Silexion Therapeutics Announces Groundbreaking Preclinical Results: SIL204 Shows Strong Efficacy in Pancreatic, Colorectal, and Lung Cancers
- Strong efficacy with ~90% inhibition rate in colorectal cancer cells
- Demonstrated effectiveness across three major cancer types (pancreatic, colorectal, and lung)
- Drug shows activity at very low (nanomolar) concentrations
- Potential to address a $30+ billion market across three cancer indications
- Enhanced delivery system through lipid-conjugated technology
- Results are only in preclinical stage, requiring extensive further testing
- Additional studies still needed for lung cancer cell lines
- No human trial data available yet
Insights
Silexion's RNAi therapy SIL204 shows ~90% inhibition of KRAS-mutated cancer cells in preclinical studies, expanding potential applications beyond pancreatic cancer.
The preclinical data for Silexion's SIL204 represents a scientifically significant advancement in RNAi therapeutics targeting KRAS mutations. The ~90% inhibition rate observed in colorectal cancer cells is particularly impressive, as achieving such high efficacy in preclinical models is uncommon. What's scientifically noteworthy is that SIL204 demonstrated efficacy across three different KRAS G12D-mutated cancer cell lines (colorectal, lung, and pancreatic), suggesting a mechanism that effectively targets a fundamental cancer driver regardless of tissue origin.
The dose-dependent response extending to nanomolar concentrations indicates potent activity at clinically achievable doses. The lipid-conjugated delivery system appears to enhance cellular uptake - a crucial advancement as delivery has historically been the primary challenge for RNA therapeutics. This modification likely improves the drug's ability to cross cell membranes and reach the cytoplasm where the RNAi machinery operates.
From a technical perspective, targeting KRAS at the RNA level potentially overcomes the limitations of protein-targeting approaches. KRAS has been notoriously difficult to drug directly at the protein level due to its smooth surface lacking clear binding pockets. By silencing the gene before protein production, SIL204 circumvents these structural challenges.
However, these remain preclinical results - the transition from cell culture to animal models and eventually humans often reveals limitations not apparent in vitro. Many promising cancer therapeutics show impressive results in cell lines but fail to translate to clinical efficacy due to delivery challenges, off-target effects, or resistance mechanisms. The true test will be whether SIL204 can maintain this efficacy in more complex biological systems while demonstrating an acceptable safety profile.
Silexion's preclinical RNAi therapy shows strong potential against three major cancer types with $30B+ market opportunity.
Silexion's preclinical results for SIL204 represent a potential breakthrough in addressing KRAS mutations - one of oncology's most elusive and high-value targets. The significance extends beyond the impressive 90% inhibition rate in colorectal cancer cells to the broader therapeutic potential across three major cancer indications with substantial commercial opportunity.
The addressable market is substantial: KRAS mutations drive approximately 90% of pancreatic cancers, 45% of colorectal cancers, and 35% of non-squamous NSCLC. Collectively, these indications represent treatment markets exceeding $30 billion annually, according to the company's cited figures. While several companies have recently brought KRAS-targeting therapies to market (primarily for the G12C mutation), most KRAS variants remain undruggable with conventional approaches.
Silexion's RNAi approach targeting the G12D mutation is particularly noteworthy as this variant is especially common in pancreatic cancer but has proven resistant to small molecule approaches. The nanomolar potency demonstrated in these preclinical studies suggests potential for effective dosing in humans, though delivery remains a critical consideration for any RNA therapeutic.
The lipid-conjugated delivery system appears to enhance cellular uptake without external carriers, potentially addressing a key limitation of RNA therapeutics. This could translate to improved bioavailability and reduced dosing requirements if confirmed in clinical studies.
While these results are promising, investors should recognize the significant gap between preclinical efficacy and FDA approval. The company must still demonstrate successful translation to animal models, establish safety parameters, and navigate the lengthy clinical trial process. Additionally, the competitive landscape for KRAS-targeting therapies continues to evolve rapidly with multiple approaches in development across the industry.
Silexion’s Revolutionary RNAi approach demonstrates powerful anti-tumor activity across three major KRAS-driven cancer types; Inhibition rate of ~
GRAND CAYMAN, Cayman Islands, May 29, 2025 (GLOBE NEWSWIRE) -- Silexion Therapeutics Corp. (NASDAQ: SLXN) ("Silexion" or the "Company"), a clinical-stage biotechnology company pioneering RNA interference (RNAi) therapies for KRAS-driven cancers, today announced compelling preclinical data demonstrating the efficacy of its next-generation RNAi therapeutic candidate, SIL204, against human pancreatic, colorectal and lung (NSCLC) cancer cell lines. These results significantly expand SIL204's therapeutic potential beyond pancreatic cancer, allowing it to potentially address major KRAS-driven cancers with substantial unmet medical needs.
Following the Company's recent announcement of completion of preclinical studies, a comprehensive analysis of the data has revealed that SIL204 effectively inhibited the proliferation and metabolic activity of human cancer cell lines harboring KRAS G12D mutations across multiple cancer types, resulting in the following obvervations:
- The data reveals SIL204 successfully inhibited the proliferation and metabolic activity of human cancer cell lines harboring a specific KRAS mutation (G12D): GP2D (colorectal), A427 (lung) and Panc-1 (pancreatic), in a statistically significant manner.
- The significant inhibition was observed in a dose-dependent manner down to nanomolar concentrations.
- As observed in the left hand graph below (figure 1), a dose-dependent reduction in cell viability was noted in GP2D colorectal cancer cells, even in the absence of external additives, due to the lipid end of SIL204.
- Notably, as can be seen in the right hand graph below (figure 2), the Company observed an inhibition rate of approximately
90% in the presence of SIL204 in GP2D colorectal cancer cells.
The Company plans to conduct an additional study focused on the inhibition effects of SIL204 on lung (NSCLC) cancer cell lines (A427) in the coming weeks to uncover further data.
"These results represent a significant expansion of SIL204's potential therapeutic applications and provide further validation to our RNAi approach of targeting KRAS mutations across multiple cancer types," said Ilan Hadar, Chairman and CEO of Silexion Therapeutics. "The data demonstrates SIL204's enhanced delivery system enables potent activity at extremely low doses across a range of KRAS-driven solid tumors – colorectal, lung, and pancreatic cancers. With these promising results, we have the potential to expand our development focus beyond pancreatic cancer to include these additional high-need indications."
SIL204 was designed to further enhance the uptake and intracellular concentration of the small interfering RNA (siRNA) product by incorporating a lipid-conjugated delivery system. The inhibiting effect of SIL204 on tumor proliferation was observed across multiple human tumor cell lines in a dose-dependent manner. These findings strengthen the clinical potential of SIL204 as a potential therapy for these difficult-to-treat, KRAS-driven solid tumor cancers. "The data clearly demonstrates SIL204's impact not just on pancreatic cancer, but also for colorectal and lung cancers, highlighting SIL204’s potential as a pan-KRAS therapy," remarked Mitchell Shirvan, Ph.D., Chief Scientific Officer of Silexion. "By silencing KRAS at the RNA level, SIL204 addresses the fundamental genetic driver of these aggressive cancers, potentially overcoming resistance mechanisms that limit conventional approaches. The consistency of results across multiple cancer types suggests broad therapeutic potential for our technology platform."
KRAS mutations are among the most common oncogenic drivers in human cancers, occurring in roughly
About Silexion Therapeutics
Silexion Therapeutics is a pioneering clinical-stage, oncology-focused biotechnology company developing innovative RNA interference (RNAi) therapies to treat solid tumors driven by KRAS mutations, the most common oncogenic driver in human cancers. The Company’s first-generation product, LODER™, has shown promising results in a Phase 2 trial for non-resectable pancreatic cancer. Silexion is also advancing its next-generation siRNA candidate, SIL204, designed to target a broader range of KRAS mutations and showing significant potential in preclinical studies. The Company remains committed to pushing the boundaries of therapeutic innovation in oncology, with a focus on improving outcomes for patients with difficult-to-treat cancers. For more information please visit: https://silexion.com
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the federal securities laws. All statements other than statements of historical fact contained in this communication, including statements regarding Silexion's business strategy, ongoing preclinical studies evaluating SIL204 in colorectal and lung cancer applications, potential expansion of development strategy, and the therapeutic potential of SIL204 across multiple cancer types, are forward-looking statements. These forward-looking statements are generally identified by terminology such as "may", "should", "could", "might", "plan", "possible", "project", "strive", "budget", "forecast", "expect", "intend", "will", "estimate", "anticipate", "believe", "predict", "potential" or "continue", or the negatives of these terms or variations of them, or similar terminology. Forward-looking statements involve a number of risks, uncertainties, and assumptions, and actual results or events may differ materially from those projected or implied by those statements. Important factors that could cause such differences include, but are not limited to: (i) Silexion's ability to successfully complete preclinical studies and initiate clinical trials; (ii) Silexion's strategy, future operations, financial position, projected costs, prospects, and plans; (iii) the impact of the regulatory environment and compliance complexities; (iv) expectations regarding future partnerships or other relationships with third parties; (v) Silexion's future capital requirements and sources and uses of cash, including its ability to obtain additional capital; (vi) Silexion’s ability to maintain its Nasdaq listing; and (vii) other risks and uncertainties set forth in the documents filed or to be filed with the SEC by the Company, including the Company's Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 18, 2025. Silexion cautions you against placing undue reliance on forward-looking statements, which reflect current beliefs and are based on information currently available as of the date a forward-looking statement is made. Forward-looking statements set forth herein speak only as of the date they are made. Silexion undertakes no obligation to revise forward-looking statements to reflect future events, changes in circumstances, or changes in beliefs, except as otherwise required by law.
Company Contact
Silexion Therapeutics Corp
Ms. Mirit Horenshtein Hadar, CFO
mirit@silexion.com
Capital Markets & IR Contact
Arx Capital Markets
North American Equities Desk
silexion@arxadvisory.com
1 (i) Pancratic Cancer Treatment Mark; (ii) Colorectal Cancer Therapeutics Market; (iii) NSCLC Lunc Cancer Therapeutics Market
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