6-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 6-K

REPORT OFFOREIGN PRIVATE ISSUER

PURSUANT TO RULE 13a-16 OR15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the Month of June 2024

Commission File Number: 001-39487

Silence Therapeutics plc

(Exact Name of Registrant as Specified in Its Charter)

72Hammersmith Road

London W14 8TH

United Kingdom

(Addressof principal executive offices)

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F ☒   Form 40-F ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐

INCORPORATION BY REFERENCE

The information contained in this Report on Form 6-K (the “Report”), excluding Exhibits 99.1 and 99.2 of this Report, shall be deemed to be incorporated by reference into the registration statements on Form S-8 (File Nos. 333-248682 and 333-273576) and the registration statements on Form F-3 (File Nos. 333-248203, 333-260265 and 333-279185) of Silence Therapeutics plc (the “Company”) and any related prospectuses, as such registration statements and prospectuses may be amended from time to time, and to be a part thereof from the date on which this Report is filed, to the extent not superseded by documents or reports subsequently furnished.

INFORMATION CONTAINEDIN THIS REPORT ON FORM 6-K

Press Release

On June 27, 2024, the Company issued a press release announcing positive initial results from the Company’s ongoing SANRECO Phase 1 repeat dose clinical trial of divesiran (SLN124), a siRNA (short referencing RNA) targeting TMPRSS6, in patients with polycythemia vera (PV), a copy of which is attached hereto as Exhibit 99.1 and is furnished herewith.

Update Regarding SANRECO Phase 1/2 Program

As previously announced in 2021, the Company initiated the Phase 1/2 clinical trial with an open-label dose escalation phase followed by a randomized, double-blind phase of divesiran in patients with PV. The 34-week, open-label Phase 1 clinical trial is evaluating divesiran in up to 24 PV patients at 3 dose levels: 3 mg/kg, 6 mg/kg and 9 mg/kg. Each dose is administered subcutaneously every 6 weeks for four doses, with a 16-week follow-up period following administration of the last dose. Key inclusion criteria for subjects in the trial include a PV diagnosis and a history of the patient prior to screening requiring: (i) at least three phlebotomies in the last six months or (ii) five phlebotomies in the prior year. Given the exploratory nature of this Phase 1 clinical trial, both well-controlled patients, which are defined as those with hematocrit (HCT) levels at 45% or less, as well as those patients with HCT levels greater than 45% at baseline on current standard of care treatment were enrolled.

The data presented are based on a data cut-off date of March 29, 2024, and include analysis of 16 patients over a time range of approximately 4 to 34 weeks of study involvement. Of the 16 patients, 8 patients are considered well-controlled and 8 patients have HCT levels over 45% at baseline. To date, divesiran has been observed to be well tolerated with no major safety issues.

None of the 8 patients entering the trial with well-controlled HCT levels required a phlebotomy during the divesiran treatment period, which was defined in the trial as the period up to 6 weeks after the last dose. All patients in the well-controlled group maintained adequate control of HCT levels as per treatment guidelines. Of the 8 patients entering the trial with HCT levels above 45%, 2 patients each required one phlebotomy. The baseline HCTs of these 2 patients were 56% and 53%, respectively. None of the 6 other patients in this group required a phlebotomy. Notably, none of the 13 patients entering the trial with HCT levels of 50% or below – 8 well-controlled patients and 5 patients with HCT levels of 46-50%—have required a phlebotomy to-date.

In all dose groups, there was a sustained reduction in hematocrit during the treatment period and favorable effects on indices of iron metabolism. Hepcidin levels increased and were sustained within physiological levels in all dose groups, demonstrating target engagement.

As of June 27, 2024, the Company has enrolled 19 patients in the SANRECO trial, and the Company plans to complete enrollment later this month. Full results are expected to be presented at a future scientific meeting later this year.

Slide Presentation

In connection with the announcement of the initial results from the SANRECO clinical trial, the Company is hosting an investor call to present the data from the trial. A copy of the slide presentation to be presented during the investor call is attached hereto as Exhibit 99.2 and is furnished herewith. The Company undertakes no obligation to update, supplement or amend the presentation attached hereto as Exhibit 99.2.

Forward-Looking Statements

This Report contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements in this Report other than statements of historical facts are “forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this Report include, but are not limited to, statements regarding: the Company’s clinical development activities and timelines for divesiran including the expected timing for reporting further data from the SANRECO trial; the timing and future occurrence of other clinical and clinical activities including proposed clinical trial enrollment and the Company’s plans and timing to advance divesiran into Phase 2; expected clinical benefits of divesiran and the potential to produce clinically meaningful outcomes in PV patients; and the Company’s plans to submit additional data from the SANRECO trial for publication at a future conference. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this Report. Each of these forward-looking statements involves risks and uncertainties that could cause the Company’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: preliminary or topline results are based on a preliminary analysis of key efficacy and safety data; the potential that success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including the conflict in Ukraine and the conflict between Israel and Hamas, heightened inflation and uncertain credit and financial markets, on the Company’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; the Company’s ability to realize the benefits of its collaborations and license agreements; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled “Risk Factors” in the Company’s Annual Report on Form 20-F for the year ended December 31, 2023 filed with the U.S. Securities and Exchange Commission (the “SEC”) on March 13, 2024 as well as its other documents subsequently filed with or furnished to the SEC. The Company expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.

EXHIBIT INDEX

Exhibit<br><br><br>No.	Description
99.1	Press release dated June 27, 2024.
99.2	Investor Presentation.

SIGNATURE

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, thereunto duly authorized.

	SILENCE THERAPEUTICS PLC
Date: June 27, 2024	By:	/s/ Craig Tooman
		Craig Tooman
		President and Chief Executive Officer

EX-99.1

Exhibit 99.1

Silence Therapeutics Announces Positive Results from Ongoing SANRECO Phase 1 Study of Divesiran in Polycythemia Vera Patients

Divesiran eliminated the need for phlebotomy in all well-controlled patients following infrequent dosing andwas well tolerated

Data support advancing divesiran into Phase 2

Company to host conference call today at 8:30am Eastern Time

27 June 2024

LONDON, Silence Therapeutics plc (“Silence” or the “Company”), (Nasdaq: SLN), an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today announced positive results from the ongoing SANRECO Phase 1 repeat dose study of divesiran (SLN124), a siRNA (short interfering RNA) targeting TMPRSS6, in patients with polycythemia vera (PV).

“With today’s very exciting PV data, Silence is continuing to emerge as a true platform company. Both of our lead proprietary programs are now generating excellent clinical results,” said Craig Tooman, President and CEO at Silence. “Divesiran is poised to be the first siRNA for PV, and we look forward to advancing development with a phase 2 start planned by year-end.”

The 34-week, open-label Phase 1 study is evaluating divesiran (3 mg/kg, 6 mg/kg and 9 mg/kg) administered subcutaneously every 6 weeks for four doses, with a 16-week follow-up period following the date of the last administered dose in up to 24 PV patients. Key inclusion criteria include a PV diagnosis and a history of requiring at least three phlebotomies in the last six months or five in the last year prior to screening. Patients are allowed to be on stable doses of cytoreductive agents. Given the exploratory nature of this Phase 1 study, both well-controlled patients—defined as those with hematocrit (HCT) levels at 45% or less – as well as those with HCT levels greater than 45% at baseline on current standard of care treatment were enrolled.

The data being presented today are based on a data cut-off date of March 29, 2024, and include analysis of 16 patients over a time range of approximately 4 to 34 weeks of study involvement. Of the 16 patients, 8 patients are considered well-controlled and 8 patients have HCT levels over 45% at baseline.

To date, divesiran has been observed to be well tolerated with no major safety issues.

None of the 8 patients entering the trial with well-controlled HCT levels required a phlebotomy during the divesiran treatment period, which was defined in the study as the period up to 6 weeks after the last dose. All patients in the well-controlled group maintained adequate control of HCT levels as per treatment guidelines. Of the 8 patients entering the trial with HCT levels above 45%, 2 patients each required one phlebotomy. The baseline HCTs of these 2 patients were 56% and 53%. None of the 6 other patients in this group required a phlebotomy. Notably, none of the 13 patients entering the trial with HCT levels of 50% or below – 8 well-controlled patients and 5 patients with HCT levels of 46-50%—have required a phlebotomy to date.

In all dose groups, there was a sustained reduction in hematocrit during the treatment period and favorable effects on indices of iron metabolism. Hepcidin levels increased and were sustained within physiological levels in all dose groups, demonstrating target engagement.

“Divesiran treatment in PV patients results in sustained increases in hepcidin, reflecting crucial target engagement,” said Professor Tomas Ganz, MD, PhD, Distinguished Professor of Medicine and Pathology Department of Medicine, UCLA. “Divesiran exerts a beneficial effect on hematological parameters and significantly reduces phlebotomies. These exciting data suggest that divesiran has the potential to produce clinically meaningful outcomes in this patient population.”

“Based on these early results, divesiran appears to meaningfully impact key hematological parameters in this rare myeloproliferative neoplasm,” said Steven Romano, MD, Silence’s Head of Research and Development. “We are particularly encouraged by the safety profile and the potential for divesiran to be administered infrequently to PV patients requiring pharmacological intervention to manage their disease.”

As of today, Silence has enrolled 21 patients in the SANRECO study and the Company anticipates closing enrollment at the end of this month. Full results are expected to be presented at a scientific meeting later this year. Divesiran has received FDA Fast Track designation and FDA Orphan Drug Designation for PV.

Conference Call and Webcast Details

Management will host a conference call and webcast today, June 27, 2024, at 8:30 am ET to discuss results from the ongoing SANRECO phase 1 study. To access the call, please register online at https://register.vevent.com/register/BI33ea9b075fa841ea9597cc915562e79c . Participants are requested to register at a minimum of 15 minutes before the start of the call. A replay of the call will be available two hours after the call and archived on the same web page for six months.

A live webcast will also be available on the Investors section of the Company’s website at www.silence-therapeutics.com. An archived webcast will be available on the Company’s website approximately two hours after the event.

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 or thrombotic events. PV is associated with a range of burdensome symptoms including fatigue, cognitive disturbance and pruritis 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 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.

About Silence Therapeutics

Silence Therapeutics is developing a new generation of medicines by harnessing the body’s natural mechanism of RNA interference, or RNAi, to inhibit the expression of specific target genes thought to play a role in the pathology of diseases with significant unmet need. Silence’s proprietary mRNAi GOLD^™^ platform can be used to create siRNAs (short interfering RNAs) that precisely target and silence disease-associated genes in the liver, which represents a substantial opportunity. Silence’s wholly owned product candidates include zerlasiran designed to address the high and prevalent unmet medical need in reducing cardiovascular risk in people born with high levels of lipoprotein(a) and divesiran designed to address hematological diseases, including polycythemia vera. Silence also maintains ongoing research and development collaborations with AstraZeneca and Hansoh Pharma, among others. For more information, please visit https://www.silence-therapeutics.com/.

Forward-Looking Statements

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements in this press release other than statements of historical facts are “forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding: the Company’s clinical development activities and timelines for divesiran including the expected timing for reporting further data from the SANRECO trial; the timing and future occurrence of other clinical and clinical activities including proposed clinical trial enrollment and the Company’s plans and timing to advance divesiran into Phase 2; expected clinical benefits of divesiran and the potential to produce clinically meaningful outcomes in PV patients; and the Company’s plans to submit additional data from the SANRECO trial for publication at a future conference. These forward-looking statements are based on the Company’s expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties that could cause the Company’s clinical development programs, future results or performance to differ materially from those expressed or implied by the forward-looking statements. Many factors may cause differences between current expectations and actual results, including: preliminary or topline results are based on a preliminary analysis of key efficacy and

safety data; the potential that success in preclinical testing and earlier clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate; the impacts of macroeconomic conditions, including the conflict in Ukraine and the conflict between Israel and Hamas, heightened inflation and uncertain credit and financial markets, on the Company’s business, clinical trials and financial position; unexpected safety or efficacy data observed during preclinical studies or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; the Company’s ability to realize the benefits of its collaborations and license agreements; changes in expected or existing competition; changes in the regulatory environment; the uncertainties and timing of the regulatory approval process; and unexpected litigation or other disputes. Other factors that may cause the Company’s actual results to differ from those expressed or implied in the forward-looking statements in this press release are identified in the section titled “Risk Factors” in the Company’s Annual Report on Form 20-F for the year ended December 31, 2023 filed with the U.S. Securities and Exchange Commission (the “SEC”) on March 13, 2024 as well as its other documents subsequently filed with or furnished to the SEC. The Company expressly disclaims any obligation to update any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.

Inquiries:

Silence Therapeutics plc
Gem Hopkins, VP, IR and Corporate Communications
Tel: +1 (646) 637-3208<br><br><br>ir@silence-therapeutics.com
Media Relations
MKC Strategies
Mary Conway
Tel: +1 (516) 606-6545<br><br><br>mconway@mkcstrategies.com

EX-99.2

Exhibit 99.2 Results from Ongoing SANRECO Phase 1 Study of Divesiran in Polycythemia Vera June 27, 2024

Forward-Looking Statements Statements contained in this presentation regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as anticipates, believes, expects, intends, “plans,” “potential,” projects,” “would” and future or similar expressions are intended to identify forward-looking statements. Each of these forward-looking statements involves substantial risks and uncertainties that could cause actual results to differ significantly from those expressed or implied by such forward-looking statements. Forward-looking statements contained in this presentation include, but are not limited to, statements regarding the Company’s clinical development activities and timelines for divesiran including the expected timing of program updates and data disclosures from the SANRECO trial; the future occurrence of other clinical and clinical activities including proposed clinical trial enrollment and the Company’s plans and timing to advance divesiran into Phase 2; expected clinical benefits of divesiran and the potential to produce clinically meaningful outcomes in PV patients; and the Company’s plans to submit additional data from the SANRECO trial for publication at a future conference; and our our ability to identify and develop additional product candidates using our mRNAiGOLD™Platform. These forward-looking statements reflect our current beliefs and expectations. Many factors may cause differences between current expectations and actual results, including preliminary or topline results are based on a preliminary analysis of key efficacy and safety data; unexpected safety or efficacy data observed during preclinical or clinical studies; clinical site activation rates or clinical trial enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; and unexpected litigation or other disputes. These and other risks are described more fully in our filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of our Annual Report on Form 20-F filed with the SEC on March 13, 2024, and other documents we subsequently filed with or furnished to the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. Except as required by law, we assume no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of this presentation. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Solely for convenience, the trademarks and trade names in this presentation may be referred to without the ® and ™ symbols, but such references should not be construed as any indicator that their respective owners will not assert their rights thereto. 2 2

Divesiran Has the Potential to Be First siRNA for PV • To-date, divesiran has eliminated the need for phlebotomy in all well- controlled patients after infrequent dosing • To-date, divesiran has been well tolerated with no serious safety issues • Divesiran represents second wholly owned program demonstrating positive clinical results from our mRNAi GOLD™ platform • Positive data from ongoing SANRECO phase 1 trial support advancing to phase 2 by year-end • Divesiran has FDA Fast Track and Orphan Drug designations 3 3

SANRECO Phase 1 Study of Divesiran in Patients with Polycythemia Vera 4

5 Polycythemia Vera (PV): A Rare Blood Cancer with Significant Unmet Needs • Myeloproliferative neoplasm characterized by the excessive production of red blood cells (RBCs) Treatment goal is o Elevated hematocrit (Hct) is a hallmark of the disease, indicating overproduction of RBCs to control HCT <45% to reduce • Serious, chronic disease associated with increased thrombotic CV and major 1-3 and cardiovascular risks thrombotic events 4 • Rare disease with ~150,000 in the US and ~3.5m worldwide • Current standard of care approaches are inadequate for HCT 5 control • Most PV patients are iron deficient at diagnosis - repeated phlebotomy exacerbates this 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 5 5 44/100,000 global population: 7,800m, Kattamis, A. et al. Eur J Haematol (2020); 5. Verstovsek S,, et al. Real-world treatments and thrombotic events in polycythemia vera patients in the USA. Ann Hematol. 2023 Mar;102(3):571- 581 doi: 10 1007/s00277 023 05089 6 Epub 2023 Jan 13 PMID: 36637474; PMCID: PMC9977710

Our mRNAi GOLD™ Platform Considers All Elements of siRNA and Ligand Design (delivery tool) Linker GalNAc Ligand siRNA molecule • siRNA matched to target gene • Silence has developed • GalNAc ligand delivers proprietary linkers, enabling molecule to specific liver • Silence has developed chemical the attachment of targeting tissues/cells modification patterns that enhance ligands to the siRNA molecule stability and improve activity • Highly targeted to liver Continuous Fine-Tuning to Further Improve Performance 6 6

7 Divesiran Rationale for targeting TMPRSS6 > TMPRSS6 is a negative regulator of the BMP/SMAD HJV BMPR Macrophages signaling pathway; activation of the pathway induces BMP hepcidin expression > Hepcidin reduces uptake of dietary iron and the Ferroportin release of iron from storage cells P TMPRSS6 Fe > Hepcidin levels may be normal in patients with Polycythemia Vera Iron recycling P SMAD > Therapeutic hypothesis: inhibition of TMPRSS6 expression in the liver will raise hepcidin and reduce Hepcidin iron delivery to the bone marrow. Iron restriction reduces erythropoiesis resulting in lower Red Blood Cell (RBC) production. Hepcidin induction Iron absorption Fe HAMP > GalNAc siRNA approach for gene silencing in the liver DNA siRNA Ferroportin GalNAc Enterocytes Hepatocytes Hepatocyte Targeting Gene Silencing 7 7

SANRECO: Phase 1 Trial Design 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 Dosing schedule and follow-up: • Subcutaneous injections on days 1, 43, 85 and 127 • Follow up for 112 days post last injection (16 weeks) • Total duration of study 239 days (34 weeks) 8 8

SANRECO: Phase 1 Current Status (21 enrolled) as of 27 June 2024 Enrollment Status Cohort 1 - 3mg/kg • 6 patients enrolled; 4 completed study Cohort 2 - 6mg/kg • 8 patients enrolled; 5 completed study Cohort 3 - 9 mg/kg • 7 patients enrolled; 4 completed Day 127 SANRECO will stop enrolling new patients at the end of June Safety • 3 Safety Review Committees successfully conducted • To date, divesiran has been well tolerated with no major safety issues 9 9

SANRECO: Patient Baseline Characteristics Data cutoff 29 March 2024 (16 patients) Patient Cohort Age Sex Race Aspirin (mg) HydroxyUrea Hct baseline (%) 14011001 1 52 Female Caucasian 100 None 39 1000QD M-F 14071001 1 62 Male Caucasian 100 43 1500QD Sat-Sun 500QD 14071002 1 51 Female Caucasian 100 44 500 3x week 10071001 1 63 Male Asian 100 1000BID 56 10051001 2 55 Female Asian 100 500QD 46 10031001 2 62 Male Asian 75 500QD 48 10031002 2 35 Male Asian None None 56 14031001 2 36 Female Caucasian 100 None 39 10051002 2 32 Female Asian 100 None 45 500QD/M-Thr 10031003 2 68 Male Asian 75 48 1000QD/Fr-Sun 10051003 2 59 Male Asian 100 1000QD 49 10061002 2 69 Male Asian 100 1000QD 53 No historic 15021003 3 63 Male Caucasian 100 500BID 50 thrombotic events 14021005 3 40 Male Caucasian 100 500QD 40 14111001 3 58 Male Caucasian 100 None 43 recorded prior to 15021005 3 71 Male Caucasian 100 500BID 44 start of the study. 10 10

Treatment with Divesiran Substantially Reduced Phlebotomy Requirements in PV Patients Phlebotomy History 6 mos prior Screening EoS 239

Divesiran Elevated Hepcidin in PV Patients, Demonstrating Robust Target Engagement 16 Cohort 1 (n = 4) 14 Cohort 2 (n = 8) 12 Dosing 10 8 6 4 2 0 10 20 30 40 50 60 70 80 90 100 110 120 130 -2 Days Note: error bars represent +/- 1 SD 12 12 Hepcidin (nM)

Divesiran Treated PV Patients in Both Cohorts Achieved Target Hematocrit Levels of 45% or Below 55 Cohort 1 (n = 4) Cohort 2 (n = 8) 50 Dosing 45 40 35 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 13 13 Haematocrit (%)

Hematocrit Change from Baseline Suggests a Potential Dose Response 6 Cohort 1 (n = 4) 4 Cohort 2 (n = 8) 2 Dosing 0 -2 -4 -6 -8 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 14 14 Change from baseline

Divesiran Controls Hematocrit Regardless of Baseline Level 55 Hct > 45% at baseline (n = 8) Hct ≤ 45% at baseline (n = 8) 50 Dosing 45 40 35 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 15 15 Haematocrit (%)

Divesiran Increases Ferritin Levels Representing Improvement in Iron Deficient Status 140 Cohort 1 (n = 4) 120 Cohort 2 (n = 8) 100 Dosing 80 60 40 20 0 0 10 20 30 40 50 60 70 80 90 100 110 120 130 -20 Days Note: error bars represent +/- 1 SD 16 16 Ferritin (μg/L)

Divesiran is Associated with Limited Increases in Platelets 1200 Cohort 1 (n = 4) 1000 Cohort 2 (n = 8) 800 Dosing 600 400 200 0 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 17 17 Platelets (g/L)

Divesiran Effect on Platelets Does Not Appear to be Dose Dependent 600 Cohort 1 500 Cohort 2 400 Dosing 300 200 100 0 -100 -200 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: error bars represent +/- 1 SD 18 18 Change from baseline

SANRECO: Summary of Efficacy and Safety Efficacy • All divesiran treated patients who were well controlled at baseline remained so without the need for phlebotomy • All patient groups, regardless of baseline hematocrit, demonstrated reduction and control of hematocrit • Divesiran was associated with elevation of hepcidin, irrespective of iron status, demonstrating robust target engagement • Divesiran was associated with elevation of ferritin, a key indicator of systemic iron content, representing improvement in iron deficient status • Though the study is ongoing and rates can not yet be calculated, only 2 phlebotomies were recorded during divesiran treatment in contrast to a total of 59 phlebotomies reported during the 6 months prior to study entry Safety • No drug related SAEs • No withdrawals due to diverisan related AEs • Mild injection site reactions (ISRs) have been reported, all grade one and fully resolved 19 19

Silencing diseases through precision engineered medicines created with proprietary siRNA technology

Q&A Session SANRECO Phase 1 Results 21

Silencing diseases through Thank you! precision engineered medicines created with proprietary siRNA technology 22