Circio Holding

Circio Holding ASA (”Circio” or ”the Company”) published its first half report for 2026 on the 31st of August 2026, followed by a webcast with a financial and R&D update on the 1st of September 2026. The following are key events that we have chosen to highlight from the recent news flow:

• circVec 5.0 has the potential of 200x or more versus conventional AAV – possibly making it a game changer within gene therapy
• circVec’s expression advantage confirmed with a therapeutic gene in heart (LAMP2B)
• 10–60x higher expression than conventional AAV in CNS across three separate delivery routes
• Durable expression achieved with a T-cell targeting LNP at all three dose levels tested, including the lowest
• Cash and short-term investments of NOK 539.0m (6.3) after approx. NOK 620m raised during H1-26, extending the runway into 2030
• 23 active R&D collaborations, with the stated aim of a first partnering deal carrying a cash payment during 2027

circVec 5.0 Would Push the Dose Advantage into Indications AAV Cannot Currently Reach

The most consequential new information in the period is a route toward circVec 5.0, a fifth-generation design that Circio indicates could reach 200x or more the gene expression of conventional AAV, against the 40–60x demonstrated to date. That route follows the two steps by which circVec works: the delivered DNA construct is first converted into circular RNA inside the cell (biogenesis), and that circular RNA is then read by the cell to produce protein (translation). Each step caps the output independently, so Circio has screened novel genetic elements against them separately in vivo. On biogenesis, the strongest new design reached approx. 90x versus the conventional mVec comparator, a 3x improvement on circVec 3.2; on translation, approx. 170x, a 5x improvement. circVec 5.0 is intended to combine the best elements of both.

Analyst Group considers this the most important item in the update. An expression advantage of this magnitude can be applied in several ways such as more protein at the same vector dose, or equivalent protein at a substantially lower one. circVec already supports both arguments at 40–60x, and the eye data demonstrated the second directly, with low-dose circVec outperforming a 10x higher conventional dose by approx. 12x. The significance of 200x is therefore not that it introduces a new argument, but that it extends how far that argument reaches.

Many first-generation AAV programmes required high systemic doses to achieve sufficient protein expression, which has been associated with immune activation, liver toxicity and, in some cases, severe adverse events. Since AAV cannot be effectively redosed, therapeutic success depends on achieving adequate expression from a single administration. Dose also sets cost, since manufacturing scales with the amount of vector produced, and the systemically dosed products carry materially higher prices than locally delivered ones, a cost structure that has contributed to the modality’s concentration in small patient populations.

Many indications are therefore not reachable at any dose that is both safe and economic, particularly systemic cardiac and muscle disease. An expression technology that produces the same protein from far less vector attacks both limits at once, and Analyst Group accordingly assesses that a validated 200x construct would command materially more than incremental licensing terms, since the partner would be buying access to programmes it cannot currently run rather than a better version of ones it already can.

However, the 90x and 170x figures come from separate constructs, thereby 200x assumes the gains compounded when combined into one design. This is plausible but unproven, therefore the circVev 5.0 data due within twelve months is accordingly the readout Analyst Group weighs most heavily on the platform side. The licensing case does not, however, depend on it. The advantage already demonstrated across heart, eye and CNS, now confirmed with a therapeutic gene, is a competitive package in its own right, and circVec 5.0 would raise the ceiling rather than establish the floor.

Heart Data Confirmed with a Therapeutic Gene, Removing a Central Partner Objection

Circio also presented heart data generated for the first time with a therapeutic gene rather than a reporter. Using LAMP2B, circVec produced substantially more protein in heart tissue than the conventional comparator at day 57, consistently across all animals tested. Of the results confirmed during the period, Analyst Group considers this highly commercially significant, as it moves circVec from a laboratory observation to a technology a pharmaceutical company can credibly build a development programme around.

The multiples published to date used firefly luciferase, a bioluminescent reporter chosen because it can be quantified repeatedly in a living animal, but which carries no therapeutic function. That has left a standing question for prospective partners: therapeutic proteins differ from a reporter in length, sequence and cellular handling, so an expression benefit measured on one does not automatically transfer to the other.

What has not been demonstrated is that the additional protein improves the animals’ condition, the disease-model study expected within twelve months, which Analyst Group regards as the genuine trigger for a licensing agreement, since partners pay more for evidence that a technology treats a disease rather than that it produces a reporter protein.

Consistency Across Three CNS Routes Strengthens the Programme Closest to a Deal

A second new dataset covers the central nervous system, where circVec was tested using three separate routes of administration, into the cisterna magna, the cerebral ventricles and the spinal canal, measuring an advantage of approx. 10x, 30x and 60x respectively. The three-route design matters as much as the multiples themselves. All three deliver into cerebrospinal fluid but from different entry points, giving different distribution across brain and spinal cord, so a consistent advantage across them points to a reproducible effect rather than an artefact of one administration protocol. The magnitude is context-dependent, ranging from approx. 10x to 60x; a strong evidence that circVec functions as a general expression technology remains the cross-tissue picture, with comparable advantages now shown in heart, eye and CNS.

Analyst Group regards this as the most underappreciated element of the update. CNS was previously Circio’s thinnest dataset, with earlier generations showing only an approx. 4x advantage, yet it is precisely where the fully funded feasibility study with the top-5 pharmaceutical company is running. The strongest new data has been shown in the programme most likely to produce Circio’s first licensing agreement, and a partner evaluating circVec for CNS today is assessing a materially better package than existed when that collaboration was signed.

A Multi-Month Expression Window, Now Achieved at Low Dose

Circular RNA in cell therapy has drawn substantial capital over the past nine months, with BMS acquiring Orbital Therapeutics for USD 1.5bn, Eli Lilly acquiring Orna for up to USD 2.4bn, and J&J paying USD 785m for an option over Sail Biomedicines, all three reprogramming immune cells inside the patient. The unresolved problem in the field is expression duration. mRNA-based systems fade within days, which may suffice in autoimmune disease but not in cancer, where surviving tumour cells regrow, while lentiviral vectors last indefinitely by permanently altering the genome. circVec occupies the gap between them, offering months of expression without genomic integration and with the potential for repeat dosing, a combination Analyst Group has not identified elsewhere in a DNA-encoded format.

The earlier durability result came from a blunt instrument at a high dose — expression beyond three months, but delivered with an untargeted LNP at 1 mg/kg. The new study tightened both variables. Circio used an LNP formulated to home in on T-cells and tested three doses, from 0.20 down to 0.05 mg/kg. Reporter expression appeared in the spleen at all three and was still present at the final day-64 readout, whereas the mRNA comparator produced a brief signal at the top dose only. A multi-month window therefore survives both a targeted formulation and a far lower dose, which matters because LNP tolerability is dose-dependent. In vivo cell therapy remains at an early stage, but Analyst Group considers the data among the more consequential circVec has produced, since the expression window is differentiated rather than incrementally better, it now holds under conditions closer to clinical use, and partners are paying preclinical-stage prices for access to this modality.

A Balance Sheet Funded Into 2030 Strengthens the Negotiating Position

Circio raised approx. NOK 620m gross across three equity transactions during H1-26, closing the period with NOK 539.0m (6.3) in cash and short-term investments, against NOK 571.7m raised net of transaction costs. Total OPEX in H1-26 rose 108% Y-Y to NOK 42.4m (20.4), attributed to more in vivo studies and R&D collaborations, a growing R&D-team and one-offs related to deferred incentive pay as well as non-cash effects on options.  Worth noting is that 2025 does not serve as a good comparable year, as the Company back then was in a constrained financial position. Thus, the OPEX-base will naturally increase ahead as the Company continues to accelerate on the promising initiatives to gradually expand the data package.

The strategic consequence matters more than the arithmetic, as a preclinical company funded into 2030 can wait for a stronger data package, which ultimately decides the terms of a potential licensing deal, and face a potential partner from a position of relative strength.

Concluding Remarks

In summary, Analyst Group considers H1-26 to have been the most productive six-month period in Circio’s history since the repositioning around circular RNA, with R&D, partnering and financing each advancing materially. The expression advantage now reaches up to 60x across heart, eye and CNS, is confirmed with a therapeutic gene, and has a credible route toward a further step change through circVec 5.0. The collaboration portfolio has grown to 23 active arrangements including the fully funded top-5 pharma feasibility study, while NOK 539.0m in liquidity removes the funding question into 2030. The circVec 5.0 in vivo data speaks to scale, as a validated 200x construct would broaden the indication scope a licensee could realistically pursue and support terms above the platform-licensing benchmarks currently applied. The heart and eye disease-model results, alongside data from the big pharma CNS collaboration, govern probability and timing, marking the transition from reporter-level proof-of-concept to disease-relevant efficacy on which partner engagement depends. Converting either into a first agreement carrying a cash payment remains Circio’s stated target for 2027. Should the data deliver, Circio would enter licensing discussions with a financial runway to 2030 and a technology that has no established direct competitor in DNA-based, vector-encoded circular RNA expression, a distinction worth drawing, since the recent acquisitions in the field involved synthetic circular RNA delivered as RNA rather than produced inside the cell.

We will return with an updated equity research report on Circio, where we expect to make upward adjustments regarding modelled future deal dynamics in light of the strong R&D-development.