D3.447 - Pre-clinical Toxicology and Immunogenicity Evidence as a Precursor of the Successful Phase I/IIA Study with VLP Peanut

VLP Peanut is a next-generation nanoparticle-based treatment candidate for peanut allergy. Pre-clinical toxicology and immunogenicity studies in animal models (rat) were conducted to evaluate immunogenic clinical translational potential of VLP Peanut and fulfil pre-clinical toxicology regulatory requirements to support the first-in-human (FIH) Phase I/IIa clinical trial - PROTECT. Here we present findings from the dose-response immunogenicity and repeat dose toxicology studies in animal models and translation of the findings to Phase I/IIa clinical development of VLP Peanut.

A repeat dose toxicology study in rodents was conducted with control, 0.9 or 3.6 mg/rat VLP Peanut administered subcutaneously every 27-28 days for 12-weeks followed by a 4-week treatment recovery period. Systemic and local adverse changes were evaluated during the dosing period and after the 4-week recovery. An immunogenicity study was performed in rats that received escalating doses of 3 subcutaneous injections every 2 weeks. Time and dose-dependent IgG responses to CuMV_TT and Ara h2 components of VLP Peanut were assessed and correlated with the dose administered.

Repeated subcutaneous doses of VLP Peanut revealed no safety concerns at up to 3.6 mg/rat. Toxicity findings were restricted to minor non-adverse systemic effects and local site reactogenicity. Evaluation of immunogenicity responses demonstrated strong immune response (sIgG) against both Ara h2 and CuMV_TT antigens. The maximum levels of Ara h2 and CuMV_TT sIgG were measured after the third dose (Day 42) of VLP Peanut and were significantly higher (all, p ≤0.01) compared to the sIgG levels induced after the first dose. Ara h2 sIgG titers were predominant antibodies induced by VLP Peanut (3-fold higher compared to CuMV_TT sIgG), thus confirming that induced IgG titers were primarily against the antigen of interest -Ara h2. CuMV_TT IgG and Ara h2 titers induced post immunization demonstrated moderate positive and significant (p=0.041 and p=0.050, respectively) correlation with the dose administered.

Toxicology and immunogenicity assessment of VLP Peanut in rodents demonstrated compelling evidence of its benign safety profile and immunogenic translation potential to clinic. Findings from these studies were used to plan and support the FIH Phase I/IIa clinical trial PROTECT, which is in the final stage of completion.