Silexion Therapeutics’ SIL-204 shows potential to transform pancreatic cancer treatment
Silexion Therapeutics Corp. (NASDAQ: SLXN), a clinical-stage biotechnology company specializing in RNA interference (RNAi) therapies, has reported promising preclinical results for its next-generation therapeutic candidate, SIL-204. These findings provide critical validation for systemic administration as an effective delivery approach for targeting aggressive cancers like pancreatic cancer. The results revealed significant tumor growth inhibition in clinically relevant orthotopic models, marking a breakthrough in efforts to treat cancers driven by KRAS mutations.
With pancreatic cancer being one of the most difficult-to-treat malignancies, the ability to target these mutations systemically presents a potential paradigm shift in oncology. Silexion is now advancing research into how SIL-204 could address metastatic cancers, further expanding its impact.
How Does SIL-204 Work Against KRAS-Driven Cancers?
KRAS mutations are among the most prevalent oncogenic drivers, implicated in various solid tumors, including pancreatic, colorectal, and lung cancers. Silexion’s SIL-204 employs RNA interference technology to silence specific KRAS mutations, such as G12D, G12V, G12R, Q61H, and G13D, effectively reducing tumor growth and progression.
The systemic administration of SIL-204 offers a distinct advantage over traditional localized therapies by enabling the therapeutic to reach tumors more comprehensively, even in challenging metastatic settings. According to the preclinical data, SIL-204 achieved robust therapeutic activity across multiple cancer models, maintaining effective drug levels in plasma and tissues for extended durations.
What Do the Latest Preclinical Data Reveal?
The study highlighted several key findings that underscore the efficacy of SIL-204:
- In human pancreatic cancer models harboring the KRAS G12D mutation, SIL-204 reduced tumor growth by approximately 50% within 30 days, with nearly half of the tumors exhibiting complete necrosis.
- Subcutaneous administration in metastatic pancreatic orthotopic models effectively inhibited tumor progression, demonstrating its suitability for systemic treatment.
- A single dose of SIL-204 maintained therapeutic drug levels in rat plasma and tissues for over 56 days, emphasizing its potential for prolonged activity.
- Intratumoral administration further reduced tumor cell numbers and tumor area, while significantly increasing necrosis, proving its efficacy in localized treatment scenarios.
These results position SIL-204 as a versatile therapeutic with applications in both systemic and localized settings, making it an essential advancement in the fight against KRAS-driven cancers.
How Could SIL-204 Improve Pancreatic Cancer Treatment?
Pancreatic cancer remains one of the deadliest cancers, with limited treatment options and a five-year survival rate of less than 10%. Current approaches are often limited by the cancer’s rapid progression and resistance to therapies. SIL-204’s ability to inhibit KRAS mutations systemically offers a new avenue for tackling this aggressive disease.
Mitchell Shirvan, Ph.D., Chief Scientific Officer at Silexion Therapeutics, remarked, “These findings showcase the transformative potential of systemic administration for addressing KRAS-driven cancers. SIL-204’s robust tumor growth inhibition in clinically relevant models highlights its ability to target advanced and metastatic cancers effectively. We are optimistic about its impact on metastatic progression, which remains a significant challenge in oncology.”
Silexion’s work builds on the success of its first-generation therapeutic, LODER, which showed promise in Phase 2 trials for non-resectable pancreatic cancer. SIL-204, as the company’s next-generation RNAi therapy, represents a leap forward by targeting a broader range of mutations and demonstrating prolonged efficacy.
What’s Next for Silexion and SIL-204?
With these promising preclinical results, Silexion Therapeutics plans to expand its development program to evaluate SIL-204’s efficacy in treating metastatic cancers and other solid tumors driven by KRAS mutations. The company is also investigating how this approach could complement existing cancer therapies to create a more comprehensive treatment strategy.
Further studies are anticipated to assess SIL-204’s impact on metastases, an area where few effective therapies currently exist. Silexion’s commitment to pushing the boundaries of RNAi therapy innovation places it at the forefront of oncology research, with the potential to redefine treatment outcomes for patients with hard-to-treat cancers.
Why SIL-204 Matters in the Broader Oncology Landscape
The introduction of systemic RNAi therapies like SIL-204 marks a shift in cancer treatment, offering a targeted and durable approach to combating genetic drivers of malignancies. By focusing on KRAS mutations, Silexion is addressing a critical unmet need in oncology, paving the way for therapies that can improve survival rates and quality of life for patients.
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