HOOKIPA Pharma Inc. presented updated data from its ongoing Phase 2 trial of HB-200 in combination with pembrolizumab in patients with recurrent/metastatic Human Papillomavirus 16-positive (HPV16+) head and neck cancer. The preliminary data presented at the European Society for Medical Oncology (ESMO) Congress 2023 showed a 42 percent confirmed objective response rate (ORR) and disease control rate (DCR) of 74 percent across 19 evaluable patients treated with HB-200 in combination with pembrolizumab in the 1st-line, checkpoint inhibitor (CPI)-naïve setting, doubling the 19 percent ORR for pembrolizumab alone1. Best overall response for the evaluable population included one patient with a confirmed complete response, seven patients with confirmed partial responses, and six patients with stable disease.

All evaluable patients were alive at the data cutoff (DCO), and the median follow-up time at DCO was 8.3 months. Median overall survival and progression-free survival data are still maturing. Importantly, results showed significant activation of antigen-specific CD8+ T cells, the body?s primary driver of tumor killing activity.

Out of 17 patients with available peripheral blood mononuclear cells (PMBC) samples, all patients showed an increase of tumor antigen-specific circulating HPV16+ CD8+ T cells. These T cell activation data are consistent with previously reported monotherapy data for HB-200. HB-200 in combination with pembrolizumab in the 1st-line setting (NCT04180215): As of the DCO, August 7, 2023, the updated interim efficacy analysis included 19 evaluable patients with at least two imaging assessments out of the first 20 patients with HPV16+ recurrent/metastatic head and neck cancers treated with HB-200 in combination with pembrolizumab in the 1st-line setting as part of the Phase 2 trial.

Of the intent-to-treat population (n=20) one patient was not evaluable due to COVID-related death prior to the first tumor scan. All patients received HB-200 intravenously every three weeks for the first five doses and every six weeks thereafter. HB-200 is a 2-vector investigational therapy with alternating administration of Lymphocytic Choriomeningitis Virus (LCMV), and Pichinde Virus (PICV) vectors, encoding the same HPV16 E6/E7 antigens.

HB-200 in combination with pembrolizumab demonstrated promising initial anti-tumor activity with a 42 percent ORR (8 of 19 evaluable patients with confirmed responses by investigator assessment under RECIST 1.1) among CPI-naïve patients with 1st-line recurrent/metastatic HPV16+ PD-L1+ head and neck cancer. These data represent a doubling of the 19 percent ORR reported for pembrolizumab alone1 and are consistent with previously reported HB-200 data. Eight patients responded including one with a confirmed complete response and seven with confirmed partial responses.

Another six patients achieved stable disease representing a DCR of 74 percent (14 of 19 patients). While recruitment is ongoing, based on these data, HOOKIPA is preparing to start a randomized trial of HB-200 in combination with pembrolizumab as 1st-line treatment of recurrent/metastatic HPV16+ PD-L1+ head and neck cancers in 2024. Immunogenicity: Tumor-specific CD8+ T cell levels induced by HB-200 in combination with pembrolizumab are unprecedented and consistent with levels observed with HB-200 monotherapy.

Among the 17 patients with available peripheral blood mononuclear cells (PMBC) samples, all patients showed an increase in the percent of tumor antigen-specific circulating HPV16+ CD8+ T cell responses per intercellular cytokine staining analysis. Peak percentage of antigen-specific circulating HPV16+ CD8+ T cell responses reached up to 31 percent with a median of 3.36 percent. Max response on treatment vs.

before treatment of systemic HPV-16 E7 and E6 specific T cells measured by ELISPOT showed that the median fold-increase for these patients? total tumor specific T cells was a 451-fold increase over baseline, with the maximal increase of 4,000-fold. Safety and tolerability profile: Results from the HB-200 in combination with pembrolizumab in 1st-line patients arm of the Phase 2 part of the trial showed that HB-200 was generally well tolerated among 20 patients treated.

Two patients (10 percent) showed serious adverse events related to the treatment with HB-200 or pembrolizumab. Only one patient (5 percent) discontinued due to a treatment-related adverse event (related to pembrolizumab). The updated safety profile adds to the previously reported safety and tolerability data from all 132 patients across all arms of the trial who received HB-200 monotherapy or HB-200 in combination with pembrolizumab.

This generally favorable tolerability profile highlights the potential of HB-200?and arenaviral immunotherapies in general?to be successfully combined with other immunotherapies where tumor antigen-specific T cell induction is of potential benefit.