Ultragenyx Pharmaceutical Inc

Previous wording

Crysvita is also approved in the U.S. and certain other regions for the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia, or TIO, associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older. There are approximately 2,000 to 4,000 patients with TIO in the developed world. TIO can lead to severe hypophosphatemia, osteomalacia, fractures, fatigue, bone and muscle pain, and muscle weakness.

Current wording

Crysvita is also approved in the U.S. and certain other regions for the treatment of FGF23-related hypophosphatemia in TIO, associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adults and pediatric patients 2 years of age and older. There are approximately 2,000 to 4,000 patients with TIO in the developed world. TIO can lead to severe hypophosphatemia, osteomalacia, fractures, fatigue, bone and muscle pain, and muscle weakness.

Previous wording

Mepsevii is an enzyme replacement therapy administered intravenously, or IV, that replaces the missing enzyme (beta-glucuronidase), developed for the treatment of Mucopolysaccharidosis VII, also known as MPS VII or Sly syndrome. MPS VII is a rare lysosomal storage disease that often leads to multi-organ dysfunction, pervasive skeletal disease, and death. MPS VII is one of the rarest MPS disorders, affecting an estimated 200 patients in the developed world. Mepsevii is approved in the U.S., the EU and certain other regions for the treatment of children and adults with MPS VII.

Current wording

Mepsevii is an enzyme replacement therapy administered intravenously, or IV, that replaces the missing enzyme (beta-glucuronidase), developed for the treatment of MPS VII or Sly syndrome. MPS VII is a rare lysosomal storage disease that often leads to multi-organ dysfunction, pervasive skeletal disease, and death. MPS VII is one of the rarest MPS disorders, affecting an estimated 200 patients in the developed world. Mepsevii is approved in the U.S., the EU and certain other regions for the treatment of children and adults with MPS VII.

Previous wording

Dojolvi is a highly purified, synthetic, 7-carbon fatty acid triglyceride administered orally, designed to provide medium-chain, odd-carbon fatty acids as an energy source and metabolite replacement, developed for people with long-chain fatty acid oxidation disorders, or LC-FAOD. LC-FAOD represents a set of rare metabolic diseases that prevents the conversion of fat into energy and can cause low blood sugar, muscle rupture, and heart and liver disease. Dojolvi is approved in the U.S. and certain other regions as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed LC-FAOD. There are approximately 8,000 to 14,000 patients in the developed world with LC-FAOD.

Current wording

Dojolvi is a highly purified, synthetic, 7-carbon fatty acid triglyceride administered orally, designed to provide medium-chain, odd-carbon fatty acids as an energy source and metabolite replacement, developed for people with LC-FAOD. LC-FAOD represents a set of rare metabolic diseases that prevents the conversion of fat into energy and can cause low blood sugar, muscle rupture, and heart and liver disease. Dojolvi is approved in the U.S. and certain other regions as a source of calories and fatty acids for the treatment of pediatric and adult patients with molecularly confirmed LC-FAOD. There are approximately 8,000 to 14,000 patients in the developed world with LC-FAOD.

Previous wording

Evkeeza is a fully human monoclonal antibody administered by IV, that binds to and blocks the function of angiopoietin-like 3, or ANGPTL3, a protein that plays a key role in lipid metabolism, developed for the treatment of homozygous familial hypercholesterolemia, or HoFH, a rare inherited condition. HoFH occurs when two copies of the genes causing familial hypercholesterolemia are inherited, one from each parent, resulting in dangerously high levels (>400 mg/dL) of low-density lipoprotein-cholesterol, or LDL-C, which is bad cholesterol. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years. Evkeeza is approved in the U.S., where it is marketed by our partner Regeneron Pharmaceuticals, or Regeneron. It is also approved in the European Economic Area, or EEA, as a first-in-class therapy for use together with diet and other LDL-C lowering therapies to treat adults and adolescents aged five years and older with clinical HoFH. There are approximately 3,000 to 5,000 patients with HoFH in the developed world outside of the U.S.

Current wording

Evkeeza is a fully human monoclonal antibody administered by IV, that binds to and blocks the function of angiopoietin-like 3, or ANGPTL3, a protein that plays a key role in lipid metabolism, developed for the treatment of HoFH, a rare inherited condition. HoFH occurs when two copies of the genes causing familial hypercholesterolemia are inherited, one from each parent, resulting in dangerously high levels (>400 mg/dL) of low-density lipoprotein-cholesterol, or LDL-C, which is bad cholesterol. Patients with HoFH are at risk for premature atherosclerotic disease and cardiac events as early as their teenage years. Evkeeza is approved in the U.S., where it is marketed by our partner Regeneron Pharmaceuticals, or Regeneron. It is also approved in the European Economic Area, or EEA, Brazil and Japan as a first-in-class therapy for use together with diet and other LDL-C lowering therapies. In these regions, it is generally approved to treat adults and adolescents aged five years and older with clinical HoFH. There are approximately 3,000 to 5,000 patients with HoFH in the developed world outside of the U.S.

Previous wording

UX143 (setrusumab) is a fully human monoclonal antibody administered by IV that inhibits sclerostin, a protein that acts on a key bone-signaling pathway by inhibiting the activity of bone-forming cells and promoting bone resorption. Setrusumab is being developed for the treatment of OI, or brittle bone disease, which is caused by variants in the COL1A1 or COL1A2 genes, leading to either reduced or abnormal collagen and changes in bone metabolism. There are an estimated 60,000 patients in the developed world affected by OI. UX143 has received orphan drug designation from the U.S. Food and Drug Administration, or FDA, and European Medicines Agency, or EMA, rare pediatric disease designation from the FDA, and was accepted into the EMA’s Priority Medicines program, or PRIME, program. Setrusumab is subject to our collaboration agreement with Mereo and is the lead clinical asset in our bone endocrinology franchise.

Current wording

UX143 (setrusumab) is a fully human monoclonal antibody administered by IV that inhibits sclerostin, a protein that acts on a key bone-signaling pathway by inhibiting the activity of bone-forming cells and promoting bone resorption. Setrusumab is being developed for the treatment of OI, or brittle bone disease, which is caused by variants in the COL1A1 or COL1A2 genes, leading to either reduced or abnormal collagen and changes in bone metabolism. There are an estimated 60,000 patients in the developed world affected by OI. UX143 has received orphan drug designation from the U.S. Food and Drug Administration, or FDA, and European Medicines Agency, or EMA, Rare Pediatric Disease designation and Breakthrough Designation from the FDA, and was accepted into the EMA’s Priority Medicines program, or PRIME, program. Setrusumab is subject to our collaboration agreement with Mereo and is the lead clinical asset in our bone endocrinology franchise.

Previous wording

GTX-102 is an antisense oligonucleotide, or ASO, administered by intrathecal injection (IT) that inhibits expression of the paternal UBE3A antisense. GTX-102 is being developed for the treatment of Angelman syndrome, a debilitating and rare neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. There are an estimated 60,000 patients in the developed world affected by Angelman syndrome. GTX-102 has received Fast Track Designation, Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA and has been accepted into the EMA’s Priority Medicines program, or PRIME, program.

Current wording

GTX-102 is an antisense oligonucleotide, or ASO, administered by intrathecal injection (IT) that inhibits expression of the paternal UBE3A antisense. GTX-102 is being developed for the treatment of Angelman syndrome, a debilitating and rare neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. There are an estimated 60,000 patients in the developed world affected by Angelman syndrome. GTX-102 has received Fast Track Designation, Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA and has been accepted into the EMA’s PRIME program.

Previous wording

UX111 (formerly ABO-102) is an adeno-associated virus 9, or AAV9, gene therapy product candidate, administered by a one-time IV infusion that provides the cross-correcting enzyme that enables the breakdown of Heparan sulfate, or HS. UX111 is being developed for the treatment of patients with Sanfilippo syndrome type A, or MPS IIIA, a rare lysosomal storage disease with no approved treatment, which primarily affects the central nervous system. There are an estimated 3,000 to 5,000 patients in the developed world affected by Sanfilippo syndrome type A. The program was acquired through an exclusive license agreement with

Current wording

UX111 (formerly ABO-102) is an adeno-associated virus 9, or AAV9, gene therapy product candidate, administered by a one-time IV infusion that provides the cross-correcting enzyme that enables the breakdown of Heparan sulfate, or HS. UX111 is being developed for the treatment of patients with Sanfilippo syndrome type A, or MPS IIIA, a rare lysosomal storage disease with no approved treatment, which primarily affects the central nervous system. There are an estimated 3,000 to 5,000 patients in the developed world affected by Sanfilippo syndrome type A. The program was acquired through an exclusive license agreement with Abeona Therapeutics, or Abeona, that was announced in May 2022. The UX111 program has received Regenerative Medicine Advanced Therapy, or RMAT, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations in the U.S., and PRIME and Orphan Medicinal Product designations in the EU.

Previous wording

DTX401 is an adeno-associated virus 8, or AAV8, gene therapy clinical candidate, administered by a one-time IV infusion that is designed to deliver stable expression and activity of G6Pase-α, an essential enzyme in glycogen and glucose metabolism. DTX401 is being developed for the treatment of patients with glycogen storage disease type Ia, or GSDIa, and is the most common genetically inherited glycogen storage disease, with an estimated 6,000 patients in the developed world. A Pediatric Investigation Plan, or PIP, was accepted by the EMA. The DTX401 program has received RMAT, Fast Track, and Orphan Drug designations in the U.S., and PRIME and Orphan Medicinal Product Designations in the EU.

Current wording

DTX401 is an adeno-associated virus 8, or AAV8, gene therapy clinical candidate, administered by a one-time IV infusion that is designed to deliver stable expression and activity of G6Pase-α, an essential enzyme in glycogen and glucose metabolism. DTX401 is being developed for the treatment of patients with GSDIa, and is the most common genetically inherited glycogen storage disease, with an estimated 6,000 patients in the developed world. A Pediatric Investigation Plan, or PIP, was accepted by the EMA. The DTX401 program has received Rare Pediatric Disease, RMAT, Fast Track, and Orphan Drug designations in the U.S., and PRIME and Orphan Medicinal Product Designations in the EU.

Previous wording

DTX301 is an AAV8 gene therapy product candidate, administered by a one-time IV infusion that is designed to deliver stable expression and activity of the ornithine transcarbamylase, or OTC, gene. DTX301 is being developed for the treatment of patients with OTC deficiency, which is the most common urea cycle disorder, and there are approximately 10,000 patients in the developed world with OTC deficiency, of which we estimate approximately 80% are classified as late-onset, our target population. DTX301 has received Orphan Drug Designation in both the U.S. and in the EU and Fast Track Designation in the U.S.

Current wording

DTX301 is an AAV8 gene therapy product candidate, administered by a one-time IV infusion that is designed to deliver stable expression and activity of the OTC, gene. DTX301 is being developed for the treatment of patients with OTC deficiency, which is the most common urea cycle disorder, and there are approximately 10,000 patients in the developed world with OTC deficiency, of which we estimate approximately 80% are classified as late-onset, our target population. DTX301 has received Orphan Drug Designation in both the U.S. and in the EU and Fast Track Designation in the U.S.

Previous wording

Dojolvi for the treatment of LC-FAOD

Current wording

Dojolvi (triheptanoin) for the treatment of LC-FAOD

Previous wording

UX143 (setrusumab) for the treatment of Osteogenesis Imperfecta, or OI

Current wording

UX143 (setrusumab) for the treatment of OI

Previous wording

In July 2024, we announced the completion of a successful End of Phase 2 meeting the FDA supporting our Phase 3 study plans for GTX-102. The pivotal Aspire Phase 3 study will be a global, randomized, double-blind, sham-controlled trial and will include a 48-week primary efficacy analysis period enrolling approximately 120 patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score. It will also include the key secondary endpoint of the Multi-domain Responder Index (MDRI) across all five domains of cognition, receptive communication, behavior, gross motor function, and sleep. Individual secondary endpoints were also discussed and aligned on with the FDA for the domains of communication, behavior, motor function and sleep. We also discussed with the FDA plans to initiate the Aurora study, an additional, open-label clinical study to evaluate the safety and efficacy of GTX-102 for the treatment of patients with other Angelman syndrome genotypes and in other age groups.

Current wording

As previously announced, in July 2024, we successfully completed an End of Phase 2 meeting with the FDA supporting our Phase 3 study plans for GTX-102. The pivotal Aspire Phase 3 study will be a global, randomized, double-blind, sham-controlled trial and will include a 48-week primary efficacy analysis period enrolling approximately 120 patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score. It will also include the key secondary endpoint of the Multi-domain Responder Index, or MDRI, across all five domains of cognition, receptive communication, behavior, gross motor function, and sleep. Individual secondary endpoints were also discussed and aligned on with the FDA for the domains of communication, behavior, motor function and sleep. We also discussed with the FDA plans to initiate the Aurora study, an additional, open-label clinical study to evaluate the safety and efficacy of GTX-102 for the treatment of patients with other Angelman syndrome genotypes and in other age groups.

Previous wording

DTX401 for the treatment of Glycogen Storage Disease Type Ia, or GSDIA

Current wording

DTX401 for the treatment of GSDIA

Previous wording

In May 2024 we announced positive topline results from our Phase 3 GlucoGene study for the treatment of patients aged eight years and older. The study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. The mean percent reduction was 41.3% in the DTX401 group (n=20) compared with 10.3% in the placebo group (n=24) at Week 48 (p<0.0001). Across patients treated with DTX401, the mean reduction in cornstarch continued to decline over the 48-week period. In the treatment group, all patients achieved a reduction in cornstarch, with 68% achieving ≥30% reduction and 37% achieving ≥50% reduction compared to the placebo group, which achieved the same reductions in 13% and 4% of patients, respectively, at Week 48. The study also successfully met key secondary endpoints of reduction in the number of cornstarch doses per day and maintenance of glucose control at Week 48.

Current wording

In May 2024, we announced positive topline results from our Phase 3 GlucoGene study for the treatment of patients aged eight years and older. The study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48.

Previous wording

Full 48 Week data from the Phase 3 study will be presented at a scientific conference later this year. These results will be discussed with regulatory authorities to support a marketing application in 2025.

Current wording

These results will be discussed with regulatory authorities to support submitting a marketing application in mid-2025.

Previous wording

We are currently randomizing and dosing patients in our 64-week Phase 3 study of DTX301. The patients in the study will be randomized 1:1 to DTX301 (1.7 x 10^13 GC/kg dose) or placebo. We plan to enroll approximately 50 patients 12 years of age and older. The co-primary endpoints are the percentage of patients who achieve a response, as measured by discontinuation or reduction in baseline disease management, and the 24-hour plasma ammonia levels. We expect to complete enrollment for the Phase 3 study in the second half of 2024.

Current wording

We are currently randomizing and dosing patients in our 64-week Phase 3 study of DTX301. The patients in the study will be randomized 1:1 to DTX301 (1.7 x 10^13 GC/kg dose) or placebo. We plan to enroll up to 50 patients 12 years of age and older. The co-primary endpoints are the percentage of patients who achieve a response, as measured by discontinuation or reduction in baseline disease management, and the 24-hour plasma ammonia levels. We expect to complete enrollment for the Phase 3 study around the end of 2024.

Previous wording

We have incurred net losses in each year since inception. Our net loss was $131.6 million and $302.3 million for the three and six months ended June 30, 2024, respectively, and $159.8 million and $323.8 million for the three and six months ended June 30, 2023, respectively. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from selling, general and administrative costs associated with our operations.

Current wording

We have incurred net losses in each year since inception. Our net loss was $133.5 million and $435.8 million for the three and nine months ended September 30, 2024, respectively, and $159.6 million and $483.4 million for the three and nine months ended September 30, 2023, respectively. Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from selling, general and administrative costs associated with our operations.

Previous wording

Our total revenues were $147.0 million and $255.9 million for the three and six months ended June 30, 2024, respectively, and $108.3 million and $208.8 million for the three and six months ended June 30, 2023, respectively. The increase in revenue was largely driven by increases in demand for our approved products.

Current wording

Our total revenues were $139.5 million and $395.4 million for the three and nine months ended September 30, 2024, respectively, and $98.1 million and $306.9 million for the three and nine months ended September 30, 2023, respectively. The increase in revenue was largely driven by increases in demand for our approved products.

Previous wording

As of June 30, 2024, we had $874.5 million in available cash, cash equivalents, and marketable debt securities.

Current wording

As of September 30, 2024, we had $824.7 million in available cash, cash equivalents, and marketable debt securities.

Previous wording

Our management’s discussion and analysis of our financial condition and results of operations is based on our Condensed Consolidated Financial Statements, which have been prepared in accordance with U.S. generally accepted accounting principles. The preparation of these Condensed Consolidated Financial Statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. There have been no material changes in our critical accounting policies during the three and six months ended June 30, 2024, as compared to those disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations — Critical Accounting Policies and Significant Judgments and Estimates” in our Annual Report.

Current wording

Our management’s discussion and analysis of our financial condition and results of operations is based on our Condensed Consolidated Financial Statements, which have been prepared in accordance with U.S. generally accepted accounting principles. The preparation of these Condensed Consolidated Financial Statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses incurred during the reporting periods. Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. There have been no material changes in our critical accounting policies during the three and nine months ended September 30, 2024, as compared to those disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations — Critical Accounting Policies and Significant Judgments and Estimates” in our Annual Report.

Previous wording

Comparison of the three and six months ended June 30, 2024 to the three and six months ended June 30, 2023:

Current wording

Comparison of the three and nine months ended September 30, 2024 to the three and nine months ended September 30, 2023:

Previous wording

Our product sales increased by $31.6 million and $49.9 million for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023. The increases are primarily due to an increase in demand for Crysvita in Latin America resulting from an increase in the number of patients on therapy, launch of Evkeeza in Japan and several markets in Europe, Middle East and Africa territories, or EMEA, and continued increase in demand for our other approved products.

Current wording

Our product sales increased by $34.9 million and $84.8 million for the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023. The increases are primarily due to an increase in demand for Crysvita in Latin America resulting from an increase in the number of patients on therapy, launch of Evkeeza in Japan and several markets in Europe, Middle East and Africa territories, or EMEA, and continued increase in demand for our other approved products.

Previous wording

Our Crysvita royalty revenue and Crysvita collaboration revenue in the Profit-Share Territory increased by a net $7.1 million and decreased by a net $1.4 million for the three and six months ended June 30, 2024, respectively, as compared to the same periods in 2023. The increase for the three months ended June 30, 2024 primarily reflects the continuing increase in demand for Crysvita due to an increase in the number of patients on therapy. We transitioned commercial responsibilities to KKC in the Profit-Share Territory in April 2023. Post-transition, we recognize our revenue share for Crysvita sales in the Profit-Share Territory as royalty revenue, which was recorded as collaboration revenue prior to the transition. The royalty is calculated using annual revenue tiers ranging from the mid 20% up to 30%. We expect for the year ended 2024, our Crysvita annual tiered royalty revenue for North America will average at the upper end of the range.

Current wording

Our Crysvita royalty revenue and Crysvita collaboration revenue in the Profit-Share Territory increased by a net $6.5 million and $5.2 million for the three and nine months ended September 30, 2024, respectively, as compared to the same periods in 2023. The increases primarily reflect the continuing increase in demand for Crysvita due to an increase in the number of patients on therapy. We transitioned commercial responsibilities to KKC in the Profit-Share Territory in April 2023. Post-transition, we recognize our revenue share for Crysvita sales in the Profit-Share Territory as royalty revenue, which was recorded as collaboration revenue prior to the transition. The royalty is calculated using annual revenue tiers ranging from the mid 20% up to 30%. We expect for the year ended December 31, 2024, our Crysvita annual tiered royalty revenue for North America will average at the upper end of the range.

Previous wording

Our revenue from the Daiichi Sankyo arrangement decreased by $1.5 million for the six months ended June 30, 2024, compared to the same periods in 2023. The decrease was due to the completion of the technology transfer and the technology transfer period as of March 31, 2023.

Current wording

Our revenue from the Daiichi Sankyo arrangement decreased by $1.5 million for the nine months ended September 30, 2024, compared to the same periods in 2023. The decrease was due to the completion of the technology transfer and the technology transfer period as of March 31, 2023.

Previous wording

Cost of sales increased by $11.4 million and $16.6 million for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023. The increases in cost of sales were due to an increase in demand for our approved products, primarily Crysvita in Latin America and Evkeeza in Japan and several markets in EMEA.

Current wording

Cost of sales increased by $10.0 million and $26.7 million for the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023. The increases in cost of sales were due to an increase in demand for our approved products, primarily Crysvita in Latin America and Evkeeza in Japan and several markets in EMEA.

Previous wording

Total research and development expenses decreased by $3.4 million and increased by $9.3 million for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023. The change in research and development expenses was primarily due to:

Current wording

Total research and development expenses increased by $12.9 million and $22.2 million for the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023. The increase in research and development expenses was primarily due to:

Previous wording

for gene therapy programs, increases of $6.4 million and $20.6 million for the three and six months ended June 30, 2024, respectively, primarily related to continued clinical progress of the DTX301, DTX401, UX701 and UX111 programs and associated internal and external manufacturing costs related to the transition of certain programs to in-house manufacturing;

Current wording

for gene therapy programs, increases of $9.0 million and $29.6 million for the three and nine months ended September 30, 2024, respectively, primarily related to continued clinical progress of the programs and associated internal and external manufacturing costs related to the transition of certain programs to in-house manufacturing;

Previous wording

for biologic and nucleic acid programs, increases of $10.2 million and $15.2 million for the three and six months ended June 30, 2024, respectively, primarily related to the continued clinical progress of the UX143 and GTX102 programs and associated clinical development and manufacturing expenses, partially offset by a reduction in development expense on UX053 for the treatment of Glycogen Storage Disease Type III due to a greater focus on our other late-stage and larger indication clinical programs;

Current wording

for biologic and nucleic acid programs, increases of $11.4 million and $26.6 million for the three and nine months ended September 30, 2024, respectively, primarily related to the continued clinical progress of the UX143 and GTX102 programs and associated clinical development and manufacturing expenses, partially offset by a reduction in development expense on UX053 for the treatment of Glycogen Storage Disease Type III due to a greater focus on our other late-stage and larger indication clinical programs;

Previous wording

for translational research, decreases of $5.8 million and $10.5 million for the three and six months ended June 30, 2024, respectively, primarily related to decreases in manufacturing and headcount expense for IND-stage projects;

Current wording

for translational research, decreases of $4.8 million and $15.3 million for the three and nine months ended September 30, 2024, respectively, primarily related to decreases in manufacturing and headcount expense for IND-stage projects;

Previous wording

for upfront license, acquisition, and milestone fees, a decrease of $9.0 million for the three and six months ended June 30, 2024, related to fees for achievement of a clinical enrollment milestone for the UX143 program, which was achieved during the three months ended June 30, 2023;

Current wording

for upfront license, acquisition, and milestone fees, a decrease of $9.0 million for the nine months ended September 30, 2024, related to the fee for achievement of a clinical enrollment milestone for the UX143 program, which was achieved during the nine months ended September 30, 2023;

Previous wording

for approved products, decreases of $8.6 million and $14.5 million for the three and six months ended June 30, 2024, respectively, primarily due to transition of Crysvita commercialization responsibilities in North America to KKC, and reduced reimbursement of Regeneron collaboration expenses associated with pediatric and open label extension trials for Evkeeza;

Current wording

for approved products, decreases of $2.8 million and $17.3 million for the three and nine months ended September 30, 2024, respectively, primarily due to transition of Crysvita commercialization responsibilities in North America to KKC as post-marketing studies and other related research activities ramp down, and reduced reimbursement of Regeneron collaboration expenses associated with pediatric and open label extension trials for Evkeeza;

Previous wording

for infrastructure, increases of $3.0 million and $4.4 million for the three and six months ended June 30, 2024, respectively, primarily related to depreciation of the gene therapy manufacturing facility, depreciation of laboratory-related leasehold improvements and equipment, and IT-related expenses;

Current wording

for infrastructure, a decrease of $0.5 million and an increase of $3.8 million for the three and nine months ended September 30, 2024, respectively, primarily related to depreciation of the gene therapy manufacturing facility, depreciation of laboratory-related leasehold improvements and equipment, and IT-related expenses;

Previous wording

for stock-based compensation, increases of $2.5 million and $5.0 million for the three and six months ended June 30, 2024, respectively, primarily related to higher valuation of stock-based awards granted to employees; and

Current wording

for stock-based compensation, increases of $3.5 million and $8.4 million for the three and nine months ended September 30, 2024, respectively, primarily related to higher valuation of stock-based awards granted to employees; and

Previous wording

for other research and development expenses, decreases of $2.2 million and $1.8 million for the three and six months ended June 30, 2024, respectively, primarily related to decreased staffing and cost efficiencies to support internal manufacturing, and administrative and general support.

Current wording

for other research and development expenses, decreases of $2.8 million and $4.6 million for the three and nine months ended September 30, 2024, respectively, primarily related to decreased staffing and cost efficiencies to support internal manufacturing, and administrative and general support.

Previous wording

Interest income increased by $1.4 million and $4.0 million for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023, primarily due to increases in interest rates.

Current wording

Interest income increased by $4.9 million and $8.8 million for the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023, primarily due to higher marketable debt securities balances.

Previous wording

For the three and six months ended June 30, 2024, respectively, we recorded net decreases in the fair value of our equity investments of $4.0 million and $0.2 million due to unrealized losses on our investment in Solid Biosciences Inc., or Solid, common stock.

Current wording

For the three and nine months ended September 30, 2024, respectively, we recorded net increases in the fair value of our equity investments of $0.7 million and $0.4 million due to unrealized gains on our investment in Solid Biosciences Inc., or Solid, common stock.

Previous wording

The non-cash interest expense on liabilities for sales of future royalties increased by $0.6 million and $0.8 million for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023. To the extent the royalty payments are greater or less than our initial estimates or the timing of such payments is materially different than our original estimates, we prospectively adjust the effective interest rate.

Current wording

The non-cash interest expense on liabilities for sales of future royalties decreased by $2.0 million and $1.2 million for the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023. These decreases were primarily the result of a decrease in overall liability balances as payments have exceeded interest expense incurred. To the extent the royalty payments are greater or less than our initial estimates or the timing of such payments is materially different than our original estimates, we prospectively adjust the effective interest rate.

Previous wording

Other expense decreased by $0.2 million and increased by $1.8 million for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023. These changes were primarily due to fluctuations in foreign exchange rates.

Current wording

Other income increased by $3.8 million and other expense decreased by $2.0 million for the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023. These changes were primarily due to fluctuations to our exposures in foreign exchange rates.

Previous wording

The provision for incomes taxes increased by a nominal amount for the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023.

Current wording

The provision for incomes taxes decreased by a nominal amount for the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023.

Previous wording

As of June 30, 2024, we had $874.5 million in available cash, cash equivalents, and marketable debt securities. We believe that our existing capital resources will be sufficient to fund our projected operating requirements for at least the next twelve months. Our cash, cash equivalents, and marketable debt securities are held in a variety of deposit accounts, interest-bearing accounts, corporate bond securities, commercial paper, U.S. government securities, asset-backed securities, and money market funds. Cash in excess of immediate requirements is invested with a view toward liquidity and capital preservation, and we seek to minimize the potential effects of concentration and credit risk.

Current wording

As of September 30, 2024, we had $824.7 million in available cash, cash equivalents, and marketable debt securities. We believe that our existing capital resources will be sufficient to fund our projected operating requirements for at least the next twelve months. Our cash, cash equivalents, and marketable debt securities are held in a variety of deposit accounts, interest-bearing accounts, corporate bond securities, commercial paper, U.S. government securities, asset-backed securities, and money market funds. Cash in excess of immediate requirements is invested with a view toward liquidity and capital preservation, and we seek to minimize the potential effects of concentration and credit risk.