On June 9, 2023 Theolytics, a biotechnology company harnessing viruses to combat disease, reported data presentations at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which was held 2 to 6 June, 2023 in Chicago and at the European Hematology Association (EHA) (Free EHA Whitepaper) 2023 Congress, which is being held 8 to 11 June in Frankfurt (Press release, Theolytics, JUN 9, 2023, View Source [SID1234635716]).
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ASCO Abstract
Title: Evaluation of THEO-260 as a novel oncolytic virus therapy for treating stromal rich tumours
LINK to abstract
Stromal rich cancers pose a challenge to many cancer therapies due to the abundance of cancer associated fibroblasts (CAFs). This compartment of the tumour microenvironment physically blocks the penetration of drugs, immune cells and promotes resistance to many therapies. THEO-260 is a new oncolytic virus in development that is intrinsically capable of targeted killing of both cancer cells and CAFs.
The efficacy and safety of THEO-260 was assessed in multicellular spheroids, in patient-derived ex vivo fresh ovarian samples and in mouse models of human stromal tumours. Unpassaged ascites and tumour samples collected from cytoreductive surgeries for advanced ovarian cancer were treated with a clinically-relevant dose of THEO-260. THEO-260 effectively killed the cancer cell and CAF populations, being efficacious in treatment-naive and platinum-resistant patient samples. Importantly, the T cell population in these patients, in addition to primary normal fibroblasts from healthy donors, were not damaged. Ex vivo studies show THEO-260 stimulates effector T cell responses upon tumour lysis and demonstrates suitability as an IV
delivered agent. THEO-260 excels in low nutrient, low proliferative environments, typical of human solid tumours and has been developed with a view to persist in the tumour microenvironment without the need for repeated cycles of delivery. In ovarian cancer murine models containing human CAFs and cancer cells, THEO-260 shows antitumor efficacy, with a complete reduction in tumour volume in subcutaneous and intraperitoneal systems, and superiority to standard of care. Virus activity is not restricted to ovarian cancer, with cell line data demonstrating killing in additional solid tumour types, including pancreatic, colorectal, lung, and breast cancer. THEO-260 exhibits genetic and temperature based stability, and GMP manufacturing to high yields is underway.
"The positive THEO-260 data presented at ASCO (Free ASCO Whitepaper) come at an exciting time for Theolytics as we progress this lead product towards the clinic in a first-in-human study in ovarian cancer," said Charlotte Casebourne Stock, Chief Executive Officer and Co-Founder of Theolytics. "THEO-260 is a virotherapy that potentially could demonstrate something that neither chemotherapy, nor immunotherapeutic approaches have been capable of to date and has the potential to deliver a step-change for the oncolytic virus field."
EHA Poster Presentation
Title: Development of a Novel Oncolytic Virus – THEO-310 – Specialised for Targeting the Bone Marrow Tumour Microenvironment of Multiple Myeloma Patients
LINK to abstract
Session Title: 24. Gene therapy, cellular immunotherapy and vaccination – Biology & Translational Research
Poster ID: P1362
Session date and time: Friday, 9 June, 18:00 – 19:00 CEST
Session room: Poster area
Presenting Author: Dr Margaret Duffy
THEO-310 is an oncolytic virus developed for tackling the bone marrow tumour microenvironment (TME) of advanced late-stage myeloma patients. THEO-310 demonstrates efficacy in >80% of ex vivo bone marrow aspirates, across newly diagnosed, relapsed and refractory myeloma patients. In these experiments, TME immune modulation and superiority to ‘best-in-class’ oncolytic virus strains for myeloma, including the measles virus, was observed.
"These exciting set of results differentiates Theolytics’ approach to other oncolytic virus candidates. In addition to showing increased efficacy in patients ex vivo, the candidate demonstrates systemic safety as shown by cytokines levels post IV injection in vivo, whilst exhibiting >40-fold better circulation compared to a clinically validated oncolytic virus strain, thus supporting effective intravenous delivery," said Margaret Duffy, Chief Scientific Officer and Co-Founder of Theolytics. "Taken together, THEO-310 represents a new therapeutic option, with a highly differentiated mechanism independent of BCMA, for myeloma patients with relapsed refractory disease.