Pipeline shifts and 2025 results at Silence Therapeutics (SLN)
Rhea-AI Filing Summary
Silence Therapeutics reported a larger full-year 2025 net loss while highlighting progress across its siRNA pipeline. Collaboration revenue dropped to
Cash, cash equivalents and short-term investments totaled
AstraZeneca completed a Phase 1 interim analysis of SLN312 in dyslipidemia and then decided not to pursue development beyond Phase 1, after which Silence will regain exclusive global rights. Silence also advanced new preclinical programs SLN365 and SLN098 and noted leadership changes with Iain Ross serving as Interim Principal Executive Officer.
Positive
- Divesiran advancing with clear catalyst: Phase 2 SANRECO trial in polycythemia vera is fully enrolled, with topline results expected in
3Q 2026 , reinforcing divesiran as the company’s highest-priority asset. - Zerlasiran Phase 3–ready: Core Phase 3 readiness activities for zerlasiran in high Lp(a) are complete, and alignment with global regulators on Phase 3 design and endpoints has been achieved, positioning the program for partnering.
- Pipeline expansion: New preclinical programs SLN365 (GPR146) and SLN098 (INHBE) generated promising data, broadening exposure to large cardiometabolic and obesity markets with multiple anticipated 2026 preclinical readouts.
- Cost discipline in G&A: General and administrative expenses declined to
$22.3M in 2025 from$26.9M in 2024, reflecting reduced SEC reporting requirements and other cost-saving initiatives.
Negative
- Sharp revenue decline: Collaboration revenue fell to
$0.6M in 2025 from$43.3M in 2024, largely due to the conclusion of the Hansoh collaboration and lower AstraZeneca-related revenue, materially reducing top-line contribution. - Significantly higher net loss: Net loss nearly doubled to
$88.6M , or$0.63 per share, compared with a$45.3M loss, or$0.33 per share, in 2024, highlighting ongoing cash burn. - Partner steps back from SLN312: On
March 4, 2026 , AstraZeneca notified Silence it will not pursue SLN312 beyond Phase 1, removing a large partner from this dyslipidemia asset even though Silence will regain exclusive rights. - Leadership transition: The former CEO departed, and Iain Ross was appointed Interim Principal Executive Officer on
December 15, 2025 , introducing additional management-transition risk while a CEO search is underway.
Insights
Pipeline advances offset weaker revenue and partner change, creating a mixed outlook.
Silence Therapeutics showed strong clinical and preclinical momentum in 2025 but with sharply lower collaboration revenue of
Lead asset divesiran remains central, with the Phase 2 SANRECO study in polycythemia vera fully enrolled and topline data targeted for
AstraZeneca’s decision on
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of Registrant as Specified in Its Charter)
(State or Other Jurisdiction of Incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
|
|
|
|
||
(Address of Principal Executive Offices) |
|
(Zip Code) |
Registrant’s Telephone Number, Including Area Code: +
Not Applicable
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
|
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
|
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
Title of each class |
|
Trading Symbol(s) |
|
Name of each exchange on which registered |
|
|
|
||
|
* |
|
* Not for trading, but only in connection with the listing of the American Depositary Shares on The Nasdaq Stock Market LLC.
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02 Results of Operations and Financial Condition.
On March 5, 2026, Silence Therapeutics plc (the “Company”) issued a press release announcing its financial results for the fourth quarter and full year ended December 31, 2025, as well as other recent corporate updates. A copy of the press release is furnished as Exhibit 99.1 to this report and incorporated by reference.
The information in this Item 2.02 of this Current Report on 8-K, including Exhibit 99.1 hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, and shall not be deemed incorporated by reference into any of the Company’s filings under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing, except as shall be expressly set forth by specific references in such filing.
Item 7.01 Regulation FD Disclosure.
On March 5, 2026, the Company issued an updated corporate presentation to reflect certain business updates. The presentation is available in the “Investors” section of the Company’s website at silence-therapeutics.com/investors, a copy of which is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated by reference herein. The Company’s website and any information contained on the Company’s website are not incorporated by reference into this Current Report on Form 8-K.
The information contained in Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.2 hereto, is being furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section, and shall not be deemed incorporated by reference into any of the Company’s filings under the Securities Act or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing, except as shall be expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits.
Exhibit Number |
|
Description |
99.1 |
|
Press Release dated March 5, 2026 |
99.2 |
|
Silence Therapeutics plc corporate presentation dated March 2026 |
104 |
|
Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|
|
Silence Therapeutics plc |
|
|
|
|
|
Date: March 5, 2026 |
|
By: |
/s/ Iain Ross |
|
|
|
Name: Iain Ross |
|
|
|
Title: Interim Principal Executive Officer and Chairman of the Board of Directors (Principal Executive Officer)
|
EXHIBIT 99.1
Silence Therapeutics Highlights Recent Business Achievements and Reports Fourth Quarter and Full Year 2025 Financial Results
Topline results for Phase 2 SANRECO trial of divesiran, a first-in-class siRNA for polycythemia vera (PV), on-track for third quarter of 2026
5 March 2026
LONDON, Silence Therapeutics plc, Nasdaq: SLN, a global clinical-stage company developing novel siRNA (short interfering RNA) therapies, today reported financial results for the fourth quarter and full year ended December 31, 2025, and provided an update on recent business achievements.
“The past year was focused on clinical execution, demonstrated by the expedited enrollment in the Phase 2 SANRECO trial of divesiran in PV which is on-track for topline results in third quarter of 2026,” said Iain Ross, Chairman and Interim Principal Executive Officer at Silence. “Divesiran is a first-in-class siRNA product candidate in PV with broad potential in blood disorders and this program is our highest priority. We believe we are well positioned today with excellent optionality and multiple near-term value drivers ahead.”
Business Highlights
Divesiran: First-in-class siRNA for PV
Zerlasiran: Phase 3 ready program for cardiovascular disease due to high Lp(a)
SLN312: Phase 1 siRNA with a competitive profile for dyslipidemia
Discovery Pipeline
Anticipated 2026 Milestones
Corporate Updates
Full Year 2025 Financial Results
About Silence Therapeutics
Silence Therapeutics is a global clinical-stage biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines created with proprietary siRNA (short interfering RNA) technology. Silence leverages its mRNAi GOLD™ platform to create innovative siRNA therapies designed to precisely target and silence genes that cause disease. The Company is advancing a growing pipeline of siRNA product candidates targeting areas of high unmet need across rare and common diseases where treatments are limited or inadequate. For more information, please visit https://www.silence-therapeutics.com/.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. All statements other than statements of historical facts contained in this press release are forward-looking statements. These forward-looking statements include, but are not limited to, statements about: the Company’s business strategy and plans, including the Company’s clinical development activities and timelines; the potential therapeutic benefits of the Company’s product candidates; the anticipated timing of initial topline and future results from the SANRECO Phase 2 trial; the Company’s ability to deliver near- or long-term value; the Company’s ability to advance additional candidates from its mRNAi GOLD™ platform; the Company’s ability to advance extra-hepatic cell targeting or identify extra-hepatic product candidates; and the Company’s ability to identify and engage potential third-party partners for one or more of its product candidates, including the Company’s preclinical and Phase 3 ready assets. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: the company’s history of net operating losses; the company’s ability to obtain necessary capital to fund its clinical programs; the early stages of clinical development of the company’s product candidates; the company’s ability to obtain regulatory approval of and successfully commercialize its product candidates either on its own or with potential partners; any undesirable side effects or other properties of the company’s product candidates; the company’s reliance on third-party suppliers and manufacturers; the outcomes of any future collaboration agreements; and the company’s ability to adequately maintain intellectual property rights for its product candidates. These and other risks are described in greater detail under the section titled “Risk Factors” contained in the company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q and the company’s other filings with the SEC. Any forward-looking statements that the Company makes in this press release are made pursuant to the Private Securities Litigation Reform Act of 1995, as amended, and speak only as of the date of this press release. Except as required by law, the company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
Inquiries:
Silence Therapeutics plc Gem Hopkins, VP, IR and Corporate Communications ir@silence-therapeutics.com
|
Tel: +1 (646) 637-3208
|
SILENCE THERAPEUTICS plc
Consolidated Statements of income (loss)
(in thousands, except for loss per share and share data)
|
|
|
|
|
Year ended December 31, |
|
||||||
|
|
Note |
|
|
2025 |
|
|
2024 |
|
|||
|
|
|
|
|
|
|
|
|
|
|||
Revenue |
|
|
3 |
|
|
$ |
559 |
|
|
$ |
43,258 |
|
Cost of sales |
|
|
|
|
|
(215 |
) |
|
|
(11,810 |
) |
|
Gross profit |
|
|
|
|
|
344 |
|
|
|
31,448 |
|
|
Research and development costs |
|
|
|
|
|
(67,753 |
) |
|
|
(67,883 |
) |
|
General and administrative expenses |
|
|
|
|
|
(22,344 |
) |
|
|
(26,884 |
) |
|
Restructuring charges |
|
6 |
|
|
|
(1,324 |
) |
|
|
- |
|
|
Operating loss |
|
|
|
|
|
(91,077 |
) |
|
|
(63,319 |
) |
|
Foreign currency (loss)/gain, net |
|
|
|
|
|
(8,467 |
) |
|
|
646 |
|
|
Other income, net |
|
|
7 |
|
|
|
3,480 |
|
|
|
4,472 |
|
Benefit from R&D credit |
|
|
|
|
|
7,463 |
|
|
|
13,737 |
|
|
Loss before income tax expense |
|
|
|
|
|
(88,601 |
) |
|
|
(44,464 |
) |
|
Income tax expense |
|
|
18 |
|
|
|
(11 |
) |
|
|
(845 |
) |
Net Loss |
|
|
|
|
$ |
(88,612 |
) |
|
$ |
(45,309 |
) |
|
Loss per share (basic and diluted) |
|
|
8 |
|
|
$ |
(0.63 |
) |
|
$ |
(0.33 |
) |
Weighted average shares outstanding |
|
|
|
|
|
141,694,702 |
|
|
|
138,752,224 |
|
|
The accompanying notes form an integral part of these consolidated financial statements.
SILENCE THERAPEUTICS plc
Consolidated balance sheets
(in thousands, except share data)
|
|
|
|
|
Year ended December 31, |
|
||||||
|
|
Note |
|
|
2025 |
|
|
2024 |
|
|||
|
|
|
|
|
|
|
|
|
|
|||
Current assets |
|
|
|
|
|
|
|
|
|
|||
Cash and cash equivalents |
|
|
12 |
|
|
$ |
11,277 |
|
|
$ |
121,330 |
|
Short-term investments |
|
|
12 |
|
|
|
73,837 |
|
|
|
26,004 |
|
R&D benefit receivable |
|
|
|
|
|
22,007 |
|
|
|
24,396 |
|
|
Other current assets |
|
|
13 |
|
|
|
11,537 |
|
|
|
14,664 |
|
Trade receivables |
|
|
14 |
|
|
|
- |
|
|
|
972 |
|
Total current assets |
|
|
|
|
|
118,658 |
|
|
|
187,366 |
|
|
Property, plant and equipment, net |
|
|
9 |
|
|
|
1,581 |
|
|
|
1,818 |
|
Operating lease right-of-use assets |
|
|
16 |
|
|
|
167 |
|
|
|
157 |
|
Goodwill |
|
|
10 |
|
|
|
10,621 |
|
|
|
9,392 |
|
Intangible assets |
|
|
11 |
|
|
|
288 |
|
|
|
312 |
|
Other long-term assets |
|
|
13 |
|
|
|
127 |
|
|
|
3,590 |
|
Total assets |
|
|
|
|
$ |
131,442 |
|
|
$ |
202,635 |
|
|
|
|
|
|
|
|
|
|
|
|
|||
Current liabilities |
|
|
|
|
|
|
|
|
|
|||
Contract liabilities |
|
|
17 |
|
|
$ |
(168 |
) |
|
$ |
(306 |
) |
Trade and other payables |
|
|
15 |
|
|
|
(13,356 |
) |
|
|
(16,399 |
) |
Operating lease liabilities, current |
|
|
16 |
|
|
|
(89 |
) |
|
|
(117 |
) |
Total current liabilities |
|
|
|
|
|
(13,613 |
) |
|
|
(16,822 |
) |
|
Contract liabilities |
|
|
17 |
|
|
|
(55,454 |
) |
|
|
(51,790 |
) |
Operating lease liabilities, long-term |
|
|
16 |
|
|
|
(71 |
) |
|
|
- |
|
Total liabilities |
|
|
|
|
$ |
(69,138 |
) |
|
$ |
(68,612 |
) |
|
Commitments and contingencies (Note 21) |
|
|
|
|
|
|
|
|
|
|||
|
|
|
|
|
|
|
|
|
|
|||
Shareholders’ equity |
|
|
|
|
|
|
|
|
|
|||
Ordinary shares - par value £0.05 per share; 141,701,848 shares issued at December 31, 2025 (2024: 141,674,074) |
|
|
19 |
|
|
|
(10,290 |
) |
|
|
(10,288 |
) |
Additional paid-in capital |
|
|
|
|
|
(617,562 |
) |
|
|
(609,560 |
) |
|
Accumulated deficit |
|
|
|
|
|
562,572 |
|
|
|
474,044 |
|
|
Accumulated other comprehensive loss |
|
|
|
|
|
2,976 |
|
|
|
11,781 |
|
|
Total shareholders' equity |
|
|
|
|
|
(62,304 |
) |
|
|
(134,023 |
) |
|
|
|
|
|
|
|
|
|
|
|
|||
Total liabilities and shareholders' equity |
|
|
|
|
$ |
(131,442 |
) |
|
$ |
(202,635 |
) |
|
The accompanying notes form an integral part of these consolidated financial statements.
March 2026 Corporate Presentation Exhibit 99.2
Forward-Looking Statements The information contained in this presentation is being supplied and communicated to you solely for your information and may not be reproduced, further distributed to any other person or published, in whole or in part, for any purpose. The distribution of this presentation in certain jurisdictions may be restricted by law, and persons into whose possession this presentation comes should inform themselves about, and observe, any such restrictions. Although reasonable care has been taken to ensure that the facts stated in this presentation are accurate and that the opinions expressed are fair and reasonable, the contents of this presentation have not been verified by Silence Therapeutics plc (the “Company”) or any other person. Accordingly no representation or warranty, express or implied, is made as to the fairness, accuracy, completeness or correctness of the information and opinions contained in this presentation and no reliance should be placed on such information or opinions. None of the Company, or any of its respective members, directors, officers or employees nor any other person accepts any liability whatsoever for any loss howsoever arising from any use of such information or opinions or otherwise arising in connection with this presentation. No part of this presentation, or the fact of its distribution, should form the basis of or be relied upon in connection with any contract or commitment or investment decision whatsoever. This presentation does not form part of any offer of securities, or constitute a solicitation of any offer to purchase or subscribe for securities or an inducement to enter into any investment activity. Recipients of this presentation are not to construe its contents, or any prior or subsequent communications from or with the Company or its representatives as investment, legal or tax advice. In addition, this presentation does not purport to be all-inclusive or to contain all of the information that may be required to make a full analysis of any transaction. Further, the information in this presentation is not complete and may be changed. Recipients of this presentation should each make their own independent evaluation of the information and of the relevance and adequacy of the information in this document and should make such other investigations as they deem necessary. This presentation may contain forward-looking statements that reflect the Company’s current views and expectations regarding future events. In particular certain statements with regard to management’s strategic vision, aims and objectives, the conduct of clinical trials, the filing dates for product license applications and the anticipated launch of specified products in various markets, the Company’s ability to find partners for the development and commercialization of its products as well as the terms for such partnerships, anticipated levels of demand for the Company’s products (including in development), the effect of competition, anticipated efficiencies, trends in results of operations, margins, the market and exchange rates, are all forward-looking in nature. Forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward looking statements. Although not exhaustive, the following factors could cause actual results to differ materially from those the Company expects: difficulties inherent in the discovery and development of new products and the design and implementation of pre-clinical and clinical studies, trials and investigations, delays in and results from such studies, trials and investigations that are inconsistent with previous results and the Company’s expectations, the failure to obtain and maintain required regulatory approvals, product and pricing initiatives by the Company’s competitors, inability of the Company to market existing products effectively and the failure of the Company to agree beneficial terms with potential partners for any of its products or the failure of the Company’s existing partners to perform their obligations, the ability of the Company to obtain additional financing for its operations and the market conditions affecting the availability and terms of such financing, the successful integration of completed mergers and acquisitions and achievement of expected synergies from such transactions, and the ability of the Company to identify and consummate suitable strategic and business combination transactions and the risks described in our most recent Admission Document. By participating in this presentation and/or accepting any copies hereof you agree to be bound by the foregoing restrictions and the other terms of this disclaimer.
Silencing diseases through precision engineered medicines created with proprietary siRNA technology
2025 Key Milestones Achieved Achieved rapid enrollment in SANRECO Phase 2 PV study - topline results anticipated in 3Q 2026 Completed core Phase 3 readiness activities for zerlasiran in high Lp(a) Generated promising pre-clinical results for two new GOLD platform programs Advanced extra-hepatic cell targeting of siRNA with promising initial data
Our Global Footprint US OFFICE R&D OPERATIONS COMPANY HQ NEW JERSEY LONDON BERLIN siRNA expertise spanning drug discovery, design and clinical development
We are Silencing Genes to Treat Disease Natural: RNAi is a natural biological process that regulates gene expression Precise: each siRNA is intentionally designed to bind only to the target gene transcript Durable, yet Reversible: siRNA therapies can be administered infrequently and do not produce permanent changes to DNA Broad Utility: siRNA therapies can be designed to target essentially any gene The siRNA Approach
Our Toolbox Considers all Elements of siRNA and Ligand Design siRNA matched to target gene Silence has developed chemical modification patterns that enhance stability and improve activity Silence has developed proprietary linkers, enabling the attachment of targeting ligands to the siRNA molecule GalNAc ligand delivers molecule to specific liver tissues/cells Highly targeted to liver Continuous Fine-Tuning to Further Improve Performance siRNA molecule Linker GalNAc Ligand (delivery tool)
Development Pipeline of siRNA Therapies Preclinical Phase I Phase II Phase III Divesiran (TMPRSS6) SLN548 (CFB) Zerlasiran (LPA) SLN312* (ANGPTL3) SLN365 (GPR146) SLN098 (INHBE) Other Blood Disorders Complement Polycythemia Vera HoFH Obesity RARE CARDIOMETABOLIC Dyslipidemia Cardiovascular Disease *SLN312 is currently licensed to AstraZeneca. As announced in a Company Press Release dated March 5, 2026, Silence will re-gain exclusive rights globally to SLN312 following Phase 1. HoFH=Homozygous familial hypercholesterolemia
Divesiran (TMPRSS6)
Divesiran: Potential First-in-Class, First-Line siRNA Treatment for Polycythemia Vera (PV) Robust, rapid and durable efficacy in Ph1 Favorable and potentially differentiated safety profile Broad potential in iron-related disorders Less frequent dosing (every 6 or 12 weeks) Fixed dosing, no titration needed Potential for rapid and continuous symptom improvement Opportunities for improved quality of life Compelling Profile Convenient Dosing Consistent Control Targeting First-Line Treatment in All Phlebotomy-Dependent PV Patients
Myeloproliferative neoplasm characterized by the excessive production of red blood cells (RBCs) Elevated hematocrit (HCT) is a hallmark of the disease, indicating overproduction of RBCs Associated with JAK2 gain-of-function driver mutation in hematopoietic stem cells in over 90% of patients Serious, chronic disease associated with increased thrombotic and cardiovascular risks1-3 Rare disease with ~150,000 in the US and ~3.5m worldwide 4 Diagnosed typically in individuals 50-70 years of age Median survival ~20 years Polycythemia Vera (PV) is a Rare Blood Cancer with Significant Unmet Needs Treatment goal is to control HCT <45% to reduce CV and major thrombotic events 1. NORD Rare Disease Database, Polycythemia Vera. https://rarediseases.org/rare-diseases/polycythemia-vera/ 2. Spivak JL. Ann Hematol 2018; 19(2):1-14. 3. Marchioli R, et al. N Engl J Med 2013; 368:22-33 4.Using 44/100,000 global population: 7,800m, Kattamis, A. et al. Eur J Haematol (2020);
People Living with PV Have Significant Unmet Needs Inconsistent HCT Control Patients with HCT between 45-50% are ~4x more likely to die from CV causes or have major thrombotic events than those <45%1 Most patients have uncontrolled HCT with tests ≥45%2 Iron Deficiency Most patients with PV are iron deficient due to depleted bone marrow iron levels3 Some treatments exacerbate disease-related symptoms by inducing iron deficiency3,4 Disease Burden Patients with elevated HCT often require frequent phlebotomies to manage condition 30-40% of PV patients who receive cytoreductive therapy have a suboptimal response and toxicity issues5 Patients have burdensome symptoms, including fatigue and concentration problems5 1. Marchioli et al. 2013 NEJM paper; 2. Verstovsek S, et al. Ann Hematol. 2023 Mar;102(3):571-581; 3. Verstovsek S, et al. Leuk Res. 2017;56:52-59. doi:10.1016/j.leukres.2017.01.032.;4. McMullin MF, et. al. Br J Haematol. 2019 Jan; 184(2): 176-191.; 5. Mesa, R. Clin Adv Hematol Oncol (2017) “The PV aspect means that you have to have phlebotomies regularly and I think the most crippling thing about that is the fatigue.” – Nona Baker
SANRECO Phase 1 Study Overview Completed in February 2025 Design 34-week, open-label, dose-finding study of divesiran in 21 phlebotomy-dependent PV patients Study included 16-week follow-up period following last administered dose Key Inclusion Criteria PV diagnosis At least 3 phlebotomies in the last 6 months or 5 in the last year prior to screening Stable dose of cytoreductive agents allowed No hematocrit threshold Dosing & Administration 6 patients at 3 mg/kg, 8 patients at 6 mg/kg and 7 patients at 9 mg/kg Administered subcutaneously (s.c.) every six weeks (Q6W) for four doses Key Objectives Safety and tolerability Assessment of the number of phlebotomies at 3 intervals (pre-treatment, treatment and follow-up)
Divesiran Reduced Phlebotomy Frequency in All PV Patients Data Presented at the European Hematology Association. June 12, 2025. SANRECO, an On-going Phase 1/2 Study Evaluating Divesiran, Novel GalNAc-conjugated SiRNA, in Patients with Polycythemia Vera. Abstract Code: SS24; Pre-dose from D-201 to D-1, Treatment period D1 to D169 and FU D169 to D239; EoS = End of Study visit; 3. Data cut-off 24th April 2025. 79 Phlebotomies Prior to Dosing; No Well-Controlled Patients Required a Phlebotomy through the 6-month Treatment Period
Divesiran Reduced Hematocrit in All PV Patients Regardless of Baseline Levels Data Presented at the European Hematology Association. June 12, 2025. SANRECO, an On-going Phase 1/2 Study Evaluating Divesiran, Novel GalNAc-conjugated SiRNA, in Patients with Polycythemia Vera. Abstract Code: SS24; 2. Orange dotted line represent dosing dates. Error bars represent ± SEM; All data available for each time point is reported; 3. Data cut-off 24th April 2025.
Divesiran Reduced Hemoglobin in All Cohorts 1. Data Presented at the European Hematology Association. June 12, 2025. SANRECO, an On-going Phase 1/2 Study Evaluating Divesiran, Novel GalNAc-conjugated SiRNA, in Patients with Polycythemia Vera. Abstract Code: SS24; 2. Orange dotted line represent dosing dates. Error bars represent ± SEM; All data available for each time point is reported; 3. Data cut-off 24th April 2025.
Divesiran Treatment Produced Sustained Increases in Hepcidin 1. Data Presented at the European Hematology Association. June 12, 2025. SANRECO, an On-going Phase 1/2 Study Evaluating Divesiran, Novel GalNAc-conjugated SiRNA, in Patients with Polycythemia Vera. Abstract Code: SS24; 2. Orange dotted line represent dosing dates. Error bars represent ± SEM; All data available for each time point is reported; 3. Data cut-off 24th April 2025.
Divesiran Demonstrated a Favorable Safety and Tolerability Profile Divesiran was well tolerated with no dose-limiting toxicities No treatment-related serious adverse events or TEAEs leading to discontinuation
SANRECO Phase 1 Results Highlight Potential for First-in-Class siRNA Treatment for PV EFFICACY SAFETY DURABILITY Controlled HCT levels and eliminated the need for phlebotomy in target population Effects sustained during the treatment and follow-up period with Q6W dosing Well tolerated with no dose-limiting toxicities
SANRECO Phase 2 Study Overview Design 36-week, placebo-controlled, double-blind period followed by a 3-year, double-blind and open-label extension period evaluating divesiran in 48 phlebotomy-dependent PV patients Key Inclusion Criteria PV diagnosis At least 3 phlebotomies in the last 6 months or 5 in the last year prior to screening Stable dose of cytoreductive agents allowed HCT level <45% prior to dosing Dosing & Administration Divesiran 6 mg vs. placebo Administered s.c. at Q6W and Q12W intervals Key Objectives Primary endpoint: proportion of patients who maintain HCT levels below 45% without phlebotomies between weeks 18 and 36 Secondary endpoints include safety and tolerability, pharmacokinetics, and quality of life changes Study Fully Enrolled - Topline Results Expected in 3Q 2026
Zerlasiran (LPA)
Zerlasiran Silences Lp(a): an Independent Risk Factor for Cardiovascular Disease Zerlasiran Has the Potential to Address Major Unmet Needs in Cardiovascular Disease Lp(a) levels are genetically determined Recognized as a major untreated risk factor in cardiovascular disease Lp(a) levels are not significantly modifiable by approved medicines or lifestyle changes At least 20% of the global population has high Lp(a) defined as ≥125 nmol/L (~50 mg/dL)1 mg/dL: milligrams per deciliter, nmol/L: nanomoles per liter (approximate conversion factor of 2.5) 1. Lau, F. D., & Giugliano, R. P. (2022). Lipoprotein (a) and its significance in cardiovascular disease: a review. Jama Cardiology, 7(7), 760-769.
Zerlasiran Has Substantial Market Potential Blockbuster Potential Similar Medically Treated Population Patients with High Total Cholesterol vs. High Lp(a) US + EU5 Markets High Lp(a)2 ≥ 50 mg/dL (no indicated treatments) High Total Cholesterol1 US ≥ 200 mg/dL EU5 ≥ 190 mg/dL Lipitor® (atorvastatin) $12.9B peak sales Crestor® (rosuvastatin) $7.0B peak sales Zocor® (simvastatin) $5.2B peak sales Sales of Cholesterol-Lowering Drugs Peaked at >$30B3,4 Estimated medically treated Lifestyle changes High Cholesterol vs High Lp(a) in Cardiovascular Disease High Cholesterol is a Modifiable Risk Factor Lifestyle changes have no effect on Lp(a) levels High Lp(a) is a Genetic Risk Factor Lifestyle changes can have a positive impact 1 Datamonitor Healthcare | Informa 2018, 2 Varvel et al Arterioscler Thromb Vasc Biol. 2016;36:2239, Tsimikas et al. Atherosclerosis 2020;300:1, Nordestgaard et al. Eur Heart J. 2010;31:2844, 3 Biomedtracker, Internal Analysis; 4 Kidd, J., Nat Rev Drug Discov. 2006;5(10):813
Zerlasiran Phase 2 Results Support Competitive Profile with Opportunities to Further Differentiate in Phase 3 EFFICACY SAFETY DURABILITY Maximum Lp(a) reductions over 90% Lp(a) reductions persisted 60 weeks following first dose (Q16W and Q24W dosing) Well tolerated with no major safety issues 1. Journal of the American Medical Association (JAMA). November 18, 2024. Zerlasiran – A Small Interfering RNA-Targeting Lipoprotein(a) A Phase 2 Randomized Clinical Trial | Clinical Pharmacy and Pharmacology | JAMA | JAMA Network.
Zerlasiran Program Status Core Phase 3 readiness activities complete Alignment with global regulatory agencies on Phase 3 design and endpoints Next Steps: Seeking potential third-party partners for Phase 3 development First industry CVOT evaluating Lp(a) lowering therapy impact on cardiovascular events scheduled to readout in 2026
SLN312 (ANGPTL3)
SLN312: Phase 1 siRNA with a Competitive Profile for Dyslipidemia SLN312 is a Phase 1 siRNA silencing ANGPTL3 ANGPTL3 inhibitors are novel class of therapeutic agents with LDL receptor-independent mechanism of action that may benefit patients that do not respond to statins or PCSK9 inhibitors Discovered as part of an ongoing collaboration with AstraZeneca to discover, develop and commercialize siRNA therapeutics for cardiovascular, renal, metabolic and respiratory diseases using Silence’s mRNAi GOLD™ AZ completed an interim analysis of a Phase 1 trial in patients with dyslipidemia demonstrating a competitive profile; Silence will re-gain exclusive rights globally to SLN312 at the end of Phase 1 SLN312 Demonstrates Competitive Profile in Patients with Dyslipidemia Safe and well-tolerated with no serious adverse events Robust reductions in ANGPTL3 protein after single and multiple doses of SLN312 supporting infrequent dosing Lipid reductions on par with other ANGPTL3i in development Program Outlook Potential for GPR146 and ANGPTL3 combination therapy (differentiated approach) Several therapeutic options available including mixed dyslipidemia, HoFH and HeFH
SLN312 Phase 1 Results Demonstrate Robust ANGPTL3 Reductions Supporting Potential for Infrequent Dosing EFFICACY SAFETY DURABILITY Substantial and dose-dependent reductions in ANGPTL3, triglycerides and atherogenic lipoproteins Sustained effects after single and multiple doses supporting potential for infrequent dosing Well tolerated with no major safety issues Phase 1 Data Presentations Planned for Research Congresses in 2026
SLN365 (GPR146)
SLN365: Potential First-in-Class siRNA with Novel MOA in High Unmet Need Space Potential First-in-Class siRNA Silencing GPR146 Novel mechanism-of-action for managing cholesterol levels independent of LDL-C receptor (LDLR) function Hypercholesterolemia is a highly prevalent indication: around 1 in 300 individuals worldwide have the familial form HeFH (heterozygous) and around 1 in 300,000 worldwide have HoFH (homozygous) Demonstrated Preclinical Proof-of-Concept Achieved > 80% mRNA knockdown after a single injection (non-human primates) Sustained effects throughout study with ~50% or greater mRNA knockdown observed 3 months after dosing (NHP) Significant reductions in total cholesterol, LDL and triglycerides in murine disease model (LDLR KO) Program Outlook Potential IND filing in 1H 2027 First potential indication planned for the treatment of HoFH which is the area of highest unmet need where 47% of patients don’t reach the LDL-C goal despite being treated with multiple lipid lowering therapies 1. Heterozygous familial hypercholesterolemia: prevalence and control rates I 2021; 2. Homozygous Familial Hypercholesterolaemia – Worldwide Experience I 2023 1,2
GPR146: Novel Target for the Management of Cholesterol Independent of LDL-C Receptor Function LPL=Lipoprotein Lipase Note: Cholesterol modulating mechanism in other tissues not represented VLDL hepatocyte blood GPR146 ligand SREBP2 pathway VLDL secretion LDL ANGPTL3 PCSK9 LDLR Cholesterol degradation LPL APOC3 REF: Angiopoietin-Like Protein 3 (ANGPTL3) Modulates Lipoprotein Metabolism and Dyslipidemia GPR146 is a receptor present on hepatocyte membranes and responsible for VLDL production VLDL converts into LDL-C and triglycerides in the blood stream GPR146’s function is independent from LDLR Differentiated MOA: Inhibition of GPR146 expression blocks VLDL synthesis and thus TG and LDL levels and may be synergistic with ANGPTL3 and LDLR- dependent drugs
Genetic Evidence: GPR146 Deficiency Protects Against Hypercholesterolemia and Atherosclerosis Common rs2362529-C allele lower GPR146 expression lower LDL-C, ApoB, HDL, apoAI, and CRP Common rs1997243-G allele higher GPR146 expression exact opposite phenotype Human Genetic Studies Support GPR146 as a Susceptible Gene Regulating Cholesterol Levels https://doi.org/10.1161/ATVBAHA.122.317514 https://doi.org/10.1038/s41422-020-0303-z https://doi.org/10.1016/j.cell.2019.10.034
Results SLN365 treatment resulted in 84% mRNA KD at 4 weeks in the multiple dose group (3 x 3 mg/kg) Sustained KD throughout the study duration – 70% mRNA KD at week 12 in the multiple dose group Single dose of 9 mg/kg resulted in 80% mRNA KD at 4 weeks and 63% KD at week 12 No major treatment-related effect on body weight and no effect on clinical chemistry, hematology or clinical observation Liver PD Dose-Dependent GPR146 mRNA Knockdown Observed with SLN365 Treatment in Non-Human Primates
LDLR KO Reduction of Plasma Cholesterol and Triglycerides in Mice Following GPR146 siRNA Treatment WT Mouse surrogate siRNA reduced Gpr146 mRNA levels by >75% Significant reduction of total cholesterol and triglycerides following siRNA treatment observed in WT and LDLR KO mice on Western diet No accumulation of lipids in the liver following siRNA treatment n=11-12/group, high-fat diet n=11-12/group, high-fat diet -49% *** -72% *** -29% * -27% *** -7 0 7 14 21 28 35 42 0 2 4 6 8 Day P l a s m a T C [ m m o l / L ] siRNA siRNA mean and 95% CI -7 0 7 14 21 28 35 42 0.0 0.5 1.0 1.5 2.0 Day P l a s m a T G [ m m o l / L ] siRNA siRNA mean and 95% CI -7 0 7 14 21 28 35 42 0 10 20 30 40 50 Day P l a s m a T C [ m m o l / L ] siRNA siRNA mean and 95% CI -7 0 7 14 21 28 35 42 0 2 4 6 8 Day P l a s m a T G [ m m o l / L ] siRNA siRNA mean and 95% CI PBS Gpr146 siRNA Dunnet‘s test on two-factor linear model with interaction *** P < 0.001; * P<0.05 compared to PBS control Data shown for one compound, similar data was obtained with two different siRNAs
SLN098 (INHBE)
Despite Recent Advances in Obesity Treatment, Limitations of Current SoC Leave Millions at Risk of Further Complications Need for Improved Quality of Weight Loss with Differentiated Approach to Current Treatments Current obesity treatments offer weight loss of ~15-25% which plateaus after 12-24 months and are associated with up to 40% lean muscle mass loss More than two-thirds weight loss is regained within first year after discontinuation of treatment ~ 1 billion patients worldwide affected by obesity and associated comorbidities Poor tolerability and compliance with up to 30% patients discontinuing GLP/GIP agonists treatment 1. NCD-RisC, Lancet. 2024; 2. Melson et al Clinical Research 2024; 3. Kevin Hall, bioRxiv. 2023; Wilding et al, NEJM. 2021; Jastreboff et al, NEJM.2022; 4.Gomar et al, Curr Cardiol Rep. 2025; 5. West et al, BMJ.2026
SLN098 Silences INHBE: Novel Target for Obesity Supported by Human Genetics and Recent Clinical Validation Potential to Transform Weight Loss Opportunity to address unmet needs including increasing fat loss, preventing muscle mass loss and slowing weight regain INHBE is a novel target supported by human genetics, strong preclinical data, and emerging third-party clinical data Demonstrated Deep and Durable Knockdown >70% knockdown of INHBE mRNA levels sustained for nearly 3 months in non-human primates Disease model data expected Q2 2026 to further validate mechanism of action Program Outlook Potential for IND filing by 2027 year-end Opportunity to develop either as monotherapy or add-on to GLP/GIP agonists or as weight maintenance treatment
Targeting INHBE Synthesis Blocks Signalling via ALK7, Effectively Enabling Lipolysis in Adipose Tissue INHBE (Inhibin beta E) encodes Activin beta E, a peptide hormone & member of the Transforming Growth Factor Beta (TGF-b) super family Expression is elevated upon fasting, in obesity and in patients with T2D Activin beta E is a hepatokine that activates ALK7 receptor in adipose tissue, where it blocks lipolysis Inhibition of INHBE expression enhances lipolysis and redistributes fat In combination with GLP/GIP agonists, opportunity to enhance weight loss while preserving muscle mass
SLN098 Preclinical Data Demonstrating Impact on Weight Loss in Obesity Disease Model Anticipated in 2Q 2026 Study Objectives: SLN098 impact on weight gain SLN098 impact on weight loss in combination with GLP/GIP agonist SLN098 impact on quality of weight loss (lean mass/fat mass & impact on weight gain after phasing out GLP/GIP agonists) Safety data (i.e. impact on fatty liver and blood lipid levels, ALT/AST)
Anticipated 2026 Milestones 1Q 2026 2Q 2026 3Q 2026 4Q 2026 SANRECO Ph2 topline results Divesiran Polycythemia Vera SLN098 Obesity Extra-hepatic Preclinical data Results from first industry CVOT in high Lp(a) anticipated in 2026 Preclinical data SLN365 HoFH Zerlasiran High Lp(a) IND enabling studies (potential filing in 1H 2027) IND enabling studies (potential filing in 2H 2027) Preclinical data Preclinical data SLN312* Dyslipidemia *SLN312 is currently licensed to AstraZeneca. As announced in a Company Press Release dated March 5, 2026, Silence will re-gain exclusive rights globally to SLN312 following Phase 1. HoFH=Homozygous familial hypercholesterolemia Ph1 data presentations anticipated in 2026
Silencing diseases through precision engineered medicines created with proprietary siRNA technology
FAQ
How did Silence Therapeutics (SLN) perform financially in 2025?
What is the cash position of Silence Therapeutics (SLN) at year-end 2025?
What are the key upcoming milestones for divesiran at Silence Therapeutics (SLN)?
What happened to the SLN312 collaboration between Silence Therapeutics (SLN) and AstraZeneca?
How advanced is zerlasiran in Silence Therapeutics’ (SLN) pipeline?
What new pipeline programs did Silence Therapeutics (SLN) highlight in 2025?
Did Silence Therapeutics (SLN) report any leadership changes?
Filing Exhibits & Attachments
3 documents