Calliditas Therapeutics AB (publ) Stock

Calliditas Therapeutics AB (Calliditas) operates as a commercial-stage specialty pharmaceutical company with the first product approved in the U.S. and in EU for patients with the renal disease immunoglobulin A nephropathy, Nefecon, and a portfolio of innovative product candidates.

Nefecon is a proprietary, novel oral, delayed release formulation of budesonide designed to specifically target the presumed origin of the disease and provide a potentially disease modifying treatment of immunoglobin A nephropathy, or IgAN, for which there is a high unmet medical need. Budesonide is a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism, resulting in limited systemic exposure. IgAN is a progressive, chronic disease that over time results in deterioration of kidney function in patients, many of whom are at risk of developing end-stage renal disease, or ESRD, with the need for dialysis or kidney transplant. Nefecon is designed to target the origin of the disease presumed to be located in the ileum, the distal region of the small intestine, which has the highest concentration of the Peyer's patches, which are responsible for the production of pathogenic secretory immunoglobulin A, or IgA, antibodies.

The U.S. Food and Drug Administration, or FDA, approved Nefecon under the brand name TARPEYO under accelerated approval on December 15, 2021 and the company reported commercial availability in the United States in January 2022. The indication for TARPEYO (budesonide) delayed release capsules (4mg) is reduction of proteinuria in adults with primary IgAN at risk of rapid disease progression, generally a urine protein-to-creatinine ratio, or UPCR, greater than or equal to 1.5gram/gram. The European Commission, or EC, granted conditional marketing authorization for Nefecon under the name Kinpeygo (budesonide) capsules for the treatment of primary IgAN in adults at risk of rapid disease progression with a urine protein-to-creatinine ratio greater than or equal to 1.5 gram/gram on July 15, 2022 and the company's licensee STADA Arzneimittel AG, or STADA, announced commercial availability in Germany in September 2022. On February 1, 2023, the Medicines and Healthcare products Regulatory Agency, or MHRA, of the UK granted Conditional Marketing Authorization for Kinpeygo for the same indication as the EC.

TARPEYO was the first treatment ever approved for the U.S. market indicated for patients with IgAN. The FDA approved TARPEYO under the accelerated approval pathway based on the reduction in proteinuria and supportive data on the estimated Glomerular Filtration Rate, or eGFR, a measure of kidney function, shown in Part A of the company's pivotal NefIgArd trial. The company reported topline results from the full NefIgArd clinical trial in March 2023. The trial met its primary endpoint with Nefecon demonstrating a highly statistically significant benefit over placebo (p value < 0.0001) in eGFR over the two-year period of nine months of treatment with Nefecon or placebo and 15 months of follow-up off drug. The results indicate that Nefecon was generally well-tolerated and the safety profile was consistent with that observed in Part A of the trial.

Nefecon has been granted seven years orphan drug exclusivity in the United States, expiry December 15, 2028, and ten years orphan market exclusivity by the EC, expiry July 15, 2032, and by the MHRA, expiring February 1, 2033.

The company retains worldwide rights to Nefecon other than in territories where the company has established strategic collaborations. In 2019, the company entered into an agreement pursuant to which the company granted Everest Medicines II Limited, or Everest, an exclusive license to develop and commercialize Nefecon for the treatment of IgAN in Greater China and Singapore, and in March 2022, the company expanded the territory covered by the agreement to include the Republic of Korea. In July 2021, the company entered into a license agreement with STADA to commercialize Nefecon for the treatment of IgAN in the EEA, the U.K., and if approved, in Switzerland. In December 2022, the company entered into an exclusive license agreement with Viatris Pharmaceuticals Japan Inc., a subsidiary of Viatris Inc., or Viatris, to register and commercialize Nefecon for the treatment of IgAN in Japan.

The company is also developing a novel platform of nicotinamide adenine dinucleotide phosphate, or NADPH, oxidase, or NOX, inhibitors, which the company intends to primarily develop for orphan diseases with fibrotic pathology, with a main focus on kidney and liver diseases. From this platform, the company is developing setanaxib, a NOX inhibitor, for the treatment of primary biliary cholangitis, or PBC. The company is evaluating setanaxib in the TRANSFORM study, a Phase 2b/3 clinical trial, in which the company randomized the first patient in February 2022. Setanaxib will be administered to approximately 318 patients with PBC and elevated liver stiffness as well as intolerance or inadequate response to ursodeoxycholic acid, a generic drug also known as ursodiol or UDCA in a global trial conducted in up to 150 investigational centers. The primary endpoint is alkaline phosphatase (ALP) reduction, with key secondary endpoints, including change in liver stiffness and effect on fatigue and pruritus (itching). Following favorable safety data from a Phase 1 study, this trial will evaluate two dosing regimens of 1200mg/daily and 1600mg/daily. An interim analysis will be conducted once the 99th randomized patient has completed the Week 24 visit, which is expected in the first half of 2024, subject to recruitment rate, and will determine which dose of setanaxib will be used for the Phase 3 part of the study. Setanaxib was granted fast track designation by the FDA in August 2021. The company is also conducting a proof of concept, Phase 2 clinical trial of setanaxib administered in conjunction with pembrolizumab, a check point inhibitor, in squamous cell carcinoma of the head and neck, in order to explore setanaxib's use as a treatment approach in cancers with high levels of tumors associated fibroblasts, or CAFs.

In addition, the company has in-licensed Budenofalk 3 mg oral capsules and intend to develop Budenofalk in the United States for the treatment of autoimmune hepatitis, or AIH, subject to regulatory feedback. The company discussed development plans with the FDA for AIH during 2020 and has refined its clinical approach during 2021 and 2022 with a target to arrive at a definitive clinical development plan in 2023, subject to further interactions with KOLs and the FDA.

Strategy

The company's strategies are to apply for full marketing approval for TARPEYO and Kinpeygo; maximize the potential of Nefecon, where approved, through commercialization independently and through collaborations with third parties; efficiently advance the company's first-in-class NOX platform candidate setanaxib through clinical trials; leverage the company's proprietary formulations and significant experience with drug release technology to explore treatments in select orphan hepatic diseases; and complement the company's existing pipeline by selective acquisitions or in-licensing of product candidates focused on nephrology, hepatic or orphan diseases.

Commercial Product: TARPEYO for the treatment of IgAN

In November 2020, the company reported positive topline data from Part A of the company's global, pivotal Phase 3 clinical trial, which the company refers to as NefIgArd. In this trial of 200 patients, treatment with Nefecon was associated with a statistically significant and clinically meaningful reduction of protein in the urine, or proteinuria, and stabilization of kidney function.

The company reported topline results from the Phase 3 NefIgArd clinical trial in March 2023. The trial met its primary endpoint with Nefecon demonstrating a highly statistically significant benefit over placebo (p value < 0.0001) in eGFR over the two-year period of nine months of treatment with Nefecon or placebo and 15 months of follow-up off drug. The eGFR benefit was observed across the entire study population, irrespective of UPCR baseline. UPCR reductions observed were durable, reflecting a long-lasting treatment effect during the 15 month follow-up period off treatment. The results indicate that Nefecon was generally well-tolerated and the safety profile was consistent with that observed in Part A of the trial. The NefIgArd trial is expected to conclude in the third quarter of 2023 when the final 29 patients in China (not required for global submission purposes) have completed nine months of treatment and 15 months of observation.

The FDA has approved TARPEYO (developed under the name of Nefecon) under the accelerated approval pathway based on the reduction in proteinuria. TARPEYO was the first ever approved treatment on the U.S. market indicated for patients with IgAN. Continued approval for the approved indication may be contingent upon verification and description of clinical benefit in the confirmatory part of the trial.

The EC has granted conditional marketing authorization for Nefecon under the name Kinpeygo (budesonide) capsules for the treatment of IgAN in adults at risk of rapid disease progression with a urine protein-to-creatinine ratio (UPCR) greater than or equal to 1.5 gram/gram. On February 1, 2023, the MHRA granted Conditional Marketing Authorization for Kinpeygo for the same indication as the EC.

Nefecon has been granted seven years orphan drug exclusivity in the United States and ten years orphan market exclusivity by the EC and by the MHRA. Since the approval of TARPEYO in the United States in December 2021, the company has been commercializing TARPEYO independently in the United States through a targeted commercial sales infrastructure. The company launched TARPEYO in the United States in January 2022. In 2019, the company granted a license to Everest, to develop and commercialize Nefecon for IgAN and other potential indications in Greater China and Singapore. In March 2022, the company expanded the territory covered by the agreement to include the Republic of Korea. In July 2021, the company entered into a license agreement with STADA to commercialize Nefecon for the treatment of IgAN in the EEA, Switzerland, and the U.K. In December 2022, the company entered into an exclusive license agreement with Viatris, to register and commercialize Nefecon for the treatment of IgAN in Japan. The company retains worldwide rights to Nefecon other than in Greater China, Singapore, the Republic of Korea, the EEA, Switzerland, the U.K, and Japan; and has entered into a Managed Access Program Distribution Agreement with Tanner, under which Tanner agrees to act as the exclusive distributor for Calliditas to provide pre-approval access to the TARPEYO in response to requests by physicians, hospitals, pharmacies, distributors, ministries of health or other parties on behalf of specific or named patients, when the TARPEYO is not approved or licensed for use in the named patient's home country.

Solution: Nefecon

Nefecon is a proprietary, novel oral, formulation of budesonide, designed to deliver budesonide to the ileum of the small intestine, where the Peyer's patches are concentrated. Budesonide is a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism, resulting in limited systemic exposure. Nefecon was designed as a 4 mg delayed release capsule with an enteric coating so that it remains intact until it reaches the ileum. Each capsule contains beads coated with various polymers and budesonide designed to target the area with the highest concentration of Peyer's patches, with the intention of having a disease-modifying effect.

Nefecon has an enteric coating layer that delivers the capsule intact to the ileum of the small intestine, where the Peyer's patches are concentrated. The capsule contains triple coated beads that help control the rate of release of the active ingredient, budesonide. Nefecon is thought to reduce the levels of circulating galactose deficient IgA and subsequently the production of IgA or IgG antibodies that bind to galactose deficient IgA to form immune complexes that accumulate in the kidneys causing renal injury.

Nefecon has two components: an enteric-coated layer that delivers the capsule intact to the ileum and triple coated beads that control the release of the active ingredient.

Nefecon is differentiated in its indications, properties, profile and mechanism of action as compared to other marketed products that deliver budesonide to the intestine and is the only formulation of budesonide that is indicated for the treatment of IgAN. Uceris is formulated as a 9 mg extended release tablet administering budesonide specifically to the colon for the treatment of ulcerative colitis. Entocort is formulated as a 3 mg delayed release capsule used at a maximum dose of 9 mg throughout the entire approximately eight meters of the intestine in a continuous release for the treatment of Crohn's disease. Unlike Nefecon, neither of these two formulations are designed to, or are in their approved dosages capable of, delivering the dose of budesonide to the ileum that was found to be efficacious for the treatment of IgAN in the company's clinical trials. Neither have been tested in randomized, controlled clinical trials in IgAN patients. Any attempts to use these drugs to address IgAN would either be ineffective or would require dosing patients at levels several times higher than the doses approved, with unknown consequences for patient safety.

The company has combined its proprietary formulation technology with know-how developed internally to create Nefecon. This proprietary formulation will constitute a barrier to entry that would require significant time, focus and investment for a competitor to overcome. In addition, Nefecon has been granted orphan drug exclusivity in the United States until December 15, 2028 (seven years from the company's initial FDA approval in December 2021). Nefecon has also been granted orphan drug market exclusivity in the EU and the U.K., which will provide marketing exclusivity until July 15, 2032 and February 1, 2033, respectively.

Nefecon Phase 3 Clinical Trial (NefIgArd Trial)

The company is conducting a global pivotal Phase 3 clinical trial in IgAN, which the company refers to as NefIgArd. NefIgArd is a double-blind, placebo-controlled, two-part phase 3 clinical trial comparing nine months of Nefecon 16 mg once daily to placebo in IgAN patients on a stable recommended or maximum tolerated dose of RAS inhibitor therapy for control of blood pressure. The company randomized its first patient in NefIgArd in November 2018, the results of the first part of the trial were published in a peer reviewed journal in October 2022, and the company reported positive topline data in March 2023.

Trial Design

The first part of NefIgArd, which the company refers to as Part A, was designed to evaluate reduction of the surrogate marker proteinuria, measured by the urine protein to creatinine ratio, or UPCR as its primary endpoint, which is the same endpoint used in the company's previously completed NEFIGAN clinical trial. In addition, a key secondary endpoint of Part A is the difference in kidney function between treated and placebo patients as measured by eGFR. This key secondary endpoint in Part A, measured over a nine-month period, is informative of the primary endpoint of Part B.

The second part, which the company refers to as Part B, was the post-approval confirmatory part of the trial designed to provide evidence of long-term renal benefit. Completion of enrollment of the additional 160 patients required for Part B took place in January 2021. The total number of 360 patients was required to sufficiently power the trial in order to assess the difference in kidney function between Nefecon-treated and placebo patients as measured by eGFR over a two-year period from the start of dosing of each patient. The company reported positive topline results of Part B in March 2023. Across both parts, NefIgArd has enrolled a total of 366 patients in the global study.

NeflgArd Part A Results

The company reported Part A topline results in November 2020. The complete Part A results from NeflgArd were published in a peer reviewed journal, Kidney International, in October 2022. The analysis set included 199 patients diagnosed with IgAN and who were on a background of optimized and stable renin-angiotensin system, or RAS inhibitor therapy.

NeflgArd Full Results

The company reported topline results in March 2023. The analysis included 364 patients diagnosed with primary IgAN and who were on a background of optimized and stable renin-angiotensin system (RAS) inhibitor therapy.

Open-Label Extension Trial

The company has initiated an open-label extension trial or the OLE trial, for eligible patients who have completed treatment in Part A and Part B of NefIgArd. The OLE trial commenced when the first patient completed both Part A and Part B of NefIgArd, which occurred in the fourth quarter of 2020, and the company reported dosing of the first patient in February 2021. The company expects the OLE trial to complete in first half of 2024.

Nefecon Phase 2 Clinical Trial (NEFIGAN Trial)

In 2015, the company completed a double-blind, placebo-controlled clinical trial, known as NEFIGAN, in 153 adult patients. In this trial, patients were randomized to receive either 8 mg or 16 mg per day of Nefecon or placebo, each on top of optimized RAS blockade to lower blood pressure, the predominant current standard of care. This trial involved 62 sites across ten countries in Europe, and was at the time the largest double-blind trial ever conducted with an investigational candidate in IgAN patients.

The primary endpoint of mean reduction in proteinuria as measured by UPCR was achieved during the planned predefined analysis, and under the predefined protocol, no further analysis of the primary endpoint was to be conducted.

In this trial, Nefecon was also observed to statistically significantly reduce proteinuria and to provide clinical benefit by preserving kidney function, as measured by eGFR, which is considered a key metric for measuring kidney disease progression.

Nefecon was observed to be generally well tolerated. The company observed no clinically meaningful changes in blood pressure, body weight or hemoglobin A1C, a measure of blood sugar metabolism, from baseline, and there were no serious infections reported in the trial.

Nefecon Phase 2a Clinical Trial

In 2010, the company completed a single-cohort, open-label Phase 2a clinical trial in which six biopsy-confirmed IgAN patients received 8 mg of Nefecon orally daily for six months, with a three-month follow-up period after discontinuation of treatment.

Nefecon was observed to be well tolerated, with no serious adverse events reported. Of the adverse events reported, 76% were classified as mild and 24% were classified as moderate. Three patients withdrew from the trial due to adverse events.

Regulatory Plans

The FDA granted accelerated approval to TARPEYO on December 15, 2021 and the company reported commercial availability of TARPEYO in the United States in January 2022. The EC granted conditional marketing authorization for Kinpeygo on July 15, 2022 and the company's licensee STADA announced commercial availability in Germany in September 2022. On February 1, 2023, the MHRA granted Conditional Marketing Authorization for Kinpeygo.

TARPEYO has been granted orphan drug exclusivity in the United States and Kinpeygo has been granted market exclusivity in the EEA and Great Britain.

The FDA accelerated approval of TARPEYO is based on evaluation of the surrogate endpoint of proteinuria reduction. Continued approval for the approved indication may be contingent upon verification and description of clinical benefit in the confirmatory part of the trial. The EC and the MHRA apply a similar approach via the conditional approval pathway in the EU and Great Britain.

The topline results from the NefIgArd trial support filing for a full approval for adult patients with primary IgAN based on the Phase 3 study population, and the company plans to file for such approval with the FDA, during 2023.

Commercialization

Following FDA approval, the company began commercializing TARPEYO in the United States. The company's targeted commercial sales infrastructure now consists of 60 experienced rare disease account managers, focused on the approximate 4,000 nephrologists who treat the vast majority of IgAN patients in the United States. TARPEYO sales began in late January 2022 and the company's U.S. organization remains focused on disease and product education, so that physicians can identify appropriate patients for TARPEYO. In addition, the company works with advocacy organizations and has developed a comprehensive patient services program to assist with access to TARPEYO.

In 2019, the company granted a license to Everest to develop and commercialize Nefecon for IgAN and other potential indications in Greater China and Singapore. In March 2022, the company expanded the territory covered by the agreement to include the Republic of Korea. In November 2022, the company announced that Everest's New Drug Application for Nefecon was accepted for review by the Chinese National Medical Products Administration.

In July 2021, the company entered into a license agreement with STADA to commercialize Nefecon for the treatment of IgAN in the EEA, Switzerland and the U.K. STADA is commercializing the product under the brand name Kinpeygo. STADA announced commercial availability of Kinpeygo in Germany in September 2022.

In December 2022, the company entered into an exclusive license agreement with Viatris, to register and commercialize Nefecon for the treatment of IgAN in Japan.

The company retains worldwide rights to Nefecon other than in Greater China, Singapore, the Republic of Korea, Europe, and Japan; and has entered into a Managed Access Program Distribution Agreement with Tanner, under which Tanner agrees to act as the exclusive distributor for Calliditas to provide pre-approval access to the TARPEYO in response to requests by physicians, hospitals, pharmacies, distributors, ministries of health or other parties on behalf of specific or named patients, when the TARPEYO is not approved or licensed for use in the named patient's home country.

The company's pipeline: First-in-class NOX inhibitor platform with a lead product candidate: setanaxib

Setanaxib for the Treatment of PBC

Setanaxib has shown clinically relevant biochemical and anti-fibrotic activity in a Phase 2 clinical trial in PBC, an orphan liver disease in which fibrosis in an important part of the underlying pathology, despite not achieving its primary endpoint. Setanaxib is the first clinical product candidate within the newly created '-naxib' international nonproprietary name stem designated by the World Health Organization. Based on available Phase 2 clinical data and recent Phase 1 data, combined with interactions with the FDA related to setanaxib, the company has initiated a Phase 2b/3 trial in this indication, with the first patient randomized in February 2022. Setanaxib is differentiated from other approved or late-stage development candidates in PBC, due to its effect on fibrosis, inflammation, and potentially significant impact on fatigue, as seen in the Phase 2 trial. The company has received orphan drug designation for the treatment of PBC by the FDA.

Setanaxib Clinical Development

Based on earlier Phase 2 data and recent positive Phase 1 data, the company has initiated a Phase 2b/3 trial in PBC. Setanaxib is differentiated from other approved or late-stage development candidates in PBC, due to its effect on fibrosis, inflammation and potentially significant impact on fatigue, as seen in the Phase 2 trial. Setanaxib was developed initially by the Genkyotex group of companies, now the company's wholly-owned subsidiaries.

In a Phase 2 trial conducted by Genkyotex and concluded in 2019, setanaxib did not reach its selected primary endpoint of change in GGT (Gamma-glutamyl Transferase); however, it showed an effect on the secondary endpoint of ALP (Alkaline Phosphatase) and an effect on fibrosis as measured by a variety of biomarkers, as well as Fibroscan. It also resulted in a statistically significant impact on fatigue, the most commonly reported symptom of PBC, and is the only drug candidate, to the company's knowledge, to achieve this to date in this patient population.

In January 2021, Genkyotex reported positive data from its Phase 1 clinical trial to evaluate the safety and pharmacokinetics of setanaxib. The Phase 1 trial assessed the safety and pharmacokinetics of oral setanaxib at selected doses in 46 healthy adult male and female subjects. The trial consisted of a single ascending dose, or SAD, part and a multiple ascending dose, or MAD, part with dosing up to 1600 mg/day. The trial demonstrated that setanaxib was generally well tolerated at the doses tested, with no safety concerns or dose-limiting toxicity being identified.

In August 2021, the company received FDA Fast Track Designation for setanaxib in PBC.

Based on the positive data from the Phase 1 trial of setanaxib doses up to 1600 mg/day, the company has initiated a 52-week, randomized, placebo-controlled, double-blind trial in PBC with an adaptive Phase 2b/3 design, incorporating higher doses than previously used in the Phase 2 trial and using a composite biochemical response that includes the change in ALP as a primary endpoint. The first patient was randomized in this trial in February 2022. Setanaxib will be administered to approximately 318 patients with PBC and elevated liver stiffness, as well as intolerance or inadequate response to UDCA in a global trial conducted in up to 150 investigational centers. The primary endpoint is ALP reduction, with key secondary endpoints, including change in liver stiffness and effect on fatigue and pruritus (itching). The trial will evaluate two dosing regimens of 1200mg/daily and 1600mg/daily. An interim analysis will be conducted once the 99th randomized patient has completed the Week 24 visit, which is expected in the first half of 2024, subject to recruitment rate, and will determine which dose of setanaxib will be used for the Phase 3 part of the study.

Setanaxib - SCCHN

The company also intends to evaluate setanaxib in head and neck cancer, building on promising in vivo preclinical data that suggests that setanaxib could function as an adjunct therapy to immune-oncology therapies. The response to immuno-oncology therapies can be affected by the tumor microenvironment, in particular by the numbers of tumor-infiltrating lymphocytes, or TILs, and cancer-associated fibroblasts, or CAFs, in the tumor. A relationship between CAFs and prognosis in squamous cell carcinoma of the head and neck, or SCCHN, has been established.

The company is conducting a Phase 2 proof-of-concept study in patients with head and neck cancer, which will investigate administration of setanaxib in conjunction with immunotherapy targeting CAFs.

The study will likely involve approximately 50 patients. The first patient was randomized in the second quarter of 2022, with an interim biomarker readout expected in mid-2023.

Setanaxib - Other Indications

Based on supportive pre-clinical data generated during 2022, the company plans to initiate a Phase 2a study with setanaxib in about 20 patients with Alport syndrome in the second quarter of 2023. The study treatment period will be 24 weeks with the primary objective to investigate safety and tolerability, with secondary endpoints related to reduction of UPCR.

Setanaxib is also being evaluated in two Phase 2 investigator led trials. One is being conducted in type 1 diabetic kidney disease, or DKD. In addition, a grant from the United States National Institutes of Health, or NIH, of $8.9 million was awarded to the University of Alabama at Birmingham to fund a multi-year research program evaluating the role of NOX enzymes in idiopathic pulmonary fibrosis, or IPF, a chronic fibrosing lung disease. The core component of this program is a randomized, placebo-controlled Phase 2 trial with setanaxib in patients suffering from IPF for which the enrollment of a first patient was announced in September 2020.

This platform also has several other potential applications across orphan indications, focusing on anti-fibrotic and anti-inflammatory applications. Subject to positive data from ongoing trials, the company could also see setanaxib as an important potential drug candidate for larger indications in oncology and NASH. Setanaxib is the lead compound, complemented by a research effort focused on developing follow up compounds.

The company's Product Candidate: Budenofalk for the Treatment of Autoimmune Hepatitis

The company has exclusively in-licensed Budenofalk 3 mg oral capsules for the U.S. market from Dr. Falk Pharma GmbH, or Falk Pharma. Budenofalk is a formulation of budesonide originally developed to treat Crohn's disease. The company's license covers all indications for the United States market, excluding orphan indications outside of liver targets.

Budenofalk has been tested in a large, randomized, controlled clinical trial in AIH patients and is approved for the treatment of AIH in several countries in Europe, but there has been no clinical development or regulatory approval in the United States. In addition, Budenofalk has been approved for the treatment of Crohn's disease and acute episodes of collagenous colitis in several countries in Europe, but regulatory approval was never pursued in the United States. Budenofalk also has the potential to address AIH for patients in the United States. The company has received orphan drug designation for the treatment of AIH using budesonide by the FDA. The company has discussed the development plans with the FDA for AIH since 2020, but additional interaction is required before establishing any definitive clinical development plans. The company is conducting additional investigations in preparation for FDA interactions during 2023 to address outstanding questions and assess the potential of seeking approval of Budenofalk for AIH in the United States through the Section 505(b)(2) approval pathway.

Solution: Budenofalk

Budenofalk was studied in a randomized clinical trial and was observed to have greater clinical activity and fewer side effects compared to treatment with systemic corticosteroids, which may drive patient compliance and improve outcomes. Budenofalk has the potential to address the significant unmet medical need to improve outcomes for AIH patients for whom there are no approved therapies in the United States.

Collaborations and License Agreements

License Agreement with Everest

In 2019, the company entered into a license agreement with Everest, pursuant to which the company granted Everest an exclusive, royalty-bearing, non-transferable (other than in connection with a change of control transaction) license to develop, manufacture and commercialize Nefecon for IgAN, which Everest may exercise its option to develop Nefecon in other potential indications, if and when the company initiate a registrational clinical study in such indications, which the company collectively refers to as the Licensed Product. The territories covered by the Everest license are Greater China, including mainland China, Taiwan, Hong Kong and Macau, and Singapore which the company collectively refers to as the Territories. In March 2022, the company expanded the territory covered by the agreement to include the Republic of Korea.

Pursuant to the terms of the Everest license, Everest must use commercially reasonable efforts to develop the Licensed Product and to obtain, support and maintain approval of the Licensed Product in the Territories. Everest is also entitled to sublicense the rights granted under the Everest license to its affiliates and to other third-parties with the company's prior consent.

License Agreement with STADA

On July 21, 2021, the company entered into a license agreement with STADA, to register and commercialize Nefecon for IgAN in the EEA, Switzerland and the U.K.

License Agreement with Viatris

In December 2022, the company entered into a license agreement with Viatris, pursuant to which the company granted Viatris an exclusive, royalty-bearing, non-transferable license to develop, manufacture and commercialize Nefecon for IgAN in Japan.

Intellectual Property

Patents

With regards to Nefecon, the company co-owns one patent family with Kyowa Kirin Services Ltd., f/k/a Archimedes Development Ltd., to which the company has a sole and exclusive global license, even in relation to the other co-owner, in any field of use. This patent family protects a formulation for the oral delivery of budesonide and the medicinal use thereof. The patents in this patent family expire in 2029 provided all renewal fees are paid within the prescribed period, which the company intends to do. The patents in this family include a United States patent, a patent in each of China, Hong Kong and Japan and a European patent that has been validated in 15 countries (Austria, Belgium, Switzerland, Germany, Denmark, Spain, Finland, France, the U.K., Italy, the Netherlands, Norway, Poland, Sweden and Turkey). The patents in this family are not eligible for extension in the United States because the active ingredient is used in existing approved drugs. In Europe, extension of the patents is not likely subject to the recent judgement of litigation in the EU, CJEU C-443/17, related to the degree to which it is possible to obtain a Supplementary Protection Certificate for a previously authorized active ingredient.

With regards to the NOX estate, there are four patent families covering various aspects of the setanaxib asset derived from four PCT applications. The composition of matter and certain methods of therapy are covered in two of these patent families. The third covers the use of setanaxib in certain oncology indications, including head and neck cancer. The fourth covers the use of setanaxib in the prevention and/or treatment of an osteoclastogenesis dysfunction related with increased bone turnover or bone resorption of secondary cause and/or osteoporosis. There is one additional patent family that covers other NOX inhibitors and their use. As the company's NOX inhibitor patents and applications cover new chemical entities, the territorial coverage is generally quite wide, and as the compounds do not yet form part of an approved drug product, patent life may potentially be extended in countries where legislation provides for patent term extension. The two families covering setanaxib's composition of matter have projected expiry dates in 2028 and 2029, excluding potential extensions.

Government Regulation

The company's product candidates must be approved by the FDA through the NDA process before they may be legally marketed in the United States and by the EC following a positive opinion provided by the EMA through the marketing authorization application process for a drug falling within the scope of the centralized procedure or by a national Competent Authority through other marketing authorization application processes (national procedure, mutual recognition or decentralized procedure) before they may be legally marketed in the EU.

History

Calliditas Therapeutics AB was founded in 2004. The company was incorporated in 2004.