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Silence Therapeutics (SLN) reports robust Phase 2 divesiran results in polycythemia vera

(Moderate)
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Rhea-AI Filing Summary

Silence Therapeutics plc reported positive topline results from the Phase 2 SANRECO trial of its siRNA candidate divesiran in 48 phlebotomy-dependent patients with polycythemia vera (PV). The 36-week, randomized, double-blind, placebo-controlled study evaluated divesiran 6 mg/kg given subcutaneously every six or twelve weeks.

The primary endpoint was met, with an 88% response rate in divesiran-treated patients versus 19% on placebo during weeks 18–36 (p<0.0001), defined as maintaining hematocrit below 45% without phlebotomies. In a sensitivity analysis (n=40), response was 89% vs 8% (p<0.0001). The mean number of phlebotomies from weeks 0–36 was 0.2 in the divesiran arm versus 2.1 with placebo (p<0.0001). Divesiran was generally well tolerated, with safety consistent with earlier studies and only two investigator-reported grade 1 anemia events.

All patients have completed the placebo-controlled portion and entered a three-year extension. Based on these results, Silence expects to initiate a Phase 3 trial in the first half of 2027, focused on Q12W dosing versus placebo.

Positive

  • Phase 2 primary endpoint strongly met: 88% response for divesiran vs 19% for placebo during weeks 18–36, p<0.0001, with large placebo-adjusted benefits in sensitivity analysis.
  • Marked reduction in phlebotomy burden: mean phlebotomies 0.2 with divesiran vs 2.1 with placebo over weeks 0–36 (p<0.0001), aligning with the drug’s goal of durable hematocrit control.
  • Advancement toward Phase 3: based on Phase 2 data, the company expects to initiate a Phase 3 trial of divesiran in PV in the first half of 2027, a key development milestone.

Negative

  • None.

Filing Explained

The filing adds that the company has submitted the full SANRECO Phase 2 results abstract to the ASH Congress and expects an end-of-Phase 2 meeting by year-end; these are development milestones, while Phase 3 remains planned for the first half of 2027.

Item 7.01 Regulation FD Disclosure Disclosure
Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.
Item 8.01 Other Events Other
Voluntary disclosure of events the company deems important to shareholders but not covered by other items.
Item 9.01 Financial Statements and Exhibits Exhibits
Financial statements, pro forma financial information, and exhibit attachments filed with this report.
Phase 2 PV patients 48 patients Phlebotomy-dependent polycythemia vera patients enrolled in SANRECO Phase 2
Primary response rate divesiran 88% Proportion of divesiran-treated patients responding during weeks 18–36; p<0.0001
Primary response rate placebo 19% Proportion of placebo-treated patients responding during weeks 18–36; p<0.0001
Sensitivity analysis response divesiran 89% Responders in divesiran arm (n=40 subset) during weeks 18–36; p<0.0001
Sensitivity analysis response placebo 8% Responders in placebo arm (n=40 subset) during weeks 18–36; p<0.0001
Mean phlebotomies divesiran 0.2 phlebotomies Mean number of phlebotomies weeks 0–36 in divesiran arm; p<0.0001 vs placebo
Mean phlebotomies placebo 2.1 phlebotomies Mean number of phlebotomies weeks 0–36 in placebo arm; p<0.0001 vs divesiran
Planned Phase 3 start 1H 2027 Company expects to initiate Phase 3 divesiran trial in PV in the first half of 2027
polycythemia vera medical
"Phase 2 SANRECO trial of divesiran in polycythemia vera (PV)"
A rare, long-term blood disorder in which the body makes too many red blood cells, thickening the blood and raising the risk of clots, bleeding, fatigue and other complications. Think of it like a faucet left partially open that slowly overfills a sink — the excess cells create strain and danger over time. Investors care because the condition drives demand for diagnostics, treatments and ongoing care, influences clinical trial and regulatory outcomes, and can affect revenue and costs for drugmakers, hospitals and insurers.
siRNA medical
"a global clinical-stage biotechnology company developing novel siRNA therapies"
Small interfering RNA (siRNA) is a short strand of genetic material that binds to and destroys the messenger RNA that carries instructions for making a specific protein, effectively switching that gene off. Investors care because siRNA is a platform for precise medicines: successful trials or approvals can create high-value drugs, while delivery challenges, manufacturing complexity, patent positions and regulatory risk can sharply affect a biotech company's prospects.
hematocrit medical
"The aim of treatment is to maintain hematocrit less than 45%"
Hematocrit is the percentage of red blood cells in a person’s blood, similar to how a pie chart shows the proportion of different slices. It matters to investors because abnormal levels can indicate health issues that may affect a person’s well-being and productivity, potentially impacting industries like healthcare or insurance. Monitoring hematocrit helps provide insights into overall health trends that can influence market conditions.
phlebotomy-dependent medical
"SANRECO trial of divesiran in 48 phlebotomy-dependent patients with polycythemia vera"
Orphan Drug regulatory
"Divesiran has FDA Fast Track and Orphan Drug designations for PV"
A drug designated for an orphan disease is a medicine developed to treat a rare condition that affects only a small number of people. Regulators often give these drugs special incentives—such as reduced costs, faster review, and temporary exclusive selling rights—to encourage development, which matters to investors because those incentives can make a small market financially viable and reduce competition, much like a temporary patent on a niche product.
Fast Track regulatory
"Divesiran has FDA Fast Track and Orphan Drug designations for PV"
A fast track designation is a regulatory label that speeds up the review and communication between a drug developer and regulators for treatments addressing serious illnesses or unmet medical needs. For investors, it matters because it can shorten development time and reduce regulatory delays—like getting a VIP lane at the airport—raising the chance of earlier market access and potential revenue, though it does not guarantee approval.

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FAQ

What did Silence Therapeutics (SLN) report from the Phase 2 SANRECO trial in PV?

Silence Therapeutics reported positive topline Phase 2 results for divesiran in 48 phlebotomy-dependent polycythemia vera patients. The 36-week randomized, placebo-controlled study met its primary and multiple secondary endpoints, including strong hematocrit control and reduced phlebotomy needs, with a generally favorable safety profile.

How effective was divesiran in the SANRECO Phase 2 trial for SLN?

Divesiran achieved an 88% response rate vs 19% for placebo during weeks 18–36 (p<0.0001). Response was defined as maintaining hematocrit below 45% without phlebotomies, demonstrating robust control of red blood cell levels in phlebotomy-dependent PV patients.

How did divesiran affect phlebotomy requirements in SLN’s Phase 2 trial?

In SANRECO, the mean number of phlebotomies was 0.2 in the divesiran arm vs 2.1 in the placebo arm over weeks 0–36 (p<0.0001). This indicates a substantial reduction in the need for therapeutic phlebotomies for treated patients.

What are the next development steps for divesiran according to Silence Therapeutics (SLN)?

Based on Phase 2 SANRECO results, Silence expects to initiate a Phase 3 trial of divesiran in polycythemia vera in the first half of 2027, focused on quarterly (Q12W) dosing versus placebo, following an end-of-Phase 2 meeting.

How was the SANRECO Phase 2 trial in PV designed for Silence Therapeutics (SLN)?

SANRECO’s Phase 2 portion is a 36-week, randomized, double-blind, placebo-controlled study in 48 phlebotomy-dependent PV patients. It evaluates divesiran 6 mg/kg subcutaneously every six or twelve weeks, followed by a three-year double-blind and open-label extension period.

What safety findings did SLN report for divesiran in the SANRECO Phase 2 trial?

Divesiran was reported as generally well tolerated, with a safety profile consistent with earlier trials and no new safety signals. Injection site reactions were infrequent and self-limiting, and there were two investigator-reported grade 1 anemia adverse events.

What regulatory designations does divesiran have for polycythemia vera?

Divesiran has FDA Fast Track and Orphan Drug designations for polycythemia vera. These designations can facilitate development and review for serious conditions with unmet medical need, supporting its advancement through late-stage clinical trials.
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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): August 10, 2026

 

 

Silence Therapeutics plc

(Exact name of Registrant as Specified in Its Charter)

 

 

 

England and Wales   001-39487   Not Applicable

(State or Other Jurisdiction

of Incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

 

12 Hammersmith Grove  
London  
United Kingdom   W6 7AP
(Address of Principal Executive Offices)   (Zip Code)

Registrant’s Telephone Number, Including Area Code: +44 20 3457 6900

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

American Depositary Shares, each representing three ordinary shares, nominal value £0.05 per share   SLN   The Nasdaq Stock Market LLC
Ordinary share, nominal value £0.05 per share*   *   The Nasdaq Stock Market LLC

 

*

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 7.01 Regulation FD Disclosure.

On August 10, 2026, Silence Therapeutics plc (the “Company”) issued a press release announcing positive topline results from the Phase 2 SANRECO trial of divesiran in polycythemia vera (“PV”). A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

As described in the accompanying press release, the Company will host a conference call and live audio webcast today, August 10, 2026 at 8:00 a.m., Eastern Time, to discuss the presentation of data described above.

The live audio webcast may be accessed through the “Events and Presentations” section of the Company’s website at silence-therapeutics.com. A copy of the presentation to be used by the Company during the conference call is furnished as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

The information contained in Item 7.01 of this Current Report on Form 8-K, including Exhibits 99.1 and 99.2 attached hereto, 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, 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.

The Company’s website and any information contained on the Company’s website are not incorporated into this Current Report on Form 8-K.

Item 8.01 Other Events.

On August 10, 2026, the Company issued a press release announcing positive topline results from the Phase 2 SANRECO trial, a 36-week, randomized, double-blind, placebo-controlled portion of the Phase 2 trial evaluating divesiran (6 mg/kg) administered subcutaneously every six weeks (“Q6W”) or every twelve weeks (“Q12W”) met its primary endpoint and secondary endpoints. Based on the Phase 2 results, the Company expects to initiate a Phase 3 trial evaluating divesiran for Q12W dosing vs. placebo in the first half of 2027.

Key findings from the study include:

 

   

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.

 

   

The key secondary endpoint of phlebotomy rate during weeks 0-36 was also met with the mean number of phlebotomies per patient in the divesiran groups significantly reduced compared to placebo (0.2 for divesiran versus 2.1 for placebo; p<0.0001).

 

   

Divesiran groups also showed improvements in hematocrit control, iron markers including ferritin, and patient reported outcomes using the MPN-SAF Total Symptom Score (MPN-SAF TSS).

 

   

Divesiran was observed to be well tolerated and safety was in line with previous trials. No new safety findings were observed in the trial. Injection site reactions were infrequent and self-limiting. There were two investigator reported grade 1 anemia adverse event cases.

Cautionary Regarding Forward-Looking Statements

This Current Report on Form 8-K contains forward-looking statements which are subject to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, reflect management’s expectations as of the date of hereof, and involve certain risks and uncertainties. Forward-looking statements include, but are not limited to, statements herein with respect to the timing and the Company’s ability to initiate Phase 3 trial of divesiran in PV. These forward-looking statements are based on our current expectations and may differ materially from actual results due to a variety of factors including, without limitation, the factors that are described under the caption “Risk Factors” in the Company’s filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2025, filed with the SEC on March 5, 2026, and its subsequent filings with the SEC. The forward-looking statements herein are based on information available to the Company as of the date hereof, and the Company disclaims any obligation to update any forward looking statements, except as required by law.

Item 9.01 Exhibits.

(d) Exhibits.

 

Exhibit
Number
  

Description

99.1    Press Release dated August 10, 2026
99.2    Conference Call Presentation dated August 10, 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: August 10, 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

 

LOGO

Silence Therapeutics Announces Positive Topline Results from Phase 2 SANRECO

Trial of Divesiran in Polycythemia Vera, Supporting its

Potential Best-in-Class Profile

 

   

Trial met its primary endpoint, with a significantly higher proportion of clinical responders on divesiran (88%) compared to placebo (19%); placebo-adjusted response rate = 69%

 

   

Both divesiran dose groups showed substantial primary endpoint efficacy; 93.8% response rate at Q6W and 81.3% response rate at Q12W

 

   

Divesiran was observed to be well tolerated with no new safety findings

 

   

Phase 3 PV trial evaluating divesiran Q12W vs. placebo anticipated to initiate in 1H’27

 

   

Investor conference call and webcast to be held today, August 10, 2026 at 8:00 a.m. ET

10 August 2026

LONDON, Silence Therapeutics plc (Nasdaq: SLN), a global clinical-stage biotechnology company developing novel siRNA (short interfering RNA) therapies, today announced positive topline results from the Phase 2 SANRECO trial of divesiran, a first-in-class siRNA, in 48 phlebotomy-dependent patients with polycythemia vera (PV).

The 36-week, randomized, double-blind, placebo-controlled portion of the Phase 2 trial evaluating divesiran (6 mg/kg) administered subcutaneously (s.c.) every six weeks (Q6W) or every twelve weeks (Q12W) met its primary endpoint and secondary endpoints.

Key findings from the study include:

 

   

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.

 

   

The key secondary endpoint of phlebotomy rate during weeks 0-36 was also met with the mean number of phlebotomies per patient in the divesiran groups significantly reduced compared to placebo (0.2 for divesiran versus 2.1 for placebo; p<0.0001).

 

   

Divesiran groups also showed improvements in hematocrit control, iron markers including ferritin, and patient reported outcomes using the MPN-SAF Total Symptom Score (MPN-SAF TSS).

 

   

Divesiran was observed to be well tolerated and safety was in line with previous trials. No new safety findings were observed in the trial. Injection site reactions were infrequent and self-limiting. There were two investigator reported grade 1 anemia adverse event cases.


LOGO

 

“Across the SANRECO Phase 1/2 program, divesiran has been well tolerated and has consistently delivered durable hematocrit control in phlebotomy-dependent patients with PV, regardless of risk level or disease severity,” said Marina Kremyanskaya, MD, PhD, Associate Professor of Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai. “These compelling results highlight divesiran’s potential to transform PV management with convenient, infrequent dosing that reliably controls hematocrit and addresses longstanding unmet needs for patients.”

“The SANRECO Phase 2 trial delivered our best-case outcome, confirming the impressive results observed in Phase 1 with dosing every six weeks and demonstrating equally robust and durable effects with quarterly dosing,” said Curtis Rambaran, MD, Chief Medical Officer at Silence. “These results reinforce divesiran’s potential to become the first and best-in-class siRNA treatment for PV. We look forward to initiating Phase 3 development and bringing divesiran to patients as quickly as possible.”

Silence plans to present full results from the Phase 2 SANRECO trial at an upcoming medical congress.

Silence will host a conference call and webcast today, Monday, August 10, 2026 at 8:00 a.m. ET, to discuss the Phase 2 SANRECO topline results.

Investor Conference Call and Webcast Details

Conference call link: https://register-conf.media-server.com/register/BI4a60039edc0640388f2ba0a6aab560e2

Webcast link: https://edge.media-server.com/mmc/p/q6mmpxd5

A replay of the webcast will be available on the Investors section of the Silence website at www.silence-therapeutics.com/events.

SANRECO Phase 2 Study Design

The Phase 2 portion of SANRECO is an ongoing, three-part, global, randomized, placebo-controlled, double-blind study evaluating divesiran in 48 phlebotomy-dependent PV patients. The trial is evaluating the safety and efficacy of divesiran 6 mg/kg administered s.c. Q6W or Q12W in patients with uncontrolled hematocrit who are phlebotomy dependent despite standard of care treatment which could include hydroxyurea, interferon and/or ruxolitinib. The primary endpoint of the study was the proportion of patients achieving a response during weeks 18-36, which was defined as the absence of “phlebotomy eligibility.” To meet phlebotomy eligibility, patients in the study were required to have hematocrit below 45%. All patients have completed their participation in the placebo-controlled portion of the trial and are now in the 3-year, double-blind and open label extension periods.

About PV

PV is a rare, myeloproliferative neoplasm – a type of blood cancer - characterized by the excessive production of red blood cells, often resulting in elevated hematocrit levels. Elevated hematocrit above 45-percent is associated with a four-times higher rate of death from cardiovascular and thrombotic events. PV is associated with a range of burdensome symptoms including fatigue, cognitive disturbance and pruritus and additionally, longer term can transform to myelofibrosis and Acute Myeloid Leukemia. The aim of treatment is to maintain hematocrit less than 45%, a level that is associated with a reduced incidence of thrombosis and CV-associated death. The current standard of care includes repeated phlebotomies to reduce hematocrit and/or cytoreductive agents to reduce red blood cell production. There are currently no approved therapies that specifically target red blood cells and hematocrit.

About Divesiran

Divesiran is Silence’s wholly owned siRNA product candidate developed from its proprietary mRNAi GOLD platform that “silences” TMPRSS6 expressed almost exclusively in the liver. TMPRSS6 is a negative regulator of hepcidin, the body’s master regulator of iron metabolism including its absorption, distribution, and storage. By silencing TMPRSS6 in PV patients, divesiran aims to increase hepcidin production and release by liver hepatocytes, leading to the restriction of iron to the bone marrow and, thus, reducing the excessive production of red blood cells, a process dependent on availability of iron. Divesiran has FDA Fast Track and Orphan Drug designations for PV.


LOGO

 

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 potential therapeutic benefits of divesiran; divesiran’s potential to become the first and best-in-class siRNA treatment for PV; and the timing and the Company’s ability to initiate Phase 3 trial of divesiran and bring divesiran to patients as quickly as possible. 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, Head of IR and Corporate Communications

+1 (646) 637-3208

ir@silence-therapeutics.com

Media Relations

MKC Strategies

Mary Conway

+1 (516) 606-6545

mconway@mkcstrategies.com

Slide 1

August 10, 2026 SANRECO Phase 2 Topline Results in Polycythemia Vera Exhibit 99.2


Slide 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 the potential therapeutic benefits of divesiran; divesiran’s potential to become the first and best-in-class siRNA treatment for PV; and the timing and the Company’s ability to initiate Phase 3 trail of divesiran and bring divesiran to patients as quickly as possible. 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. These and other risks are described more fully in the Company's filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section in the Company's Annual Report on Form 10-K for the year ended December 31, 2025, filed with the SEC on March 5, 2026. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Except to the extent required by law, we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. 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.


Slide 3

Introduction Iain Ross, Chairman and Interim Principal Executive Officer


Slide 4

Silence – siRNA Platform Company with Compelling Clinical Data Across Multiple Programs GOLD PLATFORM Proven GalNAc siRNA technology with broad utility Potent, durable and highly specific gene silencing Infrequent dosing enabled by durable pharmacology Strong and growing IP portfolio CLINICAL RESULTS Four clinical-stage assets targeting large unmet needs in rare and cardiometabolic diseases Compelling clinical data generated across multiple programs FRANCHISE OPPORTUNITY Divesiran: first-in-class siRNA for PV ~150K U.S. / ~3.5M global PV population1 Potential best-in-class profile Additional pipeline opportunities beyond PV 1. Using 44/100,000 global population: 7,800m, Kattamis, A. et al. Eur J Haematol (2020)


Slide 5

PV: Large Unmet Need and Proven Market Value Create Significant Upside for a Best-in-Class Therapy Large Underserved Population 2-5 Many PV patients remain phlebotomy-dependent Persistent burden reflects inadequate control Broad addressable population needs better therapy Current Options are Limited 2-5 Limitations in efficacy, safety and tolerability Chronic treatment burden and poor experience Jakafi generates ~$1B annually in PV despite later-line label limitations and treatment tradeoffs1 Compelling Product Profile Robust efficacy Favorable safety Infrequent dosing Better patient experience A best-in-class PV therapy could unlock blockbuster potential in a large underserved market 1. According to Incyte financial disclosures and market share data 2. Verstovsek S, et al. Ann Hematol. 2023 Mar;102(3):571-581; 3. Verstovsek S, et al. Leuk Res. 2017;56:5259.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) 


Slide 6

SANRECO Results Support Potential Best-in-Class Treatment for Phlebotomy-Dependent PV Patients Efficacy Endpoints Safety Endpoints Infrequent Dosing


Slide 7

SANRECO Phase 2 Topline Results Steven Romano, MD, Chief R&D Officer


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Preclinical Phase I Phase II Key Milestones Divesiran (TMPRSS6) Divesiran Clinical Development Program Polycythemia Vera PV is a rare myeloproliferative neoplasm characterized by excessive production of red blood cells Elevated hematocrit (Hct) >45% Primary treatment goal is to maintain Hct <45% HEMATOLOGY Topline 36-Wk Primary EP Results Completed Completed SANRECO Phase 2, n= 48 SANRECO Phase 1, n= 21 GEMINI HV Study, n= 24 Polycythemia Vera (PV) Divesiran has orphan drug and fast track status in PV


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Phase 2 SANRECO Study is a Global Trial: 9 Countries / 4 Continents


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Phase 2 SANRECO Study: Clinical Study Design


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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


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SANRECO: Primary Efficacy Endpoint - Response Rate 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 Placebo adjusted response rate = 69% Note: Response is defined as HCT remaining below 45% and no phlebotomies received during weeks (18-36)


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SANRECO: Primary Efficacy Endpoint by Dose Groups Note: Response is defined as HCT remaining below 45% and no phlebotomies received during weeks 18-36 18.8% 81.3% 93.8%


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SANRECO: Response Rate Sensitivity Analysis (n=40)* Significantly higher proportion of clinical responders among the divesiran treated PV patients (89%) compared to those who received placebo (8%) during weeks 18-36; p<0.0001 Placebo adjusted response rate = 81% Note: Response is defined as HCT remaining below 45% and no phlebotomies received during weeks 18-36 *All patients who met the Phase 1 criterion of a minimum of 3 phlebotomies in the previous 3 months or 5 in the previous 12 months 7.7% 88.9%


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SANRECO: Key Secondary Endpoint - Phlebotomy Rate Mean number of phlebotomies in the divesiran arm was 0.2 compared to 2.1 phlebotomies in the placebo arm during weeks 0-36 (p<0.0001) 12.5% 90.6%


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SANRECO: Other Secondary Endpoints Divesiran groups also showed improvements in: Hematocrit control Iron markers, including ferritin Patient reported outcomes using MPN-SAF Total Symptom Score (MPN-SAF TSS)


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Summary of Adverse Events (Weeks 0-36) Divesiran was generally well tolerated Safety profile was in line with previous divesiran trials; no new safety findings Injection site reactions were infrequent and self-limiting There were two investigator reported grade 1 anemia adverse event cases


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Next Steps Phase 2 SANRECO full results Submitted abstract to ASH Congress (Dec 12-15, New Orleans) End of Phase 2 meeting by year end Initiate Phase 3 study in 1H 2027


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SANRECO Results Support Potential Best-in-Class Treatment for Phlebotomy-Dependent PV Patients Phase 2 profile supports potential best-in-class positioning in phlebotomy-dependent PV


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Q&A


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THANK YOU!

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