ENPP1

- Company to host conference call and webcast featuring key opinion leaders on Monday, April 8, 2024 at 8:00 a.m. ET - BOSTON, March 26, 2024 (GLOBE NEWSWIRE) -- Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” or “Inozyme”), a clinical-stage rare disease biopharmaceutical company developing novel therapeutics for the treatment of pathologic mineralization and intimal proliferation, today announced that it will host a conference call and webcast on Monday, April 8, 2024 at 8:00 a.m. Eastern Time. During the conference call and webcast, the Company will discuss topline data from its ongoing Phase 1/2 trial of INZ-701 in adults with ABCC6 Deficiency (pseudoxanthoma elasticum or PXE), and from all cohorts of its ongoing Phase 1/2 trial of INZ-701 in adults with ENPP1 Deficiency. In addition, the event will feature an update on the Company’s Natural History Study in pediatric patients with ABCC6 Deficiency, including presentations from the following key opinion leaders who will provide an overview of the unmet need in ABCC6 Deficiency: Professor Y. Joyce Liao, M.D., Ph.D., Professor of Ophthalmology and Neurology at Stanford Medicine, California, USAProfessor Zulf Mughal, M.D., Consultant in Paediatric Bone Disorders at Al Jalila Children's Specialty Hospital, Dubai, UAE Conference Call and Webcast Details The live webcast and replay will be accessible through the Investor Relations section of Inozyme’s website under Events. Alternatively, the conference call may be accessed by dialing: Domestic Dial-in Number: 1-833-816-1110International Dial-in Number: 1-412-317-0686 Participants should ask to join the Inozyme Pharma call. For those unable to participate live, a replay will be available in the Investor Relations section of Inozyme’s website for a limited time following the event. About ABCC6 Deficiency ABCC6 Deficiency is a progressively debilitating condition of the vasculature and soft tissue that is estimated to affect approximately 1 in 25,000 to 1 in 50,000 individuals worldwide. Infants with ABCC6 Deficiency are diagnosed with generalized arterial calcification of infancy (GACI Type 2), a condition that resembles GACI Type 1, the infant form of ENPP1 Deficiency. Pediatric patients who survive the first year of life may develop neurological disease, including stroke, and cardiovascular disease secondary to ongoing vascular calcification and stenosis. In older individuals, ABCC6 Deficiency presents as pseudoxanthoma elasticum (PXE), which is characterized by pathologic mineralization in blood vessels and soft tissues clinically affecting the skin, eyes, and vascular system. There are no approved therapies for ABCC6 Deficiency. INZ-701 in ABCC6 Deficiency Phase 1/2 Clinical Trial Design The ongoing Phase 1/2 open-label clinical trial enrolled 10 adult patients with ABCC6 Deficiency at sites in the United States and Europe. The trial will primarily assess the safety and tolerability of INZ-701 in adult patients with ABCC6 Deficiency, as well as characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of INZ-701, including the evaluation of levels of plasma pyrophosphate (PPi) and other biomarkers. In the Phase 1 dose-escalation portion of the trial, Inozyme assessed INZ-701 for 32 days at doses of 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg administered via subcutaneous injection twice weekly, with three patients per dose cohort. Doses were selected based on preclinical studies and PK/PD modeling. The Phase 1 dose-escalation portion of the trial sought to identify a safe, tolerable dose that increases PPi levels for further development. The open-label Phase 2 extension portion of the trial is assessing long-term safety, PK, and PD of continued treatment with INZ-701 for at least 48 weeks, where patients may self-administer INZ-701. Exploratory endpoints will include evaluations of vascular, ophthalmologic, physical function, and patient-reported outcomes. About ENPP1 Deficiency ENPP1 Deficiency is a progressively debilitating condition of the vasculature, soft tissue, and skeleton with a prevalence of approximately 1 in 64,000 pregnancies worldwide. Although ENPP1 Deficiency was initially described in patients with biallelic ENPP1 Deficiency (homozygous or compound heterozygous mutations), many patients with monoallelic ENPP1 Deficiency (heterozygous mutations) have clinical symptoms, potentially increasing the worldwide prevalence. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI Type 1) and approximately 50% of infants die within six months of birth. Children with ENPP1 Deficiency typically develop rickets, a condition diagnosed as autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults can develop osteomalacia (softened bones). ARHR2 and osteomalacia lead to pain and mobility issues. Patients can also exhibit signs and symptoms of hearing loss, arterial and joint calcification, and cardiovascular complications. There are no approved therapies for ENPP1 Deficiency. INZ-701 in ENPP1 Deficiency Phase 1/2 Clinical Trial Design The ongoing Phase 1/2 open-label clinical trial initially enrolled nine adult patients with ENPP1 Deficiency at sites in North America and Europe. The trial will primarily assess the safety and tolerability of INZ-701 in adult patients with ENPP1 Deficiency, as well as characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of INZ-701, including evaluation of the PD marker, plasma pyrophosphate (PPi) and other biomarker levels. In the Phase 1 dose-escalation portion of the trial, Inozyme assessed INZ-701 for 32 days at doses of 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg administered via subcutaneous injection twice weekly, with three patients per dose cohort. Doses were selected based on preclinical studies and PK/PD modeling. The Phase 1 dose-escalation portion of the trial sought to identify a safe, tolerable dose that increases PPi levels and that can be used for further clinical development. Following completion of the Phase 1 portion of the first three cohorts, Inozyme dosed patients in a fourth cohort at 1.2 mg/kg to investigate the potential for once-weekly dosing of INZ-701. The open-label Phase 2 extension portion of the trial is assessing long-term safety, PK, and PD of continued treatment with INZ-701 for at least 48 weeks, where patients may self-administer INZ-701. Exploratory endpoints include evaluations of skeletal, vascular, physical function, and patient-reported outcomes. About INZ-701 INZ-701, a recombinant Fc fusion protein, is an ENPP1 enzyme replacement therapy (ERT) in development for the treatment of rare disorders of the vasculature, soft tissue, and skeleton. INZ-701 metabolizes ATP to generate PPi, a natural inhibitor of mineralization, and AMP, which can be processed to phosphate and adenosine, the latter being a natural inhibitor of intimal proliferation. In preclinical studies, the experimental therapy has shown potential to prevent pathologic mineralization and intimal proliferation, which can drive morbidity and mortality in devastating disorders such as ENPP1 Deficiency, ABCC6 Deficiency and calciphylaxis. Clinical data to date have demonstrated that INZ-701 was generally safe and well tolerated and meaningfully increased PPi levels in multiple clinical trials. About Inozyme Pharma Inozyme Pharma, Inc. is a clinical-stage rare disease biopharmaceutical company developing novel therapeutics for the treatment of diseases impacting the vasculature, soft tissue, and skeleton. Inozyme is developing INZ-701, an enzyme replacement therapy, to address pathologic mineralization and intimal proliferation, which can drive morbidity and mortality in these severe diseases. INZ-701 is currently in clinical development for the treatment of ENPP1 Deficiency, ABCC6 Deficiency and calciphylaxis. For more information, please visit https://www.inozyme.com/ or follow Inozyme on LinkedIn, X (formerly Twitter), 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 timing and contents of our planned topline data update, the design of our planned clinical trials, and the potential benefits of INZ-701. 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 the 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 and Quarterly Report on Form 10-Q 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 PharmaStefan Riley, Senior Director of IR and Corporate Communications(857) 330-8871stefan.riley@inozyme.com Media: SmithSolve Matt Pera(973) 886-9150matt.pera@smithsolve.com

本文为转化医学网原创，转载请注明出处 作者：Sophia 导读： 为了逃避免疫监视，肿瘤细胞在其膜表面表达外核苷酸焦磷酸酶磷酸二酯酶 1 （ENPP1），从而降解细胞外环状 GMP-AMP （cGAMP），从而抑制干扰素基因的环状 GMP-AMP 合酶 （cGAS） 刺激物 （STING） DNA 感应途径。为了充分了解这种肿瘤隐身机制，必须确定肿瘤微环境中是否也存在其他形式的具有水解cGAMP活性的ENPP1来调节这种先天免疫途径。 2024年3月18日，上海交通大学医学院季天海、杨朝勇、吴玲玲共同通讯在《Advanced Science》上发表题为“Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS-STING Signaling”的研究论文，据报道， 多种肿瘤来源的外泌体携带ENPP1，能水解细胞产生的合成2′3′-cGAMP和内源性2′3′-cGAMP，抑制免疫细胞中的cGAS-STING通路。此外，肿瘤外泌体ENPP1还可以水解与LL-37（2′3′-cGAMP的有效转运蛋白）结合的2′3′-cGAMP，以抑制STING信号传导。此外，观察到从人乳腺癌和肺癌组织中分离出的外泌体中ENPP1的高表达，肿瘤外泌体ENPP1抑制CD8+ T细胞和CD4+ T细胞的免疫浸润。 研究结果阐明了肿瘤外泌体ENPP1在cGAS-STING通路中的基本功能，进一步加深了对肿瘤细胞和免疫系统之间串扰的理解。 https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202308131 研究背景 01 cGAS-STING通路是一种重要的先天免疫应答通路，在自身免疫性疾病和癌症中起着重要作用。从机理上讲，环状GMP-AMP合酶（cGAS）作为胞质DNA传感器，可以首先识别来自入侵微生物病原体或受损细胞的双链DNA（dsDNA），然后以三磷酸腺苷（ATP）和三磷酸鸟苷（GTP）为底物合成2′3′-环GMP-AMP（2′3′-cGAMP）。2′3′-cGAMP作为内源性第二信使，与干扰素基因刺激因子（STING）蛋白结合，募集坦克结合激酶1（TBK1）蛋白，激活干扰素调节因子IRF3。然后，磷酸化的 IRF3 进入细胞核并导致 I 型干扰素 （IFN） 的产生，从而启动抗癌和抗病毒的先天免疫反应。为了增强宿主的先天免疫反应，2′3′-cGAMP也可以输出到细胞外，以激活旁观者细胞中的cGAS-STING信号传导。事实上，2′3′-cGAMP 作为一种阴离子亲水分子，在依赖于病毒颗粒、细胞膜通道、SLC46A 溶质载体家族、工程跨膜 （TM） 缺陷 STING 蛋白或抗菌肽的细胞之间转移。 作为cGAS-STING通路的关键因素，了解细胞外cGAMP和转运蛋白-cGAMP复合物的命运是必要的。 截止目前，ENPP1是唯一可以水解免疫递质2′3′-cGAMP的可检测蛋白酶。然而， 除了分布在肿瘤细胞膜上的ENPP1蛋白外，肿瘤微环境中是否还存在其他形式的可以水解2′3′-cGAMP的ENPP1蛋白。 外泌体是由多种细胞类型分泌的脂质双层膜囊泡（直径 30-150 nm），携带母体细胞的各种生物活性分子（例如蛋白质和核酸）以促进细胞间通讯。事实上，研究表明，肿瘤来源的外泌体是肿瘤细胞与免疫细胞之间重要的通讯介质，也是肿瘤微环境中其他非肿瘤旁观者细胞之间的重要通讯介质，可以调节宿主的免疫反应。特别是，肿瘤来源的外泌体在调节先天免疫cGAS-STING信号转导中的作用逐渐被阐明。例如，经放射治疗的肿瘤细胞已被证明可以分泌携带dsDNA的外泌体，以激活免疫细胞中的STING。最近，信号转导接头分子 1 （STAM） 已被证明可以将活化的 STING 寡聚体转运到外泌体中并降解 STING 寡聚体以负调控 STING 信号转导。尽管这些研究表明外泌体在cGAS-STING通路的调控中起着重要作用，但 肿瘤来源的外泌体调节cGAMP的分子机制仍然未知，这限制了我们对肿瘤来源的外泌体在cGAS-STING信号通路和肿瘤免疫逃逸中的调控机制的充分认识。 研究结果 02 在此背景下，我们报道了各种肿瘤细胞衍生的外泌体携带 ENPP1 蛋白;事实上，ENPP1在这些外泌体中高度富集。我们发现肿瘤来源的外泌体可以帮助游离的 2′3′-cGAMP 激活 STING 信号传导。为了削弱外泌体介导的免疫增强，肿瘤外泌体ENPP1进一步水解细胞外2′3′-cGAMP，以抑制免疫细胞中的cGAS-STING通路。LL-37 作为一种由多种细胞类型表达的抗菌肽，已被证明是 2′3′-cGAMP 的有效转运蛋白，可以增强 cGAS-STING 信号转导的免疫反应。我们的研究还表明，肿瘤外泌体ENPP1可以有效地水解与LL-37结合的2′3′-cGAMP，从而抑制免疫细胞中的STING信号传导。事实上， 肿瘤外泌体 ENPP1 可能对任何形式的 2′3′-cGAMP 具有很强的降解活性，从而抑制 cGAS-STING 信号传导。 此外，我们的研究还表明，肿瘤外泌体ENPP1可以水解细胞产生的内源性2′3′-cGAMP，从而抑制旁观者细胞中的cGAS-STING通路。事实上， 我们观察到肿瘤外泌体在肺癌和乳腺癌患者的组织样本中表现出高 ENPP1 表达。重要的是，肿瘤外泌体ENPP1的表达水平分别与CD8+ T细胞和CD4+ T细胞浸润呈负相关。 肿瘤外泌体ENPP1介导的cGAS-STING信号通路在肿瘤微环境中水解2′3′-cGAMP和LL-37-2′3′-cGAMP的机制模型。 总体而言， 我们的研究揭示了肿瘤外泌体ENPP1通过水解2′3′-cGAMP抑制cGAS-STING信号传导的机制。 这突出了肿瘤来源的外泌体在先天免疫反应中的重要作用，并加深了我们对 ENPP1 介导的 cGAS-STING 通路的理解。 参考资料： https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202308131 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。 热门·直播/活动 🕓 上海｜06月14日-16日 ▶ 第六届上海国际癌症大会将于6月14-16日在上海举办，学科交叉，共同推进肿瘤研究与诊治多模态！ 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！ 点击对应文字 查看详情

– Topline data from ongoing Phase 1/2 trials of INZ-701 in adults with ABCC6 Deficiency and ENPP1 Deficiency expected in early April – – Phase 1 trial of INZ-701 in end-stage kidney disease (ESKD) patients receiving hemodialysis (SEAPORT-1) now underway (NCT06283589), with topline data expected in Q4 2024 – – Launched global patient registry (PROPEL) in partnership with GACI Global to advance understanding of ENPP1 Deficiency and infantile-onset ABCC6 Deficiency (NCT06302439) – – Cash, cash equivalents, and short-term investments as of December 31, 2023 expected to fund operations into the fourth quarter of 2025 – BOSTON, March 12, 2024 (GLOBE NEWSWIRE) -- Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” or “Inozyme”), a clinical-stage rare disease biopharmaceutical company developing novel therapeutics for the treatment of pathologic mineralization and intimal proliferation, today reported financial results for the full year ended December 31, 2023, and provided recent business highlights. “We believe we are well-positioned to continue to advance INZ-701 through several anticipated value-creating milestones in the year ahead,” said Douglas A. Treco, Ph.D., CEO of Inozyme Pharma. “Of note, we are on track to report topline data from our ongoing Phase 1/2 trials in adult patients with ABCC6 Deficiency and ENPP1 Deficiency in early April. Data from these trials along with learnings from our recently launched global patient registry in partnership with GACI Global have the potential to play a meaningful role in bringing INZ-701 closer to patients facing these challenging diseases.” Dr. Treco added, “Beyond our two lead indications, today we are pleased to announce the initiation of our Phase 1 SEAPORT-1 trial in patients with end-stage kidney disease (ESKD) receiving hemodialysis, of which calciphylaxis is a severe complication. Calciphylaxis represents a devastating condition characterized by pathologic mineralization and intimal proliferation. Clinical data to date have demonstrated that INZ-701 was generally safe and well tolerated and meaningfully increased PPi levels in adults with ENPP1 and ABCC6 Deficiencies, conditions that share similar pathology to calciphylaxis, supporting the idea that INZ-701 could ultimately serve as a therapeutic option for this underserved population.” Recent Updates and Anticipated Milestones Phase 1/2 Clinical Trials of INZ-701 in Adults with ABCC6 Deficiency (pseudoxanthoma elasticum or PXE) and ENPP1 Deficiency. The Company expects to report topline data from its ongoing Phase 1/2 trial of INZ-701 in adults with ABCC6 Deficiency and topline data from the first three cohorts of its ongoing Phase 1/2 trial in adults with ENPP1 Deficiency in early April. Global ENPP1 Deficiency and Infantile-Onset ABCC6 Deficiency Patient Registry (PROPEL NCT06302439). The Company announced the launch of a global patient registry in partnership with GACI Global, a patient advocacy group that connects families affected by generalized arterial calcification of infancy (GACI) or autosomal recessive hypophosphatemic rickets type 2 (ARHR2). The patient registry is designed to better characterize the natural history, disease course, long-term outcomes, and true disease burden in patients with ENPP1 Deficiency and infantile-onset ABCC6 Deficiency (GACI Type 2). The registry will assess three distinct cohorts: Patients of all ages with ENPP1 Deficiency with evidence of biallelic ENPP1 variantsPatients with evidence of monoallelic ENPP1 variants and disease-related symptomsPatients under 18 years of age with infantile-onset ABCC6 Deficiency with monoallelic or biallelic ABCC6 variantsTo date, the Company has identified over 1,000 patients globally with confirmed or suspected ENPP1 Deficiency and collected data on a number of symptomatic ENPP1 Deficiency patients with monoallelic ENPP1 mutations. “At GACI Global, we are dedicated to furthering the understanding of these devastating diseases in order to advance the development of potential treatments,” said Christine O’Brien, co-president of GACI Global. “Our partnership with Inozyme has played an important role in that mission while ensuring the GACI community has a voice.” Phase 1 SEAPORT-1 Trial of INZ-701 in Patients with ESKD Receiving Hemodialysis Now Underway (NCT06283589). The Company today announced the initiation of its Phase 1 SEAPORT-1 trial of INZ-701 in patients with ESKD receiving hemodialysis, of which calciphylaxis is a severe complication. The trial is designed to assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of INZ-701 in up to 10 patients with ESKD receiving hemodialysis. Patients will receive 1.8 mg/kg of INZ-701 once weekly, coinciding with their hemodialysis treatment, for a total of 30 days. The study’s primary endpoint will assess safety and change from baseline plasma PPi concentration, with secondary endpoints including PK and PD parameters. Topline data from the study are expected in the fourth quarter of 2024.Inozyme previously presented data at the American Society of Nephrology (ASN) Kidney Week 2023 in October 2023 and at the European Calcified Tissue Society Congress (ECTS) in May 2022, which showed the following: Patients with ESKD had significantly lower PPi levels compared to healthy subjectsPatients with patients with calciphylaxis had significantly lower PPi levels when compared with ESKD patients without calciphylaxisLow PPi levels were associated with morbidity and predicted 6-month mortality among ESKD patients with calciphylaxisLow PPi levels are correlated with higher numbers of skin lesions in calciphylaxis “ESKD patients suffering from calciphylaxis face a poor quality of life and, unfortunately, a particularly dismal prognosis,” said Sagar Nigwekar, M.D., MMSc, Co-Director, Kidney Research Center, Massachusetts General Hospital. “I am hopeful that INZ-701 could serve as a much-needed treatment for this underserved patient population. I look forward to the data from this study, as well as more advanced clinical trials of INZ-701 in calciphylaxis.” Anticipated Milestones ENPP1 Deficiency Topline data from first three cohorts of ongoing Phase 1/2 trial in adults through 48 weeks – Early April 2024Initiation of the ENERGY-2 pivotal trial in infants, Ex-U.S. – 2H 2024Interim data from the ENERGY-1 Phase 1b trial in infants – 2H 2024Topline data from the ENERGY-3 pivotal trial in pediatric patients – Mid-2025 ABCC6 Deficiency Topline data from ongoing Phase 1/2 trial in adults through 48 weeks – Early April 2024Initiation of Phase 3 clinical trial, subject to regulatory review and sufficient funding – Q1 2025 Calciphylaxis Interim data from SEAPORT-1 Phase 1 trial in patients with ESKD receiving hemodialysis – Q4 2024 Financial Results for the Year Ended December 31, 2023 Cash Position and Financial Guidance – Cash, cash equivalents, and short-term investments were $188.6 million as of December 31, 2023. Based on its current plans, the Company anticipates its cash, cash equivalents, and short-term investments as of December 31, 2023, will enable the Company to fund cash flow requirements into the fourth quarter of 2025. Research and Development (R&D) Expenses – R&D expenses were $54.8 million for the year ended December 31, 2023, compared to $47.8 million for the year ended December 31, 2022. This increase was primarily due to an increase in chemistry, manufacturing, and controls expense to support our ongoing clinical trials and prepare for potential commercialization and personnel-related costs. General and Administrative (G&A) Expenses – G&A expenses were $20.8 million for the year ended December 31, 2023, compared to $20.8 million for the year ended December 31, 2022. The expenses were flat year over year. Net Loss – Net loss was $71.2 million, or $1.37 loss per share, for the year ended December 31, 2023, compared to $67.1 million, or $1.78 loss per share, for the year ended December 31, 2022. About ENPP1 Deficiency ENPP1 Deficiency is a progressively debilitating condition of the vasculature, soft tissue, and skeleton with a prevalence of approximately 1 in 64,000 pregnancies worldwide. Although ENPP1 Deficiency was initially described in patients with biallelic ENPP1 Deficiency (homozygous or compound heterozygous mutations), many patients with monoallelic ENPP1 Deficiency (heterozygous mutations) have clinical symptoms, potentially increasing the worldwide prevalence. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI Type 1) and approximately 50% of infants die within six months of birth. Children with ENPP1 Deficiency typically develop rickets, a condition diagnosed as autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults can develop osteomalacia (softened bones). ARHR2 and osteomalacia lead to pain and mobility issues. Patients can also exhibit signs and symptoms of hearing loss, arterial and joint calcification, and cardiovascular complications. There are no approved therapies for ENPP1 Deficiency. About ABCC6 Deficiency ABCC6 Deficiency is a progressively debilitating condition of the vasculature and soft tissue that is estimated to affect approximately 1 in 25,000 to 1 in 50,000 individuals worldwide. Infants with ABCC6 Deficiency are diagnosed with generalized arterial calcification of infancy (GACI Type 2), a condition that resembles GACI Type 1, the infant form of ENPP1 Deficiency. Pediatric patients who survive the first year of life may develop neurological disease, including stroke, and cardiovascular disease secondary to ongoing vascular calcification and stenosis. In older individuals, ABCC6 Deficiency presents as pseudoxanthoma elasticum (PXE), which is characterized by pathologic mineralization in blood vessels and soft tissues clinically affecting the skin, eyes, and vascular system. There are no approved therapies for ABCC6 Deficiency. About Calciphylaxis Calciphylaxis is a rare disorder with a high mortality rate that mostly affects patients with end-stage kidney disease (ESKD). The disease is associated with low levels of 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 leading to poor blood flow, blood clots, painful skin ulcers, serious infections, and death. Patients with calciphylaxis have a reported one-year survival rate of approximately 50%. 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 geographies. There are no approved therapies for calciphylaxis. About INZ-701 INZ-701, a recombinant Fc fusion protein, is an ENPP1 enzyme replacement therapy (ERT) in development for the treatment of rare disorders of the vasculature, soft tissue, and skeleton. INZ-701 metabolizes ATP to generate PPi, a natural inhibitor of mineralization, and AMP, which can be processed to phosphate and adenosine, the latter being a natural inhibitor of intimal proliferation. In preclinical studies, the experimental therapy has shown potential to prevent pathologic mineralization and intimal proliferation, which can drive morbidity and mortality in devastating disorders such as ENPP1 Deficiency, ABCC6 Deficiency and calciphylaxis. Clinical data to date have demonstrated that INZ-701 was generally safe and well tolerated and meaningfully increased PPi levels in multiple clinical trials. About GACI Global GACI Global is a nonprofit organization whose mission is to connect families affected by generalized arterial calcification of infancy or hypophosphatemic rickets to each other and to the medical community. The organization strives to provide current educational resources and supports ongoing research. For more information, please visit https://gaciglobal.org. About Inozyme Pharma Inozyme Pharma, Inc. is a clinical-stage rare disease biopharmaceutical company developing novel therapeutics for the treatment of diseases impacting the vasculature, soft tissue, and skeleton. Inozyme is developing INZ-701, an enzyme replacement therapy, to address pathologic mineralization and intimal proliferation, which can drive morbidity and mortality in these severe diseases. INZ-701 is currently in clinical development for the treatment of ENPP1 Deficiency, ABCC6 Deficiency and calciphylaxis. For more information, please visit https://www.inozyme.com/ or follow Inozyme on LinkedIn, X (formerly Twitter), 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 timing and design of our planned clinical trials, the availability of data from clinical trials, the potential benefits of INZ-701, the expectations for the global patient registry and the sufficiency of the Company's cash resources. 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 the 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 and Quarterly Report on Form 10-Q 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. Consolidated Balance Sheet Data December 31, 2023 December 31, 2022Cash, cash equivalents, and short-term investments $188,589 $127,866 Total assets $200,847 $139,195 Total liabilities $60,368 $20,801 Additional paid-in-capital $426,362 $333,356 Accumulated deficit $(285,930) $(214,761) Total stockholders' equity $140,479 $118,394 Consolidated Statements of Operations and Comprehensive Loss Year Ended December 31, 2023 2022 Operating expenses: Research and development $54,847 $47,849 General and administrative 20,798 20,826 Total operating expenses 75,645 68,675 Loss from operations (75,645) (68,675) Other income (expense): Interest income 7,837 2,195 Interest expense (3,333) (262) Other expense, net (28) (319) Other income, net 4,476 1,614 Net loss $(71,169) $(67,061) Other comprehensive income (loss): Unrealized gains (losses) on available-for-sale securities 264 (198) Foreign currency translation adjustment (18) (25) Total other comprehensive income (loss) 246 (223) Comprehensive loss $(70,923) $(67,284) Net loss attributable to common stockholders—basic and diluted $(71,169) $(67,061) Net loss per share attributable to common stockholders—basic and diluted $(1.37) $(1.78) Weighted-average common shares outstanding—basic and diluted 51,839,131 37,763,168 Contacts Investors:Inozyme PharmaStefan Riley, Director of IR and Corporate Communications (857) 330-8871stefan.riley@inozyme.com Media: SmithSolve Matt Pera (973) 886-9150matt.pera@smithsolve.com