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]

Summary of Alnylam Pharmaceuticals (ALNY) 2025 Conference Call Company Overview - **Company**: Alnylam Pharmaceuticals (ALNY) - **Event**: Bank of America Healthcare Conference - **Date**: May 14, 2025 Key Industry Insights - **Impact of Executive Orders**: The recent executive order regarding most favored nation pricing is still developing, making it difficult to assess its implications for Alnylam. However, the company benefits from having orphan drugs in the U.S., which may exempt them from future price negotiations under the IRA [3][4] - **Tariffs**: Current tariffs do not materially impact Alnylam's guidance, as the majority of their manufacturing is done in the U.S. through contract manufacturing organizations (CMOs) [8][9] Product Launch and Market Dynamics - **Cardiomyopathy Launch**: The launch of the cardiomyopathy product is a significant focus. Initial metrics show that 50% of health systems have completed the PNT process and are on formulary within five weeks of launch, which is faster than anticipated [18][19] - **Revenue Guidance**: Alnylam has guided for TTR revenue between $1.6 billion and $1.725 billion for the year, representing a 36% growth at the midpoint [23] - **Patient Access**: Approximately 70% of patients on the drug have zero out-of-pocket costs, primarily due to Medicare fee-for-service coverage [30] Competitive Landscape - **Market Size and Segmentation**: There are about 18,000 new patients initiating therapy annually, with a significant opportunity to increase diagnosis rates, currently at a 20% diagnosis rate [48] - **First-Line vs. Second-Line Treatment**: Alnylam is focused on first-line treatment due to the progressive nature of the disease and the need for effective early intervention [49] Patient and Physician Engagement - **Patient Compliance**: Alnylam has observed good compliance rates with their injectable therapies, which may be more effective than oral alternatives in ensuring patients receive the necessary treatment [58][60] - **Physician Awareness**: There is a good level of awareness among physicians regarding Alnylam's products, but further education is needed as the company expands its prescriber base [74] Future Outlook - **Revenue Reporting**: Alnylam will not be able to report revenue separately for Ambutra PN and Ambutra Centimeters due to them being the same product under one SKU [67] - **Market Positioning**: Alnylam is uniquely positioned to capture a broad patient base, including both hereditary and wild-type patients, due to its comprehensive label [72][73] Additional Considerations - **Direct-to-Consumer (DTC) Marketing**: Alnylam is engaging in targeted DTC marketing but is not heavily investing in broad campaigns like some competitors [65] - **Value-Based Agreements (VBAs)**: The company is extending its VBAs to ensure adherence and compliance, which is favorable for both patients and payers [60][61]

Core Viewpoint - Alnylam Pharmaceuticals reported better-than-expected financial results for Q1 2025, with adjusted losses narrower than estimates and significant revenue growth driven by strong product sales, particularly for Amvuttra [1][2][16]. Financial Performance - The company reported total revenues of $594.2 million, exceeding the Zacks Consensus Estimate of $588.2 million, and reflecting a 20% year-over-year increase [2]. - Net product revenues reached $468.5 million, up 28% year-over-year, primarily due to increased demand for Amvuttra, Givlaari, and Oxlumo [2][6]. - Net revenues from collaborators were $99.2 million, down 16% from the previous year, largely due to a prior milestone payment from Roche [3]. Product Sales - Amvuttra generated sales of $310 million, a 59% increase year-over-year, and surpassed estimates [6]. - Givlaari recorded sales of $67 million, a 15% increase year-over-year, but slightly missed estimates [7]. - Oxlumo's sales were $42.1 million, remaining flat year-over-year and missing estimates [7]. Expenses and Cash Position - Adjusted R&D expenses were approximately $241.3 million, remaining stable year-over-year [10]. - Adjusted SG&A expenses increased by 12% to $207 million, driven by marketing efforts for Amvuttra [11]. - Cash, cash equivalents, and marketable securities totaled $2.63 billion as of March 31, 2025, down from $2.69 billion at the end of 2024 [11]. Guidance and Collaborations - The company reiterated its 2025 financial guidance, expecting net product revenues between $2.05 billion and $2.25 billion, and collaboration revenues between $650 million and $750 million [12]. - Alnylam is advancing several collaborations, including with Regeneron and Roche, which are expected to enhance its product pipeline and revenue streams [13][14][17]. Market Performance - Year-to-date, Alnylam's stock has gained 8.4%, outperforming the industry, which has seen a decline of 1.8% [8].

Financial Performance - Alnylam's combined net product revenues reached $469 million, a 28% year-over-year (YoY) increase compared to Q1 2024[15, 25] - The U S TTR franchise primarily drove this growth, experiencing a 45% YoY increase[15] - The company is on track to meet its 2025 financial guidance, projecting combined net product revenues between $2050 million and $2250 million[15] - Non-GAAP operating income was $75 million, resulting in a 13% non-GAAP operating margin[70] Franchise Performance - The Rare Franchise achieved $109 million in global net product revenues in Q1 2025, representing an 8% YoY growth[28] - GIVLAARI sales increased by 15% YoY, driven by a ~15% increase in global patients on therapy[29] - The TTR Franchise experienced a robust 36% growth, primarily driven by U S performance, reaching $359 million in global net product revenues[30, 31] - U S TTR growth was 45% YoY, driven by demand (+32%), inventory (+6%), and gross-to-net adjustments (+7%)[32] AMVUTTRA Launch and Pipeline - AMVUTTRA captured approximately 70% of new hATTR-PN patient starts in the U S in Q1 2025[32, 35] - Alnylam is optimizing access pathways for AMVUTTRA in ATTR-CM at ~170 priority health systems, covering ~80% of Rx volume[39] - Regulatory approvals for AMVUTTRA have been granted in the U S and Brazil, with a positive CHMP opinion in the European Union[56]

Financial Data and Key Metrics Changes - In Q1 2025, Alnylam Pharmaceuticals reported total product revenues of $469 million, representing a 28% year-over-year growth, driven by a 36% increase in the TTR franchise revenues [8][40] - Collaboration revenue decreased by 16% to $99 million compared to the previous year, primarily due to a milestone achieved in Q1 2024 [41] - Non-GAAP operating profit for the quarter was $75 million, reflecting a $73 million improvement year-over-year [43] Business Line Data and Key Metrics Changes - The TTR franchise generated $359 million in global net revenues, a 36% increase compared to Q1 2024, with U.S. sales growing by 45% year-over-year [15][16] - The rare disease franchise, including GIVLAARI and OXLUMO, delivered $109 million in combined product sales, representing an 8% growth year-over-year [14] Market Data and Key Metrics Changes - In the U.S., the TTR franchise saw a 32% increase in demand driven by ongoing ONPATTRO patient uptake, with Ambutra capturing approximately 70% of new patient starts in Q1 2025 [16][19] - Internationally, the TTR franchise grew by 24% compared to Q1 2024, primarily due to increased demand for Ambutra [17] Company Strategy and Development Direction - Alnylam aims to become the global leader in TTR, focusing on broad access, driving awareness, and supporting treatment initiation for patients [7][10] - The company is committed to achieving sustainable non-GAAP profitability in 2025 and emphasizes a disciplined approach to capital allocation [9][11] Management's Comments on Operating Environment and Future Outlook - Management acknowledged uncertainties related to potential policy changes, including tariffs and FDA personnel reorganization, but expressed confidence in Alnylam's positioning to mitigate impacts [9][45] - The management reiterated guidance for continued growth and a strong launch in ATTR cardiomyopathy, projecting a robust 36% year-over-year growth in TTR franchise revenues [27][39] Other Important Information - Alnylam received FDA approval for Ambutra as the first and only silencer approved in the U.S. for ATTR Centimeters, with a successful launch underway [20][30] - The company is advancing its pipeline with several pivotal studies planned, including TRITON Centimeters and TRITON PN [47] Q&A Session Summary Question: Initial patients starting treatment and prescriber base - Management noted a broad uptake among both experienced and new prescribers, indicating strong early momentum in the cardiomyopathy launch [51][53] Question: Revenue benchmarks for ATTR cardiomyopathy - Management clarified that the revenue contribution from ATTR cardiomyopathy was not included in Q1 results, as the approval came late in the quarter [57][62] Question: Commercial strategies to capture market share - Management highlighted the unique mechanism of action of Ambutra and its potential as a first-line treatment, which is driving physician interest [64][66] Question: Use of Quick Start program and formulary access - Management reported limited use of the Quick Start program, with most patients paying zero copay, and confirmed no price difference between indications [70][72] Question: Impact of TrueBee on Ambutra's launch - Management indicated no headwinds from TrueBee's launch, emphasizing the growing and unsatisfied market for ATTR treatments [76][78] Question: Metrics on health systems and patient initiation - Management confirmed that over half of the 170 priority health systems have Ambutra on formulary, with many already initiating treatments [97][99]

Financial Data and Key Metrics Changes - In Q1 2025, Alnylam Pharmaceuticals reported total product revenues of $469 million, representing a 28% year-over-year growth, driven by a 36% increase in the TTR franchise revenues [6][37] - Collaboration revenue decreased by 16% to $99 million compared to the previous year, primarily due to a milestone achieved in Q1 2024 [38] - Gross margin on product sales remained at 85%, consistent with Q1 2024, but is expected to decrease for the remainder of the year due to escalating royalty rates [39][41] Business Line Data and Key Metrics Changes - The TTR franchise generated $359 million in global net revenues, a 36% increase year-over-year, with U.S. sales growing by 45% [14][15] - The rare disease franchise, including GIVLAARI and OXLUMO, delivered $109 million in combined product sales, reflecting an 8% growth year-over-year [13] - The TTR franchise's growth was primarily driven by increased demand for ONPATTRO and Ambutra, with a 32% increase in demand noted [15][16] Market Data and Key Metrics Changes - In the U.S., Ambutra captured approximately 70% of new patient starts in the first quarter of 2025, indicating strong market leadership despite new competition [18] - Internationally, the TTR franchise grew by 24% compared to the first quarter of 2024, driven by robust patient uptake [16] - The company noted that about 80% of the global addressable population remains untreated, presenting significant growth opportunities [19] Company Strategy and Development Direction - Alnylam aims to become the global leader in TTR, focusing on broad access, driving awareness, and supporting treatment initiation for patients [5][9] - The company is committed to achieving sustainable non-GAAP profitability in 2025 while continuing to advance its high-value pipeline [7][10] - Alnylam's strategy includes leveraging its innovative pipeline with multiple multibillion-dollar opportunities and maintaining strong financial performance through disciplined capital allocation [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's positioning despite uncertainties related to potential policy changes, tariffs, and FDA reorganizations [7][8] - The management highlighted the strong early progress in the launch of Ambutra for ATTR cardiomyopathy and reiterated guidance for continued growth [6][37] - The company remains optimistic about achieving its 2025 goals, which include expanding access to its therapies and enhancing patient outcomes [10][26] Other Important Information - Alnylam received FDA approval for Ambutra as the first and only silencer approved in the U.S. for ATTR cardiomyopathy, with positive opinions from regulatory bodies in Brazil and the EU [20][29] - The company is advancing its pipeline with new clinical programs targeting various diseases, including a Phase I study for ALN434 targeting Type 2 diabetes [34][35] Q&A Session Summary Question: What is the profile of prescribers for Ambutra? - Management noted a broad uptake among both experienced prescribers and new doctors, indicating strong initial engagement with the product [48][51] Question: How does the revenue from ATTR cardiomyopathy compare to previous products? - Management clarified that the revenue from ATTR cardiomyopathy did not contribute to Q1 results, as the approval came late in the quarter [55][60] Question: What strategies are being employed to compete with tafamidis? - Management emphasized the unique mechanism of action of Ambutra and its compelling clinical data, which positions it as a first-line treatment option [62][64] Question: What are the dynamics of reimbursement for Ambutra? - Management explained that Ambutra has a single price across indications and highlighted the effectiveness of their patient support programs in facilitating access [68][70] Question: What are the expectations for formulary inclusion? - Management aims to complete formulary inclusion for all priority health systems by year-end, with encouraging early results already seen [81][82] Question: How is the early uptake of Ambutra characterized? - Management indicated that early uptake includes both switch patients and new patients, reflecting a strong initial market response [100][102]