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 June 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 | | Not ...

Exhibit 99.1 Silence Therapeutics Reports Second Quarter 2025 Financial Results and Recent Business Highlights • Presented Updated SANRECO Phase 1 Data at EHA 2025 Further Supporting Potential for Divesiran as First-in-Class siRNA in PV Divesiran for Polycythemia Vera (PV) Zerlasiran for Cardiovascular Disease • Completed core Phase 3 readiness activities, including manufacturing and supply scale up. We continue to be in dialogues with potential third-party partners for Phase 3 development of zerlasiran as ...

Group 1 - Silence Therapeutics PLC Sponsored ADR (SLN) shares have increased by 52% in the past four weeks, closing at $5.41, with a mean price target of $35.50 indicating a potential upside of 556.2% [1] - The mean estimate consists of six short-term price targets with a standard deviation of $23.86, where the lowest estimate is $3 (44.6% decline) and the highest is $75 (1286.3% increase) [2] - Analysts show strong agreement in revising earnings estimates higher, which correlates with potential stock price movements [11] Group 2 - The Zacks Consensus Estimate for SLN has increased by 4.4% due to one upward revision in the last 30 days, with no negative revisions [12] - SLN holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] - While the consensus price target may not be a reliable indicator of the stock's potential gain, it suggests a positive direction for price movement [13]

Core Viewpoint - Silence Therapeutics PLC (SLN) has shown a significant price increase of 68.5% over the past four weeks, with a mean price target of $35.50 indicating a potential upside of 590.7% from the current price of $5.14 [1] Price Targets and Analyst Consensus - The average price target for SLN includes six estimates ranging from a low of $3 to a high of $75, with a standard deviation of $23.86, indicating variability in analyst predictions [2] - The lowest estimate suggests a decline of 41.6%, while the highest points to an upside of 1359.1% [2] - A low standard deviation indicates a strong agreement among analysts regarding the stock's price direction, which can serve as a starting point for further research [9] Earnings Estimates and Analyst Optimism - Analysts have shown growing optimism regarding SLN's earnings prospects, as evidenced by a positive trend in earnings estimate revisions [11] - Over the last 30 days, one estimate has increased, leading to a 4.4% rise in the Zacks Consensus Estimate for the current year [12] - SLN holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates, suggesting strong potential for upside [13]

[PART I – FINANCIAL INFORMATION](index=5&type=section&id=PART%20I%20%E2%80%93%20FINANCIAL%20INFORMATION) [Financial Statements](index=5&type=section&id=Item%201.%20Financial%20Statements) Silence Therapeutics reported Q1 2025 revenue of $0.1 million, a net loss of $28.5 million, and cash and equivalents of $64.9 million Condensed Consolidated Statements of Operations (in thousands) | | Three months ended March 31, 2025 | Three months ended March 31, 2024 | | :--- | :--- | :--- | | **Revenue** | **$142** | **$15,699** | | Gross profit | $88 | $12,899 | | Research and development costs | $(20,813) | $(11,845) | | General and administrative expenses | $(7,684) | $(6,635) | | **Operating loss** | **$(28,409)** | **$(5,581)** | | **Net Loss** | **$(28,530)** | **$(2,312)** | | Loss per share (basic and diluted) | $(0.20) | $(0.02) | Condensed Consolidated Balance Sheet Highlights (in thousands) | | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $64,886 | $121,330 | | Short-term investments | $71,648 | $26,004 | | **Total current assets** | **$169,790** | **$187,366** | | **Total assets** | **$185,298** | **$202,635** | | Total liabilities | $(72,555) | $(68,612) | | **Total shareholders' equity** | **$112,743** | **$134,023** | Condensed Consolidated Statements of Cash Flows Highlights (in thousands) | | Three months ended March 31, 2025 | Three months ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(12,309) | $(9,143) | | Net cash used in investing activities | $(44,381) | $(49,908) | | Net cash provided by financing activities | $14 | $133,020 | - The company believes its current cash, cash equivalents, and short-term investments of **$136.5 million** are sufficient to fund operating expenses for at least the next twelve months from the financial statement issuance date[34](index=34&type=chunk)[35](index=35&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=19&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's siRNA therapeutic pipeline, Q1 2025 financial performance, and liquidity, including a $120 million private placement [Overview and Business Developments](index=19&type=section&id=MD%26A_Overview) Silence Therapeutics develops siRNA therapeutics via its mRNAi GOLD™ platform, advancing Divesiran (PV) and Zerlasiran (Lp(a)) in clinical trials - **Divesiran (SLN124)** for polycythemia vera (PV) is currently in the Phase 2 portion of the SANRECO clinical trial, with enrollment expected to complete by year-end 2025[68](index=68&type=chunk)[75](index=75&type=chunk) - **Zerlasiran (SLN360)** for high Lp(a) has received positive regulatory feedback on its Phase 3 study design, and the company is actively engaged in global partnership discussions for its development and commercialization[69](index=69&type=chunk)[70](index=70&type=chunk) - A Phase 1 study of **SLN312**, licensed to AstraZeneca, is ongoing[75](index=75&type=chunk) [Collaborations](index=20&type=section&id=MD%26A_Collaborations) AstraZeneca collaboration continues with a $10 million milestone, while Mallinckrodt and Hansoh collaborations concluded, returning rights to Silence - AstraZeneca collaboration: A Phase 1 trial for an undisclosed program triggered a **$10 million milestone payment** in February 2024, with the collaboration allowing for up to 10 targets in total[74](index=74&type=chunk) - Mallinckrodt collaboration: Concluded in March 2024 as Mallinckrodt will not pursue further development of SLN501, with Silence having previously reacquired rights to two other preclinical complement targets[78](index=78&type=chunk)[81](index=81&type=chunk) - Hansoh collaboration: Concluded in December 2024 after Hansoh decided not to pursue further development, with Silence retaining exclusive global rights for all three targets from the collaboration[79](index=79&type=chunk)[84](index=84&type=chunk) [Results of Operations](index=21&type=section&id=MD%26A_Results_of_Operations) Q1 2025 revenue decreased to $0.1 million due to fewer milestones, while R&D costs increased by $9.0 million, leading to a $28.4 million operating loss Comparison of Operations (in thousands) | | Three months ended March 31, 2025 | Three months ended March 31, 2024 | Change | | :--- | :--- | :--- | :--- | | **Revenue** | **$142** | **$15,699** | **$(15,557)** | | Research and development costs | $(20,813) | $(11,845) | $(8,968) | | General and administrative expenses | $(7,684) | $(6,635) | $(1,049) | | **Operating loss** | **$(28,409)** | **$(5,581)** | **$(22,828)** | - The **$15.6 million decrease in revenue** was mainly due to a **$14.5 million reduction** in revenue from the AstraZeneca collaboration, as no similar milestones were achieved in Q1 2025 compared to Q1 2024[105](index=105&type=chunk) - R&D costs increased by **$9.0 million**, largely due to the advancement of clinical trials and an increase in contract manufacturing activities for proprietary programs[108](index=108&type=chunk) [Liquidity and Capital Resources](index=27&type=section&id=MD%26A_Liquidity_and_Capital_Resources) As of March 31, 2025, the company held $136.5 million in cash and investments, projected to fund operations into 2028, bolstered by a $120 million private placement - The company had cash, cash equivalents, and short-term investments of **$136.5 million** as of March 31, 2025[115](index=115&type=chunk) - In February 2024, the company raised gross proceeds of approximately **$120.0 million** from a private placement of ADSs[118](index=118&type=chunk)[124](index=124&type=chunk) - Management believes existing capital resources will fund operations into **2028**, which includes receipt of anticipated milestones from collaboration agreements of **$20 million** in the next three years[115](index=115&type=chunk) [Quantitative and Qualitative Disclosures about Market Risk](index=31&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20about%20Market%20Risk) The company manages market risks including credit, liquidity, currency, and interest rate fluctuations through conservative financial practices - The company's primary market risks are credit, liquidity, currency (USD, GBP, EUR), and interest rate risk[143](index=143&type=chunk) - Currency risk is managed by maintaining cash balances in different currencies to meet foreseeable expenses and considering forward exchange contracts for significant receipts[145](index=145&type=chunk) - Interest rate risk is not expected to significantly affect operating results or cash flows due to the conservative nature of the investment portfolio[146](index=146&type=chunk) [Controls and Procedures](index=31&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2025, with no material changes to internal controls - The Chief Executive Officer and Chief Financial Officer concluded that the company's disclosure controls and procedures were **effective** as of March 31, 2025[149](index=149&type=chunk) - No material changes to internal control over financial reporting occurred during the three months ended March 31, 2025[150](index=150&type=chunk) [PART II – OTHER INFORMATION](index=33&type=section&id=PART%20II%20%E2%80%93%20OTHER%20INFORMATION) [Legal Proceedings](index=33&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings - As of the report date, the company is **not party to any material legal proceedings**[153](index=153&type=chunk) [Risk Factors](index=33&type=section&id=Item%201A.%20Risk%20Factors) The company faces evolving risks from stringent U.S. and foreign data privacy laws, including GDPR, cross-border data transfers, and regulations on generative AI - The company is subject to stringent data privacy laws like the EU/U.K. GDPR, which carry potential fines of up to **4% of annual global revenue** for non-compliance[155](index=155&type=chunk)[158](index=158&type=chunk) - Transferring personal data from Europe to the U.S. is significantly restricted and subject to legal challenges, which could interrupt operations or require relocating data processing activities at significant expense[159](index=159&type=chunk)[160](index=160&type=chunk) - The use of generative AI by employees is subject to evolving privacy laws and regulations, which could result in additional compliance costs or competitive disadvantages if its use is restricted[163](index=163&type=chunk) - A new U.S. Department of Justice rule restricts certain data transactions involving countries of concern (e.g., China, Russia), which may impact vendor engagements, data sharing, and investor agreements[161](index=161&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=35&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) There were no unregistered sales of equity securities during the period - None[169](index=169&type=chunk) [Other Information](index=35&type=section&id=Item%205.%20Other%20Information) There is no other information to report for the period - None[172](index=172&type=chunk) [Exhibits](index=36&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Form 10-Q, including CEO and CFO certifications and Inline XBRL documents - Exhibits filed include CEO and CFO certifications pursuant to Sarbanes-Oxley Act Sections 302 and 906[174](index=174&type=chunk)

Report Overview [Management Commentary](index=1&type=section&id=Management%20Commentary) In the first quarter of 2025, Silence Therapeutics' management highlighted strong clinical and operational execution, emphasizing advancement of the SANRECO Phase 2 study for divesiran and cost-saving initiatives extending cash guidance into 2028 - The company is focused on advancing enrollment in the SANRECO Phase 2 study of divesiran and expects to complete it by the end of **2025**[2](index=2&type=chunk) - Additional results from the Phase 1 portion of the SANRECO study will be presented at the European Hematology Association (EHA) meeting in **June 2025**[2](index=2&type=chunk) - Cost-saving measures have been implemented to extend the company's cash runway into **2028**, with a cash, cash equivalents, and short-term investments balance of over **$136 million** at the end of Q1 2025[2](index=2&type=chunk) [First Quarter 2025 & Recent Business Highlights](index=1&type=section&id=First%20Quarter%202025%20%26%20Recent%20Business%20Highlights) The company reported significant progress in its key clinical programs, with divesiran Phase 2 enrollment on track, zerlasiran Phase 3 readiness progressing, and a partnered Phase 1 study with AstraZeneca ongoing [Divesiran for Polycythemia Vera (PV)](index=1&type=section&id=Divesiran%20for%20Polycythemia%20Vera%20%28PV%29) Progress continues on the divesiran program for Polycythemia Vera (PV), with Phase 2 SANRECO study enrollment advancing and new Phase 1 data accepted for presentation at EHA 2025 - Patient enrollment into the Phase 2 portion of the SANRECO study is on track to be completed by **year-end 2025**[7](index=7&type=chunk) - Additional Phase 1 results from the SANRECO study will be presented orally at the EHA 2025 Annual Congress in **June**[7](index=7&type=chunk) [Zerlasiran for Cardiovascular Disease](index=1&type=section&id=Zerlasiran%20for%20Cardiovascular%20Disease) The company is advancing its zerlasiran program for cardiovascular disease with core Phase 3 readiness activities on track for mid-2025 completion and ongoing partnering discussions - Core Phase 3 readiness activities, including manufacturing and supply scale-up, are on track to be completed by **mid-2025**[3](index=3&type=chunk) - Partnering discussions for potential Phase 3 development are ongoing[3](index=3&type=chunk) [Collaborations](index=1&type=section&id=Collaborations) The company's collaboration with AstraZeneca is active, with a Phase 1 study of the licensed product, SLN312, currently ongoing - A Phase 1 study of SLN312, which is licensed to AstraZeneca, is currently ongoing[4](index=4&type=chunk) [Corporate Updates](index=1&type=section&id=Corporate%20Updates) Silence Therapeutics strengthened its leadership by appointing Tim McInerney to its Board of Directors, effective May 5, 2025, leveraging his extensive experience - Tim McInerney, an executive with over **30 years** of experience in investment and pharmaceuticals, was appointed to the Board of Directors[5](index=5&type=chunk) Financial Results and Guidance [First Quarter 2025 Financial Highlights](index=1&type=section&id=First%20Quarter%202025%20Financial%20Highlights) For the first quarter of 2025, Silence Therapeutics reported a cash position of $136.5 million, increased R&D and G&A expenses, and a significantly wider net loss of $28.5 million Q1 2025 Key Financial Metrics | Metric | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Cash, Cash Equivalents, & Short-term Investments | $136.5 million | N/A | Down from $147.3M at YE 2024 | | R&D Expenses | $20.8 million | $11.8 million | +$9.0 million | | G&A Expenses | $7.7 million | $6.6 million | +$1.0 million | | Net Loss | $28.5 million | $2.3 million | +$26.2 million | | Net Loss Per Share (basic and diluted) | $0.20 | $0.02 | +$0.18 | [Updates to 2025 Financial Guidance](index=2&type=section&id=Updates%20to%202025%20Financial%20Guidance) The company has implemented strategic cost-saving initiatives, including reductions in general and administrative costs and prioritization of early-stage research, to extend its cash runway into 2028 - Cost savings initiatives have been implemented to extend the cash runway into **2028**[8](index=8&type=chunk) - These measures involve general and administrative reductions and prioritizing early-stage research projects[8](index=8&type=chunk) [Condensed Consolidated Statements of Operations](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) For the three months ended March 31, 2025, revenue plummeted to $0.14 million from $15.7 million, while operating expenses increased, resulting in a significantly wider operating loss of $28.4 million and a net loss of $28.5 million Condensed Consolidated Statements of Operations (in thousands, except per share data) | | Three months ended March 31, | | | :--- | :--- | :--- | | | **2025** | **2024** | | Revenue | $ 142 | $ 15,699 | | Gross profit | 88 | 12,899 | | Research and development costs | (20,813) | (11,845) | | General and administrative expenses | (7,684) | (6,635) | | **Operating loss** | **(28,409)** | **(5,581)** | | **Net Loss** | **$ (28,530)** | **$ (2,312)** | | **Loss per share (basic and diluted)** | **$ (0.20)** | **$ (0.02)** | [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2025, total assets decreased to $185.3 million from $202.6 million at year-end 2024, primarily due to reduced cash, while total liabilities slightly increased to $72.6 million, resulting in a total shareholders' equity deficit of $112.7 million Condensed Consolidated Balance Sheet Highlights (in thousands) | | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $ 64,886 | $ 121,330 | | Short-term investments | 71,648 | 26,004 | | **Total current assets** | **169,790** | **187,366** | | **Total assets** | **$ 185,298** | **$ 202,635** | | Total current liabilities | (19,264) | (16,822) | | **Total liabilities** | **$ (72,555)** | **$ (68,612)** | | **Total shareholders' equity** | **(112,743)** | **(134,023)** |

Core Viewpoint - Silence Therapeutics PLC has been upgraded to a Zacks Rank 2 (Buy) due to an upward trend in earnings estimates, which is a significant factor influencing stock prices [1][3]. Earnings Estimates and Stock Price Movement - The Zacks rating system is based on changes in earnings estimates, which are closely correlated with near-term stock price movements [4][6]. - Institutional investors often rely on earnings estimates to determine the fair value of a company's shares, leading to stock price fluctuations based on their buying or selling actions [4]. Company Performance and Outlook - The upgrade for Silence Therapeutics indicates an improvement in the company's underlying business, which is expected to positively influence its stock price [5][10]. - For the fiscal year ending December 2025, Silence Therapeutics is projected to earn -$1.61 per share, reflecting a 62.6% decrease from the previous year's reported figure, although analysts have raised their estimates by 0.5% over the past three months [8]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a strong historical performance, particularly for Zacks Rank 1 stocks, which have averaged a +25% annual return since 1988 [7][9]. - Silence Therapeutics' upgrade to Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, indicating a strong potential for market-beating returns in the near term [10].

Financial Data and Key Metrics Changes - For the year ended December 31, 2024, the company recorded revenues of $43.3 million, an increase from $31.6 million in 2023, representing a growth of $11.7 million largely due to collaboration arrangements for siRNA platform development [20][21] - The company's net operating loss for 2024 was approximately $63.3 million, a slight decrease from $64.4 million in 2023, attributed to increased revenue offset by rising R&D costs [26] - The net loss for 2024 was approximately $45.3 million compared to $54.2 million in 2023, reflecting improved financial performance [27] Business Line Data and Key Metrics Changes - The Phase 2 study of zerlasiran showed positive results with Lp(a) reductions exceeding 90%, supporting its competitive profile for further development [5][6] - Divesiran's Phase 1 study eliminated the need for phlebotomy in all well-controlled patients, indicating strong efficacy and safety [8][44] - The company plans to prioritize investment in programs targeting rare conditions, with divesiran for polycythemia vera (PV) remaining a top priority [10][29] Market Data and Key Metrics Changes - The company anticipates full enrollment in the SANRECO Phase 2 study for divesiran by the end of 2024, indicating strong market interest and potential for future growth [15][30] - The collaboration with AstraZeneca continues to advance, with expectations for additional milestones [20][21] Company Strategy and Development Direction - The company will only initiate the Phase 3 outcomes study for zerlasiran once a partner is secured, extending its cash runway into 2027 [12][28] - The focus remains on developing innovative siRNA therapies for rare conditions, leveraging the company's proprietary pipeline [10][29] - The company is evaluating multiple undisclosed programs from its GOLD platform for potential development or partnership [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of zerlasiran and divesiran, highlighting the unique market opportunities for both products [12][60] - The company is actively engaged in partnership discussions for zerlasiran, with a focus on securing the right partner for development and commercialization [61] Other Important Information - Silence has transitioned to a U.S. domestic issuer effective January 1, 2025, requiring compliance with U.S. GAAP and SEC reporting [19] - The company recorded approximately $4.5 million in other income, primarily from U.S. treasury bill accretion, compared to $1.8 million in 2023 [27] Q&A Session Summary Question: Can you provide some color on partnership discussions for zerlasiran? - Management refrained from commenting specifically on ongoing partnership discussions but noted increased funding for Lp(a) studies from companies like Novartis [59][61] Question: How ready is the company for the Phase 3 trial of zerlasiran? - The company is wrapping up Phase 3 readiness activities and is prepared to make adjustments with a partner if needed [67] Question: What are the goals for divesiran regarding differentiation? - The company aims to be the first siRNA to market for PV, focusing on infrequent dosing and symptomatic improvement as key differentiators [75][76] Question: What are the biggest hurdles for partnering zerlasiran? - Hurdles vary by party, often revolving around business strategy and recognition of the large market opportunity [79][80] Question: What is the status of the candidates developed for Hansoh? - The company is interested in the programs developed in partnership with Hansoh and plans to evaluate them for potential internal development or partnership [84][86]

Financial Data and Key Metrics Changes - For the year ended December 31, 2024, the company recorded revenues of $43.3 million, an increase from $31.6 million in 2023, representing a growth of $11.7 million largely due to collaboration arrangements for siRNA platform development [20][21] - The company's net operating loss for 2024 was approximately $63.3 million, a slight decrease from $64.4 million in 2023, attributed to increased revenue offset by rising R&D costs [26] - The net loss for 2024 was approximately $45.3 million compared to $54.2 million in 2023, with cash, cash equivalents, and short-term investments totaling $147.3 million at the end of December 2024 [27] Business Line Data and Key Metrics Changes - The Phase 2 study of zerlasiran showed positive results with Lp(a) reductions exceeding 90%, supporting a competitive profile for further development in Phase 3 [5][6] - Divesiran's Phase 1 study results indicated it completely eliminated the need for phlebotomy in well-controlled patients, with a favorable safety profile [8][14] - The company plans to prioritize investment in programs targeting rare conditions, with divesiran for polycythemia vera (PV) remaining a top priority [10][29] Market Data and Key Metrics Changes - The company has received Orphan Drug Designation for divesiran from the European Commission, and it also holds FDA Fast Track and Orphan Drug Designations for PV [8] - The market opportunity for treating high Lp(a) is significant, with few cardiovascular assets targeting this unmet medical condition [12] Company Strategy and Development Direction - The company will only initiate the Phase 3 outcomes study for zerlasiran once a partner is secured, extending its cash runway into 2027 [28][53] - The focus will be on advancing innovative siRNA therapies for rare conditions, with a commitment to delivering life-changing treatments [29][56] - The company is evaluating multiple undisclosed programs from its GOLD platform for potential development or partnership [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of zerlasiran and divesiran, highlighting the positive feedback received from global regulatory agencies regarding the Phase 3 program design for zerlasiran [6][12] - The company is actively engaged in partnership discussions for zerlasiran, with a focus on securing the right partner for development and commercialization [61] Other Important Information - Silence has transitioned to a U.S. domestic issuer effective January 1, 2025, requiring compliance with U.S. GAAP and SEC reporting [19] - The company plans to start a Phase 1 study of SLN548, targeting complement factor B, in the second half of the year [50] Q&A Session Summary Question: Can you provide some color on partnership discussions for zerlasiran? - Management did not comment specifically on ongoing partnership discussions but noted increased funding for Lp(a) studies from companies like Novartis [59][61] Question: How ready is the company for the Phase 3 trial of zerlasiran? - The company is wrapping up Phase 3 readiness activities and is on track to complete them by mid-year, allowing for some adjustments with a partner [67] Question: What is the goal for divesiran regarding differentiation? - The goal is to be the first siRNA to market for PV, with a focus on infrequent dosing and symptomatic improvement as key differentiators [75][78] Question: What are the biggest hurdles for partnering zerlasiran? - Hurdles vary by party, but discussions often revolve around business strategy and the recognition of the large market opportunity [79][80] Question: What is the status of the candidates developed for Hansoh? - The company is interested in the programs developed under the partnership and will evaluate the opportunity to develop them independently or through partnerships [84]

Clinical Trial Updates - ALPACAR-360 Phase 2 study of Zerlasiran delivered positive results in high Lp(a)[9, 10] - SANRECO Phase 1 study of Divesiran delivered positive results in PV and was granted orphan drug designation for PV in EU[9, 10] - SANRECO Phase 2 study of Divesiran dosed first PV patient, with full enrollment anticipated by year-end 2025[10, 12, 48] - SLN548 (complement factor B) Phase 1 study start anticipated in 2H 2025[12, 48] Divesiran in Polycythemia Vera (PV) - Divesiran is a first-in-class siRNA for PV with FDA Fast Track and Orphan Drug Designations[26, 27] - Phase 1 study showed Divesiran reduced phlebotomy frequency in PV patients who had 79 phlebotomies prior to dosing, but only 5 in the treatment period and 2 in follow-up[29, 31] - Divesiran decreased hematocrit in all cohorts in Phase 1 study[32, 34] - Divesiran treatment produced sustained increases in Hepcidin[36, 38] - Divesiran demonstrated a favorable safety and tolerability profile, with 84% of treatment emergent adverse events (TEAEs) being grade 1[40, 41] Financial Performance and Guidance - Revenue for FY 2024 was $43258 thousand, compared to $31634 thousand in FY 2023[16] - Net loss for FY 2024 was $45309 thousand, compared to $54228 thousand in FY 2023[16] - Cash position at the end of December 2024 was $147334 thousand, including $121300 thousand in cash and cash equivalents and $26000 thousand in short-term investments[16, 17] - Projected cash runway extended into 2027[18]