divesiran (SLN124) / Silence Therap - LARVOL DELTA

Silence Therapeutics: Divesiran demonstrated strong phase II efficacy in PV, with phase III and market expansion plans advancing (TradingView) - "The session highlighted advances in siRNA technology, with divesiran showing robust phase II efficacy and a favorable safety profile in PV. Plans are underway for a rapid phase III launch, supported by recent funding, with additional indications and commercial partnerships under evaluation....Based on Silence Therapeutics 12th Annual Cantor Fitzgerald Global Healthcare Conference Audio Transcript — Sep. 9 2026."

New P3 trial • P2 data • Polycythemia Vera

Divesiran: Full data from P2 SANRECO trial (NCT05499013) for polycythemia vera at ASH (Dec 12-15, 2026) (Silence Therapeutics) - SANRECO Phase 2 Topline Results Webcast

P2 data • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Divesiran: "The primary endpoint was met: Significantly higher proportion of clinical responders among the divesiran treated PV patients (88%) compared to those who received placebo (19%) during weeks 18-36; p<0.0001"; Polycythemia Vera (Silence Therapeutics) - SANRECO Phase 2 Topline Results Webcast

P2 data • Hematological Malignancies • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera

Silence Therapeutics completes private fund raise at USD 201.3m for divesiran trial (AllSci Corp) - "Silence has stated it plans to initiate a Phase III PV trial evaluating divesiran at a Q12W dosing schedule in 1H 2027."

Financing • New P3 trial • Polycythemia Vera

Silence Therapeutics Announces Positive Topline Results from Phase 2 SANRECO Trial of Divesiran in Polycythemia Vera, Supporting its Potential Best-in-Class Profile (Businesswire) - "The primary endpoint was met, with a significantly higher proportion of clinical responders among divesiran-treated patients with PV compared to those who received placebo (88% for divesiran versus 19% for placebo; p<0.0001). The primary endpoint was the proportion of patients achieving a response, which was defined as the absence of phlebotomy and maintenance of hematocrit (HCT) below 45% during weeks 18-36. Importantly, both divesiran dose groups showed substantial primary endpoint efficacy with response rates of 93.8% and 81.3% for Q6W and Q12W, respectively....Silence plans to present full results from the Phase 2 SANRECO trial at an upcoming medical congress....Phase 3 PV trial evaluating divesiran Q12W vs. placebo anticipated to initiate in 1H’27."

New P3 trial • P2 data • Polycythemia Vera

Silence Therapeutics…announced a conference call and webcast to discuss topline results from the Phase 2 SANRECO trial of divesiran in polycythemia vera (PV) scheduled for…August 10, 2026 at 8:00 a.m. EDT (Businesswire)

P2 data • Polycythemia Vera

Divesiran: “Divesiran demonstrated strong durability with several patients phlebotomy-free nearly 1 year after last dose”; Polycythemia vera (Silence Therapeutics) - Corporate Presentation

P1 data • Hematological Malignancies • Oncology • Polycythemia Vera

DIVESIRAN, A NOVEL GALNAC CONJUGATED SIRNA, REDUCES PHLEBOTOMIES, IMPROVES IRON STORES AND SYMPTOMS IN POLYCYTHEMIA VERA PATIENTS IN SANRECO PHASE 1 STUDY. (EHA 2026) - P1/2 | "It is well-tolerated (doses up to 9 mg/kg), decreases the need for PHL, improves iron distribution and PV symptoms with a (Q6W) dosing regimen. It has a prolonged duration of effect that persists after the final dose suggesting it may be an effective and convenient treatment option for PV."

Clinical • P1 data • Cardiovascular • Hematological Disorders • Hematological Malignancies • Myeloproliferative Neoplasm • Polycythemia Vera • TMPRSS6

THERAPEUTIC SILENCING OF TMPRSS6 ATTENUATES IRON-DRIVEN INFLAMMASOME ACTIVATION AND DELAYS DISEASE PROGRESSION IN MDS MICE (EHA 2026) - "The NUP98–HOXD13 (NHD13) murine model of MDS and wild-type controls received monthly subcutaneous SLN124 (3 mg/kg) or oral deferiprone (1.25 mg/mL). Summary/Conclusion Hepatocyte-targeted Tmprss6 silencing via SLN124 reduced inflammatory activity in the BM and spleen, and delayed the onset and progression of hematological decline in MDS mice. These findings provide mechanistic insight linking dysregulated iron homeostasis to sustained innate immune activation in MDS and establish proof-of-concept for TMPRSS6 inhibition as a potential disease- modifying therapeutic strategy."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • NUP98 • PTPRC • ST14 • TMPRSS6

Silence Therapeutics Highlights Follow-Up Data at EHA 2026 Demonstrating Durable Efficacy and Potential Best-in-Class Profile for Divesiran in Polycythemia Vera (Businesswire) - "New analyses from the Phase 1 SANRECO study demonstrate potential improvements in PV symptoms and quality-of-life...In the six months prior to treatment, the 21 enrolled patients required a total of 80 phlebotomies. During the active treatment period, only 5 phlebotomies were required, all occurring in patients classified as 'uncontrolled' at baseline with HCT levels greater than 45%; During the 16-week follow-up period after the final dose, only 4 phlebotomies were reported, supporting the prolonged duration of divesiran’s effect; Among 14 patients with further follow-up data, the median time to first phlebotomy was 287 days....The ongoing Phase 2 SANRECO study (NCT05499013) is evaluating divesiran using Q6W and Q12W dosing regimens in patients with PV. Topline data are expected in August 2026."

P1 data • P2 data • Polycythemia Vera

Therapeutic Silencing of Tmprss6 Reduces Iron-Induced Inflammation and Prolongs Survival in MDS Mice. (PubMed, Am J Hematol) - "Long-term SLN124 treatment delayed disease progression and significantly prolonged survival, with 30% of treated mice surviving beyond 450 days compared with complete mortality by Day 420 in controls and deferiprone-treated mice. These findings demonstrate that Tmprss6 inhibition via SLN124 suppresses iron-driven inflammation, and mitigated disease progression in MDS mice, establishing TMPRSS6 silencing as a promising disease-modifying therapeutic approach."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Inflammation • Leukemia • Myelodysplastic Syndrome • Oncology • NUP98 • PTPRC • TMPRSS6

Divesiran: First-in-class siRNA for PV (Businesswire) - "SANRECO Phase 1 study abstract accepted for poster presentation at the European Hematology Association (EHA) 2026 Annual Congress taking place June 11-14, 2026....SANRECO Phase 2 double-blind, placebo-controlled study evaluating divesiran 6 mg (Q6W and Q12W dosing intervals) in 48 phlebotomy-dependent PV patients is ongoing with topline results on-track for August 2026."

P2 data • Polycythemia Vera

Modulators of the Hepcidin Pathway in Polycythemia Vera and Myelofibrosis. (PubMed, Blood) - "Since hepcidin levels are relatively low in PV patients, hepcidin agonists (rusfertide, divesiran, sapablursen) are undergoing clinical development to control PV associated erythrocytosis, thereby reducing the need for therapeutic phlebotomies and myelosuppressive therapeutic options. A number of strategies to lower hepcidin levels (the JAK2 inhibitors pacritinib and momelotinib, anti-hemojuvelin monoclonal antibody DISC-0974C) are currently undergoing clinical development to make systemic iron available for erythropoiesis and alleviate the degree of MF associated anemia. These new therapeutic options that modulate iron trafficking in PV and MF patients represent the application of greater knowledge of iron trafficking to create novel therapeutic options to treat patients with hematological malignancies."

Journal • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelofibrosis • Oncology • Polycythemia Vera

Business Highlights (Businesswire) - "Accelerated timing for topline results in the Phase 2 SANRECO trial of divesiran, a first-in-class siRNA for PV; now anticipated in 3Q’26 (formerly 2H’26) due to faster than expected enrollment."

P2 data • Polycythemia Vera

SANRECO: Study to Assess SLN124 in Patients With Polycythemia Vera (clinicaltrials.gov) - P1/2 | N=69 | Active, not recruiting | Sponsor: Silence Therapeutics plc | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Mar 2030 | Trial primary completion date: Dec 2024 ➔ Sep 2026

Enrollment closed • Trial completion date • Trial primary completion date • Polycythemia Vera

Iron Chelation Efficiency in Human Hepatocytes Is Enhanced By Exogenous Hepcidin (ASH 2023) - "Here we have examined whether application of exogenous hepcidin to a human hepatocyte cell line HepG2 can increase the chelation efficiency of deferiprone and whether this effect is also seen with other iron chelators such as deferasirox and deferoxamine. Two mechanisms for enhanced chelation are possible in this model; the first is by increased iron loading of hepatocytes incubated with hepcidin and secondly through the blocking by hepcidin of labile intracellular iron egress through ferroportin channels, thereby increasing the magnitude of chelatable intracellular iron pools. Future work in primary human hepatocytes will examine whether manipulation of intracellular hepcidin levels by SLN124 has similar chelation-enhancing effects."

Beta-Thalassemia • Genetic Disorders • Hematological Disorders • TMPRSS6

Initial Results from a Phase 1/2 Study Evaluating Divesiran, a Novel Galnac Conjugated siRNA, in Patients with Polycythemia Vera (SANRECO) (ASH 2024) - P1/2 | "Importantly, divesiran clearly decreased the need for PHL with a convenient dosing regimen (every 6 weeks) suggesting it serves as a potential effective treatment to control erythrocytosis in PV. These findings support further development of divesiran in PV."

Clinical • P1/2 data • Cardiovascular • Chronic Eosinophilic Leukemia • Hematological Disorders • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • TMPRSS6

Silence Therapeutics Completes Enrollment in SANRECO Phase 2 Study of Divesiran for Polycythemia Vera (PV) (Businesswire) - "Initial topline results from the SANRECO Phase 2 study are anticipated in the third quarter of 2026...Based on the sustained duration of effect observed in Phase 1, the Phase 2 study includes a second, longer dosing interval of every 12 weeks."

Enrollment closed • P2 data • Polycythemia Vera

Novel Therapies in Essential Thrombocythemia and Polycythemia Vera (SOHO 2025) - P1, P1/2, P2, P3 | "In PV, recommended cytoreductive options include hydroxyurea, pegIGN, ropeginterferon-alpha-2b (ropeginterferon), and ruxolitinib...A novel fully human IgG1 monoclonal antibody against mutant CALR (INCA033989) has demonstrated promising preclinical activity...Another phase 1 trial evaluating JNJ-88549968, a novel bispecific antibody that binds to both mutant CALR and T cells to enhance cytotoxicity, 10 is also enrolling both CALR -mutated ET and MF patients (NCT06150157)...12 A phase 2 trial of bomedemstat in high-risk ET patients who were resistant or intolerant to hydroxyurea demonstrated that 94% (34/36) of patients met hematologic response criteria after a median of 8 weeks, with stable hemoglobin levels and improved white blood cell counts...Novel Therapies in Polycythemia Vera Rusfertide and Hepcidin Mimetics Maintenance of a hematocrit <45% is a core aspect of PV therapy, which can be accomplished with a combination of therapeutic phlebotomy..."

IO biomarker • Chronic Myeloid Leukemia • Essential Thrombocythemia • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • CALR • JAK2 • KLK7 • MPL • TMPRSS6

Silence Therapeutics Reports Second Quarter 2025 Financial Results and Recent Business Highlights (Businesswire) - "Divesiran for Polycythemia Vera (PV): Exceeded 50% enrollment in the Phase 2 portion of the SANRECO trial and remain on-track to complete enrollment by year-end 2025."

Enrollment status • Polycythemia Vera

SANRECO, AN ON-GOING PHASE1/2 STUDY EVALUATING DIVESIRAN, A NOVEL GALNAC-CONJUGATED SIRNA, IN PATIENTS WITH POLYCYTHEMIA VERA (EHA 2025) - P1/2 | "Divesiran is a first in class siRNA that increases hepcidin and is being developed for treatment of PV. The results show that divesiran is safe and well-tolerated at doses up to 9 mg/kg. Divesiran decreased the need for PHL with a convenient dosing regimen (every 6 wks) suggesting it is a potential effective treatment for PV."

Clinical • P1/2 data • Cardiovascular • Myeloproliferative Neoplasm • Oncology • Polycythemia Vera • TMPRSS6

Silence Therapeutics Presents Additional Phase 1 Data Highlighting Promise of Divesiran as the Potential First-in-Class siRNA Treatment for Polycythemia Vera (Businesswire) - P1/2 | N=65 | SANRECO (NCT05499013) | Sponsor: Silence Therapeutics plc | "Silence Therapeutics plc...presented additional data showcasing the SANRECO Phase 1 study of divesiran in patients with polycythemia vera (PV) at the European Hematology Association (EHA) 2025 Annual Meeting....Divesiran increased hepcidin and ferritin, resulting in elevation of iron body content and improved iron deficiency. Divesiran demonstrated similar results in all patient groups, independent of baseline risk or prior and concurrent therapy. White blood cells were not altered over the time-course of the study. Platelets increased, reaching a plateau with no dose dependent effect. Divesiran was well tolerated with no dose-limiting toxicities....'The Phase 2 study is over 50-percent enrolled, and we remain on-track to complete patient enrollment by the end of this year'."

Enrollment status • P1 data • Polycythemia Vera

Divesiran for Polycythemia Vera (PV) (Businesswire) - "Additional Phase 1 results from the SANRECO study of divesiran in PV patients have been accepted for oral presentation during the European Hematology Association (EHA) 2025 Annual Congress being held in Milan, Italy from June 12 – 15, 2025; Advanced patient enrollment into the Phase 2 portion of the SANRECO study of divesiran in PV patients and remain on-track to complete enrollment by year-end 2025."

P1 data • Trial status • Polycythemia Vera

Recent Business Highlights (Businesswire) - "Follow-up has concluded in the SANRECO Phase 1 study of divesiran in PV patients. Data presentations at medical congresses are anticipated in 2025; Enrollment is underway in the SANRECO Phase 2 study of divesiran in PV patients. Full enrollment is anticipated by the end of 2025."

Enrollment status • P1 data • Polycythemia Vera

Exploring the Potential of Targeting Iron Overload and Immune Dysregulation in Myelodysplastic Syndromes (LCC 2025) - "NHD13 and wild-type mice received monthly subcutaneous injections of SLN124 siRNA (3 mg/kg) or the oral iron chelator deferiprone in drinking water (1.25 mg/ml). Conclusion These findings underscore the potential of SLN124 to reduce iron accumulation and inflammation, potentially slowing disease progression in MDS. They also emphasise the need for further research into the pathological effects of iron toxicity and inflammation in managing MDS."

Anemia • Hematological Disorders • Hematological Malignancies • Inflammation • Myelodysplastic Syndrome • Oncology • ASGR • MPO • MUC4 • NLRP3 • TMPRSS6