Icosavax, Inc. announced topline interim results from its ongoing Phase 1/2 clinical trial of IVX-411, a VLP vaccine candidate displaying the SARS-CoV-2 receptor-binding domain (RBD). The ongoing Phase 1/2 clinical trial (IVX-411-01) is a randomized, observer-blinded, placebo-controlled study to evaluate the safety and immunogenicity of IVX-411 in SARS-CoV-2 naïve (N=84) and previously vaccinated (N=84) adults 18 to 69 years of age. Naïve subjects received two doses, given 28 days apart, of IVX-411 at 5, 25 or 125 ug dosage levels or placebo, with or without adjuvant.

Previously vaccinated subjects were boosted with a single dose of IVX-411 at 5, 25 or 125 ug or placebo, with or without adjuvant, at 3-6 months following completion of primary licensed vaccine regimen (mRNA or adenoviral). A supplemental analysis was also conducted to assess whether sera from subjects immunized with IVX-411 neutralize the SARS-CoV-2 Omicron variant. In this topline interim data, IVX-411 was generally safe and well-tolerated.

Solicited local and systemic adverse events (AEs) were all mild or moderate, without dose-limiting reactogenicity. The most common local and systemic AEs were injection site tenderness, and headache and fatigue, respectively. There were no serious AEs deemed to be related to vaccine, AE of special interest, or AEs leading to discontinuation.

In the naïve setting, across the six dosage groups for IVX-411 with or without adjuvant, the proportion of subjects experiencing any systemic AE within seven days of any dose was 33-67%, versus 50% for placebo. In the booster setting, across the six dosage groups, 17-42% of subjects experienced any systemic AE within seven days of the booster dose, versus 25% for placebo. In the naïve setting, a clear adjuvant effect on immunogenicity and a dose response were observed with IVX-411; however, the level of immune response in this initial data was comparable to or below the Human Convalescent Sera (HCS) control.

At day 49 (or three weeks following the second dose), responses were up to 154 IU/mL across dosage groups in the live virus neutralization assay (HCS: 281 IU/mL), and up to 592 BAU/mL across groups in the spike IgG assay (HCS: 361 BAU/mL). In previously vaccinated subjects, these initial data showed that IVX-411 boosted immunity following primary vaccination with an mRNA or adenovirus vaccine, and adjuvanted and unadjuvanted groups were generally similar. Pre- versus post-boost fold increases of up to 5x (599 IU/mL) for wild type virus were observed at day 28 post boost.

For the Omicron variant, neutralizing antibody titers were up to 8-fold lower than observed for wild type virus in the same assay.