The U.K. startup Stratosvir is working to tackle the barriers to developing viral immunotherapies for cancer, including allowing intravenous delivery and making it possible to dose multiple times.
Cancer immunotherapies have made great strides in the last decade, with some of the most important advances including CAR-T cell therapy and checkpoint inhibitors.
One oncology field that has often been overshadowed in the last decade is oncolytic viruses, which are also known as viral immunotherapies. These often involve engineering a virus to hunt down cancer cells, kill them and release fragments of cancer cells to activate the immune system against the tumor.
Viral immunotherapies received a huge boost in 2015 when Amgen’s Imlygic was approved by the U.S. Food and Drug Administration (FDA) for the treatment of melanoma. However, the field has also been tarnished by Imlygic’s lukewarm commercial performance in addition to high-profile clinical trial failures including Transgene’s phase 3 flop in 2019.
“It feels like an unloved modality,” said Chris Ullman, CEO of the Stevenage-based viral immunotherapy startup Stratosvir. “We see a lot of promise in this and people that work with this modality still have a lot of faith that it can deliver.”
Stratosvir was set up by Ullman and co-founder Antonio Postigo in 2020 with funding from Cancer Research UK and the venture creator Deep Science Ventures (DSV). Ullman drove the foundation of Stratosvir in an attempt to push the boundaries of viral immunotherapy in the treatment of cancer.
“I was working as a consultant and I was trying to treat cancer using synthetic approaches such as nanoparticles and nanocages,” explained Ullman. “Those approaches do have some advantages, but I was always looking over the fence and thinking that if we are looking to deliver genes to cancer cells to modify the tumor microenvironment, viruses do this efficiently.”
Postigo, in turn, left a well-paid position at the Oxford oncolytic virus player PsiOxus Therapeutics to jump on board as Stratosvir’s CSO.
There is clinical evidence going back decades that viral infections can trigger the body to battle cancer. In one recent example, a patient with blood cancer went into remission following a COVID-19 infection.
However, one of the biggest challenges for current viral immunotherapies like Imlygic is that they must be injected directly into tumors, reducing the scope of tumors that they can target.
“There’s a lot of real-world data to show that viruses could really be a useful modality for treating cancer, but only if you can get the viruses into the tumor, which is a delivery issue,” said Ullman. “Making the viruses more stable in the bloodstream to deliver them intravenously rather than having to directly inject them into the tumor is difficult. You need to know where the tumor is and that limits your therapy to melanoma.”
Being able to deliver viral immunotherapies in the bloodstream would enable companies to treat deeper solid tumors such as pancreatic cancer. It could also allow viruses to attack late-stage cancer that spreads to other parts of the body.
Stratosvir is engineering viral immunotherapies to be stable enough to be delivered intravenously. The company uses strains of vaccinia viruses, which are thought to be better at evading the immune system in the blood than other types of viruses used in immunotherapies such as adenoviruses. The viral vector can also carry a genetic payload of 25 kilobases, which provides a lot of options regarding which therapeutic molecules the company chooses to deliver into the tumors.
“A lot of other people think that failures in the clinic have shown that the viral modalities don’t work, but we think the data from clinical trials show that the modality does work; it just doesn’t get delivered,” said Postigo. “So we homed in on this delivery issue.”
Stratosvir is currently developing lead viral immunotherapy candidates at the preclinical stage as it seeks investments to fuel the research. In the last week, the company shipped its first products to an undisclosed partner company for in vitro and in vivo testing. If the research proceeds to plan, Stratosvir expects to enter clinical testing by the end of 2025.
Unlike many biotech startups, Stratosvir wasn’t spun out of a university; it was formed specifically by DSV and Cancer Research UK to solve bottlenecks in developing viral immunotherapies for cancer. While this does mean the team lacks years of preclinical data generated in academic labs, there are numerous advantages.
“In terms of spinning out and getting investor interest, we haven’t got the practical issue of negotiating with tech transfer teams and the treacle in the process,” added Ullman. “We are quite a simple company in that we own the IP, and that’s what investors get: the know-how and the IP.”
Stratosvir is part of a large group of biotech companies that are developing viral immunotherapies. Other companies using vaccinia viruses in their immunotherapies include the U.S.-Canadian firm Turnstone Biologics, KaliVir Immunotherapeutics in the U.S., and Transgene in France. Last year, Turnstone raised $80 million in a Series D funding round, and KaliVir closed a Series A round in March 2022.
Stratosvir aims to stand out from the competition by focusing its efforts on being able to overcome the delivery challenge for viral immunotherapies.
“Others are either ignoring the problem and saying it doesn’t exist, or they have convoluted solutions such as using cell carriers,” said Ullman. In addition, Stratosvir’s method could prove more scalable in the manufacturing process than other approaches.
Another issue with viral immunotherapies is that the immune system will recognize the therapy as foreign and destroy it. This then trains the immune system to destroy the viruses even faster if the patient is dosed multiple times.
“We’d like to work on single dosing but realistically, we might need to redose,” said Ullman. “Or we might encounter patients that have pre-existing immunity. It’s not a huge issue for us with our virus. We are working with vaccinia virus and there are very few patients now that have pre-existing immunity.”
Now that oncolytic viruses are in the market, the industry is beginning to shift. Rather than simply being seen as an anti-cancer torpedo, these therapies are increasingly showing their potential as vectors to deliver therapeutic and immunostimulatory molecules in a multi-pronged assault on tumors.
The field of viral immunotherapy is undergoing a shake-up at the moment. Part of the new excitement is the major awareness boost granted to adenoviruses by the approvals of COVID-19 vaccines such as the one developed by AstraZeneca. With a laser focus on the delivery bottleneck, Stratosvir is gunning to bring viral immunotherapies into the same league as CAR-T and checkpoint inhibitors.
“I think that every time there is a failure — not only in this field — a lot of people run away and think that the modality as a whole is not viable,” said Postigo. “Focusing on what the bottlenecks are allows you to make a step change.”