· 12 of 20 patients have already been enrolled in the study; excellent safety
profile of TG01 vaccination confirmed
· TG01 vaccination led to an increase in mutant RAS T-cells in 6 patients; 5
of these patients remain on study with stable disease
· Genetic characteristics of patients mechanistically support the observed
immune responses and clinical benefit, and propose novel biomarkers for patient
selection in future trials
· Circio's strategy to develop TG01 through external collaborations continues
to demonstrate success alongside its core circular RNA program
Oslo, Norway, 16 June 2025 - Circio Holding ASA (OSE: CRNA), a biotechnology
company developing circular RNA technology for gene and cell therapy and mutant
RAS-targeting cancer vaccines, today announces that interim data from the TG01
phase 1/2 clinical trial in multiple myeloma at Oslo University Hospital (OUS)
has been presented at the European Hematology Association 2025 annual meeting in
Milan, Italy.
The results show preliminary signals of clinical efficacy for TG01 vaccination
and confirm an excellent safety profile, thus providing justification for
continued clinical development for a major unmet medical need. The trial is a
collaboration between OUS and Circio to test TG01/QS-21 vaccination as a
monotherapy in 20 KRAS or NRAS mutated multiple myeloma patients with remaining
measurable disease after completion of standard of care treatment. The aim is to
assess whether T-cell responses to mutant RAS induced by TG01 can enhance and
prolong the clinical benefit. OUS is the study sponsor, with Dr. Hanne Norseth
as the primary investigator.
"RAS-mutant multiple myeloma has poor prognosis and there are currently no
available targeted treatment options for this patient population," said Dr.
Fredrik Schjesvold, Founder and Leader Oslo Myeloma Center, at Oslo University
Hospital, and President of the Nordic Myeloma Study Group "Interim data from the
first twelve patients demonstrate the capability of TG01 to induce RAS-specific
T-cell responses in a subset of patients, and suggest that these responses are
associated with disease stabilization. This is an important early indication of
clinical benefit. We look forward to completing the study, including a broad set
of genetic and immunological analyses, which will help us build the
understanding of how TG01 vaccination can fit as a future treatment option to
deepen and prolong responses in this underserved patient population."
Oncogenic RAS mutations drive up to 30% of all cancers and an estimated 15-20%
of multiple myelomas, and remain a major unmet medical need with few effective
treatment alternatives. Circio has previously been awarded two prestigious
research grants from Innovation Norway and the Norwegian Research Council to
advance the TG mutant RAS cancer vaccine program. These grants have provided
funding towards two active clinical studies, including the present multiple
myeloma study at OUS, Norway, and a phase 2 trial at Georgetown University,
Washington D.C. USA, where TG01 is tested in pancreatic and lung cancer.
"Consistent with our prior observations in pancreatic cancer, it is very
reassuring that this early-stage multiple myeloma trial has generated results
showing immunological activity of the TG01 vaccine associated with clinical
benefit," said Dr. Victor Levitsky, Chief Scientific Officer of Circio Holding
ASA. "The biomarker findings are consistent with the current understanding of
tumor immune control requiring a proper match between the characteristics of the
tumor and the of patient´s genetic buildup. This important connection provides a
mechanistic validation of clinical benefit and suggests specific biomarkers to
select patients who can benefit most from TG01 treatment in follow-up clinical
studies. We will continue to pursue our strategy to develop TG01 through
external partnerships in parallel with our core in house circular RNA program."
Poster title:
The phase I/II TG01-study: Vaccinating against RAS-mutated Multiple Myeloma
Presentation date and location:
14 June 2025, EHA 2025 Annual Meeting, Milan - Italy
The main conclusions from the poster presentation were as follows:
· Available data demonstrate excellent tolerability and safety of TG01/QS-21
vaccination
· 50% (6/12) of vaccinated patients show vaccine-induced specific T-cell
responses against mutant K/N-RAS-peptides
· 50% (6/12) of patients remain on study with stable disease (SD), no
objective responses have so far been observed
· 67% (4/6) of patients with SD had a K/N-RAS-peptide specific immune response
by ELISPOT (1/2 negative patients fell very narrowly below positivity threshold)
· Enrollment and analysis of the TG01 vaccine-specific responses are ongoing
The poster is attached hereto and is available on the Circio
webpage (http://www.circio.com/)
For further information, please contact:
Erik Digman Wiklund, CEO
Phone: +47 413 33 536
Email: erik.wiklund@circio.com
Neil Hunter - Hunter PR
Phone:+44 7821 255568 (http://tel:+447821255568)
Email: neiljameshunter@gmail.com
About Circio
Building circular RNA expression systems for enhanced gene and cell therapies
Circio Holding ASA is a biotechnology company developing powerful circular RNA
vector expression technology for next generation nucleic acid medicine.
Circio has established a unique circular RNA (circRNA) vector expression
platform for novel DNA, RNA and viral therapeutics. The proprietary circVec
technology is based on a modular genetic cassette design for efficient
biogenesis of multifunctional circRNA inside cells, which can be deployed in
multiple therapeutic settings, including genetic medicine, cell therapy and
chronic disease. The circVec platform has demonstrated up to 15-fold enhanced
and more significantly more durable protein expression vs. classic mRNA vector
systems and has the potential to become a new gold-standard platform technology
for nucleic acid and viral therapeutics in the future. The circRNA R&D
activities are being conducted by the wholly owned subsidiary Circio AB based at
the Karolinska Institute in Stockholm, Sweden.
In parallel, Circio is continuing to develop its legacy immuno-oncology program,
TG01, through external collaborations. TG01 targets RAS-mutated cancers and is
being tested in two clinical trials in Norway and the USA run through academic
networks and industry partnerships. TG01 is a therapeutic peptide vaccine
adjuvanted by STIMULON QS-21 licensed from Antigenics Inc, a wholly owned
subsidiary of Agenus Inc. STIMULON is a trademark of SaponiQx Inc., a subsidiary
of Agenus