Staying Ahead of Viral Evolution: Q&A with Robert Allen, Ph.D

In a conversation with Pharmaceutical Executive, Robert Allen, Ph.D., chief scientific officer, Invivyd discussed how the company's Invymab platform pairs viral surveillance and predictive modeling with antibody engineering to stay ahead of viral evolution rather than react to it.

Dr. Allen explains that because viruses evolve rapidly and each family, genus, and variant is immunologically unique, the platform is built to anticipate escape mutations, continuously generate new monoclonal antibody candidates, and produce a sequential series of antibodies deployable as viruses change. Surveillance and modeling data map mutational escape routes and help predict which future variants are likely to dominate, allowing Invivyd to design antibodies proactively rather than against only current strains.

In the conversation, Dr. Allen also discussed VYD2311, positioned as a scalable prophylactic option that could serve as an alternative or complement to vaccination against Covid-19, particularly for individuals affected by vaccine hesitancy or other barriers to vaccine uptake. He described how Invivyd is applying its platform in parallel across Covid-19, RSV, and measles, noting that the underlying design engine, including B cell mining and iterative antibody engineering, is repeatable across viruses even as target selection and mutation patterns demand virus-specific science.

Reflecting on more than 30 years in infectious disease prevention, Dr. Allen pointed to advances in molecular immunology and cryo-EM methodologies that have improved the mapping of antibody-epitope interactions, while noting that improving serum half-life and scalability remain unsolved challenges for expanding access to this class of medicines.

A transcript of Dr. Allen's conversation with Pharmaceutical Executive can be found below.

Pharmaceutical Executive: Invivyd's Invymab platform combines viral surveillance and predictive modeling with antibody engineering. How do those two capabilities feed each other and how does it change what you build?
Dr. Robert Allen: We developed our proprietary monoclonal antibody platform specifically to address a key limitation in the development and construction of antiviral biologics: viruses evolve rapidly, which may render single monoclonal antibodies (mAbs) obsolete over time.

Our platform is fundamentally shaped by the need to address the fact that each family, genus, and variant species of virus is unique from an immunologic perspective and that new virus variants emerge at different rates based on population and individual immune protection status for each virus encountered. The platform allows us to anticipate and quickly respond to viral evolution rather than react after escape variants emerge, continuously generate new mAb candidates instead of relying on one specific antibody, and we can produce a “series” of antibodies that can be deployed sequentially as viruses change.

Viral surveillance and predictive modelling support the platform by continuously monitoring viral evolution across circulating strains and map “mutational escape routes”—i.e., the specific mutations that allow viruses to evade antibodies. By using this data, we can predict future variants before they become dominant.

So, in short, instead of designing antibodies against only current variants, our surveillance and modelling capabilities provide us with the ability to proactively design antibodies against likely future viral variants.

PE: VYD2311 is positioned as a "vaccine-alternative" for Covid-19. Who is this product designed for, and what gap does it fill that vaccines don't?
Dr. Allen: Fundamentally, what we are hoping to achieve is quite simple, to develop monoclonal antibodies that can help keep millions of Americans healthy. If we are successful in clinical trials and advance VYD2311 through development and regulatory approval, we see this compound that could be used as an alternative to or as a complement to a vaccine as a scalable prophylactic option capable of protecting millions of Americans from Covid-19.

The limitations that are inherent in vaccines are also some of the major barriers that impact their uptake. Another challenge is vaccine hesitancy. This can be rooted in a number of things, including personal beliefs, concerns about side effects, etc., but at the end of the day it is beginning to impact public health. We have a set of individuals who appear to need more choice in order to help themselves.

Our goal is to provide options for Americans who seek options. Monoclonal antibodies are the natural next step to help protect millions of Americans from Covid-19.

PE: Invivyd is now pursuing Covid, RSV and measles in parallel. Where does your platform give you leverage across all of those, and where does each disease demand its own bespoke science?
Dr. Allen: The platform is designed to scale across viruses such as, Covid, RSV, measles, other and emerging viral threats. The ability for the platform to stretch from virus to virus comes from repeatable capabilities, not repeatable antibodies.

Across all viruses, the platform uses the same core design engine: viral surveillance and predictive modeling, B‑cell mining to find broadly neutralizing antibodies for specific viruses and iterative engineering (affinity maturation, half-life extension) to optimize the breadth and other desired properties of the final candidate antibody.

While the platform leverages repeatable capabilities to advance mAbs for each virus, the molecular biology of each virus dictates what to target in development. This includes target selection where each virus has its own unique protein makeup, and each has a core set of vulnerable proteins which we hope to target with our mAbs.

PE: You've spent over 30 years in infectious disease prevention. What's now scientifically possible in antiviral antibody development that wasn't when you started, and where are the hardest problems still unsolved?
Dr. Allen: 30 years ago, the ability to identify and optimize monoclonal antibodies from patient materials was driven in large part by hybridoma technology in combination with iterative antibody engineering efforts. Over the past decades, advances in molecular immunology have made it possible to catalog immune responses to vaccination or infection.

Technical improvements to Cryo EM methodologies have also allowed for greater ease in mapping paratope:epitope interactions. Epitopes are selected for intrinsic structural properties as well as their relative conservation among the clinical and wastewater sequencing data that has continued to increase in quality over the past 30 years.

We still work to improve both the serum half-life and the scalability of our antibody candidates, and these advances could serve to further increase access and affordability of this class of medicines.