Icosavax Turns VLP Tech to COVID-19 Vaccine, with $16.5 Million in New Financing
Adam Simpson, CEO of Icosavax, pictured above. Photo courtesy of Icosavax.
Icosovax is turning its virus-like particle (VLP) technology to fight COVID-19. The news accompanies $16.5 million in new funding from the Bill and Melinda Gates Foundation and Open Philanthropy, and the publication of preclinical data in Cell. BioSpace’s Gail Dutton caught up with Icosavax CEO Adam Simpson to discuss its new vaccine candidate, IVX-411.
Icosovax is turning its virus-like particle (VLP) technology to fight COVID-19. The news accompanies $16.5 million in new funding from the Bill and Melinda Gates Foundation and Open Philanthropy, and the publication of preclinical data in Cell. BioSpace’s Gail Dutton caught up with Icosavax CEO Adam Simpson to discuss its new vaccine candidate, IVX-411.
Gail Dutton (GD): Why are you starting to develop a COVID-19 vaccine now, when so many others also are developing vaccines?
Adam Simpson (AS): The first generation of COVID-19 vaccines, which we all need so badly, is particularly focused on speed to market. In the developed world, we are concerned about durability of response and boostability of those vaccines. There’s a growing recognition of the need for a second, best-in-class wave of technologies. We’re also particularly concerned about the needs of special populations – namely, older adults. They have senescent immune systems. We believe that our virus-like particle (VLP) technology can deliver the really high titers that will be important to that elderly population.
Our VLP technology should also have the advantages of scalable manufacturing, easily maintainable temperatures in the supply chain and, we expect, sustained durability.
GD: How durable and robust is the antibody response elicited by IVX-411?
AS: VLPs are well-known for conferring durable immune responses. Some of the most effective, long-lasting vaccines are for HPV (human papilloma virus) and HBV (hepatitis B), which are VLPs. They are active for many years, so we expect a durable response for IVX-411.
The preclinical data in mice that the Institute for Protein Design published in Cell shows that a single administration of IVX-411 induced high neutralizing antibody titers. After a second dose, our vaccine candidate elicited 10-fold higher response than those seen with the soluble SARS-CoV-2 spike protein – which is the antigen used by so many other vaccine candidates. Importantly, the data in Cell also showed a strong B-cell response, which is critical for immune memory and a durable vaccine effect. Because the antibodies target multiple distinct epitopes on the RBD, the vaccine may offer protection even if the virus mutates.
Our first human trial for IVX-411, targeting the SARS-CoV-2 virus, will begin in mid-2021.
GD: You mentioned manufacturing scalability. Tell me more about that.
AS: We have started the necessary studies to support regulatory filings to get into the clinic and have initiated GMP manufacturing. The IVX-411 VLP uses the same platform as for our respiratory syncytial virus (RSV) vaccine candidate (IVX-121), which was designed for thermostability. We’re generating stability data now for IVX-411, and don’t expect it to require particularly restrictive cold storage temperatures (unlike some of the mRNA vaccines).
One of the key components of our COVID-19 vaccine is being manufactured by Amgen to support initial clinical studies. This came about because of a strategic partnership between the University of Washington’s Institute for Protein Design (which developed Icosavax’s computationally-designed VLP technology) and Amgen, which was announced in 2019. As a UW spinout, we were introduced to Amgen.
There are a lot of unique manufacturing technologies involved with vaccines. In our case, however, because our particles are engineered to self-assemble to form the VLP, we utilize traditional recombinant protein manufacturing technologies, and of course there’s none better at producing recombinant proteins than Amgen. As we move forward with development and commercialization, there are many additional manufacturers with a recombinant protein production skillset that can help with global supply.
GD: What, exactly, is IVX-411 and what’s its mechanism of action?
AS: IVX-411 is a self-assembling protein nanoparticle that displays 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array. We make the individual components and when they are combined, they self-organize into VLPs. The VLP mimics what the coronavirus looks like, with lots of RBDs sticking out. When the VLP is presented to the immune system, it looks like a virus, so the immune system ramps up to help protect the body.
Because we are using the RBD as the antigen instead of the full spike protein, we expect a high-quality immune response – i.e., a significantly improved binding:neutralizing ratio. You want high neutralizing antibody titers to help fight any infection. Having lots of antibodies that are binding but non-neutralizing can interfere with the immune response, so the ratio becomes important.
In a recent publication by David Veesler at the University of Washington, 90% of the neutralizing activity in SARS-CoV-2 exposed individuals targets the RBD. What’s particularly interesting is that in the Cell paper, when the RBD is used alone, there’s no neutralizing antibody response. This is likely why most other companies aren’t using this antigen. But when you put the RBD on the VLP, you get a really incredible immune response. Our VLP technology really transforms the usability of the RBD antigen, which appears superior to the spike protein in this paper.
GD: How does IVX-411 compare to the mRNA vaccines that are making the headlines now?
AS: The mRNA vaccines are incredible and their developers are using new technologies that are fast, from a development perspective. But, the most well-known of those vaccines use the spike protein as the antigen, not the RBD portion that we use. In the Cell paper, IVX-411 has 10-fold improvement in neutralizing activity with an approximate 5- to 6-fold lower dosage compared to the spike protein alone.
GD: How do you plan to use the new funding from the Bill and Melinda Gates Foundation and Open Philanthropy?
AS: The Bill and Melinda Gates foundation provided a $10 million grant to support the company’s COVID-19 vaccine program through the first in human Phase 1 trial in older adults, and Open Philanthropy provided $6.5 million to support development of the company’s vaccine platform technology and COVID-19 vaccine candidate. We want to help make sure that IVX-411 is ultimately available globally to help with this pandemic.
Our near term goal is to translate the preclinical results in the Cell paper into humans, with a special focus on adults age 65 and older. Our older adults focus is because 75% of deaths attributed to COVID-19 in the U.S. are in that age group.