x200B; ​ ​ ​ INTERIM REPORT JANUARY 1 – JUNE 30, 2023 Filing for full approval of TARPEYO Group Financial Summary Key Figures April 1

1.713.625.217.577.78

INTERIM REPORT JANUARY 1 JUNE 30, 2023

Filing for full approval of TARPEYO

Group Financial Summary

April 1 - June 30, 2023

January 1 - June 30, 2023

Significant Events in Q2 2023, in Summary

In June 2023, Calliditas had two oral presentations and two abstracts reflecting top line data and analyses from the NeflgArd Phase 3 Study, evaluating Nefecon (TARPEYO (budesonide) delayed release capsules/Kinpeygo ) in patients with IgA nephropathy (IgAN), at the European Renal Association (ERA) Congress in Milan, Italy.

In June 2023, Calliditas announced the submission of a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) seeking full approval of TARPEYO (budesonide) delayed release capsules (developed under the project name Nefecon) for the entire study population evaluated in the Phase 3 NeflgArd study. The sNDA submission was based on the full data set from the Phase 3 NefIgArd clinical trial, a randomized, double-blind, multicenter study which assessed the efficacy and safety of Nefecon dosed at 16 mg once daily versus placebo on a background of optimized RASi therapy in adult patients with primary IgAN.

The trial met its primary endpoint of kidney function, with Nefecon demonstrating a highly statistically significant benefit over placebo (p value < 0.0001) in estimated glomerular filtration rate (eGFR) over the two-year period of 9 months of treatment with Nefecon or placebo and 15 months of follow-up off drug.

Updated 2023 Outlook

For 2023, Calliditas expects revenue growth in the US where:

Net sales from TARPEYO are estimated to be USD 100-120 million for the year ending December 31, 2023.

Investor Presentation August 17, 2023 14:30 CET

Audio cast with teleconference, Q2 2023.

Web cast: https://ir.financialhearings.com/calliditas-therapeutics-q2-2023

Tele Conference: SWE +46 (8) 525 07 003, US +1 774 450 99 00, UK +44 7073 5048

sNDA submitted to the FDA for full approval

In June we submitted a supplemental New Drug Application (sNDA) to the FDA for full approval of TARPEYO for patients with primary IgAN, based on the data from our Phase 3 clinical trial, NefIgArd. This global, randomized, placebo controlled, double-blinded study successfully met its primary endpoint, demonstrating a highly statistically significant benefit over placebo (p value < 0.0001) in average estimated glomerular filtration rate (eGFR) over the two-year period of 9-months of treatment with Nefecon or placebo and 15-months of follow-up off drug. There was statistically significant impact on microhematuria and the 2-year total slope, using the Vonesh method*, showed an improvement of approximately 3.0ml/min/ year, which is significantly higher than the assumed minimum level of ~1.3ml/min/year that is often quoted as the bar the FDA looks for in terms of establishing clinical benefit. There was also a durable suppression of proteinuria, which lasted not only during the 9 months of treatment but also over the 15 months of observation off drug. These results were observed in the entire patient population, irrespective of UPCR levels at baseline, and we believe support the thesis that this drug is disease modifying, with a potential to significantly delay the need for dialysis or transplantation.

The data from the trial were first shared in late breaking presentations at the ERA EDTA conference, which took place 15 18th of June in Milan and where we had two oral presentations and two posters. The presentations were very well received by the nephrology community and there was a lot of buzz in several subsequent presentations where the data was mentioned or discussed. We have also had the opportunity to conduct some Advisory Board meetings in the US, where we have shared the recent clinical data under confidentiality and received feedback from practicing nephrologists. This has been extremely encouraging and the feedback has been consistent related to TARPEYO being perceived as a disease modifying treatment with an attractive risk / benefit profile, which is expected to become part of standard of care. We can't wait to share the data with the broader nephrology community in the US and ultimately offer physicians a medication that may significantly delay patient time to dialysis.

In the US, we reported another quarter of record enrollments of 422, and 232 new prescribers, reflecting the continued growth of the TARPEYO franchise. Total Q2 revenues were SEK 269 million, out of which net revenues from TARPEYO amounted to SEK 259 million (USD 24.7m). We have seen very positive development both in terms of enrolments as well as revenue growth from the TARPEYO franchise this year, but due to challenges primarily relating to market access friction and the reduced market opportunity related to accelerated approval with a more limited label, we have revised our guidance for 2023 to USD 100 120m of net TARPEYO revenues. We believe that, if granted, a full approval with access to the entire study population will provide significant benefits in 2024 and we are excited about continuing to build an even stronger franchise on the basis of the effect on kidney function. The operating loss for the quarter was significantly reduced to SEK 75m (USD 7.2m) and our cash position remains strong with SEK 866m on the balance sheet, which we believe will be sufficient to take us to profitability.

The publication in The Lancet this week of the positive clinical data from the first ever successful full Phase 3 study in IgA nephropathy will mark the beginning of peer-to-peer scientific dialogue with physicians, offering opportunities to educate the nephrology community about the results of the trial and discuss appropriate treatment paradigms.

In the post quarter period we also reported clinical and biomarker data from our Phase 2 setanaxib head and neck cancer trial. We were very excited to see that 6 out the 7 patients who were progression-free at the time of readout were in the treatment arm, and we

look forward to reading out the full trial in 1H 2024. This also marked an opportunity for us to conduct a transcriptomic analysis, which clearly identified the hepatic and IPF related fibrosis pathways as core pathways impacted by the drug. Based on recently reported biomarker data, as well as other factors including regulatory feedback, we have decided to revise the design of the TRANSFORM trial, our clinical study in PBC, to enable us to read out Phase 2b data in 1H 2024. This will allow us to review the optimal endpoint of a potential Phase 3 study, as well as to explore alternative or complementary indications and potential partnerships within the broader area of fibrotic disease.

We continue to make progress on our preparations for the study of setanixib in Alport syndrome, and the investigator led study in IPF. We also continue to explore additional renal indications for which we believe that setanaxib may have a beneficial effect based on its mode of action.

We look forward to continuing our commercial, regulatory and clinical work through the rest of this year and beyond as we await regulatory decisions both in China and in the US - we remain excited about the future!

Ren e Aguiar-Lucander, CEO

*Linear spline mixed-effect method for slope-based endpoints in clinical trials of chronic kidney disease

Filing for Full Approval of TARPEYO

In June 2023, Calliditas submitted a supplemental New Drug Application (sNDA) to the US Food and Drug Administration (FDA) seeking full approval of TARPEYO (budesonide) delayed release capsules for the entire study population from the Phase 3 NeflgArd study. TARPEYO is currently approved in the US under accelerated approval to reduce proteinuria in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) 1.5g/g.

The sNDA submission is based on the full data set from the Phase 3 NefIgArd clinical trial, a randomized, double-blind, multicenter study which assessed the efficacy and safety of TARPEYO (developed under the project name Nefecon ) dosed at 16 mg once daily versus placebo on a background of optimized RASi therapy in adult patients with primary IgAN. In March 2023, Calliditas read out topline data from the pivotal Phase 3 NefIgArd trial, which met its primary endpoint by demonstrating a highly statistically significant benefit over placebo (p value < 0.0001) in kidney function, as measured by estimated glomerular filtration rate (eGFR) over the two-year period of 9 months of treatment with TARPEYO or placebo and 15 months of follow-up off drug. The eGFR benefit was observed across the entire study population, irrespective of urine protein-to-creatinine ratio (UPCR) baseline, which supports the regulatory filing for full approval in the study population.

Calliditas initially filed for accelerated approval with the FDA in March 2021. The accelerated approval pathway allows drugs targeting serious conditions that fill an unmet medical need to be approved based on a surrogate endpoint. The surrogate endpoint in the NefIgArd trial was reduction of proteinuria versus placebo, an endpoint supported by a meta-analysis of clinical studies carried out by Inker et al. The FDA granted accelerated approval for TARPEYO in December 2021, and it was launched in the US on January 28, 2022.

The eGFR treatment benefit observed across the entire study population, irrespective of UPCR levels, provides further evidence that targeting IgAN at its source can offer patients a treatment that holds the promise of being disease-modifying. We are pleased to be able to provide the FDA with the full results of our Phase 3 study, and we look forward to interactions with the FDA regarding full approval of TARPEYO.

Ren e Aguiar-Lucander, CEO

1 Inker LA, Mondal H, Greene T, et al. Early Change in Urine Protein as a Surrogate End Point in Studies of IgA Nephropathy: An Individual-Patient Meta-analysis. Am J Kidney Dis.

2016;68(3):392-401. doi:10.1053/j.ajkd.2016.02.042

The NefIgArd Phase 3 Trial: Design

NefIgArd is the first Phase 3 trial specifically designed for IgA nephropathy to show a statistically significant and clinically relevant kidney protective effect as measured by eGFR.1 The sNDA submission to the FDA was based on the data from this trial, with Calliditas filing for full approval on the basis of the strong eGFR and UPCR data readout.

NefIgArd is a pivotal, global Phase 3 trial consisting of two readouts. An interim readout provided data on the efficacy and safety of Nefecon in 199 patients. The primary endpoint was the effect of Nefecon on urine protein-to-creatinine ratio (UPCR, otherwise known as proteinuria) over 9 months compared to placebo, and a key secondary endpoint was change in estimated glomerular filtration rate (eGFR), a measure of kidney function. These data were published in Kidney International in October 2022. Calliditas' initial regulatory filings with the FDA and European Medicines Agency (EMA) were based on positive data from the interim readout of the NefIgArd pivotal Phase 3 study, which read out topline data in November 2020.

The full Phase 3 NefIgArd trial consisted of a total of 364 patients, including the 200 patients in the interim analysis and included a 15-month post-treatment observational period for all study participants to confirm long-term renal protection. The endpoint of the full Phase 3 trial assessed the difference in kidney function between treated and placebo patients, as measured by eGFR, over a two-year period from the start of dosing of each patient.

Base inclusion criteria:

The full NefIgArd trial read out positive topline data in March 2023, meeting its primary endpoint of kidney function by demonstrating a statistically significant benefit in eGFR of Nefecon over placebo after 9 months of treatment and 15 months of follow-up off drug.

1 Barratt, J., Lafayette, R., Kristensen, J., et al. (2022). Results from part A of the multi-center, double-blind, randomized, placebo controlled NeflgArd trial evaluated targeted-release formulation of budesonide for the treatment of primary https://doi.

org/10.1016/j.kint.2022.09.017

The NefIgArd Phase 3 Trial: Topline Readout

The primary endpoint of the Phase 3 trial was a time-weighted average of eGFR observed at each time point over two years. The primary endpoint was met, and over the two-year period of treatment and observation, the mean decline in eGFR was 2.47 mL/min/1.73 m2 for patients who received Nefecon compared with 7.52 mL/min/1.73 m2 for patients who received placebo, a result that was highly statistically significant. On average, over the two-year period, there was therefore a 5.05 mL/min/1.73 m2 eGFR treatment benefit in favor of Nefecon compared to placebo (p<0.0001).

In placebo-treated patients, after 9 months there was a decline in eGFR of 8.2%, corresponding to a loss of 4.56 mL/min/1.73 m2. Meanwhile, in Nefecon-treated patients, eGFR increased by 1.2% versus baseline, reflecting a slight increase in eGFR of 0.66 mL/min/1.73 m2.

At 24 months, after 9 months of treatment and 15 months of observation, the eGFR decline for placebo-treated patients was 21.5%, corresponding to a loss of 12 mL/min/1.73 m2. For those patients dosed with Nefecon the eGFR decline was 11%, corresponding to a 6 mL/min/1.73 m2 decline in eGFR. Therefore, dosing with 16mg Nefecon in 364 patients resulted in 50% less loss of kidney function, as measured by eGFR, vs placebo at 24 months after a treatment of only 9 months.

There was a cumulative improvement in proteinuria in patients treated with Nefecon versus placebo during the 9-month treatment period, which continued to significantly improve at 12 months. At month 24, proteinuria levels in patients who had received Nefecon

were still at a reduced level, similar to that observed at the 9-month time point, reflecting the durability of the proteinuria reduction of a 9-month course of treatment.

Nefecon was generally well tolerated, and the adverse event profile was similar to that reported at the time of the interim results. The majority of the treatment emergent adverse events (TEAEs) were mild or moderate severity. The most commonly reported TEAEs observed with an increased frequency compared to placebo were peripheral oedema, hypertension, muscle spasms, and acne. Objective measures of mean weight and BP showed non-clinically relevant, fully reversible changes, and TEAEs led to discontinuation of study drug in fewer than 10% of Nefecon-treated patients.

Publication in a Peer-Reviewed Journal:

In August 2023 Calliditas announced the publication of this data in The Lancet.

Data Presentations at ERA-EDTA Congress

Following the trial readout of the NefIgArd study in March, Calliditas' late-breaking data presentations were selected for the 60th European Renal Association European Dialysis and Transplant Association (ERA-EDTA) Congress, which took place in Milan in June.

Long-term renal benefit over 2 years with Nefecon verified:

The NefIgArd Phase 3 full trial results

Professor Richard Lafayette presented the primary data from the final analysis of NefIgArd, comprising 9 months of treatment and 15 months of follow-up. The presentation included a detailed overview of the patient population characteristics, and an analysis of the eGFR benefit in the overall patient population and subgroups; UPCR benefit was also presented.

Nefecon Treatment Likely Modulates Downstream Pathways of Kidney Inflammation and Fibrosis in IgA Nephropathy

Karen Molyneux, PhD, of the University of Leicester, presented her research into Nefecon's effect on processes previously shown to be important in the pathogenesis of kidney injury in IgAN. Her gene ontology analysis of urine samples from 18 patients from each of the placebo and 16 mg/day arms of the NEFIGAN trial, collected at start and end of treatment, revealed that treatment with 16 mg of Nefecon led to a significant enrichment of multiple downstream pathways of kidney inflammation and fibrosis.

Hematuria reduction in patients with IgAN following Nefecon treatment:

A secondary analysis of the full 2-year NefIgArd Phase 3 trial results

This poster from Professor Richard Lafayette presented further details on a secondary efficacy endpoint in the NefIgArd trial, the presence of microhematuria (blood in the urine). Hematuria is a common clinical manifestation of IgAN, and changes in hematuria can be measured as part of the evaluation of the efficacy of IgAN treatments. In the NefIgArd trial, at randomization the proportion of patients with microhematuria was similar in the Nefecon and placebo groups. The proportion of patients with microhematuria in the Nefecon group decreased from 66.5% at baseline to 40.5% during follow-up, compared with a decrease from 67.8% to 61.2% in the

placebo group at the same time points. This secondary analysis shows that after 9 months of Nefecon 16 mg/day treatment, a clinically relevant and durable reduction in microhematuria was seen, providing further evidence for the disease-modifying effect of Nefecon.

Durable proteinuria reduction over 2 years with Nefecon treatment:

A secondary analysis of the full NefIgArd Phase 3 trial results

This poster from Professor Richard Lafayette presented further details on changes in UPCR observed in the NefIgArd trial. At 24 months, UPCR was reduced by 30.7% from baseline in the Nefecon group compared with 1% in the placebo group (comparative reductions at the end of the 9-month treatment period were 33.6% and 5.2%, respectively). The pre-defined secondary analysis of durability of proteinuria reduction showed that both UPCR and UACR (urine albumin-to-creatinine ratio) were significantly reduced over 12 24 months in the Nefecon group compared with placebo. These secondary analyses demonstrated that after 9 months of Nefecon 16 mg/day treatment, a clinically relevant reduction in proteinuria was seen in patients with primary IgAN. This effect was durable, being maintained throughout the 15-month off-drug observation period. These results lend further support to the clinical benefit of Nefecon, as well as provide further evidence of a disease-modifying effect.

Nefecon's Mechanism of Action

Nefecon was the first-ever medication approved by the FDA and European Commission for IgAN, and the only treatment specifically designed to target the origin of IgA nephropathy (IgAN) with a view to be disease-modifying.

IgAN Disease Background

IgAN is a serious progressive disease, in which up to 50% of patients end up at risk of developing end-stage renal disease (ESRD) within ten to twenty years. Although IgAN manifests in the kidney, the evidence indicates that it is a disease that starts in the distal part of the intestine, specifically in the ileum. Peyer's patches, which are concentrated within the gut-associated lymphoid tissue in the ileum, have been identified as a major source of mucosal-type IgA antibodies. Patients with IgA nephropathy have elevated levels of mucosal-type IgA, which in contrast to the majority of the IgA in the blood are predominately dimeric or polymeric and are galactose-deficient. In IgAN patients, a combination of a genetic predisposition and of environmental, bacterial and dietary factors is presumed to lead to an increased production of these galactose-deficient IgA antibodies. This increased production, potentially in conjunction with increased intestinal permeability, leads to these secretory antibodies appearing in the blood.

The galactose-deficient spot at the hinge region of the IgA antibodies is immunogenic when found in the circulation. It therefore generates an autoimmune response, attracting autoantibodies in the form of IgG or IgA, which form pathogenic immune complexes that deposit in the glomeruli, the kidney's filtration apparatus. The trapped immune complexes initiate an inflammatory cascade which damages the kidney and ultimately destroys its filtration mechanism. This leads to slow, progressive deterioration of renal function, which in many patients ultimately results in the need for dialysis or a kidney transplant.

Nefecon is an oral, delayed release formulation of budesonide, a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism, resulting in limited systemic exposure. It 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.

Continued Growth of TARPEYO

During the second quarter of 2023, the Calliditas commercial team continued to expand the TARPEYO franchise, further reinforcing the position of TARPEYO as a transformative treatment option for IgA Nephropathy (IgAN).

The ERA-EDTA presentation of key data from the Phase 3 trial including the long term kidney protective effect of the drug marked the first time the results from the full Phase 3 study population were shared with the scientific community. The presentation was received with great enthusiasm by nephrologists and there was a real buzz around the data presented. Another critical milestone this quarter was submitting the sNDA to the FDA seeking full approval for patients with primary IgAN for TARPEYO.

Net sales of TARPEYO in the US for Q2 were USD 24.7 million (SEK 259.2 million), a 39% increase over Q1 and 275% increase over the same quarter in 2022. In addition, our specialty sales force generated another record quarter of 422 enrollments, contributing to a total of 831 enrollments year-to-date. This reflects over 180% growth over the first half of 2022, which underscores the continued adoption and growing recognition of TARPEYO's clinical value among healthcare providers. Furthermore, an additional 232 new prescribers were added during the quarter.

In the second quarter, over 90% of the patients enrolled in TARPEYO Touchpoints during the quarter, excluding those still waiting for a final insurance decision, received TARPEYO. The channel mix of new patients on therapy are predominantly on commercial plans, approximately 65%, with the majority of the remaining 35% on government-subsidized plans. Compared to the first quarter, we saw a 14% improvement in the average time-to-fill, reflecting our continuous investment in supporting providers and patients in accessing TARPEYO.

Our medical and commercial teams had a robust presence at major nephrology conferences, such as the National Kidney Foundation (NKF) and ERA-EDTA Congress. During the NKF conference, we presented and discussed the clinical benefits of TARPEYO and its role in treating IgAN. This information was shared across promotional product theaters and CME programs focused on IgAN disease, which furthered the education of nephrologists. The ERA-EDTA conference proved instrumental in Calliditas' scientific exchange efforts, with NeflgArd pivotal data receiving recognition as a latebreaking presentation by Richard Lafayette.

This marked the scientific community's first encounter with these critical findings, capturing the interest level of nephrologists around the globe. Additionally, abstracts with valuable data on proteinuria and hematuria were presented from the full NeflgArd study population, which further demonstrated the uniqueness and benefits of TARPEYO in the treatment of IgAN. Discussions at ERA-EDTA centered around the evolving IgAN treatment landscape and the importance of immunomodulatory therapies to suppress pathogenic IgA production and control glomerular inflammation, highlighting Nefecon's pivotal role in the treatment paradigm.

In addition to driving scientific exchange, patient education and engaging with advocacy groups continue to be at the core of our efforts in the US. We work closely with key partners such as the IgAN Foundation, NKF, the American Kidney Fund, and Nephcure to raise awareness about rare diseases and support patients.

During Q2 we engaged with numerous patient advocacy groups and patients, providing them with valuable information about IgA Nephropathy and TARPEYO. Our commitment to empowering patients is exemplified through updates to our IgAN Connect website,

featuring additional valuable resources, including patient stories and blog posts by three inspiring patient advocates. Collaboratively with advocacy groups, we seek to provide patients with credible, up-to-date information and answers to some of their queries. We strive to stand as a trusted resource for the IgAN and TARPEYO patient community, facilitating informed dialogues between patients and their healthcare providers.

Our team is fully committed to advancing TARPEYO's commercial and medical initiatives and eagerly anticipates engaging with nephrologists at the upcoming IIgANN and ASN national conferences. Our goal is to educate the nephrology community on how TARPEYO can benefit IgAN patients by providing a disease-modifying approach to the disease.

Our Commercial Partnerships

Nefecon was granted conditional marketing authorization (CMA) by the European Commission in July 2022, and subsequently by the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom in February 2023, under the brand name Kinpeygo for the treatment of IgAN in adults at risk of rapid disease progression with a urine protein-to-creatinine ratio (UPCR) 1.5 g/gram, becoming the first and only approved treatment for IgAN in Europe.

Kinpeygo will be marketed in the European Economic Area (EEA), UK and Switzerland, if approved in this jurisdiction, exclusively by STADA Arzneimittel AG with whom Calliditas entered into a license agreement in July 2021 to register and commercialize Kinpeygo in Europe. Under the terms of the agreement, Calliditas received an initial upfront payment of EUR 20 million upon signing and has received an additional EUR 12.5 million for conditional marketing authorization and commercialization milestones. Calliditas is further entitled to up to an additional EUR 65 million in future payments linked to pre-defined regulatory and commercialization milestones. STADA will also pay tiered royalties on net sales expressed as a percentage between the low twenties and the low thirties.

STADA launched Kinpeygo in Germany in September 2022, with additional European countries to follow. In Germany it is estimated that 3.1 people per 100,000 develop IgAN each year.

Following the positive data readout from the full NefIgArd trial and the submission of an sNDA to the FDA, Calliditas is collaborating with STADA to seek full approval of Kinpeygo by the European Commission and the MHRA in the full study population.

Calliditas entered into a license agreement to develop and commercialize Nefecon for IgAN in China and Singapore with Everest Medicines (HKEX 1952.HK) in 2019. Calliditas received an initial upfront payment of USD 15 million upon signing, and has received USD 13 million in additional milestones, and may receive future payments linked to regulatory and commercialization milestones up to an additional USD 95 million, plus royalties. In March 2022, this agreement was expanded to include South Korea, resulting in an upfront payment of USD 3 million to Calliditas as well as additional future payments and royalties related to future potential approvals and commercialization of Nefecon in South Korea.

Everest Medicine's New Drug Application (NDA) for Nefecon was accepted by the Chinese regulatory authority National Medical Products Administration (NMPA) in November 2022, and in December the Center for Drug Evaluation (CDE) of the NMPA recommended Priority Review. A regulatory decision is expected in 2H 2023.

At the end of 2022, Calliditas entered into a partnership to commercialize Nefecon in Japan with Viatris Pharmaceuticals Japan, a subsidiary of Viatris Inc. (Nasdaq: VTRS). Viatris is a global healthcare company which, while headquartered in the United States, has a presence in over 165 countries and territories, and also operates approximately 40 manufacturing facilities. Calliditas received an initial upfront payment of USD 20 million upon signing and is eligible to receive up to an additional USD 80 million in future pre-defined development and commercialization milestones. Viatris will also pay mid-teens percentage royalties on net sales.

Pipeline: NOX Inhibitor Platform

Calliditas' pipeline contains development programs based on a first-in-class, novel NOX inhibitor platform. Calliditas is presently running trials with lead compound setanaxib in Squamous Cell Carcinoma of the Head & Neck (SCCHN), which read out interim data in July, as well as in Primary Biliary Cholangitis (PBC). We also plan to launch a clinical trial in Alport syndrome in the second half of 2023.

NOX enzyme inhibitors are a set of promising novel experimental drugs in a new therapeutic class, recognized by the WHO since 2019 when it approved naxib as a new stem. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, otherwise known as NOX enzymes, are the only known enzymes that are solely dedicated to produce reactive oxygen species (ROS) as their primary function. They are transmembrane enzymes that transfer electrons from NADPH in the cytoplasm across the cell membrane, which results in the formation of ROS.

At appropriate concentrations, ROS have essential functions in cellular signaling processes, but disruption of the redox homeostasis has been implicated in multiple disease pathways. When a cell is injured, excess NOX activity is triggered and redox homeostasis becomes unbalanced, leading to activation of pro-fibrogenic pathways. Cancer-associated fibroblasts in the tumor microenvironment also express NOX enzymes, which can result in tumours with low immunological activity and relative resistance to the effects of immuno-oncologic agents, such as checkpoint inhibitors.

Setanaxib, which is the first NOX inhibitor to reach the clinical trial stage, inhibits NOX1 and NOX4, enzymes that are implicated in inflammation and fibrosis pathways, and represent a high-potential therapeutic target.

Pipeline: Head and Neck Cancer