ALNYLAM PHARMACEUTICALS INC

Previous wording

AMVUTTRA is approved in the U.S. for the treatment of hereditary transthyretin-mediated amyloidosis, or hATTR amyloidosis, with polyneuropathy in adults, in the European Union, or EU, and the United Kingdom, or UK, for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, in Japan for the treatment of transthyretin, or TTR, type familial amyloidosis with polyneuropathy, and in multiple additional countries. Regulatory reviews continue in other territories. In June 2024, we reported positive topline results from the HELIOS-B trial of vutrisiran (the non-branded name of AMVUTTRA) in patients with ATTR amyloidosis with cardiomyopathy and announced that we plan to proceed with global regulatory filings later this year seeking approval of AMVUTTRA as a potential treatment for ATTR amyloidosis with cardiomyopathy, including filing a supplemental New Drug Application, or sNDA, with the United States Food and Drug Administration, or the FDA, using a Priority Review Voucher.

Current wording

AMVUTTRA is approved in the U.S. for the treatment of hereditary transthyretin-mediated amyloidosis, or hATTR amyloidosis, with polyneuropathy in adults, in the European Union, or EU, and the United Kingdom, or UK, for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, in Japan for the treatment of transthyretin, or TTR, type familial amyloidosis with polyneuropathy, and in multiple additional countries. Regulatory reviews continue in other territories. In June 2024, we reported positive topline results from the HELIOS-B clinical trial of vutrisiran (the generic name of AMVUTTRA) in patients with ATTR amyloidosis with cardiomyopathy and announced that we plan to proceed with global regulatory filings later this year seeking approval of AMVUTTRA as a potential treatment for ATTR amyloidosis with cardiomyopathy. In August and September 2024, we reported detailed results from the HELIOS-B clinical trial. On October 9, 2024, we announced that we had filed a supplemental New Drug Application, or sNDA, with the United States Food and Drug Administration, or the FDA, using a Priority Review Voucher, and on October 16, 2024, we announced that we had submitted a Type II Variation to the European Medicines Agency, or the EMA.

Previous wording

ONPATTRO is approved by the FDA for the treatment of the polyneuropathy of hATTR amyloidosis in adults and has also been approved in the EU for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, in Japan for the treatment of TTR-type familial amyloidosis with polyneuropathy, and in multiple additional countries. Patisiran (the non-branded name of ONPATTRO) is under regulatory review with the Brazilian Health Regulatory Agency (ANVISA) for the treatment of ATTR amyloidosis with cardiomyopathy.

Current wording

ONPATTRO is approved in the U.S. for the treatment of the polyneuropathy of hATTR amyloidosis in adults and has also been approved in the EU for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, in Japan for the treatment of TTR-type familial amyloidosis with polyneuropathy, and in multiple additional countries. Patisiran (the generic name of ONPATTRO) is under regulatory review with the Brazilian Health Regulatory Agency (ANVISA) for the treatment of ATTR amyloidosis with cardiomyopathy.

Previous wording

GIVLAARI is approved in the U.S. for the treatment of adults with acute hepatic porphyria, or AHP, in the EU for the treatment of AHP in adults and adolescents aged 12 years and older, and in several other countries. Regulatory filings for givosiran (the non-branded drug name for GIVLAARI) in additional territories are pending or planned during 2024 and beyond.

Current wording

GIVLAARI is approved in the U.S. for the treatment of adults with acute hepatic porphyria, or AHP, in the EU for the treatment of AHP in adults and adolescents aged 12 years and older, and in several other countries. Regulatory filings for givosiran (the generic name of GIVLAARI) in additional territories are pending or planned during 2024 and beyond.

Previous wording

OXLUMO is approved in the U.S. for the treatment of primary hyperoxaluria type 1, or PH1, to lower urinary and plasma oxalate levels in pediatric and adult patients, and in the EU and the UK for the treatment of PH1 in all age groups. OXLUMO has also been approved in several other countries and regulatory filings in additional territories are pending or planned during 2024 and beyond.

Current wording

OXLUMO is approved in the U.S. for the treatment of primary hyperoxaluria type 1, or PH1, to lower urinary and plasma oxalate levels in pediatric and adult patients, and in the EU and the UK for the treatment of PH1 in all age groups. OXLUMO has also been approved in several other countries and regulatory filings for lumasiran (the generic name of OXLUMO) in additional territories are pending or planned during 2024 and beyond.

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 European Commission, or 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 2024, Leqvio had been approved in more than 90 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 European Commission, or 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 2024, Leqvio had been registered in more than 100 countries and was commercially available in 78.

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, or AGT, 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 April 2024, we dosed the first patient in our KARDIA-3 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.

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 April 2024, we dosed the first patient in our KARDIA-3 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.

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 and cerebral amyloid angiopathy, or CAA. In 2023, we reported positive interim results from the ongoing single ascending dose part of the Phase 1 clinical trial of mivelsiran in patients with early-onset Alzheimer’s disease. These results establish the first human translation of our proprietary C16-siRNA conjugate platform for CNS delivery and are the first clinical demonstration of gene silencing in the human brain using an RNAi therapeutic. 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 and cerebral amyloid angiopathy, or CAA. In October 2024, we announced positive interim results from the multiple dose portion of the Phase 1 clinical trial of mivelsiran in patients with early-onset Alzheimer’s disease. In July 2024, we initiated dosing in the cAPPRicorn-1 Phase 2 clinical trial of mivelsiran in patients with CAA.

Previous wording

We have additional late-stage investigational programs advancing toward potential commercialization, including fitusiran for the treatment of hemophilia, which is being advanced by our collaborator Genzyme Corporation, a Sanofi Company, or Sanofi, and 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 and paroxysmal nocturnal hemoglobinuria.

Current wording

We have additional late-stage investigational programs advancing toward potential commercialization, including fitusiran for the treatment of hemophilia, which is being advanced by our collaborator Genzyme Corporation, a Sanofi Company, or Sanofi, and for which an NDA has been filed with the FDA with a target action date of March 28, 2025, and 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 and geographic atrophy and as a monotherapy in a Phase 3 clinical trial in paroxysmal nocturnal hemoglobinuria.

Previous wording

We have incurred significant losses since we commenced operations in 2002 and as of June 30, 2024, we had an accumulated deficit of $7.09 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 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. We may 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. 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.

Current wording

We have incurred significant losses since we commenced operations in 2002 and as of September 30, 2024, we had an accumulated deficit of $7.20 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. 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.

Previous wording

Our broad pipeline, including five approved products and multiple late and early-stage investigational RNAi therapeutics, addresses unmet needs in several disease areas, and spans indications in rare, specialty and select prevalent diseases. We describe our commercial and clinical-stage pipeline in more detail below. The investigational therapeutics described below are in various stages of clinical development and the scientific information included about these therapeutics is preliminary and investigative. None of these investigational therapeutics have been approved by the FDA, European Medicines Agency, or EMA, or any other health authority and no conclusions can or should be drawn regarding the safety or efficacy of these investigational therapeutics.

Current wording

Our broad pipeline, including five approved products and multiple late and early-stage investigational RNAi therapeutics, addresses unmet needs in several disease areas, and spans indications in rare, specialty and select prevalent diseases. We describe our commercial and clinical-stage pipeline in more detail below. The investigational therapeutics described below are in various stages of clinical development and the scientific information included about these therapeutics is preliminary and investigative. None of these investigational therapeutics have been approved by the FDA, EMA, or any other health authority and no conclusions can or should be drawn regarding the safety or efficacy of these investigational therapeutics.

Previous wording

During the second quarter of 2024 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 2024 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 ONPATTRO and AMVUTTRA for the second quarter of 2024 of $77.2 million and $230.1 million, respectively.

Current wording

•We achieved global net product revenues for ONPATTRO and AMVUTTRA for the third quarter of 2024 of $50.3 million and $258.6 million, respectively.

Previous wording

•We achieved global net product revenues for GIVLAARI and OXLUMO for the second quarter of 2024 of $62.1 million and $40.6 million, respectively.

Current wording

•We achieved global net product revenues for GIVLAARI and OXLUMO for the third quarter of 2024 of $71.0 million and $40.2 million, respectively.

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. In April 2024, we achieved the development milestone associated with the dosing of the first patient in the KARDIA-3 Phase 2 clinical trial, entitling us to receive a $65.0 million development milestone payment from Roche. In addition, we will be 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 the remaining 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. Upon regulatory approval, 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. 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 the remaining 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. Upon regulatory approval, 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.

Previous wording

Net product revenues increased during the three and six months ended June 30, 2024, as compared to the same periods in 2023, due to strong growth from AMVUTTRA driven by increased patient demand, as well as increased patients on GIVLAARI and OXLUMO therapies.

Current wording

Net product revenues increased during the three and nine months ended September 30, 2024, as compared to the same periods in 2023, due to growth from AMVUTTRA driven by increased patient demand, partially offset by a decrease in ONPATTRO due to patient switches to AMVUTTRA, as well as increased patients on GIVLAARI and OXLUMO therapies.

Previous wording

Royalty revenue increased during the three and six months ended June 30, 2024, as compared to the same period in 2023, due to increased royalties earned from global net sales of Leqvio by our collaborator, Novartis, primarily attributed to their ongoing launch efforts.

Current wording

Royalty revenue increased during the three and nine months ended September 30, 2024, as compared to the same period in 2023, due to increased volume and rate of royalties earned from global net sales of Leqvio by our collaborator, Novartis.

Previous wording

Cost of goods sold as a percentage of net product revenues decreased during the three and six months ended June 30, 2024, as compared to the same period in 2023, primarily due to higher costs in 2023 associated with cancelled manufacturing commitments for ONPATTRO and other adjustments to inventory, for which similar expenses did not occur in 2024.

Current wording

Cost of goods sold as a percentage of net product revenues decreased during the three and nine months ended September 30, 2024, as compared to the same periods in 2023, primarily due to higher costs in 2023 associated with cancelled 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. These decreases were partially offset by higher volume and royalty rates payable on net sales of AMVUTTRA.

Previous wording

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, predominately driven by an increase in volume and rate of royalties payable on net sales of AMVUTTRA.

Current wording

Excluding the one-time events in 2023 associated with cancelled manufacturing commitments and the impairment of ONPATTRO, we expect our cost of goods sold as a percent of net product revenues will increase in 2024, as compared to 2023, driven by the increased volume and rate of royalties payable of net sales on AMVUTTRA

Previous wording

Cost of collaborations and royalties decreased during the three and six months ended June 30, 2024, as compared to the same period in 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.

Current wording

Cost of collaborations and royalties decreased during the three and nine months ended September 30, 2024, as compared to the same periods in 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.

Previous wording

For the three and six months ended June 30, 2024, the increase in research and development expenses, as compared to the same period in 2023, was primarily due to the following:

Current wording

For the three and nine months ended September 30, 2024, the increase in research and development expenses, as compared to the same periods in 2023, was primarily due to the following:

Previous wording

•increased clinical research expenses primarily associated with zilebesiran in the KARDIA-3 clinical trial and mivelsiran in the cAPPRicorn-1 Phase 2 clinical trial due to increased startup activities, respectively;

Current wording

•increased clinical trial expenses primarily associated with zilebesiran in the KARDIA-3 trial and mivelsiran in the cAPPRicorn-1 clinical trial due to increased Phase 2 activities;

Previous wording

•increased costs associated with our preclinical activities as we continue to expand our R&D pipeline;

Current wording

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

Previous wording

•increased employee compensation and related expenses to support our R&D pipeline and development expenses; and

Current wording

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

Previous wording

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

Current wording

•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.

Previous wording

During the three and six months ended June 30, 2024 and 2023, in connection with advancing activities under our collaboration agreements, we incurred research and development expenses, primarily related to external development and clinical services, including the manufacture of clinical product.

Current wording

During the three and nine months ended September 30, 2024 and 2023, in connection with advancing activities under our collaboration agreements, we incurred research and development expenses, primarily related to external development and clinical services, including the manufacture of clinical product.

Previous wording

For the three months ended June 30, 2024, the increase in selling, general and administrative expenses, as compared to the same period in 2023, was primarily due to increased marketing investment associated with promotion of our TTR therapies and increased employee compensation expenses.

Current wording

For the three and nine months ended September 30, 2024, the increase in selling, general and administrative expenses, as compared to the same periods in 2023, was primarily due to increased marketing investment associated with promotion of our TTR therapies and increased employee compensation expenses.

Previous wording

We expect that research and development expenses combined with selling, general and administrative expenses will continue to increase during 2024, as compared to 2023, as we continue to build out our global commercial and compliance infrastructure as well as launch our commercial products into new markets, assuming regulatory approvals, advance our product candidates, including collaboration programs, into later-stage development, advance and develop our platform and pre-clinical 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 due to our determination regarding the probability of vesting for performance-based awards.

Current wording

We expect that research and development expenses combined with selling, general and administrative expenses will continue to increase during 2024, as compared to 2023, 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 for cardiomyopathy, assuming regulatory approvals, advance our product candidates, including collaboration programs, into later-stage development, advance and develop our platform and pre-clinical 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 due to our determination regarding the probability of vesting for performance-based awards.

Previous wording

Total other expense increased during the three and six months ended June 30, 2024, as compared to the same period in 2023, primarily due to increased expense associated with the change in fair value of the development derivative liability triggered by positive topline results for the HELIOS-B clinical trial announced in June 2024, partially offset by an increase in interest income driven by higher market interest rates on our marketable debt securities.

Current wording

Total other expense decreased during the three and nine months ended September 30, 2024, as compared to the same periods in 2023, primarily due to increased interest income driven by higher market interest rates on our marketable debt securities, decreased realized and unrealized losses on our marketable equity securities holdings, partially offset by increased expense associated with the change in fair value of the development derivative liability as a result of valuation updates primarily driven by the positive topline results for the HELIOS-B clinical trial announced in June 2024.

Previous wording

For the three and six months ended June 30, 2024, we recorded a provision for income taxes of $5.7 million and $8.1 million, respectively, which primarily represents tax expense for foreign subsidiaries that are profitable and state taxes.

Current wording

We recorded a provision for income taxes of $2.9 million and $11.0 million for the three and nine months ended September 30, 2024, respectively, and a provision of $3.0 million and $6.5 million for the three and nine months ended September 30, 2023, respectively, which primarily represents tax expense for foreign subsidiaries that are profitable and state taxes.

Previous wording

Net cash provided by operating activities increased during the six months ended June 30, 2024, compared to the same period in 2023, primarily due to stronger cash receipts from increased product sales in addition to decreased cash disbursements related to working capital payments.

Current wording

Net cash provided by operating activities decreased during the nine months ended September 30, 2024, compared to the same period in 2023, primarily due to decreased cash received from our collaborators, partially offset by stronger cash receipts from increased product sales.

Previous wording

Net cash used in investing activities decreased during the six months ended June 30, 2024, compared to the same period in 2023, primarily due to the timing of net investments of cash into our marketable debt securities.

Current wording

Net cash used in investing activities decreased during the nine months ended September 30, 2024, compared to the same period in 2023, primarily due to the timing of net investments of cash into our marketable debt securities.

Previous wording

Net cash provided by financing activities increased during the six months ended June 30, 2024, compared to the same period in 2023, primarily due to increased net proceeds from the issuance of common stock in connection with stock option exercises.

Current wording

Net cash provided by financing activities increased during the nine months ended September 30, 2024, compared to the same period in 2023, primarily due to increased net proceeds from the issuance of common stock in connection with stock option exercises.

Previous wording

We currently have programs focused in many therapeutic areas and, as of June 30, 2024, have received regulatory approval and commercially launched four products. 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 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.

Current wording

We currently have programs focused in many therapeutic areas and, as of September 30, 2024, have received regulatory approval and commercially launched four products. 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 indications for our approved products, including AMVUTTRA, in the future. 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.