siG12D LODER / Silexion Therapeutics - LARVOL DELTA

SIL-204 siRNA encapsulated in extended release microparticles for the treatment of localized cancer that harbors a KRAS G12x or G13D mutation. (ASCO-GI 2025) - P2 | "The preclinical results of SIL-204-MP are promising and as the potential to further enhance the anti-tumor effect demonstrated by siG12DLoder in pancreatic patients. SIL-204 is now in toxicology studies as preparation for clinical trials in non-resectable pancreatic cancer."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • KRAS

Silexion Therapeutics Announces Significant New Data from Phase 2 Trial of LODER in Non-Resectable Pancreatic Cancer (Businesswire) - P2 | N=80 | "Silexion Therapeutics Corp....announced significant new findings from its Phase 2 trial of LODER in patients with non-resectable locally advanced pancreatic cancer (LAPC) which bear the KRAS G12D or G12V mutation (approximately 70% of pancreatic cancer patients). Overall the updated analysis reveals a 56% objective response rate (ORR) in patients treated with LODER, with the ORR increasing to 67% in patients whose previously non-resectable tumors became resectable."

P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

PESG Releases Report on Silexion Therapeutics: Pioneering RNAi Technology in the Fight Against KRAS-Driven Cancers (GlobeNewswire) - P2 | N=80 | PROTACT (NCT01676259) | Sponsor: Silenseed Ltd | "Silexion's second-generation improved product, SIL-204, is an optimized siRNA formulation expected to enter Phase 2/3 clinical trials in 2025-2026....Key findings include a 9.3-month improvement in overall survival when LODER was combined with standard chemotherapy, compared to chemotherapy alone in patients with non-resectable pancreatic cancer harboring KRAS G12D/V mutations. The study also revealed an increased objective response rate (ORR) of 55% with LODER™ plus chemotherapy, compared to 20% for standard chemotherapy alone. Notably, the ORR increased to 64% when considering tumors that were initially non-resectable becoming resectable."

New P2/3 trial • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

[VIRTUAL] A phase II study of siG12D-LODER in combination with chemotherapy in patients with locally advanced pancreatic cancer (PROTACT). (ASCO 2020) - P2 | " This phase 2 study was initially designed as a randomized, two arm, open label study of gemcitabine and nab-paclitaxel with or without siG12D-LODER for patients with locally advanced pancreas cancer with planned 40 patients in each arm and primary endpoint of progression-free survival. Trial accrual is anticipated to be completed by December 2020. Research Funding: Silenseed"

Clinical • Combination therapy • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CTCs • KRAS

PROTACT: A Phase 2 Study of siG12D LODER in Combination With Chemotherapy in Patients With Locally Advanced Pancreatic Cancer (clinicaltrials.gov) - P2; N=80; Recruiting; Sponsor: Silenseed Ltd; Trial completion date: Jun 2020 ➔ Aug 2023; Trial primary completion date: Nov 2019 ➔ Oct 2022

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market. (PubMed) - Pharm Res - "...The siRNAs in focus are PF-04523655, TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, QPI-1007, and patisiran (phase 3)...Miravirsen is an AntimiR-122 for hepatitis C virus infection. The flexibility of RNAi technology is easily understood taking into account: (i) the different drug targets (i.e. p53, caspase 2, PKN3, β2-adrenergic receptor, mutated KRAS, microRNAs); (ii) therapeutic conditions, including ophthalmic diseases, kidney injury, amyloidosis, pancreatic cancer, viral hepatitis; and (iii) routes of administration (ocular, intravenous, subcutaneous, intratumoral). Although some issues are still matters of concern (delivery, toxicity, cost, and biological barriers), RNAi definitively opens a wide avenue for drug development."

Journal • Review • Biosimilar • Gastrointestinal Cancer • Hepatitis C Virus • Immunology • Oncology • Ophthalmology • Pancreatic Cancer • Renal Disease

Chemotherapy for pancreatic cancer. (PubMed, Presse Med) - "...The current standard of care is six months adjuvant chemotherapy with modified folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) in patients fit enough for this protocol, otherwise six months of gemcitabine and capecitabine based on the European Study Group for Pancreatic Cancer (ESPAC)-4 study. In patients with metastatic disease, combination chemotherapy according to the FOLFIRINOX protocol or with gemcitabine plus nab-paclitaxel is an important improvement to gemcitabine monotherapy that was the standard for many years...This trial showed no difference in overall survival in those patients with stable disease after four months of gemcitabine (with or without erlotinib) randomized to either continuation of gemcitabine therapy or chemoradiation (54Gy with capecitabine). As an alternative to radiation, other forms local therapies including radiofrequency ablation, irreversible electroporation, high-intensity focused ultrasound, microwave ablation..."

Journal • Review