Gene therapy has long promised a solution for inherited diseases untreatable with conventional medicine. One challenge that stands in the way is developing a gene transfer agent that will deliver a normal copy of the gene in question to the cells in the body where it is needed, and effectively set it to work.
The three universities that make up the UK Respiratory Gene Therapy Consortium (GTC) have developed a gene transfer agent with great promise for the treatment of cystic fibrosis, which has been licensed to the pharmaceutical company Boehringer Ingelheim. Now they have created a startup company that will use the same platform technology to treat other rare lung diseases.
After so many years of work, I couldn’t be more pleased that one part of our research has been picked up by a big pharmaceutical company, and another has a chance with a spinout. Professor Eric Alton National Heary and Lung InstituteCalled AlveoGene , the company will launch with seed funding from Oxford Science Enterprises and Harrington Discovery Institute at University Hospitals, in the USA. Old College Capital and the University of Edinburgh’s venture investment fund also participated in the
Group effortCreated in 2001, the GTC brings together researchers from Imperial and the universities of Oxford and Edinburgh to work on gene therapy treatments for cystic fibrosis. One approach uses modified lentiviruses as vectors to deliver therapeutic genes to the lungs. This lentiviral vector was the platform technology licensed to Boehringer Ingelheim for further development of cystic fibrosis gene therapy in 2021.
AlveoGene will take the same lentiviral vector technology and explore its application in other diseases, principally involving the lungs. Its first target will be alpha-1 antitrypsin (AAT) deficiency, a condition caused when a faulty gene fails to produce a protein that protects the lungs from damage when the body’s immune system is triggered to fight an infection or by irritants.
This deficiency results in a range of symptoms focused on breathing difficulties associated with emphysema. These typically emerge when people reach their thirties or forties, and an effective treatment should both relieve these debilitating symptoms and prevent ongoing damage to lung tissues.
"It’s one of the commonest of the rare diseases, and there are up to 100,000 people in America alone who have the severe form and would benefit," says Professor Alton.
Towards a treatmentAttempts have been made to treat AAT deficiency by introducing the missing protein into patients’ lungs (an approach called protein replacement therapy), but the results have not been encouraging. While licensed in some countries, this treatment is currently not approved for use in the UK due to its limited efficacy.
"Most people think not enough protein gets to the right compartment in the lung to produce clinical efficacy," says Professor Alton. "With gene therapy, we think that we can make enough of the protein in the right compartment, and that will be better than the treatments currently available."
Past attempts at gene therapy using adeno-associated virus as a vector have also proved disappointing, and the repeated doses that would be necessary in practice are not possible because the body tends to react to the virus. Preclinical work carried out with the GTC’s lentiviral vector suggests they can be administered repeatedly without problems.
A lean startupIn its first year working on AAT deficiency Alveogene will continue to collaborate closely with the researchers in the GTC. "We have the knowledge, not only about the vector platform and the gene therapy background, but also disease-specific knowhow," says Uta Griesenbach , Professor of Molecular Medicine at the National Heart and Lung Institute.
We believe AlveoGene has potential to become a leader in respiratory gene therapy. Claire Brown Oxford Science EnterprisesProfessor Alton, Professor Griesenbach and project manager Michelle Cadby will all work as consultants to the company. The R&D work AlveoGene needs in order to advance will be carried out under contract by researchers at Imperial or Oxford, or handled by a contract research organisation.
At the same time, Boehringer Ingelheim’s work on gene therapy for cystic fibrosis is expected to progress to clinical studies, applying lentiviral vectors in human lungs for the first time. "By the time that AlveoGene is ready to start a first clinical trial for AAT deficiency, we hope there will be experience with cystic fibrosis in the clinical field, providing useful learnings," Professor Alton says.
Meanwhile, AlveoGene will also evaluate the potential of its platform alongside other technologies to create a pipeline of novel inhaled gene therapies targeting other rare respiratory diseases, such as lung surfactant deficiencies and idiopathic pulmonary fibrosis.
"This work with lentiviruses is as a result of a Wellcome Portfolio Grant," recalls Professor Alton. "One of the anticipated outcomes of this award was the creation of a spin-out company to accelerate clinical translation, so we are very pleased to have this opportunity of developing new treatments for respiratory rare disease patients."
AlveoGene will be led by Executive Chair David Hipkiss, who has a successful 25-year track record in building innovative biotech companies. He is a former chief executive and co-founder of respiratory medicine company Prosonix, and a former chief executive and founder of Enesi Pharma.
"I am truly excited to lead this new venture," he said. "The combination of pioneering science, an extensively validated platform, access to world-leading expertise through our founding scientists and the backing of OSE, Harrington and OCC, provides a fantastic foundation for the company."
"AlveoGene is the culmination of an impressive and successful collaboration between leading researchers from three top-ranked universities in the UK, via the GTC," added Claire Brown, Partner (Life Sciences) at Oxford Science Enterprises. "We believe it has potential to become a leader in respiratory gene therapy."