What changed in this filing

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Item 1. Business

2025-02-21 compared with 2024-02-20 · 228 added, 213 removed, 580 unchanged (43% of the section changed)

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Our approach centers on advancing our innovative pipeline with multiple late-stage clinical programs targeting rare diseases with significant unmet medical needs.

In February 2023, the U.S.

Food and Drug Administration (FDA) granted accelerated approval to our first development program, FILSPARI® (sparsentan), which is indicated to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression.

Sparsentan is also in late-stage development for focal segmental glomerulosclerosis (FSGS).

IgAN and FSGS are rare kidney disorders that lead to kidney failure.

We are also advancing pegtibatinase, a novel investigational enzyme replacement therapy for the treatment of classical homocystinuria (HCU), a genetic disorder caused by a deficiency in a pivotal enzyme essential to the body.

In December 2023, we initiated the pivotal Phase 3 HARMONY Study to support the potential approval of pegtibatinase as the first disease modifying therapy for HCU.

Our early research efforts include partnering with patient advocacy groups and government researchers to identify potential therapeutics for Alagille syndrome (ALGS), a condition with no approved treatment options.

In September 2024, the U.S.

Food and Drug Administration (the FDA) granted full approval to our lead development program, FILSPARI (sparsentan), which is indicated to slow kidney function decline in adults with primary IgAN who are at risk of disease progression.

IgAN is a rare progressive kidney disease and the most common type of primary glomerulonephritis worldwide.

FILSPARI had previously been granted accelerated approval in February 2023 based on the surrogate marker of proteinuria.

Full approval was based on positive long-term confirmatory results from the PROTECT Study demonstrating that FILSPARI significantly slowed kidney function decline over two years compared to irbesartan.

Sparsentan is also in late-stage development for FSGS.

FSGS is a rare kidney disease and leading cause of kidney failure with no approved treatment options.

In February 2025, we announced that we had completed a Type C meeting with the FDA and that we plan to submit an sNDA around the end of the first quarter of 2025 seeking traditional approval of FILSPARI for FSGS.

We are also advancing pegtibatinase, a novel investigational enzyme replacement therapy for the treatment of HCU, a genetic disorder caused by a deficiency in a pivotal enzyme essential to the body.

W e are conducting a pivotal Phase 3 study to support the potential approval of pegtibatinase as the first disease modifying therapy for HCU.

In addition, we continue to evaluate potential opportunities to expand our pipeline and approved products through licenses and acquisitions of products in areas that will serve rare disease patients with serious unmet medical need and that we believe offer attractive growth characteristics.

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We intend to mitigate risk by employing rigorous decision criteria, favoring therapeutic candidates that have undergone at least some clinical study.

Our decision to acquire rights to a therapeutic candidate also depends on the scientific merits of the available clinical data;

Our decision to acquire rights to a therapeutic candidate also depends on the

scientific merits of the available clinical data;

the identifiable orphan patient population;

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the projected amount of capital required to develop the therapeutic candidate;

and the economic potential of the therapeutic

candidate, should it be commercialized.

and the economic potential of the therapeutic candidate, should it be commercialized.

We believe this strategy minimizes our clinical development risk and allows us to accelerate the development and potential commercialization of current and future therapeutic candidates.

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The following table summarizes the status of our clinical programs, preclinical programs and approved products, each of which is described in further detail below.

1 On February 17, 2023, the FDA granted accelerated approval of FILSPARI® (sparsentan) to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) ≥1.5 gram/gram.

On September 21, 2023, we announced topline two-year confirmatory secondary endpoint results from the pivotal Phase 3 PROTECT Study, as described below.

2 On May 1, 2023, we announced topline primary efficacy results from the pivotal Phase 3 DUPLEX Study, as described below.

1 On September 5, 2024, the FDA granted full approval of FILSPARI® (sparsentan) to slow kidney function decline in adults with primary IgAN who are at risk of disease progression.

FILSPARI had previously been granted accelerated approval in February 2023.

2 On February 11, 2025, we announced that we had completed a Type C meeting with the FDA and that we plan to submit an sNDA around the end of the first quarter of 2025 seeking traditional approval of FILSPARI for FSGS.

3 In September 2024, we voluntarily paused enrollment in the Phase 3 HARMONY Study, as described below.

FILSPARI® (sparsentan)

On February 17, 2023, the FDA granted accelerated approval of FILSPARI® (sparsentan) to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a UPCR ≥1.5 gram/gram.

FILSPARI became commercially available in the U.S.

beginning the week of February 27, 2023, and we are providing a comprehensive patient support program throughout the patient’s treatment journey.

This indication was granted under accelerated approval based on reduction in proteinuria.

The continued approval of FILSPARI may be contingent upon confirmation of a clinical benefit in the Phase 3 PROTECT Study.

As described in more detail below, in September 2023, we announced topline two-year confirmatory secondary endpoint results from the PROTECT Study, and in December 2023, we announced the completion of a successful pre-NDA meeting with the FDA for FILSPARI in IgAN.

Following our regulatory engagement, we plan to submit a supplemental New Drug Application (sNDA) in the first quarter 2024 for conversion of the existing U.S.

accelerated approval of FILSPARI to full approval.

FILSPARI, a once-daily, oral medication is designed to selectively target two critical pathways in the disease progression of IgAN (endothelin 1 and angiotensin-II) and is the first and only non-immunosuppressive therapy approved for the treatment of this condition.

On September 5, 2024, the FDA granted full approval of FILSPARI® (sparsentan) to slow kidney function decline in adults with primary IgAN who are at risk of disease progression.

FILSPARI had previously been granted accelerated approval in February 2023 based on the surrogate marker of proteinuria.

FILSPARI is the only oral, once-daily, non-immunosuppressive medication that directly targets glomerular injury in the kidney by blocking two critical pathways of IgAN disease progression (endothelin-1 and angiotensin II).

The two-year efficacy data contained in the FDA-approved label is a modified intention to treat (ITT) analysis and evaluates data from all patients regardless of treatment discontinuation.

In the final analysis of the 404 randomized patients, FILSPARI significantly reduced the rate of decline in kidney function from baseline to Week 110 compared to irbesartan.

In the ITT analysis included in the label, the mean eGFR slope from baseline to Week 110 was -3.0 mL/min/1.73 m 2 /year for FILSPARI and -4.2 mL/min/1.73 m 2 /year for irbesartan, corresponding to a statistically significant treatment effect of 1.2 mL/ min/1.73 m 2 /year (p=0.0168).

The positive treatment effects on proteinuria compared to the active control irbesartan that were observed at Week 36 were durable out to the two-year measurement period.

Additional results from the PROTECT Study demonstrated the

benefit of FILSPARI on absolute eGFR accrued over time and by Week 110 resulted in a 3.8 mL/min/1.73 m 2 difference in the mean change from baseline between FILSPARI and irbesartan.

Results from the PROTECT Study showed that FILSPARI was well tolerated with a clearly defined safety profile that has been consistent across all clinical trials conducted to date.

FILSPARI is a dual endothelin angiotensin receptor antagonist (DEARA).

Pre-clinical data have shown that blockade of both endothelin type A and angiotensin II type 1 pathways in forms of rare chronic kidney disease, reduces proteinuria, protects podocytes and prevents glomerulosclerosis and

mesangial cell proliferation.

Sparsentan has been granted Orphan Drug Designation for the treatment of IgAN in the U.S.

and the European Economic Area countries (the “EEA”) and FILSPARI has been granted seven years of Orphan Drug Exclusivity in the U.S.

for the reduction of proteinuria in adults with primary IgAN at risk of rapid disease progression.

FILSPARI has been granted seven years of Orphan Drug Exclusivity in the U.S.

(running from the date of accelerated approval) for the reduction of proteinuria in adults with primary IgAN at risk of rapid disease progression, and has been granted a separate seven years of Orphan Drug Exclusivity in the U.S.

(running from the date of full approval) to slow kidney function decline in adults with primary IgAN who are at risk for disease progression, excluding the use provided for in the aforementioned Orphan Drug Exclusivity granted in connection with the accelerated approval.

IgAN is characterized by hematuria, proteinuria, and variable rates of progressive renal failure.

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Most patients are diagnosed between the ages of 16 and 35, with up to 40% progressing to kidney failure within 15 years.

FILSPARI is the first and only non-immunosuppressive therapy approved for this condition.

We estimate approximately 30,000 to 50,000 patients in the United States to be addressable under FILSPARI's accelerated approval indication statement.

Data to support the accelerated approval of FILSPARI was generated from the Phase 3 PROTECT Study, the largest head-to-head interventional study to date in IgAN.

It is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled clinical trial that evaluated the safety and efficacy of 400mg of sparsentan, compared to 300mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite available ACE or ARB therapy, and is currently ongoing in the open label extension phase of the study.

The PROTECT Study protocol provided for an unblinded analysis of at least 280 patients to be performed after 36 weeks of treatment to evaluate the primary efficacy endpoint - the change in proteinuria (UPCR) at week 36 from baseline.

Secondary efficacy endpoints include the rate of change in estimated glomerular filtration rate (eGFR) following the initiation of randomized treatment over 58-week and 110-week periods, as well as the rate of change in eGFR over 52-week and 104-week periods following the first six weeks of randomized treatment in approximately 380 patients.

In August 2021, we announced positive topline interim results from the ongoing Phase 3 PROTECT Study.

The PROTECT Study met its pre-specified interim primary efficacy endpoint with statistical significance.

After 36 weeks of treatment, patients receiving FILSPARI achieved a mean reduction in proteinuria from baseline of 49.8 percent, compared to a mean reduction in proteinuria from baseline of 15.1 percent for irbesartan-treated patients (p<0.0001).

Results from the interim assessment in the PROTECT Study showed that FILSPARI was well tolerated with a clearly defined safety profile that has been consistent across all clinical trials conducted to date.

In PROTECT, at the interim assessment, the most common adverse reactions (≥ 5%) were peripheral edema, hypotension (including orthostatic hypotension), dizziness, hyperkalemia, and anemia.

FILSPARI is available only through a risk evaluation and mitigation strategy (REMS) approved by the FDA.

Per request from the FDA, the efficacy data contained in the FDA-approved label under accelerated approval is a post-hoc sensitivity analysis that evaluates the first 281 randomized patients, a subset of the full trial population.

The mean reduction in proteinuria from baseline in the post-hoc sensitivity analysis is 45% for FILSPARI versus 15% for the active control, irbesartan.

Both the pre-specified and post-hoc sensitivity analyses have demonstrated that FILSPARI achieves a rapid and sustained reduction in proteinuria, with statistically significant and clinically meaningful improvement compared to the active comparator irbesartan.

In September 2023, we announced topline two-year confirmatory secondary endpoint results from the PROTECT Study;

eGFR total and chronic slope are the secondary confirmatory endpoints for the U.S.

and the EU, respectively.

FILSPARI demonstrated long-term kidney function preservation and achieved a clinically meaningful difference in eGFR total and chronic slope versus irbesartan, narrowly missing statistical significance in eGFR total slope while achieving statistical significance in eGFR chronic slope for purposes of regulatory review in the EU.

All topline efficacy endpoints favored FILSPARI as compared to irbesartan.

A preliminary review of the safety results through 110 weeks of treatment indicates FILSPARI was generally well-tolerated and the overall safety profile in the study has been consistent between treatment groups.

In December 2023, we announced the completion of a successful pre-NDA meeting with the FDA for FILSPARI in IgAN.

Following our regulatory engagement, we plan to submit a supplemental New Drug Application (sNDA) in the first quarter of 2024 for conversion of the existing U.S.

accelerated approval of FILSPARI to full approval.

In August 2022, we and Vifor (International) Ltd.

("CSL Vifor"), with whom we entered into a license and collaboration agreement ("License Agreement") in September 2021, announced that the EMA had accepted for review the conditional marketing authorization ("CMA") application of sparsentan for the treatment of IgAN in the EU.

We anticipate an opinion by the Committee for Medicinal Products for Human Use (the "CHMP") in the first quarter of 2024.

FILSPARI is the first non-immunosuppressive therapy approved for IgAN and is the only oral, once-daily, non-immunosuppressive therapy approved for this condition that directly targets glomerular injury in the kidney by blocking two critical pathways of IgAN disease progression (endothelin-1 and angiotensin II).

We estimate more than 70,000 patients in the United States to be addressable under FILSPARI's full approval indication.

Data to support the approval of FILSPARI was generated from the Phase 3 PROTECT Study, the largest head-to-head interventional study to date in IgAN.

It is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled clinical trial that evaluated the safety and efficacy of 400mg of sparsentan, compared to 300mg of irbesartan, in 404 patients ages 18 years and up with IgAN and persistent proteinuria despite available angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB) therapy, and is currently ongoing in the open label extension phase of the study.

FILSPARI is available only through a risk evaluation and mitigation strategy (REMS) approved by the FDA, regarding mandatory birth control for patients of child-bearing potential regarding risk of embryo-fetal toxicity, as has been required for other approved endothelin antagonists, and a REMS for liver monitoring regarding potential risk of hepatotoxicity, as has been required for certain other approved endothelin antagonists.

As part of the liver monitoring REMS, monthly monitoring of each patient is required for the first year the patient is on treatment, and quarterly thereafter.

The Company submitted an sNDA for a potential modification to the frequency of liver monitoring for FILSPARI;

the sNDA has been accepted for review by the FDA and assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 28, 2025.

In April 2024, we and our partner CSL Vifor announced that the European Commission has granted conditional marketing authorization (“CMA”) for FILSPARI (sparsentan) for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥0.75 g/g).

The CMA is granted for all member states of the European Union, as well as in Iceland, Liechtenstein and Norway.

The European Commission's decision follows the positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in February 2024, based on results from the pivotal Phase 3 PROTECT Study of FILSPARI in IgAN.

Under the terms of our license agreement with CSL Vifor, we will be entitled to receive a regulatory milestone payment of $17.5 million upon receipt of full regulatory approval by the European Commission for IgAN, and we anticipate receiving an additional milestone payment upon achievement of market access initiatives in certain countries.

CSL Vifor submitted an application for full regulatory approval in the second quarter of 2024.

The decision on full regulatory approval, if positive, will convert the CMA to a standard Marketing Authorization (MA).

FILSPARI became commercially available in Europe under the CMA in August 2024, with an initial launch in Germany and Austria.

In October 2024, we and CSL Vifor announced that Swissmedic has granted temporary marketing authorization for FILSPARI for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥0.75 g/g).

In November 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) approved FILSPARI in the United Kingdom.

In January 2024, we announced our entry into an exclusive licensing agreement with Renalys Pharma, Inc.

("Renalys"), to bring sparsentan to patients in Japan and other countries in Asia, for the treatment of IgAN.

(Renalys), to bring sparsentan, for the treatment of IgAN, to patients in Japan and other countries in Asia.

Renalys will hold regional rights to sparsentan for Japan, South Korea, Taiwan, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand, and Vietnam.

Following successful meetings with the Pharmaceuticals and Medical Devices Agency (PMDA) in 2023, Renalys plans to initiate an open label registrational study of sparsentan in Japan in the second quarter of 2024 to support potential approval of sparsentan in Japan.

Following successful meetings with the Pharmaceuticals and Medical Devices Agency (PMDA) in 2023, in the second quarter of 2024 Renalys initiated an open label registration study of sparsentan in Japan to support potential approval of sparsentan in Japan.

In July 2024, Renalys announced that the first patient was dosed in the study, and in January 2025, Renalys announced achievement of full enrollment in the study.

Results from the urine protein/creatinine ratio (UP/C) endpoint in the study are expected in the second half of 2025 to support a submission for approval to PMDA.

In December 2024, Renalys announced that sparsentan received Orphan Drug Designation from the Japanese Ministry of Health, Labour and Welfare for the indication of primary IgA nephropathy as of November 27, 2024.

Under the terms of the licensing agreement, Renalys will be responsible for development, regulatory matters, and commercialization in the licensed territories.

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After 108 weeks of treatment, sparsentan achieved a mean reduction in proteinuria from baseline of 50%, compared to 32% for irbesartan.

Although the DUPLEX Study did not achieve its two-year primary endpoint with statistical significance over the active control irbesartan, we are encouraged by the results, including the secondary endpoints on proteinuria and topline exploratory endpoints, including renal outcomes, which trended favorably for sparsentan.

Although the DUPLEX Study did not achieve its two-year primary endpoint with statistical significance over the active control irbesartan, we are encouraged by the results, including the pre-specified secondary endpoints on proteinuria and exploratory endpoints, including renal outcomes, which trended favorably for sparsentan.

In addition, a review of the safety results through 108 weeks of treatment indicate sparsentan was generally well-tolerated and the overall safety profile in the study to date was generally consistent between treatment groups.

In December 2023, we announced that we completed our planned Type C meeting with the FDA to discuss previously reported results from the Phase 3 DUPLEX Study of sparsentan in FSGS.

The FDA acknowledged the high unmet need for approved therapies as well as the challenges in studying FSGS but indicated that the two-year results from the Phase 3 DUPLEX Study alone are not sufficient to support an sNDA submission.

In December 2023, we announced that we completed a planned Type C meeting with the FDA to discuss results from the Phase 3 DUPLEX Study of sparsentan in FSGS.

The FDA acknowledged the work being done by the larger nephrology community to better understand proteinuria and eGFR as endpoints in clinical trials of FSGS and indicated a willingness to continue to engage with us on a potential path forward for sparsentan in FSGS following our consideration of additional evidence.

Together with CSL Vifor, we also plan to engage with the EMA to determine the potential for a subsequent variation to the Conditional Marketing Authorization (CMA) of sparsentan for the treatment of FSGS, if the MAA of sparsentan in IgA nephropathy is approved.

Given the high unmet need of FSGS patients, with no medicines currently approved for the condition, and the challenges associated with studying FSGS due to its heterogeneity and other attributes, we are conducting additional analyses of FSGS data and intend to engage with regulators to evaluate potential regulatory pathways for a sparsentan FSGS indication.

If sparsentan receives marketing authorization in any of the licensed territories covered by the exclusive license to CSL Vifor, CSL Vifor will be responsible for all commercialization activities in such licensed territories.

Subsequently, a collaborative international effort referred to as the PARASOL project was initiated with a goal to define the quantitative relationships between short-term changes in biomarkers (proteinuria and GFR) and long-term outcomes in order to support the use of alternative proteinuria-based endpoints as a basis for accelerated and traditional approval.

The PARASOL project is led by several patient advocacy organizations focused on glomerular diseases, with participation from regulators and industry representatives.

The principal finding from PARASOL was that in FSGS, reduction in proteinuria over 24 months is strongly associated with a reduction in the risk of kidney failure, and responder definitions based on thresholds of proteinuria are both biologically plausible and strongly supported by epidemiological data.

Following the recent PARASOL public workshop in which a multi-stakeholder group of rare kidney disease experts aligned around a potential proteinuria-based clinical trial endpoint for FSGS, we scheduled a Type C meeting with the FDA to discuss a potential regulatory pathway for a sparsentan FSGS indication.

In February 2025, we announced that we completed a Type C meeting with the FDA and that we plan to submit an sNDA around the end of the first quarter of 2025 seeking traditional approval of FILSPARI for FSGS.

The sNDA will be based on existing data from the Phase 3 DUPLEX and Phase 2 DUET studies of FILSPARI.

Under the terms of our exclusive license to CSL Vifor, CSL Vifor is responsible for all commercialization activities in its licensed territories.

We remain responsible for the clinical development of sparsentan in the applicable territories.

If sparsentan receives marketing authorization in any of the territories covered by the exclusive license to Renalys, Renalys will be responsible for all development, regulatory matters, and commercialization activities in such licensed territories.

We remain responsible for the clinical development of sparsentan in the applicable territories and we will retain all rights to sparsentan in the United States and rest of world outside of the territories licensed to CSL Vifor and Renalys, provided that CSL Vifor has a right of negotiation to expand the licensed territories into Canada, China, Brazil and/or Mexico.

We will retain all rights to sparsentan in the United States and rest of world outside of the territories licensed to CSL Vifor and Renalys, provided that CSL Vifor has a right of negotiation to expand the licensed territories into Canada, China, Brazil and/or Mexico.

Pegtibatinase

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Classical HCU is a rare metabolic disorder characterized by elevated levels of plasma homocysteine that can lead to vision, skeletal, circulatory and central nervous system complications.

It is estimated that there are approximately 7,000 to 10,000 people living with HCU globally.

We estimate that there are approximately 7,000 to 10,000 addressable HCU patients globally.

Pegtibatinase has been granted Rare Pediatric Disease, Fast Track and Breakthrough Therapy designations by the FDA, as well as orphan drug designation in the United States and European Union.

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Pegtibatinase demonstrated dose-dependent reductions in total homocysteine (tHcy) during the 12 weeks of treatment, and in the highest dose cohort to date evaluating 1.5 mg/kg of pegtibatinase twice weekly (BIW), treatment with pegtibatinase resulted in rapid and sustained reductions in total homocysteine (tHcy) through 12 weeks of treatment, including a 55.1% mean relative reduction in tHcy from baseline as well as maintenance of tHcy below a clinically meaningful threshold of 100 μmol.

Additionally, in a dose-dependent manner in the study to date, methionine levels were

substantially reduced and cystathionine levels were substantially elevated following treatment with pegtibatinase, suggesting that pegtibatinase acts in a manner similar to the native CBS enzyme.

Additionally, in a dose-dependent manner in the study to date, methionine levels were substantially reduced and cystathionine levels were substantially elevated following treatment with pegtibatinase, suggesting that pegtibatinase acts in a manner similar to the native CBS enzyme.

In May 2023, we announced positive topline results from the sixth cohort of the Phase 1/2 COMPOSE Study, which was initiated to inform and refine formulation work for future development and commercial purposes and to further evaluate the dose response curve for pegtibatinase, and to further inform our pivotal development program to ultimately support potential approval of pegtibatinase for the treatment of HCU.

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The HARMONY Study is a global, randomized, multi-center, double-blind, placebo-controlled Phase 3 clinical trial designed to evaluate the efficacy and safety of pegtibatinase as a novel treatment to reduce total homocysteine (tHcy) levels.

Topline results from the HARMONY Study are expected in 2026.

In the beginning of 2024, the first patients were dosed in the HARMONY Study.

In September 2024, we announced a voluntary pause of enrollment in the Phase 3 HARMONY Study.

The voluntary enrollment pause enables us to work to address necessary process improvements in manufacturing scale-up to support commercial scale manufacturing as well as full enrollment in the HARMONY Study.

Patients currently enrolled in pegtibatinase studies continue to receive study medication from small scale batches which are unaffected by the scale-up process.

Currently enrolled patients will be able to continue on study medication as scheduled for the duration of the trials in which they are participating.

The voluntary enrollment pause was enacted following our determination that the desired drug substance profile was not achieved in the recent scale-up process.

We are making progress on necessary process improvements in manufacturing scale-up and currently anticipate that we should be in position to restart enrollment in the Phase 3 HARMONY Study in 2026.

We acquired pegtibatinase as part of the November 2020 acquisition of Orphan Technologies Limited.

Preclinical Programs:

We are a participant in a Cooperative Research and Development Agreement (CRADA), which forms a multi-stakeholder approach to pool resources with leading experts, and incorporate the patient perspective early in the therapeutic identification and development process.

We are partnering with the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS) and a leading patient advocacy organization, Alagille Syndrome Alliance, aimed at the identification of potential small molecule therapeutics for Alagille syndrome (ALGS).

There are no treatment options currently approved for ALGS.

Preclinical Program:

We are party to a collaboration agreement with PharmaKrysto Limited and their early-stage cystinuria discovery program, whereby we are responsible for funding all research and development expenses for the pre-clinical activities associated with the cystinuria program.

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Recurring stone formation can cause loss of kidney function in addition to substantial pain and loss of productivity associated with renal colic and stone passage.

While a portion of people living with the disease are able to manage symptoms through diet and fluid intake, the prevalence of cystinuria in the US is estimated to be 10,000 to 12,000, indicating that there may be as many as 4,000 to 5,000 affected individuals with cystinuria in the US that would be candidates for Thiola or Thiola EC.

While a portion of people living with the disease are able to manage symptoms through diet and fluid intake, the prevalence of cystinuria in the U.S.

is estimated to be 10,000 to 12,000, indicating that there may be as many as 4,000 to 5,000 affected individuals with cystinuria in the U.S.

that would be candidates for Thiola or Thiola EC.

In June 2019 we announced that the FDA approved 100mg and 300mg tablets of Thiola EC, an enteric-coated formulation of Thiola, to be used for the treatment of cystinuria.

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These generic versions of the original formulation of Thiola have impacted our sales, and these or additional generic versions of either formulation could have a material adverse impact on sales.

During 2023, two generic versions of Thiola EC (100 mg and 300 mg) were approved by the FDA.

Following receipt of paragraph IV certification notices from these manufacturers, we and our licensor Mission Pharmacal entered into agreements with these manufacturers in order to settle disputes around patent validity and infringement, providing for a license entry date of April 1, 2026 of these generic versions of Thiola EC (100mg and 300mg), or earlier under certain circumstances.

On January 30, 2024, the FDA approved an additional generic version of Thiola EC (100mg and 300mg).

Accordingly, Thiola EC is subject to immediate generic competitio n, which could impact our sales of Thiola EC.

As of December 31, 2024, several generic options for the 100mg and 300mg versions of Thiola EC have been approved by the FDA and become available.

Accordingly, Thiola EC is subject to generic competitio n.

Sale of Bile Acid Product Portfolio

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("Mirum Pharmaceuticals" or “Mirum”), pursuant to which Mirum agreed to purchase substantially all of the assets primarily related to our business of development, manufacture (including synthesis, formulation, finishing or packaging) and commercialization of Chenodal and Cholbam (also known as Kolbam, and together with Chenodal, the “Products”), collectively, the "bile acid business".

On August 31, 2023, we consummated the transactions contemplated by the Purchase Agreement (the "Closing").

This transaction was consummated on August 31, 2023.

The pharmaceutical and biotechnology industries are intensely competitive and subject to rapid and significant technological change.

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We expect that competition among products approved for sale will be based on various factors, including product efficacy, safety, reliability, availability, price, reimbursement, patent position, and regulatory exclusivity.

Pegtibatinase

Current treatment options for homocystinuria (HCU) are limited to protein-restricted diet and supplemental use of vitamin B6 and betaine.

According to public sources, Synlogic Inc.

and Ginkgo Bioworks Holdings, Inc.

are developing a microbiome therapy, SYNB1353, for the management of HCU and have completed a Phase 1 study in healthy volunteers.

There are other pre-clinical development programs in HCU that may enter the clinic.

In October 2022, Mission was granted a patent covering the treatment of cystinuria by administering Thiola EC with food (US Patent No.

11,458,104, “the ‘104 patent”) and has listed this patent in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the Orange Book).

Following Mission’s listing of the '104 patent in the Orange Book, and as of December 31, 2023, Mission has received three paragraph IV notice letters from three generic manufacturers notifying Mission that each has filed an ANDA seeking approval of a proposed generic version of Thiola EC (tiopronin) 100 mg and 300 mg oral tablets before expiration of the '104 patent and asserting that the '104 patent is not infringed and/or is invalid, with each such ANDA having been filed prior to the granting and listing of the ‘104 patent.

The ANDAs filed by Par Pharmaceutical Inc.

(Par) and Amneal EU, Limited (Amneal) for a generic version of Thiola EC (100 mg and 300 mg) were approved by the FDA in February and August 2023, respectively.

Under our agreement with Mission, we have the right to enforce the '104 patent.

We and Mission have entered into agreements with each of Par and Amneal in order to settle patent invalidity and infringement disputes related to the '104 patent and providing for a license entry date of April 1, 2026 for their generic versions of Thiola EC (100mg and 300mg), or earlier under certain circumstances.

On January 30, 2024, an ANDA filed by Torrent Pharmaceuticals Limited (Torrent) for a generic version of Thiola EC (100mg and 300mg) was approved by the FDA.

Accordingly, Thiola EC is subject to immediate generic competition.

As of January 31, 2024, two generic versions of the original formulation of THIOLA® (tiopronin) tablets have been approved in the United States.

Availability of either product is subject to the discretion of either ANDA holder (Teva Pharmaceuticals USA Inc.

and Par Pharmaceutical Inc.).

Furthermore, Thiola is subject to further competition from compounded and generic entrants, if any.

Penicillamine agents, including Cuprimine and Depen are FDA approved for the treatment of cystinuria, as well as Wilson’s disease.

Additional generic versions of penicillamine have been approved by the FDA and some have entered the market.

Captopril is not FDA approved for the treatment of cystinuria but has been prescribed for patients with cystinuria.

Advicenne Pharma is developing ADV-7103, a microtablet formulation containing potassium citrate monohydrate and potassium bicarbonate, for the potential oral treatment of cystinuria.

Based on public sources, there are other preclinical assets in development that may enter the clinic for the treatment of cystinuria.

FILSPARI/Sparsentan

FILSPARI is the first and only non-immunosuppressive therapy approved to reduce proteinuria in adults with IgAN at risk of rapid disease progression.

There are currently no non-immunosuppressive pharmacological treatments approved by the European Commission for IgAN or by the FDA or European Commission for the treatment of FSGS.

For IgAN, the traditional standard of care has been renin-angiotensin-aldosterone system (RAAS) blockade with immunosuppression.

FILSPARI (sparsentan) is the first non-immunosuppressive therapy approved for IgAN and is the only oral, once-daily, non-immunosuppressive medication that directly targets glomerular injury in the kidney by blocking two critical pathways of IgAN disease progression (endothelin-1 and angiotensin II).

FILSPARI received accelerated approval in the U.S.

in February 2023 and full approval in September 2024 and is indicated to slow kidney function decline in adults with primary IgAN who are at risk for disease progression.

In April 2024, the European Commission granted conditional marketing authorization (“CMA”) for FILSPARI for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥0.75 g/g).

The IgAN treatment landscape is evolving rapidly.

Historically, traditional standard of care has been renin-angiotensin-aldosterone system (RAAS) blockade with immunosuppression.

RAAS blockade is also commonly used in patients with significant proteinuria or rapidly progressive glomerulonephritis.

In December 2023, the FDA granted full approval for Calliditas’ budesonide delayed release capsules (Tarpeyo) to reduce the loss of kidney function in adults with primary IgAN at risk for disease progression.

The same product was previously granted accelerated approval in December 2021 to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a UPCR ≥1.5 gram/gram.

Calliditas' partner, Everest Medicines, has additionally filed for approval for the same product in other jurisdictions including South Korea, Taiwan, and Singapore.

In July 2022, the European Commission issued a conditional marketing authorization to Calliditas (along with EU/UK licensee, Stada Arzneimittel) for the same product (branded as Kinpeygo) for the treatment of primary IgAN in adults at risk of rapid disease progression with a UPCR ≥1.5 gram/gram.

In September 2023, Calliditas and Stada filed for full marketing authorization of Kinpeygo in the EU.

In the fourth quarter of 2023, Novartis announced Phase 3 data from their IgAN studies with iptacopan (Factor B complement inhibitor) and atrasentan (endothelin receptor antagonist), and we anticipate potential approvals could begin in 2024.

Additionally, Novartis has also announced the commencement of a Phase 3 IgAN study with zigakibart (an anti-APRIL monoclonal antibody (mAb)).

Both atrasentan and zigakibart were obtained by Novartis via the acquisition of Chinook Therapeutics in 2023.

We are aware of three additional Phase 3 IgAN programs that are ongoing and/or enrolling in the United States and Europe.

Roche initiated their Phase 3 study with (licensed via Ionis Pharmaceuticals) sefaxersen (Factor B complement inhibitor) and Vera Therapeutics with atacicept (BAFF / APRIL inhibitor).

Otsuka Corporation started their Phase 3 study in IgAN with sibeprenlimab (anti-APRIL mAb) in 2022.

Based on public sources, Alpine Immune Sciences Inc., Arrowhead Pharmaceuticals, AstraZeneca (with its subsidiary Alexion Pharmaceuticals), BioCity Pharmaceutics Corporation, BioCryst Pharmaceuticals, Calliditas Therapeutics, DiaMedica Therapeutics, Eledon Pharmaceuticals, Everest Medicines, Human Immunology Biosciences Inc., Ionis Pharmaceuticals, Jiangsu HengRui Medicine Corporation, MorphoSys, Novartis (and subsidiaries), Omeros Corporation, Otsuka (Visterra), RemeGen, Roche, Stada Arzneimittel, Takeda Pharmaceuticals, Vera Therapeutics, and Viatris Pharmaceuticals Japan Inc.

have programs in clinical development for the treatment of IgAN.

Some of the listed companies have several assets that are in development for IgAN and some of these programs may no longer be active or may be deprioritized in favor of other indications.

Additionally, there are several pre-clinical, Phase 1, and later-stage programs/assets in development (including those that are academia-sponsored) that may enter the clinic for the treatment of IgAN or related conditions (such as diabetic and non-diabetic chronic disease).

In 2021-2023, there were global regulatory label expansions of two SGLT2 inhibitors, AstraZeneca's Farxiga/Forxiga and Boehringer Ingelheim and Eli Lilly’s Jardiance, in chronic kidney disease, which could potentially be competitive with or complementary to sparsentan for the treatment of IgAN and/or FSGS.

Notably, Travere has and continues to generate combination data with this class of therapies.

In August 2024, Kidney Disease Improving Global Outcomes (“KDIGO”) published draft guidelines for public comment that include updated recommendations for the treatment of IgAN.

The draft KDIGO guidelines recommend FILSPARI as a foundational kidney-targeted therapy for IgAN patients who are at risk of progressive kidney function loss, and advocate for lowering the targeted proteinuria level for all IgAN patients to under 0.5 g/day, or preferably under 0.3 g/day.

The draft KDIGO guidelines suggest that combination treatment should be initiated simultaneously in most cases where patients are at risk of progressive kidney function decline.

FILSPARI is the only oral, once-daily, non-immunosuppressive medication that directly targets glomerular injury in the kidney by blocking two critical pathways of IgAN disease progression:

endothelin-1 and angiotensin II.

This aligns with the draft KDIGO guidelines' emphasis on early diagnosis, aggressive proteinuria reduction, and the use of combination therapies to manage IgAN.

In addition to FILSPARI, other therapies currently available in the IgAN market include RAAS blockade therapies, and IgAN-indicated treatments including Calliditas’ Tarpeyo (budesonide delayed-release capsules), and Novartis’ iptacopan (Fabhalta) (a Factor B complement inhibitor currently approved under accelerated approval).

In addition, interim proteinuria data from Novartis’ Phase 3 IgAN study (ALIGN) with atrasentan (an endothelin receptor antagonist, or ERA) read out in 2024, and the company disclosed that their NDA was submitted to FDA in the second quarter of 2024, and that a potential approval could take place in the first half of 2025.

Based on public sources, the confirmatory portions of the Phase 3 studies of iptacopan and atrasentan are expected to begin reading out in the fourth quarter of 2025 or in 2026.

Additionally, Novartis has an ongoing Phase 3 IgAN study with zigakibart (an anti-APRIL monoclonal antibody (mAb)).

Based on public sources, multiple companies have programs in clinical and/or pre-clinical development for the treatment of IgAN or related conditions, including several Phase 3 IgAN programs that are ongoing and/or enrolling in the United States, Europe, and parts of Asia:

Corporation with sibeprenlimab (anti-APRIL mAb), (2) Roche with sefaxersen (Factor B complement inhibitor) (licensed via Ionis Pharmaceuticals), (3) Vera Therapeutics with atacicept (BAFF / APRIL inhibitor), (4) AstraZeneca with ravulizumab (Ultomiris) (C5 complement inhibitor), and (5) Vertex Pharmaceuticals Inc.

with povetacicept (BAFF / APRIL inhibitor).

RemeGen is reportedly conducting a Phase 3 IgAN study with telitacicept in China only.

In 2025, we are anticipating at least two additional Phase 3 IgAN studies to be initiated, including Biogen’s felzartamab (anti-CD38) and Takeda Pharmaceutical Company’s mezagitamab (anti-CD38).

In October 2024, Otsuka announced that sibeprenlimab (anti-APRIL mAb) met its primary endpoint at the prespecified interim analysis and potentially will submit for accelerated approval in 2025.

In 2021-2023, there were global regulatory label expansions of two SGLT2 inhibitors, AstraZeneca’s Farxiga/Forxiga and Boehringer Ingelheim and Eli Lilly’s Jardiance, in chronic kidney disease, which could potentially be complementary to sparsentan for the treatment of IgAN and/or FSGS.

Additionally, although patients diagnosed with IgAN are not part of the label (nor were they included in the initial pivotal studies), Bayer’s non-steroidal mineralocorticoid receptor antagonist, Kerendia, could be used in patients with diabetic kidney disease and theoretically, those with concurrent IgAN and is currently studied in patients with chronic kidney disease without diabetes.

Finally, there are ERAs (endothelin receptor antagonists) that are developed for CKD and CKD-related conditions which could potentially be used (if approved) in CKD patients without a specific IgAN diagnosis.

In December 2022 and January 2023, Idorsia Pharmaceuticals submitted an application for approval of aprocitentan with FDA and EMA, with potential approvals expected in 2024.

Finally, there are endothelin receptor antagonists, or ERAs, that are developed for chronic kidney disease (CKD) and CKD-related conditions which could potentially be used (if approved) in CKD patients without a specific IgAN diagnosis.

Idorsia Pharmaceuticals’ aprocitentan (branded as Tryvio in the U.S.

and Jeraygo in Europe) was approved for the treatment of resistant hypertension by the FDA and EMA, in March 2024 and June 2024, respectively;

the pivotal study was in patients with resistant hypertension, including those with Stage 3 & 4 CKD.

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Patients with IgAN are not excluded from the study.

For FSGS, the current standard of care includes steroids, ACE/ARBs, calcineurin inhibitors, dialysis, and renal transplant.

Currently, there are no products approved by the FDA or the European Commission for the treatment of FSGS.

The current standard of care for FSGS includes steroids, ACE/ARBs, calcineurin inhibitors, dialysis, and renal transplant.

Moreover, as an adjuvant apheresis device which works to remove lipoproteins from blood, the Liposorber® LA-15 System (Kaneka Pharma America LLC) is FDA-approved for the treatment of adult and pediatric patients with Nephrotic Syndrome associated with primary FSGS when standard options are unsuccessful or post-transplant with FSGS recurrence.

A post-approval study with this device is ongoing.

Based on public sources, Amgen Inc., AstraZeneca / Ionis Pharmaceuticals, Boehringer Ingelheim, Dimerix Bioscience, Maze Therapeutics, Novartis, River 3 Renal Corp., Vertex Pharmaceuticals, and ZyVersa Therapeutics may have programs in clinical development for the treatment of FSGS or related conditions.

Some of these programs may no longer be active or may be deprioritized in favor of other indications.

Dimerix is conducting a Phase 3 study in pediatric and adult FSGS patients with their CCR2 blocker, DMX-200.

Dimerix has indicated that an interim analysis will be made available in the second half of 2025.

Additionally, Vertex Pharmaceuticals is conducting the Phase 3 portion of their Phase 2/3 study in adult and pediatric patients with APOL1-mediated kidney disease, which can include a subset of FSGS patients with known APOL1 mutations (G1/G1, G2/G2, or G1/G2).

Based on public sources, several other companies have programs in clinical and/or pre-clinical development for the treatment of FSGS or related conditions.

Pegtibatinase

Current treatment options for homocystinuria (HCU) are limited to protein-restricted diet and supplemental use of vitamin B6 and betaine.

According to public sources, Syntis Bio, Inc.

has a pre-clinical development program for a microbiome therapy for the management of HCU.

Additionally, in July 2024, Innorna announced that they received FDA’s Rare Pediatric Disease Designation for IN022 (pre-clinical) for the treatment of HCU.

Based on public sources, there are other pre-clinical development programs in HCU that may enter the clinic.

Thiola and Thiola EC (tiopronin)

In May 2021, a generic option for the 100mg version of the original formulation of Thiola (tiopronin tablets) became available and in June 2022, a second option for the 100mg version of the original formulation of Thiola (tiopronin tablets) was approved.

As of December 31, 2024, several generic options for the 100mg and 300mg versions of Thiola EC have been approved by the FDA and become available.

Accordingly, Thiola EC is subject to generic competition.

Thiola also faces potential competition from compounded formulations and additional generic entrants.

In addition, certain penicillamine agents including but not limited to Cuprimine and Depen are FDA approved for the treatment of cystinuria.

Additional generic versions of penicillamine have been approved by the FDA and some have entered the market.

Captopril is not FDA approved for the treatment of cystinuria but has been prescribed for patients with cystinuria.

Advicenne Pharma is developing a microtablet formulation containing potassium citrate monohydrate and potassium bicarbonate, for the potential oral treatment of cystinuria.

Based on public sources, there are other preclinical assets in development that may enter the clinic for the treatment of cystinuria.

Licenses and Royalties

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As consideration for the license, we are required to make substantial payments upon the achievement of certain milestones, totaling up to $114.1 million.

In March 2023, we capitalized a $23.0 million milestone payment to Ligand (and Bristol-Myers Squibb Company ("BMS")) that was triggered upon the accelerated approval of FILSPARI in February 2023.

Pursuant to the Ligand License Agreement, we are obligated to pay to Ligand (and BMS) an escalating royalty between 15% and 17% of net sales of sparsentan, with payments due quarterly.

Through December 31, 2024, we have capitalized $47.2 million for contractual milestones achieved under the Ligand License Agreement, including $5.8 million for the year ended December 31, 2024.

Pursuant to the Ligand License Agreement, we are obligated to pay to Ligand (and Bristol-Myers Squibb Company ("BMS")) an escalating royalty between 15% and 17% of net sales of sparsentan, with payments due quarterly.

We began incurring costs associated with such royalties following the February 2023 approval of FILSPARI (sparsentan).

For the year ended December 31, 2023, the Company capitalized $4.4 million to intangible assets for royalties owed on net sales of FILSPARI.

For the years ended December 31, 2024 and 2023, we capitalized $20.3 million and $4.4 million, respectively, to intangible assets for royalties owed on net sales of FILSPARI.

Under the terms of the license agreement, BMS has a right of first negotiation and Ligand has a right of second negotiation with respect to any license arrangement for a licensed compound, except to the extent such rights may be waived.

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We may terminate the license agreement due to a material uncured breach of the agreement by Ligand.

Thiola License Agreement

Mission License Agreement

In 2014, we entered into a license agreement with Mission Pharmacal, pursuant to which we obtained an exclusive, royalty-bearing license to market, sell and commercialize Thiola (tiopronin) in the United States and Canada, and a non-exclusive license to use know-how relating to Thiola to the extent necessary to market Thiola.

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We cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the future will be commercially useful in protecting our product candidates, discovery programs and processes.

As of December 31, 2023, our patent portfolio for FILSPARI (sparsentan) was comprised of six distinct patent families, one of which is exclusively licensed from Ligand (the “Ligand patent family”).

As of February 1, 2025, our patent portfolio for FILSPARI (sparsentan) was comprised of six distinct patent families, one of which is exclusively licensed from Ligand (the “Ligand patent family”).

The other five patent families are owned by Travere (the "Travere patent families").

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The Ligand patent family is directed to methods of using sparsentan in the treatment of various diseases, including glomerulosclerosis and IgAN.

As of December 31, 2023, this patent family included two US patents (US Patent No.

9,662,312, which we refer to herein as the ‘312 patent, and US Patent No.

9,993,461, which we refer to herein as the ‘461 patent), a pending US application (Application Serial No.

17/951,830, filed September 23, 2022), two European patents (European Patent No.

As of December 31, 2024, this patent family included two U.S.

patents (U.S.

9,662,312, which we refer to herein as the ‘312 patent, and U.S.

9,993,461, which we refer to herein as the ‘461 patent), a pending U.S.

application, 18/797,336, filed August 25, 2024, two European patents (European Patent No.

EP2732818, which we refer to herein as the European ‘818 patent, and European Patent No.

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The ‘461 patent and the European '277 patent each claim both the use of sparsentan for treating glomerulosclerosis and the use of sparsentan for treating IgAN.

We expect the US and foreign patents in this patent family to expire in March 2030.

In November 2020, a third party filed an opposition to the European ‘277 patent and we are vigorously defending the European '277 against the opposition.

and foreign patents in this patent family have a stated expiration date in March 2030, which may potentially be extended in the United States via a pending patent term extension application.

In November 2020, a third party filed an opposition to the European ‘277 patent.

In March 2024, our patent claims were upheld by the European Patent Office Board of Opposition and in May the opponent filed an appeal thereto.

We are continuing to vigorously defend the European '277 against the opposition.

If we were to be unsuccessful in doing so, we would expect to rely on the data and/or marketing exclusivity that may be available in the EU, as described below under “Regulatory Exclusivity.”

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As of December 31, 2024, this patent family was comprised of a granted U.S.

10,864,197, which we refer to herein as the ‘197 patent) and pending patent applications in the US, Australia, Brazil, Canada, China, the European Patent Office, Hong Kong, Japan, Korea, New Zealand and South Africa.

The ‘197 patent claims use of sparsentan for treating Alport syndrome.

10,864,197, which we refer to herein as the ‘197 patent) and pending patent applications in the U.S., Australia, Brazil, Canada, China, the European Patent Office, Hong Kong, Japan, Korea, New Zealand and South Africa.

The ‘197 patent claims use of sparsentan for treating Alport syndrome and has a stated expiration date in October 2037.

The pending patent claims in this patent family are directed at the use of sparsentan for treating FSGS and IgAN.

The second Travere patent family is directed to methods of using sparsentan for treating hearing loss associated with Alport syndrome.

As of December 31, 2024, this patent family was comprised of a granted U.S.

11,207,299) and pending patent applications in the US, Australia Brazil, Canada, China, the European Patent Office, Hong Kong, Israel, Japan, Korea, Mexico, New Zealand and South Africa.

The third Travere patent family is directed to an amorphous form of sparsentan.

As of December 31, 2023, this patent family was comprised of pending patent applications in the United States, Australia, Brazil, Canada, China, the European Patent Office, Hong Kong, India, Israel, Japan, Korea, Mexico, New Zealand, Russia and South Africa.

The fourth Travere patent family is comprised of a pending international patent application related to methods of treating kidney diseases or disorders.

The fifth Travere patent family is comprised of a U.S.

provisional patent application, related to methods of treating a kidney disease or disorder comprising sparsentan, and a SGLT2 inhibitor.

11,207,299) and pending patent applications in the U.S., Australia Brazil, Canada, China, the European Patent Office, Hong Kong, Israel, Japan, Korea, Mexico, New Zealand and South Africa.

The third Travere patent family is comprised of a pending international patent application, related to methods of treating a kidney disease or disorder comprising sparsentan, and a SGLT2 inhibitor.

The fourth Travere patent family is comprised of a pending international patent application, related to methods of treating IgA mediated diseases or disorders comprising sparsentan.

The fifth Travere patent family is comprised of a pending international patent application, related to methods of treating IgA mediated kidney diseases or disorders comprising sparsentan.

The sixth Travere patent family is comprised of a pending provisional patent application directed to additional methods of use of sparsentan for treating FSGS and IgAN.

and some countries outside the U.S.

similarly offer forms of patent term extension or restoration.

For example, Supplementary Protection Certificates are available to extend the life of a European patent up to an additional five years (subject to a 15-year cap from European Medicines Agency (EMA) approval) and in Japan patent terms can be extended up to five years.

We have filed an application for patent term extension of the ‘461 patent, which may be extended under the provisions of the Hatch-Waxman Act.

Patent term extension also may be available in certain foreign jurisdictions upon regulatory approval.

Likewise, it is possible, if sparsentan achieves regulatory approval in the EU and depending upon the date of any such approval, that the term of either the European ‘818 patent or the European '277 patent may be extended in various European countries under the provisions governing Supplementary Protection Certificates (SPCs).

Patent term extensions or Supplemental Protection Certificates (SPCs) also may be available in certain foreign jurisdictions upon regulatory approval.

In the EU, a conditional marketing authorization (“CMA”) for FILSPARI was issued by the European Commission in April 2024 (the ”FILSPARI CMA”).

Because there has been no prior European approval for FILSPARI, we and Vifor are pursuing SPCs throughout the European Economic Area (EEA) based on this FILSPARI CMA.

Likewise, it is possible, if sparsentan achieves regulatory approval elsewhere in the world, depending upon local law and regulation, patent term extensions or SPCs may be pursued in additional jurisdictions.

Pegtibatinase

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The Mission patent family is directed to a new formulation of Thiola, known as Thiola EC.

As of December 31, 2023, this patent family included a granted US patent (US Patent No.

11,458,104, which we refer to herein as the ‘104 patent) and a pending US patent application.

As of December 31, 2024, this patent family included a granted U.S.

11,458,104, which we refer to herein as the ‘104 patent) and a pending U.S.

patent application.

The '104 patent claims a method for treating cystinuria by administering a formulation of tiopronin with food.

Regulatory Exclusivity

If we obtain marketing approval for sparsentan for the treatment of FSGS in the United States or in certain jurisdictions outside of the United States, or for sparsentan for the treatment of IgAN in certain jurisdictions outside of the United States, we may be eligible for regulatory exclusivity for the approved therapy.

If we obtain marketing approval for sparsentan for the treatment of FSGS in the United States or in certain jurisdictions outside of the United States, we may be eligible for regulatory exclusivity for the approved therapy.

For example, in the United States, an FDA-approved therapy may be eligible to receive five years of new chemical entity ("NCE") exclusivity or, for drugs granted an orphan designation by the FDA, seven years of orphan drug exclusivity ("Orphan Drug Exclusivity" or "ODE").

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FILSPARI (sparsentan) received orphan drug designation in the United States and in the European Union for the treatment of IgAN in 2021 and FSGS in 2015.

In the United States, FILSPARI has been granted seven years of Orphan Drug Exclusivity for the reduction of proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a UPCR ≥1.5 gram/gram.

FILSPARI has been granted seven years of Orphan Drug Exclusivity in the U.S.

Thiola does not have regulatory exclusivity in the United States.

Our trademark portfolio includes both Travere-owned and Travere-licensed trademarks and is comprised of various US and foreign registered trademarks and pending trademark applications relating to our company name, our commercial products (FILSPARI, Thiola, and Thiola EC), and sparsentan.

More specifically, as of December 31, 2023, our trademark portfolio included an allowed US trademark application and foreign registered trademark and trademark applications for the mark “Travere Therapeutics”, US and foreign trademark applications and foreign registered trademarks relating to sparsentan, a registered US trademark for the mark “TOTALCARE”, a registered US trademark for the TotalCare logo, and a registered US trademark for a leaves logo.

In addition, under our license agreement with Mission we have an exclusive license to use Mission’s trademarks related to Thiola and Thiola EC, including three registered US trademarks and one registered Canadian trademark for the mark “THIOLA”, and one registered US trademark for the mark "Thiola EC", in the United States and Canada.

Our trademark portfolio includes both Travere-owned and Travere-licensed trademarks and is comprised of various U.S.

and foreign registered trademarks and pending trademark applications relating to our company name, our commercial products (FILSPARI, Thiola, and Thiola EC), and sparsentan.

More specifically, as of December 31, 2024, our trademark portfolio included registered U.S.

and foreign trademarks for the wordmark “Travere Therapeutics” and its logo, registered U.S.

and foreign trademarks relating to FILSPARI (sparsentan), registered U.S.

trademarks for both the wordmark “TOTALCARE”, and its logo, a registered trademark for both the wordmark “TOTAL CARE HUB” and its logo, and a registered trademark for “In Rare for Life”.

In addition, under our license agreement with Mission we have an exclusive license to use Mission’s trademarks related to Thiola and Thiola EC, including three registered U.S.

trademarks and one registered Canadian trademark for the mark “THIOLA”, and one registered U.S.

trademark for the mark "Thiola EC", in the United States and Canada.

Trade Secrets

In addition to patents, we rely on trade secrets and know-how to develop and maintain our competitive position.

We seek to protect our proprietary data and processes, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific

advisors, contractors, and partners.

We seek to protect our proprietary data and processes, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors, and partners.

These agreements are designed to protect our proprietary information.

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Sales, Marketing and Distribution

In 2023, we continued to utilize our specialty sales force to market our FDA-approved products in the US.

In 2024, we continued to utilize our specialty sales force to market our FDA-approved products in the U.S.

Through our deep understanding of patient and healthcare provider needs, we believe we are able to:

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• support access to and reimbursement coverage for our products without significant restrictions;

• minimize the number of patients who discontinue treatment or have low compliance with our products by providing patients with support services and disease education, to the extent and in the manner permitted under applicable laws, to help them utilize our products in a manner consistent with the label and maximize the benefits of treatment;

• support compliant use by providing patients with support services and disease education, to the extent and in the manner permitted under applicable laws, to help them utilize our products in a manner consistent with the label and maximize the benefits of treatment;

• successfully launch new treatment options once approved.

Our US commercial initiatives are designed to support patients living with rare diseases and clinicians treating these patients.

We believe that it is possible to commercialize our products in the United States with a relatively small specialty sales force.

commercial initiatives are designed to support patients living with rare diseases and clinicians treating these patients.

We commercialize our products in the United States with a relatively small specialty sales force.

Nephrologists are the primary call point for FILSPARI.

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Our sales force is differentiated by its high level of experience, averaging more than 20 years in pharmaceutical sales including over five years of experience in rare disease.

Our commercial management and operations team has an average of more than 15 years of pharmaceutical experience focused on specialty and rare disease.

Our commercial management and operations team also has an average of more than 20 years of pharmaceutical experience focused on specialty and rare disease.

Our marketing and patient access teams, supported by third-party agencies with rare disease experience, drive our commercialization and disease awareness efforts in the United States.

Specifically, we implement a variety of industry accepted programs to educate physicians, including direct-to-physician contact by sales representatives, peer-to-peer educational programs, and participation in targeted medical convention programs.

We distribute FILSPARI through three direct to patient pharmacies, and operate Travere TotalCare, pursuant to which we provide our comprehensive patient support services.

We distribute FILSPARI in the United States through two direct to patient pharmacies, and operate Travere TotalCare, pursuant to which we provide our comprehensive patient support services.

This patient support program for FILSPARI in the United States provides services, assistance and resources that help patients understand IgAN, manage the insurance process, fill their prescriptions and initiate treatment.

We distribute our other products through one direct to patient pharmacy, Eversana, who also provides our comprehensive patient support services in the US for Thiola and Thiola EC (i.e., Travere TotalCare).

We distribute our other products, Thiola and Thiola EC, through one direct to patient pharmacy, Eversana, who also provides our comprehensive patient support services in the United States.

This patient support program includes a case-managed approach to patient education, insurance verification and reimbursement support, co-pay and other financial assistance for eligible patients, monitoring and support of adherence, and 24/7 access to pharmacist counseling.

In August 2022, we and CSL Vifor, with whom we entered into a license and collaboration agreement ("License Agreement") in September 2021, announced that the EMA had accepted for review the CMA application of sparsentan for the treatment of IgAN in the EU.

We anticipate an opinion by the Committee for Medicinal Products for Human Use (the "CHMP") in the first quarter of 2024.

If sparsentan receives marketing authorization in any of the licensed territories, CSL Vifor will be responsible for all commercialization activities in such licensed territories.

In April 2024, we and CSL Vifor, with whom we entered into a license and collaboration agreement ("License Agreement") in September 2021, announced that the European Commission granted conditional marketing authorization (CMA) for FILSPARI (sparsentan) for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or urine protein-to-creatinine ratio ≥0.75 g/g).

The CMA is granted for all member states of the European Union, as well as in Iceland, Liechtenstein and Norway.

Additionally, in October 2024 Swissmedic granted temporary marketing authorization for FILSPARI for the same patient population in Switzerland, and in November 2024, the Medicines and Healthcare products Regulatory Agency (MHRA) approved FILSPARI in the United Kingdom.

CSL Vifor is responsible for all commercialization activities in such licensed territories.

We remain responsible for the clinical development of sparsentan and will retain all rights to sparsentan in the United States and rest of world outside of the licensed territories, provided that CSL Vifor has a right of negotiation to expand the licensed territories into Canada, China, Brazil and/or Mexico.

In January 2024, we announced our entered into an exclusive licensing agreement with Renalys, to bring sparsentan for the treatment of IgAN to patients in Japan and other countries in Asia.

In January 2024, we announced our entry into an exclusive licensing agreement with Renalys, to bring sparsentan for the treatment of IgAN to patients in Japan and other countries in Asia.

Renalys will hold regional rights to sparsentan for Japan, South Korea, Taiwan, Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand, and Vietnam.

Following successful meetings with the Pharmaceuticals and Medical Devices Agency (PMDA) in 2023, Renalys plans to initiate an open label registration study of sparsentan in Japan in the second quarter of 2024 to support potential approval of sparsentan in Japan.

Results from the urine protein/creatinine ratio (UP/C) endpoint in the study are expected in the second half of 2025 to support a submission for approval to PMDA.

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The Federal Food, Drug, and Cosmetic Act, and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling and import and export of pharmaceutical products.

Failure to comply with applicable US requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending new drug or new biologic license applications, or NDAs and BLAs, respectively, warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties and criminal prosecution.

Failure to comply with applicable U.S.

requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending new drug or new biologic license applications, or NDAs and BLAs, respectively, warning

or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties and criminal prosecution.

Firms are also subject to potential inspection by FDA.

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Such supplements typically are reviewed within 10 months of receipt.

Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition—generally a disease or condition that affects fewer than 200,000 individuals in the US.

Orphan drug designation must be requested before submitting an NDA.

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Orphan drug designation in and of itself does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

The first NDA applicant to receive FDA approval for a particular active ingredient to treat a particular indication with FDA orphan drug designation is entitled to a seven-year exclusive marketing period in the US for that product, for that indication.

for that product, for that indication.

During the seven-year exclusivity period, the FDA may not approve any other applications to market the same drug for the same disease, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.

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Other than the requirement for bioequivalence testing, ANDA applicants are not required to conduct, or submit results of, preclinical or clinical tests to prove the safety or effectiveness of their drug product.

Drugs approved in this way are commonly referred to as “generic equivalents” to the listed drug, and can often be substituted by pharmacists under prescriptions written for the original listed drug.

Drugs approved in this way are commonly

referred to as “generic equivalents” to the listed drug, and can often be substituted by pharmacists under prescriptions written for the original listed drug.

The ANDA applicant is required to certify to the FDA concerning all patents listed for the approved product in the FDA’s Orange Book.

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Patients are unlikely to use our products unless coverage is provided and reimbursement is adequate to cover all or a significant portion of the cost of our products.

Therefore, coverage and adequate reimbursement is critical to product acceptance.

Therefore, coverage and adequate reimbursement is critical to product

Further, coverage policies and third-party payer reimbursement rates may change at any time.

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As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payer separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

In addition, it is possible that future legislation in the US and other jurisdictions could be enacted which could potentially influence the coverage and reimbursement rates for our products and also could further impact the levels of discounts and rebates paid to federal and state government entities, as well as commercial payers.

In addition, it is possible that future legislation in the U.S.

and other jurisdictions could be enacted which could potentially influence the coverage and reimbursement rates for our products and also could further impact the levels of discounts and rebates paid to federal and state government entities, as well as commercial payers.

Any legislation that influences these areas could impact, in a significant way, our ability to generate revenues from sales of products that, if successfully developed, we bring to market.

There have been a number of enacted or proposed legislative and regulatory changes affecting the healthcare system and pharmaceutical industry that could affect our commercial success.

For example, in March 2010, President Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, (collectively, the “PPACA”) a law intended to, among other things, broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against healthcare fraud and abuse, add new transparency requirements for healthcare and health insurance industries, impose new taxes and fees on pharmaceutical and medical device manufacturers and impose additional health policy reforms.

Specifically, by way of example, the PPACA revised the definition of “average manufacturer price” for reporting purposes, which could increase the amount of Medicaid drug rebates to states.

PPACA also increased the mandated Medicaid rebate from 15.1% to 23.1% of the average manufacturer price, expanded the rebate to Medicaid managed care utilization and increased the types of entities eligible for the federal 340B drug discount program.

There have been executive, judicial and Congressional challenges to certain aspects of the PPACA.

For example, on June 17, 2021, the U.S.

Supreme Court dismissed a challenge on procedural grounds that argued the PPACA is unconstitutional in its entirety because the "individual mandate" was repealed by Congress.

Further, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (“IRA”) into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in PPACA marketplaces through plan year 2025.

For example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, (collectively, the “PPACA”) was signed into law, which intended to, among other things, broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against healthcare fraud and abuse, add new transparency requirements for healthcare and health insurance industries, impose new taxes, rebates and fees on pharmaceutical and medical device manufacturers and impose additional health policy reforms.

There have been executive, judicial and Congressional challenges and amendments to certain aspects of the PPACA.

For example, on August 16, 2022, the Inflation Reduction Act of 2022 (“IRA”) was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in PPACA marketplaces through plan year 2025.

The IRA also eliminates the "donut hole" under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.

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This includes aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect beginning on April 1, 2013 and, due to subsequent legislative amendments, will stay in effect until 2032, unless additional Congressional action is taken.

Additionally, in January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, reduced Medicare payments to several providers, including hospitals and imaging centers.

Moreover, the Drug Supply Chain Security Act imposes additional obligations on manufacturers of pharmaceutical products related to product tracking and tracing.

Legislative and regulatory proposals have been made to expand post-approval requirements and alter sales and promotional activities for pharmaceutical products.

There has been increasing legislative and enforcement interest in the United States with respect to therapy pricing practices.

Specifically, there have been several recent US Congressional inquiries and numerous proposed and enacted legislation at both the state and federal levels designed to, among other things, bring more transparency to therapy pricing, reduce the cost of prescription therapies under Medicare, expedite generic competition, review the relationship between pricing and manufacturer patient programs, institute therapy re-importation, and reform government program reimbursement methodologies for therapies.

At the federal level, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, the U.S.

Department of Health and Human Services (HHS) released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

Further, the IRA, among other things (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions take effect progressively starting in fiscal year 2023.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

In response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

It is unclear whether the models will be utilized in any health reform measures in the future.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.

Specifically, there have been several recent U.S.

Congressional inquiries and numerous proposed and enacted legislation at both the state and federal levels designed to, among other things, bring more transparency to therapy pricing, reduce the cost of prescription therapies under Medicare, expedite generic competition, review the relationship between pricing and manufacturer patient programs, institute therapy re-importation, and reform government program reimbursement methodologies for therapies.

For example, the IRA, among other things (i) directs the U.S.

Department of Health and Human Services (HHS) to negotiate the price of certain high-expenditure, single-source drugs that have been on the market for at least 7 years covered under Medicare (the “Medicare Drug Price Negotiation Program”), and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions began to take effect progressively in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon price of the first ten drugs that were subject to price negotiations, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges.

On January 17, 2025, HHS selected fifteen additional drugs covered under Part D for price negotiation in 2025.

Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.

Further, on December 7, 2023, an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act was announced.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

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We expect that the PPACA, the IRA, as well as other federal and state healthcare reform measures that have been and may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any of our products, and could seriously affect our future revenues.

In addition, it is possible that future legislation in the United States and other jurisdictions could be enacted which could potentially impact the reimbursement rates for the products we are developing and may develop in the future and also could further

impact the levels of discounts and rebates paid to federal and state government entities.

Any legislation that impacts these areas could impact, in a significant way, our ability to generate revenues from sales of products that, if successfully developed, we bring to market.

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Also, many states have similar fraud and abuse statutes or regulations, including state anti-kickback and false claims laws, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payer.

The US Foreign Corrupt Practices Act, and similar worldwide anti-bribery laws generally prohibit companies and their intermediaries from making improper payments to government officials for the purpose of obtaining or retaining business.

Foreign Corrupt Practices Act, and similar worldwide anti-bribery laws generally prohibit companies and their intermediaries from making improper payments to government officials for the purpose of obtaining or retaining business.

Our policies mandate compliance with these anti-bribery laws.

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Like the federal anti-kickback statute, the PPACA amended the intent standard for certain healthcare fraud provisions under HIPAA such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

In addition, we may be subject to data privacy and security regulation by both the federal government and the states in which we conduct our business.

In addition, we are subject to data privacy and security regulation by both the federal government and the states in which we conduct our business.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act ("HITECH"), and their respective implementing regulations, imposes specified requirements relating to the privacy, security and transmission of individually identifiable health information.

maintains or transmits protected health information for or on behalf of a covered entity for a function or activity regulated by HIPAA and their covered subcontractors.

Among other things, HITECH, through its implementing regulations, makes certain of HIPAA’s privacy and security standards directly applicable to business associates, defined as a person or organization, other than a member of a covered entity’s workforce, that creates, receives, maintains or transmits protected health information for or on behalf of a covered entity for a function or activity regulated by HIPAA and their covered subcontractors.

Additionally, the federal Physician Payments Sunshine Act within the PPACA, and its implementing regulations, require that certain manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to annually report information related to certain payments or other transfers of value made or distributed to physicians and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, physicians (defined to include to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners), and teaching hospitals and to report annually certain ownership and investment interests held by physicians and their immediate family members.

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Individual EU Member States retain the power to authorize the conduct of clinical trials on their territory.

The extent to which on-going clinical trials will be governed by the CTR will depend on the duration of the individual clinical trial.

For clinical trials in relation to which an application for approval was made on the basis of the CTD before January 31, 2023, the CTD will continue to apply on a transitional basis until January 31, 2025.

By that date, all ongoing trials will become subject to the provisions of the CTR.

The CTR will apply to clinical trials from an earlier date if the related clinical trial application was made on the basis of the CTR or if the clinical trial has already transitioned to the CTR framework before January 31, 2025.

The CTR foresaw a three-year transition period that ended on January 31, 2025.

Since this date, all new or ongoing trials are subject to the provisions of the CTR.

In all cases, clinical trials must be conducted in accordance with GCP and the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki.

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(i) the product is intended for the diagnosis, prevention or treatment of life-threatening or chronically debilitating conditions;

(ii) either (a) such conditions affect not more than 5 in 10,000 persons in the EU when the application is made, or (b) the product without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the necessary investment in developing the medicinal product;

(ii) either (a) such conditions affect not more than five in 10,000 persons in the EU when the application is made, or (b) the product without the benefits derived from orphan status, would not generate sufficient return in the EU to justify the necessary investment in developing the medicinal product;

and (iii) there exists no satisfactory authorized method of diagnosis, prevention, or treatment of the condition that has been authorized in the EU, or even if such method exists, the product will be of significant benefit to those affected by that condition.

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We consider our current employee relations to be good.

We are committed to creating a multigenerational, multiracial, and multibackground workforce by welcoming each member’s unique experiences, backgrounds and talents and empowering them to reach their highest potential.

We desire to have our organization be representative of the communities we aim to serve with our treatments, and we are placing an increased focus on ways in which we can gain greater ethnic and racial diversity within our workforce, as well as other underrepresented groups, both throughout the organization and in leadership roles.

We support a number of initiatives that directly impact our human capital, including efforts to further diversity, equity, inclusion and belonging ("DEIB") initiatives

within our recruitment, retention and developmental programs, and increase cultural awareness and engagement.

We disclose information about our DEIB efforts on our website.

Information on our website is not incorporated in this annual report on Form 10-K.

We are committed to cultivating a workplace where individuals of all backgrounds feel valued, supported, and empowered to reach their fullest potential.

We desire to have our organization be representative of the communities we serve, while fostering a culture of inclusivity and a strong sense of belonging.

We know from our experience over more than a decade that rare diseases affect individuals across all demographics, and there are clear disparities in diagnosis, access to care, and support that remain significant barriers for many.

By fostering inclusivity within our workforce, we are better able to incorporate diverse viewpoints, which we believe positively influences our ability to achieve our objectives and ultimately impact patient outcomes – this is key to operating within our mission, and successfully helping the patients we aim to serve.

In line with embracing this

inclusivity, we support a number of initiatives that directly impact our human capital, workforce and community, such as efforts focused on professional development, cultural awareness, and engagement.

Additionally, we provide information about these efforts on our website, though the information on our website is not incorporated in this annual report on Form 10-K.

We strive to provide compensation, benefits and support services that help meet the varying needs of our employees.

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comprehensive healthcare benefits;

paid time off and paid holidays, and the opportunity for equity ownership through our equity incentive plan and our employee stock purchase plan, as well as a suite of wellness focused offerings introduced during the pandemic.

paid time off and paid holidays, and the opportunity for equity ownership through our equity incentive plan and our employee stock purchase plan, as well as a suite of wellness focused offerings.

We also sponsor a 401(k) plan that includes a discretionary matching contribution.

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Also during 2024, we continued to enhance our hybrid workforce program that provides a variety of virtual and in-person collaboration opportunities.

In 2024, we solicited feedback on ways to enhance employees' experience, with a focus on engagement and collaboration, and expect to implement new offerings in 2025.

As we continue to navigate through new ways of working, we take pride in the role we play in helping to ensure our employees are as productive and engaged as possible and their physical and emotional health, well-being and safety remains a key priority.

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

What changed 10-K

Item 1. Business