This is a Phase 1/2, multicenter study with an open-label dose escalation followed by a randomized placebo controlled and double-blind phase of SLN124 in adult patients with Polycythemia Vera (PV) to assess the safety, tolerability, efficacy, pharmacokinetic (PK), and Pharmacodynamic (PD) response of SLN124.

Start Date26 Jan 2023

Sponsor / Collaborator

Silence Therapeutics Plc

NCT04718844 / CompletedPhase 1

A Randomised, Single-blind, Placebo-controlled, Phase 1, Single-ascending and Multiple-dose Study in Adult Subjects With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome to Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124.

This study will investigate the safety and tolerability of SLN124 in patients with Thalassaemia or patients with Very Low- and Low-risk Myelodysplastic Syndrome (MDS) after single ascending s.c. doses and multiple doses in healthy male and female subjects. Up to 7 cohorts of 56 patients with Thalassaemia and up to 7 cohorts of 56 patients with MDS will be enrolled. Each subject will receive single or multiple doses of SLN124 or placebo given by subcutaneous (s.c) injection.

Start Date14 Apr 2021

Sponsor / Collaborator

Silence Therapeutics Plc

NCT04559971 / CompletedEarly Phase 1

A Randomised, Double-blind, Placebo-controlled Phase 1 Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered SLN124 in Healthy Volunteers

This study will evaluate the safety and tolerability of SLN124 in healthy volunteers.

Start Date03 Sep 2020

Sponsor / Collaborator

Silence Therapeutics Plc

100 Clinical Results associated with Divesiran

100 Translational Medicine associated with Divesiran

100 Patents (Medical) associated with Divesiran

Literatures (Medical) associated with Divesiran

01 Sep 2023·American journal of hematology

SLN124, a GalNAc conjugated 19-mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers.

Article

Author: Campion, Giles V ; Scrimgeour, Alison ; James, Leo ; Schaeper, Ute ; Aleku, Manuela ; Martinez, Alberto ; Wilkes, Denise ; Wilson, Rosamund ; Boyce, Malcolm ; Porter, John B ; Muckenthaler, Martina

SLN124, an N-acetylgalactosamine conjugated 19-mer short interfering RNA, is being developed to treat iron-loading anemias (including beta-thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis. This first-in-human, phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of SLN124 (1.0, 3.0, and 4.5 mg/kg) in healthy volunteers. Twenty-four participants were randomized in three sequential cohorts of eight subjects, each to receive a single dose of either SLN124 or placebo (6:2 randomization), administered subcutaneously. There were no serious or severe adverse events, or discontinuations due to adverse events, and most treatment-emergent adverse events were mild, including transient mild injection site reactions, resolving without intervention. SLN124 was rapidly absorbed, with a median t_max of 4-5 h across all treatment groups, and largely eliminated from plasma by 48 h. Plasma concentrations increased in a greater than dose proportional fashion between treatment groups. In all SLN124 groups, a dose-related effect was observed across iron metabolism markers, and across erythroid markers, SLN124 resulted in increased plasma hepcidin levels, peaking around Day 29, and consequent dose-related sustained reductions in plasma iron and transferrin saturation with decreased reticulocyte production, MCHC, and MCV. Results suggest duration of action lasting up to 56 days after a single SLN124 dose, on hepcidin and hematological parameters of iron metabolism (serum iron and TSAT).

01 Jul 2021·British journal of haematologyQ2 · MEDICINE

SLN124, a GalNac‐siRNA targeting transmembrane serine protease 6, in combination with deferiprone therapy reduces ineffective erythropoiesis and hepatic iron‐overload in a mouse model of β‐thalassaemia

Q2 · MEDICINE

Article

Author: Eisermann, Mona ; Vadolas, Jim ; Schaeper, Ute ; Crouch, Peter J. ; Ng, Garrett Z. ; Grigoriadis, George ; Nualkaew, Tiwaporn ; Kysenius, Kai ; Vilcassim, Shahla ; Dames, Sibylle

Summary:

Beta‐thalassaemia is an inherited blood disorder characterised by ineffective erythropoiesis and anaemia. Consequently, hepcidin expression is reduced resulting in increased iron absorption and primary iron overload. Hepcidin is under the negative control of transmembrane serine protease 6 (TMPRSS6) via cleavage of haemojuvelin (HJV), a co‐receptor for the bone morphogenetic protein (BMP)‐mothers against decapentaplegic homologue (SMAD) signalling pathway. Considering the central role of the TMPRSS6/HJV/hepcidin axis in iron homeostasis, the inhibition of TMPRSS6 expression represents a promising therapeutic strategy to increase hepcidin production and ameliorate anaemia and iron overload in β‐thalassaemia. In the present study, we investigated a small interfering RNA (siRNA) conjugate optimised for hepatic targeting of Tmprss6 (SLN124) in β‐thalassaemia mice (Hbbth3/+). Two subcutaneous injections of SLN124 (3 mg/kg) were sufficient to normalise hepcidin expression and reduce anaemia. We also observed a significant improvement in erythroid maturation, which was associated with a significant reduction in splenomegaly. Treatment with the iron chelator, deferiprone (DFP), did not impact any of the erythroid parameters. However, the combination of SLN124 with DFP was more effective in reducing hepatic iron overload than either treatment alone. Collectively, we show that the combination therapy can ameliorate several disease symptoms associated with chronic anaemia and iron overload, and therefore represents a promising pharmacological modality for the treatment of β‐thalassaemia and related disorders.

HemaSphere

SLN124, a GalNAc-siRNA Conjugate Targeting TMPRSS6, Efficiently Prevents Iron Overload in Hereditary Haemochromatosis Type 1

Article

Author: Löffler, Kathrin ; Müdder, Katja ; Frauendorf, Christian ; Eisermann, Mona ; Neves, Joana ; Altamura, Sandro ; Dames, Sibylle ; Muckenthaler, Martina U ; Schaeper, Ute

News (Medical) associated with Divesiran

09 Dec 2024

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Silence Therapeutics Presents Promising Phase 1 Data in Polycythemia Vera Patients at the American Society of Hematology (ASH) Annual Meeting

LONDON--( BUSINESS WIRE )--Silence Therapeutics plc (“Silence” or the “Company”) (Nasdaq: SLN), a global clinical-stage company developing novel siRNA (short interfering RNA) therapies, today announced additional results from the Phase 1 open label portion of the SANRECO study of divesiran, a siRNA targeting TMPRSS6 , in patients with polycythemia vera (PV) were presented at the American Society of Hematology (ASH) Annual Meeting being held in San Diego, California. “Additional divesiran data presented at ASH continue to support a compelling profile in PV and highlight the broad potential of our siRNA platform to target both rare and common genetic diseases,” said Craig Tooman, President and CEO at Silence. “Based on these very encouraging results, we are committed to advancing divesiran development as the first-in-class siRNA in PV and will prioritize our resources to ensure we are well positioned to progress this very promising program. To this end, we are pleased to have dosed the first subject in the Phase 2 portion of the SANRECO study, which is currently underway.” Initial results from the SANRECO Phase 1 study were presented in June 2024 and showed that all doses of divesiran substantially reduced phlebotomy frequency and lowered hematocrit (HCT) in 16 phlebotomy dependent PV patients regardless of baseline HCT levels. Additional data presented at ASH further support those findings and included 19 PV patients with a combined history of 79 phlebotomies prior to enrolment. Following divesiran dosing, only five phlebotomies occurred during the 18-week treatment period – all were in patients who entered the study with high baseline HCT levels (over 45%). Two phlebotomies occurred in the 16-week follow-up period following the last administered dose. Consistent with results reported in June, there was a sustained reduction in HCT 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 consistent target engagement. Importantly, divesiran continues to be well tolerated to-date with no dose-limiting toxicities. “PV patients could benefit from a novel treatment option that effectively manages their condition without causing serious adverse effects,” said Marina Kremyanskaya, MD, PhD, Associate Professor of Medicine, Hematology and Medical Oncology, at the Icahn School of Medicine at Mount Sinai. “In the Phase 1 portion of the SANRECO study, divesiran substantially reduced the need for phlebotomy and lowered hematocrit levels following infrequent dosing in a range of PV patients. I’m particularly impressed by the long duration of effect and clean safety/tolerability profile. These data are very exciting and support further development of divesiran in PV.” The ASH presentation is available on the Company’s website, linked here . The Phase 1 portion of the SANRECO study has enrolled 21 patients and is ongoing until all patients complete follow-up which is expected to conclude in February 2025. Silence also announced today the first subject has been dosed in the Phase 2 portion of the SANRECO Study. Divesiran has FDA Fast Track and Orphan Drug designation in the US. SANRECO Phase 1 Study Design The Phase 1 portion of SANRECO is a 34-week, open-label study 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 21 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 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. 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 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. 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 siRNAs designed to precisely target and silence disease associated genes in the liver, which represents a substantial opportunity. Silence focuses on areas of high unmet medical need with programs advancing in cardiovascular disease, hematology and rare diseases. Silence also maintains 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 safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. 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. All statements in this press release, other than statements of historical facts, are forward-looking statements. 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 continued advancement of Phase 2 clinical trial; expected clinical benefits, efficacy and safety of divesiran and the potential to produce clinically meaningful outcomes in PV patients; and the Company’s business strategy and plans to focus on the development of divesiran as the first-in-class siRNA product candidate for treatment of PV. Any forward-looking statements are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond the Company’s control. These risks and uncertainties include, but are not limited to: the impact of worsening 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; the risk that success in preclinical testing and earlier clinical trials is not replicated in later clinical trials; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; the Company’s ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; 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. These and other risks and uncertainties are identified in the section titled "Risk Factors" in the Company’s most recent 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 updated by the section titled “Risk Factors” in the Company’s Report on Form 6-K filed with the SEC on November 14, 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.

Clinical ResultPhase 1Orphan DrugFast TrackASH

14 Nov 2024

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Silence Therapeutics Reports Third Quarter 2024 Financial Results and Recent Business Highlights

LONDON--( BUSINESS WIRE )--Silence Therapeutics plc, Nasdaq: SLN (“Silence” or “the Company”), a global clinical stage biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today reported its financial results for the third quarter ended September 30, 2024 and reviewed recent business highlights. “The Silence team is focused on continued execution across the business,” said Craig Tooman, President and Chief Executive Officer at Silence. “We look forward to presenting additional data from our wholly owned clinical programs at upcoming medical meetings and progressing our pipeline to bring innovative gene silencing medicines to patients around the world.” “We ended the quarter with more than $172 million and are well positioned to advance our lead clinical programs,” said Rhonda Hellums, Chief Financial Officer at Silence. “We are continuing to be prudent with cash and prioritizing investment in key areas where we believe we can deliver the highest value to our shareholders and patients.” Third Quarter 2024 & Recent Business Highlights R&D Highlights Results from the ALPACAR-360 Phase 2 study of zerlasiran in atherosclerotic cardiovascular disease (ASCVD) patients with high Lp(a) will be presented during the Late-Breaking Science Session of the American Heart Association (AHA) Annual Scientific Sessions in Chicago, Illinois, on Monday, November 18, 2024. Results from the Phase 1 portion of the SANRECO Phase 1/2 study of divesiran in polycythemia vera (PV) patients have been selected for oral presentation at the American Society of Hematology (ASH) Annual Meeting taking place December 7-10, 2024, in San Diego, California. The ASH abstract and viewing details are listed below. Presentation Title: Initial Results from a Phase 1/2 Study Evaluating Divesiran, a Novel Galnac Conjugated siRNA, in Patients with Polycythemia Vera (SANRECO) Abstract Number: 656 Presentation Date & Time: Sunday, Dec. 5, 4:45 p.m. PST Location: Manchester Grand Hyatt San Diego, Grand Hall D Presenter: Dr. Marina Kremyanskaya Additional Business Updates On June 30, 2024, the market value of our ordinary shares held by non-affiliates exceeded $700.0 million. Starting January 1, 2025, we will be classified as a “large accelerated filer” by U.S. Securities and Exchange Commission (SEC) and will follow periodic disclosure and reporting requirements applicable to U.S. domestic issuers. Financial Highlights for the Period Ended September 30,2024 Cash Position: Cash, cash equivalents and U.S. Treasury Bills of £129.0 million ($172.7 million) as of September 30, 2024, compared with £54.0 million ($68.8 million) as of December 31, 2023. Collaboration Revenue: Collaboration revenue for the three and nine months ended September 30, 2024, was £1.1 million (September 30, 2023: £2.7 million) and £14.0 million (September 30, 2023: £22.8 million), respectively. Revenue from the current year period primarily related to our AstraZeneca collaboration. R&D Expenses: Research and development (R&D) expenses for the three and nine months ended September 30, 2024, was £15.3 million (September 30, 2023: £8.9 million) and £35.5 million (September 30, 2023: £34.1 million), respectively. The increase compared to the prior year period primarily related to the timing of clinical studies and manufacturing activities. G&A Expenses: General and administrative (G&A) expenses for the three and nine months ended September 30, 2024, was £5.6 million (September 30, 2023: £5.0 million) and £16.1 million (September 30, 2023: £16.5 million), respectively. The £0.6 million increase compared to the prior three-month period was mainly due to increased professional services costs. The £0.5 million decrease from the prior nine-month period was mainly due to decreased payroll costs and equity-based compensation. Net Loss: Net loss for the three and nine months ended September 30, 2024, was £27.0 million, or 19.1 pence basic and diluted net loss per share, (September 30, 2023: £8.2 million or 7.4 pence) and £44.4 million, or 32.3 pence basic and diluted net loss per share (September 30, 2023: £28.9 million or 26.4 pence), respectively. Total ADSs outstanding were approximately 47,214,829, as of September 30, 2024. 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 siRNAs designed to precisely target and silence disease associated genes in the liver, which represents a substantial opportunity. Silence focuses on areas of high unmet medical need with programs advancing in cardiovascular disease, hematology and rare diseases. Silence also maintains research and development collaborations with AstraZeneca and Hansoh Pharma, among others. For more information, please visit https://www.silence-therapeutics.com/ . Forward-Looking Statements Certain statements made in this announcement are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other securities laws, including with respect to the Company’s clinical and commercial prospects, potential partnerships or collaborations under new and existing collaborations and the initiation, advancement or completion of the Company’s clinical trials. These forward-looking statements are not historical facts but rather are based on the Company's current assumptions, beliefs, expectations, estimates and projections about its industry. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” and similar expressions are intended to identify forward-looking statements. These statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties, and other factors, some of which are beyond the Company's control, are difficult to predict, and could cause actual results to differ materially from those expressed or forecasted in the forward-looking statements, including those risks identified in the Company’s most recent Admission Document and its Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on March 13, 2024. The Company cautions security holders and prospective security holders not to place undue reliance on these forward-looking statements, which reflect the view of the Company only as of the date of this announcement. The forward-looking statements made in this announcement relate only to events as of the date on which the statements are made. The Company will not undertake any obligation to release publicly any revisions or updates to these forward-looking statements to reflect events, circumstances, or unanticipated events occurring after the date of this announcement except as required by law or by any appropriate regulatory authority. Condensed consolidated income statement (unaudited) Three months ended Three months ended Nine months ended Nine months ended September 30, 2024 September 30, 2023 September 30, 2024 September 30, 2023 £000s (except per share information) £000s £000s £000s £000s Revenue 1,142 2,798 14,146 23,276 Cost of sales (2,774 ) (1,607 ) (7,625 ) (8,972 ) Gross profit (1,632 ) 1,191 6,521 14,304 Research and development costs (15,305 ) (8,934 ) (35,479 ) (34,088 ) General and administrative expenses (5,600 ) (4,956 ) (16,058 ) (16,521 ) Operating loss (22,537 ) (12,699 ) (45,016 ) (36,305 ) Finance and other expenses (8,602 ) (8 ) (8,627 ) (97 ) Finance and other income 981 2,046 2,679 1,058 Loss for the period before taxation (30,158 ) (10,661 ) (50,964 ) (35,344 ) Taxation 3,146 2,411 6,514 6,489 Loss for the period after taxation (27,012 ) (8,250 ) (44,450 ) (28,855 ) Loss per ordinary share (basic and diluted) (19.1) pence (7.4) pence (32.3) pence (26.4) pence Condensed consolidated balance sheet (unaudited) September 30, 2024 December 31, 2023 £000s £000s Non-current assets Property, plant and equipment 1,647 1,813 Goodwill 7,538 7,840 Other intangible assets 258 284 Other long term assets 2,144 2,580 Financial assets at amortized cost 284 284 11,871 12,801 Current assets Cash and cash equivalents 61,953 54,031 Financial assets at amortized cost 67,037 - R&D tax credit receivable 16,271 17,627 Other current assets 11,963 9,135 Trade receivables 288 228 157,512 81,021 Non-current liabilities Contract liabilities (57,955 ) (58,910 ) Lease liability - (93 ) (57,955 ) (59,003 ) Current liabilities Contract liabilities (2,503 ) (5,161 ) Trade and other payables (14,271 ) (12,429 ) Lease liability (139 ) (179 ) (16,913 ) (17,769 ) Net assets 94,515 17,050 Capital and reserves attributable to the owners of the parent Share capital 7,082 5,942 Capital reserves 432,367 313,769 Translation reserve 1,714 1,951 Accumulated losses (346,648 ) (304,612 ) Total shareholders' equity 94,515 17,050

Financial StatementAHAASH

15 Aug 2024

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Silence Therapeutics Reports Second Quarter 2024 Financial Results and Recent Business Highlights

LONDON--( BUSINESS WIRE )--Silence Therapeutics plc, Nasdaq: SLN (“Silence” or “the Company”), an experienced and innovative biotechnology company committed to transforming people’s lives by silencing diseases through precision engineered medicines, today reported its financial results for the second quarter ended June 30, 2024 and reviewed recent business highlights. “The first half of this year has been marked by strong execution across Silence, including outstanding clinical results in both our wholly owned clinical programs and advancing our first partnered program into the clinic under our AstraZeneca collaboration,” said Craig Tooman, President and Chief Executive Officer at Silence. “Silence’s siRNA technology is continuing to demonstrate itself in the clinic and we expect that positive momentum to continue into the second half of this year and beyond.” “With the $120 million equity raise and milestones from our collaborations, we are well positioned to execute on key clinical objectives for both our zerlasiran and divesiran programs,” said Rhonda Hellums, Chief Financial Officer at Silence. “We will continue to evaluate partnering opportunities for our proprietary mRNAi GOLD™ platform and zerlasiran program with the ultimate goal of delivering maximum value to Silence shareholders and patients.” Second Quarter 2024 & Recent Business Highlights Zerlasiran for cardiovascular disease Announced positive topline 48-week data from the ALPACAR-360 Phase 2 study of zerlasiran in patients with elevated lipoprotein(a) (Lp(a)). Zerlasiran produced highly significant and sustained reductions in Lp(a) to week 48 (end of treatment period) and was well tolerated. Data support advancing zerlasiran into Phase 3. Divesiran for hematological diseases Announced positive results from the ongoing SANRECO Phase 1 study of divesiran in polycythemia vera (PV) patients. Divesiran eliminated the need for phlebotomy in all well-controlled patients following infrequent dosing and was well tolerated. Data support advancing divesiran into Phase 2. Collaborations Achieved a $2.0 million research milestone payment under our collaboration with Hansoh Pharmaceutical Group Company Limited (Hansoh). Organizational updates Promoted Rhonda Hellums, Silence’s Chief Financial Officer, and Steven Romano, MD, Silence’s Chief R&D Officer, to Executive Vice President. Hired Gianine Esposito as Chief Human Resources Officer (CHRO). Gianine brings 25 years of Human Resources experience with over 15 years of pharmaceutical experience and joins Silence from Shionogi Inc. where she was the SVP and CHRO. In her time at Shionogi, Gianine assisted in building out its US-based clinical and commercial organizations through different stages of growth. Hired Marianna Anesti as Vice President, Head of Business Development. Marianna brings 18 years of diverse Biotech & Pharmaceutical experience and joins Silence from Siga Technologies where she was the VP, Business Development & Corporate Strategy. In her time at Siga, Marianna built a pipeline of M&A opportunities, strategic partnerships, and potential in-licensing deals. Prior to Siga, Marianna was Director, R&D Strategy & Consulting at Pfizer where she partnered with Senior R&D leaders across the business to help shape new BD strategies. Financial Highlights for the Period Ended June 30,2024 Cash Position: Cash, cash equivalents and U.S. Treasury Bills of £149.6 million ($189.2 million) as of June 30, 2024, compared with £50.2 million ($63.4 million) as of June 30, 2023. Collaboration Revenue: Collaboration revenue for the three and six months ended June 30, 2024 was £0.6 million (June 30,2023: £9.0 million) and £12.9 million (June 30, 2023: £20.2 million), respectively. Revenue from the current year period primarily related to our ongoing AstraZeneca and Hansoh collaborations and from our Mallinckrodt collaboration we completed in March 2024. R&D Expenses: Research and development (R&D) expenses for the three and six months ended June 30, 2024 was £11.0 million (June 30,2023: £12.6 million) and £20.2 million (June 30, 2023: £25.2 million), respectively. The decrease compared to the prior year period primarily related to the timing of clinical studies and manufacturing activities for our divesiran clinical program. G&A Expenses: General and administrative (G&A) expenses for the three and six months ended June 30, 2024 was £5.3 million (June 30,2023: £5.1 million) and £10.5 million (June 30, 2023: £11.6 million), respectively. The decrease from the prior year six-month period was mainly due to decreased payroll costs and equity-based compensation. Net Loss: Net loss for the three and six months ended June 30, 2024 was £15.6 million, or 11.1 pence basic and diluted net loss per share, (June 30,2023: £10.4 million or 9.6 pence) and £17.4 million, or 12.8 pence basic and diluted net loss per share (June 30, 2023: £20.6 million or 19.0 pence), respectively. Total ADSs outstanding were approximately 46,797,823, as of June 30, 2024. 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 (SLN360) 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 (SLN124) designed to address rare 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 Certain statements made in this announcement are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other securities laws, including with respect to the Company’s clinical and commercial prospects, potential partnerships or collaborations under new and existing collaborations and the initiation, advancement or completion of the Company’s clinical trials. These forward-looking statements are not historical facts but rather are based on the Company's current assumptions, beliefs, expectations, estimates and projections about its industry. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” and similar expressions are intended to identify forward-looking statements. These statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties, and other factors, some of which are beyond the Company's control, are difficult to predict, and could cause actual results to differ materially from those expressed or forecasted in the forward-looking statements, including those risks identified in the Company’s most recent Admission Document and its Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on March 13, 2024. The Company cautions security holders and prospective security holders not to place undue reliance on these forward-looking statements, which reflect the view of the Company only as of the date of this announcement. The forward-looking statements made in this announcement relate only to events as of the date on which the statements are made. The Company will not undertake any obligation to release publicly any revisions or updates to these forward-looking statements to reflect events, circumstances, or unanticipated events occurring after the date of this announcement except as required by law or by any appropriate regulatory authority. Condensed consolidated income statement (unaudited) Three months ended Three months ended Six months ended Six months ended June 30, 2024 June 30, 2023 June 30, 2024 June 30, 2023 £000s (except per share information) £000s £000s £000s £000s Revenue 598 9,104 13,004 20,478 Cost of sales (2,638 ) (2,831 ) (4,851 ) (7,365 ) Gross profit (2,040 ) 6,273 8,153 13,113 Research and development costs (10,995 ) (12,615 ) (20,174 ) (25,154 ) General and administrative expenses (5,288 ) (5,115 ) (10,458 ) (11,565 ) Operating loss (18,323 ) (11,457 ) (22,479 ) (23,606 ) Finance and other expenses (183 ) (893 ) (25 ) (1,753 ) Finance and other income 1,065 340 1,698 676 Loss for the period before taxation (17,441 ) (12,010 ) (20,806 ) (24,683 ) Taxation 1,879 1,609 3,368 4,078 Loss for the period after taxation (15,562 ) (10,401 ) (17,438 ) (20,605 ) Loss per ordinary share (basic and diluted) (11.1) pence (9.6) pence (12.8) pence (19.0) pence Condensed consolidated balance sheet (unaudited) June 30, 2024 December 31, 2023 £000s £000s Non-current assets Property, plant and equipment 1,686 1,813 Goodwill 7,662 7,840 Other intangible assets 267 284 Other long term assets 2,361 2,580 Financial assets at amortized cost 284 284 12,260 12,801 Current assets Cash and cash equivalents 109,482 54,031 Financial assets at amortized cost 40,112 - R&D tax credit receivable 12,852 17,627 Other current assets 12,244 9,135 Trade receivables 1,686 228 176,376 81,021 Non-current liabilities Contract liabilities (58,187 ) (58,910 ) Lease liability - (93 ) (58,187 ) (59,003 ) Current liabilities Contract liabilities (2,766 ) (5,161 ) Trade and other payables (14,992 ) (12,429 ) Lease liability (184 ) (179 ) (17,942 ) (17,769 ) Net assets 112,507 17,050 Capital and reserves attributable to the owners of the parent Share capital 7,019 5,942 Capital reserves 423,831 313,769 Translation reserve 1,807 1,951 Accumulated losses (320,150 ) (304,612 ) Total shareholders' equity 112,507 17,050

Clinical ResultFinancial StatementPhase 2Executive ChangePhase 1

100 Deals associated with Divesiran

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Polycythemia Vera	Phase 2	US	Silence Therapeutics Plc	26 Jan 2023
Polycythemia Vera	Phase 2	AU	Silence Therapeutics Plc	26 Jan 2023
Polycythemia Vera	Phase 2	BG	Silence Therapeutics Plc	26 Jan 2023
Polycythemia Vera	Phase 2	MY	Silence Therapeutics Plc	26 Jan 2023
Polycythemia Vera	Phase 2	PL	Silence Therapeutics Plc	26 Jan 2023
Thalassemia	Phase 1	DE	Silence Therapeutics Plc	14 Apr 2021
Thalassemia	Phase 1	IL	Silence Therapeutics Plc	14 Apr 2021
Thalassemia	Phase 1	IT	Silence Therapeutics Plc	14 Apr 2021
Thalassemia	Phase 1	JO	Silence Therapeutics Plc	14 Apr 2021
Thalassemia	Phase 1	MY	Silence Therapeutics Plc	14 Apr 2021

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04559971 (Pubmed) Manual	Phase 1	-	24	SLN124	hkyplcmgev(yzppbfxmpv) = none blaingawjm (qrxpzrmzsn ) View more	Positive	01 Sep 2023
NCT04559971 (Pubmed) Manual	Phase 1	-	24	Placebo		Positive	01 Sep 2023
NCT04718844 (GEMINI II, BusinessWire) Manual	Phase 1	Thalassemia	24	SLN 124	juwshgvumv(oefxgdgdrj) = eieqhziytu rbmbhkgngl (fzehwwkcig )	Positive	29 Sep 2022

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Divesiran

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