A detailed analysis of Silexion Therapeutics’ recent announcement reveals promising preclinical data alongside critical logical and methodological concerns that must be addressed for scientific credibility.
Summary:
Silexion Therapeutics recently reported promising preclinical results for their RNA interference (RNAi) therapy, SIL204, in orthotopic pancreatic cancer models, highlighting significant tumor reduction and decreased metastatic spread. However, a thorough INGA314.com analysis identified important inconsistencies, such as unexplained effectiveness in KRAS wild-type models, overly confident claims relative to preclinical evidence, selective data reporting, and incomplete statistical disclosures.
Original announcement, March 5th: https://www.biospace.com/press-releases/silexion-therapeutics-reports-groundbreaking-positive-initial-data-from-systemic-administration-of-sil204-in-orthotopic-pancreatic-cancer-models
Key Findings from Silexion’s Announcement:
- Tumor Reduction: SIL204 showed substantial reductions (~70-80%) in tumor bioluminescence across multiple cell lines.
- Metastasis Reduction: Demonstrated reduced metastatic spread to secondary organs (liver, intestine, spleen, stomach).
- Systemic Administration: Confirmed the effectiveness of subcutaneous systemic administration for targeting tumors and metastases.
Critical Issues Identified by INGA314.com:
1. Mechanistic Contradiction:
- SIL204 is designed specifically to target KRAS-driven cancers. Yet, it exhibited significant effectiveness (~80% reduction) in the KRAS wild-type model (BxPC-3), contradicting its stated targeted mechanism.
2. Epistemic Overconfidence:
- The announcement uses language implying high certainty (e.g., “proved effective”), despite inherent uncertainties in translating preclinical results to clinical efficacy.
3. Selection and Reporting Bias:
- Only positive results were reported, with no mention of neutral or negative data, raising concerns of selective reporting.
4. Incomplete Statistical Transparency:
- Crucial details such as sample sizes, full statistical methods, and comprehensive significance reporting were omitted, diminishing scientific rigor.
Recommendations from INGA314.com Analysis:
- Clarify Mechanism of Action: Clearly explain how SIL204 could be effective in KRAS wild-type models, addressing potential off-target or alternative mechanisms.
- Accurately Calibrate Claims: Modify language to accurately reflect the preclinical nature of the evidence and its limitations.
- Comprehensive Data Reporting: Include neutral or negative experimental results for balanced transparency.
- Enhanced Statistical Transparency: Provide detailed statistical and methodological information to strengthen scientific credibility.
In conclusion, while Silexion Therapeutics’ SIL204 presents encouraging preclinical findings, addressing the critical logical and methodological issues identified by INGA314.com will greatly enhance the validity and trustworthiness of future scientific communications.
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