The French investor Sofinnova Partners has injected a total of €6M into three Italian gene therapy companies, cementing Italy’s reputation as a European center for cell and gene therapies.
Last month, the venture capitalist Sofinnova Partners used its Telethon fund to inject cash into AAVantgarde Bio, Borea Therapeutics, and Alia Therapeutics. The three firms will share a total of €6M in seed funding to fuel the development of treatments for rare inherited diseases.
Sofinnova’s move follows a €20M injection through the same fund last year in three other early-stage Italian gene therapy companies – Genespire, Epsilen Bio, and PinCell.
Sofinnova’s Telethon Fund is the largest investment pot for biotechnology in Italy and was set up in 2018 with the Telethon Foundation charity, which has been supporting research into new treatments for rare and genetic disorders for the past 30 years.
Sofinnova Partners’ Managing Partner Graziano Seghezzi told me Italy was a hub of excellence in gene therapy due to long-term support from the charity. The country has many startups due to the abundance of biotech researchers and academics and a strong tradition of excellence in science education.
“Now more than ever there’s a surge of scientific activity taking place in Italy to help reach patients suffering from rare, genetic diseases who today have very few therapeutic options,” he said.
“We believe the Italian market has significant potential to treat these conditions and experience growth in long-term biotech development.”
More than half of the latest round of funding – €3.7M – will go to Milan-based AAVantgarde Bio, which aims to begin clinical trials of gene therapies for inherited retinal disorders. The company delivers large therapeutic genes to the patient’s cells in vivo using adeno-associated viral (AAV) vectors — a form of technology that has traditionally been limited to delivering small genes.
Sofinnova will also invest €1.5M in another Milan-based company called Borea Therapeutics. Borea aims to treat genetic and chronic diseases using chemically altered AAV vectors that enable its gene therapies to reach areas such as the central and peripheral nervous system.
“Borea is developing the next generation viral vectors to enable targeting of specific cells and tissues,” explained tech transfer specialist Lucia Faccio, a member of the Borea board of directors and a Partner at Sofinnova Partners.
“Our inability to do this today is a major limitation of current AAV gene therapies. If we are able to overcome this challenge, it would open the door to lower dosages and therefore the ability to develop therapies that have less toxic side effects and are thus safer.”
The final €1M will be used by Alia Therapeutics, a spinoff from the University of Trento, which plans to use CRISPR gene editing approaches to treat retinal degeneration. The company will use the funding to develop a form of CRISPR-Cas9 gene editing that produces fewer off-target edits than other forms, which could make it safer for use in gene therapies.
“Alia is developing next-generation in vivo gene editing approaches by increasing on-target specificity thus increasing the safety of gene editing in vivo,” said Paola Pozzi, a Partner at Sofinnova Partners and investment partner in Alia Therapeutics.
“Alia’s approach is unique in that it aims to tackle multiple mutations thus enabling treatment of genetic disorders caused by multiple mutations in the same gene.”
In addition to a world-class football team, Italy has become known for developing advanced therapies such as gene therapies, stem cells, and tissue engineering over the past decade. For example, four of the 17 such treatments approved by the EU originate from Italian researchers.
The first ex-vivo stem cell gene therapy approved in Europe – Strimvelis in 2016 for the rare genetic immunodeficiency condition ADA-SCID – was developed by GSK and the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) in Milan. The same institute also contributed to Orchard Therapeutics’ development of Libmeldy, a gene therapy approved by the EU for a rare neurodegenerative disease last year.
The reasons behind Italy’s success are multifaceted. For example, some benefits may arise from the country’s robust clinical expertise and the speed of its institutions in translating preclinical research to clinical trials.
“There is a push for fostering an entrepreneurial mindset in academic and research organizations to identify the best acceleration path to validate the technology and move it forward to the clinic, bringing it closer to patients,” said Serghezzi.
The establishment of SR-TIGET in the 1990s played a key role in bringing back key Italian scientists from abroad. Major efforts have also been made at San Raffaele Hospital to build competences and facilities through the creation of MolMed, a clinical-stage biomed company. Last year, MolMed was acquired by AGC Biologics, a US lentiviral gene therapy Contract Development and Manufacturing Organization (CDMO).
Michela Gabaldo, Head of Alliance Management and Regulatory Affairs at the Telethon Foundation, suggests lessons learned during the coronavirus disease pandemic could benefit Italian research further.
Writing in the journal Nature earlier this year, she pointed out that the pandemic has demonstrated how the pathway from lab and clinic can be shortened and this now needs to be applied to innovations such as stem cells, gene therapy, and orphan diseases.
Gabaldo maintains that studies “must be designed from the outset in translational terms” and include early constructive dialogue with regulatory authorities, with access to high-quality manufacturing facilities.
She points out that an Italian expert task force and ethics committee set up by the Italian Medicines Agency and the Lazzaro Spallanzani National Institute of Infectious Diseases assesses all Covid-19 studies submitted, in the same way as the European Medicines Agency does at a central level.
“This has allowed consistent and competent assessments and constant international comparison,” she maintains “Even after the pandemic, these measures will remain crucial in such a specific and complex area as advanced therapies.”
Cover image from Elena Resko