Amarna Therapeutics is a young dedicated biotechnology company started in November 2008 having its head office the Bioscience Park in Leiden, The Netherlands. The driving force of Amarna’s dedicated team is the ambition to develop new unique therapies and treatment options to improve the quality of life for many people suffering severe genetic disorders, degenerative diseases, cancer, as well as autoimmune diseases. To achieve this, Amarna has developed a new viral gene delivery platform.
A new old friend: SV40
The current viral vector landscape – using mainly lentiviral and AAV vectors – suffers from pre-existing immune memory in humans. Amarna Therapeutics based its existence on the idea to exploit well-known viral vector, derived from SV40. This particular virus was discovered during the early nineteen sixties as a contamination in the polio vaccine. Because of the fact that already millions had been vaccinated with this polio vaccine, meticulous research was carried out to study the effects of the contamination. SV40 was the first virus that was analyzed on a molecular level during the seventies and eighties and of which the genome was mapped. This research has confirmed the non-immunogenic charac¬ter of the virus and the vector derived from it.
The vaccinated population was followed for fifty years, but disturbing effects could not be noticed. A safety trial of this size is unequalled.
Vector particles were produced in monkey cell lines stably transfected with SV40 DNA. “It was at that moment impossible to make sufficiently pure vector material. The result: wild type SV40 emerged during production. That is why the vector at the time was inadequate for clinical application. After that, everyone has gone looking for human viruses as vectors and SV40 was history. Until we, now five years ago, thought that it might provide the solution for the delivery problem.” says Peter de Haan, CSO.
SV40 vectors are non-immunogenic in humans and therefore are excellently suited for safely and effectively treating genetic disorders and autoimmune diseases.
To get it right: Wildtype-free, large-scale vector production
Thus, an alternative to the old vector production systems had to be found. Amarna Therapeutics has developed an SV40-derived vector platform, denoted SVac which allows for the production of clinical grade vector batches. The vector platform overcomes the limitations of the conventional SV40 production systems – such as the generation of wild type SV40 particles – during the vector production process. Recombinant replication-deficient vector particles are produced at high titers by transduction of a proprietary engineered Vero producer cell line denoted SuperVero. This enables cost-effective, safe and large scale production of SVac particles in bioreactors. As such, the production process of vector particles is similar to current vaccine manufacturing processes, in which master seed viruses are seeded to Vero cells in large fermentors.
Pre-eminent for a wide range of indications
The excellent safety profile and the unsurpassed efficacy in transducing the liver make SV40 the vector of choice for liver-targeted therapies. This is not limited to indications for classical gene replacement therapies (e.g. Haemophilia, Crigler-Najjar, Hyperoxaluria, etc.), but it also opens the door for the development of reverse vaccines to treat degenerative diseases including a wide range of auto-immune diseases (e.g. Multiple Sclerosis, Autoimmune Uveitis, ALS, etc.).
With the capability to transduce T-lymphocytes in vivo, SVac is excellently suitable for expressing Chimeric Antigen Receptors in T-lymphocytes of cancer patients to treat a wide variety of human malignancies.
Not limited to a single administration
Just another beneficial feature of SV40, is the option to re-administer. This quality clearly sets SV40 apart from other currently used vector systems, where a humoral immune response is mounted after the initial vector administration, preventing re-administration. The unique cellular entry pathway of SV40 via so called ‘caveasomes’ may contribute to this eminent feature.
Partners are crucial
According to Ben van Leent, CEO of the Amarna Therapeutics, co-operation with the right partners is crucial to bring the SVac-based therapies to the patients. “We do almost everything together with partners and we outsource a lot of work. In co-development you develop faster and you reduce costs. Furthermore, in collaboration you can select exactly the right expertise for projects. Collaboration is therefore quite logical for us: the delivery platform is ours, but the therapeutic development programs are mostly done together with partners. We will not market end products by ourselves; our business model is based on licensing. The first licensing deal has already been closed. We are busy negotiating with large pharmaceutical companies for a number of follow-up deals, to be announced later this year.”
Peter de Haan, CSO