Ultimovacs (Norway)

Human telomerase reverse transcriptase is highly expressed in head and neck squamous cell carcinoma (HNSCC). The FOCUS study examines the role of the telomerase-directed vaccine UV1 in combination with pembrolizumab in patients with recurrent or metastatic (R/M) HNSCC. The FOCUS trial, a two-armed, open-label, randomized, multicenter phase 2 study, was designed to assess the efficacy and feasibility of UV1 as an add-on to pembrolizumab in the first-line treatment of patients with R/M PD-L1+ HNSCC. A progression-free survival (PFS) rate at 6 months of 40% was deemed promising for further development in a phase 3 setting. The trial was conducted in 10 centers in Germany (this study was registered at ClinicalTrials.gov: NCT05075122). From August 2021 to July 2023, 25 patients were enrolled in the pembrolizumab arm and 50 patients in the pembrolizumab + UV1 arm. The PFS rate at 6 months was 40% in the pembrolizumab arm and 30% in the pembrolizumab + UV1 arm. No specific safety signals were observed in the pembrolizumab + UV1 arm apart from a reversible allergic reaction that appeared in one patient. At a median follow-up of 11.3 months, median overall survival was 13.1 months in the pembrolizumab arm and 12.6 months in the pembrolizumab + UV1 arm. The addition of UV1 to pembrolizumab was safe but did not show an efficacy signal in this study population. The legal sponsor of the trial was the University Medical Center Halle (Saale), Germany and was funded by a grant from Ultimovacs.

During the current COVID-19 pandemic, a need for evaluation of already available drugs for treatment of the disease is crucial. Hereby, based on literature review from the current pandemic and previous outbreaks with corona viruses we analyze the impact of the virus infection on cell stress responses and redox balance. High levels of mortality are noticed in elderly individuals infected with SARS-CoV2 and during the previous SARS-CoV1 outbreak. Elderly individuals maintain a chronic low level of inflammation which is associated with oxidative stress and inflammatory cytokine production, a condition that increases the severity of viral infections in this population. Coronavirus infections can lead to alterations of redox balance in infected cells through modulation of NAD + biosynthesis, PARP function along with altering proteasome and mitochondrial function in the cell thereby leading to enhanced cell stress responses which further exacerbate inflammation. ROS production can increase IL-6 production and lipid peroxidation resulting in cell damage. Therefore, early treatment with anti-oxidants such as NAC during COVID-19 can be a way to bypass the excessive inflammation and cell damage that lead to severe infection, thus early NAC as intervention should be evaluated in a clinical trial setting.