Circio (CRNA) R&D Update summary

Platform technology and R&D progress

• circVec generation 4.0 delivers a 50% increase in protein expression over generation 3, with validated improvements in heart, eye (7x), and CNS tissues, and reduced toxicity compared to conventional AAVs and mRNA approaches.

• Achieved up to 40-fold higher protein expression in heart-targeted AAVs and demonstrated over six months of durable in vivo expression using DNA vectors and circVec constructs.

• circVec technology shows higher tissue specificity, particularly heart-centric and CNS expression, and lower cellular stress compared to mRNA vectors.

• Enhanced expression and better target selectivity confirmed in vivo, expanding potential therapeutic applications to heart, eye, and CNS diseases.

• Reduced toxicity observed with circVec-AAV, with less UPR pathway activation despite higher expression.

Clinical and pipeline updates

• Lead program targets Danon disease, aiming for lower AAV doses and improved safety; efficacy data in mouse models expected by end of next year, with animal PoC for Danon and wet AMD anticipated in 2026.

• Pipeline includes heart, eye (wet AMD), and CNS indications, with ongoing optimization and preclinical testing of therapeutic proteins.

• In vivo cell therapy program shows six-month expression in spleen and is advancing toward targeted T-cell delivery for oncology applications, with key readouts anticipated in 2026.

• TG01 immuno-oncology program for RAS-mutated cancers continues via external collaborations, with ongoing clinical trials in Norway and the USA.

• TG01 uses a peptide vaccine adjuvanted by STIMULON QS-21 licensed from Agenus Inc.

Business development and partnerships

• Entered a fully funded R&D collaboration with a major global pharmaceutical company to test circVec AAV in a specific disease area, validating the technology and opening new partnership opportunities.

• Actively seeking additional R&D collaborations, especially for T-cell targeted delivery and engineered AAV capsids for tissue-specific targeting.

• Recent industry deals highlight strong pharma interest and significant transaction values in AAV, circRNA, and in vivo CAR therapy spaces.

• Ongoing and new R&D collaborations, including a feasibility study with a global pharma, may lead to licensing opportunities.

• Rich pipeline of R&D and business development milestones expected over the next 12 months.