Core Insights - Codexis, Inc. reported revenue of $15.3 million for Q2 2025, exceeding the analyst consensus estimate of $14.1 million, and showing significant growth from $8.0 million in Q2 2024 [1][12] - The company raised $27.3 million through an at-the-market (ATM) facility and a loan from Innovatus to support the expansion of its ECO Synthesis platform [2][7] - Codexis is experiencing a strategic shift with over 30 ongoing engagements related to its ECO Synthesis technology, which is aimed at enhancing the manufacturing of RNAi therapeutics [3][7] Financial Highlights - Total revenues for Q2 2025 were $15.3 million, a 92.5% increase from $7.9 million in Q2 2024 [12] - Product gross margin improved to 72% in Q2 2025 from 45% in Q2 2024, attributed to a shift towards more profitable products [12] - Research and Development expenses rose to $13.8 million in Q2 2025 from $11.4 million in Q2 2024, driven by increased headcount [12] - Selling, General & Administrative expenses decreased to $12.3 million in Q2 2025 from $15.7 million in Q2 2024, mainly due to lower stock-based compensation [12] - The net loss for Q2 2025 was $13.3 million, or $0.16 per share, compared to a net loss of $22.8 million, or $0.32 per share, in Q2 2024 [12] Business Developments - Six presentations at the 2025 TIDES USA annual meeting highlighted the ECO Synthesis platform, showcasing its capabilities in siRNA manufacturing [2][7] - Codexis appointed Cynthia Collins to its Board of Directors, bringing expertise in the CDMO landscape [7] - The company anticipates achieving pilot scale production of GLP-grade siRNA material in 2025 and aims to sign a GMP scale-up partner by the end of 2025 [7][12]

Core Insights - Alnylam Pharmaceuticals reported second-quarter 2025 earnings of $0.32 per share, significantly surpassing the Zacks Consensus Estimate of a loss of $0.03, primarily due to increased revenues from its lead drug, Amvuttra [1][11] - Total revenues for the quarter reached $773.7 million, exceeding the Zacks Consensus Estimate of $673 million, and reflecting a 17% year-over-year increase [2] - The company's net product revenues were $672.2 million, a 64% increase year-over-year, driven by strong demand for Amvuttra, Givlaari, and Oxlumo [3] Revenue Breakdown - Alnylam's net product revenues from Amvuttra amounted to $492 million, representing a 114% increase year-over-year, aided by expanded label use and patient switches from Onpattro [8][11] - Givlaari generated sales of $80.8 million, a 30% year-over-year increase, while Oxlumo recorded revenues of $46.9 million, up 15% year-over-year [9] - Net revenues from collaborators were $61.5 million, down 73% from the previous year, primarily due to a significant milestone payment received in the prior quarter [4] Financial Guidance - Alnylam raised its 2025 product revenue guidance to a range of $2.65 billion to $2.8 billion, up from the previous range of $2.05 billion to $2.25 billion [11][16] - The guidance for net revenues from collaborations and royalties remains unchanged at $650 million to $750 million [16] Research and Development - Adjusted R&D expenses increased by 11% year-over-year to $274.1 million, reflecting costs associated with new studies in partnership with Roche [13] - Adjusted SG&A expenses rose by 26% year-over-year to $261.2 million, driven by higher employee compensation and marketing investments related to Amvuttra [14] Cash Position - As of June 30, 2025, Alnylam's cash, cash equivalents, and marketable securities totaled $2.86 billion, an increase from $2.63 billion as of March 31, 2025, primarily due to net cash inflows from operating activities [15]

Core Viewpoint - Novartis has received FDA approval for an updated label for Leqvio® (inclisiran), allowing its use as a monotherapy to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, alongside diet and exercise [1][2][3] Group 1: Product Information - Leqvio is now indicated for use as a standalone treatment, removing the previous requirement for combination with statin therapy [3] - The updated label specifies "hypercholesterolemia" instead of "primary hyperlipidemia," focusing on LDL-C reduction [3] - Leqvio is administered twice a year by healthcare providers, which may enhance patient adherence and long-term management of LDL-C levels [2][8] Group 2: Market Need and Impact - Up to 80% of patients with atherosclerotic cardiovascular disease (ASCVD) in the US do not achieve the recommended LDL-C target of less than 70 mg/dL, highlighting a significant unmet medical need [2][8] - The 2025 ACC/AHA guidelines recommend more aggressive treatment strategies to meet LDL-C targets, further emphasizing the importance of Leqvio's new indication [2][8] Group 3: Company Background - Novartis has global rights to develop, manufacture, and commercialize Leqvio through a collaboration with Alnylam Pharmaceuticals, a leader in RNAi therapeutics [4] - The company aims to address critical challenges in cardiovascular disease management and improve patient outcomes through innovative treatments [10][11]

Financial Data and Key Metrics Changes - Alnylam reported total net product revenues of $672 million for Q2 2025, representing a 64% year-over-year growth [9][37] - The TTR franchise generated $544 million in revenues, reflecting a 77% increase year-over-year [8][11] - The company increased its total net product revenue guidance for 2025 from a range of $2.05 billion to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, a 27% increase at the midpoint [9][42] Business Line Data and Key Metrics Changes - The TTR franchise in the U.S. saw combined sales of ONPATTRO and Ambutra rise by 80% compared to Q1 2025, driven primarily by the launch of Ambutra [14][16] - The rare franchise, including GIVLAARI and OXLUMO, delivered $128 million in combined Q2 sales, up 24% year-over-year [12][11] - The U.S. TTR franchise grew 125% compared to 2024, primarily due to the demand from the ATTR Centimeters launch [15][11] Market Data and Key Metrics Changes - International markets are expected to contribute to Ambutra's revenues in the second half of 2025, with launches in Germany and Japan [15][27] - The U.S. TTR franchise achieved $383 million in Q2 2025, indicating robust growth dynamics [16][11] - The company has yet to recognize any ATTR Centimeters revenue internationally, but anticipates strong growth as international launches commence [15][11] Company Strategy and Development Direction - Alnylam focuses on three core elements: TTR leadership, growth through innovation, and strong financial performance [6][7] - The company aims to establish long-term leadership in TTR and expand its pipeline of RNAi therapeutics [6][9] - Alnylam is committed to disciplined capital allocation and sustainable growth, with a focus on patient and customer centricity [28][9] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong early performance of Ambutra and its potential for sustainable growth [9][28] - The company highlighted the importance of real-world evidence generation and the development of next-generation RNAi therapeutics [27][9] - Management remains optimistic about achieving its Alnylam Pizza Fit by 25 goals, reinforcing its position as a top-tier biotech company [10][9] Other Important Information - The FDA granted fast track designation to nucrisiran for ATTR Centimeters, enhancing its development prospects [9][31] - Alnylam's gross margin on product sales was 79% for the quarter, down from 84% in 2024, primarily due to increased royalties [39][37] - The company ended the quarter with cash, cash equivalents, and marketable securities of $2.9 billion, an increase from $2.7 billion at the end of 2024 [41][37] Q&A Session Summary Question: Can you provide details on the patient profiles for Ambutra? - Management noted broad uptake across first-line patients and stabilizer progressors, with a healthy mix emerging [48][49] Question: How are you thinking about net price for Ambutra moving forward? - The expectation is for a mid-single-digit reduction in net price for Ambutra in 2025 compared to 2024 [56][57] Question: Was there any bolus effect in cardiomyopathy scripts in Q2? - Management confirmed solid commercial execution and emphasized that results are not just a flash in the pan, expecting continued sustainable growth [60][61] Question: Can you comment on the criteria physicians are using for stabilizer progressors? - Clinical evidence suggests that 30% to 50% of patients on stabilizers may progress, and physicians are using a variety of factors to determine treatment [81][82] Question: How should we think about the rate of new patient starts per quarter? - Management expects both categories of patients to continue growing, with a balanced uptake between new patients and stabilizer progressors [97][98]

Financial Performance - Total Q2 Net Product Revenues reached $672 million, a 64% increase year-over-year[17, 24] - Total TTR Net Revenues in Q2 were $544 million, representing a 77% year-over-year growth[17] - Rare Franchise Net Product Revenues in Q2 totaled $128 million, a 24% increase year-over-year[28] - Alnylam increased its 2025 Total Net Product Revenue Guidance to a range of $2650 million to $2800 million[17, 74] - The company's Q2 Non-GAAP Operating Income was $95 million[70] Commercial Highlights - U S ATTR-CM launch contributed approximately $150 million in revenue during Q2[33, 34] - There are approximately 1,400 ATTR-CM patients receiving AMVUTTRA as of June 30, 2025[17, 37, 45] - U S TTR franchise experienced 125% year-over-year growth in Q2[32] - GIVLAARI saw a 30% year-over-year growth, driven by an approximately 18% increase in global patients on therapy[29] - OXLUMO experienced a 15% year-over-year growth, driven by an approximately 16% increase in global patients on therapy[29] Pipeline Development - The TRITON-CM Phase 3 study for nucresiran in ATTR-CM has been initiated, with a targeted launch around 2030[17, 60] - Phase 1 multidose results for mivelsiran in Alzheimer's Disease were announced[17] - A Phase 1 study for ALN-4324 in Type 2 Diabetes was initiated[17]

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]