Burosumab-TWZA

First quarter total revenue of $109 million, Crysvita® revenue of $83 million and Dojolvi® revenue of $16 million Reaffirmed 2024 expected total revenue guidance between $500 million to $530 million, Crysvita revenue of $375 million to $400 million, and Dojolvi revenue of $75 million to $80 million Presented positive interim Phase 1/2 data from GTX-102 Angelman syndrome study demonstrating that Expansion Cohorts showed rapid, clinically meaningful improvement across multiple domains consistent with or exceeding Dose-escalation Cohort data at Day 170 NOVATO, Calif., May 02, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, today reported its financial results for the quarter ended March 31, 2024 and reaffirmed its financial guidance for 2024. “In the first quarter we continued to see rapid revenue growth in the international markets with steady progress globally across our four commercial products. We also just completed enrollment of our Phase 3 program in osteogenesis imperfecta supported by strong enthusiasm from treating physicians and the patient community,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “Last month we shared new data from the GTX-102 program for Angelman syndrome and have received an overwhelming response of excitement and support from the clinical experts and advocates in the Angelman community. We are on track to hold regulatory discussions in mid-2024 with the goal of initiating a Phase 3 trial before the end of the year.” First Quarter 2024 Selected Financial Data Tables and Financial Results Revenues (dollars in thousands), (unaudited) Three Months Ended March 31, 2024 2023Crysvita Product sales$36,241 $21,234Revenue in Profit-Share Territory 40,402 49,906Royalty revenue in European Territory 5,942 4,882Total Crysvita Revenue 82,585 76,022Dojolvi 16,362 14,303Mepsevii 6,611 8,480Evkeeza 3,275 212Daiichi Sankyo — 1,479Total revenues$108,833 $100,496 Total RevenuesUltragenyx reported $109 million in total revenue for the first quarter of 2024, which represents 8% growth compared to the same period in 2023. First quarter 2024 Crysvita revenue was $83 million, which represents 9% growth compared to the same period in 2023. This includes product sales of $36 million from Latin America and Turkey, which represents 71% growth compared to the same period in 2023. In April 2023, commercialization responsibilities in the Profit-share Territory transitioned to Kyowa Kirin Co and commensurately, revenue in that region transitioned from a profit-share to a royalty ranging from the mid-20’s to 30% calculated based on annual revenue tiers. Dojolvi revenue in the first quarter 2024 was $16 million, which represents 14% growth compared to the same period in 2023. Selected Financial Data (dollars in thousands, except per share amounts), (unaudited) Three Months Ended March 31, 2024 2023 Total revenues$108,833 $100,496 Operating expenses: Cost of sales 17,533 12,257 Research and development 178,487 165,698 Selling, general and administrative 78,160 76,646 Total operating expenses 274,180 254,601 Net loss$(170,684) $(163,972)Net loss per share, basic and diluted$(2.03) $(2.33) Operating Expenses Total operating expenses for the first quarter of 2024 were $274 million, including non-cash stock-based compensation of $37 million. In 2024, annual operating expenses are expected to be stable or to decrease as the company continues to manage its costs and focus its investment on advancing multiple Phase 3 programs and executing on commercial product launches. Net Loss For the first quarter of 2024, Ultragenyx reported net loss of $171 million, or $2.03 per share basic and diluted, compared with a net loss for the first quarter of 2023 of $164 million, or $2.33 per share, basic and diluted. Net Cash Used in Operations and Cash BalanceNet cash used in operations for the quarter ended March 31, 2024 was $191 million. Cash, cash equivalents, and marketable debt securities were $569 million as of March 31, 2024. 2024 Financial Guidance For the full year 2024, the company reaffirms: Total revenue in the range of $500 million to $530 millionCrysvita revenue in the range of $375 million to $400 million. This includes all regions where Ultragenyx will recognize revenue: product sales in Latin America and Turkey, royalties in Europe, which have been ongoing, and royalties in North America, which began in April 2023.Dojolvi revenue in the range of $75 million to $80 millionNet Cash Used in Operations to be less than $400 million Recent Updates and Clinical Milestones UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Enrollment complete for Phase 3 Orbit and Cosmic studies; expect additional Phase 2 data update in second half of 2024 The Phase 3 portion of the Orbit study has completed enrollment with 158 patients. Orbit is a randomized placebo-controlled study evaluating the effect of setrusumab compared to placebo on the rate of annualized clinical fractures in patients aged 5 to <25 years. Additional longer-term safety and efficacy data from the Phase 2 portion of the Orbit study are expected in the second half of 2024. The Phase 3 Cosmic study has also completed enrollment with 66 patients randomized or in screening. Cosmic is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients aged 2 to <7 years. GTX-102 antisense oligonucleotide for Angelman syndrome: Positive interim Phase 1/2 data shared in April; expect End of Phase 2 meeting with Food and Drug Administration (FDA) in mid-2024New interim data from the Phase 1/2 study were presented at a company presentation and at the 76th Annual American Academy of Neurology Meeting. Patients in Expansion Cohorts A & B treated with a set dose and regimen of GTX-102 showed rapid and clinically meaningful improvement across multiple domains consistent with or exceeding Dose Escalation Cohorts 4-7 data at Day 170. Treatment of the Dose Escalation Cohorts 4-7 showed long-term increasing and sustained clinical benefit far exceeding Natural History data at Day 758. As previously reported and as of the data cut-off on April 5, 2024, there were two patients who had mild or moderate lower extremity weakness across 53 patients who completed the loading phase in the Expansion Cohorts A-E. Both were in Cohorts A & B and none reported in Cohorts C–E. The lower extremity weakness resolved rapidly without sequelae and patients remain in the study without ongoing safety concerns and are expected to continue dosing. The FDA and other regulatory agencies were notified and raised no issues nor required additional actions. There were no other unexpected serious adverse events. We expect to share additional long-term safety and efficacy data from the Phase 1/2 study and plan to continue to provide routine safety updates with efficacy updates. We currently expect to have an End of Phase 2 meeting with the FDA in mid-2024 and meetings with other regulatory agencies in the second half of 2024. UX701 AAV gene therapy for Wilson disease: Last patient in Cohort 3 dosed; expect interim Stage 1 data in the second half of 2024All patients in the three dose-escalation cohorts of Stage 1 have been dosed. During Stage 1, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2, the pivotal, randomized, placebo-controlled stage of the study. Data from Stage 1 are expected in the second half of 2024, which will be followed by dose selection and initiation of Stage 2. UX111 AAV gene therapy for Sanfilippo syndrome (MPS IIIA): Discussions ongoing with FDA, seeking accelerated approval pathIn February 2024, Ultragenyx participated in a workshop hosted by the Reagan-Udall Foundation for the FDA that brought together FDA representatives, patient advocates, scientists, and industry leaders to discuss the use of CSF heparan sulfate as a relevant biomarker to enable accelerated approval in neuronopathic mucopolysaccharidoses (MPS). Discussions are ongoing with the FDA in seeking an accelerated review path for UX111. DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study complete; expect Phase 3 data readout in the second quarter of 2024In May 2023, Ultragenyx announced the last patient was dosed in the Phase 3 study. The 48-week study enrolled 49 patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 safety and efficacy data are expected in the second quarter of 2024. DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients; expect enrollment to be completed in the second half of 2024Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the second half of 2024. Conference Call and Webcast Information Ultragenyx will host a conference call today, Thursday, May 2, 2024, at 2 p.m. PT/5 p.m. ET to discuss the first quarter 2024 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations. To participate in the live call, please register by clicking on the following link (https://register.vevent.com/register/BI7c62f78f6df84941acb020e8220f4d81) and you will be provided with dial-in details. The replay of the call will be available for one year. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, for which there are typically no approved therapies treating the underlying disease. The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency. For more information on Ultragenyx, please visit the company's website at: www.ultragenyx.com. Forward-Looking Statements and Use of Digital Media Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx's expectations and projections regarding its future operating results and financial performance, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, risks related to serious or undesirable side effects of our product candidates, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, our limited experience in generating revenue from product sales, risks related to product liability lawsuits, our dependence on Kyowa Kirin for the commercial supply of Crysvita, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, the transition back to Kyowa Kirin of our exclusive rights to promote Crysvita in the United States and Canada and unexpected costs, delays, difficulties or adverse impact to revenue related to such transition, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the company’s future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of Ultragenyx’s products and drug candidates. Ultragenyx undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of Ultragenyx in general, see Ultragenyx's Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 21, 2024, and its subsequent periodic reports filed with the SEC. In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/mycompany/). Contacts Ultragenyx Pharmaceutical Inc.InvestorsJoshua Higair@ultragenyx.com Ultragenyx Pharmaceutical Inc.Selected Statement of Operations Financial Data(in thousands, except share and per share amounts)(unaudited) Three Months Ended March 31, 2024 2023 Statement of Operations Data: Revenues: Product sales$62,489 $44,229 Royalty revenue 46,344 4,882 Collaboration and license — 51,385 Total revenues 108,833 100,496 Operating expenses: Cost of sales 17,533 12,257 Research and development 178,487 165,698 Selling, general and administrative 78,160 76,646 Total operating expenses 274,180 254,601 Loss from operations (165,347) (154,105)Change in fair value of equity investments 3,746 (334)Non-cash interest expense on liabilities for sales of future royalties (15,847) (15,636)Other income, net 7,219 6,598 Loss before income taxes (170,229) (163,477)Provision for income taxes (455) (495)Net loss$(170,684) $(163,972)Net loss per share, basic and diluted$(2.03) $(2.33)Shares used in computing net loss per share, basic and diluted 84,286,292 70,368,478 Ultragenyx Pharmaceutical Inc.Selected Activity included in Operating Expenses(in thousands)(unaudited) Three Months Ended March 31, 2024 2023 Non-cash stock-based compensation$36,934 $31,939 Ultragenyx Pharmaceutical Inc.Selected Balance Sheet Financial Data(in thousands)(unaudited) March 31, December 31, 2024 2023Balance Sheet Data: Cash, cash equivalents, and marketable debt securities $568,661 $777,110Working capital 350,392 451,747Total assets 1,307,080 1,491,013Total stockholders' equity 140,264 275,414

Favorable safety and immunogenicity pro ABCC6 Deficiency, with clinical improvements in vascular pathology, visual function and patient reported outcomes (PROs) Natural history study highlights stroke as common feature among patients with early-onset ABCC6 Deficiency Favorable safety, immunogenicity and clinical outcome data were maintained through 48 weeks in Cohorts 1-3 in ENPP1 Deficiency; Data from Cohort 4 support once weekly dosing in ongoing and future clinical trials Company to host conference call and webcast today at 8:00 a.m. ET BOSTON, April 08, 2024 (GLOBE NEWSWIRE) -- Inozyme Pharma, Inc. (Nasdaq: INZY) (“the Company” or “Inozyme”), a clinical-stage rare disease biopharmaceutical company developing novel therapeutics for the treatment of pathologic mineralization and intimal proliferation, today announced positive topline safety, pharmacokinetic (PK), pharmacodynamic (PD) and exploratory efficacy data from the Company’s ongoing Phase 1/2 clinical trials of INZ-701 in adults with ABCC6 Deficiency (PXE, pseudoxanthoma elasticum) and ENPP1 Deficiency. “We are excited by the excellent safety and preliminary efficacy pro INZ-701 in adults with ABCC6 Deficiency,” said Douglas A. Treco, Ph.D., CEO of Inozyme Pharma. “Our investigations into the natural history of this disease have identified a substantial and previously overlooked pediatric population with a high risk of stroke. We believe these patients represent a critical unmet need in this genetic disease and that changes observed in adults treated with INZ-701 will translate to clinical benefits in a future trial in children.” “The high risk of ischemic stroke in pediatric patients with ABCC6 Deficiency and its devastating consequences represents a serious unmet need in this population,” commented Professor Zulf Mughal, M.D., Consultant in Paediatric Bone Disorders at Al Jalila Children's Specialty Hospital, Dubai, UAE. “I am very encouraged to see that INZ-701 may improve vascular pathology and believe that this effect may translate to clinical benefits in patients of all ages.” ABCC6 Deficiency Data The ongoing Phase 1/2 trial in ABCC6 Deficiency enrolled 10 adults with heavy disease burden, as evidenced by serious cardiovascular disease and retinal disease. The patients were assigned to three dose cohorts of INZ-701: 0.2 mg/kg (n=3), 0.6 mg/kg (n=3), and 1.8 mg/kg (n=4). For trial design details, please see the section entitled “INZ-701 in ABCC6 Deficiency Phase 1/2 Clinical Trial Design” below. Exploratory Clinical and Efficacy Data Exploratory markers of clinical benefit were collected throughout the study to provide evidence of the potential for disease modification with ongoing INZ-701 treatment. Notable changes were observed, including: Carotid intima-media thickness (cIMT) stabilized and decreased cIMT, a predictive marker for cardiovascular disease and stroke, increases at a faster rate in people with PXE than in the general population. Reduction or stabilization of cIMT was observed across all dose cohorts (seven of eight evaluable patients), indicating a potential beneficial effect of INZ-701 on vascular pathology. Choroidal thickness increased The choroid is the vascular layer between the sclera and retina. Choroidal thinning is associated with degenerative retinal changes in people with PXE and progresses with age. Increased choroidal thickness was observed across all dose cohorts (seven of eight evaluable patients), which indicates a potential beneficial effect of INZ-701 on retinal disease. Global Visual Function Questionnaire (VFQ-25) scores indicated preservation and improvement of visual function over 48 weeks Four of six evaluable patients with VFQ-25 scores below normal at baseline improved over 48 weeks. Improvement in visual function was greater in older patients. A correlation between improvements in VFQ-25 and increases in choroidal thickness was preserved after 48 weeks. Global Impression of Change Scale (GIC): Concordant improvement in GIC scores reported by patients (P-GIC) and clinicians (C-GIC)observed in all three dose cohorts All evaluable patients (nine of nine) showed improvement from baseline on C-GIC, and seven of nine evaluable patients showed improvement from baseline on P-GIC. PD and PK Data Rapid increase in plasma pyrophosphate (PPi) levels observed at 1.8 mg/kg dose level and was sustained to levels comparable to those observed in Inozyme’s study of healthy subjects (n=10). Safety Data INZ-701 was generally well tolerated and exhibited a favorable safety profile, with no serious or severe adverse events (AEs). All AEs were mild to moderate in severity. For previously reported data on AEs, please read here. Eight patients remain in the trial and seven continue on home self-administration of INZ-701 treatment. Time on study ranged from 45 to over 631 days. Total time on treatment across all cohorts corresponds to approximately 12+ patient-years. Anti-Drug Antibody (ADA) Data INZ-701 exhibited a favorable immunogenicity pro low titers of non-neutralizing ADAs observed in eight of 10 patients. The ADA levels were transient in three of eight patients. Natural History Studies The Company conducted a comprehensive retrospective, natural history study, and a prospective, longitudinal, observational study to characterize the natural progression of early-onset ABCC6 Deficiency and inform future clinical trial design. Findings indicate a substantial disease burden among pediatric patients with ABCC6 Deficiency, manifesting in a high incidence of major clinical events, notably stroke, severe neurological disease, and severe cardiovascular disease, occurring early in life. Seven out of 12 patients across the natural history studies either experienced stroke or are at risk, with strokes resulting in severe outcomes such as seizure disorders, paresis, and significant disability. Furthermore, 10 out of 12 patients were diagnosed with GACI Type 2, underscoring the considerable morbidity risk among pediatric survivors beyond the critical infancy period. Development Plans for INZ-701 in Pediatric ABCC6 Deficiency Given the high risk of cerebrovascular disease in the pediatric population, the Company believes that endpoints predictive of ischemic stroke (for example, progression of cerebral vasculopathy) may provide a suitable basis for Accelerated Approval in the US and Conditional Marketing Authorisation in the EU of INZ-701 in children with ABCC6 Deficiency. The Company plans to work expeditiously with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) on a pivotal trial design. Subject to regulatory review and sufficient funding, the Company expects to initiate a pivotal trial in pediatric patients with ABCC6 Deficiency in Q1 2025. ENPP1 Deficiency Data Thirteen adults with ENPP1 Deficiency were enrolled in the ongoing Phase 1/2 trial across three twice weekly dose cohorts (0.2 mg/kg [n=3], 0.6 mg/kg [n=3], and 1.8 mg/kg [n=3]) and one once-weekly dose cohort (1.2 mg/kg [n=4]) of INZ-701. For trial design details, please see the section entitled “INZ-701 in ENPP1 Deficiency Phase 1/2 Clinical Trial Design” below. Exploratory Biomarker Data Exploratory biomarker data were collected throughout the study to provide evidence of the potential for disease modification with ongoing treatment with INZ-701. For previously reported exploratory biomarker data, please read here. Notable changes in key biomarkers were observed and support Inozyme’s clinical hypothesis, including: Significant reduction of fibroblast growth factor-23 (FGF-23) in the 1.8 mg/kg dose cohort (Cohort 3) through week 48. Most patients with ENPP1 Deficiency have elevated levels of FGF-23, which leads to increased phosphate wasting and hypophosphatemia, a key driver of osteomalacia and rickets. Increase in bone specific alkaline phosphatase (BSAP) levels and decrease in c-telopeptide (CTX) in the 1.8 mg/kg dose cohort (Cohort 3) through week 48, which indicate the restoration of proper bone mineralization. Exploratory Efficacy Data Outcome measures were collected to assess the potential clinical benefit of ongoing treatment with INZ-701 and to inform the design and patient selection of future trials in adolescents and adults. For previously reported exploratory efficacy data, please read here. Notable changes in PROs and functional outcomes were observed in all three twice-weekly dose cohorts, including: Favorable responses on the Patient-Reported Outcome Measurement Information Scales (PROMIS) of Pain Intensity, Fatigue and Pain Interference and P-GIC were maintained. PD and PK Data Data from the once-weekly dose cohort showed increased PPi levels comparable to those observed in Inozyme’s study of healthy subjects (n=10). Consistent exposure was observed with 1.2 mg/kg once weekly dosing when compared to 0.6 mg/kg twice weekly dosing. Long-term data showed a sustained increased PPi levels in the once-weekly dose cohort. Safety Data INZ-701 was generally well-tolerated and exhibited a favorable safety profile, with no serious or severe AEs attributed to INZ-701 and no AEs leading to study withdrawal. For previously reported data on adverse events, please read here. Eleven patients remain in the trial and 10 continue on home self-administration of INZ-701 treatment. Time on study ranged from 22 to over 742 days. Total time on treatment across all dose cohorts corresponds to approximately 12+ patient-years. ADA Data INZ-701 exhibited a favorable immunogenicity pro low titers of non-neutralizing ADAs observed in 11/14 patients. The ADA levels were transient in three of 11 patients. Conference Call and Webcast Details The live webcast and replay will be accessible through the Investor Relations section of Inozyme’s website under Events. Alternatively, the conference call may be accessed by dialing: Domestic Dial-in Number: 1-833-816-1110 International Dial-in Number: 1-412-317-0686 Participants should ask to join the Inozyme Pharma call. For those unable to participate live, a replay will be available in the Investor Relations section of Inozyme’s website for a limited time following the event. About ABCC6 Deficiency ABCC6 Deficiency is a progressively debilitating condition of the vasculature and soft tissue that is estimated to affect approximately 1 in 25,000 to 1 in 50,000 individuals worldwide. Infants with ABCC6 Deficiency are diagnosed with generalized arterial calcification of infancy (GACI Type 2), a condition that resembles GACI Type 1, the infant form of ENPP1 Deficiency. Pediatric patients who survive the first year of life may develop neurological disease, including stroke, and cardiovascular disease secondary to ongoing vascular calcification and stenosis. In older individuals, ABCC6 Deficiency presents as pseudoxanthoma elasticum (PXE), which is characterized by pathologic mineralization in blood vessels and soft tissues clinically affecting the skin, eyes, and vascular system. There are no approved therapies for ABCC6 Deficiency. INZ-701 in ABCC6 Deficiency Phase 1/2 Clinical Trial Design The ongoing Phase 1/2 open-label clinical trial enrolled 10 adult patients with ABCC6 Deficiency at sites in the United States and Europe. The trial is primarily assessing the safety and tolerability of INZ-701 in adult patients with ABCC6 Deficiency, as well as characterizing the pharmacokinetic (PK) and pharmacodynamic (PD) pro INZ-701, including the evaluation of levels of plasma pyrophosphate (PPi) and other biomarkers. In the Phase 1 dose-escalation portion of the trial, Inozyme assessed INZ-701 for 32 days at doses of 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg administered via subcutaneous injection twice weekly, with three patients per dose cohort. Doses were selected based on preclinical studies and PK/PD modeling. The Phase 1 dose-escalation portion of the trial sought to identify a safe, tolerable dose that increases PPi levels for further development. The open-label Phase 2 extension portion of the trial is assessing long-term safety, PK, and PD of continued treatment with INZ-701 for at least 48 weeks, where patients may self-administer INZ-701. Exploratory endpoints include evaluations of vascular, ophthalmologic, physical function, and patient-reported outcomes. About ENPP1 Deficiency ENPP1 Deficiency is a progressively debilitating condition of the vasculature, soft tissue, and skeleton with a prevalence of approximately 1 in 64,000 pregnancies worldwide. Although ENPP1 Deficiency was initially described in patients with biallelic ENPP1 Deficiency (homozygous or compound heterozygous mutations), many patients with monoallelic ENPP1 Deficiency (heterozygous mutations) have clinical symptoms, potentially increasing the worldwide prevalence. Individuals who present in utero or in infancy are typically diagnosed with generalized arterial calcification of infancy (GACI Type 1) and approximately 50% of infants die within six months of birth. Children with ENPP1 Deficiency typically develop rickets, a condition diagnosed as autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults can develop osteomalacia (softened bones). ARHR2 and osteomalacia lead to pain and mobility issues. Patients can also exhibit signs and symptoms of hearing loss, arterial and joint calcification, and cardiovascular complications. There are no approved therapies for ENPP1 Deficiency. INZ-701 in ENPP1 Deficiency Phase 1/2 Clinical Trial Design The ongoing Phase 1/2 open-label clinical trial initially enrolled nine adult patients with ENPP1 Deficiency at sites in North America and Europe. The trial is primarily assessing the safety and tolerability of INZ-701 in adult patients with ENPP1 Deficiency, as well as characterizing the pharmacokinetic (PK) and pharmacodynamic (PD) pro INZ-701, including evaluation of the PD marker, plasma pyrophosphate (PPi) and other biomarker levels. In the Phase 1 dose-escalation portion of the trial, Inozyme assessed INZ-701 for 32 days at doses of 0.2 mg/kg, 0.6 mg/kg, and 1.8 mg/kg administered via subcutaneous injection twice weekly, with three patients per dose cohort. Doses were selected based on preclinical studies and PK/PD modeling. The Phase 1 dose-escalation portion of the trial sought to identify a safe, tolerable dose that increases PPi levels and that can be used for further clinical development. Following completion of the Phase 1 portion of the first three cohorts, Inozyme dosed patients in a fourth cohort at 1.2 mg/kg to investigate the potential for once-weekly dosing of INZ-701. The open-label Phase 2 extension portion of the trial is assessing long-term safety, PK, and PD of continued treatment with INZ-701 for at least 48 weeks, where patients may self-administer INZ-701. Exploratory endpoints include evaluations of skeletal, vascular, physical function, and patient-reported outcomes. About 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 well tolerated, exhibited a favorable safety profile, and meaningfully increased PPi levels in multiple clinical trials. About Inozyme Pharma Inozyme Pharma, Inc. is a clinical-stage rare disease biopharmaceutical company developing novel therapeutics for the treatment of diseases impacting the vasculature, soft tissue, and skeleton. Inozyme is developing INZ-701, an enzyme replacement therapy, to address pathologic mineralization and intimal proliferation, which can drive morbidity and mortality in these severe diseases. INZ-701 is currently in clinical development for the treatment of ENPP1 Deficiency, ABCC6 Deficiency and calciphylaxis. For more information, please visit or follow Inozyme on LinkedIn, X (formerly Twitter), and Facebook. Cautionary Note Regarding Forward-Looking Statements Statements in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward- looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the timing and contents of our planned topline data update, the initiation, timing, and design of our planned clinical trials, our regulatory strategy, including our plan to seek accelerated approval in the U.S. and conditional approval in the E.U, and the potential benefits of INZ-701. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the Company's ability to conduct its ongoing clinical trials of INZ-701 for ENPP1 Deficiency, ABCC6 Deficiency and calciphylaxis; enroll patients in ongoing and planned trials; obtain and maintain necessary approvals from the FDA and other regulatory authorities; continue to advance its product candidates in preclinical studies and clinical trials; replicate in later clinical trials positive results found in preclinical studies and early-stage clinical trials of its product candidates; advance the development of its product candidates under the timelines it anticipates in planned and future clinical trials; obtain, maintain, and protect intellectual property rights related to its product candidates; manage expenses; comply with the covenants under its outstanding loan agreement; and raise the substantial additional capital needed to achieve its business objectives. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company's actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" section in the Company's most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors, in the Company's most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views as of the date hereof and should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so. Contacts Investors: Inozyme Pharma Stefan Riley, Senior Director of IR and Corporate Communications (857) 330-8871 stefan.riley@inozyme.com Media: SmithSolve Matt Pera (973) 886-9150 matt.pera@smithsolve.com