Summary of Silence Therapeutics Conference Call Company Overview - Silence Therapeutics is a global clinical stage biopharmaceutical company with a proprietary small interfering RNA (siRNA) technology platform known as GOLD (GalNAc Oligonucleotide Discovery platform) targeting liver diseases [3][4] Technology and Programs - The company utilizes GalNAc-directed ligands to effectively target hepatocytes, focusing on conditions where disease-associated proteins are produced in the liver [3] - Silence has a robust intellectual property library and is continuously optimizing its technology [4] Current Clinical Programs 1. **SLN360 (Targeting Lp(a))** - Phase three ready but awaiting partnership for cardiovascular outcome trial [5][6] - Lp(a) is a genetically defined cardiovascular risk factor, not modifiable by diet or exercise [6] - The company has received positive feedback from regulatory agencies (FDA, EMA, PMDA) [5] 2. **SLN124 (Targeting Polycythemia Vera)** - Currently in phase two, targeting TMPRSS6 to manage overproduction of red blood cells [7][9] - The mechanism of action involves increasing hepcidin to restrict iron availability to bone marrow, reducing RBC production [9][10] - The market for polycythemia vera is estimated at 150,000 patients in the US and approximately 3.5 million worldwide [14] 3. **AstraZeneca Partnership** - Collaboration allows for the advancement of up to 10 potential programs, with the first in phase one [42] Phase One Data Highlights for SLN124 - The phase one study included 21 patients, with half maintaining hematocrit below 45% without the need for phlebotomy [17][18] - Significant reductions in hematocrit levels were observed, with improvements in iron status indicated by elevated ferritin levels [19][20] - The phase two trial is set to confirm the Q6 week dosing strategy and explore quarterly dosing [21][24] Competitive Landscape - Silence Therapeutics differentiates its Lp(a) program by targeting a broader population of high-risk patients and potentially lowering entry criteria for trials [35][36] - The company aims to demonstrate robust and durable effects with less frequent dosing compared to competitors [30][34] Upcoming Milestones - Completion of the phase two trial for SLN124 is expected in the early third quarter of 2026 [25] - Anticipated key events in the Lp(a) space include Novartis and Amgen trials demonstrating cardiovascular outcomes related to Lp(a) lowering [43][44] - Silence is also exploring preclinical opportunities and targeting extrahepatic conditions with its siRNA technology [44][45] Financial Position - As of September 30, Silence Therapeutics reported approximately $102 million in cash, sufficient to support operations until 2028 [47]

I think Silence Therapeutics ( SLN ) is currently at an interesting stage. I see it as a focused, clinical-stage RNAi-focused drug development company, but its valuation continues to reflect historical execution concerns and general small-cap biotech exhaustion more soI have a strong inclination towards high-growth companies, often treading in sectors poised for exponential expansion. My expertise lies in understanding and investing in disruptive technologies and forward-thinking enterprises. My approach is ...

I think Silence Therapeutics ( SLN ) is currently at an interesting stage. I see it as a focused, clinical-stage RNAi-focused drug development company, but its valuation continues to reflect historical execution concerns and general small-cap biotech exhaustion more soI have a strong inclination towards high-growth companies, often treading in sectors poised for exponential expansion. My expertise lies in understanding and investing in disruptive technologies and forward-thinking enterprises. My approach is ...

Core Insights - The drugmaker's results for giredestrant indicate a potential new treatment option for early-stage cancer, which is significant as most patients are diagnosed at this stage [1] Company Summary - The introduction of giredestrant could enhance the treatment landscape for early-stage cancer patients, potentially leading to improved patient outcomes [1]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2025 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ____________ to ____________ Commission File Number: 001-39487 Silence Therapeutics plc (Exact name of registrant as specified in its charter) | England and Wales | ...

Exhibit 99.1 Silence Therapeutics Reports Third Quarter 2025 Financial Results and Recent Business Highlights SANRECO Phase 2 study of divesiran in polycythemia vera (PV) fully enrolled; topline results anticipated in 3Q 2026 Strong balance sheet and cash runway into 2028 6 November 2025 • Completed enrollment in the SANRECO Phase 2 study of divesiran for the treatment of PV. The Phase 2 portion of SANRECO is a global, randomized, double-blind, placebo-controlled trial that enrolled 48 phlebotomy-dependent ...

Company Overview - Silence Therapeutics has over 20 years of experience in siRNA technology, boasting a strong intellectual property portfolio [3] - The company has undergone a reverse merger with a German firm and has established labs in Berlin and the UK, along with a newly opened office in the U.S., indicating a global presence [3] Technology and Efficacy - The siRNA technology utilized by Silence Therapeutics is noted for its safety, durability, and outstanding efficacy demonstrated in various studies [3] - The company is currently engaged in three clinical programs targeting significant areas such as cardiovascular diseases related to Lp(a) and conditions like polycythemia vera (PV) [3]

Summary of Silence Therapeutics FY Conference Call Company Overview - Silence Therapeutics is focused on siRNA technology and has developed a strong intellectual property portfolio over two decades [2][3] - The company has a global presence with labs in Berlin, the UK, and a recently opened office in the US [2] - Silence Therapeutics has partnerships, notably with AstraZeneca, to explore various therapeutic areas [2][3] Core Technology and Advantages - The mRNAi GOLD™ platform offers advantages over traditional small molecules and antibodies, including efficacy, safety, durability, and reversibility [4][5] - The technology targets messenger RNA to silence disease-associated proteins, demonstrating robustness and specificity [6] Clinical Programs Polycythemia Vera (PV) - PV is a rare blood cancer characterized by the overproduction of red blood cells, leading to significant unmet medical needs [9] - Approximately 150,000 patients in the U.S. and 3.5 million worldwide are affected, with many being undertreated [10] - Current management involves phlebotomy and cytoreductive agents, with Silence Therapeutics being first in class in the siRNA arena for this condition [11] - Phase 1 trial results showed nearly 100% efficacy in well-controlled patients, with significant reductions in hematocrit levels [11][15] - The ongoing Phase 2 study aims to maintain control of hematocrit levels while reducing the need for phlebotomies, with enrollment expected to complete by year-end 2025 [18][19] Lp(a) Program - Silence Therapeutics is preparing for a Phase 3 trial for Lp(a), a condition affecting up to 20% of the global population, with no approved treatments currently available [38][39] - Phase 1 results demonstrated over 90% reduction in Lp(a) levels, with durable effects observed [41][42] - The company is seeking partners for the large-scale cardiovascular outcome trial (CVOT) due to the significant investment required [38] Competitive Landscape - The siRNA technology is positioned competitively against other treatments, such as antisense oligonucleotides and PCSK9 inhibitors, which have shown modest effects [52][55] - Silence Therapeutics emphasizes the potency and durability of its siRNA compounds, aiming for a less frequent dosing schedule compared to competitors [36][52] Collaboration with AstraZeneca - Silence Therapeutics has a multi-target collaboration with AstraZeneca, focusing on cardiovascular, metabolic, respiratory, and renal areas [56][59] - The collaboration allows for up to 10 targets to be explored, with AstraZeneca handling clinical development [56] Financial Position - The company reported $114 million in cash at the end of Q2 2025, providing a runway into 2028 [67] - This financial position supports ongoing clinical trials and operational needs [67] Macro Considerations - The rise of biotech innovation in China is acknowledged as a long-term competitive factor [68] - Silence Therapeutics is leveraging artificial intelligence and machine learning in its discovery and development processes to enhance efficiency and effectiveness [69][70] Future Focus Areas - The primary focus will be on the PV trial and Lp(a) program, with continued collaboration with AstraZeneca [83] - The company aims to manage costs while exploring additional pipeline opportunities [83]

[PART I – FINANCIAL INFORMATION](index=5&type=section&id=PART%20I%20%E2%80%93%20FINANCIAL%20INFORMATION) This section presents the unaudited condensed consolidated financial statements and management's discussion and analysis for the company [ITEM 1. Financial Statements (Unaudited)](index=5&type=section&id=ITEM%201.%20Financial%20Statements%20(Unaudited)) This section presents the unaudited condensed consolidated financial statements, including balance sheets, statements of operations, comprehensive loss, shareholders' equity, and cash flows [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This statement presents the company's financial position, including assets, liabilities, and equity, at specific points in time | Metric | June 30, 2025 ($000s) | December 31, 2024 ($000s) | | :-------------------------- | :--------------------- | :------------------------ | | Cash and cash equivalents | 41,739 | 121,330 | | Short-term investments | 72,416 | 26,004 | | Total current assets | 148,553 | 187,366 | | Total assets | 165,233 | 202,635 | | Total current liabilities | (14,768) | (16,822) | | Total liabilities | (71,078) | (68,612) | | Total shareholders' equity | (94,155) | (134,023) | [Condensed Consolidated Statements of Operations](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) This statement details the company's revenues, expenses, and net loss over specific reporting periods | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | | :-------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | | Revenue | 224 | 756 | 366 | 16,455 | | Gross profit | 139 | (2,577) | 227 | 10,322 | | Research and development costs | (17,647) | (13,802) | (38,460) | (25,647) | | General and administrative expenses | (5,131) | (7,009) | (12,815) | (13,644) | | Restructuring charges | (1,324) | — | (1,324) | — | | Operating loss | (23,963) | (23,388) | (52,372) | (28,969) | | Net Loss | (27,354) | (19,755) | (55,884) | (22,067) | | Loss per share (basic and diluted) | (0.19) | (0.14) | (0.39) | (0.16) | [Condensed Comprehensive Loss](index=7&type=section&id=Condensed%20Comprehensive%20Loss) This statement presents the net loss and other comprehensive income/loss components for the reporting periods | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | | :-------------------------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | | Net Loss | (27,354) | (19,755) | (55,884) | (22,067) | | Foreign exchange differences on consolidation (net of tax) | 6,680 | 186 | 10,376 | 129 | | Total comprehensive loss for the period | (20,674) | (19,569) | (45,508) | (21,938) | [Condensed Consolidated Statements of Shareholders' Equity](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Shareholders'%20Equity) This statement outlines changes in the company's equity accounts, including ordinary shares, paid-in capital, and accumulated deficit | Metric | At June 30, 2025 ($000s) | At December 31, 2024 ($000s) | | :-------------------------- | :--------------------- | :------------------------ | | Ordinary Shares | 10,290 | 10,288 | | Additional paid-in capital | 615,113 | 609,560 | | Accumulated deficit | (529,844) | (474,045) | | Accumulated other comprehensive income | (1,404) | (11,780) | | Total shareholders' equity | 94,155 | 134,023 | [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This statement summarizes cash inflows and outflows from operating, investing, and financing activities for the reporting periods | Metric | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | | :------------------------------------------ | :----------------------------------- | :----------------------------------- | | Net cash (outflow) from operating activities | (34,093) | (14,552) | | Net cash (outflow) from investing activities | (45,943) | (49,951) | | Net cash inflow from financing activities | 15 | 134,213 | | (Decrease) increase in cash and cash equivalents | (80,021) | 69,710 | | Cash and cash equivalents at end of period | 41,739 | 138,450 | [Notes to the Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20the%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed explanations and disclosures for the financial statements, covering accounting policies, revenue, segments, and equity [1. General information](index=10&type=section&id=1.%20General%20information) This note provides an overview of Silence Therapeutics plc's primary business activities - Silence Therapeutics plc is primarily involved in the discovery, delivery, and development of **RNA therapeutics**[26](index=26&type=chunk) [2. Summary of significant accounting policies](index=10&type=section&id=2.%20Summary%20of%20significant%20accounting%20policies) This note outlines the key accounting principles, reporting standards, and going concern considerations applied in the financial statements - The interim financial statements are prepared in accordance with **U.S. GAAP** for interim reporting and should be read with the Annual Report on Form 10-K for December 31, 2024[27](index=27&type=chunk) - The Group transitioned from **International Financial Reporting Standards (IFRS)** to **U.S. GAAP** retrospectively for all periods due to losing its foreign private issuer status, effective January 1, 2025[28](index=28&type=chunk)[30](index=30&type=chunk) - The reporting currency changed from British pound sterling (GBP) to **U.S. Dollars (USD)** retrospectively, effective January 1, 2025[29](index=29&type=chunk)[30](index=30&type=chunk) - The Group incurred net losses of **$55.9 million** for the six months ended June 30, 2025, and had accumulated losses of **$529.8 million** as of June 30, 2025[33](index=33&type=chunk) - Management believes current cash and cash equivalents are sufficient to fund operating expenses for at least the **next twelve months**, supporting the going concern basis[36](index=36&type=chunk) - The Group will need **additional funding** for future operations and capital expenditures, potentially through public/private financings, debt, or collaboration agreements, with future milestone payments being uncertain[37](index=37&type=chunk) [3. Revenue](index=12&type=section&id=3.%20Revenue) This note details the sources and recognition of revenue, primarily from collaboration agreements - Revenue for the three and six months ended June 30, 2025, primarily related to the **AstraZeneca collaboration agreement**[41](index=41&type=chunk) Revenue by Source | Revenue Source | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | | :-------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | | Research collaboration - AstraZeneca | 224 | 348 | 366 | 15,046 | | Research collaboration - Hansoh | - | 408 | - | 688 | | Research collaboration - Mallinckrodt plc | - | - | - | 578 | | Royalties | - | - | - | 143 | | Total revenue from contracts with customers | 224 | 756 | 366 | 16,455 | - No milestone payments were achieved from the AstraZeneca collaboration during the six months ended June 30, 2025, compared to **$10.0 million** in the prior year period[42](index=42&type=chunk) [4. Segment reporting](index=14&type=section&id=4.%20Segment%20reporting) This note provides information on the company's operating segments and geographic revenue distribution - The Group operates as **one reportable segment** focused on RNA therapeutics[43](index=43&type=chunk) Consolidated Revenue and Net Loss by Period | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | | :-------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | | Revenue | 224 | 756 | 366 | 16,455 | | Consolidated net loss | (27,354) | (19,755) | (55,884) | (22,067) | Non-current Assets and Revenue by Geographic Location | Geographic Location | Non-current assets (Dec 31, 2024, $000s) | Non-current assets (June 30, 2025, $000s) | Revenue (6 Months Ended June 30, 2024, $000s) | Revenue (6 Months Ended June 30, 2025, $000s) | | :------------------ | :--------------------------------------- | :--------------------------------------- | :--------------------------------------------- | :--------------------------------------------- | | U.K. | 4,103 | 4,320 | 16,312 | 366 | | Germany | 11,166 | 12,360 | 143 | - | | Total | 15,269 | 16,680 | 16,455 | 366 | [5. Loss per share (basic and diluted)](index=15&type=section&id=5.%20Loss%20per%20share%20(basic%20and%20diluted)) This note presents the calculation of basic and diluted loss per share for the reporting periods Loss Per Share Calculation | Metric | 3 Months Ended June 30, 2025 | 3 Months Ended June 30, 2024 | 6 Months Ended June 30, 2025 | 6 Months Ended June 30, 2024 | | :----------------------------------- | :--------------------------- | :--------------------------- | :--------------------------- | :--------------------------- | | Net loss | (27,354) | (19,755) | (55,884) | (22,067) | | Weighted-average shares outstanding | 141,696,047 | 140,208,929 | 141,687,438 | 136,045,022 | | Net loss per share (basic and diluted) | (0.19) | (0.14) | (0.39) | (0.16) | - Options outstanding were considered **anti-dilutive** due to the Group being **loss-making**[48](index=48&type=chunk) [6. Goodwill](index=15&type=section&id=6.%20Goodwill) This note provides information on the company's goodwill balance and impairment assessment - Goodwill is assessed **annually for impairment**, and **no triggering events** were identified during the period[49](index=49&type=chunk) Goodwill Balance | Metric | 2025 ($000s) | 2024 ($000s) | | :---------------- | :----------- | :----------- | | Balance at January 1 | 9,392 | 9,981 | | Translation adjustment | 1,225 | (589) | | Balance at period-end | 10,617 | 9,392 | [7. Contract liabilities](index=16&type=section&id=7.%20Contract%20liabilities) This note details the nature and balance of contract liabilities, primarily from collaboration agreements - Contract liabilities represent **advance consideration** received from customers, primarily from the **AstraZeneca collaboration**[51](index=51&type=chunk)[52](index=52&type=chunk) Contract Liabilities | Metric | June 30, 2025 ($000s) | December 31, 2024 ($000s) | | :-------------------------- | :--------------------- | :------------------------ | | Current contract liabilities | 457 | 306 | | Non-current contract liabilities | 56,310 | 51,790 | | Total contract liabilities at period end | 56,767 | 52,096 | [8. Benefit from R&D credit](index=16&type=section&id=8.%20Benefit%20from%20R%26D%20credit) This note outlines the R&D tax credits recognized and received by the company R&D Tax Credits Recognized | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | | :-------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | | R&D tax credits recognized | 2,371 | 2,732 | 5,050 | 5,228 | - The Group received **$11.0 million** related to the 2023 claim for past R&D tax credits during the six months ended June 30, 2025[55](index=55&type=chunk) [9. Shareholders' equity](index=17&type=section&id=9.%20Shareholders'%20equity) This note provides details on the number of shares and ADSs in issue and recent equity financing activities Shares and ADSs in Issue | Metric | June 30, 2025 | December 31, 2024 | | :-------------------------- | :------------ | :---------------- | | Number of shares in issue | 141,701,848 | 141,674,074 | | Number of ADSs in issue | 47,233,949 | 47,224,691 | - In February 2024, the Group completed a **private placement** of **5,714,286 ADSs** at **$21.00 per ADS**, generating **$120.0 million gross proceeds**[57](index=57&type=chunk) [10. Equity-settled share-based compensation](index=18&type=section&id=10.%20Equity-settled%20share-based%20compensation) This note provides a summary of share option activity and outstanding options Share Option Activity | Options | Number of ADSs | Weighted Average Exercise Price ($) | | :------------------------ | :------------- | :-------------------------------- | | Outstanding at January 1, 2025 | 5,818,463 | | | Granted during the period | 1,580,285 | | | Lapsed or forfeited during the period | (363,643) | | | Exercised during the period | (9,258) | | | Outstanding at June 30, 2025 | 7,025,847 | 14.17 | | Exercisable at the period-end | 3,714,364 | | [11. Capital commitments and contingent liabilities](index=19&type=section&id=11.%20Capital%20commitments%20and%20contingent%20liabilities) This note discloses the company's capital commitments and contingent liabilities - There were **no capital commitments** at June 30, 2025, or 2024[62](index=62&type=chunk) [12. Restructuring charges](index=19&type=section&id=12.%20Restructuring%20charges) This note details the restructuring charges incurred due to workforce reduction - The Group incurred **$1.3 million** in restructuring charges during the three months ended June 30, 2025, due to a **workforce reduction**, with a remaining accrual of **$0.9 million**[63](index=63&type=chunk) [13. Related party transactions](index=19&type=section&id=13.%20Related%20party%20transactions) This note confirms the absence of any reported related party transactions - **No related party transactions** were reported[64](index=64&type=chunk) [14. Subsequent events](index=19&type=section&id=14.%20Subsequent%20events) This note reports on events occurring after the balance sheet date - **No subsequent events** were reported[65](index=65&type=chunk) [ITEM 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=20&type=section&id=ITEM%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's perspective on the company's financial condition, operations, liquidity, and critical accounting policies [Overview](index=20&type=section&id=Overview) This section provides a high-level summary of the company's biotechnology focus and key product candidates - Silence Therapeutics is a biotechnology company focused on discovering and developing **RNA therapeutics** using its proprietary **mRNAi GOLD™ platform** to silence specific target genes in the liver for cardiovascular disease, hematology, and rare diseases[68](index=68&type=chunk) - **Divesiran (SLN124)** is a wholly-owned siRNA product candidate in **Phase 2** development for **polycythemia vera (PV)**, with **Fast Track** and **orphan drug designations**, showing potential to lower HCT levels and reduce phlebotomy needs[69](index=69&type=chunk) - **Zerlasiran (SLN360)** is a wholly-owned siRNA product candidate that lowers Lp(a) levels, a cardiovascular risk factor, showing substantial Lp(a) reduction in **Phase 1 and 2 trials**, and the company is seeking a third-party partner for **Phase 3 development**[70](index=70&type=chunk)[71](index=71&type=chunk) - A third siRNA product candidate from the mRNAi GOLD platform is in **Phase 1 development** through a collaboration with **AstraZeneca**, and the company is also advancing extra-hepatic programs[72](index=72&type=chunk) [Second Quarter 2025 Business Developments](index=21&type=section&id=Second%20Quarter%202025%20Business%20Developments) This section highlights key operational and clinical milestones achieved during the second quarter of 2025 - **Exceeded 50% enrollment** in the **SANRECO Phase 2 trial** of **divesiran** in PV patients, on track for completion by **year-end 2025**[76](index=76&type=chunk) - Presented updated Phase 1 data for divesiran at EHA 2025, showing **essential elimination of therapeutic phlebotomies** and **maintained HCT levels below 45%** in PV patients[76](index=76&type=chunk) - Completed **core Phase 3 readiness activities** for **zerlasiran**, including manufacturing and supply scale-up, and continues **partnership discussions** for Phase 3 development and commercialization[76](index=76&type=chunk) - Prioritizing **extra-hepatic activities** due to promising preclinical activity in mice models, leading to a **pause in initiating a Phase 1 study of SLN548** for complement-mediated diseases[76](index=76&type=chunk) - A **Phase 1 trial of SLN312**, licensed to **AstraZeneca**, is ongoing[76](index=76&type=chunk) [Components of Results of Operations](index=22&type=section&id=Components%20of%20Results%20of%20Operations) This section details the components of financial results, including revenue, cost of sales, operating expenses, foreign currency, other income, and taxation [Revenue](index=22&type=section&id=Revenue_Components) This subsection explains the sources and recognition policies for the company's revenue - The company has no commercially approved products and expects future revenue primarily from **product sales** and **strategic collaborations**[81](index=81&type=chunk) - Revenue from collaboration agreements (upfront payments, milestones, research funding) is recognized **over time**[82](index=82&type=chunk) - No revenue was recognized from **Mallinckrodt Collaboration** in H1 2025 (vs. **$0.7 million** in H1 2024) as all development activities concluded in March 2024[83](index=83&type=chunk) - Revenue from **AstraZeneca Collaboration** was **$0.4 million** in H1 2025 (vs. **$15.0 million** in H1 2024), with **no milestone payments** achieved in H1 2025[84](index=84&type=chunk) - No revenue was recognized from **Hansoh Collaboration** in H1 2025 (vs. **$0.6 million** in H1 2024) as Hansoh concluded further development in December 2024[85](index=85&type=chunk) - No royalty income from **Alnylam** was recognized in H1 2025 (vs. **$0.1 million** in H1 2024) as royalties were eligible until December 2023[86](index=86&type=chunk) [Cost of Sales](index=23&type=section&id=Cost%20of%20Sales_Components) This subsection defines the components included in the cost of sales related to revenue-generating contracts - Cost of sales includes **R&D expenditure directly related to revenue-generating contracts**, such as salary costs, materials, and CRO expenses[87](index=87&type=chunk) [Operating Expenses](index=23&type=section&id=Operating%20Expenses_Components) This subsection describes the categories and components of the company's operating expenses - Operating expenses are categorized into **research and development costs** and **general and administrative expenses**, with **personnel costs** being a significant component of both[88](index=88&type=chunk) - Research and development costs are **expensed as incurred** and include contracted development costs (CROs, manufacturing, materials), personnel costs (salaries, benefits, consultants), and other R&D costs (facilities, equipment, patent rights, depreciation)[89](index=89&type=chunk)[90](index=90&type=chunk)[91](index=91&type=chunk)[94](index=94&type=chunk) - R&D costs are expected to **increase significantly** as programs advance to later clinical stages[91](index=91&type=chunk) - General and administrative expenses include personnel costs, professional services (legal, audit, tax), public/investor relations, office costs, insurance, and public company compliance costs[93](index=93&type=chunk)[96](index=96&type=chunk) [Restructuring Charges](index=26&type=section&id=Restructuring%20Charges_Components) This subsection explains the nature of non-recurring restructuring charges incurred by the company - **Non-recurring restructuring charges** were incurred due to a **reduction in force** during the three months ended June 30, 2025[97](index=97&type=chunk) [Foreign Currency Gain (loss), net](index=26&type=section&id=Foreign%20Currency%20Gain%20(loss),%20net_Components) This subsection describes the primary sources of foreign exchange gains and losses - Foreign exchange gains and losses primarily arise from **cash and short-term investments held in foreign currencies** (USD and Euros)[98](index=98&type=chunk) [Other Income, net](index=26&type=section&id=Other%20Income,%20net_Components) This subsection outlines the main components of the company's other income - Other income primarily consists of **interest earned** on cash, cash equivalents, and **accretion on U.S. treasury bills**[99](index=99&type=chunk) [Taxation and Benefit from R&D credit](index=26&type=section&id=Taxation%20and%20Benefit%20from%20R%26D%20credit_Components) This subsection details the company's tax exposure, R&D tax credits, and accumulated tax losses - The company is subject to corporate taxation in the **UK, US, and Germany**, and has generated losses since inception; income tax credit represents **recoverable UK R&D tax credits**[100](index=100&type=chunk) - The UK R&D tax credit regime allows for a cash rebate of **up to 26.97%** of qualifying R&D expenditure for R&D-intensive SMEs, but future changes or challenges could impact cash flow[101](index=101&type=chunk) - Accumulated tax losses for carry forward were **$214.7 million in the UK** and **$52.6 million in Germany** as of June 30, 2025[102](index=102&type=chunk) [Comparison of the three months and six months ended June 30, 2025, and 2024](index=27&type=section&id=Comparison%20of%20the%20three%20months%20and%20six%20months%20ended%20June%2030,%202025,%20and%202024) This section compares financial performance for the three and six months ended June 30, 2025, against 2024, detailing changes in key metrics [Revenue](index=27&type=section&id=Revenue_Comparison) This subsection compares revenue performance for the three and six months ended June 30, 2025, and 2024 Revenue Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | Change ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | Change ($000s) | | :------- | :----------------------------------- | :----------------------------------- | :------------- | :----------------------------------- | :----------------------------------- | :------------- | | Revenue | 224 | 756 | (532) | 366 | 16,455 | (16,089) | - Revenue decreased by **$0.5 million** for the three months and **$16.1 million** for the six months ended June 30, 2025, primarily due to **concluded Hansoh Collaboration activities** and **no milestone achievements from AstraZeneca** in 2025[108](index=108&type=chunk)[109](index=109&type=chunk) [Cost of sales](index=27&type=section&id=Cost%20of%20sales_Comparison) This subsection compares cost of sales for the three and six months ended June 30, 2025, and 2024 Cost of Sales Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | Change ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | Change ($000s) | | :---------- | :----------------------------------- | :----------------------------------- | :------------- | :----------------------------------- | :----------------------------------- | :------------- | | Cost of sales | (85) | (3,333) | 3,248 | (139) | (6,133) | 5,994 | - Cost of sales decreased by **$3.2 million** for the three months and **$6.0 million** for the six months ended June 30, 2025, due to fluctuations in collaboration agreement activities and project progression[110](index=110&type=chunk)[111](index=111&type=chunk) [Research and development costs](index=28&type=section&id=Research%20and%20development%20costs_Comparison) This subsection compares research and development costs for the three and six months ended June 30, 2025, and 2024 Research and Development Costs Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | | :-------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | :----------------------------------- | | Contracted development costs | 12,232 | 7,771 | 26,905 | 14,074 | | Personnel costs | 4,479 | 5,138 | 10,035 | 10,055 | | Other costs | 936 | 893 | 1,520 | 1,518 | | Total R&D costs | 17,647 | 13,802 | 38,460 | 25,647 | - R&D costs increased by **$3.8 million** for the three months and **$12.8 million** for the six months ended June 30, 2025, driven by the advancement of the **divesiran Phase 2 clinical trial** and increased **contract manufacturing for zerlasiran Phase 3 readiness**[113](index=113&type=chunk) [General and administrative expense](index=28&type=section&id=General%20and%20administrative%20expense_Comparison) This subsection compares general and administrative expenses for the three and six months ended June 30, 2025, and 2024 General and Administrative Expense Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | Change ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | Change ($000s) | | :-------------------------------- | :----------------------------------- | :----------------------------------- | :------------- | :----------------------------------- | :----------------------------------- | :------------- | | General and administrative expenses | (5,131) | (7,009) | 1,878 | (12,815) | (13,644) | 829 | - G&A expenses decreased by **$1.9 million** for the three months and **$0.8 million** for the six months ended June 30, 2025, due to **reduced reporting/compliance requirements** and **administrative cost reduction efforts related to restructuring**[114](index=114&type=chunk) [Restructuring charges](index=28&type=section&id=Restructuring%20charges_Comparison) This subsection compares restructuring charges for the three and six months ended June 30, 2025, and 2024 Restructuring Charges Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | Change ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | Change ($000s) | | :------------------ | :----------------------------------- | :----------------------------------- | :------------- | :----------------------------------- | :----------------------------------- | :------------- | | Restructuring charges | (1,324) | - | (1,324) | (1,324) | - | (1,324) | - Non-recurring restructuring charges of **$1.3 million** were incurred during the three months ended June 30, 2025, due to a **limited reduction in force**[115](index=115&type=chunk) [Foreign currency gain (loss), net](index=28&type=section&id=Foreign%20currency%20gain%20(loss),%20net_Comparison) This subsection compares foreign currency gains and losses for the three and six months ended June 30, 2025, and 2024 Foreign Currency Gain (Loss) Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | Change ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | Change ($000s) | | :-------------------------- | :----------------------------------- | :----------------------------------- | :------------- | :----------------------------------- | :----------------------------------- | :------------- | | Foreign currency gain/loss, net | (6,613) | (222) | (6,391) | (10,382) | 129 | (10,511) | - Net foreign exchange losses **increased significantly**, primarily due to the **remeasurement of U.S. treasury bills** held in USD to the related functional currency[116](index=116&type=chunk) [Other Income (expenses), net](index=28&type=section&id=Other%20Income%20(expenses),%20net_Comparison) This subsection compares other income and expenses for the three and six months ended June 30, 2025, and 2024 Other Income (Expenses) Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | Change ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | Change ($000s) | | :------------------ | :----------------------------------- | :----------------------------------- | :------------- | :----------------------------------- | :----------------------------------- | :------------- | | Other income, net | 861 | 1,351 | (490) | 1,830 | 2,017 | (187) | - Other income primarily relates to **accretion from U.S. treasury bills** and **interest on cash accounts**[117](index=117&type=chunk) [Benefit from R&D credit](index=28&type=section&id=Benefit%20from%20R%26D%20credit_Comparison) This subsection compares the benefit from R&D credits for the three and six months ended June 30, 2025, and 2024 Benefit from R&D Credit Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | Change ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | Change ($000s) | | :------------------------ | :----------------------------------- | :----------------------------------- | :------------- | :----------------------------------- | :----------------------------------- | :------------- | | Benefit from R&D credit | 2,371 | 2,732 | (361) | 5,050 | 5,228 | (178) | - Benefit from R&D tax credit relates to **U.K. research and development tax credits**[118](index=118&type=chunk) [Taxation](index=28&type=section&id=Taxation_Comparison) This subsection compares taxation expenses for the three and six months ended June 30, 2025, and 2024 Taxation Comparison | Metric | 3 Months Ended June 30, 2025 ($000s) | 3 Months Ended June 30, 2024 ($000s) | Change ($000s) | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | Change ($000s) | | :--------- | :----------------------------------- | :----------------------------------- | :------------- | :----------------------------------- | :----------------------------------- | :------------- | | Taxation | (10) | (228) | 218 | (10) | (472) | 462 | - Taxation expense relates to **foreign taxation expenses**[119](index=119&type=chunk) [Liquidity and Capital Resources](index=29&type=section&id=Liquidity%20and%20Capital%20Resources) This section analyzes the company's financial position, funding sources, cash flows, and future capital requirements [Overview](index=29&type=section&id=Overview_Liquidity) This subsection provides a summary of the company's liquidity position and funding strategy - The company has incurred **significant operating losses** and **negative cash flows** since inception and expects this to continue, requiring **additional capital** from equity, debt, research funding, or collaborations[120](index=120&type=chunk) - As of June 30, 2025, cash, cash equivalents, and short-term investments totaled **$114.2 million**, believed to be sufficient to fund operations **into 2028**, including **$20 million in anticipated collaboration milestones**[121](index=121&type=chunk) - Operations have been financed primarily through **equity issuances** and **upfront/milestone payments** from collaboration agreements[122](index=122&type=chunk) - In 2024, the company raised **$27.7 million** from **ADS sales** under an Open Market Sale Agreement and **$120.0 million gross proceeds** from a **private placement of ADSs**[123](index=123&type=chunk)[124](index=124&type=chunk) [Cash Flows](index=29&type=section&id=Cash%20Flows_Liquidity) This subsection analyzes the company's cash flows from operating, investing, and financing activities Cash Flows Summary | Metric | 6 Months Ended June 30, 2025 ($000s) | 6 Months Ended June 30, 2024 ($000s) | | :------------------------------------------ | :----------------------------------- | :----------------------------------- | | Net cash (outflow) from operating activities | (34,093) | (14,552) | | Net cash (outflow) from investing activities | (45,943) | (49,951) | | Net cash inflow from financing activities | 15 | 134,213 | | (Decrease) increase in cash and cash equivalents | (80,021) | 69,710 | - Net cash outflow from operating activities increased by **$19.5 million** in H1 2025, mainly due to **reduced collaboration milestones** and **increased contracted development costs**[128](index=128&type=chunk) - Net cash outflow from investing activities primarily relates to **purchases and redemptions of U.S. treasury bills**[129](index=129&type=chunk) - Financing activities in 2024 included **$120 million from a private placement** and proceeds from **at-the-market facility sales**, with no significant related activities in 2025[130](index=130&type=chunk) [Operating and Capital Expenditure Requirements](index=30&type=section&id=Operating%20and%20Capital%20Expenditure%20Requirements) This subsection discusses expected increases in operating expenses and future funding needs - The company expects operating expenses to **increase with pipeline growth**, **additional hires**, and **R&D**, and will incur **significant public company expenses**[131](index=131&type=chunk)[132](index=132&type=chunk) - Future funding requirements depend on **clinical trial scope**, **R&D success**, **manufacturing costs**, **patent prosecution**, **regulatory approvals**, **commercialization**, and **hiring**[133](index=133&type=chunk)[135](index=135&type=chunk) [Contractual Obligations and Commitments](index=30&type=section&id=Contractual%20Obligations%20and%20Commitments) This subsection details the company's contractual obligations and contingent payment arrangements Contractual Obligations | Metric | June 30, 2025 ($000s) | December 31, 2024 ($000s) | | :-------------------- | :--------------------- | :------------------------ | | Total lease liability | - | 117 | - As of June 30, 2025, the company had a gross commitment of **$0.6 million** for **office rentals** in **Berlin** and the **United States** payable within the **next year**, with **no amounts payable after more than one year**[136](index=136&type=chunk) - **Contingent payment obligations** to CROs and manufacturers are not included as amounts, timing, and likelihood are not fixed or determinable[137](index=137&type=chunk) [Critical Accounting Policies, Judgments and Estimates](index=31&type=section&id=Critical%20Accounting%20Policies,%20Judgments%20and%20Estimates) This section outlines key accounting policies, significant estimates, and judgments, especially for revenue recognition and clinical trial expenses [Critical Accounting Estimates](index=31&type=section&id=Critical%20Accounting%20Estimates) This subsection highlights significant accounting estimates, particularly for revenue recognition and clinical trial expenses - **Revenue recognition** under **collaboration agreements**, particularly with **AstraZeneca, Mallinckrodt, and Hansoh**, involves significant estimates[140](index=140&type=chunk)[141](index=141&type=chunk) - For collaboration agreements, revenue for each element of consideration is recognized over the contract period using a **cost-to-cost method**, and variable consideration is recognized when it is **highly probable that a significant reversal will not occur**[144](index=144&type=chunk)[145](index=145&type=chunk) - Recognition of **clinical trial expenses** requires estimating **accrued expenses** based on open contracts, purchase orders, and communication with personnel to identify services performed but not yet invoiced[146](index=146&type=chunk) [Recent Accounting Pronouncements](index=32&type=section&id=Recent%20Accounting%20Pronouncements) This subsection discusses the company's evaluation of recently issued accounting standards - The company is evaluating the impact of **ASU 2023-09 (Income Taxes)** and **ASU 2024-03/2025-01 (Expense Disaggregation Disclosures)** on its financial statements and disclosures[39](index=39&type=chunk)[40](index=40&type=chunk)[147](index=147&type=chunk) [ITEM 3. Quantitative and Qualitative Disclosures about Market Risk](index=32&type=section&id=ITEM%203.%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) This section describes the company's exposure to market risks, including interest rate and currency exchange rate fluctuations [Credit and Liquidity Risk](index=32&type=section&id=Credit%20and%20Liquidity%20Risk) This section addresses risks related to credit quality of financial institutions and management of liquid resources - Cash, cash equivalents, and U.S. treasury bills are held with **high-credit-quality financial institutions**, potentially **exceeding federally insured limits**[149](index=149&type=chunk) - Liquid resources are invested based on **expected expenditure timing**, and **adequate bank balances** are maintained for short-term financial liabilities[149](index=149&type=chunk) [Currency Risk](index=33&type=section&id=Currency%20Risk) This section discusses the company's exposure to foreign currency fluctuations and its management strategies - The company is exposed to currency risk from transactions denominated in **GBP, USD, and Euros**, and manages this by **maintaining appropriate cash balances** and considering **forward exchange contracts** for significant foreign currency receipts[150](index=150&type=chunk) [Interest Rate Risk](index=33&type=section&id=Interest%20Rate%20Risk) This section describes the company's exposure to interest rate fluctuations on its investment portfolio - As of June 30, 2025, cash, cash equivalents, and short-term investments totaled **$114.2 million**[151](index=151&type=chunk) - Due to the **conservative nature of its investment portfolio** (**capital preservation**, **short-term maturities**), the company does **not expect significant impact** from changes in market interest rates[151](index=151&type=chunk) [ITEM 4. Controls and Procedures](index=33&type=section&id=ITEM%204.%20Controls%20and%20Procedures) This section details the company's disclosure controls and procedures and reports on changes in internal control over financial reporting [Disclosure Controls and Procedures](index=33&type=section&id=Disclosure%20Controls%20and%20Procedures) This section reports on the effectiveness of the company's disclosure controls and procedures - Management, with CEO and CFO participation, evaluated the effectiveness of disclosure controls and procedures as of June 30, 2025, and concluded they were **effective at a reasonable assurance level**[152](index=152&type=chunk)[153](index=153&type=chunk) [Changes in Internal Control Over Financial Reporting](index=33&type=section&id=Changes%20in%20Internal%20Control%20Over%20Financial%20Reporting) This section reports on any material changes in internal control over financial reporting - **No changes in internal control over financial reporting** occurred during the fiscal quarter ended June 30, 2025, that materially affected or are reasonably likely to materially affect it[154](index=154&type=chunk) [PART II – OTHER INFORMATION](index=34&type=section&id=PART%20II%20%E2%80%93%20OTHER%20INFORMATION) This section provides additional information not covered in the financial statements, including legal, risk factors, and exhibits [ITEM 1. Legal Proceedings](index=34&type=section&id=ITEM%201.%20Legal%20Proceedings) This section confirms the company is not currently involved in any material legal proceedings - The company is **not currently involved in any material legal proceedings**[157](index=157&type=chunk) [ITEM 1A. Risk Factors](index=34&type=section&id=ITEM%201A.%20Risk%20Factors) This section updates significant risks to the company's business, focusing on data privacy laws and healthcare regulatory reforms - The company is subject to **stringent and evolving U.S. and foreign data privacy and security laws** (e.g., GDPR, CCPA, U.S. Department of Justice rule on sensitive personal data), and **non-compliance could lead to investigations, litigation, fines, and business disruptions**[159](index=159&type=chunk)[161](index=161&type=chunk)[162](index=162&type=chunk)[165](index=165&type=chunk)[166](index=166&type=chunk)[171](index=171&type=chunk) - **Transferring personal data from Europe to the U.S. faces significant restrictions and scrutiny**, with no assurance that current mechanisms will remain compliant, potentially impacting operations or requiring relocation[163](index=163&type=chunk)[164](index=164&type=chunk) - **Healthcare legislative and regulatory reforms** in the U.S. (e.g., OBBBA, drug pricing initiatives) and EU (e.g., CTR, HTA Regulation, revised pharmaceutical legislation) could **negatively impact product approval, post-approval activities, and profitability**[173](index=173&type=chunk)[174](index=174&type=chunk)[175](index=175&type=chunk)[177](index=177&type=chunk)[179](index=179&type=chunk) - The **UK's regulatory alignment with the EU post-Brexit is uncertain**, potentially affecting clinical trial costs and marketing authorization processes[176](index=176&type=chunk) [ITEM 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=38&type=section&id=ITEM%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) This section reports no unregistered sales of equity securities or use of proceeds - **No unregistered sales of equity securities or use of proceeds** were reported[180](index=180&type=chunk) [ITEM 3. Defaults Upon Senior Securities](index=38&type=section&id=ITEM%203.%20Defaults%20Upon%20Senior%20Securities) This section confirms no defaults upon senior securities were reported - **No defaults upon senior securities** were reported[182](index=182&type=chunk) [ITEM 4. Mine Safety Disclosures](index=38&type=section&id=ITEM%204.%20Mine%20Safety%20Disclosures) This section clarifies that mine safety disclosures are not applicable to the company - **Mine safety disclosures are not applicable**[183](index=183&type=chunk) [ITEM 5. Other Information](index=38&type=section&id=ITEM%205.%20Other%20Information) This section confirms no other information is reported - **No other information** was reported[184](index=184&type=chunk) [ITEM 6. Exhibits](index=39&type=section&id=ITEM%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including certifications and XBRL documents - The report includes various exhibits such as **Amended and Restated Articles of Association**, **certifications by executive officers (31.1, 31.2, 32.1)**, and **Inline XBRL documents (101.INS, 101.SCH, 104)**[186](index=186&type=chunk) [Signatures](index=40&type=section&id=Signatures) This section contains the certifications by the Chief Executive Officer and Chief Financial Officer - The report is signed by **Craig Tooman, Chief Executive Officer**, and **Rhonda Hellums, Chief Financial Officer**, on **August 7, 2025**[191](index=191&type=chunk)

[Executive Summary](index=1&type=section&id=Executive%20Summary) Silence Therapeutics reported positive Phase 1 data for divesiran in Polycythemia Vera, with the SANRECO Phase 2 trial on track, and maintained a strong financial position with $114.2 million in cash, extending its runway into 2028 [Q2 2025 Business and Strategic Highlights](index=1&type=section&id=Q2%202025%20Business%20and%20Strategic%20Highlights) The second quarter of 2025 was marked by positive updated Phase 1 data for divesiran in Polycythemia Vera, reinforcing its therapeutic potential. The SANRECO Phase 2 trial remains a top priority, progressing towards full enrollment by year-end 2025 - Presented updated SANRECO Phase 1 data at EHA 2025, further supporting divesiran's potential as a first-in-class siRNA in PV[1](index=1&type=chunk)[2](index=2&type=chunk) - The SANRECO Phase 2 study for divesiran is on-track for complete enrollment by year-end 2025 and remains the company's top priority[1](index=1&type=chunk)[2](index=2&type=chunk) [Q2 2025 Financial Overview](index=1&type=section&id=Q2%202025%20Financial%20Overview) Silence Therapeutics maintained a strong financial position, ending Q2 2025 with approximately $114.2 million in cash and cash equivalents and short-term investments, which is expected to fund operational plans into 2028 | Metric | Value (as of June 30, 2025) | | :----- | :-------------------------- | | Cash and cash equivalents and short-term investments | $114.2 million | | Cash runway guidance | Into 2028 | [Business and R&D Updates](index=1&type=section&id=Second%20Quarter%202025%20%26%20Recent%20Business%20Highlights) The company advanced divesiran for Polycythemia Vera with positive Phase 1 data and ongoing Phase 2 enrollment, completed Phase 3 readiness for zerlasiran, and prioritized extra-hepatic siRNA targeting while pausing SLN548 development [Divesiran for Polycythemia Vera (PV)](index=1&type=section&id=Divesiran%20for%20Polycythemia%20Vera%20%28PV%29) Divesiran continues to show compelling therapeutic potential for Polycythemia Vera, with updated Phase 1 data demonstrating durable hematocrit control and improved iron deficiency. The Phase 2 SANRECO trial is progressing well, exceeding 50% enrollment and remaining on track for year-end completion - Divesiran is being developed as a first-in-class siRNA for Polycythemia Vera (PV)[2](index=2&type=chunk)[3](index=3&type=chunk) - The SANRECO Phase 2 trial for divesiran in PV patients is a top priority and continues to progress towards full enrollment this year[2](index=2&type=chunk)[6](index=6&type=chunk) [SANRECO Phase 1 Data Presentation](index=1&type=section&id=SANRECO%20Phase%201%20Data%20Presentation) Updated Phase 1 data for divesiran demonstrated durable hematocrit control, reduced phlebotomy needs, and improved iron deficiency, with good tolerability - Divesiran treatment led to durable hematocrit control (<45%) and essentially eliminated the need for phlebotomies in the targeted population[6](index=6&type=chunk) - Divesiran increased hepcidin and ferritin, resulting in elevation of iron body content and improved iron deficiency[6](index=6&type=chunk) - Divesiran was well tolerated with no dose-limiting toxicities[6](index=6&type=chunk) [SANRECO Phase 2 Study Progress](index=1&type=section&id=SANRECO%20Phase%202%20Study%20Progress) The SANRECO Phase 2 trial has exceeded 50% enrollment and remains on schedule for completion by year-end 2025 - Exceeded **50% enrollment** in the Phase 2 portion of the SANRECO trial[6](index=6&type=chunk) - Remains on-track to complete enrollment by year-end 2025[6](index=6&type=chunk) [Zerlasiran for Cardiovascular Disease](index=1&type=section&id=Zerlasiran%20for%20Cardiovascular%20Disease) Silence Therapeutics has completed core Phase 3 readiness activities for zerlasiran, including manufacturing and supply scale-up, and is actively seeking third-party partners for its Phase 3 development and potential commercialization - Completed core Phase 3 readiness activities for zerlasiran, including manufacturing and supply scale up[4](index=4&type=chunk) - Actively in dialogues with potential third-party partners for Phase 3 development of zerlasiran as well as potential future commercialization activities[4](index=4&type=chunk) [Other Research & Development Activities](index=1&type=section&id=Other%20R%26D%20Updates) The company is prioritizing extra-hepatic cell targeting of siRNA due to promising initial preclinical activity in mice models, leading to the decision to pause the initiation of a Phase 1 study for SLN548, an siRNA for complement-mediated diseases - Prioritizing extra-hepatic activities due to promising initial preclinical activity in mice models for extra-hepatic cell targeting of siRNA[5](index=5&type=chunk) - Decided to pause initiating a Phase 1 study of SLN548, a wholly owned siRNA for complement-mediated diseases[5](index=5&type=chunk) [Collaborations](index=2&type=section&id=Collaborations) A Phase 1 study for SLN312, a siRNA product candidate licensed to AstraZeneca, is currently ongoing, indicating continued progress in external partnerships - A Phase 1 study of our siRNA product candidate, SLN312, which is licensed to AstraZeneca, is ongoing[7](index=7&type=chunk) [Financial Performance](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Highlights) Silence Therapeutics reported an increased net loss in Q2 2025 due to higher R&D expenses and foreign currency losses, while maintaining a strong cash position with a runway into 2028 [Second Quarter 2025 Financial Highlights](index=2&type=section&id=Second%20Quarter%202025%20Financial%20Highlights) Silence Therapeutics reported a net loss of $27.4 million for Q2 2025, an increase from $19.8 million in Q2 2024, primarily due to higher R&D expenses driven by clinical trial advancements and contract manufacturing. G&A expenses decreased due to efficiency efforts. The company ended the quarter with $114.2 million in cash and short-term investments, projecting a cash runway into 2028 | Financial Metric | Q2 2025 (in millions) | Q2 2024 (in millions) | Change (YoY) | | :--------------- | :-------------------- | :-------------------- | :----------- | | R&D Expenses | $17.6 | $13.8 | +$3.8 (+27.5%) | | G&A Expenses | $5.1 | $7.0 | -$1.9 (-27.1%) | | Net Loss | $27.4 | $19.8 | +$7.6 (+38.4%) | - The increase in R&D expenses was primarily driven by the advancement of clinical trials and an increase in contract manufacturing activities[11](index=11&type=chunk) - The decrease in G&A expenses was primarily due to a reduction in reporting and compliance requirements, as well as efforts to increase operating efficiencies[11](index=11&type=chunk) | Metric | Value (as of June 30, 2025) | | :----- | :-------------------------- | | Cash and cash equivalents, and short-term investments | $114.2 million | | Expected cash runway | Into 2028 | [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of June 30, 2025, total assets decreased to $165.2 million from $202.6 million at December 31, 2024, primarily driven by a reduction in cash and cash equivalents. Total liabilities increased slightly, while total shareholders' equity improved from a larger deficit | Balance Sheet Item | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | Change | | :----------------- | :--------------------------- | :------------------------------- | :----- | | Total assets | $165,233 | $202,635 | -$37,402 | | Total liabilities | $(71,078) | $(68,612) | -$2,466 (increase in absolute value) | | Total shareholders' equity | $(94,155) | $(134,023) | +$39,868 (reduction in deficit) | | Cash and cash equivalents | $41,739 | $121,330 | -$79,591 | | Short-term investments | $72,416 | $26,004 | +$46,412 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For the three months ended June 30, 2025, Silence Therapeutics reported a net loss of $27.4 million, an increase from $19.8 million in the prior year period. This was influenced by a significant foreign currency loss and increased R&D costs, despite a decrease in G&A expenses | Income Statement Item | Three months ended June 30, 2025 (in thousands) | Three months ended June 30, 2024 (in thousands) | Change (YoY) | | :-------------------- | :---------------------------------------------- | :---------------------------------------------- | :----------- | | Revenue | $224 | $756 | -$532 (-70.4%) | | Gross profit | $139 | $(2,577) | +$2,716 (swing to profit) | | Research and development costs | $(17,647) | $(13,802) | -$(3,845) (+27.9%) | | General and administrative expenses | $(5,131) | $(7,009) | +$1,878 (-26.8%) | | Operating loss | $(23,963) | $(23,388) | -$(575) (+2.5%) | | Foreign currency (loss)/gain, net | $(6,613) | $(222) | -$(6,391) (significant increase in loss) | | Net Loss | $(27,354) | $(19,755) | -$(7,599) (+38.5%) | | Loss per share (basic and diluted) | $(0.19) | $(0.14) | -$(0.05) (+35.7%) | - The company incurred a significant foreign currency loss of **$6.6 million** in Q2 2025, compared to a loss of **$0.2 million** in Q2 2024[17](index=17&type=chunk) [Corporate Information](index=2&type=section&id=Corporate%20Information) Silence Therapeutics is a clinical-stage biotechnology company focused on siRNA therapies for cardiovascular, hematology, and rare diseases, with forward-looking statements subject to inherent risks [About Silence Therapeutics](index=2&type=section&id=About%20Silence%20Therapeutics) Silence Therapeutics is a global clinical-stage biotechnology company dedicated to transforming lives through precision-engineered siRNA medicines. It utilizes its mRNAi GOLD™ platform to target disease-associated genes, primarily in the liver, focusing on cardiovascular, hematology, and rare diseases - Silence Therapeutics is a global clinical-stage biotechnology company focused on developing novel siRNA therapies[9](index=9&type=chunk) - The company leverages its mRNAi GOLD™ platform to create siRNAs designed to precisely target and silence disease-associated genes, primarily in the liver[9](index=9&type=chunk) - Focuses on areas of high unmet medical need, with programs advancing in cardiovascular disease, hematology, and rare diseases[9](index=9&type=chunk) [Forward-Looking Statements](index=2&type=section&id=Forward-Looking%20Statements) The report contains forward-looking statements regarding business strategy, clinical development, therapeutic benefits, trial timelines, collaborations, value delivery, and cash runway. These statements are subject to risks and uncertainties, including operating losses, capital needs, regulatory approvals, side effects, reliance on third parties, and intellectual property, as detailed in SEC filings - The press release contains forward-looking statements regarding business strategy, clinical development activities and timelines, therapeutic benefits, trial enrollment timing, collaborations, value delivery, and anticipated cash runway[10](index=10&type=chunk) - Forward-looking statements are subject to risks and uncertainties, including net operating losses, ability to obtain capital, early stages of clinical development, regulatory approval, undesirable side effects, reliance on third-party suppliers, and intellectual property rights[10](index=10&type=chunk)[12](index=12&type=chunk) - The company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law[12](index=12&type=chunk) [Inquiries](index=3&type=section&id=Inquiries) Contact information for investor relations and corporate communications is provided for inquiries regarding Silence Therapeutics - Inquiries can be directed to Gem Hopkins, VP, IR and Corporate Communications, via email or phone[13](index=13&type=chunk)