Silexion Therapeutics Reports Groundbreaking Positive Initial Data from Systemic Administration of SIL204 in Orthotopic Pancreatic Cancer Models

Rhea-AI Summary

Silexion Therapeutics (NASDAQ: SLXN) announced positive initial data from orthotopic pancreatic cancer models for their SIL204 treatment. The study demonstrated that subcutaneously administered SIL204 effectively reduces both primary tumor growth and metastatic spread.

Key findings include:

• ~70% reduction in tumor cell numbers in AsPC-1 (KRAS G12D mutation) by day 28
• In Panc-1 (KRAS G12D), tumor cells decreased 12% while control group increased >100% by day 14
• ~80% reduction in BxPC-3 (KRAS wild-type) by day 28
• Significant reduction in metastatic spread across liver, intestine, spleen and stomach in Panc-1 and BxPC-3 models

The results validate SIL204's efficacy in a more clinically relevant setting, where human pancreatic tumor cells are implanted directly into the pancreas. The company is finalizing an updated development strategy based on these findings.

Positive

• Strong efficacy data: 70-80% tumor reduction in multiple cancer cell lines
• First demonstration of metastasis reduction across multiple organs
• Successful systemic delivery via subcutaneous administration
• Effective against both KRAS mutant and wild-type tumors

Negative

• Still in preclinical stage, requiring further clinical validation
• Results to animal models, human efficacy yet to be demonstrated

Insights

Oncology Researcher

Silexion's new data represents a significant technical advancement in their RNAi therapeutic approach for pancreatic cancer. The transition from subcutaneous xenograft models to orthotopic models – where tumor cells grow in their native pancreatic environment – is a important step forward in preclinical validation.

The efficacy demonstrated across multiple cell lines with different KRAS mutation profiles (70-80% reduction in tumor burden) is particularly promising. KRAS mutations, especially G12D, are notorious drivers in pancreatic cancer with targeted treatment options. What's most impressive is SIL204's ability to reduce metastatic spread while being administered subcutaneously – addressing two major challenges in pancreatic cancer treatment: metastatic disease and delivery method.

Pancreatic cancer's poor prognosis stems largely from its tendency to metastasize early, often before diagnosis. A therapy that can simultaneously target primary tumors and metastases through minimally invasive administration would be revolutionary if these results translate to humans.

However, these remain preclinical results – the path from orthotopic models to human efficacy is still substantial. The company appears to be planning their clinical strategy, but investors should understand that years of clinical development likely remain before potential commercialization. The efficacy signals are encouraging, but human trials will need to confirm both safety and efficacy in this difficult-to-treat cancer type.

Biotech Investment Analyst

These preclinical results potentially strengthen Silexion's competitive position in the KRAS-targeting therapeutic landscape. With a market cap of $8.8 million and significant progress in their lead candidate, the company appears undervalued compared to other early-stage oncology biotechs targeting similar pathways.

RNAi approaches for KRAS-driven cancers represent a differentiated strategy in a field where many companies pursue small molecule inhibitors with mixed results. The systemic delivery validation is particularly valuable – addressing the long-standing challenge of RNA therapeutic delivery to solid tumors.

Notably, SIL204 showed efficacy in both KRAS-mutant and wild-type models, suggesting potential broader application beyond just KRAS-mutated cancers. This could significantly expand the addressable patient population if confirmed in clinical studies.

The company's announcement of an upcoming development strategy update signals potential acceleration in their timeline. For investors, key upcoming catalysts will likely include IND-enabling studies, regulatory interactions, and early clinical trial designs. The pancreatic cancer market, while smaller than some other oncology indications, represents a high unmet need with competition and potential for premium pricing.

While encouraging, these results should be viewed in context – many promising preclinical cancer therapies fail in human testing. The company will need substantial additional funding to advance through clinical trials, likely resulting in dilution for current shareholders. The path to market remains long, but these data strengthen Silexion's scientific foundation.

i

Silexion's latest preclinical data represents a meaningful scientific advancement in the development of their RNA interference therapy SIL204 for pancreatic cancer. The transition to orthotopic models - where human cancer cells grow in the actual pancreatic environment - provides substantially stronger evidence of potential efficacy than their previous models.

The data demonstrates two critical capabilities that address fundamental challenges in pancreatic cancer treatment:

• Significant reduction in both primary tumors (70-80% reduction in tumor burden across multiple cell lines) and metastatic spread
• Effective delivery through simple subcutaneous administration, avoiding the need for complex delivery systems

Pancreatic cancer's dismal survival rates stem largely from its rapid metastasis and resistance to treatment. SIL204's demonstrated ability to reduce metastatic burden in secondary organs (liver, intestine, spleen, stomach) is particularly noteworthy, as metastatic disease is typically what proves fatal.

The efficacy across different KRAS profiles (both mutant and wild-type) suggests potential broader application beyond specific genetic subtypes, potentially expanding the addressable patient population.

For investors, this represents an important derisking event that strengthens the scientific rationale for advancing toward clinical trials. However, significant hurdles remain - including toxicology studies, IND filing, and the long path through human clinical trials. The company's upcoming development strategy update will be important for understanding timeline and funding requirements to advance this promising approach toward potential commercialization.

Silexion Therapeutics' Latest Data Demonstrates that Subcutaneously Administered SIL204 Reduces Both Primary Tumors and Metastases in Clinically Relevant Orthotopic Models Where Human Pancreatic Cancer Cells Grow in Their Native Environment

Grand Cayman, Cayman Islands, March 05, 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 positive data from orthotopic pancreatic cancer models demonstrating that subcutaneously administered SIL204 effectively reduces both primary tumor growth and metastatic spread.

These findings represent a significant advancement over previously reported data by providing further validation of SIL204's efficacy in the more clinically relevant orthotopic setting, where human pancreatic tumor cells are implanted directly into the pancreas to better mimic human disease progression, including, for the first time, in metastasis patterns.

Key New Findings

• Initial validation using orthotopic models: SIL204 administered subcutaneously (systemically) showed significant efficacy in orthotopic xenograft models where tumors grow in their native pancreatic environment, representing a more clinically relevant setting than our previous subcutaneous xenograft models.
• Cell line-specific efficacy profiles: SIL204 showed robust activity across multiple pancreatic cancer cell lines with different KRAS mutation profiles:
  • In AsPC-1 (harboring KRAS G12D mutation): ~70% reduction in overall bioluminescence (an indication of tumor cell number) as compared to the control group, by day 28.
  • In Panc-1 (harbouring KRAS G12D mutation): Bioluminescence or tumor cell numbers decreased dramatically in a dose-dependent manner, with the highest-dose group showing the most significant effect. Bioluminescence in the control group increased by approximately more than 100% while in the SIL204 treated group it decreased by 12% compared to baseline, a substantial reduction by day 14 compared with the control group (P-value < 0.05), demonstrating the significant therapeutic impact of SIL204.
  • In BxPC-3 (additional KRAS wild-type model): ~80% reduction in overall  bioluminescence, as compared to the control group, by day 28.
• Metastasis reduction demonstrated for the first time: SIL204 treatment significantly reduced metastatic spread to secondary organs; substantially lowering metastatic burden across the liver, intestine, spleen and stomach in the two models checked for the various organs, Panc-1 and BxPC-3 models.
• Initial validation for systemic delivery efficacy: Subcutaneous administration of SIL204 proved effective in reaching and treating pancreatic tumors and their metastases, confirming systemic delivery as a viable administration route.

"These orthotopic model results represent a pivotal advancement in our development program," said Mitchell Shirvan, Ph.D., CSO of Silexion. "While our previous data showed SIL204's ability to reduce tumor growth in standard models, these new findings provide initial validation of its potential effectiveness in a much more clinically relevant setting. Particularly exciting is the demonstration that SIL204 can significantly reduce metastatic spread when administered subcutaneously, suggesting potential for treating both primary and metastatic disease with a minimally-invasive delivery method."

Based on these encouraging results, Silexion is actively exploring an expanded development plan for SIL204 using the systemic administration approach. The Company is finalizing an updated development strategy that leverages these new findings and expects to provide more detailed information in the coming weeks, as previously indicated in recent announcements.

"These results mark the first time we've demonstrated SIL204's ability to address metastatic disease through subcutaneous administration," added Ilan Hadar, Chairman and CEO of Silexion. "The ability to deliver our therapy systemically and still effectively target both primary pancreatic tumors and their metastases represents a significant potential advantage for treating this devastating disease."

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 clinical 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

Notice 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 and ongoing studies 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 in 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; and (vi) other risks and uncertainties set forth in the documents filed or to be filed with the SEC by the company, including the registration statement on Form S-1 filed with the SEC on February 12, 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 Advisors
North American Equities Desk
silexion@arxadvisory.com

FAQ

What were the key efficacy results of SIL204 in pancreatic cancer models?

SIL204 showed 70% tumor reduction in AsPC-1, 12% decrease in Panc-1 (vs 100% increase in control), and 80% reduction in BxPC-3 models by day 28.

How does SLXN's SIL204 treatment affect cancer metastasis?

SIL204 significantly reduced metastatic spread to liver, intestine, spleen and stomach in both Panc-1 and BxPC-3 models.

What is the administration method for Silexion's SIL204 treatment?

SIL204 is administered subcutaneously (under the skin), providing systemic delivery to treat both primary tumors and metastases.

Which KRAS mutations did SLXN's SIL204 show efficacy against?

SIL204 showed efficacy against KRAS G12D mutations (in AsPC-1 and Panc-1 cells) and KRAS wild-type (in BxPC-3 cells).