What changed in this filing

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Item 1. Business

2026-02-19 compared with 2025-02-21 · 238 added, 179 removed, 629 unchanged (40% of the section changed)

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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.

Food and Drug Administration ("FDA") granted full approval to our lead development program, FILSPARI (sparsentan), which is indicated to slow kidney function decline in adults with primary Immunoglobulin A nephropathy (" 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.

FILSPARI had previously been granted accelerated approval for IgAN 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.

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

In February 2025, we announced that we had completed a Type C meeting with the FDA and in March 2025, we announced that we had submitted an sNDA to the FDA seeking traditional approval of FILSPARI for the treatment of FSGS.

In May 2025, we announced that the FDA accepted the sNDA, assigned a PDUFA target action date of January 13, 2026, and initially indicated that it planned to hold an advisory committee meeting to discuss the application.

In September 2025, following further review of the sNDA, the FDA informed us that an advisory committee meeting was no longer needed.

In January 2026, we announced that the FDA extended the review timeline for the sNDA, and the new PDUFA target action date is April 13, 2026.

The extension followed the recent submission of responses requested by the FDA to further characterize the clinical benefit of FILSPARI.

The FDA determined that the additional responses constituted a Major Amendment to the sNDA and extended the action date accordingly.

The sNDA remains under review by the FDA with a PDUFA target action date of April 13, 2026.

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

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

Following further optimization of the manufacturing process in 2025, we restarted enrollment activities for the pivotal Phase 3 HARMONY Study in the first quarter of 2026.

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 believe that our research, development, and commercialization capabilities in rare disease represent distinct competitive advantages.

We leverage our development capabilities in rare disease to focus on advancing therapeutic candidates with life-changing potential.

We leverage our development

capabilities in rare disease to focus on advancing therapeutic candidates with life-changing potential.

Given these capabilities, the well-established regulatory model and the ability to demonstrate clinical effects in small clinical studies, we believe that we can successfully bring new therapies to patients living with severe unmet medical needs.

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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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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 had previously been granted accelerated approval for IgAN in February 2023.

2 In May 2025, we announced that the FDA accepted our sNDA for traditional approval of FILSPARI for the treatment of FSGS and assigned a PDUFA target action date of January 13, 2026.

In January 2026, we announced that the FDA extended the review timeline for the sNDA and the new PDUFA target action date is April 13, 2026.

3 Following a voluntary pause in enrollment, we restarted enrollment activities for the pivotal Phase 3 HARMONY Study in the first quarter of 2026.

FILSPARI® (sparsentan)

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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.

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.

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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 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).

FILSPARI was 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.

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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 is available only through a risk evaluation and mitigation strategy ("REMS") approved by the FDA for liver monitoring regarding potential risk of hepatotoxicity, as has been required for certain other approved endothelin antagonists.

Initially, as part of the liver monitoring REMS, monthly monitoring of each patient was required for the first year a patient was on treatment, and quarterly thereafter.

In August 2025, the FDA approved updated REMS labeling, reducing the frequency of liver monitoring to every three months from the onset of treatment and also removing the embryo-fetal toxicity monitoring requirement from the REMS.

In April 2024, we and our partner CSL Vifor announced that the European Commission had 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 ("UPCR") ≥0.75 g/g), and in April 2025, we and CSL Vifor announced that the European Commission had converted the CMA into a standard marketing authorization (“MA”) for FILSPARI for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or UPCR ≥0.75 g/g).

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

As a result of the standard MA approval, we received a regulatory milestone payment of $17.5 million in May 2025 under the terms of the License Agreement.

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 April 2025, the Medicines and Healthcare products Regulatory Agency ("MHRA") in the UK converted its conditional approval of FILSPARI in IgAN to standard approval.

In the fourth quarter of 2025, we received a $40.0 million market access milestone payment from CSL Vifor.

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

("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, 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.

In the fourth quarter of 2025, Renalys announced positive topline results from its Phase 3 study of sparsentan in Japanese patients with IgAN.

Renalys has also announced that it has reached an agreement with the Pharmaceuticals and Medical Devices Agency ("PMDA") regarding development plans for two other Phase 3 clinical trials of sparsentan, one investigating the use of sparsentan in FSGS and the other in Alport syndrome, in Japan.

In the fourth quarter of 2025, Renalys was acquired by and merged into Chugai Pharmaceutical Co., Ltd.

Through the acquisition, Chugai gained exclusive rights to develop and commercialize sparsentan in Japan, South Korea, and Taiwan.

As a minority shareholder in Renalys, we received $10.2 million at the closing of the transaction, and we are also eligible to receive multiple milestones according to the progress of sparsentan regulatory approval, and consideration linked to sparsentan's net sales in the applicable territory.

Under the terms of the licensing agreement, Chugai is responsible for development, regulatory matters, and commercialization in the licensed territories.

Chugai plans to file for the regulatory approval for sparsentan in Japan in 2026.

Clinical-Stage Programs:

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There are currently no FDA-approved pharmacologic treatments for FSGS and there remains a high unmet need for patients living with FSGS as off-label treatments such as ACE/ARBs, steroids, and immunosuppressant agents are effective in only a subset of patients and use of some of these off-label treatments may be further inhibited by their safety profiles.

Every year approximately 5,400 patients are diagnosed with FSGS and we estimate that there are more than 40,000 FSGS patients in the United States and a similar number in Europe with approximately half of them being candidates for sparsentan.

Every year approximately 5,400 patients are diagnosed with FSGS and we estimate that there are more than 40,000 FSGS patients in the United States and a similar number in Europe.

We believe that there are up to 30,000 FSGS patients in the United States that are potentially addressable with FILSPARI, if approved.

In 2016, we generated positive data from our Phase 2 DUET study in FSGS.

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The DUPLEX Study is a global, randomized, multicenter, double-blind, parallel-arm, active-controlled clinical trial evaluating the safety and efficacy of sparsentan in 371 patients.

The DUPLEX Study protocol provided for an unblinded analysis of at least 190 patients to be performed after 36 weeks of treatment to evaluate the interim efficacy endpoint - the proportion of patients achieving a FSGS partial remission of proteinuria endpoint (FPRE), which is defined as urine protein-to-creatinine ratio (UPCR) ≤1.5 g/g and a >40% reduction in UPCR from baseline, at week 36.

The DUPLEX Study protocol provided for an unblinded analysis of at least 190 patients to be performed after 36 weeks of treatment to evaluate the interim efficacy endpoint - the proportion of patients achieving a FSGS partial remission of proteinuria endpoint ("FPRE"), which is defined as UPCR ≤1.5 g/g and a >40% reduction in UPCR from baseline, at week 36.

In February 2021, we announced that the ongoing Phase 3 DUPLEX Study achieved its pre-specified interim FSGS partial remission of proteinuria endpoint following the 36-week interim period.

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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 a planned Type C meeting with the FDA to discuss results from the Phase 3 DUPLEX Study of sparsentan in FSGS.

In December 2023, we announced that we had 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 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 were not sufficient to support an sNDA submission.

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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.

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 for full approval of sparsentan in IgA nephropathy is approved.

Following the PARASOL public workshop in the fourth quarter of 2024, 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 September 2025, following further review of the sNDA, the FDA informed us that an advisory committee meeting was no longer needed.

In January 2026, we announced that the FDA extended the review timeline of the sNDA, and that the new PDUFA target action date is April 13, 2026.

The extension followed the recent submission of responses requested by the FDA to further characterize the clinical benefit of FILSPARI.

The FDA determined that the additional responses constituted a Major Amendment to the sNDA and extended the action date accordingly.

The sNDA remains under review by the FDA with a PDUFA target action date of April 13, 2026.

The sNDA is supported by two of the largest and most rigorous head-to-head interventional studies conducted to date in FSGS, the Phase 3 DUPLEX Study and the Phase 2 DUET Study.

In these studies, FILSPARI demonstrated rapid, superior and sustained reductions in proteinuria when compared with maximum labeled dose irbesartan across adult and pediatric patients.

As published in the New England Journal of Medicine, DUPLEX showed statistically significant and clinically meaningful proteinuria remission at 36 weeks that was durable through 2 years.

The treatment effect of FILSPARI strengthened at more stringent thresholds down to complete remission.

Patients who achieved partial or complete proteinuria remission in the DUPLEX Study, irrespective of the treatment arm, had a 67% to 77% lower risk of kidney failure, respectively.

The results from these studies are in alignment with the findings of the independent PARASOL workgroup that support the importance of proteinuria in FSGS.

If approved, FILSPARI could become the first and only FDA-approved medicine indicated for FSGS.

Together with CSL Vifor and Chugai, we continue to evaluate the potential for a regulatory pathway forward for sparsentan in FSGS in Europe and Japan.

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 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.

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

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

Pegtibatinase

Pegtibatinase is a novel investigational human enzyme replacement candidate being evaluated for the treatment of classical homocystinuria (HCU).

Pegtibatinase is a novel investigational human enzyme replacement candidate being evaluated for the treatment of classical HCU.

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.

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In December 2021, we announced positive topline results from the Phase 1/2 COMPOSE Study, a double blind, randomized, placebo-controlled dose escalation study to assess its safety, tolerability, pharmacokinetics, pharmacodynamics and clinical effects in patients with classical HCU.

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.

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 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.

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.

In this cohort, five patients were randomized in a blinded fashion to receive 2.5 mg/kg of lyophilized pegtibatinase or placebo twice weekly (BIW), with four patients assigned to the treatment group.

In this highest dose cohort to date, treatment with pegtibatinase resulted in rapid and sustained reductions in total homocysteine (tHcy), with a 67.1% mean relative reduction in tHcy from baseline, as well as maintenance of mean tHcy below the clinically meaningful threshold of 100 μmol, over weeks 6 to 12.

In this cohort, five patients were randomized in a blinded fashion to receive 2.5 mg/kg of lyophilized pegtibatinase or placebo BIW, with four patients assigned to the treatment group.

In this highest dose cohort to date, treatment with pegtibatinase resulted in rapid and sustained reductions in tHcy, with a 67.1% mean relative reduction in tHcy from baseline, as well as maintenance of mean tHcy below the clinically meaningful threshold of 100 μmol, over weeks 6 to 12.

In the double-blind period, pegtibatinase was generally well-tolerated , with no discontinuations due to treatment-related adverse events.

In December 2023, we initiated the pivotal Phase 3 HARMONY Study to support the potential approval of pegtibatinase for the treatment of classical HCU.

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.

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.

The voluntary enrollment pause was enacted following our determination that the desired drug substance profile was not achieved in the initial scale-up process, and it enabled us to address necessary process improvements in manufacturing scale-up to support initial commercial scale manufacturing as well as full enrollment in the HARMONY Study.

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

participating.

Following further optimization of the manufacturing process in 2025, we restarted enrollment activities for the pivotal Phase 3 HARMONY Study in the first quarter of 2026.

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

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.

Other Commercial Products:

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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.

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.

To date, 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.

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On July 16, 2023, we entered into an Asset Purchase Agreement (the “Purchase Agreement”) with Mirum Pharmaceuticals, Inc.

("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".

This transaction was consummated on August 31, 2023.

A portion of the consideration for the sale is in the form of potential milestone payments that only become payable upon the achievement of certain milestones based on specified amounts of annual net sales of the Products.

Mirum achieved the first such milestone based on its annual net sales in 2025, we recognized a milestone of $25.0 million during 2025, and expect to receive payment in the second quarter of 2026, as a result of such achievement.

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

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FILSPARI/Sparsentan

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).

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

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).

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

In April 2024, the

European Commission granted CMA for FILSPARI and in April 2025, the European Commission converted the CMA into a standard MA for FILSPARI for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or UPCR ≥0.75 g/g).

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

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

In October 2024, the Company 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 UPCR ≥0.75 g/g).

In April 2025, the MHRA in the UK converted its conditional approval of FILSPARI in IgAN to standard approval.

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 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 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.

In November 2023, AstraZeneca initiated a registrational fixed-dose combination (FDC) study with zibotentan and Farxiga in CKD patients with high proteinuria.

Patients with IgAN are not excluded from the study.

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

Historically, traditional standard of care has been centered on renin-angiotensin system ("RAS") blockade, with immunosuppressive therapies used selectively in certain higher-risk patients.

In 2025, Kidney Disease Improving Global Outcomes (“KDIGO”) published updated guideline recommendations for the treatment of IgAN.

The updated KDIGO guidelines suggest FILSPARI as a foundational kidney-targeted therapy for IgAN patients who are at risk of progressive kidney function loss and advocate for lowering targeted proteinuria levels for all IgAN patients to under 0.5 g/day, or ideally under 0.3 g/day, where achievable.

The updated guidelines provide a high-level treatment framework that recognizes immune-mediated disease activity and progressive kidney damage as key contributors to kidney function decline in IgAN.

The guidelines emphasize that patients with IgAN who are at risk of progressive loss of kidney function, defined as patients with proteinuria of ≥0.5 g/day, should receive early, risk-appropriate treatment approaches that both target kidney injury already present and address immune-mediated disease drivers.

Under the current framework, these two categories of treatment are viewed as complementary, with treatment sequencing and selection individualized based on patient risk, disease characteristics, and therapy availability.

On the kidney-targeted side, recent clinical guidance and emerging evidence support the use of foundational kidney-targeted therapies, such as optimized RAS inhibition or FILSPARI as a DEARA, as well as sodium-glucose cotransporter-2 (“SGLT2”) inhibitors which can be used in combination with the foregoing therapies, as appropriate.

Recent clinical guidance and emerging evidence support the need for foundational kidney-targeted therapy to manage the consequences of IgAN-induced kidney damage, including glomerular hyperfiltration, persistent proteinuria, tubulointerstitial injury, and progressive decline in kidney function.

Therapies in this category are positioned as long-term treatments.

FILSPARI is the only therapy to date to demonstrate a statistically significant slowing of kidney function decline in a Phase 3 study compared to an active, maximally titrated RAS inhibitor.

Other kidney-targeted agents under clinical development include Novartis’s atrasentan (Vanrafia), an endothelin receptor antagonist indicated to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression, generally defined as a UPCR ≥1.5 g/g, which is currently approved under the FDA’s accelerated approval pathway.

Based on publicly available information, confirmatory Phase 3 data for atrasentan are expected to begin reporting in 2026.

In addition to kidney-targeted therapies, there are several therapies that are approved or in development that target the upstream immunopathogenesis of IgAN.

Approved immune-targeted therapies include targeted-release budesonide, such as Calliditas’s Tarpeyo, which has received full regulatory approval in the United States.

Systemic corticosteroids remain used in clinical practice in selected patients, including under guideline-described regimens.

There is also a growing group of novel immune-targeted therapies that have received regulatory approval under accelerated approval pathways or are in late-stage clinical development.

These include APRIL- and BAFF-pathway inhibitors designed to modulate pathogenic IgA production, such as Otsuka’s sibeprenlimab (Voyxact), which has received accelerated approval, as well as Vera Therapeutics’ atacicept, telitacicept (licensed to Vor Bio outside Greater China), Vertex’s povetacicept, and Novartis’s zigakibart, all of which are currently in late-stage clinical development.

Additional upstream immune-targeted approaches include complement pathway inhibitors, such as Novartis’s iptacopan (Fabhalta), which has received accelerated approval, and sefaxersen (Roche/Ionis), which is in late-stage clinical development.

Terminal complement inhibitors, such as Alexion’s ravulizumab (Ultomiris), and plasma cell-directed therapies, such as Biogen’s felzartamab and Takeda’s mezagitamab, are also currently being evaluated in late-stage (Phase 3) IgAN studies, along with other B-cell- or plasma cell-directed therapies that remain under investigation.

From 2021 to 2024, there were global regulatory label expansions of two SGLT2 inhibitors—AstraZeneca’s Farxiga/Forxiga and Boehringer Ingelheim and Eli Lilly’s Jardiance—into chronic kidney disease ("CKD"), positioning this class as a potential background or complementary therapy to sparsentan in the treatment of IgAN and/or FSGS.

Additionally, although patients diagnosed with IgAN are not included in the approved label and were not enrolled in the initial pivotal studies, Bayer’s non-steroidal mineralocorticoid receptor antagonist, Kerendia, could potentially be used in patients with diabetic kidney disease and concurrent IgAN and is currently being studied in patients with CKD without diabetes.

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

Idorsia Pharmaceuticals’ aprocitentan (branded as Tryvio in the United States and Jeraygo in Europe) was approved for the treatment of resistant hypertension by the FDA and the European Medicines Agency in March 2024 and June 2024, respectively;

the pivotal study enrolled patients with resistant hypertension, including those with Stage 3 and Stage 4 CKD.

In November 2023, AstraZeneca initiated a registrational fixed-dose combination study of zibotentan and Farxiga in CKD patients with high proteinuria.

Patients with IgAN are not excluded from the study, and primary completion is anticipated in 2027.

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

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

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A post-approval study with this device is ongoing.

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.

Dimerix is conducting a Phase 3 study of its CCR2 blocker DMX-200 in adult patients with FSGS, including primary, genetic, and undetermined causes, with an independent adolescent cohort also being evaluated.

Boehringer Ingelheim has announced plans to conduct a Phase 3 study with BI 764198 (TRPC6 inhibitor) in adults and adolescent primary FSGS patients and FSGS patients with a TRPC6 gene mutation.

Apellis Pharmaceuticals is conducting a dedicated sequential Phase 2/3 study in adults, followed by adolescents, with FSGS.

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.

Based on publicly available information, interim data is expected in 2026.

There are currently two other clinical stage APOL1 programs in development:

Maze Therapeutics’ MZE829 and AstraZeneca/Ionis’ AZD2373 (an APOL1-targeting antisense oligonucleotide).

Based on public sources, several other companies have programs in clinical and/or pre-clinical development for the treatment of FSGS or related conditions, including, among others, the following Phase 2 and 3 programs:

Vera Therapeutics (atacicept), Novartis (atrasentan), Sanofi (frexalimab, rilzabrutinib, brivekimig), Akebia (praliciguat).

In addition to its FSGS program, Apellis Pharmaceuticals’ pegcetacoplan is in a Phase 3 trial for other rare glomerular diseases (C3G/IC-MPGN).

Pegtibatinase

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According to public sources, Syntis Bio, Inc.

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

has two pre-clinical development programs 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.

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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.

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.

To date, 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.

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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.

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.

Through December 31, 2025, we have capitalized $47.2 million for contractual milestones achieved under the Ligand License Agreement.

Pursuant to the Ligand License Agreement, we are obligated to pay 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).

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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.

We paid Mission an up-front license fee of $3.0 million and over the term of the agreement will pay the greater of $2.0 million, representing the guaranteed minimum royalty, or 20% of our net sales of Thiola in the United States and Canada during each calendar year.

In October 2015, the license agreement was amended to allow for us to secure enough API to ensure an adequate level of safety stock to prevent an interruption in the supply of Thiola and to prepare for a reformulation development project.

In March 2016, the license agreement was amended to, among other things, include a new formulation development project for tiopronin tablets.

In November 2017, we amended the license agreement to extend the term through May 2029.

In November 2018, the license agreement was amended to remove all territorial restrictions on our license rights.

As consideration for the expanded territory, we paid an up-front fee of $0.3 million and will pay the greater of $0.1 million, representing the guaranteed minimum royalty, or 20% of our Thiola net sales generated outside of the United States during each calendar year.

In 2014, we entered into a license agreement with Mission Pharmacal ("Mission"), 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 ("Mission License Agreement").

Under the terms of the Mission License Agreement, as subsequently amended, which runs through May 2029, we are obligated to pay to Mission, the greater of $2.1 million, representing the guaranteed minimum royalty, or 20%, of our Thiola net sales generated globally during each calendar year.

Intellectual Property

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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 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”).

As of December 31, 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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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.

application, 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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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.

In November 2020, a third party filed an opposition to the European ‘277 patent in the European Patent Office ("EPO").

While we are vigorously defending the European '277 patent against the opposition, there is no guarantee that we will be successful in doing so.

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.”

The first Travere patent family is directed to methods of using sparsentan in the treatment of various kidney diseases, including focal segmental glomerulosclerosis (FSGS) and IgAN, e.g., by achieving a specified urine protein-to-creatinine ratio.

The first Travere patent family is directed to methods of using sparsentan in the treatment of various kidney diseases, including FSGS and IgAN, e.g., by achieving a specified UPCR.

As of December 31, 2025, 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 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.

10,864,197, which we refer to herein as the ‘197 patent) and issued patents and pending patent applications in the U.S., and in certain jurisdictions outside the U.S., including Australia, Brazil, Canada, China, the EPO, 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.

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As of December 31, 2025, this patent family was comprised of a granted U.S.

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.

11,207,299) and issued patents and pending patent applications in the U.S., and in certain jurisdictions outside the U.S., including Australia, Brazil, Canada, China, the EPO, 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 fourth Travere patent family is comprised of a pending international patent application, related to methods of treating IgA mediated diseases or disorders comprising sparsentan as well as corresponding pending patent applications in the U.S.

and in certain foreign jurisdictions.

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.

In addition, we have filed pending U.S.

provisional patent applications directed to additional methods of use of sparsentan.

provisional patent applications are not published and may not result in issued patents unless we timely file corresponding non-provisional applications;

accordingly, we do not include such provisional filings in the patent family count described above.

and some countries outside the U.S.

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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.

We have filed an application for patent term extension of the ‘461 patent, and subsequently filed a supplement to this application to reflect the FDA-determined regulatory review period for sparsentan, which, if granted, could extend the term of the ‘461 patent to January 2033.

There is no guarantee that such patent term extension will be granted to such date, or at all.

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.

In the EU, a CMA for FILSPARI was issued by the European Commission in April 2024 (the ”FILSPARI CMA”) and was converted into a standard MA by the European Commission in April 2025.

Because there has been no prior European approval for FILSPARI, we and Vifor have obtained certain SPCs and are pursuing additional 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.

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Our patent portfolio for Thiola is comprised of a patent family which is exclusively licensed from Mission Pharmacal (the “Mission patent family”).

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

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

As of December 31, 2025, 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.

11,458,104, which we refer to herein as the ‘104 patent).

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

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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").

In addition, both the five-year NCE period and the seven-year ODE period may be extended by six months upon submission of satisfactory written reports to the FDA of clinical studies conducted in pediatric populations.

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

In addition, both the five-year NCE period and the seven-year ODE period may be extended by six months if the FDA grants pediatric exclusivity, which generally requires that the FDA issue a written request for pediatric studies and that the sponsor submit satisfactory written reports of such studies.

There can be no assurance that we will qualify for any such pediatric exclusivity.

Likewise, if we obtain marketing approval for pegtibatinase in the United States or in certain jurisdictions outside of the United States, we may be eligible for regulatory exclusivity for the approved product.

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In the United States, an FDA-approved biologic product may be eligible to receive twelve years of regulatory exclusivity.

In addition, the twelve-year BLA exclusivity period may be extended by six months upon submission of satisfactory written reports to the FDA of clinical studies conducted in pediatric populations.

In the European Union and European Free Trade Association ("EFTA") countries, innovative medicinal products approved by the European Commission may receive eight years of data exclusivity and 10 years of market exclusivity.

The 10-year period of market exclusivity may extend to 11 years if, during the eight-year period of data exclusivity, the product receives marketing authorization for a second therapeutic that provides a significant clinical benefit in comparison to existing therapies.

In addition, the twelve-year BLA exclusivity period may be extended by six months if the FDA grants pediatric exclusivity, which generally requires that the FDA issue a written request for pediatric studies and that we submit satisfactory written reports.

There can be no assurance that we will qualify for any such pediatric exclusivity.

The 10-year period of data and market exclusivity may extend to 11 years if, during the eight-year period of data exclusivity, the product receives marketing authorization for a second therapeutic that provides a significant clinical benefit in comparison to existing therapies.

Additionally, upon approval by the European Commission, orphan drugs may receive 10 years of market exclusivity or, in the case of orphan drugs for which a pediatric investigational plan ("PIP") has been completed, 12 years of market exclusivity.

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There can be no assurance that we will qualify for any such regulatory exclusivity, or that any such exclusivity will prevent competitors from seeking approval solely on the basis of their own studies.

In addition, future changes to EU legislation may affect the availability, scope, or duration of rights granted after such changes take effect.

See “Government Regulation” below.

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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.

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

More specifically, as of December 31, 2025, our trademark portfolio included registered U.S.

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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”.

trademarks for both the wordmark “TRAVERE TOTAL CARE”, 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.

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These agreements are designed to protect our proprietary information.

We also seek to preserve the integrity and confidentiality of our data, trade secrets and know-how by maintaining physical security of our premises and physical and electronic security of our information technology systems.

We also seek to preserve the integrity and confidentiality of our data, trade secrets and know-how by maintaining physical security of our premises and physical and electronic security of

our information technology systems.

Trade secrets and know-how can be difficult to protect.

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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.

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

Nephrologists are the primary call point for FILSPARI.

The primary call points for Thiola and Thiola EC include urologists and nephrologists.

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 also has an average of more than 20 years of pharmaceutical experience focused on specialty and rare disease.

Our sales force is differentiated by its deep pharmaceutical experience and significant expertise in rare disease.

Our commercial management and operations team similarly has extensive experience in pharmaceutical commercialization, particularly in specialty and rare disease markets.

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

We distribute our other products, Thiola and Thiola EC, through a direct-to-patient pharmacy that 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 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 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.

Under the terms of the agreement, Renalys will be responsible for development, regulatory matters, and commercialization in the 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 CMA for FILSPARI (sparsentan) for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or UPCR ≥0.75 g/g), and in April 2025, we and CSL Vifor announced that the European Commission had converted the CMA

into a standard MA for FILSPARI for the treatment of adults with primary IgAN with a urine protein excretion ≥1.0 g/day (or UPCR ≥0.75 g/g).

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

As a result of the standard MA approval, we received a regulatory milestone payment of $17.5 million in May 2025 under the terms of the License Agreement.

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

In April 2025, the MHRA in the UK converted its conditional approval of FILSPARI in IgAN to standard approval.

In the fourth quarter of 2025, we received a $40.0 million market access milestone payment from CSL Vifor.

In June 2025, the CSL Vifor License Agreement was amended in order to, among other things, expand the license to cover the following additional countries:

Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates (collectively, the "Gulf Cooperation Council Countries"), and Brazil, Chile and Israel (together with Europe, Australia and New Zealand, the "CSL Vifor Licensed Territories") and to provide that the license rights to each additional country will revert to the Company if CSL Vifor does not take certain specified actions within specified timelines with respect to such country.

CSL Vifor is responsible for all commercialization activities in the CSL Vifor Licensed Territories.

CSL Vifor also has first right of negotiation to expand the licensed territories into Canada and/or Mexico.

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

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

In the fourth quarter of 2025, Renalys announced positive topline results from its Phase 3 study of sparsentan in Japanese patients with IgAN.

Renalys has also announced that it has reached an agreement with the PMDA regarding development plans for two other Phase 3 clinical trials of sparsentan, one investigating the use of sparsentan in FSGS and the other in Alport syndrome, in Japan.

In the fourth quarter of 2025, Renalys was acquired by and merged into Chugai.

Through the acquisition, Chugai gained exclusive rights to develop and commercialize sparsentan in Japan, South Korea, and Taiwan.

As a minority shareholder in Renalys, we received a portion of the upfront payment at the closing of the transaction, and we are also eligible to receive multiple milestones according to the progress of sparsentan regulatory approval, and consideration linked to sparsentan's net sales in the applicable territory.

Under the terms of the licensing agreement, Chugai is responsible for development, regulatory matters, and commercialization in the licensed territories.

Chugai plans to file for the regulatory approval for sparsentan in Japan in 2026.

Medical Affairs

We have a global medical affairs team located in the United States and Europe which supports data dissemination, education, external stakeholder engagement and data generation in therapeutic areas relevant to our pipeline and commercial assets.

The responsibilities of our medical affairs personnel include execution of real-world evidence studies, scientific exchange with external stakeholders, medical communication through scientific publications and presentations at medical congresses, providing medical information support to HCPs and patients related to our pipeline and our post-approval clinical commitments, organizing medical advisory boards to obtain input from experts and practitioners, and supporting grants for investigator sponsored research and independent medical education programs on medical topics relevant to our products and diseases.

We have a global Medical Affairs organization with teams located in the United States and Europe that supports scientific exchange, data dissemination, education, and evidence generation across therapeutic areas relevant to our pipeline and commercial products.

Our Medical Affairs activities are designed to advance scientific understanding, support the appropriate use of our therapies, and engage external stakeholders.

The responsibilities of our Medical Affairs personnel include execution and support of real-world evidence studies, scientific exchange with external stakeholders, medical communications through peer-reviewed publications and presentations at medical congresses, and providing medical information support to HCPs regarding our pipeline products and approved therapies.

Medical Affairs also conducts scientific advisory boards to obtain insights from experts and practitioners and reviews and supports independent medical education grants and research on topics relevant to our products and associated disease states.

Government Regulation

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Failure to comply with applicable U.S.

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

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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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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or (iv) the listed patent is invalid or will not be infringed by the new product.

The ANDA applicant may also elect to submit a section viii statement certifying that its proposed ANDA label does not contain (or carves out) any language regarding the patented method-of-use rather than certify to a listed method-of-use patent.

The ANDA applicant may also elect to submit a section viii statement certifying that its proposed ANDA label does not contain (or

carves out) any language regarding the patented method-of-use rather than certify to a listed method-of-use patent.

If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired.

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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

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

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

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Government authorities and other third-party payers have and are developing methods of controlling healthcare costs, such as by limiting coverage and the amount of reimbursement for particular medications.

For example, the U.S.

Department of Health and Human Services ("HHS") imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis.

In addition, HHS has been empowered to negotiate the price of certain single-source biologics that have been on the market for at least 11 years covered under

Medicare as part of the Medicare Drug Price Negotiation Program.

Each year up 20 products will be selected by HHS for the Medicare Drug Price Negotiation Program.

Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

Increasingly, third-party payers are requiring that therapeutic companies provide them with predetermined discounts/rebates from list prices as a condition of coverage, are using restrictive formularies and preferred therapy lists to leverage greater discounts in competitive classes, and are challenging the prices charged for medical products.

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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.

The IRA, discussed in more detail below, also established new pricing pressures, including government price setting for certain therapies and mandatory rebates on price increases over inflation.

For example, on July 4, 2025, the One Big Beautiful Bill Act ("OBBBA") was signed into law, which narrowed access to PPACA marketplace exchange enrollment and declined to extend the PPACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired PPACA subsidies.

In addition, other legislative changes have been proposed and adopted since the PPACA was enacted.

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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.

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

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.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

The current administration is pursuing policies to reduce regulations and expenditures across government agencies including at HHS, the FDA, CMS and related agencies.

These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

For example, the current administration has announced agreements with pharmaceutical companies that require the drug manufacturers to offer, through a direct-to-consumer platform, U.S.

patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues.

Other recent actions, for example, include (1) directing agencies to reduce agency workforce and cut programs;

(2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products;

(3) imposing tariffs on imported pharmaceutical products;

and (4) as part of the Make America Healthy Again Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising.

Additionally, the current administration recently called on Congress to enact “The Great Healthcare Plan,” to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager payment methodologies, among other things.

These actions and policies may significantly reduce U.S.

drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.

In June 2024, the U.S.

Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program.

At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs.

in some cases, designed to encourage importation from other countries and bulk purchasing.

For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program (“SIP”) proposal to import certain drugs from Canada for specific state healthcare programs.

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Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs.

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.

We expect that the PPACA and 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.

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Violations of these laws, or allegations of such violations, could disrupt our business and result in criminal or civil penalties or remedial measures, any of which could have a material adverse effect on our business, financial condition and results of operations and could cause the market value of our common stock to decline.

The federal Health Insurance Portability and Accountability Act of 1996 ("HIPAA"), created new federal criminal statutes that prohibit, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payers, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

payers, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

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.

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Under European Union regulatory systems, a company may not market a medicinal product without a marketing authorization.

In the EU, medicinal products can only be commercialized after a related marketing authorization (“MA”), has been granted.

In the EU, medicinal products can only be commercialized after a related MA, has been granted.

To obtain an MA for a product in the EU, an applicant must submit a Marketing Authorization Application (“MAA”), either under a centralized procedure administered by the EMA or one of the procedures administered by the competent national authorities of EU Member States:

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The resulting assessment report is submitted to the concerned EU Member States who, within 90 days of receipt, must decide whether to approve the assessment report and related materials.

If a concerned EU Member State cannot approve the assessment report and related materials due to concerns relating to a potential serious risk to public health, disputed elements may be referred to the Heads of Medicines Agencies’ Coordination Group for Mutual Recognition and Decentralised Procedures – Human, or CMDh, for review.

The subsequent decision of the European Commission is binding on all EU Member States.

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An MA may also be granted “under exceptional circumstances” where the applicant can show that it is unable to provide comprehensive data on efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced.

These circumstances may arise in particular when the intended indications are very rare and, in the state of scientific knowledge at that time, it is not

possible to provide comprehensive information, or when generating data may be contrary to generally accepted ethical principles.

These circumstances may arise in particular when the intended indications are very rare and, in the state of scientific knowledge at that time, it is not possible to provide comprehensive information, or when generating data may be contrary to generally accepted ethical principles.

Like a conditional MA, an MA granted in exceptional circumstances is reserved to medicinal products intended to be authorized for treatment of rare diseases or unmet medical needs for which the applicant does not hold a complete data set that is required for the grant of a standard MA.

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The period of market exclusivity may, however, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria on the basis of which it received orphan medicinal product destination, including where it can be demonstrated on the basis of available evidence that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold.

Additionally, an MA may be granted to a similar medicinal product with the same

orphan indication during the 10 year period if:

Additionally, an MA may be granted to a similar medicinal product with the same orphan indication during the 10 year period if:

(i) if the applicant consents to a second original orphan medicinal product application, (ii) if the manufacturer of the original orphan medicinal product is unable to supply sufficient quantities;

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The holder of an MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance who is responsible for oversight of that system.

Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.

Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports ("PSURs").

All new MAAs must include a risk management plan, or RMP, describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product.

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We consider our current employee relations to be good.

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.

We are committed to cultivating a workplace where every individual feels seen and appreciated, understanding that our strength lies in embracing the rich diversity of our employees’ lives and experiences.

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 and a strong sense of belonging 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.

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We do this by listening to our employees through many avenues, including formal engagement initiatives, such as surveys, as well as informal listening sessions hosted by senior leaders, including our CEO and our human resources department.

The response rate for our latest employee engagement survey, which was conducted in November 2024, was 84%.

The response rate for our latest employee engagement survey, which was conducted in September 2025, was 86%.

During 2025 we continued to focus on ways to maximize a people-centered, inclusive, and recognition-based company culture, building on initiatives that have been implemented over the last several years.

Also during 2025, 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.

In 2024, we solicited feedback on ways to enhance employees' experience, with a focus on engagement and collaboration, and we implemented several of the suggestions over the last year.

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.

We are committed to providing a safe and healthy working environment for our employees and to avoiding adverse impact to the environment and the communities in which we do business.

We are committed to providing a safe and healthy working environment for our employees.

Available Information

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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