Pharma Equity Group’s subsidiary, Reponex Pharmaceuticals A/S, reports highly positive final results from the phase-2 clinical trial of the company’s patented drug candidate RNX-051. - Seite 2

Protocol
Twelve patients and ten patients were treated in the respective arms of the trials with RNX-051 given in a muco-adhesive spray and the adenomas or tumor were removed approximately one week after the intervention. Through advanced microscopy analyses targeting certain bacteria and certain cells of the tumor microenvironment, and advanced immune analyses including genomic analyses of both the bacteria and the precursor and cancer lesions, an in-depth overall picture of the precursor lesions and the cancer before and after treatment was obtained.

Results
In the adenoma arm, the main goal of the study, to demonstrate an impact on the bacterial biomass, was reached, with a massive reduction in the biofilm of the bowel lining (more than 30-fold reduction) one week after the treatment, from a mean of 0.003% to 0.0001% of bacterial biomass (p=0.025). An impact on the occurrence of specific immune-cells known to be crucial in the immune response against cancer was shown (macrophages and T-cells). For macrophages, the density was 2.2% in non-treated adenomas and 3.4% in treated adenomas (p=0.030), and for CD3 T-cells, the density was 524 cells/mm² in non-treated adenomas and 727 cells/mm² in treated adenomas (p=0.018). In the metagenome sequencing to assess the diversity of bacteria and the specific composition of bacteria before and after treatment, there was no reduction in the diversity of bacteria, while there was an increase of the genus Bacteroides (median 6.9% vs 10.8% , p=0.016), a commensal gut bacterium containing both anti- and pro-inflammatory species.

In the cancer arm, for patients with a high content of bacterial biofilm, there was a statistically significant reduction of biofilm in the tumor periphery from a mean of 0.255% to 0.013% of bacterial biomass (p=0.025). At the same time, a shift in the balance of immune cells in the tumor core could be seen, resulting in an increase in the ratio of T-cells that are particularly active in promoting tumor cell death, from a mean 0.30 CD8/CD3 ratio to a mean ratio of 1.19 (p=0.016). In the metagenome sequencing to assess the diversity of bacteria and the specific composition of bacteria before and after treatment, a clear and statistically significant effect was seen. The RNX-051 application drastically reduced or eliminated the cancer-promoting Fusobacterium nucleatum (median 15.2% to 0%, p=0.008) and increased the cancer-protecting Lactobacillales (median 0.23% to 2.72% p=0.023) in the tumor center without reducing the diversity of the mucosa-associated gut microbiota.