Silexion Therapeutics Reports Breakthroughs From SIL-204 Preclinical Studies

Rhea-AI Summary

Silexion Therapeutics (NASDAQ: SLXN) has reported significant breakthroughs in preclinical studies for its second-generation siRNA candidate, SIL-204. The latest findings show that the SIL-204-microparticle formulation can inhibit growth and induce necrosis in human pancreatic cell lines with the KRAS G12D mutation, which represents the largest segment of pancreatic cancer subtypes.

Key findings include substantial tumor reduction in mouse xenograft studies with a single administration of SIL-204 encapsulated in an extended-release formulation, and a superior extended-release profile resulting from the transition to PLGA microparticles. Silexion plans to initiate toxicology studies soon and aims to advance SIL-204 into Phase 2/3 clinical trials in the first half of 2026, focusing on locally advanced pancreatic cancer (LAPC).

Positive

• SIL-204 demonstrated substantial tumor reduction in human pancreatic tumor cell lines with KRAS G12D mutations
• New extended-release formulation shows efficacy with a single administration
• Histopathological examination revealed high induction of tumor necrosis
• Improved PLGA-microparticle formulation shows superior properties over previous extended-release formulations
• Plans to advance SIL-204 into Phase 2/3 clinical trials in the first half of 2026

Negative

• None.

Insights

Medical Research Analyst

The preclinical breakthroughs for SIL-204 are highly promising for Silexion Therapeutics. Key findings include:

• Significant anti-tumor activity against KRAS G12D mutated pancreatic cancer cells with a single dose of the new formulation
• Improved extended-release profile using PLGA microparticles
• High induction of tumor necrosis in treated tumors

These results address critical challenges in RNAi therapy delivery and efficacy. The G12D mutation targeted by SIL-204 represents a large subset of pancreatic cancers, potentially expanding the drug's market. The planned advancement to Phase 2/3 trials by 2026 for locally advanced pancreatic cancer (LAPC) could be a game-changer, given the high mortality rate of this disease. Additionally, exploring colorectal cancer applications broadens the potential impact. While still early-stage, these developments significantly de-risk Silexion's pipeline and increase the likelihood of clinical and commercial success in the challenging field of RNAi therapeutics for cancer.

Financial Analyst

This preclinical breakthrough could significantly impact Silexion's financial outlook and market position:

• Potential acceleration of the development timeline, possibly leading to earlier revenue generation
• Expanded addressable market by targeting multiple KRAS mutations and cancer types
• Improved drug delivery system could lead to better efficacy and patient outcomes, potentially commanding premium pricing
• Positive results may attract partnership opportunities or additional funding

However, investors should note that Silexion, with a market cap of $5.2 billion, is still years away from potential commercialization. The company will likely require substantial capital to fund clinical trials through 2026 and beyond. While these results are promising, the path to FDA approval remains long and risky. Investors should closely monitor cash burn rates, upcoming milestones and any potential dilution from future funding rounds. Overall, this news strengthens Silexion's position in the competitive oncology space, potentially justifying its current valuation if clinical trials prove successful.

Latest preclinical studies reveal significant improvements in stability, efficacy, and KRAS targeting range for next-generation siRNA candidate SIL-204

GRAND CAYMAN, Cayman Island--(BUSINESS WIRE)-- Silexion Therapeutics Corp. (NASDAQ: SLXN) (“Silexion” or the “Company”), a clinical-stage biotech developing RNA interference (RNAi) therapies for KRAS-driven cancers, today announced new preclinical findings for SIL-204, its second-generation siRNA candidate, following the optimization of its extended-release formulation. These latest findings demonstrate that the latest SIL-204-microparticle formulation can inhibit the growth and induce necrosis of the human pancreatic cell line that bears the KRAS G12D mutation xenotransplanted into mice. Given that this mutation constitutes the largest segment of pancreatic cancer subtypes, it represents a significant in the development of SIL-204.

Key new pre-clinical findings include:

• Significant Anti-tumor Activity: In recent mouse xenograft studies, SIL-204 demonstrated substantial tumor reduction in the human pancreatic tumor cell lines with the KRAS G12D (Panc -1) mutations using the innovative approach of oncogene silencing with siRNA. Previous studies showed this effect using unformulated siRNA with daily injections. The new studies further show this effect with a single administration of SIL-204 encapsulated in an extended-release formulation. Moreover, histopathological examination of treated tumors showed a very high induction of tumor necrosis.
• Improved Formulation In Vivo: The transition from PLGA depot rods to PLGA microparticles (MPs) has resulted in a superior extended-release profile, enhancing the therapeutic potential. We now report in vivo results indicating that our new modified PLGA-microparticle formulation has superior properties over previous extended-release formulations (Loder).

Silexion plans to initiate toxicology studies with SIL-204 within the upcoming months and has plans to advance SIL-204 into Phase 2/3 clinical trials in the first half of 2026, focusing initially on locally advanced pancreatic cancer (LAPC) which has a notoriously high mortality rate. In parallel, the company plans to initiate preclinical studies for SIL-204, in colorectal cancer models.

"These optimizations represent a significant step forward in our development of SIL-204," said Ilan Hadar, Chairman and CEO of Silexion. "The improvements in cellular uptake and the enhanced extended-release formulation further strengthen our confidence in SIL-204's potential. We look forward to commencing our next set of studies in preparation for our Phase 2/3 clinical trial."

About Silexion Therapeutics

Silexion Therapeutics (NASDAQ: SLXN) 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, SIL-204, 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

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 plans and objectives of management for future operations, are forward-looking statements. These forward-looking statements are generally identified by terminology such as "pro forma", "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 market opportunity; (ii) Silexion’s strategy, future operations, financial position, projected costs, prospects and plans; (iii) the impact of the regulatory environment and complexities with compliance related to such environment; (iv) expectations regarding future partnerships or other relationships with third parties; (v) Silexion’s future capital requirements and sources and uses of cash, including Silexion’s ability to obtain additional capital in the future; and (vi) other risks and uncertainties set forth in the documents filed or to be filed with the SEC by the company, including the proxy statement/prospectus filed with the SEC on July 17, 2024. 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20241001946039/en/

Company Contact

Silexion Therapeutics Corp

Ms. Mirit Horenshtein Hadar, CFO

mirit@silexion.com

Investor Contact

ARX | Capital Markets Advisors

North American Equities Desk

silexion@arxadvisory.com

Source: Silexion Therapeutics Corp.

FAQ

What are the key findings from Silexion Therapeutics' (SLXN) preclinical studies for SIL-204?

Silexion Therapeutics reported significant tumor reduction in mouse xenograft studies using SIL-204, improved extended-release formulation efficacy with a single administration, and high induction of tumor necrosis in treated tumors.

When does Silexion Therapeutics (SLXN) plan to start Phase 2/3 clinical trials for SIL-204?

Silexion Therapeutics plans to advance SIL-204 into Phase 2/3 clinical trials in the first half of 2026, focusing initially on locally advanced pancreatic cancer (LAPC).

What cancer type is Silexion Therapeutics (SLXN) targeting with SIL-204?

Silexion Therapeutics is primarily targeting pancreatic cancer with the KRAS G12D mutation, which represents the largest segment of pancreatic cancer subtypes. They also plan to initiate preclinical studies for colorectal cancer models.

How has Silexion Therapeutics (SLXN) improved the formulation of SIL-204?

Silexion Therapeutics has transitioned from PLGA depot rods to PLGA microparticles (MPs), resulting in a superior extended-release profile and enhanced therapeutic potential for SIL-204.