SR-8541A

– 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

SUNNYVALE, CA, USA I October 20, 2023 I Riboscience, LLC, today announced the first presentation of data from the ongoing Phase 1 clinical trial of the ENPP1 inhibitor RBS2418 that will be delivered by Dr. Thomas U. Marron, MD, PhD, from Mount Sinai, New York at the European Society for Medical Oncology (ESMO) Congress 2023 on October 21, 2023. RBS2418 is the first ENPP1 inhibitor in clinical development. Clinical study RBS2418-1001 (NCT05270213) is a Phase 1, open-label, non-randomized study in adult patients with advanced, unresectable, recurrent or metastatic solid tumors, who have progressed on, or are ineligible for standard therapies. The dose escalation phase of the study follows a 3+3 design with increasing doses of RBS2418 given orally as monotherapy or in combination with Pembrolizumab. Riboscience presents data from an ongoing Phase 1 trial of a new immunotherapy in patients with advanced cancers The ESMO presentation #1025MO summarizes the safety, PK and PD results and clinical outcomes of treatment with RBS2418 from the first 19 patients in the dose escalation phase of the study. There are 11 different cancer types represented and 84% of patients had failed 3 or more lines of prior treatment. The concentration of RBS2418 in plasma and in tumor samples exceeded the human serum EC90 of ENPP1 inhibition in all patients at all dose levels (100, 200, 400 mg) and at all time points tested. Median plasma Cmax and Ctrough levels of RBS2418 increased dose proportionally. No DLTs, no treatment-related SAEs or treatment-related AEs above grade 2 were observed for treatment durations up to 1 year. Immune activation and tumor infiltration of CD4 and CD8 cells was observed in patients who expressed ENPP1 and cGAS protein in baseline tumor samples, EG(+) phenotype. The EG(+) phenotype was present in 53% of the patients at baseline. This phenotype predicted outcome with RBS2418 treatment, as 60% of treated EG(+) patients experienced stable disease as compared to 0% of patients who did not express ENPP1 or cGAS in the baseline tumor sample, EG(-) phenotype. Progression-free survival (PFS) was significantly increased in EG(+) vs EG(-) phenotypes (p=0.0013). Clinical benefit from RBS2418 was dependent on the presence of the drug target (ENPP1), indicating target-inhibition dependent clinical benefit with RBS2418 treatment, consistent with the PK/PD results that demonstrated full ENPP1 inhibition and cGAMP stabilization at all dose levels. These results show a target-inhibition-dependent immune activation and significant clinical benefit of a well-tolerated oral RBS2418 treatment and support further clinical development of this novel first-in-class immunotherapy agent. The clinical study is proceeding into a dose-expansion phase. About Riboscience, LLC Riboscience is a private clinical-stage biotechnology company leveraging a proprietary library of nucleoside and non-nucleoside analogs to rationally design drug candidates that are highly selective for essential targets in the virology and oncology spaces. Nucleoside analogs are examples of ribose-based molecules that have become important drugs for the treatment of a number of viral diseases and cancers. The Riboscience library of nucleoside and non-nucleoside molecules is rationally designed to deliver drug candidates that are highly efficacious and highly selective for essential targets in the virology and oncology spaces. About RBS2418 RBS2418 is a nucleoside-derived small molecule that has been optimized for potent (picomolar binding affinity) and selective binding to the active site of ENPP1. ENPP1 is the only enzyme known in humans to hydrolyze the immune-activating messenger molecule cGAMP that is generated in tumor cells in the context of replication errors, DNA damage and a variety of replication defects. ENPP1 also hydrolyzes ATP and contributes to the generation of increased immune-suppressive adenosine levels in the TME. ENPP1 upregulation is commonly observed in tumors and is associated with immune evasion, cold tumor phenotype, disease progression, metastasis, and non-response to checkpoint inhibitors. The orally administered RBS2418 is the first clinical stage ENPP1 inhibitor and is being investigated in a Phase 1a/b dose escalation  and expansion study as monotherapy and in combination with Pembrolizumab. Refer to the clinicaltrials.gov overview for more information: RBS2418 Evaluation in Subjects With Unresectable or Metastatic Tumors - Full Text View - ClinicalTrials.gov For additional information, please visit Https://www.Riboscience.com Previously, RBS2418 was evaluated in an expanded access study RBS2418-EA-001, the results of which have been presented at the ESMO-IO conference 2022 (#169P). This was an expanded access study in a patient with advanced adrenal cancer, who had previously progressed on multiple treatments, including a treatment with pembrolizumab and cabozantinib. The results showed that weekly intra-patient escalation of doses from 100 mg BID to 400 mg BID in combination with pembrolizumab was safe, well tolerated with no DLTs. RBS2418 PK data showed oral bioavailability with plasma levels leading to complete serum ENPP1 inhibition at all time points already at the 100 mg starting dose level. The treatment induced increases in peripheral cDCs, proliferation of CD4 and CD8 T cells and hyperexpansion of TCR clonotypes in peripheral blood as well as upregulation of T cell cytotoxic granule protein gene expression, consistent with a treatment-induced immune activation from a baseline cold tumor phenotype. These results are consistent with the preliminary results from the Phase 1 a/b study presented at ESMO 2023. SOURCE: Riboscience