Executive Summary

Q1 2025 revenue and profitability outperformed expectations: total revenues $594.2M (+20% Y/Y) and non-GAAP operating income $74.8M, with non-GAAP EPS of $(0.01) vs S&P Global consensus of $(1.01), and revenue $594.2M vs $581.2M consensus; beat driven by 36% Y/Y growth in TTR franchise and steady Rare franchise growth . Revenue/EPS estimates from S&P Global marked with asterisk below.*
AMVUTTRA ATTR-CM approved in the U.S. on March 20 and launch is “off to an exceptional start”: >50% of priority health systems (of ~170) had added AMVUTTRA to formulary within four weeks; early initiations across Medicare FFS/MA/commercial; broad first-line use and switches observed .
Guidance reiterated: FY25 total net product revenue $2.05–$2.25B, TTR $1.60–$1.725B, Rare $450–$525M; collaboration+royalty revenue $650–$750M; non-GAAP operating income to achieve profitability; CFO noted potential ~$50M FX upside if current rates persist .
Catalysts: Japan/EU AMVUTTRA ATTR-CM decisions (expected Q2/Q3), TRITON-CM (nucresiran) Phase 3 initiation in 1H25, and KARDIA-3 hypertension combo data 2H25; management emphasized strong early CM uptake and sustained TTR growth as near-term stock drivers .

What Went Well and What Went Wrong

What Went Well
- TTR franchise strength: Global TTR net product revenue $359.5M (+36% Y/Y) with AMVUTTRA $310M and ONPATTRO $49M; U.S. TTR +45% Y/Y, international +24% Y/Y, despite new competitors .
- AMVUTTRA ATTR-CM launch momentum: inclusion on formulary in >50% of ~170 key systems in ~4 weeks; broad payer coverage, most patients with $0 copay; first-line use and switches observed; “launch is off to an exceptional start” .
- Profitability and margin: 85% gross margin on product sales; non-GAAP operating income $74.8M vs $1.9M a year ago, reflecting leverage on strong top-line growth .
What Went Wrong
- Collaboration revenue down 16% Y/Y to $99.2M due to absence of prior-year $65M Roche milestone (KARDIA-3 first patient dosed) offset partly by Regeneron activity and $30M from Vir amendment .
- GAAP bottom line impacted by non-cash items: other expense included a $58.9M charge from change in fair value of development derivative liability tied to AMVUTTRA ATTR-CM approval, pressuring GAAP EPS (−$0.44) .
- Royalty step-ups expected to compress gross margin through 2025 as AMVUTTRA sales scale and royalty tiers increase, per CFO; margin pressure likely near term despite product growth .

Financial Results

Revenue, EPS, margins vs prior year, prior quarter, and estimates

Metric	Q1 2024	Q4 2024	Q1 2025	Q1 2025 Consensus*
Total Revenues ($M)	$494.3	$593.2	$594.2	$581.2*
Net Product Revenues ($M)	$365.2	$450.8	$468.5	—
GAAP EPS	$(0.52)	$(0.65)	$(0.44)	—
Non-GAAP EPS	$(0.16)	$0.06	$(0.01)	$(1.01)*
Gross Margin on Product Sales	85% (implied from 15% COGS)	—	85%	—
Non-GAAP Operating Income ($M)	$1.9	—	$74.8	—

Beat/miss vs S&P Global consensus (Q1 2025)

Metric	Actual	Consensus*	Surprise	Surprise %
Total Revenues ($M)	$594.2	$581.2*	+$13.0	+2.2%
Non-GAAP EPS	$(0.01)	$(1.01)*	+$1.00	n/m

Segment and product breakdown (Q1 2025)

Segment/Product	Revenue ($M)	Y/Y %
TTR (AMVUTTRA + ONPATTRO)	$359.5	+36%
• AMVUTTRA	$310.0	—
• ONPATTRO	$49.0	—
Rare (GIVLAARI + OXLUMO)	$109.1	+8%
• GIVLAARI	$67.0	—
• OXLUMO	$42.0	—
Total Net Product Revenues	$468.5	+28%
Net Revenues from Collaborations	$99.2	−16%
• Roche	$17.1	−77%
• Regeneron	$51.0	+91%
• Novartis	$0.0	−100%
• Other	$31.1	n/m
Royalty Revenue	$26.5	+149%
Total Revenues	$594.2	+20%

Key performance indicators (Q1 2025)

KPI	Q1 2025	Notes
Cost of Goods Sold as % of Net Product Revenue	15.0%	Consistent Y/Y
Gross Margin on Product Sales	85%	Expected to decline in 2025 as AMVUTTRA royalties step up
Cash, Cash Equivalents & Marketable Securities	$2.63B	Down from $2.69B at 12/31/24
Non-GAAP R&D Expense	$241.3M	Flat Y/Y
Non-GAAP SG&A Expense	$207.0M	+12% Y/Y (ATTR-CM launch)
Other Expense, net	$(59.7)M	Includes $(58.9)M fair value charge tied to AMVUTTRA ATTR-CM approval

Guidance Changes

Metric	Period	Previous Guidance (Q4’24)	Current Guidance (Q1’25)	Change
Total TTR Net Product Revenues (AMVUTTRA, ONPATTRO)	FY 2025	$1.600B–$1.725B	$1.600B–$1.725B	Maintained
Total Rare Net Product Revenues (GIVLAARI, OXLUMO)	FY 2025	$450M–$525M	$450M–$525M	Maintained
Total Net Product Revenues	FY 2025	$2.050B–$2.250B	$2.050B–$2.250B	Maintained
Net Product Revenue Growth vs 2024 (reported FX)	FY 2025	25%–37%	25%–37%	Maintained
Net Product Revenue Growth vs 2024 (CER)	FY 2025	26%–39%	26%–39%	Maintained
Net Revenues from Collaborations & Royalties	FY 2025	$650M–$750M	$650M–$750M	Maintained
Non-GAAP R&D + SG&A	FY 2025	$2.10B–$2.20B	$2.10B–$2.20B	Maintained
Non-GAAP Operating Income	FY 2025	Achieve profitability	Achieve profitability	Maintained

Notes: Guidance assumes U.S. AMVUTTRA ATTR-CM approval (achieved), and launches in Germany and Japan in 2H25; FX rates as of 12/31/24. CFO indicated ~+$50M potential FX tailwind if current rates persist; to be reassessed in Q2 .

Earnings Call Themes & Trends

Topic	Q3 2024 (prior-2)	Q4 2024 (prior-1)	Q1 2025 (current)	Trend
ATTR-CM launch	Prepping for launch; HELIOS-B data showcased; filings submitted in U.S./EU	U.S. PDUFA 3/23; building access pathways; 1,000+ alternate sites; second-half weighted ramp expected	FDA and Brazil approvals; positive CHMP; “exceptional” early U.S. launch with >50% of ~170 systems on formulary in ~4 weeks	Accelerating execution
Payer/access dynamics (Part B vs Part D; VBAs)	Emphasis on building VBAs; positioning for smooth access	Expect Part B dynamics similar to PN; VBAs to extend to CM; second-half revenue ramp	Broad coverage across Medicare FFS/MA/commercial; most patients $0 copay; value agreements include CM	Favorable setup
Product performance	TTR net product rev +34% Y/Y; ~5,000 global patients on therapy	TTR +35% Y/Y in Q4; U.S. TTR +42% Y/Y despite competition	TTR +36% Y/Y; U.S. +45% Y/Y; intl +24% Y/Y	Sustained growth
Tariffs/macro	—	—	Minimal impact from current tariffs; limited exposure to potential pharma tariffs	Benign
Gross margin outlook	3Q margin improvement vs 2023; Q4 margin to be lower on royalty rate	2025 GM on product sales expected lower; AMVUTTRA royalties rising to mid/high-20s %	85% GM in Q1; expect lower as royalty tiers rise	Gradual compression
Pipeline/R&D	Nucresiran >90% 6-mo knockdown; CNS programs progressing	Nucresiran ODD; Phase 3 CM to start 1H25; zilebesiran Phase 3 outcomes in 2H25	TRITON-CM 1H25; KARDIA-3 2H25; expanding tissue delivery	Advancing to pivotal

Management Commentary

“2025 is off to a strong start… we delivered $469 million in combined net product revenues… robust 45% year-over-year growth of our U.S. TTR franchise.” — CEO Yvonne Greenstreet .
“Our teams’ focused efforts enabled inclusion of AMVUTTRA formulary in more than half of the health systems within short 4 weeks of label expansion… the launch is off to an exceptional start.” — CCO Tolga Tanguler .
“Gross margin on product sales was 85%… for the balance of the year… expected to decrease as the AMVUTTRA average royalty rate escalates.” — CFO Jeff Poulton .
“We are reiterating our guidance for the year… and our goal of achieving sustainable non-GAAP profitability in 2025.” — CEO Yvonne Greenstreet .

Q&A Highlights

Early launch mix and prescribers: Broad uptake across cardiologists familiar and new to AMVUTTRA; both first-line and switch patients; focus on formulary readiness (over half of ~170 systems) to enable 2H pull-through .
Access dynamics: Smooth coverage across Medicare FFS/MA/commercial; most patients $0 copay; no meaningful step edits observed to date; Part B dynamics favorable and analogous to PN experience .
Competitive landscape: Category growth expected with additional options; management emphasizes differentiated RNAi mechanism, mortality benefit, and quarterly HCP-administered dosing .
Guidance transparency: Company plans more quantitative launch indicators with Q2 results; reiterated that 2H is the primary revenue ramp for CM .
Tariffs: No material impact from current tariffs; limited exposure to potential pharma tariffs given U.S.-based IP and supply chain .

Estimates Context

Q1 2025 vs S&P Global consensus: Revenue $594.2M vs $581.2M estimate (+2.2% beat); non-GAAP EPS $(0.01) vs $(1.01) estimate (≈$1.00 beat), driven by 36% Y/Y TTR growth and disciplined OpEx; collaboration revenue declined as expected on prior-year milestone comp . Values marked with asterisk are from S&P Global.*
Estimate implications: Management reiterated FY25 guidance and flagged a potential ~$50M FX tailwind if rates persist; Street models may shift toward a more back-half-weighted trajectory reflecting access/formulary ramp and international CM approvals in Q2/Q3 .

Key Takeaways for Investors

Strong execution with clear top-line and non-GAAP EPS beats, anchored by robust AMVUTTRA growth and an “exceptional” early CM launch setup .
Reiterated FY25 guide with upside FX optionality; second-half skew remains central as payer and health-system processes complete and international CM launches commence .
Near-term margin headwinds (royalty step-ups) are well telegraphed; longer-term margin relief possible with next-gen nucresiran (no Sanofi royalty) if successful .
Pipeline momentum provides multiple 2025 catalysts (TRITON-CM start, KARDIA-3 data), supporting medium-term growth beyond current TTR expansions .
Competitive noise likely expands category; AMVUTTRA’s differentiated mechanism, mortality benefit, and quarterly dosing position it well for first-line use and switches .
Watch Q2 for quantitative launch indicators and FX update; Japan/EU decisions could accelerate ex-U.S. contribution in 2H .

Footnotes and Disclosures:

All company results, guidance, and commentary cited from the Q1 2025 8-K/press release and earnings call: - - -. Prior-quarter references: Q4 2024 8-K and call -; Q3 2024 8-K and call -. Regulatory update: CHMP positive opinion -.
*Values retrieved from S&P Global: Consensus revenue and EPS estimates (and estimate counts) are from S&P Global (GetEstimates).

ALNYLAM PHARMACEUTICALS, INC. (ALNY)·Q1 2025 Earnings Summary