Jun 22, 2023

Circio Thu, Jun 22, 2023 07:00 CET TG01 monotherapy will be evaluated in 20 patients with RAS-mutated multiple myeloma. The trial is sponsored by Oslo University Hospital and led by Dr. Fredrik Schjesvold, an international leader in the field and founder of the Oslo Myeloma Center, the largest Myeloma center in the Nordics Oslo, Norway, 22 June 2023 - Circio Holding ASA (OSE: CRNA), today announces that the first multiple myeloma (MM) patient has been dosed with mutant RAS cancer vaccine TG01 at Oslo University Hospital (OUS). The study is led by multiple myeloma expert Dr. Fredrik Schjesvold in a clinical collaboration between OUS and Circio. OUS is the study sponsor, with Dr. Schjesvold as the principal investigator, in collaboration with project lead Dr Hanne Norseth and Research medical student Hedda Monsen. Circio will provide TG01 drug supply, scientific support and a financial contribution. Mutations in the RAS genes are commonly found in pancreatic cancer, colon cancer myeloma and lung cancer but outside of lung cancer there are no RAS-targeted therapies available for these patients. TG01 is a mutant RAS therapeutic cancer vaccine adjuvanted by QS-21 STIMULON, which targets the seven most commonly found RAS mutations. TG01 has previously demonstrated robust immune responses and survival benefit in resected pancreatic cancer combined with standard of care chemotherapy. In this study, TG01 vaccination will be tested as a monotherapy in 20 KRAS or NRAS mutated myeloma patients who have either high risk smoldering myeloma or have evidence of disease after completion of standard of care (SoC) therapy. The treatment period is 12 months. In the first 3 months TG01 is given every other week, and thereafter it is given once every second month for 9 months. The aim is to assess whether anti-RAS T-cell priming induced by TG01 can delay the disease progression and enhance the clinical response. Dr. Fredrik Schjesvold, Founder and Leader Oslo Myeloma Center, at Oslo University Hospital, and President of the Nordic Myeloma Study Group, said: “There are no targeted therapy options available for RAS-mutated multiple myeloma patients which continue to have a clear need for better and more tolerable treatments. I believe the TG01 vaccine has the potential to eliminate residual disease and delay recurrence following standard of care treatment, and we look forward to work with Circio to test this therapeutic concept at our center.” Margrethe Sørgaard, VP and Head of Clinical Development of Circio Holding ASA, added: “Having the first patient dosed in Dr. Schjesvold´s study in multiple myeloma is an important milestone for the TG program. It is the first time the TG01 cancer vaccine will be tested in this indication, and the first time the new and enhanced vaccine format of sub-cutaneous single-injection TG01 adjuvanted by QS-21 STIMULON has been administered to a patient in Europe. We firmly believe that TG01 can bring targeted clinical benefit, with a favorable safety profile, to this underserved area of RAS-mutated multiple myeloma.” About TG01 mutant RAS vaccine Oncogenic mutations in the RAS family of genes drive up to 30% of all cancers and remain a major unmet medical need with few good treatment alternatives. Circio was recently awarded two prestigious research grants from Innovation Norway and the Norwegian Research Council, totaling NOK 18m, to advance its TG mutant RAS cancer vaccine program. About Agenus, QS-21 STIMULON Agenus is a clinical-stage immuno-oncology company focused on the discovery and development of therapies that engage the body's immune system to fight cancer and infections. In March 2022, Circio announced a collaboration with Agenus to utilize the proprietary adjuvant QS-21 STIMULON as an immune-stimulatory component of the TG vaccines for future development and commercialization. QS-21 STIMULON has consistently demonstrated powerful antibody and cell-mediated immune responses both in cancer trials and as a component of the commercial Shingrix*, Mosquirix* and Arexvy* vaccines. QS-21 STIMULON is expected to further potentiate the TG vaccines by driving stronger anti-RAS T-cell responses. *Trademarks owned by GSK. Erik Digman Wiklund, CEO Circio Holding ASA is a biotechnology company developing novel circular RNA and immunotherapy medicines. Building on deep experience in RNA biology, immunotherapy and viral vector engineering, Circio has established a unique circular RNA (circRNA) platform to develop novel circRNA medicines for cancer, vaccines, protein replacement for genetic disorders and cell therapy. The proprietary circVec technology is based on a modular genetic cassette design for efficient biogenesis of multifunctional circRNA from DNA-based vectors that can be deployed for multiple purposes. The most advanced therapeutic concept, circAde, builds on the company´s experience in oncolytic viruses to use engineered adenoviruses for delivery of circRNA to cancer cells. This unique approach is the only currently known circRNA program targeting solid tumors. Circio´s strategy is to develop novel circAde cancer medicines in-house and seek partnerships in other therapeutic areas to demonstrate the broad potential of the circVec platform and accelerate our circRNA pipeline development. The circRNA R&D activities are being conducted by the wholly owned subsidiary Circio AB based at the Karolinska Institute in Stockholm, Sweden. Circio´s clinical immunotherapy programs are designed to activate the patient´s own immune system to fight cancer cells and provide benefit to patients with no or few treatment alternatives. Lead candidate ONCOS-102 is an oncolytic adenovirus (AdV5) carrying a genetic cassette for mRNA-based expression of the cytokine GM-CSF, designed to selectively target cancer cells and drive an anti-tumor immune response. ONCOS-102 has demonstrated an excellent safety profile, strong immune responses and clinical efficacy in several cancer types in Phase 1/2 studies, both as monotherapy and in combinations with checkpoint inhibitors or standard-of-care chemotherapy. Circio is aiming to progress ONCOS-102 into a phase 2 trial in melanoma patients resistant to PD-1 checkpoint inhibitor treatment, subject to additional external financing and/or partnerships to support the program. Circio’s second clinical stage program is an immunotherapy targeting KRAS driver mutations. Lead candidate TG01 has previously shown robust immune responses and encouraging clinical benefit in surgically resected pancreatic cancer, and is currently being tested in two clinical trials in RAS-mutated pancreatic cancer and multiple myeloma in the USA and Norway. These studies are being run through industry and academic collaborative networks, supported by prestigious research grants from Innovation Norway and the Norwegian Research Council, creating broad future optionality for the TG01 program at low cost to Circio.