Rickets

Hyloris Reports Full Year Results for 2023 & Provides Business Outlook Total revenue and other income amounted to €4.4 millionStronger growth expected in 2024 of both sales and gross margin, mainly fueled by the recent launch in the U.S. of Maxigesic® IV and Podofilox gel, the global roll out of Maxigesic IV® and commercial dealsIncreased operating R&D expenses while net operating cash outflow remained stable versus 2022Significant R&D progress including clinical and regulatory achievements with multiple NDA submissions expected within the next 15 monthsAttractive commercial deals, including an out-licensing deal for Atomoxetine Oral Liquid in CanadaPromising new product candidates driving innovation, targeting a portfolio of 30 assets by 2025€30.2 million in cash & cash equivalents, no financial debtWebcast on 14 March 2024 at 1PM GMT / 2PM CET/ 9AM EST (Register here) Liège, Belgium – 14 March 2023 – 7AM CET – Regulated Information – Inside Information - Hyloris Pharmaceuticals SA (Euronext Brussels: HYL), a specialty biopharma company committed to addressing unmet medical needs through reinventing existing medications, today announces its financial and operational results for the year ending on 31 December 2023, as well as its business outlook for 2024. Stijn Van Rompay, Chief Executive Officer of Hyloris, commented: “Despite a challenging year for the global healthcare industry, 2023 proved to be a year of significant accomplishment for Hyloris. As a company built on the unique and successful strategy of repurposing and reformulating existing pharmaceuticals, we achieved a major milestone with the U.S. approval of Maxigesic® IV in partnership with AFT Pharmaceuticals, marking a crucial step in delivering this innovative pain management solution to American patients. Additionally, approval was secured for Podofilox gel, the first generic version of Condylox® Gel, expanding access to this medication. Our unwavering commitment to research and development yielded impressive progress across our diverse product pipeline. These advancements solidify our position as a leader in providing solutions to unmet medical needs in the years to come. We are incredibly proud of our team's dedication and resilience throughout this transformative year. Looking ahead to 2024, Hyloris is poised for continued growth and innovation. We plan to significantly bolster our pipeline with the addition of several new product candidates addressing critical unmet medical needs. Recent additions, including treatments for Vulvar Lichen Sclerosus and Burning Mouth Syndrome, demonstrate our commitment to expanding our portfolio and addressing a wider range of patient needs. We remain confident in our ability to continue delivering value to patients, shareholders, and all stakeholders and expect continued growth beyond 2024. Commercial Highlights Maxigesic® IV is a patented, unique combination, intravenous formulation for the treatment of post-operative pain and is currently licensed to partners covering over 100 countries across the globe. During 2023 and early 2024: A marketing authorization was granted by the United States Food and Drug Administration (FDA) in October 2023.Hikma Pharmaceuticals (Hikma), a leading supplier of complex injectable hospital products, has launched the product in the U.S. under the tradename Combogesic® IV. An exclusive license and distribution agreement had previously been signed between Hyloris’ partner AFT Pharmaceuticals (AFT) and Hikma.Additional submissions for marketing authorization were made in 13 countries in the Middle East, Africa, Latin America, and Asia.Additional marketing authorizations have been granted in 8 countries including Poland, South Africa, and Spain. In early 2024, Health Canada granted approval bringing the total number of approvals to 50.Launches occurred in 14 countries including Norway, Singapore, Belgium, The Netherlands, the Czech Republic, and Romania. Imminent launches are expected in several additional countries, bringing the total number of countries where Maxigesic® IV will be available up to more than 30. In the United States, chronic opioid usage in patients following surgery averages around 9%, ranging from 4% to 24% among various specialties. Drug overdoses involving opioids resulted in over 80.000 deaths in the U.S. in 2021. Patients who experienced an opioid overdose accounted for nearly $2 billion in annual hospital costs. Sotalol IV is a patented, intravenous formulation of Sotalol for the treatment of atrial fibrillation, and life-threatening ventricular arrhythmias developed for the U.S. Sotalol IV potentially allows to significantly reduce the length of hospital stay and the overall cost of care and potentially improve patient outcomes. Hyloris is taking further steps targeting to increase product related revenues in the future (see also: Ongoing Legal Proceedings). Podofilox Gel (Product previously referenced as HY-016) In December 2023, our partner Padagis US LLC (Padagis) received marketing authorization for Podofilox gel 0.5% from the FDA. Padagis launched the product in December 2023. It is the first generic for Condylox® Gel in the U.S. Podofilox Gel is an antimycotic drug for the topical treatment of external genital and perianal warts caused by certain types of the Human Papilloma Virus (HPV). Around 1% of the sexually active population in the U.S. presents with genital or perianal warts.1 To date there is a vaccine for HPV but no cure. For the 12 months period ending December 2022, Condylox® Gel had U.S. sales of approximately $9 million according to IQVIA Health. Other Commercial Highlights Tranexamic Acid RTU Additional out-licensing agreements were signed for Tranexamic Acid RTU in 2023. These agreements cover a large European country and several major Asian countries, with a combined population of over 60 million people. Previous agreements have been signed in 2021 for Australia, New-Zealand and Canada. In 2023, our licensing partner for Canada submitted an application for approval by Health Canada. Additional regulatory submissions in the partnered territories are in progress, and more out-licensing agreements are expected going forward. An Abbreviated New Drug Application (ANDA) has been submitted to the U.S. FDA. Tranexamic acid injection is an established antifibrinolytic agent used in emergency situations with major hemorrhages and is also used as a prophylactic agent in surgeries. Hyloris is developing a ready-to-use (RTU) formulation for infusion. Atomoxetine Oral Liquid An out-licensing agreement was signed with Kye Pharmaceuticals (Kye) in October 2023. Kye will exclusively commercialize the product in Canada where atomoxetine is currently not available as an oral liquid formulation. The introduction of an oral liquid formulation in the ADHD (Attention Deficit Hyperactivity Disorder) medication category has historically led to significant market share gains2. This suggests a strong potential for Atomoxetine Oral Liquid in Canada, where an estimated 1.8 million people (or 4-6% of adults and 5-7% of children) are diagnosed with ADHD3. ADHD is a chronic condition, with symptoms persisting into adulthood for 60-80% of patients4. Under the terms of the agreement, Hyloris will be eligible to receive attractive sales-related milestone payments (totaling up to USD 7.5 million), and a substantial share of the generated revenue. New Pipeline Product Candidates Our business development team leverages its expertise in existing products, real-world data, and a vast network to identify unmet medical needs. This includes collaborating with healthcare professionals, patient groups, insurers (payors), and industry partners. In 2023 over 87 opportunities were screened and 3 product candidates will meet our investment criteria of €7 million5 in 7 years or less. For product candidates which Hyloris intends to out-license, the strategic goal is to capture a substantial part of the net product margin realized by our commercial partners. Hyloris aims to achieve this by partnering these assets close to regulatory submission, except in countries where additional local clinical trials are required. In general, we will prioritize in-market product sales or profit-based participation over (upfront) milestone payments. We aim to increase our product portfolio to 30 assets by 2025, with a focus on accelerating pipeline growth in the near future. HY-091, a novel topical treatment candidate for Vulvar Lichen Sclerosus (VLS) was announced in January 2024. VLS is a chronic inflammatory condition affecting an estimated 3% of women, causing severe pain, itching, and discomfort, significantly impacting their quality of life. HY-091 is being developed as a convenient and user-friendly treatment specifically designed to target these VLS symptoms. Hyloris has partnered with AFT for co-development, registration, and worldwide commercialization. HY-090, a promising new treatment candidate for Burning Mouth Syndrome (BMS) was announced in December 2023. BMS is a chronic condition affecting millions, primarily postmenopausal women, causing a burning, tingling, or scalding sensation in the mouth for months at a time. While the mouth appears healthy, sufferers may also experience dry mouth or taste alterations, the exact cause of BMS remains unknown. Studies suggest that 0.7% to 5% of individuals in the U.S. might be affected6. Hyloris has partnered with AFT to co-develop and commercialize the product worldwide. HY-088 was announced in January 2023. This novel, proprietary oral formulation will be administered to patients with hypophosphatemia – a condition where the blood level of phosphorus is lower than 2.5mg/dL. Patients can develop hypophosphatemia from either a genetic abnormality (such as Cushing Syndrome or osteomalacia) or an acquired condition (like long-term use of diuretics or phosphate binders). It is estimated hypophosphatemia affects around 5% of hospitalized patients, and a subpopulation needs direct treatment during and/or after their hospital stay. Treatment protocols for patients deficient in phosphate are well-established and have proven useful in other situations of bone mineral imbalance. Oral administration is the preferred way of treating hypophosphatemia, although in most countries no approved drugs exist. Currently, physicians mostly rely on compounded drugs which have, by definition, not been submitted for regulatory scrutiny regarding safety, efficacy, and quality. R&D Update Throughout 2023, Hyloris achieved significant advancements across the entire R&D portfolio, propelling the 18 product candidates and 3 high-barrier generics closer to commercialization. Key milestones were met for multiple programs, and discussions with regulatory agencies and partners are underway to solidify development plans. As a result, Hyloris anticipates submitting multiple INDs (Investigational New Drug applications) and NDAs (New Drug Applications) throughout 2024 and early 2025. Enhanced Capabilities Drive Efficiency Further bolstering our R&D efforts, Hyloris officially opened its new and improved R&D lab at the Montlegia Science Park in June 2023. This on-site facility allows Hyloris to perform drug formulation and analytical activities in-house, streamlining processes and optimizing resource allocation for the expanding pipeline. Cardiovascular Portfolio Hyloris is actively engaged in advancing a comprehensive portfolio dedicated to addressing a wide range of conditions within the largest global treatment category – cardiovascular care. These products are currently progressing through or towards clinical trials, with the aim of significantly enhancing the quality of life for patients. Main highlights for 2023 and selected expected milestones for 2024 include: Aspirin IV: Registration batches have been manufactured and the stability study is ongoing. An NDA submission is planned for the U.S. as soon as all necessary data has been collected. Aspirin IV is an intravenous (IV) formulation of acetylsalicylic acid (ASA) to be used in an emergency setting. Aspirin is not available in the U.S. as an IV product. Currently, most patients suspected of having an emergency cardiovascular event (such as a myocardial infarction or stroke) are immediately given oral aspirin to decrease their risk of morbidity and mortality. Milrinone: The optimization of the extended-release formulation for alcohol resistance marked a significant development milestone. Preparations for a pilot pharmacokinetic (PK) study are in progress. Oral milrinone is being developed as a novel, extended-release formulation offering convenient oral dosing for a selected population of end-stage heart failure (HF) patients who have Left Ventricular Assist Devices (LVADs). HY-074: All non-clinical studies were completed in 2023. A patent application was filed through the Patent Cooperation Treaty (PCT) which allows an applicant to seek patent protection in several different countries – including the U.S. Hyloris is targeting an IND submission for Q2 2024 for the PK bridging study expected to start at the end of 2024. HY-074 is an intravenous formulation of current standard of care treatment for acute coronary syndrome (ACS) to offer faster onset of action, more convenient administration, and dosage control. It is currently available in oral form, which should allow for an optimal switching strategy from the oral form to an IV in a hospital setting. Dofetilide IV: Registration batches have been manufactured and the stability study is ongoing. A CRO has been selected for the required clinical study. An NDA submission is planned for the U.S. as soon as all necessary data has been collected. A pivotal clinical study to support regulatory submission for Dofetilide IV is nearing completion, with results expected by Q3 2024. Additional U.S. patent applications have been filed to bolster the drug's intellectual property protection. Other Value-Added Programs Hyloris, in collaboration with its development partners, is achieving consistent progress on all stages of our value-added programs. Main highlights for 2023 and expected milestones for 2024 include: Tranexamic Acid Oral Mouth Rinse (previously HY-004): A Type A meeting with the FDA resulted in alignment on the phase 3 study protocol. The phase 3 trial began in November 2023, enrolling the first patient in early 2024. Completion of enrollment (Last Patient Last Visit - LPLV) is expected by year-end, with study results anticipated in the first half of 2025. This rinse targets patients on blood thinners (anticoagulant therapies) undergoing dental procedures with a high risk of excessive bleeding. Additionally, Hyloris intends to explore the effectiveness in a wider range of related oral surgery procedures, encompassing both patients with and without bleeding disorders who could benefit from a localized treatment to reduce blood clotting. Miconazole/Domiphen Bromide: Hyloris is co-developing Miconazole/Domiphen Bromide (MCZ/DB) with Purna Female Healthcare, a topical cream combining miconazole and domiphen bromide. This innovative treatment targets Recurrent Vulvovaginal Candidiasis (rVVC), a chronic and often debilitating vaginal yeast infection affecting nearly 1 in 10 women throughout their lives. The Phase 2 clinical trial, completed in late 2023 (Q4), showed promising results. The low-dose group exhibited evidence of delayed disease recurrence at day 29. These findings will be used to design the next clinical trial, scheduled to begin by year-end 2024. MCZ/DB presents a strong scientific and commercial potential for addressing rVVC. AlenuraTM: Hyloris is co-developing Alenura™ with Vaneltix. It is a first-in-class drug candidate designed to bring immediate pain relief to patients suffering from interstitial cystitis/bladder pain syndrome (IC/BPS). This chronic condition affects at least 6 million people in the U.S. alone. Alenura™ stands out for its innovative dual mode-of-action. It combines a new, alkalinized form of lidocaine for fast pain relief with heparin to potentially aid in the regeneration of the bladder lining. This unique approach holds promise for providing both immediate symptom relief and long-term benefits for IC/BPS patients. June 2023 marked a significant milestone with the enrollment of the first patient in the Phase 2 clinical trial of Alenura™. This pivotal study will compare the effectiveness of Alenura™ against its individual components (lidocaine and heparin) as well as a placebo. PTX-252: PTX-252 is a novel chelating agent in development for the treatment of Acute Myeloid Leukemia (AML). This product candidate incorporates a novel molecular entity that is a derivative of a known established molecule. This advancement was followed by positive news: Hyloris' co-development partner, Pleco, secured Orphan Drug Designation from the FDA for PTX-252 specifically for AML. PTX-252's potential lies in its ability to potentially improve the effectiveness of existing chemotherapy for AML patients. This is particularly significant as AML affects approximately 160,000 people globally. Previous research suggests a correlation between high levels of toxic metals and lower survival rates in AML patients. A Pre-Investigational New Drug (PIND) meeting with the FDA is planned. Valacyclovir: A successful study demonstrating bioequivalence was completed in 2023. An additional pivotal study can be expected to start and close in H1 of 2024. Registration batches have been manufactured to demonstrate pharmaceutical quality of the product and robustness of the manufacturing process. Hyloris is developing a liquid formulation of valacyclovir which is currently only available in oral solid form. Valayclovir is an antiviral drug commonly used to treat the Herpes Simplex Viruses (HSV) that cause cold sores, genital herpes, chicken pox, and shingles. Management & Board changes The total headcount of the Company grew to 42 people, with several key recruitments occurring over the summer. To enhance the development activities, only limited additional hiring is required. Both the C-level executives and all board members remained in their respective positions, providing continuity in the company's leadership. Business Outlook With 18 reformulated and repurposed molecules, and 3 high-barrier generics, several clinical trials are expected to start and/or finish within 2024. The Company is actively accelerating the growth of its product pipeline, aiming to reach 30 product candidates by 2025. The company is expecting several clinical and regulatory achievements in the next 15 months. Several clinical studies will be initiated or completed. The Company is anticipating multiple NDA submissions to the U.S. FDA and other regulatory agencies. Webcast Details The Company will host a webcast conducted in English to present its 2023 annual results and 2024 Business Outlook, followed by a live Q&A session. The webcast will start on March 14th 2024 at 2PM CET / 1PM GMT / 9AM EST. To join the webcast, please register at the following link: Hyloris: 2023 Full Year Results, Outlook for 2024, and Q&A For those unable to join via webcast, please find dial in information below: Phone Conference ID: 598 167 742# Belgium: +32 4 290 22 87France: +33 1 73 24 00 56Netherlands: +31 20 708 1382Switzerland: +41 43 434 66 31United Kingdom: +44 20 7660 8327United States: +1 347 378 4531Japan: +81 3 4540 5088 Financial Highlights 2023 Year ended 31 December (in € thousand)20232022 Restated*VarianceTotal Revenues and Other income4,4062,38685%Revenues2,8141,951*44%Other operating income1,5924357266%Operating expenses(20,642)(14,024)47%Cost of sales(93)(94)(1%)Research and development expenses(14,749)(10,272)44%General and administration expenses(5,653)(3,517)61%Share of result of equity-accounted investees, net of tax(147)(130)13%Other operating expenses-(12) Operating result (EBIT)(16,236)(11,638)*40%Net financial result474(127)-473%Income Taxes-(4) Profit/(Loss) for the period(15,762)(11,770)*34%Net operating cash flow(12,726)(12,499)82%Other investment-10,000 Cash and cash equivalents30,19633,457-10%Total cash and Other investment30,19643,457 *See Note: Restatement of the year 2022 and Press Release dated 14th of March 2024 related to restatement for additional information on HY-038 and HY-088. Total Revenue and Other Income In 2023, total revenue and other income increased to €4,406 thousand compared to €2,386 thousand in 2022, which is 85% higher compared to last year. The strong growth is mainly driven by increase of royalties of the 3 early-stage commercialized products, services provided to external partners and non-dilutive funding which we received from a US State Government and the Walloon region in Belgium. Results The Company realized a net loss of €15,762 thousand in 2023, compared to a net loss of €11,770 thousand last year. The net loss is mainly resulting from the increase in R&D expenditure and G&A expenses for supporting the development of the Company. R&D expenditure during 2023 amounted to €14,749 thousand, compared to €10,272 thousand in 2022. The increase was mainly driven by the progressive shift from early to late-stage development of several product candidates as well as the increased headcount of the research and development team leading to additional costs. General and administrative expenses increased to €5,653 thousand in 2023 versus €3,517 thousand in 2022, mainly driven by higher legal costs related to the AltaThera’s litigation compared to last year. The net financial income in 2023 was €474 thousand compared to a net financial loss of €127 thousand in 2022. The positive evolution of the financial result is mainly due to the impact of an active cash management strategy in a context of high short term interest rates both in EURO and USD. As a result, net losses in 2023 increased to €15,762 thousand versus €11,770 thousand in the same period of 2022. Balance Sheet The Company’s non-current assets mainly consist of (1) investments in joint ventures of € 3,801 thousand, (2) intangible assets of €3,828 thousand including capitalized development, purchased assets and in-licensing costs, versus €3,600 thousand in 2022, (3) Right of use assets related to the leasing of the office, lab and cars, (4) shares in Pleco of €1,000 thousand, (5) a prepayment of future royalties to a third party of $700 thousand and (6) a tax credit. Hyloris does not capitalize research and development expenses until the filing for a marketing authorization for the applicable product candidate. Research and development expenditures incurred during the period were accounted for as operating expenses. When an intangible asset is acquired and capitalized, the amortization begins when the asset is available for commercialization. The Company’s current assets mainly consist of €30,196 thousand in cash and cash equivalents on total assets of €47.61 million, and trade and other receivables of €4.1 million. The increase in Right-of-use assets and borrowings is due to the start of the lease for the new lab. The Company received an advance payment related to a government grant from the Walloon region. €43 thousand of this advance is a financial liability and €37 thousand is part of Trade and other liabilities. Cash Position and cash flow The Company maintains its strong cash position, with a current cash and cash equivalents totaled €30,196 thousand at the end of 2023, compared to €43,457 thousand at the end of 2022 (which includes a deposit for an amount of €10 million which has been reclassified to Other investment in 2022). Net cash outflow generated from operating activities was €12,726 thousand in 2023, compared to a net operating cash outflow of €12,499 thousand in 2022. The stable net operating cash outflow is attributed to an internal control system implemented to oversee expenditure and cash flow, which includes effective management of working capital. CONSOLIDATED STATEMENT OF FINANCIAL POSITION FOR THE YEAR ENDED DECEMBER 31 ASSETS (in thousands of euros) 31-Dec-23 31-Dec-22 Restated* Non-current assets12,33611,063 Intangible assets3,8283,607 Property, plant and equipment429176 Right-of-use assets1,724885 Equity accounted investments3,8013,948 Other investment, including derivatives1,0001,000 Trade and other receivables1.5541.447 Current assets35,27649,801 Trade and other receivables4,1004,127 Other investment, including derivatives49910,4699 Prepayments4811,748 Cash and cash equivalents30,19633,4579 TOTAL ASSETS47,61260,864 EQUITY AND LIABILITIES(in thousands of euros) 31-Dec-23 31-Dec-22 Restated* Equity 38.82254.045 Share capital140140 Share premium121,513121,513 Retained earnings, excluding profit (loss) for the reporting period(65,246)(53,476) Result of the period, profit (loss) for the reporting period(15,762)(11,770) Share based payment2.1611,621 Cost of Capital(4,460)(4,460) Other reserves476476 Non-current liabilities1.8531,047 Borrowings1,510747 Other financial liabilities344300 Current liabilities6,9375,772 Borrowings241138 Other financial liabilities3,2003,212 Trade and other liabilities3,4962,422 Current tax liabilities-- TOTAL EQUITY AND LIABILITIES47,61260,864 CONSOLIDATED STATEMENT OF PROFIT OR LOSS AND OTHER COMPREHENSIVE INCOME FOR THE YEAR ENDED DECEMBER 31 in € thousands20232022 restated*VarianceRevenue 2,8141,95147%Other operating income1,5924353252%Operating income4,4062,38685%Cost of sales(93)(94)(1%)Research and development expenses(14,749)(10,272)1044%Selling, general and administrative expenses(5,653)(3,517)61%Share of result of equity-accounted investees, net of tax(147)(130)13%Other operating expenses-(12) Operating expenses(20,642)(14,024)47%Operating profit/(loss) (EBIT)(16,236)(11,638)40%Financial income86746686%Financial expenses(393)(594)-34%Profit/(loss) before taxes(15,762)(11,766)34%Income taxes-(4) PROFIT/(LOSS) FOR THE PERIOD(15,762)(11,770)34% CONSOLIDATED STATEMENT OF CHANGES IN EQUITY FOR THE YEAR ENDED DECEMBER 31 2023 (in thousands of euros) Attributable to equity holders of the CompanyTotal EquityShare capital Share premium Other reservesRetained earnings Share-based payment reserveCost of CapitalOther reservesBalance at December 31, 2021129103,6932,391(3,827)476(54,805)48,056Private Placement Via an Accelerated Bookbuild Offering514,995 (634) 14,366Equity Transaction via Transaction Warrants 62,826(1,329) 1,3292,832Share-based payments 560 560Total comprehensive income (11,770)(11,770)Balance at December 31, 2022140121,5131,622(4,460)476(65,246)54,045Share-based payments 539 539Total comprehensive income (15,762)(15,762)Balance at December 31, 2023140121,5132,161(4,460)476(81,008)38,822 CONSOLIDATED STATEMENT OF CASH FLOWS FOR THE YEAR ENDED DECEMBER 31 2023 in € thousands20232022 Restated* CASH FLOW FROM OPERATING ACTIVITIES Net result(15,762)(11,770) Adjustments to reconcile net loss to net cash provided by operating activities: Depreciation, amortisation and impairments349196 Share-based payment expense539560 Derivatives financial instruments(52)52 Interest income on deposits and current accounts-164 Net finance result(474)- Change in fair value of financial assets311- Loss on derecognition of shareholders loans-486 Equity transaction costs-29 Share of profit of equity-accounted investees, net of tax147130 Losses on disposal of PPE-16 Other non-cash adjustments(17)16 Changes in working capital: Trade and other receivables(293)(921) Other investment, including derivatives(31)4 Prepayments1,268(650) Trade and Other liabilities1,236(468) Cash generated from operations(12,779)(12,157) Interest paid527 Income Taxes paid-(349) Net cash generated from operating activities(12,726)(12,499) CASH FLOW FROM INVESTING ACTIVITIES Interest received403 Purchases of property, plant and equipment(298)(101) Purchases of Intangible assets(425)(638) Acquisition of Other Investments(0)(500) Loans made to third parties- (655) Deposits10,000(10,000) Discontinued operations Net cash provided by/(used in) investing activities9,654(11,894) CASH FLOW FROM FINANCING ACTIVITIES Reimbursements of borrowings and other financial liabilities(12)(7,376) Proceeds from borrowings and other financial liabilities44- Reimbursements of lease liabilities(222)(79) Modifications/terminations Right of Use Assets2- Proceeds from Private Placement via Accelerated Book Building- 14,337 Proceeds from Execution Transactions Warrants-2,832 Interests paid-(1,877) Net cash provided by/(used in) financing activities(188)7,838 NET INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS(3,261)(16,555) CASH AND CASH EQUIVALENTS at beginning of year33,45750,012 CASH AND CASH EQUIVALENTS at end of year, calculated30,19633,457* RESTATEMENT OF THE YEAR 2022 and HALF-YEAR 2023 Accounting treatment of the transactions with Qliniq Hyloris initially recognized (a) €1 million in revenue in 2022 from the divestment of HY-038, and (b) € 1 million in R&D expenses and € 0,2 million in intangible assets in H1 2023 for the purchase of HY-088. A reassessment determined that both transactions qualify as a non-monetary exchange because negotiations and valuations occurred simultaneously. Due to the development stage of the products exchanged, the fair value of neither the asset received, nor the asset given up can be reliably determined. As a result of this reassessment, the restated financials for 2022 will reverse the €1 million revenue from the divestment of HY-038. This adjustment will also affect the half-year 2023 financial statements, resulting in a reversal of €1 million in R&D expenses for HY-088. These expenses are offset against the €1 million received by Hyloris for HY-038. (See Press Release dated 14th of March 2024 on the restatement for more information) The following tables summarize the impact of the restatement on the consolidated financial statements. Consolidated statement of financial position Per 31 December 2022(in € thousands) Impact of correction of errorAs previously reportedAdjustmentAs restatedCurrent assets50.801-1.00049.801Trade and other receivables5.127-1.0004.127Total assets61.864-1.00060.864 Equity55.045-1.00054.045Result of the period(10.770)-1.000(11.770)Total equity and liabilities61.864-1.00060.864 Consolidated statement of profit or loss and other comprehensive income For the year ended 31 December 2022(in € thousands) Impact of correction of errorAs previously reportedAdjustmentAs restatedRevenues2.951-1.0001.951Gross profit2.857-1.0001.857Operating profit/(loss) (EBIT)(10.638)-1.000(11.638)Profit (loss) before taxes(10.766)-1.000(11.766)PROFIT (LOSS) FOR THE PERIOD(10.770)-1.000(11.770)TOTAL COMPREHENSIVE INCOME FOR THE PERIOD(10.770)-1.000(11.770)For the year ended 31 December 2022(in €) Impact of correction of errorAs previously reportedAdjustmentAs restatedBasic/diluted earnings/(loss) per share(0.380)(0.035)(0.435) Consolidated statement of cash flows Even though there was an actual cash inflow of EUR 1 million from the out-licensing of HY-038 and a cash outflow of EUR 1.2 million resulting from the in-licensing of HY-088, the transactions are presented in the consolidated statement of cash flows for the year ended per December 31, 2023 (i.e., EUR 200k prepaid expenses), as this most faithfully presents the substance of the transactions. There is no impact on the consolidated statement of cash flows for the year ended per December 31, 2022, as no cash inflow occurred yet. Audit Report The statutory auditor, KPMG Bedrijfsrevisoren - Réviseurs d’Entreprises, represented by Olivier Declercq, has informed us that the audit procedures were not yet completed. ONGOING LEGAL PROCEEDINGS In August 2022, AltaThera Pharmaceuticals LLC filed a complaint before the District Court for the Northern District of Illinois against Academic Pharmaceuticals Inc, Dr. Somberg and Hyloris Pharmaceuticals, for (a.o.) alleged misappropriation of AltaThera’s trade secrets and confidential information, improper inventorship, and breach of contract, which seeks (punitive) damages and termination of the agreement whereby Hyloris licenses Sotalol IV to AltaThera (the “Litigation”). Hyloris moved to dismiss the complaint for improper service of process and lack of jurisdiction. Further, in November 2022, Hyloris initiated an arbitration against AltaThera for breach of the same licensing agreement between Hyloris and AltaThera in relation to Sotalol IV, including the failure of AltaThera to use commercially reasonable efforts in selling Sotalol IV as required under the licensing agreement, which seeks damages and termination of the licensing agreement (the “Arbitration”). AltaThera responded and counter-demanded, reasserting its claims from the Litigation. At the end of August 2023, all parties agreed to stipulate to the dismissal of the Litigation and to consolidate the Litigation and the Arbitration before the American Arbitration Association (“AAA”) in New York. Hyloris contests the claims asserted by AltaThera and, based upon Hyloris’ assessment of the documents and expert reports put forward to date by AltaThera to support its claims, Hyloris is of the view that there is no convincing evidence supporting AltaThera’s claims for liability or damages. On the other hand, Hyloris believes strongly in the merits of its claims against AltaThera, and that its position is well supported by its expert reports and other documents and evidence submitted to the arbitration panel. Arbitration hearings are scheduled in April 2024 with a final decision expected by the end of H1 2024. Hyloris remains fully confident about the outcome of this litigation in its favor. Hyloris however cannot guarantee that the outcome of the litigation, even if in its favor, may not have a negative impact on future sales of Sotalol IV. About Hyloris Pharmaceuticals SA Hyloris is a specialty biopharma company focused on innovating, reinventing, and optimizing existing medications to address important healthcare needs and deliver relevant improvements for patients, healthcare professionals and payors. The Company’s development strategy primarily focuses on leveraging established regulatory pathways, such as the FDA’s 505(b)2 pathway in the U.S or equivalent regulatory frameworks in other regions which are specifically designed for pharmaceuticals for which safety and efficacy of the molecule have already been established. This approach can reduce the clinical burden required for market entry, and significantly shorten the development timelines, leading to reduced costs and risks. Hyloris has built a broad, patented portfolio of 18 reformulated and repurposed value-added medicines that have the potential to offer significant advantages over existing alternatives. Two products are currently in early phases of commercialization in collaboration with commercial partners: Sotalol IV for the treatment of atrial fibrillation, and Maxigesic® IV, a non-opioid post-operative pain treatment. In addition to its core strategic focus, the Company has 1 approved high barrier generic product launched in the U.S. and 2 high barrier generic products in development. Hyloris is based in Liège, Belgium. For more information, visit www.hyloris.com and follow-us on LinkedIn. For more information, contact Hyloris Pharmaceuticals:Stijn Van Rompay, CEOstijn.vanrompay@hyloris.com+32 (0)4 346 02 07Jean-Luc Vandebroek, CFOjean-luc.vandebroek@hyloris.com+32 (0)478 27 68 42Jessica McHarguejessica.mchargue@hyloris.com+1 919 451 4740 Disclaimer and forward-looking statements Hyloris means “high yield, lower risk”, which relates to the 505(b)(2) regulatory pathway for product approval on which the Company focuses, but in no way relates or applies to an investment in the Shares. Certain statements in this press release are “forward-looking statements.” These forward-looking statements can be identified using forward-looking terminology, including the words "believes", "estimates," "anticipates", "expects", "intends", "may", "will", "plans", "continue", "ongoing", "potential", "predict", "project", "target", "seek" or "should", and include statements the Company makes concerning the intended results of its strategy. These statements relate to future events or the Company’s future financial performance and involve known and unknown risks, uncertainties, and other factors, many of which are beyond the Company’s control, that may cause the actual results, levels of activity, performance or achievements of the Company or its industry to be materially different from those expressed or implied by any forward-looking statements. The Company undertakes no obligation to publicly update or revise forward-looking statements, except as may be required by law. 1 https://www.aafp.org/pubs/afp/issues/2010/1115/p1209.html2 IQVIA3 https://caddac.ca/about-adhd/4 https://journals.sagepub.com/doi/10.1177/10600280135106995 Not adjusted for inflation6 Based on combination of different sources: population-based study, clinical based study and key opinion leaders' estimation7 Reclassification of the withholding tax on R&D salaries. (payroll tax rebates)8 Reclassification of the loan to third-party from Operating to Investing activities in the Cash flow statement9 Reclassification of deposit from Cash and cash equivalents to Other investment including derivatives for an amount of €10 million in 202210 Reclassification of the withholding tax on R&D salaries. (payroll tax rebates) for an amount of €120k Attachment 20240314 Full Year Results 2023 ENG

– 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.