Icosavax is advancing VLP vaccine candidates that have shown stimulation of high neutralizing antibody titers in preclinical studies. These vaccines could protect the most vulnerable populations, including older adults, against severe respiratory diseases.
VLP technology underlying all candidates is licensed from the University of Washington
* Icosavax does not plan to pursue the IVX-121 RSV monovalent candidate as a standalone candidate for RSV in older adults, and plans to transition development to the IVX-A12 bivalent RSV/hMPV candidate following Phase 1.
^ Icosavax has worldwide nonexclusive rights with exception of South Korea (which is not included in the licensed territory), which will convert to exclusive rights in North America and Europe (including Switzerland and United Kingdom) starting in 2025, with non-exclusivity maintained elsewhere. No plan to further advance IVX-411 following completion of the recent investigation and decision to focus development on a bivalent strategy.
About VLP Vaccines
Virus-like particle (VLP) vaccines have the potential to be a best-in-class, second generation vaccine that can deliver safe, effective, and durable protection with a single dose. VLPs are multiprotein structures that mimic viruses but lack the viral genome. Because they contain no genetic material, they are non-infectious and can potentially provide a safer alternative to other vaccine technologies.
IVX-121: RSV VLP Vaccine Candidate
IVX-121 targets respiratory syncytial virus (RSV), a major cause of viral pneumonia for which no vaccine has been FDA approved. IVX-121 incorporates a stabilized prefusion F antigen licensed from NIAID/NIH (DS-Cav1; Science 2019). RSV F is known to undergo major structural changes that allow viral entry into the host cell, and during that process, critical protective epitopes are lost. Protein design methods have stabilized prefusion F, leading to improved neutralizing responses in humans.
Our VLP technology further enhances the magnitude, quality and durability of the response to prefusion RSV F, as shown in extensive preclinical studies conducted at IPD (Cell 2019) and Icosavax. The enhanced response to VLP-based prefusion F could be particularly important in older adult populations that show reduced responsiveness to conventional vaccines due to immunosenescence and is expected to translate into a superior product profile.
IVX-A12: RSV/hMPV Bivalent VLP Vaccine Candidate
IVX-A12 is a bivalent combination of IVX-121 and IVX-241, a human metapneumovirus (hMPV) VLP vaccine candidate. IVX-A12 is being designed to target both RSV and hMPV in a single vaccine candidate. hMPV is being increasingly recognized as a major contributor to acute respiratory infection and pneumonia with rates of pneumonia (Clinics in Chest Medicine 2017) and hospitalization (JID 2012) similar to that of RSV and influenza. RSV, hMPV, and influenza seasons show high seasonal overlap and have similar clinical presentation; as such, hMPV is underdiagnosed and often mistaken for RSV or influenza given the similarity in clinical presentation. There are no FDA approved vaccines for hMPV. Similar to RSV, prospective cohort studies have shown that higher baseline hMPV nAbs are associated with reduced risk of hMPV symptomatic virus infection (Vaccine 2010), so the goal of vaccination is to increase hMPV nAbs.
Our hMPV candidate IVX-241 incorporates a pre-fusion stabilized F protein antigen and was selected based on its stability profile and ability to induce high nAb titers in preclinical studies.
We believe combining two VLP vaccine candidates, IVX-121 and IVX-241, into a single combination vaccine, IVX-A12 will provide potential benefit to vaccinators and patients over monovalent vaccines in clinical development.
About RSV and
For older adults, RSV can be a life-threatening respiratory infection, with comparable severity to that of influenza.
Respiratory syncytial virus (RSV) causes infection of the respiratory tract, with symptoms that can sometimes be confused with influenza. It is a ubiquitous pathogen that infects 100% of the population by age 2. With outbreaks each year during the Northern Hemisphere winter, RSV is a major viral cause of pneumonia, which is most severe in infants and young children and in older adults (NEJM 2005). Worldwide, RSV disease affects an estimated 64 million people and causes 160,000 deaths each year (NIAID). There are no specific antiviral therapies or vaccines for RSV.
In the United States, it is estimated that more than 177,000 older adults are hospitalized, and 14,000 of them die due to RSV infection (CDC). The highest burden of RSV healthcare costs in the United States are in those aged ≥65 years (PLOS ONE 2017). Estimates of total RSV-attributable healthcare costs for all elderly aged ≥65 years in the United States range $150 million–$680 million to $1 billion (BMC Health Services Research, 2018).
The global cost in lives and health care expenditures is significant, especially amongst the very young and very old, and a vaccine solution is desperately needed.
“An effective RSV vaccine could help millions of people around the world to relieve a substantial disease burden and reduce significant healthcare costs.”
– Tadataka (Tachi) Yamada, M.D., co-founder of Icosavax
IVX-411: SARS-CoV-2 VLP Vaccine Candidate
IVX-411 targets SARS-CoV-2, the coronavirus that causes COVID-19. Developed using cutting-edge structure-based design techniques at the Institute for Protein Design at the UW School of Medicine, IVX-411, our lead vaccine candidate for COVID-19, 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.
Preclinical data on IVX-411 and precursor candidates in mice and non-human primates show induction of robust neutralizing antibody titers and protection from viral challenge (Cell 2020, Nature 2021). Titers after the second administration were ten-fold higher than those seen with the soluble SARS-CoV-2 spike protein that forms the basis of many other vaccine candidates. The data also show a strong B-cell response after immunization, critical for immune memory and a durable vaccine effect, with antibodies that target multiple distinct epitopes on the RBD, suggesting potential protection from escape mutations.
Icosavax has received a $10 million grant from the Bill & Melinda Gates Foundation to support the company’s COVID-19 vaccine program through the first in human Phase 1 clinical trial in young and older adults. Clinical trials are underway.
IVX-421: SARS-CoV-2 Beta (B.1.351) Variant VLP Vaccine Candidate
Icosavax has initiated development of IVX-421, a SARS-CoV-2 vaccine candidate that incorporates an RBD antigen with critical mutations found in the SARS-CoV-2 beta strain.
and Older Adults
Adults over 65 account for over 75% of all COVID-19 deaths in the U.S.
COVID-19 symptoms can range from no symptoms to severe illness. Older adults and people of any age who have serious underlying medical conditions may be at higher risk for more severe illness. Vaccines are especially important for older adults, as their immune systems weaken (immunosenescence) making it more difficult to fight off infections. This can lead to long-term illness and life-threatening complications; adults over 65 account for over 75% of all COVID-19 deaths in the U.S. (CDC). Most currently used vaccines are less immunogenic and effective in the elderly compared to younger adults. Thus new vaccine technologies that can deliver higher immunogenicity and greater efficacy are greatly needed, especially for older adults