The leader in circular RNA expression systems

R&D and corporate update 24 November 2025

Human circRNA was first described by Circio scientists

Dr Thomas B Hansen Dr Erik D Wiklund

8,000 citations

Circio has developed a powerful alternative to the main dogma of molecular biology

The circVec dogma:

DNA → circular RNA → Protein

circVec is a platform technology for vector -based gene delivery
circVec enables enhanced and prolonged gene expression
Circio has unique expertise, IP & know -how covering circVec

Circio is deploying the circVec technology to enhance conventional gene and cell therapy

AAV benchmark

AAV circVec

>40x increased protein expression for circRNA- vs. mRNA-based AAVs
Enhanced, safer and lower cost AAV gene therapy

LNP:DNA benchmark

LNP:DNA circVec

>6 month durability for circRNA- vs. <3 weeks for mRNA-based vectors
Durable and re-dosable in vivo CAR-T therapy

circVec value proposition for AAV gene therapy: unlocking dose reduction to lower toxicity and cost

AAV gene therapy for Danon disease:

Clinical benefit demonstrated, but severe toxicity
Very high AAV dose level required (= high tox & cost)
➢ Severe adverse events, incl. risk of death

Circio ´s circVec technology can unlock:

Significant AAV dose reduction with same clinical benefit
Reduced toxicity and cost, better commercial viability
➢ Better, safer and lower cost AAV gene therapy

Development plan with near -term R&D milestones

Technical In vitro concept PoC	In vivo In vivo technical PoC disease model	IND Target milestones enabling next 6-9 months
Heart – Cardiomyopathy CNS & eye	safer Enhanced and , lower therapy cost gene	Q4´25 – circVec 3.2/4.0 heart Q4´25 – circVec 3.2 eye + CNS in vivo data Q1´26 – Danon disease construct first data Q1´26 – wAMD disease construct first data
Spleen	Durable and re-dosable in vivo therapy CAR-T	Q4´25 – circVec CAR vectors in vitro testing Q1´26 – T-cell targeted LNP delivery in vivo Q1´26 – In vivo T-cell reporter expression Q2´26 – In vivo T-cell CAR transduction

Main updates to be presented today

circVec generation 4 established, 50% boost vs. generation 3

Strengthened in vivo validation of circVec-AAV gene therapy in heart, emerging positive data in brain / CNS

LNP:circVec in vivo cell therapy demonstrated 6 months durability

Entered first fully funded collaboration with major pharma company

Platform development circVec 4.0

1. circVec-AAV gene therapy
1. In vivo cell therapy

Summary & outlook

circVec

Circio ´s unique and proprietary circRNA based gene expression platform technology

circVec substantially extends RNA half -life and increases protein expression in vivo

In vivo RNA half-life, pDNA vector-expressed RNA

8h 610h >75x longer half-life vs. mRNA mRNA vector circRNA vector

In vivo luminescence; intramuscular injection of pDNA

New circVec generation 4 established: 40 -50% improvement over generation 3

circVec generation 1.X – 4.X, design schematics

circVec protein quantification, Western blot

2

circVec -AAV gene therapy

1. In vivo cell therapy
1. Summary & outlook

AAV -specific circVec 3.2 expression construct

Heart -specific AAV -circVec significantly outperforms a conventional mRNA -based AAV

AAV f-luc signal profile from head to tail

40x enhanced steady -state expression level in heart

Early circVec 4.0 data shows 50% benefit in vivo vs. optimized circVec 3.2 design

AAV -circVec advantage confirmed by ex vivo analysis, higher and more specific heart expression

Increased gene expression in heart, ex vivo tissue analysis

…and reduced off-taget liver expression

In vivo data supports reduced toxicity of AAV-circVec

Cellular stress response, UPR pathway activation

Unfolded Protein Response (UPR) activation is a major contributor to AAV toxicity in patients
AAV-circVec shows less activation of UPR pathway in heart than AAVmVec at same dose
Despite 40x increased gene expression
Confirmed in various cell lines

Summary : AAV -circVec confers three major advantages for the treatment of genetic heart disorders

circVec-AAV compared to benchmark mVec-AAV:

Additional opportunity: circVec -AAV local delivery to eye

Luminescence, local intra-vitreal inj. of AAV-circVec 2.0 vs. AAV-mVec

F-luc signal quantification in eye, Day 7-63

Additional opportunity: circVec -AAV local delivery to brain

Local ICV injection to brain (intra-cerebro-ventricular)

Local injection of AAVs in the brain ventricles, bypassing the bloodbrain-barrier

10+ completed/ongoing clinical trials* using ICV injection of AAV for treatment of neurological disorders

mVec circVec2.1 Quantification of luminescence, IVIS

Heart, eye and CNS selected as top three target tissues for continued AAV -circVec development

	Heart		Eye			CNS
	40x increased activity for circVec 3.2	7x increased activity for circVec 2.0		4x increased activity for circVec 2.1 (ongoing)
	4.0 testing ongoing		3.2/4.0 testing 4Q´25			3.2/4.0 testing 1Q´26
	Increase on-target expression		Maximize local payload secretion		Enhanced local CNS payload expression
	Reduce systemic dose, → lower tox and cost	Reduced local dose → less inflammation, cost		Open new AAV opportunities in challenging CNS diseases
	1. Danon disease n = 1,500-2,000	1. Wet AMD n = 6-7 mill.		Tay-Sachs, Krabbe Gaucher disease ++
	2. Fabry disease n= 30-40,000	2.	Diabetic Mac´lr Edema (DME) n= 20-25 mill.		Partner with CNS-AAV companies
Opportunity 1: Danon disease No approvals, validated target, low technology risk			Opportunity 2: wet AMD Very large market, delivery issues for approved options			Opportunity 3: Several diseases with major unmet need, broad pharma activity

AAV -circVec Danon disease (heart) lead program: animal PoC data expected first half 2026

Take -home messages: transforming AAV gene therapy

AAV-circVec outperforms on expression, specificity and toxicity

Advantage shown in three tissues in vivo: heart, eye and CNS

Several commercial & partnering opportunities, near-term news flow

In-house

Establish PoC for Danon disease (heart) and wet AMD (eye)

Next step: Test specific disease-targeted circVec-AAVs

Partnering

Entered partnership with major global pharma company

Next step: Establish collaboration for engineered AAV capsids

In vivo cell therapy

Summary & outlook

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circVec has a unique window of opportunity for in vivo cell therapy applications

In vivo CAR modalities - duration

Days Months Permanent mRNA & circRNA circVec-DNA opportunity Lentiviral

Non-genome integrating
> 6 months duration of expression on single dose
Redosable
Avoids liver-expression

circVec -DNA benefits Therapeutic applications

Cancer, e.g. lymphoma
Ex vivo CAR-T effective, but expensive
Lentiviral risk of secondary malignancies
RNA in vivo CAR not sufficient duration
Autoimmune disease, e.g. Lupus
secondary opportunity

In vivo cell therapy: circVec expression duration now confirmed to over 6 months on single dose

LNP-mVec (mRNA), luminescence Systemic I.V. delivery, single dose on Day 0

LNP-circVec (circRNA), luminescence Systemic I.V. delivery, single dose on Day 0

LNP-delivery formulation

DNA -circVec in vivo cell therapy development timeline: animal PoC data expected first half 2026

Take -home messages: circVec cell therapy

> 6 months duration of expression vs. < 2 days for mRNA in vivo CAR

circVec expression shown in both T- and B-cells in spleen

circVec CD19 CAR-expression technically validated

In-house

Evaluate T-cell-specific transduction in vitro and in vivo

Next step: Active T-cell targeting delivery in vivo testing

Partnering

Establish R&D collaborations with RNA in vivo CAR companies

Next step: Test circVec in validated partner delivery system

Recent deal activity highlights substantial commercial opportunities in Circio areas

Licensing, November 2025

\$75m up-front

+ \$400m milestones

AAV gene therapy for genetic eye disease

AAV engineering platform
Phase 1, novel therapeutic candidate for vision loss

M&A, October 2025

\$1.5b

in cash buy out

circRNA in vivo CAR-T therapy for autoimmune disease

LNP-delivered synthetic circular RNA platform
Pre-clinical, CD19 CAR-T

M&A, June 2025

\$2.1b