Silexion Therapeutics Releases CEO Letter to Shareholders Highlighting 2025’s Significant Achievements and Outlining Upcoming Milestones for 2026

Rhea-AI Summary

Silexion Therapeutics (NASDAQ: SLXN) reported 2025 preclinical and operational progress for its lead RNAi asset SIL204, including >90% tumor inhibition in multiple human KRAS-mutant models and validated activity against 8 KRAS mutations. The company completed two‑species toxicology with no systemic organ toxicity reported, received positive written scientific advice from Germany’s BfArM, raised >$18 million, regained Nasdaq compliance, and established manufacturing and CRO partnerships. Silexion plans a Phase 2/3 LAPC trial with regulatory submissions and clinical start targeted in H1 2026 (Q1 regulatory responses expected).

Positive

• >90% tumor growth inhibition in preclinical models
• Validated activity against 8 KRAS mutations
• Raised $18+ million in 2025
• Completed two‑species toxicology with no systemic organ toxicity
• Planned Phase 2/3 LAPC trial starting in H1 2026

Negative

• Clinical benefit unproven: human data pending from 2026 trials
• Regulatory approvals pending: responses expected in Q1 2026
• Initial safety run‑in limited to ~18 patients before expansion

Key Figures

KRAS market potential $30+ billion annually Estimated global KRAS-driven cancer market for pan-KRAS platform

KRAS inhibitor market $10 billion Projected KRAS inhibitor market size by 2032

Pancreatic KRAS prevalence 90% Approximate share of pancreatic cancers with KRAS mutations

Colorectal KRAS prevalence 45% Approximate share of colorectal cancers with KRAS mutations

Lung adenocarcinoma KRAS 30–35% Approximate share of lung adenocarcinomas with KRAS mutations

Metastatic mortality share Over 80% Share of pancreatic cancer mortality attributed to metastatic disease

2025 financing Over $18 million Aggregate financing raised during 2025

Trial enrollment sizes ≈18 + 166 patients Safety run-in ~18 patients, then randomized stage ~166 patients

Market Reality Check

$2.10 Last Close

Volume Volume 141,156 is 2.56x the 20-day average of 55,096, showing elevated interest ahead of 2026 milestones. high

Technical Shares at $2.20 are trading below the 200-day MA of $8.53 and remain 95.75% under the 52-week high.

Peers on Argus

SLXN gained 17.02% on heavy volume while close peers showed mixed, smaller moves (e.g., QLGN +7.72%, DRMA +3.29%, ENTO -5.68%), pointing to a stock-specific reaction.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 16	Clinical trial filing	Positive	+1.2%	Israel Phase 2/3 application for SIL204 targeting Q2 2026 start.
Dec 02	Regulatory feedback	Positive	-7.6%	Positive BfArM advice confirming key Phase 2/3 design elements.
Nov 26	Investor conference	Neutral	+20.4%	Announcement of presentation at Noble Capital Markets conference.
Nov 25	Toxicology update	Positive	+7.6%	Two-species tox studies showed no systemic organ toxicity for SIL204.
Nov 12	Earnings & update	Neutral	+3.6%	Q3 2025 results, new capital, SIL204 preclinical data, Nasdaq compliance.

Pattern Detected

Recent news has usually led to positive price reactions, with only one notable divergence despite generally constructive clinical updates.

Recent Company History

Over the last few months, Silexion has advanced SIL204 toward a planned Phase 2/3 trial in locally advanced pancreatic cancer, including toxicology completion, positive BfArM feedback, and an Israeli trial application. Financial updates on Nov 12, 2025 highlighted new capital and regained Nasdaq compliance. Today’s shareholder letter largely reiterates and consolidates these 2025 achievements while outlining 2026 clinical milestones, fitting into a pattern of steady de‑risking of the SIL204 program.

Regulatory & Risk Context

Active S-3 Shelf Registration 2025-10-31

$4.9 million registered capacity

An effective resale shelf filed on Oct 31, 2025 covers up to 1,292,348 shares and 372 warrants for selling securityholders. The company would receive up to $4.9 million only if 344,063 registered warrants are exercised for cash; otherwise, it does not obtain proceeds from these registered securities.

Market Pulse Summary

This announcement summarizes a “transformational” 2025 for Silexion, highlighting strong preclinical KRAS data, completion of two-species toxicology, and positive BfArM guidance while outlining a Phase 2/3 design with ~18 safety run‑in patients and ~166 in the randomized stage. It also notes over $18 million raised in 2025 and an addressable KRAS-driven cancer market potentially above $30 billion. Investors may track regulatory decisions, enrollment progress, and financing use against these milestones.

Key Terms

rna interference (rnai) medical

"pioneering RNA interference (RNAi) therapies for KRAS-driven cancers"

A natural cellular process in which small RNA molecules shut down the production of a specific protein by blocking the instructions that make it, like flipping a precise light switch to silence one appliance without affecting others. For investors, RNA interference is important because it underpins a class of highly targeted therapies and research tools that can create new drugs, shorten development paths, and change the potential market and regulatory risks for companies working on gene-based treatments.

kras medical

"KRAS mutations, present in approximately 90% of pancreatic cancers"

KRAS is a gene that makes a protein acting like a switch to control cell growth; certain changes (mutations) can lock that switch on and drive uncontrolled cell multiplication, which is a common cause of many cancers. Investors care because drugs or tests targeting KRAS mutations can create large markets or avoidable risks depending on trial results and regulatory decisions, much like a key product feature deciding a gadget’s commercial success.

oncogenes medical

"rna-based approaches that silence oncogenes at the genetic level"

Oncogenes are genes that, when changed or overly active, push cells to grow and divide uncontrollably — like a gas pedal stuck down in a car. They matter to investors because they are common targets for cancer tests and drugs; knowing whether a tumor is driven by an oncogene can determine whether a therapy will work, shape clinical trial outcomes, regulatory approval chances and potential market size for diagnostics and treatments.

orthotopic medical

"In clinically relevant orthotopic pancreatic cancer models, SIL204 demonstrated"

Orthotopic describes placing tissue, cells, an organ, or a disease model in its normal anatomical location—for example, transplanting a liver into the liver bed or studying a tumor in the organ where it naturally grows. Investors watch for orthotopic approaches because they tend to produce results that better predict real-world safety and effectiveness than unnatural models, so they can improve the credibility of clinical data and influence regulatory and commercial prospects.

intratumoral medical

"dual-route strategy combines intratumoral delivery for primary tumors"

"Intratumoral" describes something that occurs or exists within a tumor, which is an abnormal growth of tissue. For investors, understanding intratumoral is important because it relates to medical treatments or research aimed at targeting the tumor directly, potentially leading to more effective therapies. Think of it as focusing treatment straight into the problem area, much like fixing a leak by working directly on the pipe itself.

systemic administration medical

"intratumoral delivery for primary tumors with systemic administration for metastases"

Systemic administration is giving a drug or biological therapy so it circulates through the bloodstream and reaches tissues throughout the body, rather than being applied to one spot. For investors, this matters because systemic delivery can widen a product’s patient reach and potential sales but also raises higher safety, manufacturing and regulatory hurdles—similar to watering an entire garden versus targeting a single plant, which affects cost, risk and marketability.

adenocarcinomas medical

"30–35% of lung adenocarcinomas—have remained among the most challenging"

Adenocarcinomas are cancers that start in gland-like cells that line organs and produce fluids or mucus, such as in the lung, colon, pancreas, breast or prostate. They matter to investors because they define large, specific patient groups for drug development, clinical trials and medical devices—akin to identifying a market niche—and influence potential sales, regulatory risk and healthcare spending tied to treatments and diagnostics.

locally advanced pancreatic cancer (lapc) medical

"Phase 2/3 clinical trial in LAPC Planned for H1 2026"

Locally advanced pancreatic cancer (LAPC) is cancer that has grown beyond the pancreas into nearby tissues or major blood vessels but has not spread to distant organs, making surgical removal impractical. It matters to investors because this stage defines the need for medical treatments, clinical trials and longer-term care rather than a one-time cure; successful therapies can represent substantial, sustained market opportunity while setbacks can delay approvals and reduce projected revenues, like fixing a critical but hard-to-reach section of a vital pipeline.

AI-generated analysis. Not financial advice.

SIL204 Demonstrated Significant Tumor Inhibition in Positive Pre Clinical Studies with Activity Across Pancreatic, Colorectal, and Lung Cancer Models

Company’s Platform Seeks to Address an Estimated $30+ Billion Global KRAS-Driven Cancer Market with Pan-KRAS Therapeutic Platform

Initiation of Phase 2/3 Clinical Trial in LAPC Planned for H1 2026 Following Positive Regulatory Feedback and Successful Toxicology Studies

Grand Cayman, Cayman Islands, Jan. 06, 2026 (GLOBE NEWSWIRE) -- Silexion Therapeutics Corp (NASDAQ: SLXN), a clinical-stage biotechnology company pioneering RNA interference (RNAi) therapies for KRAS-driven cancers, today released a letter to shareholders from Chairman and Chief Executive Officer, Mr. Ilan Hadar. The letter outlines the Company’s major progress in 2025, including positive preclinical data demonstrating significant inhibition in human KRAS-mutated cancer cell line models, successful completion of regulatory toxicology studies, positive feedback from Germany’s Federal Institute for Drugs and Medical Devices (BfArM) on Phase 2/3 trial design, and strategic manufacturing and clinical development collaborations positioning SIL204 for its planned human clinical trial initiation in 2026. In parallel, the letter outlines the vision ahead for 2026 and significant expected near-term milestones.

Dear Shareholders,

2025 was a transformational year for Silexion Therapeutics. We positioned our lead asset, SIL204, to enter human clinical trials in the first half of 2026, bringing us significantly closer to delivering breakthrough treatments for some of the most aggressive and difficult-to-treat cancers.

The oncology landscape is evolving rapidly. While the industry has made important strides in targeted cancer therapy over the past decade, KRAS mutations, present in approximately 90% of pancreatic cancers, 45% of colorectal cancers, and approximately 30–35% of lung adenocarcinomas—have remained among the most challenging targets in oncology. According to industry estimates, the KRAS inhibitor market is projected to reach approximately $10 billion by 2032¹, yet the only KRAS-targeted therapies currently approved are mutation-specific, addressing a limited subset of KRAS alterations, and the majority of KRAS-driven cancers still lack effective targeted treatment options. I believe Silexion is nearing an important inflection point. As the limitations of small molecule KRAS inhibitors become increasingly apparent  -restricted mutation coverage, drug resistance, and limited efficacy in certain tumor types, the industry is beginning to recognize the potential of RNAi-based approaches that silence oncogenes at the genetic level before cancer-driving proteins are expressed. I see SIL204 as a reflection of this next generation of cancer therapy, targeting KRAS at the genetic level and preventing the production of the mutated proteins that drive cancer growth from the outset.

We believe the long-term broader addressable market for our solution may exceed $30 billion annually when considering pancreatic, colorectal, and lung cancer treatment globally.² More importantly, over 80% of pancreatic cancer mortality is attributed to metastatic disease, a challenge that existing therapies have not adequately addressed. Our approach is designed specifically to target this unmet need.

Significant Scientific Progress in 2025

Throughout 2025, we generated compelling preclinical evidence demonstrating SIL204’s exceptional potency and broad applicability. Our pre-clinical results showed significant inhibition of cancer cell growth in human cancer cell line models, which consistently exceeded 90% across multiple models. We validated activity against eight distinct KRAS mutations, including G12D, G12V, G12R, G12C, G13C, G12A, Q61H, and G13D.

Importantly, we demonstrated preclinical efficacy across five different cancer types, including pancreatic, colorectal, lung, gastric, and additional solid tumor models. In clinically relevant orthotopic pancreatic cancer models, SIL204 demonstrated significant reduction of both primary tumor growth and metastatic spread to secondary organs following systemic administration. We confirmed drug distribution to major metastatic sites, including liver, peritoneum, and lung, with measurable reductions in tumor burden at clinically relevant doses.

Beyond generating compelling scientific data, we executed systematically on operational requirements. We completed two-species toxicology studies confirming no systemic organ toxicity, received positive written Scientific Advice from Germany’s Federal Institute for Drugs and Medical Devices (BfArM) on our Phase 2/3 trial design, established strategic collaborations with Catalent for clinical manufacturing and AMS Advanced Medical Services as our contract research organization, and raised over $18 million in aggregate financing during 2025 while regaining full Nasdaq compliance.

2026: Clinical Validation and Upcoming Value-Creating Milestones

As recently reported, we have completed our regulatory submissions in Israel to initiate our Phase 2/3 clinical trial of SIL204 in locally advanced pancreatic cancer (LAPC). We anticipate receiving a response during the first quarter of 2026, with clinical trial commencement planned for the first half of 2026.

Additional regulatory submissions to Germany are planned for the first quarter of 2026, with additional European Union submissions expected later in 2026 and a U.S. IND submission anticipated in the second half of 2026.Our innovative dual-route strategy combines intratumoral delivery for primary tumors with systemic administration for metastases, addressing both components of this deadly disease. The initial safety run-in will evaluate this approach in combination with standard chemotherapy in approximately 18 patients, assessing safety, tolerability, and preliminary efficacy signals. Following successful completion, we plan to expand into a second stage of the phase 2/3 clinical trial which would include a randomized study of approximately 166 patients.

We believe that the human data generated during the first stage of our clinical program in 2026 will be critical in demonstrating the potential of our approach and may serve as a foundation for future strategic collaborations and financing as we work to advance SIL204 toward a first-in-class and first-line therapy for pancreatic cancer.

As we advance into human trials in 2026, we remain focused on rigorous execution, scientific integrity, and our ultimate goal: delivering meaningful clinical benefit to patients with KRAS-driven cancers who currently have limited options. The progress we achieved in 2025 reflects the dedication of our team, the expertise of our partners, and the continued support of our shareholders.

Thank you for your trust in our mission.

Sincerely,

Ilan Hadar
Chairman and Chief Executive Officer
Silexion Therapeutics Corp

About Silexion Therapeutics
Silexion Therapeutics is a pioneering clinical stage, oncology-focused biotechnology company dedicated to the development of innovative treatments for unsatisfactorily treated solid tumor cancers which have the mutated KRAS oncogene, generally considered to be the most common oncogenic gene driver in human cancers. The Company conducted a Phase 2a clinical trial in its first-generation product which showed a positive trend in comparison to the control of chemotherapy alone. Silexion is committed to pushing the boundaries of therapeutic advancements in the field of oncology, and further developing its lead product candidate for locally advanced pancreatic cancer. 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 the initiation, progress, and timing of regulatory submissions in Israel, Germany, the European Union, and the United States; the planned initiation and conduct of the Phase 2/3 clinical trial of SIL204 in the first half of 2026; the planned safety run-in and subsequent expansion of the clinical trial; the timing of additional regulatory submissions and approvals; and the potential therapeutic profile and clinical utility of SIL204 based on preclinical data, 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, proceed with planned regulatory submissions, 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; (vi) Silexion's ability to maintain its Nasdaq listing; and (vii) other risks and uncertainties set forth in the documents filed by the Company with the SEC, including the Company's Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 18, 2025. 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

Investor Contact:
Arx Investor Relations
North American Equities Desk
silexion@arxhq.com

---

¹ https://www.biospace.com/how-upcoming-kras-inhibitors-are-expected-to-shape-the-future-oncology-market-landscape

²  (i) Pancratic Cancer Treatment Market; (ii) Colorectal Cancer Therapeutics Market; (iii) NSCLC Lunc Cancer Therapeutics Market

FAQ

What is Silexion's plan for the SIL204 Phase 2/3 trial and timeline for SLXN?

Silexion plans a Phase 2/3 LAPC trial with regulatory responses expected in Q1 2026 and clinical start targeted in H1 2026.

Which KRAS mutations did SIL204 show preclinical activity against in Silexion's 2025 data?

Preclinical results validated activity against 8 KRAS mutations including G12D, G12V, G12R, G12C, G13C, G12A, Q61H, and G13D.

How large will the initial SLXN clinical cohorts be in the SIL204 trial?

The initial safety run‑in will enroll about 18 patients, with a planned randomized expansion of approximately 166 patients.

What operational milestones did Silexion achieve in 2025 relevant to SLXN investors?

In 2025 Silexion completed two‑species toxicology with no systemic organ toxicity, raised $18+ million, regained Nasdaq compliance, and secured manufacturing and CRO partners.

Does SIL204 show activity across cancer types according to Silexion's announcement?

Yes; preclinical efficacy was reported across five cancer types including pancreatic, colorectal, lung, gastric, and other solid tumors.