AAVantgarde, a clinical-stage biotechnology company, is eyeing a large Series C or crossover funding round to advance two gene therapy programmes through late-stage trials and commercialisation, CEO Natalia Misciattelli told this news service.

The Italian and UK-based company specialising in ophthalmic treatments has sufficient funding through to the end of 2027, after raising USD 141m in a Series B round in November.

However, Misciattelli acknowledged that Phase III trials of the two therapies and commercialisation will require significantly more capital than raised to date.

“We will need a Series C or crossover round,” Misciattelli said, adding that the next raise will exceed previous rounds, but noted that efficiencies from shared clinical centres for the two treatments should help keep costs in check.

Two benchmark transactions in the ophthalmology space are Beacon Therapeutics’ USD 170m series B and Atsena Therapeutics’ USD 150m series C, Misciattelli noted.

AAVantgarde’s near-term focus is on achieving proof of concept, using human data, for two gene therapy programmes targeting inherited retinal disorders (IRDs). The first programme, LUCE, addresses Usher syndrome — a rare and devastating condition in which children born deaf progressively lose their sight.

“You can imagine how devastating this is for a child, who was just learning to communicate through sign language, then they start to lose their sight,” Misciattelli said. The treatment aims to halt disease progression by correcting the underlying genetic defect.

The company has already dosed 94% of its 15-patient cohort for LUCE’s Phase I/II trial and is awaiting data maturity. Animal studies have shown compelling results, but translating these into human efficacy is a critical derisking step, Misciattelli noted.

The second programme, CELESTE, targets Stargardt Disease, the most prevalent form of macular dystrophy in young people. Beginning in childhood, Stargardt leads to progressive blindness, severely impacting independence, employment prospects and quality of life, Misciattelli said. Historically, only one treatment has existed for IRDs, leaving a significant unmet need. AAVantgarde’s approach uses gene augmentation therapy to deliver the full-length ABCA4 protein, enabling treatment regardless of mutation type.

AAVantgarde’s platform strategy addresses large genes that have historically been difficult to treat. The company’s technology could eventually be applied to a broader range of genetic mutations, Misciattelli said.

Stargardt therapy has the potential to become a blockbuster treatment and generate significant revenue, Misciattelli noted, citing bank research. While AAVantgarde retains the option to take its drugs to market independently — given that patients are treated in specialist centres, reducing infrastructure costs — the company remains open to partnerships or even a sale if presented with an attractive offer, she said.

“Whether or not we take it to market, or somebody else decides this is an attractive target and makes an attractive offer, that is not what I am in control of,” Misciattelli said. “What I am in control of … I will develop the best possible drug that we can.”

The company’s ownership structure provides flexibility. AAVantgarde is backed by venture investors including Schroders Capital, Atlas Venture, Forbion, Sofinnova Partners and Longwood Fund. Telethon Foundation, a major Italian charity focused on rare diseases, retains a stake following its role in originating the intellectual property.

AAVantgarde was spun out of the Telethon Institute for Genetics and Medicine (TIGEM) and the University of Naples “Federico II”.

Following Misciattelli’s appointment as CEO in 2022, the company has made a series of appointments to strengthen the team for future growth, including Lauren Kaskiel, as chief business officer and Nina Kotsopoulou as chief technical officer.

In April 2025, the company appointed Rasmus Holm-Jorgesen as chief financial officer, bringing public markets experience that could underpin an eventual US IPO.

“If we were listing, we would list in the US, most likely,” Misciattelli said, citing the well-trodden path for biotech companies seeking optimal access to capital.

The timing of any IPO or strategic transaction will hinge on clinical progress.

Positive Phase I and II data typically trigger acquisitions in the sector, though some companies are bought at pre-clinical stage. AAVantgarde expects to follow a traditional biotech path to markets but will consider regional partnerships or a “fantastic” sale offer if it aligns with shareholder interests.

Competitively, AAVantgarde differentiates itself by addressing the root cause of disease through gene augmentation, offering the potential to halt progression or even improve vision.

This contrasts with rivals such as Belite Bio, which has a phase III read out on a Tinlarebant, a small-molecule pill that slows Stargardt Disease progression but requires ongoing treatment. Belite Bio completed Phase III trials in September and now commands a USD 5.5bn market cap. Alkeus, another competitor, is conducting Phase II trials for a therapy targeting toxic retinal build-up, which can cause several diseases which lead to blindness.

AAVantgarde’s current funding will allow it to sustain operations until late 2027, supporting completion of proof-of-concept trials for LUCE and CELESTE. The company is pursuing expedited timelines and global trial execution, with studies already conducted in the UK and US.

Should AAVantgarde opt for independent commercialisation, building US infrastructure would be a future priority, given the market’s size and regulatory efficiency, Misciattelli said. She added the group may be open to a regional partnership for future funding, without specifying the region or details.

Ultimately, AAVantgarde’s trajectory will be shaped by data. “Clinical trial progress remains the key derisking event for investors,” Misciattelli said. With two programmes approaching critical inflection points, the company is positioning itself for a pivotal year.