FGF23

WALTHAM, Mass., Oct. 24, 2024 (GLOBE NEWSWIRE) -- Ardelyx, Inc. (Nasdaq: ARDX), a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs, today announced that data supporting additional positive clinical observations of XPHOZAH® (tenapanor) was presented in a series of poster presentations at the American Society of Nephrology’s (ASN) Kidney Week, currently taking place in San Diego. Ardelyx is also hosting an Exhibitor Spotlight discussing hyperphosphatemia management. XPHOZAH, the first and only phosphate absorption inhibitor (PAI), is approved by the U.S. Food and Drug Administration to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. XPHOZAH offers a different mechanism of action that blocks phosphate absorption at the primary pathway and is administered as a single tablet taken twice daily. “We are pleased to be able to continue to expand our understanding of the significant impact XPHOZAH can have to help patients with chronic kidney disease on dialysis with elevated phosphorus,” said David Spiegel, MD, senior vice president, nephrology at Ardelyx. “Patients on dialysis and their healthcare providers have long struggled to achieve and maintain serum phosphate levels within guideline-established levels. The addition of XPHOZAH is an important tool in phosphate management and these data demonstrate the benefit that XPHOZAH’s blocking mechanism can offer patients.” Poster #TH-PO164, entitled “Sustained Phosphate Reduction Assessed by P AUC With Tenapanor Is Associated With Reduced Fibroblast Growth Factor 23 in Patients With Chronic Kidney Disease and Hyperphosphatemia on Dialysis,” is a post-hoc analysis of the PHREEDOM Phase 3 clinical trial, and assessed whether long-term phosphate (P) control measured using average phosphate area under the curve (P AUC) with tenapanor is associated with lower iFGF23. iFGF23 is elevated in patients with chronic kidney disease and is associated with increased cardiovascular mortality. The analysis observed greater percent reductions from baseline in iFGF23 in P AUC categories representative of better P control than categories representative of worse control. Poster #TH-PO169, entitled “Tenapanor Reduces Serum Phosphate With Similar Efficacy and Tolerability Profiles When Added to Various Phosphate Binders,” is a post hoc analysis of data from the AMPLIFY Phase 3 clinical trial and OPTIMIZE open-label clinical trial and examined the efficacy and tolerability of tenapanor when added to different phosphate binders (PBs). The analysis found that tenapanor added to PBs provided a clinically meaningful serum P reduction with similar efficacy and tolerability regardless of the type of PB. Poster presentations are now publicly available and can be accessed on demand here. In addition to the poster presentations during ASN Kidney Week, Ardelyx is sponsoring an Exhibitor Spotlight titled: “A Different Perspective on Hyperphosphatemia Management: Evaluating Current Strategies,” on October 25, 2024, from 11:00 – 11:45 AM PDT, where Steven Fishbane, MD, will discuss first-in-class PAI, XPHOZAH. The presentation will review the XPHOZAH mechanism of action, efficacy and safety data from the Phase 3 clinical trial program and will include a discussion about the clinical application of XPHOZAH as add-on therapy for the many dialysis patients on a phosphate binder with serum phosphorus levels above guideline-established targets. About XPHOZAH® (tenapanor)XPHOZAH, discovered and developed by Ardelyx, is a first-in-class, phosphate absorption inhibitor with a differentiated mechanism of action that acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3), thereby reducing phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption. XPHOZAH is a single tablet, taken twice daily. Diarrhea was the most common side effect experienced by patients taking XPHOZAH in clinical trials. Please see additional full Prescribing Information. About HyperphosphatemiaHyperphosphatemia is a serious condition, defined as elevated levels of phosphate in the blood, which affects the vast majority of the 550,000 patients in the United States with chronic kidney disease (CKD) on maintenance dialysis. The kidneys are responsible for eliminating excess phosphate and as kidney function declines, phosphate is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD on maintenance dialysis, with internationally recognized KDIGO treatment guidelines that recommend lowering elevated phosphate levels toward the normal range (2.5-4.5mg/dL). IMPORTANT SAFETY INFORMATION CONTRAINDICATIONSXPHOZAH is contraindicated in: Pediatric patients under 6 years of agePatients with known or suspected mechanical gastrointestinal obstruction WARNINGS AND PRECAUTIONSDiarrhea Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea. MOST COMMON ADVERSE REACTIONS Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in the XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials. INDICATION XPHOZAH (tenapanor), 30 mg BID, is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. For additional safety information, please see full Prescribing Information. About ArdelyxArdelyx was founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs. Ardelyx has two commercial products approved in the United States, IBSRELA® (tenapanor) and XPHOZAH® (tenapanor). Ardelyx has agreements for the development and commercialization of tenapanor outside of the U.S. Kyowa Kirin commercializes PHOZEVEL® (tenapanor) for hyperphosphatemia in Japan. A New Drug Application for tenapanor for hyperphosphatemia has been submitted in China with Fosun Pharma. Knight Therapeutics commercializes IBSRELA in Canada. For more information, please visit https://ardelyx.com/ and connect with us on X (formerly known as Twitter), LinkedIn and Facebook. Investor and Media Contacts: Caitlin Lowieclowie@ardelyx.com

- INZ-701 was well-tolerated and significantly increased plasma pyrophosphate (PPi) levels in patients with end-stage kidney disease (ESKD) undergoing hemodialysis; low PPi levels are associated with calciphylaxis, a rare, life-threatening complication of ESKD - - Company plans to initiate a registrational trial in calciphylaxis in 2025 subject to regulatory alignment and sufficient funding - BOSTON, Oct. 24, 2024 (GLOBE NEWSWIRE) -- Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” or “Inozyme”), a clinical-stage biopharmaceutical company developing innovative therapeutics for rare diseases that affect bone health and blood vessel function, today announced positive interim data from its ongoing Phase 1 SEAPORT 1 trial of INZ-701 in patients with end-stage kidney disease (ESKD) undergoing hemodialysis ( NCT06283589 ). These data will be presented at the American Society of Nephrology’s (ASN) Kidney Week 2024 , which is being held October 24-27, 2024, in San Diego. “The interim data from the SEAPORT 1 trial demonstrate that INZ-701 significantly raised PPi levels in patients with end-stage kidney disease and was well-tolerated in this high-risk population,” said Douglas A. Treco, Ph.D., CEO and Chairman of Inozyme Pharma. “Low PPi levels are linked to the development of calciphylaxis, a rare and life-threatening complication of end-stage kidney disease, as well as the associated morbidity and mortality. Pending alignment with regulatory authorities and sufficient funding, these encouraging results provide a strong foundation for advancing INZ-701 into a registrational trial in calciphylaxis.” “Calciphylaxis represents one of the most challenging complications of end-stage kidney disease, with profound impacts on patient quality of life and survival. The interim results from the SEAPORT 1 trial are encouraging, showing that INZ-701 elevated PPi levels in patients with end-stage kidney disease. PPi levels are critically deficient in patients with calciphylaxis and by addressing this underlying deficiency, INZ-701 has the potential to modify the course of this disease and offer hope where no approved therapies currently exist,” added Sagar Nigwekar, MD, MMSc, Co-Director, Kidney Research Center, Massachusetts General Hospital. Key Findings from the Interim Analysis of SEAPORT 1 The open-label trial investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of INZ-701 in adults with ESKD and low PPi levels undergoing hemodialysis. On average, ESKD patients have lower PPi levels compared with healthy individuals, and those with calciphylaxis have even lower plasma PPi levels. The trial screened hemodialysis patients for PPi levels and identified the population with significantly reduced levels (<700nM) for enrollment. INZ-701 is an ENPP1-Fc fusion enzyme replacement therapy (ERT) designed to increase both PPi and adenosine. Patients (n=11) received weekly subcutaneous doses of 1.8 mg/kg of INZ-701 over a four-week dosing period; PD data from eight patients who completed the trial will be included in the ASN Kidney Week 2024 presentation. The interim data to be presented at ASN Kidney Week 2024 demonstrated the following: PPi Levels: INZ-701 significantly increased PPi levels in ESKD patients receiving hemodialysis, with levels rising into the normal range by week 3 of the trial’s four-week dosing schedule. The largest changes occurred in patients with the lowest baseline PPi levels. Timepoint Mean PPi (nM) ± SEM (n=8) Baseline-Day 3 pre-dose* 619±74 Day 10 pre-dose 931±255 Day 17 pre-dose 1498±224 Day 24 pre-dose 1551±270 *Baseline consists of three timepoints collected prior to the initiation of dosing The Company’s study of healthy subjects (n=10) showed PPi levels between 1002nM and 2169nM. Mineral Metabolism: INZ-701 led to reductions in biomarkers of mineral metabolism, including serum phosphate (Pi) and fibroblast growth factor-23 (FGF-23), which are implicated in the pathogenesis of vascular calcification in ESKD. These findings suggest INZ-701 may mitigate the risk of pathologic calcification in these patients. Safety: INZ-701 was generally well-tolerated and exhibited a favorable safety profile, with no drug-related treatment-emergent adverse events (TEAEs) reported in the 11 patients who completed the four-week treatment period. All observed TEAEs were mild to moderate in severity except for one case of hyperkalemia requiring urgent dialysis. Pharmacokinetics: Consistent drug exposure to INZ-701 was observed with 1.8 mg/kg weekly dosing and PK profiles were consistent with the Company’s prior studies in non-hemodialysis patients. We believe these results suggest consistent drug PK profiles can be maintained in dialysis patients, providing further confidence in dose selection for future trials. Anti-Drug Antibodies (ADAs): Low titers of ADAs were detected in three out of 11 patients at the end-of-study timepoint, approximately 30 days after the last dose. Two of these patients became ADA-negative by Day 60 after the last dose. The presence of ADAs was not associated with any adverse events. Additional follow-up data, including characterization of genetic markers associated with PPi and adenosine metabolism and PK/PD analyses, will be presented at a future medical conference. Based on these results, the Company plans to initiate a registrational trial of INZ-701 in patients with calciphylaxis in 2025, subject to regulatory alignment and sufficient funding. About Calciphylaxis and the PPi-Adenosine Pathway Calciphylaxis (also known as calcific uremic arteriolopathy, or CUA) is a rare disorder with a high mortality rate that predominantly affects patients with end-stage kidney disease (ESKD). The disease is associated with low levels of inorganic pyrophosphate (PPi) and is characterized by pathologic mineralization (i.e., calcification) and intimal proliferation (the overgrowth of smooth muscle cells inside blood vessels) of the vasculature in the skin and fatty tissue. This leads to poor blood flow, blood clots, painful skin ulcers, serious infections, and often death, with a reported one-year survival rate of approximately 50%. Currently, there are no approved therapies for calciphylaxis. The estimated incidence of calciphylaxis is approximately 3.5 per 1,000 patients with ESKD with approximately 5,000 new patients presenting annually across major addressable markets. The PPi-Adenosine Pathway plays a critical role in regulating both pathologic mineralization and intimal proliferation. The ENPP1 enzyme generates PPi, a potent inhibitor of pathologic mineralization, by hydrolyzing extracellular adenosine triphosphate. Additionally, adenosine, produced by the CD73 enzyme regulates intimal proliferation, preventing the abnormal growth of smooth muscle cells within blood vessels, which can contribute to vascular occlusion. Recent genetic research has shown that polymorphisms in the ENPP1 or CD73 genes have been linked to an increased risk of arterial calcification in ESKD patients and/or calciphylaxis, further substantiating the role of the PPi-Adenosine Pathway in this condition. INZ-701 is designed to restore PPi levels and increase adenosine production, addressing both key elements of the PPi-Adenosine Pathway. By normalizing these processes, INZ-701 has the potential to prevent the progression of calciphylaxis, which could offer a promising therapeutic solution for this high-risk and underserved patient population. About Inozyme Pharma Inozyme Pharma is a pioneering clinical-stage biopharmaceutical company dedicated to developing innovative therapeutics for rare diseases that affect bone health and blood vessel function. We are experts in the PPi-Adenosine Pathway, where the ENPP1 enzyme generates inorganic pyrophosphate (PPi), which regulates mineralization, and adenosine, which controls intimal proliferation (the overgrowth of smooth muscle cells inside blood vessels). Disruptions in this pathway impact the levels of these molecules, leading to severe musculoskeletal, cardiovascular, and neurological conditions, including ENPP1 Deficiency, ABCC6 Deficiency, calciphylaxis, and ossification of the posterior longitudinal ligament (OPLL). Our lead candidate, INZ-701, is an ENPP1 Fc fusion protein enzyme replacement therapy (ERT) designed to increase PPi and adenosine, enabling the potential treatment of multiple diseases caused by deficiencies in these molecules. It is currently in clinical development for the treatment of ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis. By targeting the PPi-Adenosine Pathway, INZ-701 aims to correct pathological mineralization and intimal proliferation, addressing the significant morbidity and mortality in these devastating diseases. For more information, please visit or follow Inozyme on LinkedIn , X , and Facebook . Cautionary Note Regarding Forward-Looking Statements Statements in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the initiation, enrollment, timing, and design of our planned clinical trials, including the Company’s plans to initiate a registrational trial study in calciphylaxis, availability of data from clinical trials, the potential benefits of INZ-701, and our regulatory strategy. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the Company’s ability to conduct its ongoing clinical trials of INZ-701 for ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis; enroll patients in ongoing and planned trials; obtain and maintain necessary approvals from the FDA and other regulatory authorities; continue to advance its product candidates in preclinical studies and clinical trials; replicate in later clinical trials positive results found in preclinical studies and early-stage clinical trials of its product candidates; advance the development of its product candidates under the timelines it anticipates in planned and future clinical trials; obtain, maintain, and protect intellectual property rights related to its product candidates; manage expenses; comply with covenants under its outstanding loan agreement; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section in the Company’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors, in the Company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company’s views as of the date hereof and should not be relied upon as representing the Company’s views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. Contacts: Investors : Inozyme Pharma Stefan Riley, Senior Director of IR and Corporate Communications (857) 330-8871 stefan.riley@inozyme.com Media : Biongage Communications Todd Cooper (617) 840-1637 Todd@biongage.com

WALTHAM, Mass., Oct. 15, 2024 (GLOBE NEWSWIRE) -- Ardelyx, Inc. (Nasdaq: ARDX), a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs, today announced that additional data supporting XPHOZAH® (tenapanor) will be presented at the American Society of Nephrology’s (ASN) Kidney Week, to be held October 24-27, 2024, in San Diego. XPHOZAH, the first and only phosphate absorption inhibitor (PAI), is approved by the U.S. Food and Drug Administration to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. XPHOZAH offers a different mechanism of action that blocks phosphate absorption at the primary pathway and is administered as a single tablet taken twice daily. Information regarding ASN's Kidney Week, including copies of presentation abstracts, can be found here. Title: Sustained Phosphate Reduction Assessed by P AUC With Tenapanor Is Associated With Reduced Fibroblast Growth Factor 23 in Patients With Chronic Kidney Disease and Hyperphosphatemia on DialysisAuthors: Kevin J. Martin, Simon Higgins, Yang Yang, David P. Rosenbaum, David M. SpiegelPoster Number: TH-PO164Date/Time: October 24, 2024, from 10:00 AM – 12:00 PM PDT (UTC –7) Title: Tenapanor Reduces Serum Phosphate With Similar Efficacy and Tolerability Profiles When Added to Various Phosphate BindersAuthors: Stuart M. Sprague, David P. Tietjen, Jesslyn Roesch, Yang Yang, Suling Zhao, Susan A. Edelstein, David P. Rosenbaum, David M. SpiegelPoster Number: TH-PO169Date/Time: October 24, 2024, from 10:00 AM – 12:00 PM PDT (UTC –7) In addition to the poster presentations during ASN Kidney Week, Ardelyx is sponsoring an Exhibitor Spotlight titled: “A Different Perspective on Hyperphosphatemia Management: Evaluating Current Strategies,” on October 25, 2024, from 11:00 – 11:45 AM PDT, where Steven Fishbane, MD, will discuss first-in-class PAI, XPHOZAH. The presentation will review the XPHOZAH mechanism of action, efficacy and safety data from the Phase 3 clinical trial program and will include a discussion about the clinical application of XPHOZAH as add-on therapy for the many dialysis patients on a phosphate binder with serum phosphorus levels above guideline-established targets. About XPHOZAH® (tenapanor)XPHOZAH, discovered and developed by Ardelyx, is a first-in-class, phosphate absorption inhibitor with a differentiated mechanism of action that acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3), thereby reducing phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption. XPHOZAH is a single tablet, taken twice daily. Diarrhea was the most common side effect experienced by patients taking XPHOZAH in clinical trials. Please see additional full Prescribing Information. About HyperphosphatemiaHyperphosphatemia is a serious condition, defined as elevated levels of phosphate in the blood, which affects the vast majority of the 550,000 patients in the United States with chronic kidney disease (CKD) on maintenance dialysis. The kidneys are responsible for eliminating excess phosphate and as kidney function declines, phosphate is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD on maintenance dialysis, with internationally recognized KDIGO treatment guidelines that recommend lowering elevated phosphate levels toward the normal range (2.5-4.5mg/dL). IMPORTANT SAFETY INFORMATION CONTRAINDICATIONSXPHOZAH is contraindicated in: Pediatric patients under 6 years of agePatients with known or suspected mechanical gastrointestinal obstruction WARNINGS AND PRECAUTIONSDiarrhea Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea. MOST COMMON ADVERSE REACTIONS Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in the XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials. INDICATION XPHOZAH (tenapanor), 30 mg BID, is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. For additional safety information, please see full Prescribing Information. About ArdelyxArdelyx was founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs. Ardelyx has two commercial products approved in the United States, IBSRELA® (tenapanor) and XPHOZAH® (tenapanor). Ardelyx has agreements for the development and commercialization of tenapanor outside of the U.S. Kyowa Kirin commercializes PHOZEVEL® (tenapanor) for hyperphosphatemia in Japan. A New Drug Application for tenapanor for hyperphosphatemia has been submitted in China with Fosun Pharma. Knight Therapeutics commercializes IBSRELA in Canada. For more information, please visit https://ardelyx.com/ and connect with us on X (formerly known as Twitter), LinkedIn and Facebook. Investor and Media Contacts: Caitlin Lowieclowie@ardelyx.com