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Background VerImmune is developing VERI-101, a novel immune-oncology therapeutic candidate that redirects pre-existing human cytomegalovirus (HCMV) CD8+ memory T-cells to recognize and eliminate tumor cells. VERI-101 is based on VerImmune’s proprietary Virus-inspired Particles (ViPs), which naturally target tumors. Each ViP is composed of 60 copies of a papillomavirus-derived capsid that self-assembles into a T=1 icosahedral structure. ViPs are surface-conjugated with a CD8+ T cell viral peptide antigen. With VERI-101, the ViP is conjugated with an HLA-A*0201 restricted peptide epitope (NLVPMVATV, [NLV]), derived from the CMV pp65 antigen with an upstream furin protease cleavage site. The efficacy of VERI-101 and its surrogate product (VERI-003) has been demonstrated. To support clinical development, additional efficacy studies were conducted with a focus on safety.Methods Two types of in vivo studies were performed: (1) A preliminary repeat-dose toxicity study at a dose of 400µg in naïve mice to assess acute toxicity of VERI-101, and (2) an efficacy study in a murine cytomegalovirus (mCMV) model that recapitulates the natural infection of CMV to assess in vivo tumor efficacy and pharmaco-dynamic safety observations. VERI-101 could not be used in this latter study as HCMV does not infect mice. Instead, a surrogate product VERI-003 was used as a monotherapy or in combination with anti-PD-1 in PD-1-resistant MC38 tumor-bearing mice. Safety endpoints including body weight, temperatures, inflammatory cytokine expression and histology were collected from these mice.Results Both VERI-101 and VERI-003 treatment showed no indications of treatment-related toxicities. In addition, VERI-003 or combination treatment led to statistically significant reductions in tumor growth and in certain cases, complete regression of tumors compared to untreated controls.Conclusions Overall, current data indicates a good safety profile for VERI-101 with no maximum tolerated dose observed. Collectively, our previous and current results demonstrate the tumor antigen-agnostic therapeutic potential of VERI-101 as a potentially safe and effective novel class of immuno-therapeutic drugs known as Virus-inspired Drug Conjugates (ViDCs), which can be used either as a monotherapy or in combination with checkpoint inhibitors.Ethics Approval This study was conducted under Aragen’s Animal Use Protocol AUP_24-0516-M (Non-GLP Study: Evaluating Efficacy of Antiviral Biotherapeutics against mouse Cytomegalovirus infection in mice) and AUP_24-0712-MR (Oncology Preclinical Service: Anti-Cancer Efficacy and Other Studies (Pharmacokinetics, Pharmaco-dynamics, and MTD) in Rodents).