Icosavax, Inc. announced the results from an end-to-end drug product investigation of IVX-411, a VLP vaccine candidate displaying the SARS-CoV-2 receptor-binding domain (RBD). This investigation was initiated following the company's Phase 1/2 topline interim data results in which the immunologic response observed for IVX-411 was inconsistent with expectations based on known data for the company's platform and VLP technology. The investigation involved a review of in vitro antigen stability and characterization (drug substance intermediate, drug substance, and drug product), and in vivo potency, as well as a review of data and protocols relating to the transport, storage, and administration of the vaccine.

Icosavax tested a range of relevant samples, including a lab-scale VLP reference that was associated with robust and durable neutralizing titers in Non-Human Primate studiesi, and the Icosavax clinical VLP lot (GMP drug product) stored at 2-8 °C to assess its stability. Results of the investigation confirmed the company's initial hypothesis that the reduced potency observed for IVX-411 was antigen-specific (i.e., related to the Receptor Binding Domain (RBD) antigen), and data to date indicate that this antigenic instability is not observed in other Icosavax vaccine candidates, including for RSV and hMPV. Specifically: The RBD antigen component (Component A) of IVX-411 becomes unstable during manufacturing and subsequent storage at 2-8 °C. An in vivo assessment in mice demonstrated that instability of the RBD antigen on the VLP surface translated to a loss of potency for IVX-411 consistent with that seen in the company's Phase 1/2 results.

No similar pattern of instability has been seen in data to date with the company's IVX-121 (RSV) and IVX-241 (hMPV) antigen components (Component A), or the fully assembled IVX-121 and IVX-241 VLPs, at 2-8 °C.