PART I. FINANCIAL INFORMATION [Financial Statements (Unaudited)](index=6&type=section&id=ITEM%201.%20FINANCIAL%20STATEMENTS%20%28UNAUDITED%29) This section presents unaudited condensed consolidated financial statements for Q2 2025, including balance sheets, statements of operations, and cash flows, reporting a net loss of $66.3 million Balance Sheet Summary (in thousands) | Financial Metric | June 30, 2025 (in thousands) | December 31, 2024 (in thousands) | | :--- | :--- | :--- | | **Total Assets** | $4,566,019 | $4,239,983 | | **Total Liabilities** | $4,315,428 | $4,172,895 | | **Total Stockholders' Equity** | $250,591 | $67,088 | Condensed Consolidated Statements of Operations (in thousands) | Income Statement Item | Three Months Ended June 30, 2025 (in thousands) | Three Months Ended June 30, 2024 (in thousands) | | :--- | :--- | :--- | | **Total Revenues** | $773,689 | $659,825 | | **Total Operating Costs and Expenses** | $789,888 | $611,211 | | **Net Loss** | $(66,277) | $(16,889) | | **Net Loss Per Share (basic and diluted)** | $(0.51) | $(0.13) | [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Detailed disclosures support financial statements, covering accounting policies, revenue breakdowns, collaboration agreements, and legal contingencies, highlighting strong AMVUTTRA product revenue growth Net Product Revenues (in thousands) | Product Revenue (in thousands) | Q2 2025 | Q2 2024 | YTD 2025 | YTD 2024 | | :--- | :--- | :--- | :--- | :--- | | **AMVUTTRA** | $491,953 | $230,109 | $801,945 | $425,350 | | **ONPATTRO** | $52,538 | $77,244 | $102,027 | $146,461 | | **GIVLAARI** | $80,849 | $62,127 | $147,817 | $120,183 | | **OXLUMO** | $46,872 | $40,608 | $88,961 | $83,257 | | **Total Net Product Revenues** | **$672,212** | **$410,088** | **$1,140,750** | **$775,251** | Collaboration Revenues (in thousands) | Collaboration Revenue (in thousands) | Q2 2025 | Q2 2024 | YTD 2025 | YTD 2024 | | :--- | :--- | :--- | :--- | :--- | | **Roche** | $18,267 | $16,506 | $35,323 | $91,186 | | **Regeneron Pharmaceuticals** | $32,542 | $207,429 | $83,581 | $234,193 | | **Novartis AG** | $0 | $2,304 | $0 | $16,820 | | **Other** | $10,687 | $1,099 | $41,777 | $3,687 | | **Total** | **$61,496** | **$227,338** | **$160,681** | **$345,886** | - The company is involved in patent infringement lawsuits filed in March 2022 against Moderna and Pfizer concerning their mRNA COVID-19 vaccines, with court rulings generally **unfavorable to Alnylam** and judgments of **non-infringement** entered, though appeals are being considered[107](index=107&type=chunk)[111](index=111&type=chunk)[112](index=112&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations (MD&A)](index=27&type=section&id=ITEM%202.%20MANAGEMENT%27S%20DISCUSSION%20AND%20ANALYSIS%20OF%20FINANCIAL%20CONDITION%20AND%20RESULTS%20OF%20OPERATIONS) Management discusses strong AMVUTTRA product revenue growth, offset by decreased collaboration revenue, detailing the Alnylam P5x25 strategy, pipeline updates, and operating expense analysis [Overview and Pipeline](index=27&type=section&id=Overview%20and%20Pipeline) Alnylam, a commercial-stage biopharmaceutical company, executes its 'Alnylam P5x25' strategy, driven by AMVUTTRA's expanded approval and a robust late-stage pipeline - The company is pursuing its **"Alnylam P5x25" strategy** with the goal of becoming a **top-tier biotech company by the end of 2025**, focusing on **sustainable innovation and strong financial performance**[126](index=126&type=chunk) - A **major growth driver** is the recent approval of AMVUTTRA for the treatment of cardiomyopathy of ATTR amyloidosis in the **U.S. (March 2025)**, **EU (June 2025)**, and other key global markets[127](index=127&type=chunk) - Key late-stage pipeline programs include: - **Zilebesiran (Hypertension):** Partnered with Roche, with a Phase 3 trial expected to start in H2 2025 - **Nucresiran (ATTR Amyloidosis):** Phase 3 trial (TRITON-CM) initiated - **Mivelsiran (Alzheimer's & CAA):** Phase 2 trial in AD expected in H2 2025; Phase 2 in CAA initiated[134](index=134&type=chunk)[135](index=135&type=chunk) [Results of Operations](index=33&type=section&id=Results%20of%20Operations) Q2 2025 total revenues increased 17% to $773.7 million, driven by 64% growth in net product revenues from AMVUTTRA, despite a 73% decrease in collaboration revenue Total Revenues (in thousands) | Revenue Line Item (in thousands) | Q2 2025 | Q2 2024 | % Change | | :--- | :--- | :--- | :--- | | Net product revenues | $672,212 | $410,088 | 64% | | Net revenues from collaborations | $61,496 | $227,338 | (73)% | | Royalty revenue | $39,981 | $22,399 | 78% | | **Total revenues** | **$773,689** | **$659,825** | **17%** | - The sharp decrease in collaboration revenue in Q2 2025 compared to Q2 2024 was primarily driven by the recognition of **$185.0 million** in revenue from Regeneron in June 2024 related to a license for cemdisiran[164](index=164&type=chunk)[168](index=168&type=chunk) Operating Costs and Expenses (in thousands) | Operating Costs (in thousands) | Q2 2025 | Q2 2024 | % Change | | :--- | :--- | :--- | :--- | | Cost of goods sold | $142,029 | $67,271 | 111% | | Research and development | $323,621 | $294,142 | 10% | | Selling, general and administrative | $323,314 | $248,397 | 30% | | **Total operating costs** | **$789,888** | **$611,211** | **29%** | [Liquidity and Capital Resources](index=38&type=section&id=Liquidity%20and%20Capital%20Resources) As of June 30, 2025, the company held $1.11 billion in cash and $1.74 billion in marketable securities, sufficient to fund operations for at least 12 months Condensed Consolidated Statements of Cash Flows (in thousands) | Cash Flow Activity (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash provided by operating activities | $35,416 | $42,643 | | Net cash used in investing activities | $(27,612) | $(33,680) | | Net cash provided by financing activities | $97,841 | $160,407 | - The company believes its cash, cash equivalents, and marketable securities of **$2.86 billion** as of June 30, 2025, are sufficient to fund operations for **at least the next 12 months** from the filing date[186](index=186&type=chunk)[216](index=216&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=38&type=section&id=ITEM%203.%20QUANTITATIVE%20AND%20QUALITATIVE%20DISCLOSURES%20ABOUT%20MARKET%20RISK) No significant changes to financial market risks, primarily interest rate-related, were reported since fiscal year 2024 - There have been **no significant changes** to the company's financial market risk exposures, which are mainly related to **interest rates**, as of June 30, 2025, compared to December 31, 2024[187](index=187&type=chunk) [Controls and Procedures](index=38&type=section&id=ITEM%204.%20CONTROLS%20AND%20PROCEDURES) Management concluded disclosure controls and procedures were effective as of June 30, 2025, with no material changes in internal control over financial reporting - The CEO and CFO concluded that as of June 30, 2025, the company's disclosure controls and procedures were **effective at the reasonable assurance level**[189](index=189&type=chunk) - **No changes** in internal control over financial reporting occurred during the quarter ended June 30, 2025, that have materially affected, or are reasonably likely to materially affect, these controls[190](index=190&type=chunk) PART II. OTHER INFORMATION [Legal Proceedings](index=40&type=section&id=ITEM%201.%20LEGAL%20PROCEEDINGS) This section refers readers to Note 12 of the condensed consolidated financial statements for material pending legal proceedings - For a discussion of material pending legal proceedings, the report refers to **Note 12, "Commitments and Contingencies,"** in the financial statements section[192](index=192&type=chunk) [Risk Factors](index=40&type=section&id=ITEM%201A.%20RISK%20FACTORS) This section outlines significant risks including commercial success, financial losses, future funding needs, third-party reliance, and drug development uncertainties [Financial and Commercial Risks](index=41&type=section&id=Financial%20and%20Commercial%20Risks) The company faces significant financial and commercial risks, including AMVUTTRA's success, an accumulated deficit of $7.41 billion, and securing substantial future funding - The **commercial success** of approved products, especially AMVUTTRA for ATTR amyloidosis with cardiomyopathy, is uncertain and **critical to achieving profitability**[201](index=201&type=chunk) - The company has a history of **significant operating losses**, with an **accumulated deficit of $7.41 billion** as of June 30, 2025, and may not achieve or sustain profitability[204](index=204&type=chunk) - **Substantial funds are required** to continue research, development, and commercialization activities, and **additional funding may be necessary** but might not be available on acceptable terms[206](index=206&type=chunk)[208](index=208&type=chunk) [Risks Related to Dependence on Third Parties](index=45&type=section&id=Risks%20Related%20to%20Dependence%20on%20Third%20Parties) Alnylam's business heavily relies on third-party collaborators and CMOs for development, commercialization, and supply, posing risks of partnership termination or manufacturing disruptions - The company's business could be **adversely affected** if collaborators like Roche, Regeneron, or Novartis **terminate their agreements** or **fail to perform their obligations**, potentially delaying or halting the development and commercialization of key products[227](index=227&type=chunk) - There is a risk that **Roche could terminate** the zilebesiran collaboration before the Phase 3 trial begins, which would result in the **loss of a significant milestone payment** and could impact the company's ability to achieve operating profitability in 2025[229](index=229&type=chunk) - The company relies on a **limited number of third-party Contract Manufacturing Organizations (CMOs)** for drug substance and all drug product requirements, where the loss of a supplier or their inability to provide sufficient supply could **delay clinical trials** and **harm commercial supply**[233](index=233&type=chunk)[234](index=234&type=chunk) [Risks Related to Development, Clinical Testing and Regulatory Approval](index=51&type=section&id=Risks%20Related%20to%20Development%2C%20Clinical%20Testing%20and%20Regulatory%20Approval) Product candidates face high failure risks in development due to expensive, lengthy, and uncertain clinical trials, with potential for undesirable side effects and extensive ongoing regulatory oversight - Product candidates may **fail in development or experience significant delays**, as nonclinical and clinical testing is expensive, lengthy, and has a **high historical failure rate**[257](index=257&type=chunk) - **Undesirable side effects or unexpected adverse properties** in products or product candidates could **delay or prevent regulatory approval**, limit commercial potential, or result in significant negative consequences post-approval[268](index=268&type=chunk) - Marketed products and approved candidates are subject to **extensive and ongoing regulatory oversight**, and **failure to comply** with continuing U.S. and foreign requirements could result in **limited or withdrawn approvals** and other penalties[286](index=286&type=chunk) [Risks Related to Competition](index=71&type=section&id=Risks%20Related%20to%20Competition) The company faces intense competition from large pharmaceutical companies and existing treatments, with AMVUTTRA competing against lower-priced oral drugs and alternative technologies - The company faces **intense competition** from large pharmaceutical companies with **greater resources** and from existing approved drugs for the same conditions[371](index=371&type=chunk) - **AMVUTTRA for ATTR-CM competes with orally administered drugs** VYNDAQEL/VYNDAMAX (Pfizer) and ATTRUBY (BridgeBio), which have **lower list prices** in the U.S., potentially impacting AMVUTTRA's commercial success[372](index=372&type=chunk) - The company faces **direct competition from other companies developing RNAi therapeutics** (e.g., Arrowhead, Roche, Silence Therapeutics) and from **alternative platforms like antisense technology** (e.g., Ionis)[378](index=378&type=chunk)[379](index=379&type=chunk) [Other Information](index=76&type=section&id=ITEM%205.%20OTHER%20INFORMATION) This section discloses that during Q2 2025, certain officers and directors entered into Rule 10b5-1 trading plans for the future sale of company securities - During the quarter ended June 30, 2025, certain officers and directors adopted **Rule 10b5-1 trading plans** for the sale of company securities, including: - **Dennis A. Ausiello, M.D.** (Director) - **Colleen F. Reitan** (Director) - **Tolga Tanguler** (Chief Commercial Officer)[405](index=405&type=chunk)[406](index=406&type=chunk)[407](index=407&type=chunk)[408](index=408&type=chunk) [Exhibits](index=77&type=section&id=ITEM%206.%20EXHIBITS) This section lists exhibits filed with the Form 10-Q, primarily consisting of certifications from the principal executive and financial officers and Inline XBRL documents - The exhibits filed with this report include **certifications by the CEO and CFO** pursuant to SEC rules, as well as **Inline XBRL data files**[409](index=409&type=chunk)

Exhibit 99.1 Contacts: Alnylam Pharmaceuticals, Inc. Christine Akinc (Investors and Media) 617-682-4340 Josh Brodsky (Investors) 617-551-8276 Alnylam Pharmaceuticals Reports Second Quarter 2025 Financial Results and Highlights Recent Period Progress − Generated Q2 2025 Total Net Product Revenues of $672 Million (64% Growth Compared with Q2 2024), Driven Primarily by Total TTR Revenues of $544 Million (77% Growth Compared with Q2 2024) – − Achieved Approximately 1,400 ATTR-CM Patients on AMVUTTRA (vutrisiran ...

The market expects Alnylam Pharmaceuticals (ALNY) to deliver a year-over-year decline in earnings on higher revenues when it reports results for the quarter ended June 2025. This widely-known consensus outlook is important in assessing the company's earnings picture, but a powerful factor that might influence its near-term stock price is how the actual results compare to these estimates.The stock might move higher if these key numbers top expectations in the upcoming earnings report, which is expected to be ...

Alnylam Pharmaceuticals (ALNY) could be a solid addition to your portfolio given its recent upgrade to a Zacks Rank #2 (Buy). This upgrade primarily reflects an upward trend in earnings estimates, which is one of the most powerful forces impacting stock prices.The sole determinant of the Zacks rating is a company's changing earnings picture. The Zacks Consensus Estimate -- the consensus of EPS estimates from the sell-side analysts covering the stock -- for the current and following years is tracked by the s ...

警察在公开宣判日籍男子的北京第二中级人民法院前执勤（7月16日，Kyodo） 据相关人士称，此次判决把该男子接受日本信息机构的委托、向其传递中国国内的信息并获取报酬的行 为认定为间谍活动。据悉，中国有关部门在调查该男子时，向其说明了如若认罪就能减轻量刑的制度， 规劝其坦白交代…… 日本经济新闻日前获悉，针对北京的法院以在中国实施间谍活动为由而作出实刑判决的安斯泰来制药日 籍男子员工，中国有关部门曾促使其坦白。中日关系相关人士透露了这一消息。这是旨在减轻量刑的事 实上的司法交易，该男子似乎承认了嫌疑并接受处罚。 据悉，中国有关部门在调查该男子时，向其说明了如若认罪就能减轻量刑的制度，规劝其坦白交代。在 日本人被扣案件中，司法交易的实际情况被披露实属罕见。 北京市第二中级人民法院7月16日对安斯泰来员工作出3年6个月有期徒刑的判决。据相关人士称，此次 判决把该男子接受日本信息机构的委托、向其传递中国国内的信息并获取报酬的行为认定为间谍活动。 中国实行两审终审制，如果当事人对一审判决不服，可以提出上诉。据悉，该男子已向周围的人表明了 不上诉的意向。 中国有关部门于2023年3月在该男子即将结束驻华任期准备返回日本之 ...

日本经济新闻（中文版：日经中文网）田岛如生 北京报道 安斯泰来 版权声明：日本经济新闻社版权所有，未经授权不得转载或部分复制，违者必究。 日本驻华大使馆的职员正在就旁听审判进行协调。日本政府多次要求中国方面尽早释放。中 方则表示将依法进行处罚，未同意日方要求…… 日经中文网 https://cn.nikkei.com 北京市第二中级人民法院将于7月16日对被起诉间谍罪的日本安斯泰来制药日籍男员工进行公 开宣判。日本驻华大使馆的职员正在就旁听审判进行协调。中日相关人士透露了上述消息。 该法院7月9日向日本大使馆转达了消息。围绕该男子被拘事件，包括日本首相石破茂在内， 日本政府多次要求中国方面尽早释放。中方则表示将依法进行处罚，未同意日方要求。 该男子是日本安斯泰来制药的当地法人高管，2023年3月在北京被逮捕。中国检察机关于 2024年8月以间谍罪起诉该男子，但并未透露具体罪状。该法院于2024年11月进行了首次公 审。 ...

Core Insights - Alnylam Pharmaceuticals (ALNY) is currently in Phase 10 of its 18-phase Adhishthana Cycle, with expectations for a peak formation in Phase 11, scheduled to end in September 2025 [1][5][6] Phase Analysis - The stock experienced a significant gap-up of over 30% on June 24 after positive results from its drug Vutrisiran for treating transthyretin amyloid cardiomyopathy, aligning with the principles of the Adhishthana framework [4][5] - Phase 9 was characterized by powerful structural shifts, leading to the current bullish stance in Phase 10, which is still building without signs of a peak [5][6] - Peak formation in Phase 10 typically occurs between the 18th and 23rd bars, but ALNY has not yet shown signs of this peak [6] Monthly Chart Insights - On the monthly chart, ALNY is in Phase 6, associated with the creation of a Nirvana level, projected to emerge around $240 by September 30, 2025 [9][10] - The stock has been forming its monthly Adhishthana Cakra since Phase 4 and is currently near the upper arc of this structure, indicating potential exhaustion as Phase 10 matures [10] Investor Outlook - Existing investors are advised to hold while monitoring for signs of structural breakdown, which would indicate a descent phase, referred to as the "Wrath of Ganga" [11] - New entrants are cautioned against entering during Phase 10 due to poor risk-reward dynamics, as the stock is trading near the higher arc of the monthly Adhishthana Cakra [12]

Core Insights - Alnylam Pharmaceuticals has received European Commission approval for the label expansion of its RNAi therapeutic Amvuttra to treat wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy [1][9] - Year-to-date, Alnylam's stock has increased by 29.1%, significantly outperforming the industry, which has seen a decline of 0.9% [2] Approval Details - The European Commission's approval was based on positive results from the late-stage HELIOS-B study, where Amvuttra met all 10 pre-specified primary and secondary endpoints [3][9] - The HELIOS-B trial demonstrated statistically significant reductions in all-cause mortality and recurrent cardiovascular events, along with major improvements in functional capacity, health status, and heart failure symptoms [4][9] Competitive Advantage - Amvuttra is administered quarterly via subcutaneous injection, providing an advantage over existing therapies that require daily oral dosing [5] - The drug's novel RNAi mechanism allows for rapid knockdown of transthyretin (TTR), addressing the disease at its source [6] Market Impact - The approval in the EU follows similar approvals in the United States and Brazil, expanding Amvuttra's global footprint [6] - Alnylam reported better-than-expected first-quarter 2025 results, with revenue growth driven by increasing Amvuttra sales due to heightened patient demand [10][11]

Summary of Alnylam Pharmaceuticals (ALNY) FY Conference Call - June 09, 2025 Company Overview - **Company**: Alnylam Pharmaceuticals (ALNY) - **Industry**: Biotechnology - **Key Product**: Ambutra for TTR cardiomyopathy Core Points and Arguments 1. **European Approval**: Alnylam secured European approval for Ambutra for cardiomyopathy, enhancing its global momentum in the TTR franchise [3][4] 2. **Five-Year Strategy**: The company is on track to achieve its 2021 five-year goals, including sustainable non-GAAP profitability by the end of 2025 [5][6] 3. **Revenue Growth**: Alnylam's revenues are primarily driven by the TTR franchise, with a robust pipeline for future growth [6][7] 4. **Pipeline Programs**: - Zarbisiran for hypertension and a program for Huntington's disease are highlighted as significant growth levers [10][11] - ARN 6400 targeting plasminogen is noted for its potential as a vessel hemolytic agent [12] 5. **Market Dynamics**: The company is experiencing rapid progress in treating patients with TTR cardiomyopathy, with over 50% of priority health systems having Ambutra on formulary [16][17] 6. **Financial Guidance**: Alnylam provided guidance for TTR revenue between $1.6 billion and $1.725 billion, representing approximately 36% year-over-year growth at the midpoint [22] 7. **Polyneuropathy Growth**: The polyneuropathy segment is growing at a rate of 28-34% year-over-year, with expectations for continued growth alongside cardiomyopathy [23][24] 8. **Patient Access**: The company reports broad access across payer types, with the majority of patients paying $0 out of pocket [33][35] 9. **Patient Services**: Alnylam has a comprehensive patient services organization to support access and adherence, with over 95% adherence rates in polyneuropathy [31][38] 10. **Pricing Strategy**: The company anticipates modest adjustments to Ambutra pricing over time, but specifics are not yet available [42] 11. **Global Launch Plans**: Alnylam plans to launch Ambutra in Germany and Japan in the second half of 2025, with additional launches expected throughout 2026 [45] 12. **Clinical Data**: The HELIOS B trial data shows a 36% reduction in all-cause mortality and a 33% reduction in cardiovascular mortality, reinforcing the drug's value proposition [47][48] 13. **Pipeline Expansion**: Alnylam is committed to advancing its pipeline, with multiple programs in various stages of development, including obesity and diabetes treatments [62][64] Additional Important Content - **Regulatory Strategy**: The orphan drug designation for Alnylam's products has positioned the company favorably in negotiations related to pricing and access [14] - **Commercial Strategy**: The company emphasizes a "buy and build" approach for its products, focusing on establishing a strong commercial footprint [20] - **Innovation Engine**: Alnylam aims to deliver 2-4 new INDs per year, expanding its siRNA technology across various tissues [59][60] - **Capital Allocation**: The company plans to focus on progressing its existing pipeline rather than pursuing significant business development opportunities at this time [64]

Core Insights - The recent announcement of former US President Biden's prostate cancer diagnosis has brought attention to prostate cancer, the second most common malignancy among men globally [2] - The incidence and mortality rates of prostate cancer in China are rising, with 134,200 new cases and 47,500 deaths reported in 2022 [2] - The treatment landscape for prostate cancer is evolving, with numerous innovative pharmaceutical companies developing new therapies, enhancing treatment options for patients [2][4] Market Dynamics - The global prostate cancer treatment market was valued at $35.3 billion in 2022 and is projected to grow to $56.4 billion by 2028, with a compound annual growth rate (CAGR) of 8.3% [4] - Major pharmaceutical companies are competing in this lucrative market, with Pfizer and Astellas' enzalutamide generating $5.926 billion in global sales in 2023, ranking sixth among oncology drugs [3][4] - Chinese pharmaceutical companies are transitioning from generic to innovative drug development, with Heng Rui Medicine's new drug, Rivelutamide, set to launch in December 2024 [4] Treatment Advances - Treatment options for prostate cancer have expanded significantly, with survival rates improving from 2-3 years to over 5 years due to advancements in therapies such as new anti-androgens and PARP inhibitors [3] - The introduction of targeted therapies, such as Novartis' Pluvicto, which achieved $271 million in its first year, indicates a shift towards precision medicine in prostate cancer treatment [3][4] Screening Challenges - Early detection of prostate cancer remains a challenge, with many patients diagnosed at advanced stages due to the disease's asymptomatic nature in early stages [5][6] - The five-year survival rate for prostate cancer patients in China is approximately 66.4%, significantly lower than over 95% in developed countries, highlighting the need for improved screening practices [5] - PSA testing is the primary screening method, and initiatives are underway to increase screening coverage in China, aiming for 40% coverage in the next five years [7]