Product Development and Clinical Trials - INZ-701 is a lead product candidate designed to treat ENPP1 Deficiency and ABCC6 Deficiency by increasing plasma levels of inorganic pyrophosphate (PPi) and adenosine, addressing significant morbidity and mortality associated with these diseases[89]. - During the three months ended March 31, 2025, the company advanced ongoing clinical trials of INZ-701, with key highlights including interim data showing a significant increase in plasma PPi levels across all dose cohorts[91][93]. - In the Phase 1/2 clinical trial for ENPP1 Deficiency, a mean baseline plasma PPi level of 426±407 nM was observed, with significant increases noted post-treatment[94]. - The ENERGY 1 trial reported that 80% of infants treated with INZ-701 survived beyond their first year, compared to a historical survival rate of approximately 50%[97]. - INZ-701 demonstrated a favorable safety profile, with no serious adverse events attributed to the drug and low titers of anti-drug antibodies (ADAs) observed in 10 of 13 patients[95][98]. - The company plans to file a Biologics License Application (BLA) for INZ-701 for ENPP1 Deficiency, with strategic reprioritization of activities to support this goal[87][93]. - The ENERGY 3 trial for INZ-701 in pediatric patients with ENPP1 Deficiency enrolled 27 patients, with a 2:1 randomization to treatment and control arms, and is expected to report topline data in Q1 2026[104][107]. - Interim data from the ENERGY 3 trial showed a mean serum phosphate increase of +8.2% at Week 13 in the INZ-701 arm, compared to a -0.04% decrease in the conventional treatment arm[110]. - At Week 39, mean serum phosphate levels in the INZ-701 arm increased by +12.1%, while the conventional treatment arm saw a -9.0% decrease, with 35% of INZ-701 patients achieving normal serum phosphate levels[110]. - The SEAPORT 1 trial for INZ-701 in patients with end-stage kidney disease (ESKD) showed significant increases in plasma PPi levels, reaching normal ranges by week three[123]. - In SEAPORT 1, mean baseline plasma PPi was 668 nM, increasing to 1582 nM by Day 24, indicating effective pharmacodynamic response[124]. - INZ-701 was well-tolerated in the SEAPORT 1 trial, with no drug-related treatment-emergent adverse events reported in 11 patients[126]. - The ENERGY 2 trial for infants with ENPP1 Deficiency is ongoing, with patient recruitment underway and co-primary endpoints focused on plasma PPi and survival[103][115]. - The ongoing ADAPT trial is evaluating long-term safety of INZ-701 in patients with ENPP1 or ABCC6 Deficiencies who have previously received the treatment[134]. Regulatory and Market Strategy - The FDA granted Orphan Drug Designation and fast track designation for INZ-701 for the treatment of ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis, facilitating expedited development[90]. - In May 2025, the company reached an agreement with Japan's Pharmaceuticals and Medical Devices Agency to accept ex-Japan clinical data for filing, streamlining the regulatory process[93]. - The company plans to submit marketing applications for INZ-701 in the US and EU, with potential commercial launch as early as H1 2027[115][116]. - The company is prioritizing activities for the BLA filing for INZ-701 for ENPP1 Deficiency, while future trials in ABCC6 Deficiency and calciphylaxis will be postponed[121][130]. Financial Performance and Projections - INZ-701-related research and development expense increased by $1.3 million to $14.446 million for the three months ended March 31, 2025, compared to $13.105 million in the same period of 2024[159]. - Total operating expenses rose to $27.688 million for the three months ended March 31, 2025, up from $24.345 million in 2024, reflecting an increase of $3.343 million[158]. - The net loss for the three months ended March 31, 2025, was $28.039 million, compared to a net loss of $23.347 million in 2024, representing an increase of $4.692 million[158]. - Research and development expenses are expected to remain consistent in 2025 compared to 2024 due to prioritization of activities in the ENPP1 Deficiency program[152]. - Restructuring charges amounted to $1.9 million for the three months ended March 31, 2025, with no equivalent charge in the prior year[163]. - As of March 31, 2025, the company had cash, cash equivalents, and short-term investments of $84.8 million, which is projected to fund operations into the first quarter of 2026[149]. - The company has not yet commercialized any products or generated revenue from product sales, focusing on research and development activities[144]. - Significant operating losses have been incurred since inception, with future profitability dependent on the successful development and commercialization of INZ-701[145]. - The company expects to incur substantial additional costs related to ongoing clinical trials and potential commercialization efforts[149]. - Interest income for Q1 2025 decreased by approximately $1.3 million compared to Q1 2024 due to a lower cash balance[164]. - Net cash used in operating activities increased by approximately $4.6 million in Q1 2025 compared to Q1 2024, primarily due to a $4.7 million increase in net loss[174]. - Net cash provided by investing activities increased by approximately $23.3 million in Q1 2025 compared to Q1 2024, driven by a $31.4 million decrease in purchases of marketable securities[175]. - As of March 31, 2025, total cash, cash equivalents, and short-term investments amounted to approximately $84.8 million, down from $113.1 million as of December 31, 2024[172]. - The company had $45.0 million of outstanding principal indebtedness under its Loan Agreement as of March 31, 2025[178]. - Net proceeds from the August 2023 underwritten offering were approximately $64.4 million after deducting underwriting discounts and commissions[171]. - Approximately $17.0 million remained available for sale under the Open Market Sale Agreement as of March 31, 2025[169]. - The company expects to incur significant commercialization expenses if marketing approval for INZ-701 is obtained, indicating a need for substantial additional funding[177]. - The company sold 230,045 shares of common stock for aggregate net proceeds of $0.2 million in Q1 2025 under the Open Market Sale Agreement[169]. - The company anticipates that its cash, cash equivalents, and short-term investments will not be sufficient to fund operations for at least the next twelve months, raising substantial doubt about its ability to continue as a going concern[178]. - As of March 31, 2025, the aggregate principal amount outstanding under the Loan Agreement was $45.0 million, with an interest rate of 9.60%[185]. - The company borrowed an additional $20.0 million in February 2023, $7.5 million in June 2023, and $12.5 million in December 2023 under the Loan Agreement[185]. Market Risks and Economic Factors - The company is not currently exposed to significant market risk related to changes in foreign currency exchange rates, but may contract with foreign vendors in Europe in the future[186]. - Inflation has generally increased the company's cost of labor and clinical trial costs, but it did not have a material effect on the business during the three months ended March 31, 2025 and 2024[187].

- Interim data from ENERGY 3 trial highlight INZ-701’s potential to modify disease course in ENPP1 Deficiency, with sustained phosphate increases and favorable safety and immunogenicity profile to date - - ENERGY 3 trial on track for topline data in first quarter of 2026; no patient dropouts, dose adjustments or discontinuations, and no new safety signals - - Petra Duda, M.D., Ph.D. appointed Chief Medical Officer - BOSTON, May 14, 2025 (GLOBE NEWSWIRE) -- Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” ...

Phenotypic Characterization of ENPP1 Deficiency JBMR image of the phenotypic characterization of ENPP1 Deficiency - Data from the largest retrospective analysis of ENPP1 Deficiency provides insights into the evolution of the disease’s serious cardiovascular and musculoskeletal complications - - Findings highlight the urgent need for early and improved diagnosis, care and treatments that address the long-term systemic effects of ENPP1 Deficiency - BOSTON, April 10, 2025 (GLOBE NEWSWIRE) -- Inozyme Pharma ...

Inozyme Pharma is a clinical-stage biopharmaceutical company 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 (ERT) designed to restore PPi and adenosine levels. INZ-701 is currently in late-stage clinical development in EN ...

Financial Performance - The company reported net losses of $102.0 million and $71.2 million for the years ended December 31, 2024 and 2023, respectively, with an accumulated deficit of $388.0 million as of December 31, 2024[676]. - Total operating expenses were $104.0 million and $75.6 million for the years ended December 31, 2024 and 2023, respectively[677]. - The company reported a net loss of $102.0 million for the year ended December 31, 2024, compared to a net loss of $71.2 million in 2023, reflecting an increase of $30.9 million[696]. - Interest expense increased by $2.2 million in 2024 compared to 2023, primarily due to additional borrowings under the Loan Agreement[703]. - General and administrative expenses remained consistent at approximately $20.8 million for both 2023 and 2024[692]. - The company has not generated any revenue since inception and plans to finance operations through equity offerings and debt financings[705]. - As of December 31, 2024, there is substantial doubt about the company's ability to continue as a going concern without raising additional capital[716]. Cash and Investments - As of December 31, 2024, the company had cash, cash equivalents, and short-term investments of $113.1 million, which may not be sufficient to fund operations for the next twelve months[678]. - As of December 31, 2024, total cash, cash equivalents, and short-term investments amounted to approximately $113.1 million, down from $188.6 million as of December 31, 2023[710]. - Net cash used in operating activities increased by approximately $21.2 million in 2024, primarily due to a $30.9 million increase in net loss[712]. - Net cash provided by investing activities changed by approximately $120.6 million in 2024, mainly due to a $114.3 million decrease in purchases of marketable securities[713]. - Net cash provided by financing activities decreased by approximately $114.6 million in 2024, primarily due to a $64.4 million decrease related to the July 2023 equity offering[714]. Research and Development - Research and development expenses increased by $28.4 million from $54.8 million in 2023 to $83.2 million in 2024, primarily due to a $25.0 million increase in INZ-701-related expenses[698]. - INZ-701-related research and development expenses rose by $25.0 million, driven by a $10.1 million increase in chemistry, manufacturing, and controls expenses and a $14.9 million increase in clinical development costs[699]. - The company is prioritizing activities to support the planned BLA filing for INZ-701, postponing future trials in ABCC6 Deficiency and calciphylaxis[715]. Clinical Trials and Product Development - The company received fast track designation from the FDA for INZ-701 for the treatment of calciphylaxis in January 2025[673]. - Enrollment in the ENERGY 3 pivotal trial of INZ-701 in pediatric patients with ENPP1 Deficiency was completed in January 2025, with topline data expected in the first quarter of 2026[673]. - Positive interim data for INZ-701 in infants and young children with ENPP1 Deficiency was announced in January 2025[673]. - The company initiated the SEAPORT 1 trial in February 2024, which demonstrated significant increases in PPi levels in ESKD patients receiving hemodialysis[668]. - The company has not yet commercialized any products or generated revenue from product sales[675]. - The company expects to incur significant commercialization expenses if marketing approval for INZ-701 is obtained, necessitating substantial additional funding[715]. Financing and Debt - The loan agreement provides up to $70.0 million in term loans, with a first tranche commitment of $25.0 million[680]. - The term loan carries a variable interest rate with a maximum of 9.60% and matures on August 1, 2026[681]. - The company entered into a Loan Agreement providing up to $70.0 million in term loans, with $45.0 million principal outstanding as of December 31, 2024[708]. - The company closed an underwritten offering in August 2023, selling 14,375,000 shares of common stock, generating net proceeds of approximately $64.4 million[709]. - The company borrowed an additional $20.0 million in February 2023, $7.5 million in June 2023, and $12.5 million in December 2023 under the Loan Agreement[729]. Market and Economic Conditions - The company is not currently exposed to significant market risk related to foreign currency exchange rates, but may face fluctuations in the future due to contracts with foreign vendors in Europe[730]. - Inflation has increased the cost of labor and clinical trial costs, but it did not have a material effect on the company's financial condition or results of operations for the years ended December 31, 2024 and 2023[731].

Financial Position - The estimated cash, cash equivalents, and short-term investments for Inozyme Pharma, Inc. as of December 31, 2024, are approximately $113.1 million[4]. Clinical Trials and Results - Interim data from the ENERGY 1 trial showed that 80% of infants treated with INZ-701 survived beyond their first year, compared to a historical survival rate of approximately 50%[10]. - Substantial reductions or stabilization of arterial calcifications were observed in all surviving patients treated with INZ-701, with some instances of complete resolution[10]. - The ENERGY 3 pivotal trial has completed enrollment with 25 patients, providing over 90% power to detect meaningful differences in clinical endpoints[13]. - The planned ASPIRE pivotal trial in children with ABCC6 Deficiency is expected to enroll approximately 70 patients, with preliminary support from U.S. and EU regulators[15]. - The adult study of INZ-701 demonstrated positive improvements in vascular and retinal pathology after 48 weeks of treatment, supporting further development in pediatric populations[14]. - The Company anticipates completing the one-year dosing period for all patients in the ENERGY 3 trial by January 2026, with topline data expected in early 2026[13]. - INZ-701 was well-tolerated in infants and young children, with no serious treatment-related adverse events reported[10]. - The Company plans to continue regulatory engagement to finalize the ASPIRE trial protocol, aiming to initiate the trial in early 2026[16]. - The Company reported low, often transient, anti-drug antibody levels in some children and adults, with no impact on pharmacokinetics or pharmacodynamics[10].

Core Insights - Inozyme Pharma reported significant progress in its ENPP1 Deficiency program, completing enrollment in the pivotal ENERGY 3 trial and announcing promising interim data in early 2025 [2][5] - The company is focusing resources on advancing its lead therapy, INZ-701, towards potential approval for ENPP1 Deficiency, while postponing future trials for other indications [3][4] Financial Overview - As of December 31, 2024, Inozyme had cash, cash equivalents, and short-term investments totaling $113.1 million, which is expected to support operations into the first quarter of 2026 [14] - Research and Development (R&D) expenses increased to $83.2 million in 2024 from $54.8 million in 2023, driven by clinical development costs [14] - The net loss for the year ended December 31, 2024, was $102.0 million, or $1.62 loss per share, compared to a net loss of $71.2 million, or $1.37 loss per share, in 2023 [15] Strategic Initiatives - The company has implemented a workforce reduction of approximately 25% to extend its operational runway and maximize the advancement of INZ-701 [3][4] - Enrollment in the ENERGY 3 trial was completed with 27 pediatric patients, and topline data is expected in the first quarter of 2026 [5][8] Clinical Developments - Positive interim data from the ENERGY 1 trial and Expanded Access Program showed improvements in patients with generalized arterial calcification of infancy (GACI) treated with INZ-701 [6][8] - ENPP1 Deficiency is a serious rare disease with no approved therapies, affecting approximately 1 in 64,000 pregnancies worldwide [9][10]

Core Insights - Inozyme Pharma, Inc. is a clinical-stage biopharmaceutical company focused on developing therapeutics for rare diseases affecting bone health and blood vessel function [3][4] - The company will present at the TD Cowen 45th Annual Health Care Conference on March 3, 2025, from 1:10-1:40pm ET [1] - The lead candidate, INZ-701, is an enzyme replacement therapy targeting the PPi-Adenosine Pathway, currently in clinical development for ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis [4] Company Overview - Inozyme Pharma specializes in the PPi-Adenosine Pathway, where the ENPP1 enzyme plays a crucial role in generating inorganic pyrophosphate (PPi) and adenosine, which are vital for regulating mineralization and controlling smooth muscle cell proliferation in blood vessels [3] - Disruptions in this pathway can lead to severe conditions such as ENPP1 Deficiency, ABCC6 Deficiency, calciphylaxis, and ossification of the posterior longitudinal ligament (OPLL) [3] Product Development - INZ-701 is designed to increase levels of PPi and adenosine, potentially treating multiple diseases caused by deficiencies in these molecules [4] - The therapy aims to correct pathological mineralization and intimal proliferation, addressing significant morbidity and mortality associated with these diseases [4]

Core Insights - Inozyme Pharma is presenting data on INZ-701, an enzyme replacement therapy for ENPP1 Deficiency, at the CHOP Cardiology Annual Meeting [1][2] - ENPP1 Deficiency is a rare and serious disease affecting blood vessels and bones, with no approved therapies currently available [2][3] Company Overview - Inozyme Pharma is a clinical-stage biopharmaceutical company focused on developing therapeutics for rare diseases impacting bone health and blood vessel function [3][4] - The company specializes in the PPi-Adenosine Pathway, which is crucial for regulating mineralization and controlling smooth muscle cell proliferation in blood vessels [3] Product Information - INZ-701 is an ENPP1 Fc fusion protein designed to increase levels of inorganic pyrophosphate (PPi) and adenosine, potentially treating multiple diseases linked to deficiencies in these molecules [4] - The therapy is currently in clinical development for ENPP1 Deficiency, ABCC6 Deficiency, and calciphylaxis, aiming to address significant morbidity and mortality associated with these conditions [4]

Core Insights - Inozyme Pharma announced positive interim results from its ENERGY 1 trial and Expanded Access Program (EAP) for INZ-701 in infants and young children with ENPP1 Deficiency, showing improvements in survival, heart function, and reductions in ectopic calcification and hypophosphatemia [1][4][7] - The company completed enrollment in the ENERGY 3 pivotal trial for pediatric patients with ENPP1 Deficiency and received regulatory guidance for the ASPIRE pivotal trial in children with ABCC6 Deficiency [5][6][10] Positive Interim Data from ENERGY 1 Trial and EAP - Interim data showed that 80% of infants treated with INZ-701 survived beyond their first year, compared to a historical survival rate of approximately 50% [7] - All surviving patients exhibited substantial reductions or stabilization of arterial calcifications, with some achieving complete resolution [7] - Improvements in left ventricular ejection fraction (LVEF) were noted in all surviving patients [7] - No radiographic evidence of rickets was observed in patients evaluated beyond one year of age, supported by stabilization or increases in serum phosphate levels [7] - INZ-701 demonstrated a favorable safety profile, with no serious treatment-related adverse events reported [7] Enrollment and Regulatory Progress - Enrollment in the ENERGY 3 pivotal trial is complete, with dosing expected to finish in January 2026 and topline data anticipated in early 2026 [6][9] - The trial's design includes a 2:1 randomized approach, providing over 90% power to detect meaningful differences in clinical endpoints [9] - Preliminary support from U.S. and EU regulators has been received for the ASPIRE trial, which aims to address severe complications of ABCC6 Deficiency in children [10][11] About ENPP1 and ABCC6 Deficiency - ENPP1 Deficiency is a rare disease affecting blood vessels, soft tissues, and bones, with a significant mortality rate in infants [13] - ABCC6 Deficiency similarly affects blood vessels and soft tissues, leading to severe complications in pediatric patients [14][15] - Both conditions currently lack approved therapies, highlighting a significant unmet medical need [13][15] About Inozyme Pharma - Inozyme Pharma is a clinical-stage biopharmaceutical company focused on developing innovative therapeutics for rare diseases affecting bone health and blood vessel function [16][17] - The lead candidate, INZ-701, is designed to increase levels of inorganic pyrophosphate (PPi) and adenosine, targeting multiple diseases caused by deficiencies in these molecules [17]