N4 Pharma posts optimistic Nuvec research update

The AIM-traded company said its ongoing double-loaded siRNA research had made significant strides, indicating that Nuvec held substantial potential in knocking down two independent pathways, potentially leading to more effective cancer treatments by reducing the likelihood of tumour escape.

Over recent months, N4 has been investigating the ability of Nuvec nanoparticles to simultaneously load and deliver two different siRNA molecules known to inhibit relevant oncology targets.

The results demonstrated that Nuvec could load two separate siRNA molecules without altering their size or charge - crucial for successful cellular uptake.

Initial investigations focussed on inhibiting epidermal growth factor receptor (EGFR) and B-cell lymphoma 2 (BCL-2) using PC-9 cancer cells.

While each siRNA, when separately loaded onto Nuvec, achieved cell inhibition, the expression level of BCL-2 in PC9 cells was extremely low, making it challenging to measure a knockdown response curve.

As a result, alternative cellular pathways such as Bromodomain-containing-protein 4 (BRD4) and Polo Like Kinase 1 (PLK1) were explored as potential targets for siRNA loaded alongside EGFR.

Nuvec successfully loaded with individual siRNA molecules and effectively knocked down the respective targets while reducing cell viability dose-dependently.

However, an interaction occurred when BRD4 or PLK1 were loaded alongside EGFR, resulting in a reduced knockdown of the EGFR receptor.

Nevertheless, the reduction in cell viability was maintained.

N4 said the mechanism behind this interaction was under investigation, with potential explanations including the lack of correlation between knockdown and functional cell death.

The firm planned to vary the amount of each siRNA loaded on Nuvec to understand how it affected the degree of interaction while maintaining cellular inhibition.

Additionally, investigations would be carried out to determine the lowest effective dose for achieving functional cell inhibition, potentially offering a dose-sparing advantage with Nuvec.

Regarding oncology strategy, N4 said it recognised that the precise combinations of siRNA in terms of target and concentration may vary depending on the specific cell type and desired clinical outcome.

“There has been a lot of work undertaken in what is a highly complex scientific area and we have repeatedly shown that Nuvec is successful in always loading and delivering dual siRNA, however the interactions between the siRNA vary depending on which two are chosen and which cells they are tested in so we continue to test these interactions,” said chief executive officer Nigel Theobald.

“The work we have done so far is extremely encouraging and is demonstrating that Nuvec has considerable potential to be able to knockdown two independent pathways leading to more effective cancer treatments by reducing the ability for tumour escape.

“This is a highly desirous and innovate approach in developing novel cancer treatments.”

At 1223 GMT, shares in N4 Pharma were up 3.45% at 0.78p.

Reporting by Josh White for Sharecast.com.