New Versant Ventures startup goes ‘gutless’ for next-generation gene delivery

New Versant Ventures startup goes ‘gutless’ for next-generation gene delivery


 

One reason engineered viruses are used to deliver genetic medicines is that viruses are very good at getting into cells. But the adeno-associated viruses (AAV) used today have drawbacks. They have a limited capacity for genetic cargo. Circulating in the body, they preferentially go to certain tissues or away from others. These viruses can also trigger dangerous immune responses.

Vector BioPharma is taking a different approach with a delivery vehicle that’s like a virus, but devoid of the features that limit viral vectors. The Basel, Switzerland-based company formally launched on Wednesday, backed by a $30 million Series A round of financing from Versant Ventures, the venture capital firm that formed the startup.

Vector delivers its medicines with virus-like particles, said co-founder and CEO Lorenz Mayr, whose experience includes executive roles at AstraZeneca and GE Healthcare Life Sciences. The company takes an adenovirus and removes all viral genes. What’s left is what Mayr describes as a “gutless” particle that’s no longer a virus. Rather than trying to trick an AAV to do something that it can’t, Vector designs its VLPs to do what it wants.

The VLP has a large capacity of 36 kilobases (kb), compared with the 4.7 kb capacity of AAV. Genetic medicines are enveloped in a protein shell called a capsid. Vector calls its capsids “shields” that pose low risk of sparking an immune response. That’s important because the viral components of AAV, including the capsid, can prompt an immune response. Also, the antibodies that the immune system produces against the virus prevent redosing because those antibodies would render a second dose ineffective.

Vector aims to make redosable therapies that are directed to their destinations by targeting proteins located on the shield. These proteins are engineered to seek out the desired cell type. Changing the destination of a therapy is a matter of swapping out the proteins on the shield.

“It’s a completely tunable system and we are confident we can recognize probably 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 engineered VLPs that can achieve the delivery of large genetic cargo to specific cells and tissues. Plückthun is a co-founder of Vector, which is the latest startup to emerge from Ridgeline Discovery Engine, Versant’s biotech startup incubator. Versant’s prior genetic medicines investments include the founding of CRISPR Therapeutics and Graphite Bio.

Versant is always looking out for breakthrough technologies, said Alex Mayweg, managing director at the firm and a Vector board member. The field of genetic medicines research includes approaches intended to improve targeting by first searching for capsids that have a bias for going to or away from particular types of tissue. By contrast, Vector uses protein engineering to rationally design its therapies to go to a desired target.

“We’re making it completely rational, rather than taking some screening platform and hope we get bias to some tissue,” Mayweg said.

The capability to deliver a large genetic cargo to a wide range of cells and tissues in the body opens the door to many different therapeutic possibilities, Mayweg said. In vivo gene editing and the delivery of molecules into tumors are areas that the company has tested. Another potential application is a CAR T-therapy in which those cells are produced inside the patient, Mayweg said. Such in vivo capability would circumvent the lengthy and cumbersome ex vivo manufacturing process for such cell therapies.

Vector has tested these approaches in preclinical research. Mayweg said the next steps for the company are optimizing these therapies and selecting drug candidates. The financing will be used to produce more data in areas that include immuno-oncology and gene editing. The company expects to have in vivo data for its lead programs in the first half of next year.

The field of genetic medicines research is continuing to move toward therapies intended to overcome the limitations of AAV. Like Vector, Code Biotherapeutics takes a modular approach to genetic medicines, but with technology that’s based on synthetic DNA. The Philadelphia-area based startup launched in June backed by a $75 million Series A financing. San Diego-based Relay uses an engineered version of the herpes simplex virus, which it claims offers up to 30 times the capacity of AAV. Relay unveiled a $55 million seed financing last month.

Vector isn’t the only biotech taking a so-called gutless approach to genetic medicines. Boston-based Ensoma is developing in vivo gene therapies delivered by adenoviruses stripped of viral genetic material. The startup, which is focusing first on rare diseases, emerged last year with a $70 million Series A round of funding and a partnership with Takeda Pharmaceutical.

Partnerships are also a possibility for Vector, which has had some early discussions with big pharmaceutical companies, Mayweg said. Those companies are looking for systemically administered genetic medicines that can seek out particular tissue types in the body. They also want those therapies to have larger payload capacity. The potential applications of Vector’s technology are broad. Vector will choose its therapeutic areas of focus and seek partnerships in other areas, Mayweg said.

Image: 4X-image, Getty Images

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