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 GOLDâ"¢ 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 ...

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]

Core Insights - Silence Therapeutics (SLN) is positioned as a focused, clinical-stage RNAi drug development company, but its valuation is impacted by historical execution concerns and the general fatigue in the small-cap biotech sector [1] Company Analysis - The company is seen as having high growth potential, particularly in sectors that are expected to experience exponential expansion [1] - There is a strong emphasis on the importance of innovation in generating substantial returns, indicating a forward-looking approach to investment in disruptive technologies [1] Market Context - The current market sentiment reflects a broader exhaustion in the small-cap biotech space, which may affect investor confidence and company valuations [1]

Core Viewpoint - Silence Therapeutics (SLN) is positioned as a focused, clinical-stage RNAi drug development company, but its valuation is impacted by historical execution concerns and the general fatigue in the small-cap biotech sector [1] Company Analysis - Silence Therapeutics is currently at an interesting stage, indicating potential for growth despite its valuation challenges [1] - The company operates in the RNA interference (RNAi) space, which is a sector expected to see significant expansion [1] Investment Perspective - There is a strong inclination towards investing in high-growth companies, particularly those involved in disruptive technologies [1] - The approach to investment combines fundamental analysis with predictions of future trends, emphasizing the potential for innovation to generate substantial returns [1]

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]

Revenue and Collaborations - The company has not generated any revenue from product sales and does not expect to until regulatory approvals are obtained for its product candidates[80]. - The AstraZeneca collaboration has resulted in upfront payments totaling $60 million, with potential milestone payments of up to $140 million per target and tiered royalties on net sales[74][75][83]. - The company recognized $0.5 million in revenue under the AstraZeneca collaboration for the nine months ended September 30, 2025, a decrease from $16.3 million for the same period in 2024[83]. - The Hansoh collaboration concluded in December 2024, with the company retaining exclusive rights globally for three targets after receiving a total of $22 million in upfront and milestone payments[79][84]. - The company has not recognized any revenue under the Mallinckrodt collaboration during the nine months ended September 30, 2025, compared to $0.6 million for the same period in 2024[82]. - Revenue for the three months ended September 30, 2025, was $0.2 million, a decrease of $1.3 million compared to the same period in 2024, primarily due to reduced activity in the AstraZeneca Collaboration[107]. - Revenue for the nine months ended September 30, 2025, was $0.5 million, reflecting a decrease of $17.4 million from the same period in 2024, mainly due to a $15.7 million decline in revenue from the AstraZeneca Collaboration[108]. Research and Development - Divesiran (SLN124) is in Phase 2 development for polycythemia vera (PV) and has shown promising results in lowering hematocrit levels, with initial topline results expected in Q3 2026[70][76]. - Zerlasiran (SLN360) has demonstrated substantial lowering of Lp(a) levels in clinical trials, with positive regulatory feedback received for its Phase 3 cardiovascular outcomes study design[71][72]. - The ongoing SANRECO Phase 2 clinical trial of divesiran has fully enrolled 48 phlebotomy-dependent PV patients[76]. - The company has a third siRNA product candidate in Phase 1 development through collaboration with AstraZeneca, aiming to maximize its mRNAi GOLD platform[73]. - Research and development costs for the three months ended September 30, 2025, increased by $0.4 million to $20.5 million, driven by a $1.4 million increase in other costs[112]. - Research and development costs for the nine months ended September 30, 2025, rose by $13.2 million to $59.0 million, largely due to a $12.3 million increase in contracted development costs[113]. - The benefit from R&D tax credit decreased due to changes in the U.K. R&D tax credit regime, affecting eligible costs for claims[118]. Financial Position and Cash Flow - As of September 30, 2025, the company had cash, cash equivalents, and short-term investments of $102.2 million, expected to fund operations into 2028[121]. - The company anticipates needing additional capital to fund operations, which may come from equity financings, debt financings, or collaborations[120]. - For the nine months ended September 30, 2025, net cash outflow from operating activities was $(44.984) million, an increase of $4.8 million compared to $(40.159) million in the prior period[127][128]. - The company reported a net cash inflow from investing activities of $5.346 million for the nine months ended September 30, 2025, compared to a net cash outflow of $(88.091) million in the prior period[127]. - As of September 30, 2025, total lease liabilities amounted to $182,000, up from $117,000 as of December 31, 2024[134]. - The company has contractual obligations related to lease liabilities and payments to CROs and manufacturers, with a gross commitment of $0.6 million for office rentals in the next year[137][138]. - The company is exposed to interest rate risk, but does not expect significant impact on operating results due to the conservative nature of its investment portfolio[152]. Profitability and Expenses - The company has not achieved profitability since inception and expects to incur net losses in the future due to ongoing research and development expenses[131]. - The company anticipates that existing capital resources will be sufficient to fund operations for at least the next twelve months[132]. - General and administrative expenses decreased by $1.9 million for the three months ended September 30, 2025, and by $2.7 million for the nine months ended September 30, 2025, compared to the same periods in 2024[114]. - The company incurred non-recurring restructuring charges associated with a limited reduction in workforce implemented in June 2025[115]. - The accumulated tax losses for carry forward in the U.K. were $221.0 million as of September 30, 2025, down from $236.8 million as of September 30, 2024[102]. - In 2024, the company raised additional proceeds of $27.7 million from sales of ADSs under the Open Market Sale Agreement[123]. - The company completed a Private Placement on February 7, 2024, raising approximately $120.0 million before deducting $7.7 million in fees[124].

Financial Performance - Revenue for Q3 2025 was $159,000, compared to $1.5 million in Q3 2024[11] - Gross profit for Q3 2025 was $95,000, compared to a gross loss of $2.1 million in Q3 2024[11] - Net loss for Q3 2025 was $21.0 million, down from $35.5 million in Q3 2024, largely due to foreign currency loss[4] - Research and development expenses for Q3 2025 were $20.5 million, slightly up from $20.2 million in Q3 2024[4] - General and administrative expenses decreased to $5.8 million in Q3 2025 from $7.7 million in Q3 2024, a reduction of $1.9 million[4] Cash Position - Cash and cash equivalents, and short-term investments totaled $102.2 million as of September 30, 2025, expected to fund operations into 2028[4] Clinical Development - Completed enrollment in the SANRECO Phase 2 study of divesiran for polycythemia vera (PV) with 48 patients enrolled[4] - Anticipated topline results from the SANRECO Phase 2 study are expected in Q3 2026[4] - The company aims to advance additional candidates from its mRNAi GOLD™ platform, indicating potential for future growth[2] Share Information - The weighted average shares outstanding for Q3 2025 were 141,701,848[11]

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)