One reason why engineered viruses are used to deliver genetic medicines is that viruses are very good at getting into cells. But the adeno-associated virus (AAV) used today has drawbacks. Their genetic cargo capacity is limited. While circulating in the body, they preferentially enter certain tissues or move away from others. These viruses can also trigger dangerous immune responses.
Vector BioPharma is taking a different approach, using a viral-like delivery vehicle, but without the limiting features of viral vectors.The Basel, Switzerland-based company, which officially launched on Wednesday, has received $30 million Series A financing From Versant Ventures, the venture capital firm that founded the startup.
Vector’s co-founder and chief executive Lorenz Mayr, whose experience includes holding executive positions at AstraZeneca and GE Healthcare Life Sciences, said Vector provides drugs containing virus-like particles. The company takes adenovirus and removes all viral genes. What’s left are what Meier calls “gullless” particles that are no longer viruses. Vector isn’t trying to trick the AAV into doing something it can’t, it’s designing its VLP to do what it wants.
VLP has a large capacity of 36 kb, while AAV has a capacity of 4.7 kb. Gene drugs are encased in a protein shell called a capsid. Vector calls its capsid a “shield,” and the risk of triggering an immune response is low. This is important because the viral components of AAV, including the capsid, can promote immune responses. In addition, antibodies against the virus produced by the immune system prevent re-dosing because these antibodies would render a second dose ineffective.
Vector aims to create reusable therapies by targeting proteins located on the shield. These proteins are engineered to find the desired cell type. The purpose of changing the treatment is to replace the protein on the shield.
“This is a completely tunable system, and we believe we can recognize any cell or epitope,” Mayr said.
Vector’s technology platform comes from the research of Andreas Plückthun, a professor of biochemistry at the University of Zurich and an expert in protein engineering. At the university, Plückthun designed VLPs that enable the delivery of large genetic cargoes to specific cells and tissues. Plückthun is a co-founder of Vector, the latest startup from Versant’s biotech startup incubator, Ridgeline Discovery Engine. Versant’s previous genetic medicine investments include the creation of CRISPR Therapeutics and Graphite Bio.
Versant is always on the lookout for breakthrough technologies, said Alex Mayweg, the company’s managing director and a member of Vector’s board of directors. The field of genetic medicine research includes methods aimed at improving targeting by first finding capsids that are biased into or away from specific types of tissues. In contrast, Vector uses protein engineering to rationally design its therapeutics to achieve desired goals.
“We’re making it completely rational, rather than taking some screening platform and hoping we’re biased against certain organizations,” Mayweg said.
The ability to deliver large gene cargoes to various cells and tissues in the body opens the door to many different therapeutic possibilities, Mayweg said. In vivo gene editing and delivering molecules into tumors are areas the company has already tested. Another potential application, Mayweg said, is CAR T therapy, in which these cells are produced in a patient. This in vivo capability would bypass the lengthy and cumbersome in vitro manufacturing process for this cell therapy.
Vector tested these methods in preclinical studies. The next step for the company is to optimize these therapies and select drug candidates, Mayweg said. The funding will be used to generate more data in areas such as immuno-oncology and gene editing. The company expects to have in vivo data from its lead program in the first half of next year.
The field of genetic medicine research continues to evolve toward therapies aimed at overcoming the limitations of AAV. like a vector, Code Biotherapeutics takes a modular approach to developing genetic medicines, but using synthetic DNA-based technology. The Philadelphia-area startup launched in June with a $75 million Series A round.in San Diego Relay uses an engineered version of the herpes simplex virus, which it claims offers 30 times the capacity of AAV. Relay announced a $55 million seed round last month.
Vector isn’t the only biotech company taking a so-called gutless approach to genetic medicine. Boston-based Ensoma is developing in vivo gene therapy delivered by adenoviruses that remove the virus’ genetic material. The startup is first focusing on rare diseases, Raised $70 million in Series A funding last year and formed a partnership with Takeda Pharmaceuticals.
There are also potential partnerships for Vector, which has had some early discussions with Big Pharma, Mayweg said. These companies are looking for systemically administered genetic medicines that can seek out specific tissue types in the body. They also want these therapies to have a larger payload capacity. The potential applications of Vector technology are vast. Vector will select its focus therapeutic area and pursue partnerships in other areas, Mayweg said.
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