Silexion Therapeutics Announces Additional Promising Preclinical Data for SIL-204, Demonstrating Impressive Synergy with First-Line Pancreatic Cancer Chemotherapies
Silexion Therapeutics (NASDAQ: SLXN) has announced promising new preclinical results for its second-generation siRNA candidate, SIL-204, showing significant synergistic activity when combined with standard pancreatic cancer chemotherapies. The data demonstrates that SIL-204 enhances the effectiveness of 5-fluorouracil, irinotecan, and gemcitabine in human pancreatic tumor cell lines with KRAS G12D mutations.
The combination of SIL-204 with 5-fluorouracil and irinotecan achieved a significant reduction in cancer cell confluence after three days compared to chemotherapy alone (p < 0.0005). These results build upon previous successes with the company's first-generation product, LODER™, which demonstrated improved overall survival in Phase 2 trials.
Silexion plans to initiate toxicology studies for SIL-204 in the coming months and advance to Phase 2/3 clinical trials in the first half of 2026, focusing on locally advanced pancreatic cancer (LAPC). The company also plans to begin preclinical studies for SIL-204 in colorectal cancer models.
Silexion Therapeutics (NASDAQ: SLXN) ha annunciato promettenti nuovi risultati preclinici per il suo candidato siRNA di seconda generazione, SIL-204, che mostra un'attività sinergica significativa quando combinato con le chemioterapie standard per il cancro pancreatico. I dati dimostrano che SIL-204 potenzia l'efficacia di 5-fluorouracile, irinotecano e gemcitabina in linee cellulari tumorali pancreatiche umane con mutazioni KRAS G12D.
La combinazione di SIL-204 con 5-fluorouracile e irinotecano ha raggiunto una riduzione significativa della confluente delle cellule cancerose dopo tre giorni rispetto alla chemioterapia da sola (p < 0.0005). Questi risultati si basano sui successi precedenti del primo prodotto di Silexion, LODER™, che ha dimostrato un miglioramento della sopravvivenza complessiva negli studi di Fase 2.
Silexion prevede di avviare studi di tossicologia per SIL-204 nei prossimi mesi e di passare agli studi clinici di Fase 2/3 nella prima metà del 2026, concentrandosi sul cancro pancreatico localmente avanzato (LAPC). L'azienda prevede inoltre di iniziare studi preclinici per SIL-204 in modelli di cancro colorettale.
Silexion Therapeutics (NASDAQ: SLXN) ha anunciado prometedores nuevos resultados preclínicos para su candidato de siRNA de segunda generación, SIL-204, que muestra una actividad sinérgica significativa cuando se combina con las quimioterapias estándar para el cáncer de páncreas. Los datos demuestran que SIL-204 mejora la efectividad de 5-fluorouracilo, irinotecán y gemcitabina en líneas celulares tumorales pancreáticas humanas con mutaciones KRAS G12D.
La combinación de SIL-204 con 5-fluorouracilo e irinotecán logró una reducción significativa en la confluencia de células cancerosas después de tres días en comparación con la quimioterapia sola (p < 0.0005). Estos resultados se basan en los éxitos anteriores del primer producto de la compañía, LODER™, que demostró una mejor supervivencia general en ensayos de Fase 2.
Silexion planea iniciar estudios de toxicología para SIL-204 en los próximos meses y avanzar a ensayos clínicos de Fase 2/3 en la primera mitad de 2026, enfocándose en el cáncer de páncreas localmente avanzado (LAPC). La compañía también planea comenzar estudios preclínicos para SIL-204 en modelos de cáncer colorrectal.
시렉시온 제약(SILEXION THERAPEUTICS, NASDAQ: SLXN)은 두 번째 세대 siRNA 후보 물질인 SIL-204의 유망한 새로운 전임상 결과를 발표했습니다. 이 후보는 표준 췌장암 화학요법과 병행했을 때 상당한 시너지를 보이고 있습니다. 데이터에 따르면 SIL-204는 KRAS G12D 변이가 있는 인간 췌장 종양 세포주에서 5-플루오로우라실, 이리노테칸 및 젬시타빈의 효과를 강화시킵니다.
SIL-204와 5-플루오로우라실 및 이리노테칸의 조합은 화학요법 단독으로 진행한 경우에 비해 3일 뒤 암세포 합류율이 유의미하게 감소하였습니다(p < 0.0005). 이러한 결과는 회사의 1세대 제품인 LODER™의 성공적인 사례를 바탕으로 하며, 해당 제품은 2상 시험에서 전체 생존율을 개선한 것으로 나타났습니다.
시렉시온은 앞으로 몇 달 이내에 SIL-204에 대한 독성 연구를 시작하고, 2026년 상반기에는 국소 진행성 췌장암(LAPC)을 대상으로 2/3상 임상 시험을 진행할 예정입니다. 또한 SIL-204에 대한 대장암 모델의 전임상 연구도 시작할 계획입니다.
Silexion Therapeutics (NASDAQ: SLXN) a annoncé de nouveaux résultats précliniques prometteurs pour son candidat siRNA de deuxième génération, SIL-204, montrant une activité synergique significative lorsqu'il est associé à des chimiothérapies standard pour le cancer du pancréas. Les données démontrent que SIL-204 améliore l'efficacité de 5-fluorouracile, d'irinotécan et de gemcitabine dans des lignées cellulaires tumorales pancréatiques humaines présentant des mutations KRAS G12D.
La combinaison de SIL-204 avec 5-fluorouracile et irinotécan a entraîné une réduction significative de la confluence cellulaire cancéreuse après trois jours par rapport à la chimiothérapie seule (p < 0.0005). Ces résultats s'appuient sur les succès précédents du premier produit de la société, LODER™, qui a démontré une amélioration de la survie globale lors des essais de phase 2.
Silexion prévoit de commencer des études de toxicologie pour SIL-204 dans les mois à venir et d'avancer vers des essais cliniques de phase 2/3 au cours du premier semestre 2026, en se concentrant sur le cancer du pancréas localement avancé (LAPC). L'entreprise prévoit également de lancer des études précliniques pour SIL-204 dans des modèles de cancer colorectal.
Silexion Therapeutics (NASDAQ: SLXN) hat vielversprechende neue präklinische Ergebnisse für seinen siRNA-Kandidaten der zweiten Generation, SIL-204, bekannt gegeben, der in Kombination mit herkömmlichen Chemotherapien gegen Pankreaskrebs signifikante synergistische Aktivitäten zeigt. Die Daten zeigen, dass SIL-204 die Wirksamkeit von 5-Fluorouracil, Irinotecan und Gemcitabin in menschlichen Pankreas-Tumorzelllinien mit KRAS G12D-Mutationen verbessert.
Die Kombination von SIL-204 mit 5-Fluorouracil und Irinotecan erzielte nach drei Tagen eine signifikante Verringerung der Zellkonfluenz von Krebszellen im Vergleich zur Chemotherapie allein (p < 0.0005). Diese Ergebnisse bauen auf den vorherigen Erfolgen des ersten Produkts der Firma, LODER™, auf, das in Phase-2-Studien eine verbesserte Gesamtüberlebensrate zeigte.
Silexion plant, in den kommenden Monaten toxikologische Studien für SIL-204 zu beginnen und in der ersten Hälfte des Jahres 2026 mit Phase-2/3-Studien zu beginnen, die sich auf lokal fortgeschrittenen Pankreaskrebs (LAPC) konzentrieren. Zudem plant das Unternehmen, präklinische Studien für SIL-204 in Modellen von Dickdarmkrebs zu starten.
- Demonstrated significant synergistic activity with standard chemotherapy drugs in preclinical trials
- Achieved statistically significant reduction in cancer cell confluence (p < 0.0005)
- Previous product LODER™ showed improved overall survival in Phase 2 trials
- Clear development timeline with Phase 2/3 trials planned for 2026
- Clinical trials not yet initiated
- Phase 2/3 trials still 1.5 years away
- Efficacy only demonstrated in preclinical settings so far
Insights
The preclinical data for SIL-204 represents a significant scientific breakthrough in RNAi therapeutics for KRAS-mutated cancers. The synergistic activity with standard chemotherapy agents (5-fluorouracil, irinotecan and gemcitabine) is particularly noteworthy, as it suggests potential for improved treatment efficacy without developing new drug resistance mechanisms. The p-value of <0.0005 indicates extremely strong statistical significance in the reduction of cancer cell confluence.
What's particularly compelling is SIL-204's demonstrated activity against KRAS G12D mutations, which occur in approximately 36% of pancreatic cancers and have historically been extremely challenging to target effectively. The successful combination with existing first-line treatments could potentially lower the barrier to clinical adoption, as it works within established treatment protocols rather than requiring a complete paradigm shift.
From a market perspective, this preclinical data strengthens Silexion's competitive position in the lucrative KRAS inhibitor space. With a market cap of
The expansion into colorectal cancer models indicates a broader market strategy, potentially multiplying the addressable market. The global KRAS inhibitor market is projected to reach
Significant new preclinical results demonstrate synergistic activity of SIL-204 with 5-fluorouracil and irinotecan as well as gemcitabine, reinforcing its potential to improve outcomes in KRAS-mutated pancreatic cancer and other cancers treated with similar therapies.
Cayman Islands, January 15, 2025 – 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 results demonstrating the synergistic efficacy of its proprietary second-generation siRNA candidate, SIL-204, in combination with components of first-line chemotherapy for pancreatic cancer. The additional preclinical data show that SIL-204 exhibits significant synergistic activity with 5-fluorouracil and irinotecan—two main components commonly used in pancreatic cancer treatments—when tested in human pancreatic tumor cell lines harboring KRAS G12D mutations, the most common mutation in pancreatic cancer. Moreover, synergistic activity was also observed with the chemotherapeutic agent gemcitabine.
This promising synergistic activity was observed after the confluence of these tumor cell lines, reflecting how SIL-204 may enhance the effects of 5-fluorouracil and irinotecan when used together, as well as that of gemcitabine. For example, in preclinical models, the combination of 5-fluorouracil and irinotecan with SIL-204 led to a significant reduction in cancer cell confluence after about three days compared to treatment with the chemotherapy agents alone (p < 0.0005), further supporting the synergistic potential of SIL-204 in enhancing standard chemotherapy treatments. This comes on top of previous recent announcements from Silexion regarding pre-clinical findings from the ongoing development of SIL-204, in line with earlier successes with the company’s first-generation product, LODER™ (siG12DLoder), which showed a significant improvement in overall survival in the siRNA plus chemotherapy arm compared to chemotherapy alone in Phase 2 trials.
“These new findings, combined with the substantial milestones we have recently reported in developing SIL-204, suggest that Silexion’s approach could potentially revolutionize the treatment landscape not only for pancreatic cancer but also for a wide range of KRAS-mutated cancers, which remain some of the most difficult to treat. The synergy demonstrated between SIL-204 and first-line chemotherapies underscores its potential to enhance existing treatment regimens and address significant unmet needs across multiple oncology indications,” said Ilan Hadar, Chairman and CEO of Silexion.
As previously reported, Silexion is gearing up for the clinical development of SIL-204, Planning to initiate toxicology studies with SIL-204 within the upcoming months and 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.
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, ongoing studies, and plans for future trials, 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 companyy, 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.
CONTACT:
Silexion Therapeutics Corp
Ms. Mirit Horenshtein Hadar, CFO
mirit@silexion.com
ARX | Capital Markets Advisors
North American Equities Desk
silexion@arxadvisory.com
FAQ
What are the key findings from SLXN's latest preclinical trials for SIL-204?
When will Silexion (SLXN) begin Phase 2/3 clinical trials for SIL-204?
How does SLXN's SIL-204 perform compared to standard chemotherapy alone?
What types of cancer is Silexion (SLXN) targeting with SIL-204?
What is the next immediate step for SLXN's SIL-204 development?
