parts. Part A (Phase 1) aims to evaluate the safety and tolerability of THEO-260 and to establish the recommended Phase 2 dose (RP2D).^[1] Part B (Phase 2a) aims to evaluate preliminary efficacy by measuring the objective response rate (ORR), which is the proportion of patients whose tumours shrink or disappear, using CT or MRI scans and RECIST v1.1 criteria.^[1] The primary outcomes include assessment of dose-limiting toxicities (DLTs), adverse events, laboratory parameters, vital signs, and anti-tumour activity.^[1]

What side effects are known?

Because THEO-260 is still in early clinical development, the full side effect profile in humans is not yet known. The trial is designed to assess safety and tolerability as a primary objective, including evaluation of dose-limiting toxicities and adverse events.^[1] Preclinical toxicology studies in mice showed that THEO-260 was well tolerated, with no clinical signs, behavioural changes or body weight loss observed at planned clinical dose level equivalents.^[4] The trial will specifically monitor for immune-related adverse events, cytokine release syndrome (CRS) and pneumonitis.^[1]