Hypophosphatemia, Familial

– 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

- Presentations Highlight Potential Benefits of Therapies Incorporating J-Brain Cargo®, JCR’s Proprietary, Blood-Brain Barrier-Penetrating Technology - HYOGO, Japan--(BUSINESS WIRE)-- JCR Pharmaceuticals Co., Ltd. (TSE 4552; Chairman and President: Shin Ashida; “JCR”) today announced the presentation of several datasets demonstrating the potential benefits of its investigational therapies for lysosomal storage disorders (LSDs). In a series of oral and poster presentations at the 20th Annual WORLDSymposium™ in San Diego, Calif., JCR highlighted several programs that rely on J-Brain Cargo®, a proprietary technology developed by JCR, to deliver medicines across the blood-brain barrier (BBB). “Lysosomal storage disorders present a lifelong burden for patients because of the somatic, and most importantly, the progressive neurological signs and symptoms associated with these devastating and life-threatening diseases for which there are inadequate treatment options or no approved therapies available. JCR is dedicated to address the unmet medical needs for this community,” said Shin Ashida, President and CEO of JCR Pharmaceuticals. “The clinical data presented at the WORLDSymposium™ demonstrate the safety and efficacy of JR-141 in individuals with MPS II and the potential of our proprietary J-Brain Cargo® technology across multiple lysosomal storage disorders. In addition, we’re excited to present preclinical data focused on retinal function and bone abnormalities.” There are three JR-141 presentations, including one presentation focused on the long-term safety and efficacy and behavioral effects of JR-141 (pabinafusp alfa) for mucopolysaccharidosis type II (MPS II, or Hunter syndrome). JR-141 is a recombinant iduronate-2-sulfatase (I2S) enzyme replacement therapy (ERT) that was approved in March 2021 by the Ministry of Health, Labour and Welfare (MHLW) in Japan, where it is marketed as IZCARGO® for the treatment of patients with MPS II. The second JR-141 presentation details the global phase III clinical trial study. Finally, the third JR-141 presentation is pre-clinical and highlights the recovery of retinal function in mice with MPS II. “We are pleased to be able to offer IZCARGO® to patients with MPS II in Japan,” said Yoshikatsu Eto, M.D., Ph.D., Institute of Neurological Disorders, Advanced Clinical Research Center, Kanagawa, Japan. “As we continue gathering new data from the Japanese and Brazilian long-term efficacy study and from the ongoing phase III global JR-141 clinical study, currently in recruitment, we look forward to providing updates as appropriate. These data sets will make it more certain that JR-141 can treat not only the somatic symptoms of MPS II, but also the neurocognitive symptoms of this devastating and life-threatening disease.” In addition to the three JR-141 presentations, the WORLDSymposium™ 2024 scientific program featured presentations focusing on: 52-week interim data from the JR-171 phase I/II clinical trial (Hurler syndrome, Hurler-Scheie syndrome or Scheie syndrome); pre-clinical data on an ERT with JR-171 preventing bone deformities in a mouse model of MPS I; JR-441 global clinical trial study design (Sanfilippo syndrome type A). JR-141 MPS II Datasets The following poster presentation provides additional evidence and context for the use of JR-141 in the treatment of MPS II: Integrated long-term efficacy and safety data on enzyme replacement therapy with pabinafusp alfa for neuronopathic mucopolysaccharidosis II (MPS-II): updated clinical data from Japan and Brazil (Abstract 81) Presenter: Yoshikatsu Eto, M.D., Ph.D. (Institute of Neurological Disorders, Advanced Clinical Research Center, Kanagawa, Japan) This abstract analyzes the long-term efficacy and safety data on pabinafusp alfa for the treatment of individuals with MPS II. This study analyzed 104 patients over 260 weeks. In terms of safety, the data include four pabinafusp alfa-related serious adverse events (consciousness disturbance, hypotension, pyrexia and facial palour) in one individual, but all four were managed and resolved. Infusion-associated reactions were noted to gradually decrease in frequency as the length of exposure to pabinafusp alfa increased. The Kyoto Scale of Psychological Development, Bayley Scale for Infant Development, Kaufman Assessment Battery for Children, and Vineland Adaptive Behavioral Scale were used to evaluate the efficacy of pabinafusp alfa against neurocognitive impairment. A developmental quotient (DQ) of >70 was identified as the best predictor of treatment response in achieving age-equivalent neurodevelopment. Another predictor was age at initiation of treatment, with initiation before 36 months of age associated with the most favorable response in subjects with severe MPS II. Analysis of adaptive behavior showed a trend to overall improvement in most individuals with the attenuated subtype, and some improvement in those with the severe subtype and a DQ of >70, while changes, as expected, were limited in those with a DQ of <70. Notable sustained efficacy was seen in terms of liver and spleen volumes, joint range of motion, and left ventricular mass index. These outcomes of ERT with pabinafusp alfa for more than five years provide good evidence of its safety as well as peripheral efficacy, with preliminary data of central efficacy particularly in certain patients with attenuated form of the disease. Post-marketing studies will last for a total of 10 years and provide long-term evidence of pabinafusp alfa’s safety and efficacy. The following poster presentation provides an overview of the global phase III clinical trial study design for JR-141 in the treatment of MPS II: A global phase III study of pabinafusp alfa (JR-141) for neuronopathic mucopolysaccharidosis type II: updated study design (Abstract 154) Presenter: Toshiaki Ikeda (JCR Pharmaceuticals) This abstract provides an overview of the ongoing global phase III clinical trial of pabinafusp alfa (JR-141) for neuronopathic MPS II. The trial began in February 2022 and spans 10 countries as of now. The study consists of two cohorts with a total of 80 patients with MPS II. Cohort A includes individuals with the severe (neuronopathic) subtype aged 30 to 71 months, who are randomized into a treatment arm given a weekly administration of JR-141 at 2.0 mg/kg, and a control arm receiving ERT idursulfase; the total study duration is 24 months, and the purpose is to demonstrate that the efficacy of JR-141 in patients with neuronopathic MPS II is superior to that of conventional ERT. Cohort B consists of attenuated patients aged 6 years and older, randomized into two arms in the same manner as above; the study duration is 12 months, and the purpose is to evaluate the efficacy of JR-141 in patients with somatic symptoms in comparison with that of idursulfase. Primary efficacy endpoints are assessed on the basis of HS levels in the CSF and neurocognitive test (BSID-III) results. Key secondary outcome measures include liver and spleen volumes and further neurological outcomes. The study thus designed is expected to establish the efficacy of JR-141 against both the central nervous system (CNS) and peripheral/somatic symptoms. Details of other outcome measures and study design components will be presented at the symposium. The following poster presentation showcases preclinical data on retinal function for the use of JR-141 in the treatment of MPS II: Recovery of retinal function in MPS II mice by treatment with pabinafusp alfa (Abstract 155) Presenter: Atsushi Imakiire (JCR Pharmaceuticals) This abstract explains how pabinafusp alfa addresses one of the difficult-to-treat complications of MPS II: Retinal disorders in individuals with MPS II are known to be resistant to conventional intravenous ERT due to the presence of the blood-retinal barrier (BRB), which interferes with drug transport into the eye. The retinal function assessed by electroretinography (ERG) was found to worsen with age in a murine model of MPS II (hTfR knock-in/Ids knock-out mice). The presented study demonstrates that pabinafusp alfa crosses the BRB and reaches the retina in MPS II mice. Repeated intravenous dose of pabinafusp alfa started at an early age decreased HS deposition in the retina, optic nerve, and visual cortex and preserved or improved ERG response in MPS II mice. Retinal degeneration was also ameliorated by pabinafusp alfa. Recombinant non-fused I2S did not enter the retina and minimally affected the retinal disease. These results substantiate the postulate that pabinafusp alfa penetrates the BRB and exerts beneficial effects on retinal dysfunction in MPS II. JR-171 MPS I Datasets The following poster presentation focuses on the use of JR-171 in the treatment MPS I: Efficacy and safety data (52-week) from a phase 1/2 trial and extension study of JR-171 (lepunafusp alfa) used in enzyme replacement therapy for patients with MPS I (Abstract 113) Presenter: Roberto Giugliani, M.D., Ph.D. (Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil) This abstract reports the 52-week safety and efficacy data from the first-in-human, open-label, multicenter phase I/II trial and an extension study of JR-171 used to treat 14 individuals with MPS I. The 14 individuals had a broad spectrum of disease severity. 12 of them had received treatment with laronidase prior to enrollment, one was treated with laronidase after hematopoietic stem cell transplantation, and the other individual was treatment-naïve. The most common adverse drug reactions were infusion-associated reactions, all manageable without requiring discontinuation of the test drug. Ability to target the neuronopathy was evaluated by measuring HS levels in the CSF from baseline through weeks 13, 26, and 52, all of which were significantly reduced in all subjects. Also, in several individuals with the severe subtype whose treatment started early, neurocognitive data suggested some stabilization of neurodevelopmental decline in comparison with the natural history data. Liver and spleen volumes were stabilized in most of the patients. Other somatic signs and symptoms, including urine and serum HS/DS concentrations, were well-controlled in the subjects switched from laronidase, while they decreased significantly and then remained stable in the naïve patients. These data provide further evidence that JR-171 is delivered across the BBB to address the CNS manifestations of MPS I as well as the somatic/peripheral symptoms while maintaining an appropriate safety profile. A pivotal phase III clinical trial is planned to establish the efficacy and safety of the drug. The following poster presentation highlights preclinical data on bone deformities for the use of JR-171 in the treatment of MPS I: Enzyme replacement therapy with a blood-brain barrier-penetrating antibody-fused a-L-iduronidase prevents bone deformities in a mouse model of mucopolysaccharidosis I (Abstract 229) Presenter: Hiroki Morioka (JCR Pharmaceuticals) This abstract reports on the effect of JR-171 on the CNS and bone abnormalities in hTfR knock-in/Idua knock-out mice, an animal model of MPS I. JR-171 was intravenously administered to the mice once a week at 2.0 and 4.0 mg/kg for 24 weeks. The long-term intravenous treatment with JR-171 markedly reduced HS and DS concentrations and improved histopathological changes in the peripheral and CNS tissues. In addition, using micro-computed tomography, MPS I mice were found to have skeletal abnormalities such as increased bone mass and density. The treatment with JR-171 prevented or improved the skeletal abnormalities observed in MPS I mice. These results suggest the potential efficacy of JR-171 against neurodegeneration and neurological impairments, and demonstrate the beneficial effects on bone deformities characteristic of MPS I. The following late-breaking abstract discloses patient experiences upon treatment with JR-171: The impact of lepunafusp alfa (JR 171) on the disease burden in MPS I: Patient reported outcomes (Abstract LB-39) Presenter: Ana Maria Martins (Reference Center in Inborn Errors of Metabolism, Federal University of Sao Paulo, Brazil) This late-breaking abstract presents data on patient reported outcomes of individuals treated in an ongoing phase I/II study with lepunafusp alfa, a fusion protein consisting of a transferrin-receptor binding domain and α-L-iduronidase, the enzyme missing or malfunctioning in MPS I. JR-441 MPS IIIA Dataset The following poster presentation showcases the company’s pipeline of innovative, BBB-penetrating ERT products for the treatment of MPS IIIA: A phase I/II clinical trial of JR-441 for treatment of Sanfilippo syndrome type A (MPS IIIA) (Abstract 234): Presenter: Nicole Muschol, M.D. (University Medical Center Hamburg-Eppendorf, International Center for Lysosomal Disorders (ICLD), Hamburg, Germany) This abstract reports the Phase I/II clinical trial study design of JR-441 as a first-in-human, open-label, single-center trial to evaluate the optimal dose, safety/tolerability, pharmacokinetics and exploratory efficacy in individuals with MPS IIIA aged ≥1 year to ≤18 years. This study consists of a treatment period (52-week), a drug holiday period (6-week), and an extension period (202-week). After confirming the tolerability in the first 6 individuals with MPS IIIA in a dose escalating manner, a total of 12 individuals are then treated with JR-441 for approximately 5 years. During the drug holiday period, potential rebound effects due to withholding JR-441 are evaluated. Following dose escalation, all individuals are randomized to 2 treatment doses until an optimal dose is determined, which is applied thereafter to all of the enrolled subjects. A broad range of assessments are performed including substrate levels in the CSF, blood and urine, MRI of the brain, liver and spleen, neurodevelopmental function tests, adaptive behavior tests, quality-of-life questionnaires, and life-habit-related questionnaires regarding sleeping, eating and stool to identify and validate suitable endpoints to inform the design of a future global registrational trial. About Pabinafusp Alfa (JR-141) Pabinafusp alfa is a recombinant fusion protein of an antibody against the human transferrin receptor and idursulfase, the enzyme missing or malfunctioning in subjects with Hunter syndrome. It utilizes J-Brain Cargo®, JCR’s proprietary blood-brain barrier (BBB)-penetrating technology, to cross the BBB via transferrin receptor-mediated transcytosis. Uptake into cells is mediated through the mannose-6-phosphate receptor or the transferrin receptor. This novel mechanism of action is expected to make IZCARGO® effective against the CNS symptoms of Hunter syndrome. In pre-clinical studies, JCR has confirmed both high-affinity binding of pabinafusp alfa to transferrin receptors and passage across the BBB into neuronal cells. In addition, JCR has confirmed enzyme uptake in various brain tissues. The company has also confirmed a reduction of substrate accumulation in the CNS and peripheral organs in an animal model of Hunter syndrome.1,2 In several clinical trials with pabinafusp alfa, JCR obtained evidence of reducing heparan sulfate (HS) concentrations in the CSF, a biomarker that is believed to reflect substrate reduction in the brain and changes in CNS function. These results were consistent with those obtained in pre-clinical studies. Clinical studies have also demonstrated positive effects of pabinafusp alfa on CNS symptoms.3,4,5,6 Pabinafusp alfa was approved by the Ministry of Health, Labour and Welfare in Japan and marketed since May 2021 under the brand name “IZCARGO® I.V. Infusion 10mg.” In September 2021, JCR and Takeda announced a collaboration and license agreement to commercialize JR-141. Under the agreement, Takeda will exclusively commercialize JR-141 outside of the United States, including Canada, Europe, and other regions (excluding Japan and certain other Asia-Pacific countries). Takeda also received an option for an exclusive license to commercialize JR-141 in the U.S. upon completion of the phase III program. Important Safety Information INDICATION: IZCARGO® is indicated for the treatment of mucopolysaccharidosis type II (MPS II), which is also known as Hunter syndrome. IZCARGO® is approved in Japan only. CONTRAINDICATION: IZCARGO® is contraindicated in patients with a history of anaphylactic shock to any of its components. WARNINGS AND PRECAUTIONS: Warnings Since serious anaphylaxis and shock may occur with the use of IZCARGO®, adequate emergency measures should be made ready for application before initiation of administration, and the patient should be closely monitored during and after the administration. If a serious infusion associated reaction (IAR) occurs, administration of IZCARGO® should be discontinued, and appropriate actions should be taken. When IZCARGO® is administered to patients with severe respiratory failure or acute respiratory disease, an IAR may lead to acute exacerbation of symptoms. The patient’s condition should be closely monitored, and appropriate actions should be taken as needed. Precautions for Use IZCARGO® is a protein medicinal product and may cause anaphylactic shock, for which close monitoring is required. If any signs of anaphylaxis are noted, discontinue the infusion, and take appropriate actions. Considering the onset of such symptoms, emergency measures should be made ready for application. IZCARGO® may cause IARs such as headache, chills, syncope, fatigue, dizziness, pyrexia, rash, erythema, urticaria, or other symptoms. If an IAR occurs, reduce the rate or temporarily discontinue the infusion, and initiate appropriate drug treatment (e.g., corticosteroids, antihistamines, antipyretic analgesics, anti-inflammatory drugs) or emergency procedures (e.g., oxygen administration, securing of airway, adrenaline administration). Premedication with antihistamines, corticosteroids, etc. should be considered for the subsequent infusion of IZCARGO®. ADVERSE REACTIONS: The most commonly reported adverse reactions were pyrexia and urticaria. About the J-Brain Cargo® Platform Technology JCR Pharmaceuticals has developed a proprietary BBB-penetrating technology J-Brain Cargo®, to bring biotherapeutics into the CNS. The first drug developed based on this technology and approved in Japan for the treatment of MPS II (mucopolysaccharidosis type II) is IZGARGO® (INN: pabinafusp alfa). Based on the same platform technology, JR-171 (INN:lepunafusp alfa) and JR-441 are advancing into global clinical stage. JCR intends to start clinical trials on four additional programs from its LSD pipeline by FY2028. About Mucopolysaccharidosis II (Hunter Syndrome) Mucopolysaccharidosis II (Hunter syndrome) is an X-linked recessive LSD caused by a deficiency of iduronate-2-sulfatase, an enzyme that breaks down complex carbohydrates called glycosaminoglycans (GAGs, also known as mucopolysaccharides) in the body. Hunter syndrome, which affects an estimated 7,800 individuals worldwide (according to JCR research), gives rise to a wide range of somatic and neurological symptoms. The current standard of care for Hunter syndrome is ERT. CNS symptoms related MPS II have been unmet medical needs so far. About Mucopolysaccharidosis I (Hurler, Hurler-Scheie, Scheie syndrome) MPS I is an autosomal recessive lysosomal storage disorders (“LSD”) caused by a deficiency of α-L-iduronidase, an enzyme that breaks down glycosaminoglycans (mucopolysaccharides) in the body. The current worldwide prevalence of MPS I is estimated to be approximately 3,000 (according to JCR internal research). MPS I gives rise to a wide range of somatic and neurological symptoms. A major limitation of current ERT is that it does not address CNS symptoms because of the enzyme’s inability cross the BBB. MPS I is the only LSD in which hematopoietic stem cell transplantation (“HSCT”) is part of the standard of case for the severe form of the disease. Significant unmet medical need persists in all forms of MPS I. About Sanfilippo Syndrome (MPS III) Sanfilippo syndrome is an autosomal recessive disease caused by a deficiency of the enzymes that metabolize mucopolysaccharides within the body. The disease is classified into four subtypes (A, B, C, and D) according to the respective deficient enzymes. Symptoms include accumulation of heparan sulfate in tissues throughout the body. Notably, the rapidly progressive form of the disease frequently affects neurologic development, which peaks around two or three years of age, before subsequently deteriorating, resulting in a complete loss of speech by the age of seven or eight. Progression further gives rise to symptoms such as sleep disorders, hepatosplenomegaly, seizures, and neurobehavioral abnormalities. About JCR Pharmaceuticals Co., Ltd. JCR Pharmaceuticals Co., Ltd. (TSE 4552) is a global specialty pharmaceuticals company that is redefining expectations and expanding possibilities for people with rare and genetic diseases worldwide. We continue to build upon our 49-year legacy in Japan while expanding our global footprint into the US, Europe, and Latin America. We improve patients’ lives by applying our scientific expertise and unique technologies to research, develop, and deliver next-generation therapies. Our approved products in Japan include therapies for the treatment of growth disorder, Fabry disease, MPS II (Hunter syndrome), acute graft-versus host disease, and renal anemia. Our investigational products in development worldwide are aimed at treating rare diseases including MPS I (Hurler, Hurler-Scheie and Scheie syndrome), Hunter syndrome, Pompe disease, and more. JCR strives to expand the possibilities for patients while accelerating medical advancement at a global level. Our core values – reliability, confidence, and persistence – benefit all our stakeholders, including employees, partners, and patients. Together we soar. For more information, please visit . Cautionary Statement Regarding Forward-Looking Statements This document contains forward-looking statements that are subject to known and unknown risks and uncertainties, many of which are outside our control. Forward-looking statements often contain words such as “believe,” “estimate,” “anticipate,” “intend,” “plan,” “will,” “would,” “target” and similar references to future periods. All forward-looking statements regarding our plans, outlook, strategy and future business, financial performance and financial condition are based on judgments derived from the information available to us at this time. Factors or events that could cause our actual results to be materially different from those expressed in our forward-looking statements include, but are not limited to, a deterioration of economic conditions, a change in the legal or governmental system, a delay in launching a new product, impact on competitors’ pricing and product strategies, a decline in marketing capabilities relating to our products, manufacturing difficulties or delays, an infringement of our intellectual property rights, an adverse court decision in a significant lawsuit and regulatory actions. This document involves information on pharmaceutical products (including those under development). However, it is not intended for advertising or providing medical advice. Furthermore, it is intended to provide information on our company and businesses and not to solicit investment in securities we issue. Except as required by law, we assume no obligation to update these forward-looking statements publicly or to update the factors that could cause actual results to differ materially, even if new information becomes available in the future. References 1: Sonoda, et al. A blood-brain-barrier-penetrating anti-human transferrin receptor antibody fusion protein for neuronopathic mucopolysaccharidosis II. Mol. Ther. 2018; 26(5):1366-1374. 2: Morimoto, et al. Clearance of heparin sulfate in the brain prevents neurodegeneration and neurocognitive impairment in MPS II mice. Mol. Ther. 2021; 29(5): 1853-1861. 3: Okuyama, et al. Iduronate-2-sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1/2 Trial. Mol Ther. 2020; 27(2): 456-464. 4: Okuyama, et al. A Phase 2/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II. Mol Ther. 2021; 29(2): 671-679. 5: Giugliani, et al. Iduronate-2-sulfatase fused with anti-human transferrin receptor antibody, pabinafusp alfa, for treatment of neuronopathic and non-neuronopathic mucopolysaccharidosis II: Report of a phase 2 trial in Brazil. Mol Ther. 2021; 29(7): 2378-2386. 6: Giugliani, et al. Enzyme Replacement Therapy with Pabinafusp Alfa for Neuronopathic　Mucopolysaccharidosis II; an Integrated Analysis of Preclinical and Clinical Data. Int. J. Mol. Sci. 2021, Volume 22, Issue 20, 10938.

BridgeBio Pharma announced it has granted Kyowa Kirin exclusive rights in Japan to develop and sell infigratinib for achondroplasia and related bone growth disorders. As part of the deal announced Wednesday, Kyowa Kirin will pay BridgeBio $100 million upfront plus unspecified milestones, along with up to high-20s percent royalties on potential future sales.Infigratinib is a selective oral ATP-competitive inhibitor of fibroblast growth factor receptors designed to target FGFR3-driven skeletal dysplasias such as achondroplasia and hypochondroplasia at their source. In December, BridgeBio dosed the first patient in the Phase III PROPEL 3 trial evaluating infigratinib in children with achondroplasia after a mid-stage study showed that it significantly increased annual height velocity by an average +3.38 cm/year through to six months.Providing a "once-daily oral treatment option" is a key goal for the programme based on patient community needs, according to Justin To, chief executive of QED Therapeutics, BridgeBio’s skeletal dysplasia-focused subsidiary. Japanese trial in 2025Kyowa Kirin aims to begin a pivotal trial in Japan next year for infigratinib, which adds to its portfolio in bone disorders and rare diseases. The Japanese drugmaker previously partnered with Ultragenyx Pharmaceutical to develop injectable Crysvita (burosumab-twza), a monoclonal antibody that blocks FGF23 to treat X-linked hypophosphataemia as well as tumour-induced osteomalacia.If approved, infigratinib could compete against BioMarin Pharmaceutical's once-daily injectable treatment Voxzogo (vosoritide), which Japan’s Ministry of Health, Labor and Welfare greenlight in 2022 to treat achondroplasia in children of all ages, whose growth plates are not closed.  BridgeBio continues deal spreeThe arrangement with Kyowa Kirin adds to the tally of recent deals done by BridgeBio to help fund its burgeoning pipeline of drugs focused on addressing genetically well-defined conditions amid stiff competition.Earlier this year it reached a royalty agreement with Blue Owl and CPP Investments that will see it pocket a $500-million milestone payment if another pipeline drug, acoramidis, scores an approval in the US for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). The total financing from the two funds could climb to as much as $1.25 billion. Acoramidis, which is currently under review by the FDA with a decision expected by November 29, is expected to compete against Pfizer's ATTR-CM treatment Vyndamax (tafamidis).