The ENABLE Study: An Open-Label, Long-Term Safety and Efficacy Study of INZ-701 in Patients With Ectonucleotide Pyrophosphatase/ Phosphodiesterase 1 (ENPP1) Deficiency

The purpose of Study INZ701-108 (ENABLE) is to assess the safety and efficacy of INZ-701 in patients 1 year of age and older with ENPP1 Deficiency who have not previously received INZ-701 and are not eligible for existing Inozyme-sponsored clinical studies that are still open to enrollment.

开始日期2025-01-31

申办/合作机构

Inozyme Pharma, Inc.

NCT06462547

/ Recruiting临床2期

The ADAPT Study: An Open-label, Long-term Safety Study of INZ-701 in Patients With ENPP1 Deficiency and ABCC6 Deficiency

The purpose of this study (Study INZ701-304 [ADAPT]) is to assess the long-term safety of INZ-701 in patients with ENPP1 Deficiency or ABCC6 Deficiency who have received INZ-701 in an existing clinical study and choose to continue dosing for the potential treatment of their condition.

开始日期2024-06-19

申办/合作机构

Inozyme Pharma, Inc.

NCT06283589

/ Completed临床1期

The SEAPORT 1 Study: An Open-label Exploratory Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of INZ-701 in Study Participants With End-Stage Kidney Disease Undergoing Hemodialysis

The purpose of this study is to determine if multiple doses of INZ-701, given once per week over 4 weeks are safe and increase pyrophosphate (PPi) levels in hemodialysis-dependent (HD) end stage kidney disease (ESKD) study participants who have low PPi levels. In addition, the effect of hemodialysis on the pharmacokinetics of INZ-701 and PPi levels will be evaluated.

开始日期2024-02-12

申办/合作机构

Inozyme Pharma, Inc.

100 项与 INZ-701 相关的临床结果

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100 项与 INZ-701 相关的转化医学

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100 项与 INZ-701 相关的专利（医药）

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项与 INZ-701 相关的文献（医药）

2024-11-01·MOLECULAR THERAPY

Novel treatment for PXE: Recombinant ENPP1 enzyme therapy

Article

作者: Stabach, Paul R. ; Braddock, Demetrios T ; Stabach, Paul R ; Jacobs, Ida Joely ; Braddock, Demetrios T. ; Obiri-Yeboah, Dora ; Li, Qiaoli

Pseudoxanthoma elasticum (PXE) is a genetic multisystem ectopic calcification disorder caused by inactivating mutations in the ABCC6 gene encoding ABCC6, a hepatic efflux transporter. ABCC6-mediated ATP secretion by the liver is the main source of a potent endogenous calcification inhibitor, plasma inorganic pyrophosphate (PPi); the deficiency of plasma PPi underpins PXE. Recent studies demonstrated that INZ-701, a recombinant human ENPP1 that generates PPi and is now in clinical trials, restored plasma PPi levels and prevented ectopic calcification in the muzzle skin of Abcc6^-/-mice. This study examined the pharmacokinetics, pharmacodynamics, and potency of a new ENPP1-Fc isoform, BL-1118, in Abcc6^-/- mice. When Abcc6^-/- mice received a single subcutaneous injection of BL-1118 at 0.25, 0.5, or 1 mg/kg, they had dose-dependent elevations in plasma ENPP1 enzyme activity and PPi levels, with an enzyme half-life of approximately 100 h. When Abcc6^-/- mice were injected weekly from 5 to 15 weeks of age, BL-1118 dose-dependently increased steady-state plasma ENPP1 activity and PPi levels and significantly reduced ectopic calcification in the muzzle skin and kidneys. These results suggest that BL-1118 is a promising second generation enzyme therapy for PXE, the first generation of which is currently in clinical testing.

2022-07-01·Experimental dermatology

INZ‐701, a recombinant ENPP1 enzyme, prevents ectopic calcification in an Abcc6^−/− mouse model of pseudoxanthoma elasticum

Article

作者: Thompson, David ; Sabbagh, Yves ; Ralph, Douglas ; Li, Qiaoli ; Jacobs, Ida Joely ; Flaman, Lisa ; Uitto, Jouni ; Howe, Jennifer ; Cheng, Zhiliang ; O'Brien, Kevin

Abstract:

Pseudoxanthoma elasticum (PXE), a heritable multisystem ectopic calcification disorder, is predominantly caused by inactivating mutations in ABCC6. The encoded protein, ABCC6, is a hepatic efflux transporter and a key regulator of extracellular inorganic pyrophosphate (PPi). Recent studies demonstrated that deficiency of plasma PPi, a potent endogenous calcification inhibitor, is the underlying cause of PXE. This study examined whether restoring plasma PPi levels by INZ‐701, a recombinant human ENPP1 protein, the principal PPi‐generating enzyme, prevents ectopic calcification in an Abcc6−/− mouse model of PXE. Abcc6−/− mice, at 6 weeks of age, the time of earliest stages of ectopic calcification, were injected subcutaneously with INZ‐701 at 2 or 10 mg/kg for 2 or 8 weeks. INZ‐701 at both doses increased steady‐state plasma ENPP1 activity and PPi levels. In the 8‐week treatment study, histopathologic examination and quantification of the calcium content in INZ‐701‐treated Abcc6−/− mice revealed significantly reduced calcification in the muzzle skin containing vibrissae, a biomarker of the calcification process in these mice. The extent of calcification corresponds to the local expression of two calcification inhibitors, osteopontin and fetuin‐A. These results suggest that INZ‐701 might provide a therapeutic approach for PXE, a disease with high unmet needs and no approved treatment.

2020-12-01·Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research1区 · 医学

INZ-701 Prevents Ectopic Tissue Calcification and Restores Bone Architecture and Growth in ENPP1-Deficient Mice

1区 · 医学

Article

作者: Howe, Jennifer ; O'Brien, Kevin ; Lynch, Angela ; Jungles, Steven ; Thompson, David ; Schrier, Denis ; Sabbagh, Yves ; Sullivan, Caitlin ; Cheng, Zhiliang

ABSTRACT:

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the major enzyme that cleaves extracellular adenosine triphosphate (ATP) to generate pyrophosphate (PPi), an inorganic metabolite with potent anticalcification activity. Loss-of-function mutations cause hypopyrophosphatemia and lead to a state of ENPP1 deficiency, which has an acute infantile phase known as generalized arterial calcification of infancy (GACI) and a pediatric to adult phase known as autosomal-recessive hypophosphatemic rickets type 2 (ARHR2). ENPP1 deficiency manifests as ectopic calcification of multiple tissues, neointimal proliferation, premature mortality, impaired growth, and bone deformities. INZ-701, a human ENPP1-Fc protein, is in clinical development as an enzyme replacement therapy for the treatment of ENPP1 deficiency. The pharmacokinetic and pharmacodynamic profile and therapeutic effect of INZ-701 were investigated in Enpp1asj/asj mice, a murine model of ENPP1 deficiency. Enpp1asj/asj mice have undetectable plasma PPi, lower plasma phosphate, and higher FGF23 levels compared with wild-type (WT) mice. Enpp1asj/asj mice on the acceleration diet, containing high phosphate and low magnesium, quickly develop clinical signs, including dehydration, rough hair coat, pinned ears, stiffed legs, and hunched back. Enpp1asj/asj mice treated with vehicle had aforementioned clinical signs plus severe ectopic calcification in multiple tissues and bone defects, characteristics of the clinical phenotype observed in GACI and ARHR2 patients. Our results showed a durable PPi response for more than 3 days after a single dose of INZ-701. Treatment of ENPP1-deficient mice every other day with INZ-701 for 8 weeks restored circulating levels of PPi, prevented pathological calcification in all the tested organs, restored growth parameters, corrected bone defects, improved clinical signs, and decreased mortality in Enpp1asj/asj mice, demonstrating the potential of INZ-701 to treat ENPP1 deficiency. © 2021 American Society for Bone and Mineral Research (ASBMR).

113

项与 INZ-701 相关的新闻（医药）

2025-05-17

·PipelineReview

BioMarin Strengthens Enzyme Therapy Business with Acquisition of Inozyme Pharma

Acquisition is Strong Strategic Fit for BioMarin, Adding INZ-701, a Phase 3 Enzyme Replacement Therapy Being Developed for Treatment of ENPP1 Deficiency First Pivotal Data Readout in Children Expected in Early 2026 with Potential Launch in 2027; Additional Clinical Programs to Expand to Patients of all Ages Potential First-in-Disease Treatment for ENPP1 Deficiency Conference Call and Webcast Scheduled Today at 8:45 a.m. ET SAN RAFAEL, CA and BOSTON, MA, USA I May 16, 2025 I BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) and Inozyme Pharma, Inc. (Nasdaq: INZY) announced today that BioMarin has entered into a definitive agreement to acquire Inozyme for $4.00 per share in an all-cash transaction for a total consideration of approximately $270 million. The transaction has been unanimously approved by the Boards of Directors of both companies and is expected to close in the third quarter of 2025, subject to regulatory approval, successful completion of a tender offer and other customary closing conditions. The acquisition will strengthen BioMarin’s enzyme therapies portfolio, adding a late-stage enzyme replacement therapy, INZ-701, which is currently being assessed for the treatment of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Deficiency, a rare, serious and progressive genetic condition that affects blood vessels, soft tissues and bones. The condition is associated with increased cardiovascular mortality risk across all age groups, especially in infants. It is also associated with severe rickets and osteomalacia in children and adults. Data from the first Phase 3 pivotal study of INZ-701 in children is expected in early 2026, with potential regulatory approval in 2027. “BioMarin has been deeply committed to advancing enzyme therapies for children and adults living with serious genetic conditions for more than 25 years, and today’s agreement builds on our legacy,” said Alexander Hardy, President and Chief Executive Officer of BioMarin. “This acquisition brings to BioMarin an important medicine that has the potential to be the first treatment for children and adults with ENPP1 Deficiency, improving care for people living with this serious condition. As BioMarin continues our transformation and delivers on our corporate strategy, we will continue to evaluate external innovation alongside internal innovation. We are in a strong financial position to bring in additional assets as we accelerate the development of medicines for patients with significant unmet need.” “Today’s announcement gives greater hope to patients who may benefit from INZ-701, a potentially transformative therapy that aims to address the underlying causes and systemic impacts of ENPP1 Deficiency,” said Douglas A. Treco, Ph.D., Chief Executive Officer and Chairman of Inozyme. “BioMarin has paved the way over the past two and a half decades, successfully launching five first-in-disease enzyme therapies. I’d like to thank the team at Inozyme and our partners for their outstanding work and dedication, as we pass this important potentially life-changing therapy to the leading innovator in genetically defined conditions.” INZ-701 and ENPP1 Deficiency INZ-701 is a potential first-in-class, subcutaneous enzyme replacement therapy that is being developed for infants, pediatric and adult patients with ENPP1 Deficiency across a continuum of phenotypes. In addition to the ongoing Phase 3 pivotal study in children, Inozyme is currently enrolling infants in a pivotal study, and a supportive study for adolescents and adults is being planned. In a Phase 1/2 study of adults living with ENPP1 Deficiency, INZ-701 demonstrated a favorable safety profile, with no serious adverse events attributed to INZ-701. Improvements in pyrophosphate levels, bone mineralization biomarkers and quality of life were all observed, suggesting prospect for benefit in patients. ENPP1 Deficiency is a lifelong, rare, progressive, multisystemic condition, caused by mutations in the ENPP1 gene, leading to loss of ENPP1 enzymatic activity that results in low pyrophosphate, upregulation of fibroblast growth factor-23 and phosphate wasting. The condition affects blood vessels, soft tissues and bones. It is associated with high risk of cardiovascular mortality in patients of all ages, especially infants. It is also associated with severe rickets and osteomalacia in children and adults. Patients require considerable multidisciplinary lifelong medical and surgical management of complications. Currently there are no approved therapies for ENPP1 Deficiency. Terms of the Transaction Under the terms of the merger agreement, BioMarin will promptly commence a cash tender offer to acquire all of the outstanding shares of Inozyme common stock at a price of $4.00 per share. Inozyme’s Board of Directors unanimously recommends that Inozyme’s stockholders tender their shares in the tender offer. The consummation of the tender offer is subject to customary closing conditions, including the tender of at least a majority of the outstanding shares of Inozyme, the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, and other customary conditions. Following the successful completion of the tender offer, a wholly owned subsidiary of BioMarin will merge with Inozyme and the outstanding Inozyme shares not tendered in the tender offer will be converted into the right to receive the same $4.00 per share in cash paid in the tender offer. The transaction is not subject to any financing condition. BioMarin also today reaffirmed previously provided full-year 2025 financial guidance, excluding the impact of the accounting treatment of this transaction in accordance with Generally Accepted Accounting Principles (GAAP) upon closing, as well as its plan to achieve 40% Non-GAAP Operating Margin in 2026. Advisors Goldman Sachs & Co. LLC is acting as exclusive financial advisor to BioMarin, and Cooley LLP is serving as legal counsel. Centerview Partners LLC is acting as exclusive financial advisor to Inozyme, and Goodwin Procter LLP is serving as legal counsel. Conference Call BioMarin will host a conference call and webcast to discuss the acquisition today, May 16, 2025, at 8:45 a.m. ET. This event can be accessed through this link or on the investor section of the BioMarin website at www.biomarin.com . About BioMarin BioMarin is a global biotechnology company dedicated to translating the promise of genetic discovery into medicines that make a profound impact on the life of each patient. The San Rafael, California-based company, founded in 1997, has a proven track record of innovation with eight commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that offer new possibilities for people living with genetically defined conditions around the world. To learn more, please visit www.biomarin.com . About Inozyme Inozyme Pharma is a clinical-stage biopharmaceutical company, with approximately 50 employees based in Boston. The company is dedicated to developing innovative therapeutics that target the PPi-Adenosine Pathway, a key regulator of bone health and blood vessel function. Disruptions in this pathway underlie a range of severe diseases, including ENPP1 Deficiency. Our lead investigational therapy, INZ-701, is an ENPP1 Fc fusion protein enzyme replacement therapy designed to restore pyrophosphate and adenosine levels. INZ-701 is currently in late-stage clinical development in ENPP1 Deficiency, with the potential to expand into additional indications where deficiencies in the Pyrophosphate-Adenosine Pathway contribute to disease pathology, including ABCC6 Deficiency and calciphylaxis. Through our pioneering work, we aim to transform treatment options for patients affected by these devastating conditions. To learn more, please visit www.inozyme.com . SOURCE: BioMarin Pharmaceutical

并购临床3期

2025-05-16

·FierceBiotech

BioMarin inks $270M Inozyme buyout, bagging phase 3 prospect in first M&A move of the Sabry era

BioMarin has agreed to buy Inozyme for $4 a share.\n BioMarin has followed through on its shift to external innovation, inking a deal to buy Inozyme for $270 million to add a phase 3 enzyme replacement therapy to its pipeline.California-based BioMarin signaled a change in its approach to business development last year. The company hired James Sabry, M.D., Ph.D., an ex-Roche dealmaker, as chief business officer and began considering opportunities beyond its traditional focus on early-stage deals. Now, the biopharma has landed on Inozyme as the first big acquisition of its new business development era. Inozyme completed enrollment in a phase 3 trial of INZ-701 in January, putting it on track to post topline data early next year. The study is testing the enzyme replacement therapy in children with ENPP1 deficiency, a condition associated with increased cardiovascular mortality risk in infants. Giving INZ-701 to people who are missing or have mutated forms of the enzyme could reverse the effects of pathologic mineralization, such as calcification of the arteries, tendons and ligaments. Inozyme has shared interim biomarker and anti-drug antibody data from the trial but has struggled to convince public investors, who sent its share price down 70% in the 12 months leading up to the BioMarin deal. BioMarin has agreed to buy Inozyme for $4 a share, more than twice the biotech’s closing price before news of the deal emerged. The deal suggests BioMarin sees merits in the argument Inozyme\'s CEO Douglas Treco, Ph.D., put forward at a Needham event last month. Treco admitted that the visibility of ENPP1 deficiency and awareness of the condition among physicians are low. But the CEO said investors are missing that “there\'s a predictive genetic prevalence” of the rare disease, adding that Inozyme is “finding patients and building a registry.” The ultimate test, Treco said, will be how well INZ-701 sells once it is on the market and “there\'s good diagnosis and awareness.”Responsibility for driving diagnoses and awareness will fall on BioMarin, a biopharma with a long history of developing and selling enzyme replacement therapies such as Aldurazyme and Naglazyme. The decision to buy a molecule that aligns with a traditional stronghold of BioMarin fits with the company’s focus on acquiring assets in areas where it has “a strength and a right to win.”BioMarin CEO Alexander Hardy, who delivered the “right to win” line on an earnings call this month, said in a statement Friday that the company “will continue to evaluate external innovation alongside internal innovation.” Hardy previously said BioMarin was aiming to do “at least one business development deal this year.”

并购临床3期

2025-05-16

·Firstwordpharma

BioMarin grows enzyme portfolio with $270M Inozyme buy

BioMarin Pharmaceutical will acquire Boston-based Inozyme Pharma for $4.00 per share in an all-cash transaction for a total of about $270 million, adding a late-stage enzyme replacement therapy to its portfolio of treatments for rare genetic disorders. The transaction is expected to close in the third quarter.The deal centres on Inozyme's lead investigational treatment INZ-701, currently in Phase III for ENPP1 deficiency, a rare genetic condition affecting blood vessels, soft tissues and bones that can cause increased cardiovascular mortality and severe skeletal complications. If approved, the therapy would become the first treatment option for patients with the progressive disease.Initial pivotal data from paediatric testing is expected in early 2026, with a potential commercial launch in 2027.More to follow.

并购临床3期

100 项与 INZ-701 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	美国	Inozyme Pharma, Inc.	2023-11-05
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	澳大利亚	Inozyme Pharma, Inc.	2023-11-05
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	加拿大	Inozyme Pharma, Inc.	2023-11-05
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	法国	Inozyme Pharma, Inc.	2023-11-05
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	沙特阿拉伯	Inozyme Pharma, Inc.	2023-11-05
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	西班牙	Inozyme Pharma, Inc.	2023-11-05
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	土耳其	Inozyme Pharma, Inc.	2023-11-05
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	阿拉伯联合酋长国	Inozyme Pharma, Inc.	2023-11-05
外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	临床3期	英国	Inozyme Pharma, Inc.	2023-11-05
低磷血症佝偻病	临床2期	-	Inozyme Pharma, Inc.	2025-01-31

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04686175 (Phase 1/2 Open Label Study, ENDO2024)	临床1/2期	外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症 inorganic pyrophosphate (PPi) \| FGF-23 \| serum phosphate ... 更多	9	INZ-701 0.2 mg/kg	遞窪鏇網鹽蓋範鹽鏇構(夢鏇鏇獵夢鏇膚憲餘範) = 憲願鏇齋淵鹽獵鑰鹹夢醖選鏇積壓觸製鬱獵鬱 (夢衊艱夢廠築築鏇壓憲, 10.5) 更多	积极	2024-06-01
NCT04686175 (Phase 1/2 Open Label Study, ENDO2024)	临床1/2期		9	INZ-701 0.6 mg/kg	遞窪鏇網鹽蓋範鹽鏇構(夢鏇鏇獵夢鏇膚憲餘範) = 窪網繭襯鹹積簾餘醖夢醖選鏇積壓觸製鬱獵鬱 (夢衊艱夢廠築築鏇壓憲, 10.9) 更多	积极	2024-06-01
NCT05030831 (Corporate Publications) 人工标引	临床1/2期	ABCC6缺乏症 \| 外核苷酸焦磷酸酶/磷酸二酯酶 1 缺乏症	9	INZ-701	淵醖積製簾構遞廠觸鏇(築憲艱遞積糧顧鏇醖糧) = 觸鏇淵膚築齋醖廠憲衊淵網齋築餘願醖選製繭 (積願選壓鬱選鏇憲願壓 )	积极	2023-09-26