PESG Report on Silexion Therapeutics: Leading RNAi in KRAS-Driven Cancer Fight

Silexion Therapeutics, listed on NASDAQ as SLXN, is carving a niche in the precision oncology sector with a focus on RNA interference (RNAi) therapies targeting KRAS-driven cancers. Following its merger with Moringa Acquisition Corp, Silexion has strategically positioned itself in the burgeoning field of targeted cancer treatments, especially for pancreatic and other KRAS-driven cancers.

The core of Silexion's innovative approach is its proprietary LODER™ (Local Drug EluteR) platform, which has shown promising results in Phase 2 clinical trials for advanced pancreatic cancer. This technology is distinguished by its dual pharmacological functions: oncogene silencing and localized drug delivery. Unlike small molecule KRAS inhibitors targeting already oncogenic proteins, Silexion's siRNA inhibits the production of oncogenic proteins from the start. The LODER™ system effectively bypasses tumor barriers, enabling higher drug concentrations directly within the tumor, thus enhancing efficacy and minimizing systemic side effects.

Silexion's advanced product, SIL-204, is an optimized siRNA formulation slated for Phase 2/3 clinical trials between 2025 and 2026. SIL-204 marks a significant leap in RNAi technology, capable of targeting a broader range of KRAS mutations (pan KRAS G12x). This broader targeting potential is crucial as it could address a wide spectrum of KRAS-driven cancers, contrasting with current KRAS inhibitors that focus only on KRAS G12C mutations, present in a minor fraction of pancreatic cancer cases.

Pancreatic cancer remains one of the toughest cancers to treat, with a five-year survival rate of merely 12.8%. This is primarily due to late detection, aggressive tumor growth, early metastasis, and a dense tumor microenvironment that hampers drug penetration. Additionally, KRAS mutations, present in over 90% of pancreatic cancer cases, pose a significant challenge for conventional therapies. Compounding these issues is the cancer's propensity to develop resistance to standard treatments, leading to poor long-term outcomes.

Silexion's LODER™ and SIL-204 technologies aim to tackle these challenges head-on by silencing KRAS mutations at the genetic level and delivering treatments locally. This approach could potentially overcome the barriers that have historically hindered effective pancreatic cancer treatments.

Clinical trials of Silexion's LODER™ technology have yielded encouraging results. Phase 2 studies demonstrated a 9.3-month improvement in overall survival when LODER™ was combined with standard chemotherapy, compared to chemotherapy alone for non-resectable pancreatic cancer patients with KRAS G12D/V mutations. The trials also showed an increased objective response rate (ORR) of 55% with the combination therapy, compared to 20% with chemotherapy alone. Notably, the ORR increased to 64% in initially non-resectable tumors that became resectable.

Looking beyond pancreatic cancer, Silexion's innovative RNAi technology and LODER™ platform have the potential for broader applications in other KRAS-driven cancers. This could significantly expand Silexion's market opportunity and impact in precision oncology. Their pipeline includes plans to target other pancreatic cancer types and cancers like colorectal cancer, which are also associated with KRAS mutations.

The ability of Silexion's technology to target a wider range of KRAS mutations, compared to current small molecule inhibitors, positions the company advantageously for addressing multiple cancer types. This versatility is particularly valuable since KRAS mutations are prevalent in various cancers beyond pancreatic, including lung and colorectal cancers. Additionally, the localized delivery system of the LODER™ platform could be adapted for other solid tumors, offering a unique advantage for treating difficult-to-target cancers.

As Silexion advances its clinical trials and eyes expansion into additional indications, it stands to significantly broaden its addressable market, aligning with the growing trend in precision medicine towards versatile platforms that can treat multiple cancer types driven by similar genetic mutations.

The precision medicine market, especially in oncology, is experiencing rapid growth, with significant interest from major pharmaceutical companies. This trend is driving a surge in M&A activity, as companies seek innovative assets to enhance their oncology pipelines. Silexion's focus on RNAi technology for KRAS-driven cancers, and its innovative approach to pancreatic cancer treatment, positions it as a potential acquisition target in this dynamic landscape.

With initial promising clinical trial results, Silexion's unique technology aligns well with industry trends toward targeted and personalized cancer therapies. As large pharmaceutical companies continue to seek differentiated assets, Silexion's approach to addressing high-unmet-need cancers could make it a valuable addition to a larger company's portfolio.