NOX1

In recent years, the treatment of primary biliary cholangitis (PBC) has seen remarkable progress, with the continuous introduction of new drugs bringing good news to PBC patients worldwide. According to reports from authoritative institutions, the global PBC treatment market is thriving and is expected to experience explosive growth in the coming years. However, despite the fact that three PBC treatment drugs have already been approved, the market still has a significant unmet need, and the industry's expectations for new therapeutic drugs are becoming increasingly urgent.   First, let's understand the three PBC treatment drugs currently on the market. Ursodeoxycholic acid (UDCA) is the recognized first-line treatment drug and has been widely used in clinical practice for many years. However, it is regrettable that about 40% of patients do not respond well to this treatment, leaving them in urgent need of more effective treatment options. Against this backdrop, Ocaliva and Elafibranor emerged, being approved as second-line treatment options for PBC in 2016 and 2021, respectively. The introduction of these two drugs has undoubtedly brought new hope to PBC patients.   However, market competition has not stopped. Industry insiders generally believe that Seladelpar has the potential to become the fourth novel PBC drug approved globally. Seladelpar is an oral, potent, and selective PPARδ agonist, and its unique mechanism of action gives it significant advantages in regulating bile acid synthesis, inflammation, fibrosis, and lipid metabolism. Based on preclinical and clinical data, Seladelpar has demonstrated good efficacy and safety in the treatment of PBC. Currently, the drug is undergoing priority review in the United States and is expected to receive approval for marketing in August 2024. At that time, it is expected to bring a safer and more effective treatment option to PBC patients worldwide.   In addition to Seladelpar, the industry is also paying attention to other PBC drug candidates in development. For example, Setanaxib is a new drug that targets NOX4 and NOX1, and it has unique potential in the field of PBC treatment. Furthermore, domestic pharmaceutical companies are also actively engaged in the development of PBC drug research, such as the dual-target peptide drug TB001 developed by a well-known pharmaceutical company. The successive launch of these candidate drugs will bring new development opportunities to the PBC treatment market.   It is worth mentioning that with the advancement of technology and the depth of research, the PBC treatment field is facing unprecedented development opportunities. More and more new drugs and new technologies are emerging, bringing more treatment options to PBC patients. At the same time, as global medical standards improve and medical resources are optimized, the treatment experience of PBC patients will also be significantly improved. We have reason to believe that in the near future, PBC patients will be able to enjoy safer, more effective, and more convenient treatment services.

Calliditas Therapeutics’ stock rose initially before falling back toward its opening price. Calliditas Therapeutics had a typical to-do list for its midphase head and neck cancer study. Step one, show the molecule shrinks tumors. Step two, look for early evidence of effect on survival. The Swedish biotech fell at the first obstacle on that timeworn path, seeing no change in tumor size, but bounced back up with early evidence of an effect on progression-free (PFS) and overall survival (OS). The double-blind, randomized phase 2 trial compared the effect of adding setanaxib or placebo to Merck & Co.’s PD-1 checkpoint inhibitor Keytruda. Setanaxib is designed to inhibit NOX1 and NOX4, enzymes expressed by cancer-associated fibroblasts (CAFs) in solid tumors. Researchers have linked high levels of CAFs to poor survival and resistance to immunotherapy. Calliditas identified setanaxib as a way to improve the penetration of immune cells into tumors and make checkpoint inhibitors effective in more patients. The biotech put that idea to the test in a phase 2 trial of 55 people with recurrent or metastatic head and neck cancer. Setanaxib was no better than placebo on the primary endpoint of best percentage change from baseline in tumor size. Calliditas is yet to share the response rates, a typical midphase endpoint, but did disclose that 70% of patients on setanaxib had at least stable disease, compared to 52% of people on placebo.  The biotech focused on the PFS and OS results. Median PFS was five months in the setanaxib arm and 2.9 months in the placebo cohort. Similarly, the OS rate at nine months was 88% on setanaxib and 58% on the control. The biotech reported a similar divergence in OS rates after six months.  Calliditas brushed over the failure to hit the primary endpoint—relegating the finding to a single line almost 300 words into its press release—but Chief Medical Officer Richard Philipson was clear about the importance of showing a reduction in tumor size on an earnings call in February. “We think this is an important endpoint in a study at this stage of development. It’s a little bit more sensitive than just looking at response rates,” Philipson said. “Clearly, what we want to see is a significant reduction in tumor size in patients who are receiving setanaxib on top of pembrolizumab versus patients who are receiving placebo on top of pembrolizumab.” Calliditas’ statement lacks an explanation for why patients may live longer on setanaxib if it has no effect on tumor size. The biotech plans to host an R&D day later this month to share more information on the phase 2 trial and other data supporting the mechanism of action of setanaxib.  Investors appeared unsure what to make of the data, with Calliditas’ stock initially rising before falling back toward its opening price.

STOCKHOLM, Nov. 30, 2023 /PRNewswire/ -- Calliditas Therapeutics AB (Nasdaq: CALT) (Nasdaq Stockholm: CALTX) ('Calliditas') today announced the initiation of a Phase 2 clinical study to evaluate setanaxib in Alport syndrome. Calliditas is a company focused on developing and commercializing novel treatments in rare diseases with significant unmet medical needs. This randomized, double-blind, placebo-controlled study will evaluate setanaxib in approximately 20 patients with a genetic diagnosis of Alport syndrome and significant proteinuria despite treatment with a renin-angiotensin system (RAS) blocker. The duration of treatment is 24 weeks. The objective is to evaluate the safety and tolerability of setanaxib in patients with Alport syndrome, as well as the effect of setanaxib on UPCR and eGFR compared to placebo. "There is an urgent clinical need in Alport syndrome for treatments that delay the progression to kidney failure," said Dr Rachel Lennon, Professor of Nephrology and Honorary Consultant Pediatric Nephrologist, University of Manchester (UK), and Coordinating Investigator for the study. "Alport syndrome can occur as early as the teenage years, when it causes major disruption to learning and education. Clinical trials allow new treatments such as setanaxib to be evaluated for safety and effectiveness in Alport syndrome." Setanaxib is also being evaluated in Phase 2 studies in squamous cell carcinoma of the head and neck, primary biliary cholangitis, and idiopathic pulmonary fibrosis. For further information, please contact: Åsa Hillsten, Head of IR & Sustainability, Calliditas Tel.: +46 76 403 35 43, Email: [email protected] The information was sent for publication, through the agency of the contact persons set out above, on November 30, 2023 at 8:30 a.m. CET. About Calliditas Calliditas Therapeutics is a commercial stage biopharma company based in Stockholm, Sweden focused on identifying, developing and commercializing novel treatments in orphan indications, with an initial focus on renal and hepatic diseases with significant unmet medical needs. Calliditas' lead product, developed under the name Nefecon®, has been granted accelerated approval by the US FDA under the trade name TARPEYO® and conditional marketing authorization by the European Commission under the trade name Kinpeygo®. Kinpeygo is being commercialized in the European Union Member States by Calliditas' partner, STADA Arzneimittel AG. Additionally, Calliditas is conducting a Phase 2b clinical trial in primary biliary cholangitis, a Phase 2 proof-of- concept trial in head and neck cancer, and a Phase 2a trial in Alport syndrome with its NOX inhibitor product candidate, setanaxib. Calliditas' common shares are listed on Nasdaq Stockholm (ticker: CALTX) and its American Depositary Shares are listed on the Nasdaq Global Select Market (ticker: CALT). Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding Calliditas' strategy, clinical development plans, business plans, and regulatory submissions. The words "may," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "estimate," "predict," "project," "potential," "continue," "target," and similar expressions are intended to identify forward looking statements, although not all forward-looking statements contain these identifying words. Any forward looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, any related to Calliditas' business, operations, clinical trials (including as to the timing of the Company's clinical trial of setanaxib in Alport syndrome), strategy, goals and anticipated timelines, competition from other biopharmaceutical companies, revenue and product sales projections or forecasts and other risks identified in the section entitled "Risk Factors" in Calliditas' reports filed with the Securities and Exchange Commission. Calliditas cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Calliditas disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent Calliditas' views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. The following files are available for download: