What changed in this filing

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Item 1. Business

2026-03-17 compared with 2025-03-18 · 136 added, 86 removed, 527 unchanged (30% of the section changed)

Unless the context otherwise requires, in this “Business” section, the terms “we,” “us” and “our” generally refer to:

(i) for the period following the Closing of the Business Combination on August 15, 2024, Silexion Therapeutics Corp (formerly known as Biomotion Sciences), a Cayman Islands exempted company (“New Silexion”) and its consolidated subsidiaries, including Silexion Therapeutics Ltd., an Israeli company (“Silexion”), through which our business is primarily conducted, and, (ii) with respect to all periods prior to and through the Closing of the Business Combination, Silexion and its subsidiaries.

(i) for the period following the Closing of the Business Combination on August 15, 2024, Silexion Therapeutics Corp (formerly known as Biomotion Sciences), a Cayman Islands exempted company (“Silexion”) and its consolidated subsidiaries, including Silexion Therapeutics Ltd., an Israeli company (“Silexion Israel”), through which our business is primarily conducted, and, (ii) with respect to all periods prior to and through the Closing of the Business Combination, Silexion Israel and its subsidiaries.

Business Overview

We are a clinical-stage, oncology-focused biotechnology company engaged in the discovery and development of proprietary treatments for KRAS-driven cancers.

The KRAS gene is an oncogene that is involved in the regulation of cell division as a result of its ability to relay external signals into the cell.

Based on our research of refractory solid tumor cancers, we are actively developing a platform focused on the silencing of the KRAS oncogene using RNA-interference therapeutics.

Our lead product candidate, SIL204, consists of locally administered small interfering RNAs, or siRNA, in a solution, as a first-line treatment of locally advanced pancreatic cancer patients, or LAPC, in combination with standard-of-care chemotherapy.

The KRAS oncogene is considered to be the most common oncogenic gene driver in human cancers, and the most notable in pancreatic, lung, and gastrointestinal (GI) (including colorectal, esophagus, stomach, small bowel, and appendix) cancers.

Considered a challenging therapeutic target due to its intrinsic characteristics, recent advances have been made at directly inhibiting the KRAS proteins produced by the mutated gene.

Our platform is designed to silence the gene, and thus prevent the production of the harmful mutated KRAS proteins driving the growth of cancerous tumors.

We are currently focused on treatment for pancreatic cancer (PC) tumors bearing the KRAS G12D or KRAS G12V mutations where metastases have not been detected and are non-resectable, i.e.

they are not able to be surgically removed.

For our first indication, we are targeting the largest and least treatable form of localized pancreatic tumors referred to as locally advanced pancreatic cancer.

LAPC represents approximately 30% of the total pancreatic cancer population.

We are currently developing SIL204, a second-generation siRNA product candidate following a Phase 1 and Phase 2 clinical trial with our first-generation siRNA product candidate, siG12D-LODER, which we also refer to as Loder.

Results from the Phase 2 clinical trial showed a trend for differences between treatment groups in patients with the KRAS G12D/V mutation, with the Loder arm suggesting an overall survival advantage of 9.3 months.

SIL204 has been designed to optimize Loder with the aim of improving uptake into tumor cells, enhancing stability, and broadening the scope of its silencing activity.

We plan to conduct a Phase 2/3 prospective, randomized, controlled, multinational, open-label trial in LAPC subjects that harbor the KRAS G12D/V mutations to evaluate the efficacy, safety and tolerability of SIL204 administered intratumorally in combination with standard of care (SoC) chemotherapy versus SoC chemotherapy only.

In support of our planned Phase 2/3 trial, we held a meeting with the Federal Institute for Drugs and Medical Devices in Germany (BfArM) to discuss the planned design of the Phase 2/3 trial at which BfArM agreed, in principle, to the design.

In preparation for the study, we plan to initiate toxicology studies of SIL204 in 2025 followed by the regulatory submission in the first quarter of 2026 to initiate the Phase 2/3 trial and trial initiation in the first half of 2026.

At this time, we are focused on the further development of the core siRNA technology, SIL204, and its clinical development

We are a clinical-stage, oncology-focused biotechnology company engaged in the discovery and development of proprietary treatments for cancers driven by mutations in the mutations in the Kirsten rat sarcoma viral oncogene homolog (“ KRAS ”).

The KRAS gene, when mutated, plays a central role in many cancer types, such as pancreatic, colorectal and lung, and is therefore considered to be an oncogene.

This oncogene instructs cells to make the corresponding KRAS protein which has a controlling function in cell growth signaling in the cancer cells.

While multiple pharmaceutical companies are pursuing strategies to inhibit or tag the KRAS protein for degradation and thereby limit its downstream signaling, our approach is differentiated by targeting the root cause of oncogenic signaling— we silence the KRAS oncogene itself, preventing the production of the oncogenic protein.

Our proprietary technology is designed to prompt tumor cells to degrade the messenger RNA (mRNA) that bridges the oncogene and the cellular protein synthesis machinery, utilizing small interfering RNA (siRNA) constructs that are chemically modified to enhance stability and cellular uptake while maintaining biological activity that interferes with the mRNA function.

Our lead product candidate, SIL204, is a second-generation siRNA engineered to suppress the production’ of mutated KRAS proteins.

In pancreatic cancer, approximately 92% of patients have this mutated oncogene.

To address both localized and systemic disease, as well as the tumor’s dense desmoplastic stroma, which limits the effectiveness of current treatments, our novel delivery approach, which we refer to as an Integrated Treatment Regimen, involves administering SIL204 both directly into the tumor and systemically via subcutaneous injection, in combination with standard-of-care chemotherapy.

In a previous Phase 2 clinical trial with our first-generation siRNA, siG12D-LODER (which we also refer to as Loder), the combination of siRNA and standard-of-care chemotherapy demonstrated a trend for an overall survival benefit of 9.3 months compared to standard-of-care chemotherapy alone.

Building on preclinical advancements and regimen optimization, we believe SIL204 has the potential to further improve clinical outcomes, by improving uptake into tumor cells, enhancing stability, and broadening the scope of its silencing activity.

We are currently focused on treatment of non-resectable locally advanced pancreatic cancer (LAPC) patients which bear a KRAS mutation.

LAPC represents the least treatable form of localized pancreatic cancer where the primary tumors are too large or in a position which precludes being able to be surgically removed, and where metastases have not been detected.

Overall LAPC represent about 30% of pancreatic cancer (PC) and the KRAS G12D and KRAS G12V mutations (KRAS G12D/V) represent about 68% of PC.

Our first indication is focusing on LAPC patients bearing KRAS G12D/V which represents about 20% of all PC patients.

We are also exploring the effectiveness of our treatment (SIL204-SL) for LAPC with any KRAS mutations which represents almost a third of PC.

With our integrated treatment regimen (SIL204-IR) we target the primary tumor and the micro metastases which occur relatively early in the disease stage.

During 2025, we continued to advance operational readiness, including the onboarding of external vendors, with the initiation of clinical studies contingent upon obtaining regulatory clearance.

We held a meeting with the Federal Institute for Drugs and Medical Devices in Germany (BfArM) to discuss the planned design of the Phase 2/3 trial at which BfArM agreed, in principle, to the design.

In preparation for our initial clinical study with SIL204, we furthermore conducted toxicology studies of SIL204 in 2025, completing two-species toxicology studies that confirmed no systemic organ toxicity.

In the fourth quarter of 2025, we submitted an application to the Israeli Ministry of Health for commencing the adaptive Phase 2/3 trial with a safety run-in at several locations in Israel.

In the first quarter of 2026, we will submit to BfArM an application to conduct clinical studies in Germany.

We are expecting to initiate the first part of our Phase 2/3 clinical studies in the second quarter of 2026.

We expect to submit applications for trials in additional European Union countries early in 2027, and to submit an investigational new drug application (IND) to the U.S.

Food and Drug Administration (FDA) in Q1, 2027.

The initial stage of our clinical trials will involve a safety run-in that will evaluate our treatment approach in combination with standard of care (SoC) chemotherapy in approximately 18 patients, assessing safety, tolerability, and preliminary efficacy signals.

Subject to our successful completion of that stage, 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 prior to an interim analysis for sample size adjustment and futility as recommended by the independent DSMB as well as the DSMB recommendation for the final selected subcutaneous dose to be administered in the last segment of the trial (Phase 3 segment).

Our Market Opportunity

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Lee, etc., NPJ Precision Oncology 2022;

91 analysis).

In addition, the study found that various cancers have an amplification of the non-mutated KRAS protein.

Tumor types with a high prevalence of KRAS mutations included pancreatic ductal adenocarcinoma (PDAC) (92%), colorectal cancer (CRC) (49%), and non-squamous non-small cell lung cancer (NSCLC) (35%).

These three cancers represent 71% of the KRAS mutant pan-tumor population studied.

These three cancers represent about 70% of the KRAS mutant pan-tumor population studied.

The following chart shows the distribution of various alternations of the KRAS oncogene in various type of cancers:

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Every year in the U.S.

approximately 50,000 people die from pancreatic cancer, while approximately 66,000 new patients are diagnosed with pancreatic cancer annually (Co-Pilot Micorsoft).

approximately 50,000 people die from pancreatic cancer, while approximately 66,000 new patients are diagnosed with pancreatic cancer annually

Estimated New Cases (2024)

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This class of siRNA therapeutics exert their effect by inducing the enzymatic breakdown of the messenger (mRNA) of a targeted gene inhibiting the process called translation, which turns the message (mRNA) into a protein.

The general mechanism for the silencing the oncogene is actually an evolutionary process developed by cells for translation regulation or to protect against viruses.

We believe our approach also builds upon the validation of our target KRAS mutations as a target for cancers, as seen with the two small molecule KRAS inhibitors currently on the market for non-small cell lung cancer, and the validation of siRNA technology, as it is currently on the market for six non-oncological indications.

The general mechanism for silencing the oncogene is actually an evolutionary process developed by cells for translation regulation or to protect against viruses.

None of these agents is appropriate for our intended primary indication, but we believe they do support our premises regarding target (KRAS) and basic technology (siRNA) for use in the oncological area.

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All patients were in the safety cohort.

The KRAS mutation status was however determined post-hoc in a sample of 31 patients (21 of whom were Loder treated) in the table below:

The KRAS mutation status was determined from all retained samples that were able to be obtained.

This included 31 patients (21 of whom were Loder treated) in the table below:

A total of up to eight Loders (2.8 mg siRNA/Loder) were inserted into the pancreatic tumor per single administration.

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Overall, a total of 59 subjects with LAPC were enrolled in the study, 38 were treated with Loder and 48 subjects overall (81.3%) completed the study.

In Cohort 1, 15/19 (78.9%) completed the Loder arm and 11/18 (61.1%) completed the standard of care arm.

In Cohort 2, 21/22 (95.5%) completed the study.

The best efficacy results were observed with those patients harboring a KRAS G12D or KRAS G12V mutation (G12D/V).

Randomization to either control treatment of standard of care chemotherapy (SoC) or active treatment of SoC plus siG12D-Loder was only in Cohort 1.

In this cohort 15/19 (78.9%) completed the active treatment (siG12D-Loder) arm and 11/18 (61.1%) completed the standard of care arm.

In Cohort 2 which only had an active treatment arm, 21/22 (95.5%) completed the study.

Analysis of the cohort which had a control group (Cohort 1) and where the KRAS mutation was able to be determined showed the best efficacy results with those patients harboring a KRAS G12D or KRAS G12V mutation (G12D/V).

Below are the results of this subset analysis, which represents about 70% of the LAPC patients in the general population and the population which we will use for the primary endpoint in our next trial with SIL204.

The Objective Response Rates (ORR), as determined by the standard RECIST v1.1 criteria, in the two cohorts were similar, with 61-64% of the KRAS G12D/V patients responding positively

The primary endpoint for the trial was OS in the KRAS G12D/V population.

The Objective Response Rates (ORR), as determined by the standard RECIST v1.1 criteria, in the two cohorts were similar, with 61-64% of the KRASG12D/V patients responding positively

The primary endpoint for the trial was OS in the KRASG12D/V population.

In the overall survival (OS) analysis of the randomized cohort (Cohort 1), the median time to death in the standard of care chemotherapy group was 13.4 months.

When the treatment included the Loder, the OS was increased to 22.7 months.

This represents a numerical advantage of 9.3 months.

This represents a trend for a numerical advantage of 9.3 months.

The Hazard ratio (HR)=0.59, (95% CI, 0.18, 1.96, p=0.39), which represents ~65% increase in median overall survival (OS) LODER+SoC vs.

The Loder treatment group in this analysis of KRAS G12D/V was n=11 and for the Control group n=5.

The Loder treatment group in this analysis of KRASG12D/V was n=11 and for the Control group n=5.

Despite the relatively small size, OS of the control group is consistent with that found in the literature for non-resectable-localized-PC (Gemenetzis, G.

et al, 2019).

Although the trial was not powered for nor reached statistical significance, the results indicate a positive trend for an improvement in OS and ORR with Loder + SOC in the KRAS G12D/V mutation group.

Although the trial was not powered for nor reached statistical significance, the results indicate a positive trend for an improvement in OS and ORR with Loder + SOC in the KRASG12D/V mutation group.

Combining both Cohorts (1 + 2) (cohort 2 having only a single Loder + SOC treatment arm but adding it to the randomized treatment arm of Loder + SoC chemo) and comparing it to the Control group from Cohort 1 (SoC chemo) also showed an advantage for the Loder arm, but smaller than randomized Cohort 1 alone.

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Each cycle had ~4 injections to tumor for ~ 372 Loder injections.

The Serious Adverse Events (SAEs) related to treatment in patients with LAPC who received Loder + Chemotherapy (treatment plus EUS-endoscopy administration procedure) were as follows:

The Treatment-emergent adverse Events (TEAEs) > 10% were as follows:

In Cohort 1, all subjects in the Loder treatment group reported at least one moderate or severe treatment emergent adverse event (TEAE) (18 subjects).

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SIL204 (second generation) Pre-Clinical Studies

Studies with SIL204 in human cell line PK59 harboring a KRAS G12D mutation showed that the mRNA transcript and corresponding KRAS protein were significantly reduced

We have conducted the evaluation of SIL204 in pharmacology and pharmacokinetics (PK).

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SIL204 shows broad silencing (inhibition) of KRAS across the human KRAS mutations that are important for pancreatic, colorectal cancer, and lung cancer at sub-nanomolar concentrations, in a co-transfection model where human KRAS is transfected into mouse Hepa1-6 cells with a Dual-Glo reporter plasmid, This activity not only maintains the silencing activity of Loder but also expands its activity to additional mutations that are considered to be oncogenic.

Effect of SIL204 on the growth of human pancreatic tumor cell line

SIL204 Robustly Inhibits Growth of Human Pancreatic Tumor Cell Line (Panc-1) in Dose-Dependent Manner.

SIL204 Inhibits Growth of Human Tumor Cell Lines from Various Cancers with G12x and Q61x Mutations.

Shown is the CellTiter-Glo (CTG)) assay where IC 90 is the concentration for 90% inhibition of tumor cell growth and IC 50 is the concentration to achieve 50% inhibition.

These results support the above results in the mouse hepa cells transfected with human KRAS mutations and indicates that the growth of the various cells lines with different KRAS mutations from difference cancer types can be highly (>90%) inhibited as indicated by the IC90 values.

An in silico thermodynamic stability of potential binding of siRNA SIL204 antisense strand to mRNA of off-target sites (Genome/Transcriptome and regulatory miR) showed a strong binding to our intended target (mutated KRAS) and no off-target active anti-sense binding indicting both a low risk for side effects in general and specificity for the PC, CRC, NSCLC -cancer driving subgroup of RAS mutations (K(RAS)) indicating a low risk for side effects from general RAS inhibition.

The analysis was evaluated by Gibb’s free energy changes (ΔG) of duplex, not mismatch penalties, like BLAST, was determined using various software programs, including ThermoSearch and OMP DE (DNA Software).

The inhibition of the growth of the human tumor cell lines by SIL204 was also found to work synergistically with fluorouracil, irinotecan, and gemcitabine-containing chemotherapeutic agents.

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This is an important property for being a first-line treatment in pancreatic cancer.

Growth followed in human pancreatic cell line Panc-1 (G12D), * p<0.05, ***p<0.0005.

These results are also consistent with the clinical results where siG12DLoder + SOC improves outcomes compared to SOC chemotherapy alone.

In vivo models of efficacy

Intratumor SIL204 Significantly Reduced Tumor Volume and Growth While Increasing Tumor Necrosis (cell death) in Human Pancreatic Cancer Xenograft.

In this study on Day 1:

Capan-1 (KRAS G12V) luciferase cells were xenografted to mice (s.c.) concurrently with IT-administered SIL204 formulated in extended-release microparticles.

tumors were removed, area determined and analyzed by histology for % necrosis from tumor center slice.

***p<0.0005, s.c.

= subcutaneous tumor, intratumor (IT) SIL204-SL administration

• SIL204 administered subcutaneously (systemically) showed significant efficacy in different mouse metastatic pancreatic orthotopic models, where the human pancreatic tumor cell lines (tumors) grow in their native pancreatic environment.

o Where the tumor was the human pancreatic tumor cell line AsPC-1, which harbors the KRAS G12D mutation, SIL204 showed a 70% reduction in overall bioluminescence, an indication of tumor cell number, by day 28, at a dose whose human equivalency is a proposed SIL204 dose to be used clinically.

Where the tumor was the human pancreatic tumor cell line Panc-1, which also harbors the KRAS G12D mutation, SIL204 halted the tumor growth.

Bioluminescence or tumor cell numbers decreased dramatically in a dose-dependent manner, with the highest-dose group showing the most significant effect (control increased by ~100% while SIL204-treated decreased by 12%).

~80% reduction in bioluminescence by day 28 was also observed with tumors grown with the human pancreatic cell line BxPC-3 which does not carry a KRASG12 mutation.

When the bioliluminesence was determined in the various organs of the mice, SIL204 treatment was found to significantly reduce the metastatic spread to secondary organs, substantially lowering metastatic burden across the liver, intestine, spleen and stomach in the two models checked for the various organs, the Panc-1 and BxPC-3 models.

Safety and specificity of SIL204 as determined from in silico analyses

Potential binding sites of SIL204 to human genome/transcriptome and regulatory microRNAs (miR), when judged on Gibb’s free energy change (ΔG) of duplex, not mismatch penalties, like BLAST, was determined using various software programs, including ThermoSearch and OMP DE (DNA Software).

When analyzing first for on-target binding (KRAS G12V ), the binding values indicated a strong on-target binding (-31kcal/mol).

When analyzing for off-target effects, which might result in an adverse event, in the genome/transcriptome, or its ability to inhibit regulatory microRNAs or act as a regulatory microRNA mimic, SIL204 was determined to have a high specificity, with strong on-target binding and minimal off-target binding.

These results substantially reduce the risk of a systemic side effect from SIL204.

The results from efficacy models where SIL204 was subcutaneously administered, together with the pharmacokinetic and stability data and in silico binding data, indicate that systemic SIL204 delivery can be a viable administration route.

Response analysis (left curve below) indicates a dose-response effect and the imaging of the organs (Rt curve below) shows that in organs where pancreatic cancer metastasizes clinically, SIL204 is effective after s.c.

Tumors from human tumor cell line Panc-1 harboring KRAS G12D mutation-luciferase.

Response analysis total bioluminescence.

30% and 50% decrease considered positive at Day 14.

30%=RECIST criteria

In H2,2025, we completed a toxicology study package with rSIL204 sufficient to initiate our planned Phase 2/3 clinical trial.

This study was conducted in two relevant species and aligned with ICH S9 guidance for oncology and confirmed by regulatory agency for initiation of Phase 2/3 clinical trial.

• Established safety margins of up to 11-fold over the clinical starting dose.

• SIL204 was well-tolerated in both species with no test article-related organ toxicity or mortality observed.

• Adverse findings limited to non-adverse changes at local injection site, fully resolved at 1 month.

• No evidence of complement activation or immunotoxicity.

These toxicology studies confirmed that administration of SIL204 does not lead to systemic organ toxicity.

Manufacturing

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We have agreements with contract manufacturers for the manufacturing of SIL204 and its formulation development for clinical development.

SIL204 was manufactured for initiating the clinical trial, with the later manufacturing for the clinical trial at a commercial level manufacturing site.

Our formulation has been selected and will be manufactured for initiation of the Phase 2/3 clinical trial at a site where it can be later manufactured commercially.

SIL204 Milestones Achieved

• GMP API for Segment 1 manufactured, Segment 2 GMP manufacturing ongoing

• GMP formulation selected, manufacturing in process

• Toxicology for Segment 1 completed, for Segment 2/3 later in 2026

• Scientific Advice from national European authority, with positive response

• Go ahead from ethics committee for Phase 2/3 from major oncology center

• Submitted to Israel MoH to initiate Phase 2/3 trial, waiting for response

• Submission to German MoH for Phase 2/3 trial planned 03/26

Future Development Plans

We plan to conduct a Phase 2/3 prospective, randomized, controlled, multinational, two-arm, open-label trial in LAPC subjects that harbor the KRAS G12D/V mutations to evaluate the efficacy, safety and tolerability of SIL204 administered intratumorally in combination with SoC chemotherapy versus SoC chemotherapy only.

The study design, including the dose and dosing frequency, the combination with SoC chemotherapy, the proposed target population and safety monitoring is based on the experience with the preceding Phase 1 and 2 clinical studies with the first-generation siRNA product candidate, Loder.

The study is initially planned to enroll approximately 388 subjects and has an adaptive design with several segments— a screening period which includes a biopsy for KRAS mutations, and a CT scan and physiologic profiling to ensure subjects are qualified for treatment.

The first Phase will be a non-randomized safety run-in phase, followed by a randomized Phase 2 phase leading to the Phase 3 phase of the trial.

We plan to commence in the second quarter of 2026 prospective, randomized, controlled, multinational, multi-center, Phase 2/3, open-label trial, evaluating the efficacy, safety and tolerability of SIL204-SL Integrated Therapeutic Regimen (SIL204-IR) (various doses) in combination with Standard of Care (SoC) chemotherapy vs.

SoC chemotherapy alone for the treatment of participants with locally advanced pancreatic cancer (LAPC) harboring KRAS mutation.

This trial uses an adaptive design with three segments;

Segment 1 as safety run-in Phase 2, Segment 2 as dose-finding (planned to be initiated early in 2027) and expanded Phase 2 and Segment 3 as confirmatory Phase 3.

The study is expected to commence at three sites in Israel, and, once approval is received from the BfArM, to be conducted in parallel in Germany, and will later be expanded to other European Union countries and the U.S.

T he study is initially planned to enroll 15 to 21 participants in Segment 1, which is our first major milestone once the trial initiates and is expected to be completed within the first year, and approximately 403 participants in total for the entire Phase 2/3 trial.

There also will be an interim analysis for sample size adjustment between the Phase 2 and Phase 3 segments of the trial.

The following period for each patient will be 24 months.

The follow-up period for each patient once randomization starts in Segment 2 of the trial will be 24 months.

The study design is powered for statistical significance and designed to meet regulatory requirements to be considered a pivotal trial.

The safety will be review by an independent Data and Safety Monitoring Board (DSMB)

In support of our planned Phase 2/3 trial of SIL204, we held a meeting with the Federal Institute for Drugs and Medical Devices in Germany (BfArM) to discuss the planned design of the Phase 2/3 trial, at which BfArM agreed, in principle, to the design.

In preparation for the study, we plan to initiate toxicology studies of SIL204 in 2025 followed by the regulatory submission in Q1 2026 to initiate the Phase 2/3 trial in the first half of 2026.

Currently, we manufacture SIL204 under GMP production to be used for the clinical trial.

At this time, we are focused on the further development of the core siRNA technology underlying SIL204 as well as our clinical development of SIL204.

We are furthermore planning a preclinical study to expand our pipeline for additional indications of SIL204 and combination use.

We expect to apply in 2026 for Orphan Drug Designation in both the U.S.

The safety will be reviewed by an independent Data and Safety Monitoring Board (DSMB)

In support of our planned Phase 2/3 trial of SIL204, in 2025 we held a meeting with BfArM in Germany to discuss the planned design of the Phase 2/3 trial, at which BfArM agreed, in principle, to the design.

Currently, we are manufacturing (through our partners) SIL204 under GMP production to be used for the clinical trial.

Throughout 2026, we will focus on the clinical development of SIL204 in the Phase 2/3 trial and on expanding the pipeline with additional preclinical studies for additional indications of SIL204.

We will also initiate the toxicology program which will be sufficient to satisfy the toxicology requirements for a marketing application.

We expect to apply H1 2027 for Orphan Drug Designation in both the U.S.

In the U.S., Orphan Drug designation by the FDA gives a company exclusive marketing rights for a seven-year period, along with other benefits to recoup the costs of researching and developing drugs to treat rare diseases.

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Our Phase 2 trial with our first-generation siRNA product, Loder in LAPC patients acts as a validation of approach and foundation for our continued development efforts.

As further described in “Future Development Plans”, we plan to initiate toxicology studies of SIL204 in 2025 followed by the regulatory submission in Q1 2026 to initiate a Phase 2/3 trial of SIL204 powered for statistical significance.

At this time, we are focused on the further development of the core siRNA technology, SIL204, as well as the clinical development and expansion of our pipeline

Leveraging our platform to other oncological indications harboring the KRAS G12 mutation.

As further described in “ Future Development Plans ” above, we conducted toxicology studies of SIL204 in 2025 followed by the regulatory submission in Q1 2026 to initiate a Phase 2/3 trial of SIL204 powered for statistical significance.

At this time, we are focused on the further development of the core siRNA technology, SIL204, and on advancing its clinical development, while also expanding our pipeline for additional oncological indications.

Leveraging our platform to other oncological indications harboring the KRASG12 mutation .

Our preclinical CTG assay results in 2025 evidenced high inhibition of the SNU-601 cell line (G12D mutation), expanding SIL204's potential to a fifth cancer type-gastric cancer.

Advancing SIL204 to commercialization.

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There are a large number of companies developing or marketing treatments for cancer, including major biotechnology and pharmaceutical companies.

These treatments consist of novel treatments based on small molecule drug products, cell-based therapies, as well as traditional chemotherapy treatments.

There are also an increasing number of companies commercializing treatments and/or developing programs specifically targeting KRAS mutations, including KRAS G12D and KRAS G12V, in a variety of manners and for a variety of indications, including cancer, including Amgen Inc., Bristol-Myers Squibb Company (through the recently acquired Mirati Therapeutics, Inc.), Revolution Medicines, Inc., AstraZeneca (in collaboration with Usynova), BioNTech, Roche, Merck/Moderna, Boehringer and Gilead.

The KRAS inhibitors on the market include those from Amgen and Bristol-Myers Squibb which have a small molecule KRAS G12C inhibitors.

Clinical-stage projects with pan-KRAS activity include:

Revolution Medicines;

Chengdu Hyperway;

Erasca (ex Joyo);

Jacobio/ AstraZeneca;

Chugai (Roche);

BridgeBio Oncology;

Adlai Nortye;

Jiangsu HengRui;

Treeline Biosciences;

Alterome Therapeutics.

Other companies with selective KRAS inhibitors include AstraZeneca (in collaboration with Usynova), BioNTech, Roche, Merck/Moderna, Boehringer and Gilead.

Smaller and other early-stage companies may also prove to be significant competitors.

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Our business depends, in part, on our ability to develop and maintain the proprietary aspects of our products.

We are seeking patent protection for our product (SIL204) in International Patent Application No.

PCT/IL2023/051276 filed on December 14, 2023 (the “ 276 Application ”)

The minimum expiration date of any patent that is issued from the 276 Application is December 14, 2043.

However, given typical practice with respect to regulatory-related patent term extensions, this date may be extended up to an additional five years in many countries, depending on the length of the regulatory process, to a maximum final expiration date of December 14, 2048.

The 276 Application was published on June 20, 2024 as International Patent Publication No.

WO 2024/127405.

We are seeking patent protection for our product (SIL204) and have entered national Phase world wide, SIL-204 as a composition and for use in treatment of pancreatic and other cancers, U.S.

Patent Application No.

19/443,507, CIP of U.S.

Patent Application No.

The expected protection is until 2043 plus estimated extension to 2048.

Protection for SIL204 is also expected to come from the patent, “siRNA against KRAS G12x for regional perineural invasion or pain associated with a solid tumor U.S.

Patent Application No.

19/443,507” This patent is also at the national stage and pending.

Protection is expected until 2040 plus extension.

In 2026, we intend to file for provisions patents for methods of use of SIL204 and its combination treatment via our Integrated Treatment Regimen.

In addition to patent laws, we rely on copyright and trade secret laws to protect our proprietary rights.

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Our principal executive officers are currently located in Ramat-Gan, Israel, where we lease a space of 464 square meters consisting of offices, under a lease agreement that will expire on October 31, 2026 (initial term of two years and extension option reasonably certain to be exercised ending October 31, 2028).

As of the date of this Annual Report, we have eleven full-time and three part-time employees.

As of the date of this Annual Report, we have thirteen full-time and one part-time employees.

All of our employees are based in Israel.

None of our employees are represented by labor unions or covered by collective bargaining agreements.

None of our employees is represented by labor unions or covered by collective bargaining agreements.

We believe that we maintain good relations with all of our employees.

Grants from the Israeli Innovation Authority

During 2009 to 2020, we received several approvals from the IIA for participation in research and development activities performed by us in a total amount of $5.8 million.

The Company is obligated to pay royalties to the IIA amounting to 3%-5% of the sales of all of its product candidates and other related revenues generated from such projects, up to 100% of the grants received, linked to the U.S.

dollar and bearing interest at the rate of LIBOR.

From 2009 to 2020, we received several approvals from the IIA for participation in research and development activities performed by us in a total amount of $5.8 million.

We are obligated to pay royalties to the IIA amounting to 3%-5% of the sales of all of our product candidates and other related revenues generated from such projects, up to 100% of the grants received, linked to the U.S.

dollar and bearing interest at the rate of SOFR.

The obligation to pay these royalties is contingent upon actual sales of the products and, in the absence of such sales, no payment is required.

In October 2023, it was published that the interest rate of the grants will be replaced with the 12-month term SOFR published on the first trading day of each calendar year.

As of December 31, 2024, the total royalty amount that may be payable by the Company is approximately $5.8 million ($6.5 million including interest).

As of December 31, 2025, the total royalty amount that may be payable by us to the IIA is approximately $5.8 million ($6.7 million including interest).

Legal Proceedings

346 unchanged sentences

Since we perform a portion of the clinical studies on certain of our therapeutic candidates in Israel, we are required to obtain authorization from the ethics committee and general manager of each institution in which we intend to conduct our clinical trials, and in most cases, from the Israeli Ministry of Health.

New Silexion Corporate Information

New Silexion was formed on April 2, 2024 under the name Biomotion Sciences as a Cayman Islands exempted limited company for the purpose of effecting a business combination with Moringa and Silexion.

On April 3, 2024, New Silexion entered into the Business Combination Agreement by and among New Silexion, Moringa, Silexion, and New Silexion’s two wholly-owned subsidiaries— Merger Sub 1 and Merger Sub 2.

Silexion Corporate Information

Silexion was formed on April 2, 2024 under the name Biomotion Sciences as a Cayman Islands exempted limited company for the purpose of effecting a business combination with Moringa and Silexion.

On April 3, 2024, Silexion entered into the Business Combination Agreement by and among Silexion, Moringa, Silexion Israel, and Silexion’s two wholly-owned subsidiaries— Merger Sub 1 and Merger Sub 2.

On the Closing Date of August 15, 2024, following the approval of the Business Combination (among other matters) at Moringa’s extraordinary general meeting that was held on August 6, 2024, the transactions contemplated by the Business Combination Agreement were completed.

As a result, Moringa and Silexion merged with Merger Sub 2 and Merger Sub 1 pursuant to the SPAC Merger and Acquisition Merger, respectively, and became New Silexion’s wholly-owned subsidiaries, and their securityholders became securityholders of New Silexion at previously agreed-upon exchange ratios.

In addition, New Silexion’s ordinary shares and warrants were listed, and began trading, on the Nasdaq Global Market on August 16, 2024, and its name was changed to Silexion Therapeutics Corp.

New Silexion’s principal executive offices are located at 12 Abba Hillel Road, Ramat Gan, Israel 5250606, and its phone number is +972-3-7564999.

New Silexion’s corporate website address is www.silexion.com.

As a result, Moringa and Silexion Israel merged with Merger Sub 2 and Merger Sub 1, respectively, and became Silexion’s wholly-owned subsidiaries, and their securityholders became securityholders of Silexion at previously agreed-upon exchange ratios.

In addition, Silexion’s ordinary shares and warrants were listed, and began trading, on the Nasdaq Global Market on August 16, 2024, and its name was changed to Silexion Therapeutics Corp.

The trading of the ordinary shares and warrants was subsequently transferred to the Nasdaq Capital Market, on July 8, 2025.

Our principal executive offices are located at 12 Abba Hillel Road, Ramat Gan, Israel 5250606, and its phone number is +972-3-7564999.

Our corporate website address is www.silexion.com.

Information contained on or accessible through that website is not a part of this Annual Report, and the inclusion of that website address in this Annual Report is an inactive textual reference only.

Access to Company Information

The Company files or furnishes periodic reports and amendments thereto, including its Annual Reports on Form 10-K, its Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, proxy statements and other information with the SEC.

We file or furnish periodic reports and amendments thereto, including our Annual Reports on Form 10-K, our Quarterly Reports on Form 10-Q and Current Reports on Form 8-K, proxy statements and other information with the SEC.

In addition, the SEC maintains a website (www.sec.gov) that contains reports, proxy and information statements, and other information regarding issuers that file electronically.

New Silexion’s internet address is https://www.silexion.com.

The Company makes available, free of charge, its Annual Report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and all amendments to those reports as soon as reasonably practicable after such reports have been filed with or furnished to the SEC through its internet website.

Our internet address is https://www.silexion.com.

We make available, free of charge, our Annual Report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and all amendments to those reports as soon as reasonably practicable after such reports have been filed with or furnished to the SEC through its internet website.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business