ALNY

Alnylam Pharmaceuticals, Inc.

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Overview

Alnylam Pharmaceuticals develops RNAi therapeutics for rare genetic and cardio-metabolic diseases. Its six marketed medicines, including Amvuttra for ATTR cardi

Alnylam Pharmaceuticals develops RNAi therapeutics for rare genetic and cardio-metabolic diseases. Its six marketed medicines, including Amvuttra for ATTR cardiomyopathy and polyneuropathy, ONPATTRO, GIVLAARI, and OXLUMO, generated nearly $3 billion in 2025. The TTR franchise is the primary revenue driver, serving hundreds of thousands of patients globally. The company achieved GAAP profitability in 2025.

What They Do (Plain English & Analogies): Alnylam Pharmaceuticals is a biotechnology company that creates new medicines by using a natural process called RNA interference (RNAi). Think of our genes as instruction manuals for our bodies. Sometimes, a gene has a typo or a faulty instruction that causes a disease. RNAi therapeutics work like a 'mute button' or a 'dimmer switch' for these faulty genes. Instead of trying to fix the gene itself or block the protein it makes, Alnylam's medicines stop the bad instruction from being read in the first place, effectively silencing the gene responsible for the illness. This allows them to treat diseases that were previously very difficult or impossible to address, such as certain rare genetic conditions and heart diseases.
Very Brief History: Founded in 2002, Alnylam Pharmaceuticals pioneered the development of RNA interference (RNAi) therapeutics. Over two decades, the company has evolved from a research-focused entity to a commercial leader, bringing six Alnylam-invented medicines to market. A significant milestone was achieved in 2025 with the landmark approval of Amvuttra for ATTR cardiomyopathy, which propelled the company to nearly $3 billion in annual revenues and, importantly, achieved GAAP profitability for the full year.
"Street Stereotype": Alnylam is generally perceived as the leading innovator and commercial powerhouse in the RNAi therapeutics space. Investors and analysts view it as a high-growth biotech company with a robust, high-yielding pipeline and a proven platform that can consistently deliver new, transformative medicines, driving durable long-term growth and increasing profitability.
Subsidiaries On Linked In*: {"subsidiaries":[]}
Customer Sectors & Example Clients: Alnylam's primary customers are patients suffering from various diseases, with treatments administered through healthcare providers and hospital systems. Their therapeutic focus areas include genetic medicines, cardio-metabolic diseases, hepatic infectious diseases, central nervous system (CNS)/ocular diseases, rare diseases, hypertension, metabolic diseases (overweight/obesity, type 2 diabetes), neuroscience (Alzheimer's disease, Huntington's disease, cerebral amyloid angiopathy), and hematology (bleeding disorders). The company also engages in strategic collaborations with other pharmaceutical companies, which can be considered 'clients' or partners in development and commercialization. Example collaborators include Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, Novartis AG, Vir Biotechnology, Inc., Dicerna Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., PeptiDream, Inc., and Roche.
New Customers / Segments They'Re Targeting: Alnylam is actively targeting several new customer segments and expanding into broader markets. A key focus is the significant population of patients with ATTR cardiomyopathy, following the recent approval and launch of Amvuttra. They are also developing therapies for patients with uncontrolled hypertension (zalesiran), hereditary ATTR polyneuropathy (nuceresiran), and are expanding into metabolic diseases with programs for durable weight loss (ALN-2232, targeting an adipose target) and type 2 diabetes (ALN-4324). In neuroscience, they are targeting Alzheimer's disease and other rare tauopathies (ALN-5288, valesiran) and Huntington's disease (ALN-HTT02). Additionally, they are developing ALN-6400 for a wide range of bleeding disorders, with hereditary hemorrhagic telangiectasia as a first indication, and aim to expand RNAi delivery to 10 different tissue types.
Supply Chain And Sourcing Geographies: Alnylam manages the manufacturing and distribution of all its commercial and investigational medicines worldwide from its large-scale manufacturing facilities located in Cambridge, Massachusetts, and Norton, Massachusetts, USA. The decision to base manufacturing operations near R&D and corporate headquarters in Massachusetts was deliberate to facilitate collaboration and agility. The company has also developed and launched a proprietary enzymatic ligation-based RNAi manufacturing platform called Cyrillis (also referred to as siRELIS™), which is expected to greatly expand capacity, reduce costs, and support future launches. This platform has been accepted into the U.S. FDA's Emerging Technology Program.
Sales Geographies And Expansion Plans: Alnylam currently sells its products globally, with a strong commercial foothold in the United States and Europe. Specific sales geographies mentioned include the U.S., Japan (for cardiomyopathy launch), and Germany (for Amvuttra pricing alignment). Their European business offices are located in Maidenhead, UK, and Zug, Switzerland, with satellite offices in Munich, Germany; Amsterdam, Netherlands; Vienna, Austria; Paris, France; Milan, Italy; Madrid, Spain; and Stockholm, Sweden. Other global offices include Tokyo, Japan; Sao Paulo, Brazil; and Mississauga, Ontario, Canada. The company anticipates launching Amvuttra for ATTR cardiomyopathy in additional international markets throughout 2026, following local pricing and reimbursement reviews.
How Key Themes May Help/Hurt: Alnylam's core theme of RNAi therapeutics offers a powerful advantage by directly silencing disease-causing genes, providing a precise and potentially transformative treatment approach. This mechanism allows them to address a wide range of diseases, including those with significant unmet needs, and build a high-yielding pipeline, which can drive sustained long-term growth and market leadership. The modular and reproducible nature of their platform helps accelerate innovation and scale impact. However, this theme also carries risks. The complexity of RNAi technology means high research and development costs. While effective, these novel therapies often come with high price tags, leading to potential payer scrutiny and pricing pressure, especially in competitive markets or as they expand globally. Furthermore, the emergence of alternative gene-silencing technologies (like ASO) and disruptive one-time gene-editing cures could challenge Alnylam's chronic dosing model and market share in the long term.

3 Main Long-Term Bull Details

RNAi Leadership and Innovation Engine: Alnylam is the established leader in RNAi therapeutics, possessing a proven, reproducible, and modular process for developing medicines. This organic product engine has resulted in outsized historical success rates and underpins a 'spring-loaded' pipeline, ensuring a continuous stream of potential new therapies.
Robust and Expanding Pipeline with Blockbuster Potential: The company boasts a high-yielding pipeline with over 25 programs currently in active clinical development, with a goal to reach over 40 clinical programs by 2030. Several of these programs, beyond the TTR franchise, are identified as having multi-billion dollar blockbuster potential, indicating significant future growth drivers across rare, specialty, and prevalent indications.
Strong Financial Trajectory and Sustained Profitability: Alnylam achieved GAAP profitability for the full year 2025 and expects to sustain profitability going forward. They have set ambitious Alnylam 2030 goals, including achieving over 25% revenue CAGR through 2030 and delivering a non-GAAP operating margin of 30% across the period, with potential to reach mid-40s post-2030 if nuceresiran is successful due to lack of royalty obligations.

3 Main Long-Term Bear Details

Intense and Evolving Competition: Alnylam faces significant and growing competition in its key TTR franchise from established players like Pfizer (tafamidis) and BridgeBio (acoramidis), as well as ASO therapies from Ionis Pharmaceuticals (Wainua). The emergence of gene-editing technologies from companies like Intellia and CRISPR Therapeutics poses a long-term disruptive threat, potentially offering one-time cures that could alter the chronic dosing model and lifetime revenue assumptions for RNAi therapeutics.
Pipeline Execution and Clinical Risk: While Alnylam has a robust pipeline, the development of new medicines is inherently risky. Clinical trials for late-stage programs like zalesiran and nuceresiran, as well as earlier-stage assets for Huntington's, Alzheimer's, and obesity, could face delays, unexpected safety concerns, or fail to demonstrate sufficient efficacy, impacting future revenue streams and growth projections.
Pricing Pressure and Market Access Challenges: The high cost of novel RNAi therapeutics can lead to increasing scrutiny from payers and potential pricing pressure, especially as more competitors enter the market and in international geographies. Managing gross-to-net deductions and securing broad, favorable access for new launches will be crucial for maintaining profitability and market share.

Competitors And Differentiation: Alnylam faces competition from various pharmaceutical companies employing different therapeutic modalities. Key competitors include Ionis Pharmaceuticals (using antisense oligonucleotide (ASO) technology, with Wainua for ATTR polyneuropathy), Pfizer (with tafamidis/Vyndaqel/Vyndamax, a TTR stabilizer, dominant in ATTR cardiomyopathy), and BridgeBio (with acoramidis/Attruby, another TTR stabilizer for ATTR cardiomyopathy). Other RNAi developers like Arrowhead Pharmaceuticals and Silence Therapeutics also present competition with their proprietary delivery platforms. Longer-term threats come from gene-editing companies such as Intellia Therapeutics and CRISPR Therapeutics, which are pursuing one-time treatments. Alnylam differentiates itself through its leadership in RNAi therapeutics, leveraging its proprietary Enhanced Stabilization Chemistry (ESC) and GalNAc-conjugate delivery platform, which enables potent, subcutaneous gene silencing and infrequent dosing (e.g., quarterly for Amvuttra). They emphasize their rapid, deep, and sustained knockdown profiles, strong clinical data packages, and a broad label for Amvuttra that includes reducing the likelihood of hospitalization, death, and urgent heart failure visits. Their robust and high-yielding pipeline, coupled with strategic partnerships, further strengthens their competitive positioning.
Recent Performance & What The Market'S Focused On: Alnylam delivered a strong performance in 2025, achieving nearly $3 billion in combined net product revenues, representing 81% growth compared to 2024. This was primarily driven by the landmark approval and successful launch of Amvuttra for ATTR cardiomyopathy in the U.S., contributing to a more than doubling of revenue in their TTR franchise. The company also achieved GAAP profitability for the full year 2025, exceeding its P5x25 goals. For 2026, Alnylam anticipates combined net product sales of $4.9 billion to $5.3 billion, representing 71% growth at the midpoint, with the TTR franchise expected to grow by 83%. The market is currently focused on the continued strong uptake and market share gains of Amvuttra in ATTR cardiomyopathy, particularly its traction in first-line patients and broad access. Investors are also closely watching the progress of key pipeline assets like nuceresiran (expected launch 2028/2030) and zalesiran (expected launch 2030), as well as early-stage de-risking data for programs in Huntington's disease and obesity. The company's ability to sustain profitability amidst increasing R&D and SG&A investments, and navigate competitive dynamics and pricing in its core markets, remains a key area of market attention.

Revenue Segments And Estimated Mix: Combined Net Product Revenues — Mix: n/m; Source: FY2025 actual: ~$3 billion; 2026 guidance: $4.9B-$5.3B; Trend: 81% growth in 2025 vs 2024; 71% growth at midpoint of 2026 guidance vs 2025
TTR Franchise (Amvuttra, ONPATTRO) — Mix: ~89.2% of 2026 product sales guidance; Source: 2025 actual: more than doubled vs 2024; 2026 guidance: $4.4B-$4.7B; Trend: 151% growth in Q4 2025 YoY; 83% growth at midpoint of 2026 guidance vs 2025
Rare Disease Franchise (GIVLAARI, OXLUMO) — Mix: ~10.8% of 2026 product sales guidance; Source: 2025 actual: $500 million; 2026 guidance: $500M-$600M; Trend: 26% growth in Q4 2025 YoY; 10% growth at midpoint of 2026 guidance vs 2025
Collaboration Revenue — Mix: n/m; Source: 2025 actual: $553 million; 2026 guidance: $400M-$500M; Trend: 8% growth in 2025 vs 2024; 38% decrease at midpoint of 2026 guidance vs 2025 (due to one-time milestone in 2025)
Royalty Revenue — Mix: n/m; Source: 2025 actual: $104 million; Trend: 90% increase in 2025 vs 2024 (driven by higher Leqvio sales from Novartis)
Product Brands: ONPATTRO
GIVLAARI
OXLUMO
Amvuttra
zalesiran
nuceresiran
ALN-2232
ALN-5288
ALN-4285
ALN-4915
cemdisiran
valesiran
ALN-HTT02
ALN-6400
ALN-4324
Cyrillis

Bull / Bear Details

Alnylam, a leader in RNAi therapeutics, is poised for sustained growth driven by its expanding TTR franchise, notably Amvuttra's strong ATTR cardiomyopathy laun

Thesis

Alnylam, a leader in RNAi therapeutics, is poised for sustained growth driven by its expanding TTR franchise, notably Amvuttra's strong ATTR cardiomyopathy launch and future nuceresiran potential. The company achieved GAAP profitability in 2025 and targets over 25% revenue CAGR through 2030, supported by a high-yielding pipeline and strategic 'Alnylam 2030' goals. Despite Q1 2026 revenue phasing and competitive dynamics, the robust pipeline and financial discipline make the bull case compelling as of April 26, 2026.

Bull case

Alnylam delivered a transformational 2025, achieving nearly $3 billion in combined net product revenues, an 81% increase over 2024, driven by Amvuttra's blockbuster launch in ATTR cardiomyopathy. The company achieved GAAP profitability and expects to sustain it. For 2026, Alnylam projects combined net product sales of $4.9 billion to $5.3 billion, representing 71% growth at the midpoint, with a goal to lead the TTR market in revenue by 2030.
Alnylam's 'Alnylam 2030' strategy targets a pipeline of over 40 clinical programs and the delivery of two or more transformative blockbuster medicines beyond TTR. Key Phase 3 programs include zalesiran for hypertension and nuceresiran for ATTR amyloidosis, with expected launches in 2030 and 2028/2030 respectively. Additionally, promising early-stage assets in obesity (ALN-2232), Alzheimer's (ALN-5288), and bleeding disorders (ALN-6400) are advancing, offering significant long-term growth.
Alnylam achieved GAAP profitability for the full year 2025 and expects to sustain this going forward. The company's 'Alnylam 2030' goals target a non-GAAP operating margin of 30% across the period. Furthermore, the anticipated launch of nuceresiran, which will not incur royalty obligations, has the potential to significantly boost operating margins to the mid-40s post-2030, demonstrating strong financial discipline and long-term value creation.

Bear case

Alnylam anticipates "considerably lower" quarter-on-quarter TTR revenue growth in Q1 2026 compared to Q4 2025, driven by an expected $25 million reduction in international revenues due to Germany pricing alignment and U.S. seasonality (fewer shipping weeks, insurance reauthorizations). The company also forecasts a mid-single-digit net price decrease for Amvuttra in 2026, which could temper overall revenue growth despite strong demand.
While Alnylam acknowledges the large and underserved ATTR cardiomyopathy market, the upcoming competitive silencer data from rivals, such as those developing WAINUA, pose a potential threat. Although Alnylam expects competitor studies to be positive, there is a risk that a competitor could achieve a differentiated profile or a broader label, potentially impacting Amvuttra's market share and pricing power, despite Alnylam's current strong position.
A significant portion of Alnylam's ambitious 'Alnylam 2030' growth and margin expansion targets are contingent on the successful development and commercialization of pipeline assets like nuceresiran and zalesiran. Delays in pivotal Phase 3 trials (TRITON-CM/PN, ZENITH), unexpected safety signals, or challenges in market access and uptake for these future products could significantly impact the company's ability to achieve its long-term financial and strategic goals.

Bull / Bear Case

Bear Case: Despite a strong 2025, Alnylam faces near-term headwinds and significant valuation concerns. The company anticipates "considerably lower" quarter-on-quarter TTR revenue growth in Q1 2026, driven by an expected $25 million reduction in international revenues due to Germany pricing adjustments and U.S. seasonality. A mid-single-digit net price decrease for Amvuttra in 2026 is also projected, potentially tempering overall revenue growth. The upcoming competitive silencer data for ATTR cardiomyopathy from rivals poses a material threat, as a differentiated profile or broader label could impact Amvuttra's market share and pricing power. Furthermore, Alnylam's ambitious 'Alnylam 2030' goals are contingent on successful, timely development and commercialization of pipeline assets, with any delays or unexpected safety signals posing substantial risks to long-term financial targets.
Bull Case: Alnylam Pharmaceuticals is positioned for robust, long-term growth, underpinned by its leadership in RNAi therapeutics and a proven innovation engine. The company achieved a transformational 2025, marked by the landmark approval and blockbuster launch of Amvuttra for ATTR cardiomyopathy, driving nearly $3 billion in combined net product revenues (81% growth year-over-year) and achieving GAAP profitability. Management's 'Alnylam 2030' goals target over 25% revenue CAGR, global TTR market leadership, and a pipeline of over 40 clinical programs, including high-potential assets like nuceresiran (expected 2028/2030 launch) and zalesiran. The anticipated launch of nuceresiran without royalty obligations could significantly boost operating margins to the mid-40s post-2030, demonstrating strong financial discipline and future value creation.
More Compelling & Why: Bear. Given the current price/valuation, the bear case is more compelling. Alnylam's P/E ratio, ranging from 131 to 191, is significantly higher than the biotechnology industry average of approximately 48, indicating a rich valuation that prices in substantial future growth. The stock's underperformance relative to the SPY since the earnings call, coupled with anticipated Q1 revenue choppiness and increasing competitive threats, suggests the market is wary of this high valuation. The strongest argument for the bear case is the elevated valuation multiples leaving little room for execution missteps or competitive pressure. My view would flip if Alnylam consistently outperforms revenue guidance, demonstrates resilience against new competitors, and shows clear, positive de-risking data from its pipeline, leading to a more justified valuation.

Key Factors5 rows

Key Factor	Why It Matters	What To Watch	What It Signals	Where/How To Track	Free Alt Data	Paid Alt Data
Non-GAAP Operating Margin Trend	Achieving and sustaining GAAP profitability in 2025 and targeting a 30% non-GAAP operating margin by 2030 (potentially mid-40s post-2030) demonstrates financial discipline and scalability, crucial for long-term value creation and investor confidence.	Reported non-GAAP operating margin in Q1 2026 earnings and subsequent quarters; trends in non-GAAP R&D and SG&A expenses relative to revenue growth, especially in light of 2026 guidance for combined non-GAAP R&D and SG&A expense between $2.7 billion and $2.8 billion.	Bullish: Q1 2026 non-GAAP operating margin shows improvement or exceeds expectations; operating expenses are managed efficiently relative to revenue growth. Bearish: Q1 2026 non-GAAP operating margin declines or misses targets; operating expenses grow disproportionately to revenue.	Alnylam Pharmaceuticals Q1 2026 earnings call (April 30, 2026), company press releases, SEC filings (10-Q).	N/A (internal financial metric, but general market sentiment and analyst reports can provide indirect reads).	S&P Capital IQ: Financial statement analysis and historical margin trends; Refinitiv Eikon: Consensus estimates for operating margin and expense lines.
Amvuttra U.S. ATTR Cardiomyopathy Market Share and New Patient Uptake	Amvuttra's strong launch in ATTR cardiomyopathy is the primary driver of current revenue growth and future TTR franchise leadership. Continued market share gains validate its differentiated profile and commercial execution, crucial for the long-term investment thesis.	Amvuttra's share of new treatment starts versus tafamidis; absolute number of new patient additions in the U.S. ATTR cardiomyopathy market. Watch for updates during the Q1 2026 earnings call on April 30, 2026.	Bullish: Amvuttra's share of new starts increases beyond 27% (as of September 2025) or new patient adds exceed Q4 2025 growth (20% QoQ for U.S. TTR). Bearish: Amvuttra's share of new starts declines or new patient adds significantly decelerate below Q4 2025 levels.	Alnylam Pharmaceuticals Q1 2026 earnings call (April 30, 2026), company press releases, investor presentations.	Google Trends: Search interest volume for 'Amvuttra' vs 'Tafamidis' in the US; healthcare professional forums discussing ATTR-CM treatments.	Symphony Health Solutions: New-to-brand prescriptions (NBRx) for Amvuttra vs. tafamidis; IQVIA: Patient volume and market share data for ATTR cardiomyopathy treatments.
Clinical De-risking Data for Key Pipeline Programs (ALN-6400, ALN-HTT02, ALN-2232)	These programs represent the 'next wave' of transformative medicines beyond TTR, with multibillion-dollar potential. Positive de-risking data in H2 2026 would validate Alnylam's platform and open new avenues for sustainable growth and diversification.	Release of Phase 1/2 results from the ALN-6400 program (hematology); Phase 1 data on ALN-HTT02 (Huntington's disease) and ALN-2232 (ACVR1C for obesity) programs in the second half of 2026. Look for safety, target engagement (e.g., >50% huntingtin knockdown), and proof-of-concept efficacy.	Bullish: Positive safety and efficacy data (e.g., strong knockdown, clear proof-of-concept); rapid progression to next clinical phases. Bearish: Negative safety signals; insufficient efficacy/knockdown; delays in data readout or program discontinuation.	Company press releases, scientific conferences (e.g., ASH for hematology, AAN for neurology, EASL for metabolic), investor presentations, Q2/Q3 2026 earnings calls.	PubMed/Google Scholar: Publication of study results; relevant disease-specific patient forums/advocacy groups for early insights.	BioCentury: Clinical trial news and analysis; Citeline (Informa): Drug development intelligence and pipeline tracking.
Nuceresiran Phase 3 Clinical Trial Progress (TRITON-CM and TRITON-PN)	Nuceresiran is positioned as a future blockbuster with significant margin potential due to no royalty obligations. Progress in its pivotal trials and adherence to launch timelines (2028 for polyneuropathy, 2030 for cardiomyopathy) are critical for long-term value creation.	Updates on enrollment completion for TRITON-CM (estimated 1,250 patients) and TRITON-PN (estimated 125 patients); any announcements regarding interim data reviews or regulatory interactions.	Bullish: Enrollment for TRITON-CM and TRITON-PN is on or ahead of schedule; positive updates on safety or regulatory path. Bearish: Significant delays in trial enrollment or timelines; unexpected safety signals requiring trial modification or pause.	Company press releases, SEC filings (10-K, 10-Q), investor presentations, clinical trial registries (e.g., ClinicalTrials.gov NCT07052903 for TRITON-CM, NCT07223203 for TRITON-PN).	ClinicalTrials.gov: Status updates for TRITON-CM and TRITON-PN; scientific conference abstracts and presentations.	GlobalData: Clinical trial intelligence and enrollment tracking; EvaluatePharma: Drug development timelines and market forecasts for nuceresiran.
TTR Franchise Net Product Revenue Performance (Q1 2026)	The TTR franchise is Alnylam's primary revenue engine. Meeting or exceeding the Q1 2026 revenue expectations and demonstrating resilience despite anticipated headwinds is crucial for investor confidence in the full-year guidance and long-term growth.	Reported Q1 2026 TTR net product revenue (analyst consensus for total revenue is ~ $1.13 billion); actual quarter-on-quarter TTR revenue growth compared to Q4 2025's $134 million growth; actual Q1 international revenue reduction compared to the anticipated $25 million.	Bullish: Q1 2026 TTR revenue exceeds analyst consensus or shows stronger QoQ growth than 'considerably lower' compared to Q4 2025; international revenue reduction is less than $25 million. Bearish: Q1 2026 TTR revenue misses analyst consensus or shows a steeper QoQ decline than anticipated; international revenue reduction is greater than $25 million.	Alnylam Pharmaceuticals Q1 2026 earnings call (April 30, 2026), company press releases, SEC filings (10-Q).	Industry reports on rare disease market trends; news articles on drug pricing and reimbursement in Germany.	Bloomberg Terminal: Consensus revenue estimates for ALNY; FactSet: Revenue forecasts and actuals for Alnylam's TTR franchise.

Key Reported Metrics3 rows

Metric	Why It Matters	Last Period
Total Revenue	Total Revenue is a fundamental indicator of Alnylam's overall financial performance and the market adoption of its diverse portfolio of RNAi therapeutics. Investors closely monitor this metric for sustained growth, reflecting successful commercialization and market expansion of its key products.	20%
Net Product Revenues	Net Product Revenues directly reflect the sales performance of Alnylam's commercialized drugs, such as ONPATTRO, GIVLAARI, OXLUMO, and AMVUTTRA. Strong growth in this segment, particularly from the TTR franchise, is crucial for driving profitability and validating the company's commercial strategy.	28%
Non-GAAP Research & Development (R&D) Expenses	As a biopharmaceutical company, R&D expenses are critical for advancing Alnylam's pipeline, including key assets like zilebesiran for hypertension. While flat in the last period, investors will scrutinize these expenses for efficient investment in clinical trials and future growth drivers.	0%

Key Questions

Will Amvuttra continue to gain market share in new ATTR cardiomyopathy treatment starts and maintain strong U.S. patient uptake in Q1 2026, despite anticipated

Will Amvuttra continue to gain market share in new ATTR cardiomyopathy treatment starts and maintain strong U.S. patient uptake in Q1 2026, despite anticipated Q1 seasonality?

Question 2: Will Alnylam's Q1 2026 TTR net product revenue performance meet or exceed the 'considerably lower' quarter-on-quarter growth expectation, thereby reinforcing confidence in the full-year 2026 revenue guidance?
Question 3: Will the anticipated competitive silencer data for ATTR cardiomyopathy, expected this year, reveal a differentiated profile or greater commercial impact than Alnylam projects, potentially challenging Amvuttra's market leadership?

Rerating Thresholds3 rows

Metric	What'S Needed For Rerating	Why It Matters	Earnings Date
Net Product Revenues	For Q1 2026, Combined Net Product Revenues need to exceed analyst consensus of approximately $1.13 billion by at least 3%, coupled with TTR net product revenue demonstrating positive quarter-on-quarter growth (reversing the 'considerably lower' expectation compared to Q4 2025's $134 million growth), and reaffirming or raising the full-year 2026 guidance of $4.9 billion to $5.3 billion.	Exceeding Q1 revenue expectations and showing positive TTR quarter-on-quarter growth would signal stronger Amvuttra uptake and resilience against anticipated Q1 seasonality and international pricing adjustments. This would reinforce confidence in Alnylam's ability to achieve its ambitious 2026 revenue guidance and long-term 'Alnylam 2030' goals, justifying its premium valuation and mitigating competitive concerns.	2026-04-30
Total Revenue	For Alnylam Pharmaceuticals (ALNY) to rerate higher, its Q1 2026 Total Revenue needs to exceed analyst consensus estimates, ideally surpassing $1.15 billion. This would represent a year-over-year growth rate of over 93.6% compared to Q1 2025's $594 million, demonstrating stronger-than-anticipated performance despite the company's cautious outlook for quarter-on-quarter TTR revenue growth. Additionally, the company needs to reaffirm its full-year 2026 net product sales guidance of $4.9 billion to $5.3 billion, with commentary suggesting confidence in achieving the higher end of this range.	Exceeding revenue expectations would alleviate investor concerns regarding near-term revenue choppiness, international pricing adjustments, and U.S. seasonality. This would reinforce confidence in the robust uptake of Amvuttra, Alnylam's key growth driver, and the company's ability to achieve its ambitious 'Alnylam 2030' goals and justify its current high valuation amidst competitive threats.	2026-04-30
Non-GAAP Research & Development (R&D) Expenses	For Alnylam Pharmaceuticals to rerate higher, its Non-GAAP Research & Development (R&D) Expenses for the full year 2026 need to be efficiently managed within the range of $1.47 billion to $1.59 billion. This aligns with the company's stated target of investing approximately 30% of its projected 2026 revenues, which are guided between $4.9 billion and $5.3 billion. Achieving this while simultaneously demonstrating strong pipeline progress and positive clinical de-risking data from key assets is crucial.	Hitting this range demonstrates financial discipline and effective capital allocation towards innovation, crucial for justifying Alnylam's high valuation. Efficient R&D that yields successful pipeline advancements reinforces the long-term growth thesis, supports the 'Alnylam 2030' non-GAAP operating margin goals, and addresses concerns about rising costs impacting profitability.	2026-04-30

Earnings Transcript SummaryTable

2026-02-12 · 2025Q4 Earnings Call

3 Things Management Is Most Focused On	Call Takeaway & Tone	Prior Quarter'S Y/Y Growth By Segment	3 Things Analysts Most Pressed On (And Mgmt Responses)	Revenue Segments
1. Achieving global TTR leadership and building a durable TTR franchise: Management aims to lead the TTR market in revenue by 2030 and plans to launch nuceresiran for polyneuropathy in 2028 and cardiomyopathy in 2030. This is a core part of their 'Alnylam 2030' goals. 2. Growing through sustainable innovation: The company plans to deliver two or more transformative medicines beyond TTR with blockbuster potential, achieve RNAi delivery to 10 tissue types, and have a pipeline of over 40 clinical programs by 2030. They expect to invest approximately 30% of revenues in non-GAAP R&D to accelerate organic and selectively access external innovation. 3. Scaling with discipline and agility to drive sustained, profitable growth: This includes striving for over 25% revenue CAGR through 2030 and a non-GAAP operating margin of 30% across the period, potentially reaching mid-40s post-2030 if nuceresiran is successful due to lack of royalty obligations.	The overall takeaway of the call was highly positive and confident. Management emphasized a transformational 2025, marked by the landmark approval and blockbuster launch of Amvuttra for ATTR cardiomyopathy, significant pipeline advancements, and the achievement of sustainable GAAP profitability. The tone was optimistic, reinforced by ambitious 'Alnylam 2030' goals focusing on TTR leadership, sustainable innovation, and disciplined, profitable growth. Despite anticipated Q1 seasonality and potential future competition, management expressed strong confidence in Amvuttra's continued growth trajectory and the company's long-term financial and pipeline prospects.	For Q3 2025: - Total net product revenues: 103% year-over-year growth. - Global TTR net revenues: 135% year-over-year growth. - U.S. TTR net revenues: 194% year-over-year growth. - Rare disease portfolio (GIVLAARI and OXLUMO): 14% year-over-year growth. - Collaboration revenue: Increased by $294 million compared to Q3 2024. - Royalty revenue: Doubled (100% increase) compared to Q3 2024.	1. New patient adds and the mix of first-line Amvuttra versus tafamidis switches in 2026: Management (Tolga Tanguler) responded that the fundamentals drive confidence, citing improved first-line access, strengthening physician and patient preference, and continued category growth. 2. Choppiness in Q1 TTR franchise scripts and pricing dynamics, including new potential market entries and growth in Europe: Management (Tolga Tanguler and Jeff Poulton) stated they are well-positioned for access, with most patients having first-line access without step-through requirements and paying zero out-of-pocket. They expect a mid-single-digit net price decrease for Amvuttra in 2026, similar to 2025, and that Q1 seasonality is typical for the industry but not impacting underlying momentum. They also noted an expected $25 million reduction in Q1 international revenues due to Germany pricing alignment. 3. The potential impact of competitive silencer data on Amvuttra's label and commercial prospects: Management (Tolga Tanguler and Pushkal Garg) acknowledged the difficulty in assessing impact without seeing competitor data but emphasized the large and underserved category, suggesting new entrants could help drive diagnosis. They highlighted Amvuttra's strong position with rapid, deep, and sustained knockdown, robust clinical data, and quarterly dosing. Pushkal Garg expected the competitor's study to be positive but did not foresee a materially different label or effect size compared to Amvuttra's already broad label.	For Q4 2025: - Combined net product revenues: 121% year-over-year growth. - Rare disease portfolio (GIVLAARI and OXLUMO): 26% year-over-year growth. - Global TTR net revenues: 151% year-over-year growth. - U.S. TTR franchise: 222% year-over-year growth. - Outside U.S. TTR franchise: 47% year-over-year growth. For Full Year 2025: - Combined net product revenues: 81% growth compared to 2024. - Collaboration revenue: 8% growth compared with 2024. - Royalty revenue: 90% increase compared with last year.

Transcript TidbitsTable

2026-02-12

About Expanding Eligible Market	About Competition	About The Broader Industry	Where Things Are Headed	Updates On Theme	Broader Themes Emerging	Bullish-Leaning Quotes (Short)	Bearish-Leaning Quotes (Short)	Hiring
Alnylam achieved a landmark approval of Amvuttra for ATTR cardiomyopathy in 2025, driving significant revenue growth. The company plans to launch nuceresiran in 2028 for polyneuropathy and 2030 for cardiomyopathy, aspiring to lead the TTR market in revenue by 2030. They aim to achieve RNAi delivery to 10 tissue types and have a pipeline of over 40 clinical programs by 2030. Amvuttra is being launched for ATTR cardiomyopathy in additional international markets throughout 2026. The company is investing in education, awareness, evidence generation, and diagnosis enablement to expand the ATTR cardiomyopathy category. New clinical programs include ALN-2232 for durable weight loss and visceral fat reduction, ALN-5288 for Alzheimer's disease and rare tauopathies, valesiran for cerebral amyloid angiopathy and Alzheimer's disease (a 'blue ocean opportunity'), ALN-HTT02 for Huntington's disease, and ALN-6400 for a wide range of bleeding disorders, with hereditary hemorrhagic telangiectasia affecting approximately 70,000 patients in the U.S..	Alnylam's hereditary ATTR polyneuropathy business remains robust despite competition. Amvuttra approached parity with tafamidis in share of new starts in ATTR cardiomyopathy by the second quarter post-launch. The company acknowledges upcoming competitive silencer data, expecting the study to be positive with good knockdown. However, they hypothesize that the treatment effect size for competitors will not be materially different from what Alnylam has established with HELIOS-B, and do not foresee a competitor's label being materially different based on statistical significance in a subgroup. They believe additional entrants will help drive diagnosis and treatment rates, ultimately benefiting patients and expanding the category.	The ATTR cardiomyopathy category has seen approximately 40% volume CAGR over the past six years, yet the majority of patients remain untreated, indicating significant unmet need and growth potential. The industry experiences typical Q1 seasonality. GLP-1s have revolutionized the metabolic disease space, but Alnylam sees unmet needs in weight loss and A1c reduction without muscle loss and tolerability issues, which they aim to address with their pipeline. Additional market entrants are expected to help drive diagnosis and treatment rates across the industry.	Alnylam is focused on accelerating innovation and scaling impact, guided by their new 'Alnylam 2030' goals. These goals include achieving global TTR leadership, launching nuceresiran in 2028 (polyneuropathy) and 2030 (cardiomyopathy), delivering two or more transformative blockbuster medicines beyond TTR, achieving RNAi delivery to 10 tissue types, and expanding the pipeline to over 40 clinical programs by 2030. They expect to invest approximately 30% of revenues in non-GAAP R&D and aim for over 25% revenue CAGR and a non-GAAP operating margin of 30% through 2030, potentially reaching mid-40s post-2030 with nuceresiran. The company anticipates launching Amvuttra for ATTR cardiomyopathy in additional international markets throughout 2026. They expect clinical de-risking data in 2026 for ALN-6400, Huntington's, and ACVR1C programs. Combined non-GAAP R&D and SG&A expenses are projected to be between $2.7 billion and $2.8 billion in 2026, driven by increased investment in pivotal Phase 3 studies and early pipeline, as well as ongoing Amvuttra launch activities.	RNAi	Innovation in metabolic diseases (GLP-1s).	Alnylam possesses a truly unique profile in the biotech industry, underpinned by our established and sustainable innovation engine, coupled with commercial excellence driving durable long-term growth. We achieved a landmark approval of Amvuttra for ATTR cardiomyopathy, and driven by the success of that launch, delivered nearly $3 billion in combined net product revenues, which was 81% growth compared to 2024. We can now officially declare that we have achieved GAAP profitability for the 2025 full year and expect to sustain profitability going forward. If nuceresiran is successful in demonstrating the best-in-class profile that we expect, we believe it would drive swift patient uptake and, given the lack of any royalty obligations for nuceresiran, potentially drive our operating margins to the mid-40s post 2030. Amvuttra is rapidly establishing itself as an important choice in new treatment starts. By just the second quarter post launch, Amvuttra approached parity with tafamidis in share of new starts based on available estimates.	As expected, this will create a modest near-term impact on total TTR revenue in Q1. Modest quarter-over-quarter TTR growth in Q1 compared with the $111 million of U.S. quarterly growth achieved in Q4 due to fewer product shipping weeks in Q1 and the expected impact of annual insurance reauthorizations. Collaboration and royalty revenue guidance range is $400 million to $500 million, representing a decrease of 38% compared to 2025 at the midpoint of the guidance range, driven by the one-time $300 million zalesiran development milestone achieved in 2025 that will not recur this year. My hypothesis would be I do not see any reason why the treatment effect size would be any different than what we have already established in HELIOS-B.

NotesTable

Date	Comment	Comment Type	Comment Sentiment	Link	IS CHANGE	Price Reaction
2026-02-12	Alnylam reported strong 2025 results, achieving GAAP profitability and nearly $3 billion in revenue, driven by Amvuttra's successful launch. They outlined ambitious 2030 goals for TTR leadership and pipeline expansion. However, a cautious Q1 2026 TTR revenue outlook, citing international pricing and U.S. seasonality, and projected mid-single-digit Amvuttra net price declines, likely contributed to the stock's -2.45% return (underperforming SPY) post-earnings.	Earnings Transcript	Neutral		False	-2.45% (vs SPY: -1.13%)

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Catalyst ID	Estimated Timing	Estimated Date Start	Estimated Date End	Catalyst	Why It Matters	Ticker Or Theme Specific	Transcript Date	Source Type
ALNY_7da29ce1	throughout 2026	2026-01-01	2026-12-31	Ongoing launch of Amvuttra for ATTR cardiomyopathy in additional international markets following local pricing and reimbursement reviews.	Successful launches are critical for expanding Amvuttra's global reach, driving TTR franchise revenue growth, and achieving the company's 2026 financial guidance.	Ticker	2026-02-12	earnings_transcript
ALNY_e966b7db	Q4 2026 for decision, late 2026 or early 2027 for launch	2026-10-01	2027-03-31	Potential U.S. regulatory approval for cemdisiran in generalized myasthenia gravis, a partnered product with Regeneron.	Approval would enable commercialization, leading to potential milestone payments and royalties for Alnylam, contributing to collaboration and royalty revenue.	Ticker	2026-02-12	earnings_transcript
ALNY_94ae948c	second half of the year	2026-07-01	2026-12-31	Release of Phase 1 and 2 clinical data from the ALN-6400 program (targeting plasminogen for bleeding disorders).	Positive data would de-risk the program, supporting its 'pipeline-in-a-product' potential and future development in a range of bleeding disorders, impacting long-term valuation.	Ticker	2026-02-12	earnings_transcript
ALNY_1f8d0ad4	second half of the year	2026-07-01	2026-12-31	Release of Phase 1 clinical data for ALN-HTT02 (Huntington's disease program).	Data on huntingtin protein lowering and safety are crucial for de-risking this program, which targets a devastating disease with no approved therapies, potentially accelerating its development and impacting long-term valuation.	Ticker	2026-02-12	earnings_transcript
ALNY_6acd0085	second half of the year	2026-07-01	2026-12-31	Release of Phase 1 clinical data for ALN-2232 (ACVR1C targeting for obesity & weight management).	Positive data would de-risk the program, demonstrating its potential for durable weight loss and addressing unmet needs in the overweight/obesity and diabetes space, impacting long-term valuation.	Ticker	2026-02-12	earnings_transcript
ALNY_5d72b867	H2 2026	2026-07-01	2026-12-31	Readout of Phase 3 CARDIO-TTRansform study results for Ionis Pharmaceuticals' eplontersen in transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).	Positive results could introduce a new competitive TTR silencer into the ATTR-CM market, potentially impacting Amvuttra's market share, pricing dynamics, and overall TTR franchise growth.	Theme	2026-02-12	earnings_transcript