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Item 7. Management’s Discussion and Analysis

2025-02-13 compared with 2024-02-15 · 92 added, 78 removed, 157 unchanged (52% of the section changed)

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We are a global commercial-stage biopharmaceutical company that discovers, develops, manufactures and commercializes novel therapeutics based on RNAi.

Our commercial products and broad pipeline of investigational RNAi therapeutics are focused in rare, specialty and select prevalent indications.

Our commercial products and broad pipeline of investigational RNAi therapeutics are targeting a broad range of disease areas and indications.

As described in Part I, Item 1.

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Historically, we have generated losses principally from costs associated with research and development activities, acquiring, filing and expanding intellectual property rights, and selling, general and administrative costs.

As a result of planned expenditures for research and development activities relating to our research platform, our drug development programs, including clinical trial and manufacturing costs, the establishment of late-stage clinical and commercial capabilities, including global commercial operations, continued management and growth of our patent portfolio, collaborations and general corporate activities, we expect to incur additional operating losses.

While we believe 2019 was our peak operating loss year, we expect to continue to incur annual operating losses, and will require substantial resources over the next several years as we expand our efforts to discover, develop and commercialize RNAi therapeutics, and aim to achieve financial self-sustainability by the end of 2025.

As a result of planned expenditures for research and development activities relating to our research platform, our drug development programs, including clinical trial and manufacturing costs, the continued build-out of late-stage clinical and commercial capabilities, including global commercial operations, continued management and growth of our patent portfolio, collaborations and general corporate activities, we may incur additional operating losses.

We will require substantial resources over the next several years as we expand our efforts to discover, develop and commercialize RNAi therapeutics, and aim to achieve financial self-sustainability by the end of 2025.

We anticipate that our operating results will continue to fluctuate for the foreseeable future, therefore, period-to-period comparisons should not be relied upon as predictive of the results in future periods.

We currently have programs focused on a number of therapeutic areas and, as of December 31, 2024, we generate worldwide product revenues from four commercialized products, ONPATTRO, AMVUTTRA, GIVLAARI and OXLUMO, primarily in the U.S.

However, our ongoing development efforts may not be successful and we may not be able to commence sales of any other products and/or successfully market and sell ONPATTRO, AMVUTTRA, GIVLAARI, OXLUMO or any other approved products in the future.

A substantial portion of our total revenues in recent years has been derived from collaboration revenues from collaborations with Roche, Regeneron and Novartis.

However, our ongoing development and regulatory efforts may not be successful and we may not be able to commence sales of any other products and/or successfully expand the labels of or market and sell our existing commercialized products or any other approved products in the future.

A meaningful portion of our total revenues in recent years has been derived from collaboration revenues from collaborations with Roche, Regeneron and Novartis.

In addition to revenues from the commercial sales of our approved products and potentially from sales of future products, we expect our sources of potential funding for the next several years to continue to be derived in part from existing and new strategic collaborations.

Such collaborations include, or may include in the future, license and other fees, funded research and development, milestone payments and royalties on product sales by our licensors, including royalties on sales of Leqvio made by our collaborator, Novartis, as well as proceeds from the sale of equity or debt.

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Such collaborations include, or may include in the future, license and other fees, equity investments, funded research and development, milestone payments and royalties on product sales by our licensors, including royalties on sales of Leqvio made by our collaborator Novartis.

Results of Operations

The following data summarizes the results of our operations:

Year Ended December 31, 2023 vs 2022 2022 vs 2021

Years Ended December 31,

2024 vs 2023 2023 vs 2022

(In thousands, except percentages) 2024 2023 2022 $ Change % Change $ Change % Change

Total revenues $ 2,248,243 $ 1,828,292 $ 1,037,418 $ 419,951 23 % $ 790,874 76 %

Operating costs and expenses $ 2,110,467 $ 1,822,490 $ 1,552,939 $ 287,977 16 % $ 269,551 17 %

Total operating costs and expenses $ 2,425,128 $ 2,110,467 $ 1,822,490 $ 314,661 15 % $ 287,977 16 %

Loss from operations $ (176,885) $ (282,175) $ (785,072) $ 105,290 (37) % $ 502,897 (64) %

Total other expense, net $ (200,490) $ (151,342) $ (341,921) $ (49,148) 32 % $ 190,579 (56) %

Benefit from (provision for) income taxes $ 99,218 $ (6,725) $ (4,163) $ 105,943 * $ (2,562) 62 %

Net loss $ (278,157) $ (440,242) $ (1,131,156) $ 162,085 (37) % $ 690,914 (61) %

For discussion of our 2022 results and a comparison with 2021 results please refer to “Management’s Discussion and Analysis of Financial Conditions and Results of Operations” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2022 that was filed with the SEC on February 23, 2023.

* Indicates the percentage change period over period is greater than 500%.

For a discussion of our 2023 results and a comparison with 2022 results please refer to “Management’s Discussion and Analysis of Financial Conditions and Results of Operations” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2023, which was filed with the SEC on February 15, 2024.

Discussion of Results of Operations

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Total $ 2,248,243 $ 1,828,292 $ 1,037,418 $ 419,951 23 % $ 790,874 76 %

* Indicates the percentage change period over period is greater than 500%.

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Net Product Revenues

Net product revenues consist of the following, by product and region:

Year Ended December 31, 2023 vs 2022 2022 vs 2021

Years Ended December 31,

2024 vs 2023 2023 vs 2022

(In thousands, except percentages) 2024 2023 2022 $ Change % Change $ Change % Change

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Total 252,857 354,546 557,608 (101,689) (29) % (203,062) (36) %

United States 411,169 82,521 — 328,648 398 % 82,521 N/A

Europe 70,898 4,214 — 66,684 * 4,214 N/A

Rest of World 75,771 7,060 — 68,711 * 7,060 N/A

Total 557,838 93,795 — 464,043 495 % 93,795 N/A

United States 630,613 411,169 82,521 219,444 53 % 328,648 398 %

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Total 255,871 219,251 173,144 36,620 17 % 46,107 27 %

United States 62,766 38,159 27,698 24,607 64 % 10,461 38 %

Europe 80,753 60,025 37,915 20,728 35 % 22,110 58 %

Rest of World 23,531 11,655 4,169 11,876 102 % 7,486 180 %

Total 167,050 109,839 69,782 57,211 52 % 40,057 57 %

Total net product revenues $ 1,646,228 $ 1,241,474 $ 894,329 $ 404,754 33 % $ 347,145 39 %

Net product revenues increased during the year ended December 31, 2023, compared to the year ended December 31, 2022, primarily due to the launch of AMVUTTRA in the third quarter of 2022, partially offset by a decrease of demand for ONPATTRO due to patient switches to AMVUTTRA.

Additional growth was related to an increase in patients on GIVLAARI and OXLUMO.

Please see Note 3 to our consolidated financial statements included in Part II, Item 8, “Financial Statements and Supplementary Data” of this Annual Report on Form 10-K for balances and activity in each product revenue allowance and reserve category for the years ended December 31, 2023 and 2022.

* Indicates the percentage change period over period is greater than 500%.

Net product revenues increased during the year ended December 31, 2024, compared to the year ended December 31, 2023, primarily due to growth from sales of AMVUTTRA driven by increased patient demand, partially offset by a decrease in sales of ONPATTRO due to patient switches to AMVUTTRA, as well as increased patients on GIVLAARI and OXLUMO therapies.

Please see Note 3, Net Product Revenues, to our consolidated financial statements included in Part II, Item 8, “Financial Statements and Supplementary Data” of this Annual Report on Form 10-K for balances and activity in each product revenue allowance and reserve category for the years ended December 31, 2024 and 2023.

Net Revenues from Collaborations and Royalty Revenue

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(In thousands, except percentages) 2024 2023 2022 $ Change % Change $ Change % Change

$ 337,802 $ — $ — $ 337,802 N/A $ — N/A

$ 119,489 $ 337,802 $ — $ (218,313) (65) % $ 337,802 N/A

Regeneron Pharmaceuticals 302,798 100,468 87,844 202,330 201 % 12,624 14 %

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Royalty revenue $ 91,794 $ 40,633 $ 8,177 $ 51,161 126 % $ 32,456 397 %

Net revenues from collaborations increased during the year ended December 31, 2023, as compared to the year ended December 31, 2022, primarily due to revenue recognized under our agreements with Roche and Novartis.

During 2023, we recognized $337.8 million of revenue under our Collaboration and License Agreement with Roche, which was executed in July

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2023, and under our Novartis Collaboration Agreement we recognized an additional $30.0 million of revenue, compared to 2022, associated with the achievement of specified commercialization and regulatory milestones.

Royalty revenue increased during the year ended December 31, 2023, as compared to the year ended December 31, 2022, due to increased royalties earned from global net sales of Leqvio by our collaborator, Novartis.

Net revenues from collaborations decreased during the year ended December 31, 2024, as compared to the year ended December 31, 2023, primarily driven by:

• a decrease in revenue recognized under our Roche Collaboration in 2024 due to the recognition of $310.0 million of revenue upon the transfer of licenses to Roche during the third quarter of 2023.

Partially offset by:

• revenue of $185.0 million recognized under our Regeneron Collaboration as we modified the collaboration in June 2024 and provided Regeneron with an exclusive license to develop, manufacture and commercialize cemdisiran as a monotherapy;

• recognition of $65.0 million in revenue under our Roche Collaboration associated with dosing the first patient in the zilebesiran KARDIA-3 clinical trial during 2024.

Royalty revenue increased during the year ended December 31, 2024, as compared to the year ended December 31, 2023, due to increased volume and rate of royalties earned from global net sales of Leqvio by our collaborator, Novartis.

Recognition of our combined net revenues from collaborations and royalty revenue is dependent on a variety of factors, including the level of work reimbursed by collaborators, achievement of milestones under our collaboration agreements, and royalties associated with sales of Leqvio.

We expect net revenues from collaboration will decrease in 2024, as compared to 2023, primarily driven by a reduction in the revenues recognized under our Roche Collaboration and License Agreement.

We expect our royalty revenues will increase in 2024, as compared to 2023, due to the continued growth of royalties earned from global net sales of Leqvio by our collaborator, Novartis.

The amount of revenue from collaborations that we recognize, in part, is based on estimates of total costs to be incurred.

We expect net revenues from collaborations will increase in 2025, as compared to 2024, primarily driven by higher anticipated revenues under our Roche Collaboration and License Agreement.

We expect our royalty revenue will increase in 2025, as compared to 2024, due to the continued growth of royalties earned from global net sales of Leqvio by our collaborator, Novartis.

The amount of revenue from collaborations that we recognize is based, in part, on estimates of total costs to be incurred.

These estimates reflect our historical experiences, current contractual requirements, and forecasted plans of development or manufacturing activities.

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Operating costs and expenses consist of the following:

Year Ended December 31, 2023 vs 2022 2022 vs 2021

Years Ended December 31, 2024 vs 2023 2023 vs 2022

(In thousands, except percentages) 2024 2023 2022 $ Change % Change $ Change % Change

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Cost of Goods Sold

Cost of goods sold as a percentage of net product revenues increased to 21.6% for the year ended December 31, 2023, as compared to 15.7% for the year ended December 31, 2022, primarily due to the following:

• Increased volume and rate of royalties payable on net sales of AMVUTTRA.

Our collaborator is eligible to receive tiered royalties of 15% to 30% based on global annual net sales and therefore the growth in AMVUTTRA net sales during 2023 resulted in more net sales and a higher tier rate for the applicable royalties payable;

• Increased excess and obsolete charges primarily due to cancelling manufacturing commitments and the impairment of ONPATTRO inventory that had been manufactured for future demand associated with the use of patisiran for the treatment of patients with ATTR amyloidosis with cardiomyopathy for which we did not receive regulatory approval in the U.S.

We anticipate variability in our cost of goods sold as a percentage of net product revenues in 2024, as compared to 2023.

We expect our cost of goods sold will increase during 2024, as compared to 2023, primarily as a result of an expected increase in net product sales as well as increased royalties.

Cost of goods sold as a percentage of net product revenues decreased to 18.6% for the year ended December 31, 2024, as compared to 21.6% for the year ended December 31, 2023.

Approximately 5.0% of the 21.6% of cost of goods sold as a percentage of net product revenues for the year ended December 31, 2023 was attributable to cancelled manufacturing commitments and the impairment of ONPATTRO inventory that had been manufactured for future demand associated with the use of ONPATTRO for the treatment of patients with ATTR amyloidosis with cardiomyopathy, for which we did not receive regulatory approval in the U.S.

These one-time charges in 2023 did not recur in 2024, resulting in the decrease in cost of goods sold as a percentage of net product revenues in 2024, which was partially offset by higher volume and royalty rates payable on net sales of AMVUTTRA in 2024.

We expect our cost of goods sold, including cost of goods sold as a percentage of net product revenues, will increase during 2025, as compared to 2024, primarily as a result of an expected increase in net product revenues and increased royalties on net sales of AMVUTTRA.

Cost of Collaborations and Royalties

Cost of collaborations and royalties increased during the year ended December 31, 2023, as compared to the year ended December 31, 2022, primarily due to increased demand of GalNAc material supplied to our collaborators to support certain product manufacturing and ongoing clinical trials and increased royalties payable to third parties on the net sales of licensed products by Novartis.

We expect our cost of collaborations and royalties will decrease during 2024, as compared to 2023, primarily due to a decrease in demand of GalNAc material supplied to our collaborators in support of certain product manufacturing as our collaborators begin to transition to producing the material independently.

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Cost of collaborations and royalties decreased during the year ended December 31, 2024, as compared to the year ended December 31, 2023, primarily due to decreased demand for GalNAc material supplied to our collaborators in support of certain

product manufacturing as our collaborators transition to producing the material independently, as well as reduced royalties payable from the expiration of licenses of third-party intellectual property.

We expect our cost of collaborations and royalties will decrease during 2025, as compared to 2024, primarily as a result of our collaborators transitioning to produce GalNAc material independently.

Research and Development

Research and development expenses consist of the following:

Year Ended December 31, 2023 vs 2022 2022 vs 2021

Years Ended December 31,

2024 vs 2023 2023 vs 2022

(In thousands, except percentages) 2024 2023 2022 $ Change % Change $ Change % Change

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Occupancy and all other costs (1)

161,425 160,987 126,847 438 — % 34,140 27 %

Stock-based compensation 127,749 97,273 92,161 30,476 31 % 5,112 6 %

$ 1,126,232 $ 1,004,415 $ 883,015 $ 121,817 12 % $ 121,400 14 %

(1) Occupancy and all other costs includes facilities, information technology, depreciation and certain departmental expenses.

Research and development expenses increased during the year ended December 31, 2024, as compared to the year ended December 31, 2023, primarily due to the following:

• Increased compensation and related expenses as a result of increased headcount to support our R&D pipeline and development expenses;

• Increased clinical research and outside services primarily associated with zilebesiran as we reached full enrollment for our KARDIA-1 and KARDIA-2 clinical studies and additional costs associated with manufacturing batches associated with those clinical activities.

Costs associated with clinical trials of other programs such as ALN-TTRsc04 and our ongoing early development studies also were higher when compared to 2022;

• Increased occupancy and all other costs as a result of higher costs related to infrastructure and other professional services to support our growing clinical footprint.

• increased clinical trial expenses mainly related to the advancement of our KARDIA-3 and cAPPRicorn-1 clinical programs;

• increased costs associated with our preclinical activities as we develop our clinical pipeline of RNAi therapeutics targeting multiple tissue types;

• increased employee compensation and related expenses to support our research and development pipeline and development expenses;

• increased stock-based compensation expenses primarily due to the accounting for certain performance-based awards.

Partially offset by:

• decreased expenses within other clinical programs, specifically the APOLLO-B Phase 3 clinical trial of patisiran due to the wind down of clinical activities during the open label extension period;

• decreased costs due to the timing of manufacturing of zilebesiran for clinical activities.

During the years ended December 31, 2024, 2023 and 2022, in connection with advancing activities under our collaboration agreements, we incurred research and development expenses, primarily related to external development and clinical expenses, including the manufacture of clinical product.

The following table summarizes research and development expenses incurred, for which we recognize revenue, that are directly attributable to our collaboration agreements, by collaborator:

Year Ended December 31,

Years Ended December 31,

(In thousands) 2024 2023 2022

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Selling, general and administrative expenses consist of the following:

Year Ended December 31, 2023 vs 2022 2022 vs 2021

Years Ended December 31, 2024 vs 2023 2023 vs 2022

(In thousands, except percentages) 2024 2023 2022 $ Change % Change $ Change % Change

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$ 975,526 $ 795,646 $ 770,658 $ 179,880 23 % $ 24,988 3 %

Selling, general and administrative expenses increased during the year ended December 31, 2023, as compared to the year ended December 31, 2022, primarily due to increased headcount and other investments supporting our strategic growth including the global launch of AMVUTTRA.

We expect that research and development expenses combined with selling, general and administrative expenses will increase during 2024, as compared to 2023, as we continue to advance and develop our platform and pipeline, advance our product candidates, including collaborated programs, into later-stage development, prepare regulatory submissions and continue to build-out our global commercial and compliance infrastructure as well as launch our commercial products into additional

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markets, assuming regulatory approvals.

However, we expect that certain expenses will be variable depending on the timing of manufacturing batches, clinical trial enrollment and results, regulatory review of our product candidates and programs, and stock-based compensation expenses due to our determination regarding the probability of vesting for performance-based awards.

(1) Occupancy and all other costs includes facilities, information technology, depreciation and certain departmental expenses.

Selling, general and administrative expenses increased during the year ended December 31, 2024, as compared to the year ended December 31, 2023, primarily due to higher costs associated with marketing investments to promote our TTR therapies and prepare for the potential launch of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy and increased employee compensation expenses.

We expect that research and development expenses combined with selling, general and administrative expenses will increase during 2025, as compared to 2024, as we continue to build out our global commercial and compliance infrastructure, launch our current commercial products into new markets, prepare for future commercial product launches, including the launch of AMVUTTRA in cardiomyopathy, assuming regulatory approvals, advance our product candidates, including collaborated programs, into later-stage development, advance and develop our platform and preclinical pipeline, and prepare regulatory submissions.

However, we expect that certain expenses will be variable depending on the timing of manufacturing batches, clinical trial enrollment and results, regulatory review of our product candidates and programs, and stock-based compensation expenses based on our determinations regarding the probability of vesting for performance-based awards.

Other (Expense) Income

Other (expense) income consists of the following:

Year Ended December 31, 2023 vs 2022 2022 vs 2021

Years Ended December 31,

2024 vs 2023 2023 vs 2022

(In thousands, except percentages) 2024 2023 2022 $ Change % Change $ Change % Change

Interest expense $ (141,858) $ (121,221) $ (155,968) $ (20,637) 17 % $ 34,747 (22) %

Other expense, net

Interest income 121,992 95,561 24,808 26,431 28 % 70,753 285 %

Realized and unrealized (losses) gains on marketable equity securities (16,944) (33,312) 55,695 16,368 (49) % (89,007) (160) %

Other expense, net

Realized and unrealized losses on marketable equity securities (3,022) (16,944) (33,312) 13,922 (82) % 16,368 (49) %

Change in fair value of development derivative liability (170,770) (90,997) (94,659) (79,773) 88 % 3,662 (4) %

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Total $ (200,490) $ (151,342) $ (341,921) $ (49,148) 32 % $ 190,579 (56) %

Total other expense, net increased during the year ended December 31, 2024, as compared to the year ended December 31, 2023, primarily due to increased loss associated with the change in fair value of the development derivative liability as a result of valuation updates driven by the positive topline results for the HELIOS-B clinical trial announced in June 2024, partially offset by increased interest income driven by higher market interest rates on our marketable debt securities.

Benefit from (Provision for) Income Taxes

Benefit from (provision for) income taxes was a follows:

Years Ended December 31,

2024 vs 2023 2023 vs 2022

(In thousands, except percentages)

2024 2023 2022 $ Change % Change $ Change % Change

Benefit from (provision for) income taxes

$ 99,218 $ (6,725) $ (4,163) $ 105,943 * $ (2,562) 62 %

* Indicates the percentage change period over period is greater than 500%.

Total other expense decreased during the year ended December 31, 2023, as compared to the year ended December 31, 2022, primarily due to increased interest income driven by higher market interest rates on our marketable debt securities, decreased interest expense as a result of a more favorable interest rate under the Convertible Senior Notes compared with the interest rate under the credit facility previously held with Blackstone and a $76.6 million loss on the extinguishment of the Blackstone credit agreement recognized in 2022.

We recorded a benefit from income taxes of $99.2 million for the year ended December 31, 2024 and a provision for income taxes of $6.7 million for the year ended December 31, 2023.

The benefit from income taxes for the year ended December 31, 2024 primarily relates to the release of the valuation allowance on our certain Switzerland deferred tax assets, which mainly consist of the tax basis of the intangible assets that were transferred to our wholly-owned Switzerland subsidiary in 2020, 2021 and 2023 and net operating loss carryforwards.

We maintained a full valuation allowance on our U.S.

deferred tax assets as of December 31, 2024.

Liquidity and Capital Resources

The following table summarizes our cash flow activities:

Year Ended December 31, $ Change

Years Ended December 31,

(In thousands) 2024 2023 2022 2024 vs 2023 2023 vs 2022

Net cash provided by (used in):

Net cash (used in) provided by:

Operating activities $ (8,312) $ 104,156 $ (541,274) $ (112,468) $ 645,430

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Operating Activities

Net cash provided by operating activities increased during the year ended December 31, 2023, compared to the year ended December 31, 2022, primarily due to receipt of a $310.0 million up-front payment received in connection with the Roche Collaboration and License Agreement and $100.0 million payment from Regeneron in connection with achieving certain criteria during early clinical development for our CNS program, ALN-APP, in addition to cash receipts from increased product sales, offset by cash disbursements related to working capital payments.

Net cash used in operating activities increased during the year ended December 31, 2024, compared to the year ended December 31, 2023, primarily due to decreased cash received from our collaborators, partially offset by stronger cash receipts from increased product sales.

Investing Activities

Net cash used in investing activities increased during the year ended December 31, 2023, compared to the year ended December 31, 2022, primarily due to net activities related to our marketable debt securities as a result of an increase of cash invested in marketable debt securities.

Net cash used in investing activities decreased during the year ended December 31, 2024, compared to the year ended December 31, 2023, primarily due to the timing of net investments of cash into our marketable debt securities.

Financing Activities

Net cash provided by financing activities decreased during the year ended December 31, 2023, compared to the year ended December 31, 2022, primarily due to greater cash received in 2022, including $136.2 million received from the issuance of convertible debt, net of repayment of the credit facility held with Blackstone and purchase of capped call transactions in September 2022, and greater net proceeds from the issuance of common stock in connection with stock option exercises and other types of equity.

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Net cash provided by financing activities increased during the year ended December 31, 2024, compared to the year ended December 31, 2023, primarily due to increased net proceeds from exercise of stock options.

Additional Capital Requirements

We currently have programs focused on a number of therapeutic areas and, as of December 31, 2023, have received regulatory approval and commercially launched four products.

We currently have programs focused in many therapeutic areas and, as of December 31, 2024, have five marketed products, including one product commercialized by a collaborator.

However, our ongoing development efforts may not be successful and we may not be able to commence sales of any other products or successfully expand the approved indications for our approved products, including AMVUTTRA, in the future.

In addition, we anticipate that we will continue to generate losses as a result of planned expenditures for research and development activities relating to our research platform, our drug development programs, including clinical trial and manufacturing costs, the establishment of late-stage clinical, manufacturing, commercial and compliance capabilities, including global operations, continued management and growth of our intellectual property including our patent portfolio, collaborations and general corporate activities.

Based on our current operating plan, we believe that our cash, cash equivalents and marketable securities as of December 31, 2023, together with the cash we expect to generate from product sales and under our current collaborations, will be sufficient to satisfy our near-term capital and operating needs for at least the next 12 months from the filing of this Annual Report on Form 10-K.

In addition, we may incur additional operating losses as a result of planned expenditures for research and development activities relating to our research platform, our drug development programs, including clinical trial and manufacturing costs, the continued build-out of late-stage clinical, manufacturing, commercial and compliance capabilities, including global operations, continued management and growth of our intellectual property, including our patent portfolio, collaborations and general corporate activities.

Based on our current operating plan, we believe that our cash, cash equivalents and marketable securities as of December 31, 2024 will be sufficient to satisfy our near-term capital and operating needs for at least 12 months from the filing of this Annual Report on Form 10-K.

Recent and expected working and other capital requirements, in addition to the above matters, also include the items described below:

• Amounts related to future lease payments for operating lease obligations at December 31, 2023 totaled $418.0 million, with $43.6 million expected to be paid within the next 12 months.

• Amounts related to future lease payments for operating lease obligations as of December 31, 2024 totaled $384.5 million, with $43.4 million expected to be paid within the next 12 months.

• Cash outflows for capital expenditures were $34.3 million in 2024 and $62.2 million in 2023.

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• Amounts related to future long-term debt total $1.02 billion, of which we do not expect to make payments on principal within the next 12 months.

• Payments associated with the liability related to the sale of future royalties were approximately $21.6 million in 2023, with an estimated $58.2 million to be paid within the next 12 months.

• Amount associated with the achievement of a development milestone payable to Blackstone was $84.5 million as of December 31, 2023, with $21.1 million to be paid within the next 12 months.

• Payments to Blackstone associated with the liability related to the sale of future royalties were $57.0 million in 2024, with an estimated $131.8 million to be paid within the next 12 months.

• Payments associated with an achieved development milestone due to Blackstone were $21.1 million in 2024, with the same amount to be paid within the next 12 months.

Further, we anticipate making an additional $76.5 million of fixed and royalty payments upon regulatory approval of AMVUTTRA for the treatment of ATTR amyloidosis with

cardiomyopathy and the first commercial sale of AMVUTTRA following regulatory approval of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy, respectively, within the next 12 months.

Since we commenced operations in 2002, we have generated significant losses and as of December 31, 2024, we had an accumulated deficit of $7.29 billion.

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We are also subject to potential rebates in connection with our value-based agreements, or VBAs, with certain commercial payors.

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We use the expected value method, which is the sum of probability-weighted amounts in a range of possible consideration amounts, or the most likely amount method, which is the single most likely amount in a range of possible considerations, to estimate variable consideration related to our product revenues.

We use the expected value method to estimate variable consideration for chargebacks, certain rebates, and other incentives and we use the most likely amount method for certain rebates and trade discounts and allowances.

A 10% increase or decrease in these estimates impacts net sales by a corresponding increase or decrease of approximately $13.0 million.

Net Revenues from Collaborations

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Revenue to be recognized is equal to the total transaction price multiplied by the ratio of actual expense incurred divided by total forecasted expense.

A 10% increase or decrease in the transaction price impacts net revenues from collaborators by a corresponding increase or decrease of approximately $43.0 million.

A 10% increase or decrease in the total forecasted costs to be incurred over the period the transfer of goods or services occurs impacts net revenues from collaborators by a corresponding decrease or increase of approximately $39.0 million.

Liability Related to the Sale of Future Royalties

We account for the liability related to the sale of future royalties as a debt financing, as we have significant continuing involvement in the generation of the cash flows.

Interest on the liability related to the sale of future royalties will be recognized using the effective interest rate method over the life of the related royalty stream.

The liability related to the sale of future royalties and the related interest expense are based on our current estimates of future royalties and commercial milestones expected to be paid over the life of the arrangement, which we determine by using third-party forecasts of Leqvio’s global net revenue.

Third-party forecasts are updated periodically as new data is obtained with respect to Leqvio’s global launch progress or as sales information becomes available.

Increases, decreases or a shift in timing of estimated revenues affects the interest rate utilized in the calculation of the liability related to the sale of future royalties.

We account for the liability related to the sale of future royalties as a debt financing.

Interest on the liability related to the sale of future royalties is recognized using the effective interest rate method over the life of the related royalty stream.

We periodically assess the expected payments and to the extent the amount or timing of our future estimated payments is materially different than our previous estimates, we account for any such change by prospectively adjusting the effective interest rate and related non-cash interest expense.

An increase or decrease of 10% to the interest rate would result in an increase or decrease to our liability related to the sale of future royalties of approximately $35.6 million.

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Actual results could vary materially from these estimates.

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Recent Accounting Pronouncements

Please read Note 2 to our consolidated financial statements included in Part II, Item 8, “Financial Statements and Supplementary Data” of this Annual Report on Form 10-K for a description of recent accounting pronouncements.

Please read Note 2, Summary of Significant Accounting Policies, to our consolidated financial statements included in Part II, Item 8, “Financial Statements and Supplementary Data” of this Annual Report on Form 10-K for a description of recent accounting pronouncements.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 7. Management’s Discussion and Analysis