ALNYLAM PHARMACEUTICALS, INC.
For the period ended Sep 30, 2025. Filed Oct 30, 2025.
View on SEC.govAbout this filing
A company's report for each of its first three quarters. The financial statements are not audited. It shows how the business has moved since the last annual report, and what management says changed.
Sep 30, 2025 · Filed Oct 30, 2025
ALNY$155.94-0.5%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-Q
Period ended 2025-06-30; filed 2025-07-31.
0001178670-25-000090
ITEM 2. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONSCurrent report: 10-Q
Period ended 2025-09-30; filed 2025-10-30.
0001628280-25-047345
ITEM 2. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONSThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 107 previous paragraphs and 127 current paragraphs.
70 unchanged; 30 reworded; 24 added; 5 removed; 2 previous and 3 current paragraphs rearranged.
Tables are not compared: 10 previous and 10 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (24)
Current report
Convertible Senior Notes and Repurchases
Current report
In September 2025, we issued $661.25 million aggregate principal amount of 0.00% Convertible Senior Notes due 2028, or the 2028 Notes. The 2028 Notes will mature on September 15, 2028, unless earlier converted, redeemed or repurchased. The 2028 Notes will not bear regular interest. Before June 15, 2028, holders of 2028 Notes will have the right to convert their 2028 Notes in certain circumstances and during specified periods. From and after June 15, 2028, the 2028 Notes will be convertible at the option of the holders of 2028 Notes at any time prior to the close of business on the trading day immediately preceding the maturity date. We will settle any conversions of 2028 Notes by paying or delivering, as applicable, cash or shares of our common stock, par value $0.01 per share, or Common Stock, or a combination of cash and shares of Common Stock, at our election.
Current report
In connection with the issuance of the 2028 Notes, we paid $35.3 million, including expenses to enter into privately negotiated capped call transactions with certain initial purchasers of the 2028 Notes or their respective affiliates and certain other financial institutions, or capped call transactions. The capped all transactions are expected generally to reduce the potential dilution upon conversion of the 2028 Notes in the event that the market price per share of our Common Stock, as measured under the terms of the capped call transactions, is greater than the strike price of the capped call transactions, which initially corresponds to the conversion price of the 2028 Notes, and is subject to anti-dilution adjustments generally similar to those applicable to the conversion rate of the 2028 Notes. The cap price of the capped call transaction will initially be approximately $837.61 per share, which represents a premium of approximately 75.0% above the U.S. composite volume weighted average price of our Common Stock from 12:30 p.m. through 4:00 p.m. Eastern Daylight Time on September 9, 2025, which was $478.6327 per share, and is subject to certain adjustments under the terms of the capped call transactions.
Current report
Concurrently with the pricing of the 2028 Notes, we entered into privately negotiated transactions, or the note repurchase transactions, with certain holders of our 1.00% Convertible Senior Notes due 2027, or the 2027 Notes, to repurchase for cash approximately $637.8 million aggregate principal amount of the 2027 Notes for a total repurchase cost (including accrued and unpaid interest) of approximately $1,105.8 million.
Current report
Revolving Credit Facility
Current report
In September 2025, we entered into a revolving credit agreement, or the Revolving Credit Agreement, among the lenders party thereto, Bank of America, N.A., as Administrative Agent, or the Agent, and the other parties named therein. The Revolving Credit Agreement provides for a $500.0 million revolving line of credit, or the Revolving Credit Facility, including a $150.0 million letter of credit sublimit. The Revolving Credit Agreement provides that we have the right at any time and from time to time to incur one or more incremental revolving commitments and/or incremental term loans, subject to certain customary conditions and other requirements.
Current report
At our option, and subject to certain conditions, borrowings bear interest at a base rate, a term Secured Overnight Financing Rate, or SOFR, rate or an alternative currency term rate, plus, in each case, an applicable margin based upon our Total Leverage Ratio (as defined in the Revolving Credit Agreement). For borrowings that bear interest at a term SOFR rate, the applicable margin is a per annum amount equal to an amount between 1.50% and 2.50% (depending on our Total Leverage Ratio). Interest is payable quarterly in arrears with respect to borrowings bearing interest at the alternate base rate or on the last day of an interest period, but at least every three months, with respect to borrowings bearing interest at a term SOFR rate or an alternative currency term rate. We are also required to pay on a quarterly basis a commitment fee in a per annum amount equal to an amount between 0.20% to 0.35% (depending on our Total Leverage Ratio) of unused available commitments under the Revolving Credit Facility. We are also obligated to pay the Agent fees customary for revolving credit facilities of this size and type.
Current report
The obligations under the Revolving Credit Agreement are required to be guaranteed by certain of our material domestic subsidiaries and are secured by substantially all of our assets and the assets of such subsidiary guarantors, subject to customary exceptions. The Revolving Credit Agreement contains customary affirmative and negative covenants and conditions to borrowing, as well as customary events of default.
Current report
Revolving loans under the Revolving Credit Agreement may be borrowed, repaid and reborrowed, without premium or penalty (subject to customary breakage costs), until their maturity date under the Revolving Credit Agreement, or the Maturity Date, at which time all amounts borrowed must be repaid. The Maturity Date is currently September 30, 2030, but may be adjusted to an earlier date upon the occurrence of certain events in accordance with the terms of the Revolving Credit Agreement.
Current report
•Reported results from the Phase 2 KARDIA-3 trial and initiated the ZENITH Phase 3 cardiovascular outcomes trial of zilebesiran, an investigational RNAi therapeutic, in patients with hypertension.
Current report
•Initiated a Phase 2 trial of ALN-6400, an investigational RNAi therapeutic targeting plasminogen for bleeding disorders, in patients with hereditary hemorrhagic telangiectasia (HHT).
Current report
•Our partner, Regeneron, announced positive results from the Phase 3 NIMBLE trial of cemdisiran, an investigational RNAi therapeutic, in generalized myasthenia gravis.
Current report
◦Cemdisiran monotherapy, dosed subcutaneously every three months, met the primary and key secondary endpoints, showing a 2.3-point placebo-adjusted improvement in the Myasthenia Gravis Activities of Daily Living total score.
Current report
◦Regeneron is planning a U.S. regulatory submission for cemdisiran monotherapy in the first quarter of 2026, pending discussions with the FDA.
Current report
•recognition of $300.0 million of milestone revenue under our collaboration with Roche in September 2025 associated with the dosing of the first patient in the ZENITH Phase 3 clinical trial of zilebesiran; and
Current report
•increased stock-based compensation expense.
Current report
Total other expense increased during the three and nine months ended September 30, 2025, as compared to the same period in 2024, primarily due to:
Current report
•loss related to convertible debt representing an inducement expense in connection with the partial repurchase of the 2027 Notes in September 2025;
Current report
Benefit from (Provision for) Income Taxes
Current report
On July 4, 2025, President Trump signed H.R. 1, the “One Big Beautiful Bill Act”, or the Act, into law. The legislation includes several changes to federal tax law that are designed to allow for more favorable deductibility of certain business expenses and more favorable rules for determining the limitation on business interest expense. The Act includes certain changes to the U.S. taxation of foreign activity, including changes to foreign tax credits, global intangible low-taxed income, foreign-derived intangible income, and base erosion and anti-abuse tax, among other changes. These changes are generally effective for tax years beginning after December 31, 2025, except for changes related to the immediate expensing of research and development expenditures and the reinstatement of 100% bonus depreciation which were retroactively effective for tax years beginning after December 31, 2024 and January 19, 2025, respectively. The changes that were retroactively enacted were reflected in the income tax provision for the three and nine months ended September 30, 2025 and did not have a material effect on our financial statements.
Current report
Net cash used in (provided by) financing activities increased during the nine months ended September 30, 2025, compared to the same period in 2024, primarily due to $1.10 billion paid for the repurchase of $637.8 million aggregate principal amount of our 2027 Notes, partially offset by $646.4 million of net proceeds from our offering of the 2028 Notes in the aggregate principal amount of $661.3 million, $35.3 million of which were used to pay the cost of the related capped call transactions. Additionally, we collected lower net proceeds from the issuance of common stock in connection with stock option exercises and made higher net payments to Blackstone Life Sciences for the development derivative liability.
Current report
In September 2025, we issued the 2028 Notes in the total aggregate principal amount of $661.3 million. We used the net proceeds from the issuance of the 2028 Notes to pay $35.3 million for the cost of the privately negotiated capped call transactions that we entered into in connection with the pricing of the notes, and the remainder of the net proceeds, together with cash on hand, to repay $637.8 million of the 2027 Notes, as further discussed below. Please refer to Note 8, Convertible Debt and Other Financing, in the “Notes to Condensed Consolidated Financial Statements” in this Quarterly Report on Form 10-Q for further information.
Current report
In September 2025, concurrently with the pricing of the 2028 Notes, we repurchased for cash $637.8 million aggregate principal amount of the outstanding 2027 Notes for a total repurchase cost (including accrued and unpaid interest) of approximately $1.11 billion. We are considering alternatives to repurchase or redeem the remaining $397.2 million aggregate principal amount of 2027 Notes that remain outstanding as of September 30, 2025. Please refer to Note 8, Convertible Debt and Other Financing, in the “Notes to Condensed Consolidated Financial Statements” in this Quarterly Report on Form 10-Q for further information.
Current report
In September 2025, we entered into the Revolving Credit Agreement, which provides for a $500.0 million revolving line of credit, including a $150.0 million sublimit for issuance of letters of credit. The Revolving Credit Agreement matures in September 2030, subject to earlier springing maturity under certain circumstances. The Revolving Credit Agreement contains customary affirmative and negative covenants and conditions to borrowing, as well as customary events of default. In addition, the Revolving Credit Agreement contains financial covenants that require us to maintain a total leverage ratio less than or equal to 3.75:1.00 and an interest coverage ratio greater than or equal to 3.00:1.00, each tested at the end of each fiscal quarter. As of September 30, 2025, we had no borrowings and $17.5 million of letters of credit outstanding under the Revolving Credit Agreement. Please refer to Note 8, Convertible Debt and Other Financing, in the “Notes to Condensed Consolidated Financial Statements” in this Quarterly Report on Form 10-Q for further information.
Removed paragraphs (5)
Previous report
•Achieved approvals of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy in numerous global markets.
Previous report
◦Received regulatory approvals from ANVISA, the EC, the MHRA, and the PMDA.
Previous report
•recognition of $185.0 million of revenue under our Regeneron Collaboration in the six months ended June 30, 2024; and
Previous report
Provision for Income Taxes
Previous report
Net cash provided by financing activities decreased during the six months ended June 30, 2025, compared to the same period in 2024, primarily due to lower net proceeds from the issuance of common stock in connection with stock option exercises, as well as higher net payments to BXLS V Bodyguard – PCP L.P. and BXLS Family Investment Partnership V – ESC L.P. for the development derivative liability.
Reworded paragraphs (30)
Previous wording
Leqvio (inclisiran), our fifth product, is being developed and commercialized by our collaborator Novartis AG, or Novartis, and has received marketing authorization from the EC for the treatment of adults with hypercholesterolemia or mixed dyslipidemia and from the FDA as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia, or HeFH, or clinical atherosclerotic cardiovascular disease, or ASCVD, who require additional lowering of low-density lipoprotein cholesterol, or LDL-C. In July 2023, the FDA approved an expanded indication for Leqvio to include treatment of adults with high LDL-C and who are at increased risk of heart disease. Leqvio has also been approved in China and Japan, and as of the end of June 2025, Leqvio had been registered in more than 106 countries worldwide and was commercially available in 86 countries.
Current wording
Leqvio (inclisiran), our fifth product, is being developed and commercialized by our collaborator Novartis AG, or Novartis, and has received marketing authorization from the EC for the treatment of adults with hypercholesterolemia or mixed dyslipidemia and from the FDA as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia, or HeFH, or clinical atherosclerotic cardiovascular disease, or ASCVD, who require additional lowering of low-density lipoprotein cholesterol, or LDL-C. In July 2023, the FDA approved an expanded indication for Leqvio to include treatment of adults with high LDL-C and who are at increased risk of heart disease. Leqvio has also been approved in China and Japan, and as of the end of September 2025, Leqvio had been registered in more than 107 countries worldwide and was commercially available in 87 countries.
Previous wording
In addition to our marketed products, as part of our Alnylam P 5 x25 strategy, we have multiple drivers of future growth, including the development of transformative medicines to treat prevalent disease. In addition to Leqvio, we are advancing zilebesiran, an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen in development for the treatment of hypertension. In 2023, we entered into a Collaboration and License Agreement, or the Roche Collaboration and License Agreement, with F. Hoffmann-La Roche Ltd. and Genentech, Inc. or, collectively, Roche, pursuant to which we established a worldwide, strategic collaboration for the joint development and commercialization of zilebesiran. In March 2024, we reported positive topline results from our KARDIA-2 clinical trial, which is designed to evaluate the safety and efficacy of zilebesiran administered biannually as a concomitant therapy in patients whose blood pressure is not adequately controlled by a standard of care antihypertensive medication. We expect to report results from our KARDIA-3 Phase 2 clinical trial, which is designed to evaluate the efficacy and safety of zilebesiran as an add-on therapy in adult patients with high cardiovascular risk and uncontrolled hypertension despite treatment with two to four standard of care antihypertensive medications, in the second half of 2025. We expect to initiate a Phase 3 cardiovascular outcomes clinical trial in the second half of 2025 following our reporting of results from the KARDIA-3 Phase 2 clinical trial.
Current wording
In addition to our marketed products, as part of our Alnylam P 5 x25 strategy, we have multiple drivers of future growth, including the development of transformative medicines to treat prevalent disease. In addition to Leqvio, we are advancing zilebesiran, an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen in development for the treatment of hypertension. In 2023, we entered into a Collaboration and License Agreement, or the Roche Collaboration and License Agreement, with F. Hoffmann-La Roche Ltd. and Genentech, Inc. or, collectively, Roche, pursuant to which we established a worldwide, strategic collaboration for the joint development and commercialization of zilebesiran. In March 2024, we reported positive topline results from our KARDIA-2 clinical trial, which is designed to evaluate the safety and efficacy of zilebesiran administered biannually as a concomitant therapy in patients whose blood pressure is not adequately controlled by a standard of care antihypertensive medication. In August 2025, we reported that our KARDIA-3 Phase 2 clinical trial, which was designed to evaluate the efficacy and safety of zilebesiran as an add-on therapy in adult patients with high cardiovascular risk and uncontrolled hypertension despite treatment with two to four standard of care antihypertensive medications, met the objective of informing the design, patient population, and dose for a global Phase 3 cardiovascular outcomes trial. In September 2025, we initiated a Phase 3 cardiovascular outcomes clinical trial, ZENITH (Zileb Esira N Card Iovascular Ou Tcome Study in Hypertension), which is designed to evaluate the potential of zilebesiran to reduce the risk of major adverse cardiovascular events in patients with uncontrolled hypertension on two or more antihypertensives, one being a diuretic.
Previous wording
We are advancing nucresiran (formerly ALN-TTRsc04), an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis. In November 2024, we announced positive results from the ongoing Phase 1 clinical trial of nucresiran in healthy volunteers. These results demonstrated that a single dose of nucresiran at 300 mg or higher resulted in mean reductions of serum TTR of greater than 90% from baseline achieved at Day 15 and were sustained through at least Day 180. We have initiated the TRITON-CM Phase 3 clinical trial of nucresiran in patients with ATTR amyloidosis with cardiomyopathy and expect to initiate the TRITON-PN Phase 3 clinical trial of nucresiran in patients with hATTR polyneuropathy in late 2025.
Current wording
We are advancing nucresiran (formerly ALN-TTRsc04), an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis. In November 2024, we announced positive results from the ongoing Phase 1 clinical trial of nucresiran in healthy volunteers. These results demonstrated that a single dose of nucresiran at 300 mg or higher resulted in mean reductions of serum TTR of greater than 90% from baseline achieved at Day 15 and were sustained through at least Day 180. We have initiated the TRITON-CM Phase 3 clinical trial of nucresiran in patients with ATTR amyloidosis with cardiomyopathy and in October 2025, we announced that initiation is underway in the TRITON-PN Phase 3 clinical trial of nucresiran in patients with hATTR polyneuropathy.
Previous wording
We are also advancing mivelsiran (formerly ALN-APP), an investigational RNAi therapeutic targeting amyloid precursor protein in development for the treatment of Alzheimer’s disease, or AD, and cerebral amyloid angiopathy, or CAA. In July 2025, we presented multiple and single dose data from the Phase 1 clinical trial of mivelsiran in patients with early-onset AD. These data demonstrated that single and multiple doses of mivelsiran were generally well tolerated and demonstrated robust, durable, dose-dependent reductions of soluble amyloid precursor protein beta (sAPPβ) in cerebrospinal fluid. Further lowering of sAPPβ was observed after administration of a second 50 mg dose of mivelsiran. We expect to initiate a Phase 2 clinical trial of mivelsiran in patients with AD in the second half of 2025. In July 2024, we initiated dosing in the cAPPricorn-1 Phase 2 clinical trial of mivelsiran in patients with CAA.
Current wording
We are also advancing mivelsiran (formerly ALN-APP), an investigational RNAi therapeutic targeting amyloid precursor protein in development for the treatment of Alzheimer’s disease, or AD, and cerebral amyloid angiopathy, or CAA. In July 2025, we presented multiple and single dose data from the Phase 1 clinical trial of mivelsiran in patients with early-onset AD. These data demonstrated that single and multiple doses of mivelsiran were generally well tolerated and demonstrated robust, durable, dose-dependent reductions of soluble amyloid precursor protein beta (sAPPβ) in cerebrospinal fluid. Further lowering of sAPPβ was observed after administration of a second 50 mg dose of mivelsiran. In July 2024, we initiated dosing in the cAPPricorn-1 Phase 2 clinical trial of mivelsiran in patients with CAA. We expect to initiate a Phase 2 clinical trial of mivelsiran in patients with AD in the fourth quarter of 2025.
Previous wording
We have additional late-stage investigational programs advancing toward potential commercialization, including cemdisiran for the treatment of complement-mediated diseases, which our collaborator, Regeneron Pharmaceuticals, Inc., or Regeneron, is advancing in combination with pozelimab in Phase 3 clinical trials in myasthenia gravis, geographic atrophy and paroxysmal nocturnal hemoglobinuria.
Current wording
We have additional late-stage investigational programs advancing toward potential commercialization, including cemdisiran for the treatment of complement-mediated diseases, which our collaborator, Regeneron Pharmaceuticals, Inc., or Regeneron, is advancing in combination with pozelimab in Phase 3 clinical trials in myasthenia gravis, geographic atrophy and paroxysmal nocturnal hemoglobinuria. In August 2025, Regeneron announced that cemdisiran monotherapy met the primary and key secondary endpoints from the Phase 3 NIMBLE clinical trial of cemdisiran in generalized myasthenia gravis, and also announced that a U.S. regulatory submission for cemdisiran monotherapy is planned for the first quarter of 2026, pending discussions with the FDA.
Previous wording
We have incurred significant losses since we commenced operations in 2002 and as of June 30, 2025, we had an accumulated deficit of $7.41 billion. 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 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. While we are targeting financial self-sustainability by the end of 2025, we will continue to require significant resources over the next several years as we expand our efforts to discover, develop and commercialize RNAi therapeutics. We anticipate that our operating results will continue to fluctuate for the foreseeable future, and therefore, period-to-period comparisons should not be relied upon as predictive of the results in future periods.
Current wording
We have incurred significant losses since we commenced operations in 2002 and as of September 30, 2025, we had an accumulated deficit of $7.16 billion. 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 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. While we are targeting financial self-sustainability by the end of 2025, we will continue to require significant resources over the next several years as we expand our efforts to discover, develop and commercialize RNAi therapeutics. We anticipate that our operating results will continue to fluctuate for the foreseeable future, and therefore, period-to-period comparisons should not be relied upon as predictive of the results in future periods.
Previous wording
During the second quarter of 2025 and recent period, we reported the following updates from our commercially approved products and our late-stage clinical programs:
Current wording
During the third quarter of 2025 and recent period, we reported the following updates from our commercially approved products and our late-stage clinical programs:
Previous wording
•We achieved global net product revenues for AMVUTTRA and ONPATTRO for the second quarter of 2025 of $492.0 million and $52.5 million, respectively.
Current wording
•We achieved global net product revenues for AMVUTTRA and ONPATTRO for the third quarter of 2025 of $685.3 million and $39.1 million, respectively.
Previous wording
•We achieved global net product revenues for GIVLAARI and OXLUMO for the second quarter of 2025 of $80.8 million and $46.9 million, respectively.
Current wording
•We achieved global net product revenues for GIVLAARI and OXLUMO for the third quarter of 2025 of $73.9 million and $52.8 million, respectively.
Previous wording
•Initiated the TRITON-CM Phase 3 trial of nucresiran in patients with ATTR amyloidosis with cardiomyopathy.
Current wording
•Announced that initiation is underway in the TRITON-PN Phase 3 trial of nucresiran in patients with hATTR-PN.
Previous wording
Roche. In July 2023, we entered into the Roche Collaboration and License Agreement, pursuant to which we and Roche established a worldwide, strategic collaboration for the joint development of pharmaceutical products containing zilebesiran. Under the Roche Collaboration and License Agreement, we granted to Roche (i) co-exclusive rights to develop zilebesiran worldwide and commercialize zilebesiran in the U.S., (ii) exclusive rights to commercialize zilebesiran outside of the U.S., and (iii) non-exclusive rights to manufacture zilebesiran for the development and commercialization of zilebesiran outside of the U.S. Roche made an upfront payment of $310.0 million and in April 2024 we achieved the development milestone associated with the dosing of the first patient in the KARDIA-3 Phase 2 clinical trial and received a $65.0 million development milestone payment from Roche. In addition, we are eligible to receive up to an additional $2.45 billion in contingent payments based on the achievement of specified development, regulatory and sales-based milestones. We are responsible for forty percent (40%), and Roche is responsible for sixty percent (60%), of development costs incurred in the conduct of development activities that support regulatory approval of zilebesiran globally. We and Roche share equally (50/50) all costs incurred in connection with development activities that are conducted to support regulatory approval of zilebesiran in the U.S., and Roche is solely responsible for all costs incurred in the conduct of development activities that primarily support regulatory approval outside the U.S. Roche will be solely responsible for costs incurred in connection with commercialization of zilebesiran outside of the U.S. and will pay us tiered, low double digit royalties based on net sales of zilebesiran on a country-by-country basis outside of the U.S. during the royalty term. We and Roche will share equally (50/50) profits and losses (including commercialization costs) of zilebesiran in the U.S.
Current wording
Roche. In July 2023, we entered into the Roche Collaboration and License Agreement, pursuant to which we and Roche established a worldwide, strategic collaboration for the joint development of pharmaceutical products containing zilebesiran. Under the Roche Collaboration and License Agreement, we granted to Roche (i) co-exclusive rights to develop zilebesiran worldwide and commercialize zilebesiran in the U.S., (ii) exclusive rights to commercialize zilebesiran outside of the U.S., and (iii) non-exclusive rights to manufacture zilebesiran for the development and commercialization of zilebesiran outside of the U.S. Roche made an upfront payment of $310.0 million and in April 2024 we achieved the development milestone associated with the dosing of the first patient in the KARDIA-3 Phase 2 clinical trial and received a $65.0 million development milestone payment from Roche. In September 2025, we achieved the development milestone associated with the dosing of the first patient in our ZENITH Phase 3 cardiovascular outcomes trial and received a $300.0 million development milestone payment from Roche. In addition, we are eligible to receive up to an additional $2.15 billion in contingent payments based on the achievement of specified development, regulatory and sales-based milestones. We are responsible for forty percent (40%), and Roche is responsible for sixty percent (60%), of development costs incurred in the conduct of development activities that support regulatory approval of zilebesiran globally. We and Roche share equally (50/50) all costs incurred in connection with development activities that are conducted to support regulatory approval of zilebesiran in the U.S., and Roche is solely responsible for all costs incurred in the conduct of development activities that primarily support regulatory approval outside the U.S. Roche will be solely responsible for costs incurred in connection with commercialization of zilebesiran outside of the U.S.
Previous wording
Regeneron. In April 2019, we entered into a global, strategic collaboration with Regeneron to discover, develop and commercialize RNAi therapeutics for a broad range of diseases by addressing therapeutic targets expressed in the eye and CNS, in addition to a select number of targets expressed in the liver, which we refer to as the Regeneron Collaboration. The
Current wording
Regeneron. In April 2019, we entered into a global, strategic collaboration with Regeneron to discover, develop and commercialize RNAi therapeutics for a broad range of diseases by addressing therapeutic targets expressed in the eye and CNS, in addition to a select number of targets expressed in the liver, which we refer to as the Regeneron Collaboration. The Regeneron Collaboration is governed by a Master Agreement, referred to as the Regeneron Master Agreement, which became effective in May 2019.
Previous wording
In May 2024, Regeneron notified us of its decision to opt-out of the further co-development of mivelsiran, an investigational RNAi therapeutic in development for the treatment of hereditary CAA and autosomal dominant Alzheimer’s Disease under our co-co collaboration agreement with respect to mivelsiran. As a result of Regeneron’s opt-out, we now have full global development and commercialization rights to mivelsiran in all indications, and we are responsible for all development and commercialization costs of mivelsiran other than Regeneron’s share of the then-current Phase 1 budget. Regeneron will no longer share potential future profits from sales of mivelsiran with us, although we remain subject to certain financial obligations to Regeneron under the mivelsiran co-co collaboration agreement. We continue to advance multiple other programs with Regeneron.
Current wording
In May 2024, Regeneron notified us of its decision to opt-out of the further co-development of mivelsiran, an investigational RNAi therapeutic in development for the treatment of hereditary CAA and autosomal dominant Alzheimer’s Disease under our co-co collaboration agreement with respect to mivelsiran. As a result of Regeneron’s opt-out, we now have full global development and commercialization rights to mivelsiran in all indications, and we are responsible for all development and commercialization costs of mivelsiran other than Regeneron’s share of the then-current Phase 1 budget. Regeneron will no longer share any potential future profits from sales of mivelsiran with us, although we remain subject to certain financial obligations to Regeneron under the mivelsiran co-co collaboration agreement. We continue to advance multiple other programs with Regeneron.
Previous wording
Net product revenues increased during the three and six months ended June 30, 2025, as compared to the same period in 2024, primarily due to growth from AMVUTTRA driven by increased patient demand, mainly in patients with ATTR-CM in the U.S., which was partially offset by a decrease in ONPATTRO due to patient switches to AMVUTTRA, and due to growth from an increased number of patients on GIVLAARI and OXLUMO.
Current wording
Net product revenues increased during the three and nine months ended September 30, 2025, as compared to the same period in 2024, primarily due to growth from AMVUTTRA driven by increased patient demand, mainly in patients with ATTR amyloidosis with cardiomyopathy in the U.S., which was partially offset by a decrease in ONPATTRO due to patient switches to AMVUTTRA, and due to growth from an increased number of patients on GIVLAARI and OXLUMO.
Previous wording
Net revenues from collaborations decreased during the three months ended June 30, 2025, as compared to the same period in 2024, primarily driven by recognition of $185.0 million of revenue under our collaboration with Regeneron Pharmaceuticals in the three months ended June 30, 2024, as we modified the collaboration in June 2024 and provided Regeneron with an exclusive license to develop, manufacture and commercialize cemdisiran as a monotherapy. Net revenues from collaborations decreased during the six months ended June 30, 2025, as compared to the same period in 2024, primarily driven by:
Current wording
Net revenues from collaborations increased during the three months ended September 30, 2025, as compared to the same period in 2024, primarily driven by recognition of $300.0 million of milestone revenue under our collaboration with Roche in September 2025 associated with the dosing of the first patient in the ZENITH Phase 3 clinical trial of zilebesiran. Net revenues from collaborations increased during the nine months ended September 30, 2025, as compared to the same period in 2024, primarily driven by:
Previous wording
•recognition of $65.0 million of milestone revenue under our Roche Collaboration in March 2024 associated with the dosing of the first patient in the zilebesiran KARDIA-3 Phase 2 clinical trial.
Current wording
•recognition of $65.0 million of milestone revenue under our collaboration with Roche in March 2024 associated with the dosing of the first patient in the KARDIA-3 Phase 2 clinical trial of zilebesiran.
Previous wording
Royalty revenue increased during the three and six months ended June 30, 2025, as compared to the same period in 2024, due to increased volume and rate of royalties earned from global net sales of Leqvio by our collaborator, Novartis.
Current wording
Royalty revenue increased during the three and nine months ended September 30, 2025, as compared to the same period in 2024, due to increased volume and rate of royalties earned from global net sales of Leqvio by our collaborator, Novartis.
Previous wording
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 and Qfitlia. 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, and royalties earned from global net sales of Qfitlia by our collaborator, Sanofi.
Current wording
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 and Qfitlia.
Previous wording
Cost of goods sold, including cost of goods sold as a percentage of net product revenues, increased during the three and six months ended June 30, 2025, as compared to the same periods in 2024, primarily as a result of increased sales of AMVUTTRA and an associated increase in royalties payable on net sales of AMVUTTRA.
Current wording
Cost of goods sold, including cost of goods sold as a percentage of net product revenues, increased during the three and nine months ended September 30, 2025, as compared to the same periods in 2024, primarily as a result of increased sales of AMVUTTRA and an associated increase in royalties payable on net sales of AMVUTTRA.
Previous wording
Cost of collaborations and royalties decreased during the three and six months ended June 30, 2025, as compared to the same periods in 2024, 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.
Current wording
Cost of collaborations and royalties decreased during the three and nine months ended September 30, 2025, as compared to the same periods in 2024, 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.
Previous wording
Research and development expenses for the three and six months ended June 30, 2025 increased as compared to the same periods in 2024, which was primarily due to:
Current wording
Research and development expenses for the three and nine months ended September 30, 2025 increased as compared to the same periods in 2024, which was primarily due to:
Previous wording
•increased clinical trial expenses associated with startup activities for zilebesiran in the Phase 3 cardiovascular outcomes trial and nucresiran in the TRITON-CM Phase 3 trial in patients with ATTR-CM.
Current wording
•increased clinical trial expenses for the ZENITH Phase 3 trial of zilebesiran and the TRITON-CM Phase 3 trial of nucresiran in patients with ATTR amyloidosis with cardiomyopathy, and
Previous wording
•decreased expenses within other clinical programs, in particular for zilebesiran in the KARDIA-2 Phase 2 clinical trial due to the wind-down of clinical activities.
Current wording
•decreased expenses within other clinical programs, in particular for the KARDIA-1 and KARDIA-2 Phase 2 trials of zilebesiran due to the wind-down of clinical activities.
Previous wording
Selling, general and administrative expenses for the three and six months ended June 30, 2025 increased as compared to the same periods in 2024, primarily due to higher employee compensation costs, including stock-based compensation, and increased marketing investment associated with AMVUTTRA launch in ATTR-CM.
Current wording
Selling, general and administrative expenses for the three and nine months ended September 30, 2025 increased as compared to the same periods in 2024, primarily due to higher employee compensation costs, including stock-based compensation, mainly driven by higher headcount, and increased marketing investment associated with the AMVUTTRA launch in ATTR amyloidosis with cardiomyopathy.
Previous wording
Total other expense decreased during the three months ended June 30, 2025, as compared to the same period in 2024, primarily due to decreased loss associated with the change in fair value of the development derivative liability as a result of valuation updates during the three months ended June 30, 2024 driven by the regulatory approval of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy. Total other expense decreased during the six months ended June 30, 2025, as compared to the same period in 2024, primarily due to increased net realized and unrealized foreign currency transaction gains, which was partially offset by increased interest expense associated with the liability related to the sale of future royalties and increased loss associated with the change in fair value of the development derivative liability.
Current wording
•increased loss associated with the change in fair value of the development derivative liability as a result of valuation updates during the three and nine months ended September 30, 2025 driven by the regulatory approval of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy and higher estimated royalties on net sales of AMVUTTRA due to Blackstone Life Sciences; and
Previous wording
Provision for income taxes was as follows:
Current wording
Benefit from (provision for) income taxes was as follows:
Previous wording
Our provision for income taxes relates to foreign and state income taxes. The provision for income taxes increased during the three and six months ended June 30, 2025, as compared to the same periods in 2024, which primarily relates to foreign income taxes due to income generated in Switzerland, as well as state income taxes in the U.S. We expect to utilize net operating losses in Switzerland to offset taxable income and current taxes resulting in a deferred income tax provision. We continue to maintain a full valuation allowance against our net deferred tax assets in the U.S. and certain deferred tax assets in Switzerland.
Current wording
Our provision for income taxes relates to foreign and state income taxes. During the three months ended September 30, 2025, we recorded a benefit from income taxes primarily related to a reduction in the pre-tax loss in the U.S., partially offset by utilization of deferred tax assets due to income generated in Switzerland. The provision for income taxes increased during the nine months ended September 30, 2025, as compared to the same period in 2024, which primarily relates to foreign income taxes due to income generated in Switzerland, as well as state income taxes in the U.S. We expect to utilize net operating losses in Switzerland to offset taxable income and current taxes resulting in a deferred income tax provision. We continue to maintain a full valuation allowance against our net deferred tax assets in the U.S. and certain deferred tax assets in Switzerland.
Previous wording
Net cash provided by operating activities decreased during the six months ended June 30, 2025, compared to the same period in 2024, primarily due to increased employee compensation and decreased cash received from our collaborators, partially offset by stronger cash receipts from increased product sales.
Current wording
Net cash provided by operating activities increased during the nine months ended September 30, 2025, compared to the same period in 2024, primarily due to stronger cash receipts from increased product sales, partially offset by increased employee compensation and decreased cash received from our collaborators.
Previous wording
Net cash used in investing activities decreased during the six months ended June 30, 2025, compared to the same period in 2024, primarily due to the timing of sales, maturities, and purchases of our marketable securities.
Current wording
Net cash provided by (used in) investing activities increased during the nine months ended September 30, 2025, compared to the same period in 2024, primarily due to the timing of sales, maturities, and purchases of our marketable securities.
Previous wording
Based on our current operating plan, we believe that our cash, cash equivalents and marketable securities as of June 30, 2025, will be sufficient to satisfy our near-term capital and operating needs for at least the next 12 months from the filing date of this Quarterly Report on Form 10-Q. However, due to numerous factors described in more detail under the caption Part II, Item 1A, “Risk Factors” of this Quarterly Report on Form 10-Q, we may require significant additional funds earlier than we currently expect in order to continue to commercialize our approved products, and to develop, conduct clinical trials for, manufacture and, if approved, commercialize additional product candidates.
Current wording
Based on our current operating plan, we believe that our cash, cash equivalents, marketable securities, and available borrowing capacity under the Revolving Credit Agreement as of September 30, 2025, will be sufficient to satisfy our near-term capital and operating needs for at least the next 12 months from the filing date of this Quarterly Report on Form 10-Q. However, due to numerous factors described in more detail under the caption Part II, Item 1A, “Risk Factors” of this Quarterly Report on Form 10-Q, we may require significant additional funds earlier than we currently expect in order to continue to commercialize our approved products, and to develop, conduct clinical trials for, manufacture and, if approved, commercialize additional product candidates.
Rearranged current paragraphs (3)
Current report — wording carried from elsewhere
and will pay us tiered, low double digit royalties based on net sales of zilebesiran on a country-by-country basis outside of the U.S. during the royalty term. We and Roche will share equally (50/50) profits and losses (including commercialization costs) of zilebesiran in the U.S.
Current report — wording carried from elsewhere
•recognition of $185.0 million of revenue under our collaboration with Regeneron, as we modified the collaboration in June 2024 and provided Regeneron with an exclusive license to develop, manufacture and commercialize cemdisiran as a monotherapy; and
Current report — wording carried from elsewhere
•increased interest expense associated with the liability related to the sale of future royalties.
Rearranged previous paragraphs (2)
Previous report — wording carried elsewhere
◦Announced that nucresiran received Fast Track Designation from the FDA’s Division of Cardiology and Nephrology for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin mediated amyloidosis in adults to reduce mortality, cardiovascular hospitalizations, and urgent heart failure visits.
Previous report — wording carried elsewhere
Regeneron Collaboration is governed by a Master Agreement, referred to as the Regeneron Master Agreement, which became effective in May 2019.