Pseudoxanthoma Elasticum

- 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

– 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

– Patient recruitment underway in ENERGY-3 Pivotal Trial of INZ-701 in pediatric patients with ENPP1 Deficiency; topline data expected mid-2025 – – Topline data readouts from ongoing Phase 1/2 trials of INZ-701 in adults with ABCC6 Deficiency and ENPP1 Deficiency expected in first quarter of 2024 – – Cash, cash equivalents, and short-term investments as of September 30, 2023 expected to fund operations into the fourth quarter of 2025 – BOSTON, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Inozyme Pharma Inc. (Nasdaq: INZY) (“Inozyme” or the “Company”), 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 third quarter ended September 30, 2023 and provided business highlights. “We are excited to advance INZ-701 into the ENERGY-3 pivotal trial in pediatric patients with ENPP1 Deficiency. Our ongoing trial of INZ-701 in adults with ENPP1 Deficiency showed early signs of clinical impact and supports the potential of treating children with this condition,” said Douglas A. Treco, Ph.D., CEO of Inozyme Pharma. “We continue to expand our pipeline and therapeutic focus with INZ-701,” Dr. Treco added. “In addition to planning a Phase 3 trial in patients with ABCC6 Deficiency, recent data presented by our collaborators at the American Society of Nephrology Kidney Week 2023 support our plans to evaluate INZ-701 in patients with calciphylaxis, a rare but often fatal complication of hemodialysis associated with end-stage kidney disease.” Recent Highlights ENERGY-3 Pivotal Trial of INZ-701 in Pediatric Patients with ENPP1 Deficiency. Patient recruitment is underway, and the Company remains on track to report topline data in mid-2025. Phase 1/2 Clinical Trial of INZ-701 in Adults with ENPP1 Deficiency. The Company announced positive interim safety, pharmacokinetic (PK), pharmacodynamic (PD), and exploratory efficacy data from the ongoing trial. Exploratory efficacy data reported suggested clinical benefit for ENPP1 Deficiency, including improvement in key biomarkers, patient-reported outcomes (PROs), and functional outcomes. Dosing is ongoing in the Phase 2 portion of the trial, and the Company is on track to report topline clinical data from the first three cohorts through 48 weeks in the first quarter of 2024. Phase 1/2 Clinical Trial of INZ-701 in Adults with ABCC6 Deficiency (pseudoxanthoma elasticum, or PXE). The Company announced positive interim safety, PK, PD, and exploratory efficacy data from the ongoing trial. Improvements in the Global Impression of Change (GIC), a PRO, were observed in all three dose cohorts. Dosing is ongoing in the Phase 2 portion of the trial, and the Company is on track to report topline clinical data through 48 weeks in the first quarter of 2024. Genomics England Generation Study. The Company highlighted the inclusion of Generalized Arterial Calcification of Infancy (GACI), which is caused by mutations in the ENPP1 or ABCC6 genes, in the Genomics England’s Generation Study. The Generation Study is scheduled to begin in late 2023, with the goal of sequencing the genomes of more than 100,000 infants and paving the way for potential widespread implementation of whole-genome sequencing in newborn screening. Medical Conference Presentations. The Company announced the presentation of three posters at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting and an oral presentation at the American Society for Nephrology (ASN) Kidney Week 2023. Anticipated Milestones ENPP1 Deficiency Topline data from first three cohorts of ongoing Phase 1/2 trial in adults through 48 weeks – Q1 2024 Initiation of the ENERGY-2 pivotal trial in infants, Ex-U.S. – Q2 2024 Interim data from the ENERGY-1 Phase 1b trial in infants – 2H 2024 Topline 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– Q1 2024 Initiation of Phase 3 clinical trial in adults, subject to regulatory review and sufficient funding – Q4 2024 Calciphylaxis Initiation of SEAPORT-1 Phase 1 trial designed to assess safety, tolerability, PK, and PD of INZ-701 in patients with end-stage kidney disease (ESKD) receiving hemodialysis – 1H 2024 Interim data from SEAPORT-1 Phase 1 trial in patients with ESKD receiving hemodialysis – Q4 2024 Third Quarter 2023 Financial Results Cash Position and Financial Guidance. Cash, cash equivalents, and short-term investments were $192.4 million as of September 30, 2023. Based on its current plans, the Company anticipates its cash, cash equivalents, and short-term investments as of September 30, 2023 will enable the Company to fund cash flow requirements into Q4 2025. Research and Development (R&D) Expenses. R&D Expenses were $13.3 million for the quarter ended September 30, 2023, compared to $12.2 million for the prior-year period. General and Administrative (G&A) Expenses. G&A expenses were $4.7 million for each of the quarters ended September 30, 2023 and 2022. Net Loss. Net loss was $16.6 million, or $0.29 loss per share, for the quarter ended September 30, 2023, compared to $16.4 million, or $0.38 loss per share, for the prior-year period. About ENPP1 Deficiency ENPP1 Deficiency is a progressive condition that manifests as a spectrum of diseases. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI), which is characterized by extensive vascular calcification and intimal proliferation (overgrowth of smooth muscle cells inside blood vessels), resulting in myocardial infarction, stroke, or cardiac or multiorgan failure. Approximately 50% of infants with ENPP1 Deficiency 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. ENERGY-3 Pivotal Trial of INZ-701 in Pediatric Patients with ENPP1 Deficiency The ENERGY-3 pivotal trial is a multicenter, randomized, open-label trial in pediatric patients with ENPP1 Deficiency. The trial is expected to enroll up to 33 patients between the ages of one and less than 13 years across multiple sites globally and is designed primarily to assess the efficacy and safety of INZ-701 in pediatric patients with ENPP1 Deficiency. Enrollment criteria for the trial include a confirmed genetic diagnosis of ENPP1 Deficiency, radiographic evidence of skeletal abnormalities, and low plasma pyrophosphate (PPi). Patients will be randomized in a 2:1 ratio to an INZ-701 arm or a control arm (conventional therapy, i.e., oral phosphate and active vitamin D) for 52 weeks, followed by an open-label extension period during which all patients may receive INZ-701. INZ-701 will be administered at a 2.4 mg/kg once weekly dose via subcutaneous injection. Based on recommendations from the Food and Drug Administration (FDA), the primary endpoint of plasma PPi should be supported by consistent trends in appropriate secondary endpoints such as Radiographic Global Impression of Change (RGI-C), Rickets Severity Score (RSS), and Growth Z-score. Based on the agreed Paediatric Investigational Plan (PIP) with the Paediatric Committee of the European Medicines Agency (PDCO), plasma PPi and RGI-C are co-primary endpoints, with a relaxed p-value of <0.2 for RGI-C. Phase 1/2 Clinical Trial of INZ-701 in Adults with ENPP1 Deficiency 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) pro 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 ABCC6 Deficiency ABCC6 Deficiency is a rare, severe, inherited disorder caused by mutations in the ABCC6 gene, leading to low levels of plasma pyrophosphate (PPi). PPi is essential for preventing harmful soft tissue calcification and regulating bone mineralization. ABCC6 Deficiency is a systemic and progressively debilitating condition which affects more than 67,000 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. In older individuals, ABCC6 Deficiency presents as pseudoxanthoma elasticum (PXE), which is characterized by pathological mineralization in blood vessels and soft tissues clinically affecting the skin, eyes, and vascular system. There are no approved therapies for ABCC6 Deficiency. Phase 1/2 Clinical Trial of INZ-701 in Adults with ABCC6 Deficiency 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) pro 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 Calciphylaxis Calciphylaxis is a serious and 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 plasma pyrophosphate (PPi) and is characterized by pathologic mineralization and intimal proliferation of the vasculature in the skin and fatty tissue, leading to blood clots, painful skin ulcers, infections, and death. Patients with calciphylaxis have a reported one-year survival rate of approximately 50%. The estimated incidence of calciphylaxis is at least 1,800 new patients per year in the United States, and there are currently no approved therapies. About INZ-701 INZ-701, a recombinant Fc fusion protein, is an ENPP1 enzyme replacement therapy in development for the treatment of rare disorders of the vasculature, soft tissue, and skeleton. In preclinical studies, the experimental therapy has shown potential to prevent pathologic mineralization and intimal proliferation (the overgrowth of smooth muscle cells inside blood vessels), which can drive morbidity and mortality in devastating genetic disorders such as ENPP1 Deficiency and ABCC6 Deficiency. INZ-701 is currently in multiple clinical trials for the treatment of ENPP1 Deficiency and ABCC6 Deficiency. 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 multiple clinical trials for the treatment of ENPP1 Deficiency and ABCC6 Deficiency. For more information, please visit 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 clinical trials, the availability and timing of data from clinical trials, the potential benefits of INZ-701, and the period over which we believe that our existing cash, cash equivalents, and short-term investments will be sufficient to fund our cash flow requirements. 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 and ABCC6 Deficiency; 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. Condensed Consolidated Balance Sheet Data (Unaudited) September 30, 2023 December 31, 2022 Cash, cash equivalents and investments $ 192,442 $ 127,866 Total assets $ 205,702 $ 139,195 Total liabilities $ 45,489 $ 20,801 Additional paid-in-capital $ 424,671 $ 333,356 Accumulated deficit $ (264,386 ) $ (214,761 ) Total stockholders' equity $ 160,213 $ 118,394 Condensed Consolidated Statements of Operations and Comprehensive Loss (Unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2023 2022 2023 2022 Operating expenses: Research and development $ 13,341 $ 12,191 $ 36,864 $ 34,012 General and administrative 4,733 4,721 15,973 15,130 Total operating expenses 18,074 16,912 52,837 49,142 Loss from operations (18,074 ) (16,912 ) (52,837 ) (49,142 ) Other income (expense): Interest income, net 1,416 737 3,254 1,118 Other expense, net 20 (197 ) (42 ) (493 ) Other income, net 1,436 540 3,212 625 Net loss $ (16,638 ) $ (16,372 ) $ (49,625 ) $ (48,517 ) Other comprehensive income (loss): Unrealized gains (losses) on available-for-sale securities 53 (60 ) 279 (417 ) Foreign currency translation adjustment (182 ) (20 ) (152 ) (78 ) Total other comprehensive income (loss) (129 ) (80 ) 127 (495 ) Comprehensive loss $ (16,767 ) $ (16,452 ) $ (49,498 ) $ (49,012 ) Net loss attributable to common stockholders—basic and diluted $ (16,638 ) $ (16,372 ) $ (49,625 ) $ (48,517 ) Net loss per share attributable to common stockholders—basic and diluted $ (0.29 ) $ (0.38 ) $ (1.02 ) $ (1.36 ) Weighted-average common shares and pre-funded warrants outstanding—basic and diluted 56,758,395 43,657,718 48,494,175 35,755,695 Contacts Investors: Inozyme Pharma Stefan Riley, Director of IR and Corporate Communications (857) 330-8871 stefan.riley@inozyme.com Media: SmithSolve Matt Pera (973) 886-9150 matt.pera@smithsolve.com