Silenseed Reveals New Data: SIL204 May Help the Immune System Recognize and Attack Tumors

New preclinical data indicate that the treatment developed by the Israeli company acts on three key mechanisms by which cancer tumors evade the immune system, and strengthens the scientific basis for examining it in combination with anti-PD-(L)1 immunotherapy treatments.

The Israeli biotechnology company Silenseed Therapeutics (Nasdaq: SLXN) reports new preclinical findings indicating that its lead treatment, SIL204, may not only silence the cancer gene KRAS, but also make tumor cells more sensitive to immune system activity.

KRAS is one of the main genetic drivers in the development of cancer. Mutations in the gene appear in about 90% of pancreatic cancer cases and in about 30%–35% of lung adenocarcinoma cases. For years, KRAS has been considered one of the most challenging targets for drug development. SIL204, based on RNA interference technology, is designed to specifically silence the expression of mutant KRAS in cancer cells. Studies conducted on human pancreatic cancer cells and non-small cell lung cancer (NSCLC) cells carrying a variety of KRAS mutations found that the treatment acted simultaneously on three key immune pathways.

The treatment increased the expression of MHC-I, which helps cancer cells present antigens to the immune system, thereby enabling their identification. In addition, an increase in the expression of FAS ("the death receptor") was observed, which may allow immune system cells to reactivate a mechanism of programmed cell death in tumor cells. At the same time, a decrease was recorded in the expression of HLA-G, a molecule that helps tumors suppress the immune system's response and evade it.

Simply put, the data indicate that SIL204 may act on three fronts simultaneously: helping the immune system identify the tumor, increasing its sensitivity to immune attack, and reducing the evasion mechanisms it uses. The findings may have special significance in the field of immunotherapy. Treatments based on immune checkpoint inhibitors have revolutionized the treatment of several types of cancer, but in pancreatic cancer, their effectiveness as a single treatment is still limited. One of the reasons for this is that pancreatic tumors are sometimes considered "cold tumors" from an immunological perspective — those that the immune system finds difficult to identify and penetrate.

The new findings strengthen the possibility that SIL204 could in the future make these tumors more sensitive to immunotherapy, and support its examination in combination with anti-PD-1 or anti-PD-L1 treatments. However, it is important to emphasize that at this stage these are preclinical findings, and further studies are required to examine whether these effects will also translate into clinical benefit for patients.

According to Ilan Hadar, Chairman and CEO of Silenseed Therapeutics:

"We now see that SIL204 acts in a coordinated manner on three of the key mechanisms by which KRAS-driven tumors evade the immune system. The data strengthen the immuno-oncological profile of the treatment and the scientific rationale for examining its combination with immune checkpoint inhibitors, especially in types of cancer where immunotherapy alone has shown limited effectiveness to date."

The findings are being published in parallel with the company's clinical progress. At the end of July, Silenseed activated the first trial site as part of a phase 2/3 study in patients with locally advanced pancreatic cancer at the Ichilov Medical Center, ahead of the start of patient screening. The combination of clinical progress and the new preclinical data expands the scientific basis of SIL204 and strengthens its potential — both as a targeted KRAS treatment and as part of future combined immunotherapy treatment strategies.