Ovarian Cancer is one of the leading causes of cancer related deaths among women. It exhibits a stromal rich, immune-suppressed TME, abundant with cancer-associated fibroblasts (CAFs). CAFs drive chemo-resistance, relapse, exclusion of T cells and disease progression.
Theolytics’ discovery platform, with >100 million oncolytic candidates and clinically relevant phenotypic selection systems, was applied to identify a mechanistically differentiated adenovirus - THEO-260 - for high grade serous ovarian cancer. It is capable of lysing both ovarian patient cancer cells and CAFs, whilst triggering immunogenic cell death and promoting T-cell activation in preclinical studies. The potential therapeutic impact of this multi-front approach is significant, particularly in the PROC patient population, a complex solid cancer with few treatment options.
The Phase I/IIa clinical trial is designed to investigate the safety and tolerability of THEO-260 administered via intravenous delivery and determine the recommended Phase 2 dose. Demonstration of THEO-260’s differentiated oncolytic mechanism in the clinic will be supported by comprehensive biomarker analysis.
Treatment for ovarian cancer at diagnosis depends on the stage of the disease, but invariably includes a combination of surgery followed by platinum-based chemotherapy and possibly other targeted therapies” said Dr John Krell, MBChB BSc PhD MRCP Clinical Reader & Consultant Medical Oncologist, Imperial College London, and Chief Investigator. “Whilst many patients respond very well to initial treatment, relapse from remission is common and further treatment is needed to try to control the disease. Platinum-based treatments can be effective at relapse but eventually resistance to this form of therapy occurs. There remains a lack of good treatment options with few advances in the last decades and is a significant unmet need in this population. The extensive preclinical data with THEO-260 in ex vivo patient samples is very encouraging and gives promise of a differentiated approach for ovarian patient treatment.
Theolytics CSO and Co-Founder Margaret Duffy PhD, added:
Enrolling the first patient into our Phase I/IIa trial for THEO-260 marks a major milestone for Theolytics. As a team, we seek to deliver effective new treatment options for the many women who suffer from platinum resistant ovarian cancer. Using our discovery platform, THEO-260 has been developed to combat the stromal rich nature of this advanced solid cancer, and we look forward to reporting on the progress of this trial.