Silexion Therapeutics Reports Strong Tumor Growth Reduction from Systemic Administration of SIL-204 in Preclinical Pancreatic Cancer Models
Silexion Therapeutics (NASDAQ: SLXN) has reported promising preclinical data for SIL-204, its next-generation siRNA therapeutic candidate targeting KRAS-driven cancers. The key findings demonstrate that systemic administration of SIL-204 effectively reduced tumor growth by ~50% after 30 days, with ~50% of tumors showing complete necrosis in human pancreatic tumor models.
The data revealed that SIL-204 can inhibit multiple oncogenic KRAS mutations (G12D, G12V, G12R, Q61H, and G13D) and maintain effective drug levels in rat plasma and tissues for over 56 days after a single administration. In intratumoral administration tests, SIL-204 microparticles reduced tumor cell numbers by ~3-fold, tumor area by ~1.5-fold, and increased tumor necrosis by ~5-fold after 15 days.
The company is now planning further studies to evaluate SIL-204's impact on metastases and expects to announce an expanded development plan for KRAS-driven cancers.
Silexion Therapeutics (NASDAQ: SLXN) ha riportato dati preclinici promettenti per SIL-204, il suo candidato terapeutico siRNA di nuova generazione mirato ai tumori a guida KRAS. I risultati chiave dimostrano che l'amministrazione sistemica di SIL-204 ha ridotto efficacemente la crescita tumorale di circa il 50% dopo 30 giorni, con circa il 50% dei tumori che mostrava necrosi completa in modelli umani di tumore pancreatico.
I dati hanno rivelato che SIL-204 può inibire diverse mutazioni oncogeniche di KRAS (G12D, G12V, G12R, Q61H e G13D) e mantenere livelli efficaci del farmaco nel plasma e nei tessuti dei ratti per oltre 56 giorni dopo una singola somministrazione. Nei test di somministrazione intratumorale, le microparticelle di SIL-204 hanno ridotto il numero di cellule tumorali di circa 3 volte, l'area tumorale di circa 1,5 volte e hanno aumentato la necrosi tumorale di circa 5 volte dopo 15 giorni.
L'azienda sta ora pianificando ulteriori studi per valutare l'impatto di SIL-204 sulle metastasi e si aspetta di annunciare un piano di sviluppo ampliato per i tumori a guida KRAS.
Silexion Therapeutics (NASDAQ: SLXN) ha informado datos preclínicos prometedores para SIL-204, su candidato terapéutico de siRNA de próxima generación dirigido a cánceres impulsados por KRAS. Los hallazgos clave demuestran que la administración sistémica de SIL-204 redujo efectivamente el crecimiento tumoral en aproximadamente un 50% después de 30 días, con alrededor del 50% de los tumores mostrando necrosis completa en modelos humanos de tumor pancreático.
Los datos revelaron que SIL-204 puede inhibir múltiples mutaciones oncogénicas de KRAS (G12D, G12V, G12R, Q61H y G13D) y mantener niveles efectivos del fármaco en plasma y tejidos de ratas durante más de 56 días después de una sola administración. En pruebas de administración intratumoral, las micropartículas de SIL-204 redujeron el número de células tumorales en aproximadamente 3 veces, el área tumoral en aproximadamente 1.5 veces y aumentaron la necrosis tumoral en aproximadamente 5 veces después de 15 días.
La compañía ahora está planeando estudios adicionales para evaluar el impacto de SIL-204 en las metástasis y espera anunciar un plan de desarrollo ampliado para los cánceres impulsados por KRAS.
실렉시온 테라퓨틱스 (NASDAQ: SLXN)가 KRAS에 의해 유도되는 암을 목표로 하는 차세대 siRNA 치료제 후보 SIL-204에 대한 유망한 전임상 데이터를 보고했습니다. 핵심 결과는 SIL-204의 전신 투여가 30일 후 약 50%의 종양 성장을 효과적으로 감소시켰으며, 인간 췌장 종양 모델에서 약 50%의 종양이 완전 괴사를 보였다는 것을 보여줍니다.
데이터는 SIL-204가 여러 온코겐 KRAS 변이(G12D, G12V, G12R, Q61H 및 G13D)를 억제하고 단일 투여 후 56일 이상 동안 쥐 혈장과 조직에서 효과적인 약물 수치를 유지할 수 있음을 밝혔습니다. 종양 내 투여 테스트에서 SIL-204 미세 입자는 종양 세포 수를 약 3배 줄였고, 종양 면적을 약 1.5배 줄이며, 15일 후 종양 괴사를 약 5배 증가시켰습니다.
회사는 이제 SIL-204의 전이 영향 평가를 위한 추가 연구를 계획하고 있으며, KRAS 유도 암에 대한 확장된 개발 계획을 발표할 것으로 예상하고 있습니다.
Silexion Therapeutics (NASDAQ: SLXN) a rapporté des données précliniques prometteuses pour SIL-204, son candidat thérapeutique de siRNA de nouvelle génération ciblant les cancers induits par KRAS. Les principales conclusions montrent que l'administration systémique de SIL-204 a réduit efficacement la croissance tumorale d'environ 50 % après 30 jours, avec environ 50 % des tumeurs montrant une nécrose complète dans des modèles humains de tumeur pancréatique.
Les données ont révélé que SIL-204 peut inhiber plusieurs mutations oncogéniques de KRAS (G12D, G12V, G12R, Q61H et G13D) et maintenir des niveaux de médicament efficaces dans le plasma et les tissus de rat pendant plus de 56 jours après une seule administration. Dans des tests d'administration intratumorale, les microparticules de SIL-204 ont réduit le nombre de cellules tumorales d'environ 3 fois, la surface tumorale d'environ 1,5 fois et augmenté la nécrose tumorale d'environ 5 fois après 15 jours.
L'entreprise prévoit maintenant d'autres études pour évaluer l'impact de SIL-204 sur les métastases et s'attend à annoncer un plan de développement élargi pour les cancers induits par KRAS.
Silexion Therapeutics (NASDAQ: SLXN) hat vielversprechende präklinische Daten für SIL-204, seinen next-generation siRNA-Therapiekandidaten, der sich auf KRAS-getriebene Krebserkrankungen konzentriert, berichtet. Die wichtigsten Ergebnisse zeigen, dass die systemische Verabreichung von SIL-204 das Tumorwachstum nach 30 Tagen um etwa 50 % effektiv reduzierte, wobei etwa 50 % der Tumoren vollständige Nekrose in menschlichen Pankreastumormodellen zeigten.
Die Daten zeigten, dass SIL-204 mehrere onkogene KRAS-Mutationen (G12D, G12V, G12R, Q61H und G13D) hemmen kann und effektive Medikamentenspiegel im Plasma und in den Geweben von Ratten über 56 Tage nach einer einmaligen Verabreichung aufrechterhält. Bei der intratumoralen Verabreichung verringerten SIL-204-Mikropartikel die Anzahl der Tumorzellen um etwa das 3-fache, die Tumorfläche um etwa das 1,5-fache und erhöhten die Tumornekrose nach 15 Tagen um etwa das 5-fache.
Das Unternehmen plant nun weitere Studien, um die Auswirkungen von SIL-204 auf Metastasen zu bewerten, und erwartet, einen erweiterten Entwicklungsplan für KRAS-getriebene Krebserkrankungen anzukündigen.
- SIL-204 demonstrated 50% tumor growth reduction with 50% complete necrosis in pancreatic tumor models
- Single administration maintains effective drug levels for over 56 days
- Successful inhibition of multiple KRAS mutations (G12D, G12V, G12R, Q61H, G13D)
- Intratumoral administration showed significant tumor reduction metrics
- Further studies still needed to evaluate impact on metastases
- Data to preclinical stage, yet to demonstrate efficacy in human trials
Insights
The latest preclinical results for SIL-204 represent a significant advancement in RNAi therapeutics for pancreatic cancer treatment. The ~50% tumor growth reduction and 50% complete tumor necrosis in KRAS G12D mutant tumors are particularly noteworthy, as G12D mutations are present in approximately 40% of pancreatic cancer cases and have historically been considered "undruggable."
The extended release formulation maintaining therapeutic levels for 56 days is a important differentiator, potentially allowing for monthly or bi-monthly dosing compared to weekly or bi-weekly administration required by many cancer therapeutics. This could significantly improve patient compliance and quality of life while potentially reducing treatment costs.
The broad coverage of multiple KRAS mutations (G12D, G12V, G12R, Q61H and G13D) positions SIL-204 as a potential pan-KRAS inhibitor, addressing approximately 90% of KRAS-mutant pancreatic cancers. The successful systemic administration is particularly significant as it overcomes one of the major hurdles in pancreatic cancer treatment - the dense stromal barrier that typically limits drug delivery.
However, investors should note that while the 3-fold reduction in tumor cells and 5-fold increase in tumor necrosis in G12V models are promising, these results are from preclinical studies. The translation of these findings to human patients, particularly regarding metastasis prevention, remains to be demonstrated in clinical trials. The company's cautious optimism about metastasis impact suggests that this critical aspect requires further validation.
These preclinical results significantly strengthen Silexion's position in the highly competitive KRAS inhibitor market. The successful systemic delivery approach, combined with the extended release formulation, addresses two critical commercial barriers: delivery efficiency and dosing frequency. The 56-day sustained drug level could translate to substantial cost advantages and improved patient compliance compared to currently approved KRAS inhibitors requiring more frequent dosing.
The pancreatic cancer market represents a $4.2 billion opportunity with high unmet need, as current treatments show efficacy. SIL-204's demonstrated ability to target multiple KRAS mutations expands its potential market reach beyond single-mutation therapies. The robust tumor response data, particularly the 50% complete necrosis rate, suggests potential for superior efficacy compared to existing treatments.
The expanded development plan announcement expected shortly could catalyze near-term value creation. With these positive preclinical results, Silexion is well-positioned to attract potential strategic partnerships, particularly from larger pharmaceutical companies seeking to expand their oncology portfolios. The RNAi approach, if successful in clinical trials, could establish a new paradigm in KRAS-targeted therapy, potentially commanding premium pricing and favorable reimbursement terms.
New preclinical findings provide validation for Silexion’s new systemic administration approach for SIL-204, demonstrating inhibition of tumor growth in a clinically relevant orthotopic model; Further studies aim to evaluate its impact on metastases
Cayman Islands, January 28, 2025 – 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 promising new preclinical data for SIL-204, its next-generation siRNA therapeutic candidate. The findings contribute to validating systemic administration as an effective delivery approach, demonstrating significant tumor growth reduction in orthotopic pancreatic cancer models, a platform designed to mimic human cancer progression.
This data underscores SIL-204’s potential to address one of the most aggressive and challenging cancers, validating its ability to target KRAS mutations systemically while achieving prolonged therapeutic activity. While the current data shows robust tumor growth inhibition, further studies aim to evaluate its impact on metastases, which the Company is cautiously optimisic about.
The Company is actively exploring how this promising data can inform an expanded next-generation treatment strategy for KRAS-driven cancers and expects to announce details of its expanded development plan shortly.
Key Preclinical Data Highlights
- SIL-204 administered in an extended release formulation reduced tumor growth by ~
50% after 30 days, with ~50% of tumors showing complete necrosis, in human pancreatic tumors harboring a G12D mutation xenografted into mice. - SIL-204 administered subcutaneously inhibited tumor growth in mouse metastatic pancreatic orthotopic models.
- A single systemic administration of SIL-204 maintained effective drug levels in rat plasma and tissues for over 56 days.
- SIL-204 inhibits key oncogenic KRAS mutations, including G12D, G12V, G12R, Q61H, and G13D.
- Intratumoral administration of SIL-204 microparticles reduced tumor cell numbers by ~3-fold, tumor area by ~1.5-fold, and increased tumor necrosis by ~5-fold after 15 days in human pancreatic cancer xenograft harboring a KRAS G12V mutation in mice.
“We are thrilled to share these results, which showcase systemic administration as an effective method for targeting KRAS-driven cancers,” Mitchell Shirvan, Ph.D., CSO of Silexion. “By demonstrating robust tumor growth inhibition in a clinically relevant model, SIL-204 shows significant potential to address advanced cancers. We look forward to future studies evaluating its impact on metastatic progression.”
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, 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
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 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.
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 results of SLXN's SIL-204 preclinical trials in January 2025?
Which KRAS mutations can Silexion's SIL-204 target?
What were the intratumoral administration results for SLXN's SIL-204?
How long does SIL-204's therapeutic effect last after a single administration?
What is the next step in SLXN's development plan for SIL-204?
