AAVantgarde closes $141 million series B round to tackle inherited eye diseases 

Today, AAVantgarde Bio raises $141 million (€122 million) in a series B round to advance its gene therapy programs for inherited eye diseases, marking one of Europe’s largest private financings in ophthalmic biotech this year. The round was led by Schroders, alongside existing investors Atlas Venture and Forbion, with participation from Amgen Ventures and several new backers. 

The Italian company is developing treatments for Stargardt disease and Usher syndrome type 1B, two genetic forms of vision loss caused by mutations in unusually large genes that conventional adeno-associated virus (AAV) vectors cannot accommodate. Its proprietary platform is designed to bypass this limitation, potentially broadening the reach of gene therapy to patients long considered untreatable. 

Natalia Misciattelli, AAVantGarde Bio’s CEO, explained: “We can treat the root cause even when the gene is larger than standard AAVs allow. We have a proprietary platform that uses two technologies: DNA splicing and protein splicing to deliver the large protein that we need.” 

While the first approved gene therapy for blindness, Luxturna, proved that replacing a missing gene could restore sight, its uptake remained limited by the rarity of its target mutation. AAVantgarde Bio is betting that by tackling more prevalent conditions, it can turn a niche success story into a platform with far broader clinical and commercial impact. 

What AAVantgarde Bio does and how the tech works 

At the heart of AAVantgarde Bio’s approach lies a problem that has frustrated gene therapy researchers for years: size. Most AAV vectors can only carry about 4.7 kilobases of DNA, barely enough for many of the genes implicated in inherited retinal diseases. Both diseases AAVantgarde Bio chose to target have long been seen as technically undruggable, not because their biology is obscure, but because their genes are simply too large to fit inside a conventional viral vector. 

The first disease AAVantgarde Bio is aiming to treat with its candidate AAVB-081, Usher syndrome type 1B, is a rare disorder that causes congenital deafness and progressive vision loss through mutations in the MYO7A gene. Earlier gene therapy attempts using lentiviral vectors were discontinued over safety and manufacturing hurdles, leaving the field without an effective delivery option. 

Its second program, AAVB-039 for Stargardt disease, addresses a more common but equally difficult target. Stargardt is a disease where the genetics are clear, the unmet need is huge, but the ABCA4 gene is far too big for standard vectors. AAVantgarde Bio’s intein-based construct aims to solve that by reassembling the ABCA4 protein inside the cell. 

The first approach, which the company calls its Dual-Hybrid platform, splits the genetic sequence in two. Each half is packed into its own AAV vector, and once both reach the same cell nucleus, the fragments rejoin to re-create the complete gene. This is the technology behind AAVantgarde Bio’s program for Usher 1B, where the company uses an AAV8 capsid, a targeted promoter, and subretinal injection to deliver the therapy directly to the layer of cells that support vision.  

“What is important to note is that this DNA splicing technology was invented by our founder [Alberto Auricch],” said Misciattelli. 

For Stargardt disease, AAVantgarde Bio takes a slightly different path. Instead of reconnecting DNA fragments, its Intein platform works at the protein level. The therapeutic gene is divided into two parts, each producing a fragment of the protein that then “self-stitches” back together inside the cell using naturally occurring inteins, molecular links first discovered in cyanobacteria. “For our Stargardt program, we’re using protein splicing,” said Misciattelli. “We’re using a specific set of inteins and it is 92% as efficient as a single vector, you could almost not get as efficient as that.” 

That efficiency claim, if it holds up in patients, would be a major step forward for large-gene delivery. The company has already demonstrated high expression levels in knockout pig models and in non-human primates, suggesting that its constructs can achieve biologically relevant activity before moving into the clinic. 

Both rely on well-characterized components, particularly the AAV8 vector and subretinal delivery technique, which are already established in ophthalmology. “From a risk point of view, ophthalmology is a sensible area to test a platform technology, so we are not keen on stacking risk on top of risk. That’s the reason why we use AAV8 vectors that have been tried and tested on thousands of patients,” explained Misciattelli. 

In theory, these same splicing technologies could be adapted to thousands of other human genes that exceed AAV’s natural limit. “There are 4,000 other larger genes that could also be interesting to use this technology [on],” Misciattelli said. “We know that we can express other large genes for other tissues as well.” For now, though, the company’s focus remains on inherited retinal diseases, conditions where the genetics are clear, the anatomy is contained, and the need for effective therapies is urgent, but Misciatelli said expanding the platform’s application is on the map for the future.  

Lessons from gene therapy’s first generation: what went right and wrong 

When Luxturna became the first approved gene therapy for an inherited form of blindness in 2017, it marked a defining moment for the field. Developed by Spark Therapeutics and later acquired by Roche, the one-time treatment for RPE65-mediated retinal dystrophy showed that replacing a faulty gene could restore meaningful vision in patients who were losing it. Clinically, Luxturna was an undeniable success: trial data demonstrated sustained functional improvements, and patient testimonials were widely celebrated. 

Commercially, though, the story was more complicated. The eligible population for RPE65 mutations was estimated at only 1,000 to 2,500 patients in the U.S., limiting the therapy’s reach. Despite a launch price of around $850,000 for both eyes, Luxturna generated roughly $250 million in total revenue between 2018 and 2023, far below the $500–700 million once forecast by analysts. Uptake was also slowed by the need for highly specialized surgical centers capable of administering subretinal injections and by the logistical burden of identifying eligible patients. 

From AAVantgarde Bio’s perspective, Luxturna’s story isn’t one of failure but of scale. “If you speak to the patient community, they will tell you that Luxturna has been an extraordinary success, The issue was there were not so many RP65 patients. So, from a commercial point of view, it’s a question of knowing where the patients are, and knowing the epidemiology. Stargardt is very prevalent, and Usher 1B is the most common subtype.” 

That commercial logic underpins AAVantgarde Bio’s focus. By targeting Stargardt disease, estimated to affect about 12% of the 5.5 million people (660,000 people) suffering from macular dystrophy globally, and Usher syndrome type 1B, the company is betting that its therapies can reach far larger patient populations while tackling technically difficult genes. 

The other early cautionary tale in the field came from ProQR Therapeutics, whose RNA-based therapy sepofarsen aimed to correct CEP290 mutations causing Leber congenital amaurosis 10 (LCA10). The treatment showed early promise but ultimately failed its phase 2/3 trial in 2022, missing its primary endpoint on visual acuity. That result reinforced how difficult it can be to capture functional vision improvement in small patient groups and to design endpoints sensitive enough to measure subtle gains. 

Unlike ProQR’s approach, which sought to repair RNA to restore protein expression indirectly, AAVantgarde Bio’s therapies use gene augmentation, delivering a working copy of the gene itself to produce the missing protein directly. The company’s team sees that as a more straightforward and durable solution to monogenic retinal diseases. 

AAVantgarde’s two lead programs echo a previous chapter in retinal gene therapy: both MYO7A (Usher 1B) and ABCA4 (Stargardt) were once pursued by Sanofi and Oxford Biomedica under the lentiviral programs SAR421869 and SAR422459. Both programs were dropped by Sanofi in 2020. 

The Stargardt race: Different routes to the same destination 

AAVantgarde Bio isn’t alone in trying to restore ABCA4 function in Stargardt disease. The field is converging on the same genetic goal with very different toolkits. 

SpliceBio is a direct modality neighbor: its candidate SB-007 also relies on protein splicing to rebuild ABCA4, but via the company’s own dual-AAV architecture. The phase 1/2 trial dosed its first patient in March 2025, and the company frames SB-007 as aiming to treat all ABCA4 mutations. That makes SpliceBio a head-to-head comparator on both target and delivery concept. 

Ascidian Therapeutics takes a different path entirely: RNA exon editing. Instead of delivering a replacement gene, ACDN-01 edits ABCA4 transcripts at the RNA level after a subretinal procedure. The program is in a phase 1/2 study, with FDA Fast Track granted; separately, Roche partnered with Ascidian on the same platform in neurology, an external validation of the editing approach. For patients, the practical question is whether RNA editing can achieve enough functional rescue in vivo without the payload limits of DNA delivery. 

VeonGen Therapeutics, formerly ViGeneron, is another clinical-stage contender in Stargardt disease. The Munich-based company is developing VG801, a dual-AAV therapy designed to deliver the full-length ABCA4 gene. The program is already in a phase 1/2 clinical trial and has received FDA Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug, and Rare Pediatric Disease designations. 

For AAVantgarde Bio, success will need to show up on several levels. Clinically, the next two years will be about proving that its dual-vector and intein approaches can safely deliver meaningful, lasting improvements in vision. Early readouts from the LUCE-1 and CELESTE trials will focus on safety and biological markers of activity, but true success will mean functional gains that patients can feel.