How a soccer ball and a computer inform new vaccines

RSV is a complicated virus, and traditional vaccine methods have not worked. But UW’s Institute for Protein Design may have solved the problem using computational design. With the help of an innovative computer program, Icosavax has constructed virus-like particles (VLPs) using a two-part assembly (like a soccer ball). Adam Simpson, CEO of Icosavax, talks to Lu Rahman.

Icosavax is the second company that Adam Simpson has helped spinout from the Institute of Protein Design (IPD) at University of Washington. The first was PvP Biologics, which was acquired by Takeda in February 2020. Icosavax was founded on technologies developed in Dr. Neil King’s lab at IPD for the design of self-assembling virus-like proteins (VLPs) with a straightforward manufacturing process that have the potential to create potent and durable immune responses.

“Today we understand how important vaccines are to protect health and the ability to go about our day-to-day lives. But when we closed the Series A forIcosavax in 2019, vaccines were a tougher sell to investors – that is why we targeted several investors who had a history with vaccines,” says Simpson. “We were also lucky to have initial seed funding from supporters of IPD to perform extensive studies at IPD and Icosavax showing that we could create a vaccine candidate that provides high and durable neutralising titers against respiratory syncytial virus (RSV) in multiple preclinical models (Cell 2019: Publication, Preview). RSV is a life-threatening respiratory virus that disproportionately affects older adults. The virus has defied previous vaccine technologies, so there is currently no approved vaccine against RSV. That is where our technology comes into play.”

Simpson says that Icosavax often describes its technology as a soccer ball. “The black parts are at the base of the antigens (eg. the prefusion structure of the RSV F glycoprotein or the SARS-Co-V receptor binding domain) and the white parts are there as the second piece to help create an icosahedral particle in the middle of the vaccine.” When mixed together, the black and white parts self-assemble into the soccer ball, displaying the antigens in a repetitive fashion, much like a virus.

“In 2019 with preclinical data in hand for an RSV VLP, we raised a significant Series A financing led by Qiming Venture Partners USA and joined by Adams Street Partners, Sanofi Ventures, and NanoDimension,” reveals Simpson.

Icosavax has since been working to advance an RSV vaccine candidate into clinical trials, and in October 2020, initiated a vaccine program for COVID-19.

Simpson says that Icosavax utilises its technology to address a significant unmet medical need in infectious disease vaccines – protecting older adults. “As we age, the immune system undergoes immunosenescence, which is a progressive deterioration in the ability to respond to infections and to develop immunity after vaccination. This is one of the reasons why these respiratory viruses like RSV have a higher mortality rate in the elderly.”

He adds that is also challenging for traditional vaccine technology to induce a robust immune response in the older adult population, which is why Icosavax believes that a technology that induces higher neutralising antibody titers will have the best chance of optimal and lasting protection in older adults.

“The idea behind our VLP vaccine technology is that the immune system has evolved to detect things that are symmetric and repetitive, like viruses, as a danger signal, and to react strongly to them. We take a subunit of the virus, also known as an antigen, that we want the immune system to attack, and precisely place the antigens in a highly immunogenic array on a nanoparticle to maximise potency. For example, we can display 20 RSV-F trimers on our RSV vaccine candidate,” he explains.

From the preclinical data of both its RSV and COVID-19 vaccine candidates, Icosavax saw that its nanoparticle VLP vaccine candidates elicited a strong immune response with high neutralising titers even with low doses.

“Because our vaccine candidates have shown a strong, durable immune response in preclinical models, we believe they may be especially important for older adults, where immunosenescence plays a role in the effectiveness and durability of other vaccine technologies. Furthermore, from a global health and access perspective, the high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable, and our final vaccine product is not expected to require subzero storage,” Simpson notes.

Icosavax plans to move both of its vaccine candidates (RSV, IVX-121 and SARS-CoV-2, IVX-411) into Phase I clinical trials this year. “For COVID-19, we plan to advance our SARS-CoV-2 receptor binding domain VLP vaccine candidate into initial clinical studies in mid 2021. Based on our preclinical data, we are hopeful that our VLP technology will offer a viable and durable vaccine during this pandemic that is different from those currently on the market. Data from our SARS-CoV-2 study will inform potential development paths in the COVID vaccine landscape,” he adds.

Simpson is clear on the company’s aims: “Several key vaccines have historically proven difficult to create. RSV was discovered in 1956, and there is still no approved vaccine or antiviral therapies to protect against it. RSV is a major viral cause of pneumonia, which is most severe in infants and young children and in older adults. Worldwide, RSV disease affects an estimated 64 million people and causes 160,000 deaths each year (NIAID). VLP vaccines have the potential to be extremely effective. For example, naturally occurring VLPs have delivered effective licensed vaccines, including against human papillomavirus (HPV) and Hepatitis B. But reworking naturally occurring VLPs has been difficult to do for the display of complex heterologous antigens, such as RSV.”

The idea behind the company’s technology is to not rely on molecules that naturally form nanoparticles, but to start from scratch and use the power of computational protein design to create fully self-assembling proteins. “We do not have to rely on the limits of what we see in nature and we can optimise the particles accordingly via our technology,” Simpson explains.

Icosavax’s computationally designed virus-like particle technology solves the problem of constructing and manufacturing VLPs displaying complex antigens. The technology generates computationally designed proteins that separate the folding of individual protein subunits from the assembly of the final macromolecular structure. The individual proteins are expressed and purified using traditional recombinant technologies and then self-assemble into VLPs when mixed together.

“We see computationally designed VLP technology as a platform technology, and it has the potential to generate vaccines against viruses that have been historically intractable to other technologies. For Icosavax, right now, we are focused on vaccine candidates to protect the elderly from life-threatening respiratory diseases as well as on a COVID-19 vaccine candidate,” Simpson says.

Icosavax has been named as a Top Academic Spinout by Nature Biotechnology. According to Simpson, the breakthrough potential of the technology upon which Icosavax was founded would not have been possible without Dr. Neil King at UW’s IPD who invented the technology.

“In addition, IPD’s Translational Investor Program supported the development of the computationally designed VLP technology we use at Icosavax. Further, CoMotion, the University of Washington’s collaborative innovation hub, was an important part of making it possible to spinout the company. This honour of being named a Top Academic Spinout belongs to all of us,” he adds.

“Vaccines are the most important medical intervention of all time after clean water. However, when we founded Icosavax, vaccines were not en vogue. With COVID-19, we see the urgent and important need to have advanced vaccine technologies ready and available. The pandemic spurred an increased vested public interest in viable vaccines that can quickly be brought to market. As such, biotech and pharma companies have an opportunity to meet this global medical need, not just for COVID-19, but for other diseases as well,” he says.

He believes that we need both fast technologies, like DNA and RNA vaccines, as well as technologies that can deliver potent and durable immune responses, like Icosavax’s. “And we need it not just against SARS-CoV-2, but also against life-threatening respiratory viruses, such as RSV, that circulate every year. An effective RSV vaccine could help millions of people around the world to relieve a substantial disease burden and reduce significant healthcare costs.

“With all the scientific and technological advancements in medicine, we must remember that vaccines are the most cost-effective way to protect our health, and our health is the foundation upon which the world works.”

Volume 22, Issue 2 – Spring 2021

Biography

Adam Simpson, CEO of Icosavax is a serial entrepreneur. Before Icosavax, Simpson was CEO of PvP Biologics, another spinout from the University of Washington’s IPD, acquired by Takeda. He holds a B.S. in biochemistry from the University of California, San Diego, and a J.D. from University of Minnesota Law School.

 

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