Good morning, thank you for joining us for the Inozyme February 2023 Virtual Investor and Analyst Event. Today's remarks will be followed by a question and answer session with the management team and key opinion leaders. Please dial in via telephone to participate. Before we begin our formal remarks, I would like to point you to our forward-looking statements disclaimer. I would now like to turn the event over to Axel Bolte, Co-founder, President, and Chief Executive Officer of Inozyme Pharma. Good morning, welcome to our First Investor and analyst event from our labs in Boston. Inozyme has made tremendous progress over the past year. We are developing a potential first-in-class therapy for ENPP1 deficiency and ABCC6 deficiency, two rare mineralization disorders where patients suffer severely with up to 50% mortality and have no approved therapeutic options. With INZ-701, we have a phase III-ready asset that has shown a favorable safety profile. As an enzyme replacement therapy, now with proof of concept data in patients in hand, we are optimistic that we can successfully complete clinical development and obtain regulatory approval. Lastly, we see an addressable market with blockbuster potential for ENPP1 deficiency alone based on our own pre-commercialization work. We already have identified more than 500 patients with ENPP1 deficiency, and the list keeps growing as we plan to move toward a phase III clinical trial that could support regulatory approval and a potential launch. Today, we are delighted to share top-line data from all those cohorts in our two ongoing phase I-II clinical trials in adult patients suffering from ENPP1 deficiency and ABCC6 deficiency, respectively. We are also excited to share the first glimpse of the clinical effects of INZ-701 in ENPP1 deficiency. Patients are in desperate need of a therapeutic option. The burden on them, their parents, and caregivers is enormous. Dr. Michael Levine will share a powerful first-hand account of what it means to diagnose and manage patients with ENPP1 deficiency. Our second indication, ABCC6 deficiency, is commonly known as pseudoxanthoma elasticum, or PXE, and causes progressively worsening morbidity. You will be hearing from Dr. Wilco Spiering about his experience with PXE patients. INZ-701, our lead drug candidate, is an incredible product opportunity. As an enzyme replacement therapy, INZ-701 builds upon the success of many other approved ERTs for severe disorders. The ability to normalize levels of pyrophosphate or PPI, a central metabolite controlling mineralization in mammals and a key pharmacodynamic marker, supports the biological activity of INZ-701. Our most recent data from all three dose cohorts in patients with ENPP1 and ABCC6 deficiency will be shared by our Chief Scientific and Medical Officers. We are delighted that the encouraging safety, predictable pharmacokinetic profile, and most importantly, the significant pharmacodynamic activity of INZ-701 continue to be borne out in the ongoing studies. Over the coming quarters, we plan to release additional exploratory clinical data from the phase II portion of these studies with the goal of selecting a dose for phase III. In consultation with global regulatory agencies, we are developing our phase III program and plan to initiate a phase III clinical trial of INZ-701 in ENPP1 deficiency in the third quarter of this year. The market opportunity for INZ-701 is significant. Dr. Mark Kiel, the Chief Scientific Officer at Genomenon, will be sharing a detailed genetic analysis of the pathogenic ENPP1 and ABCC6 mutations, leading to a more accurate assessment of the true market. Henric Bjarke, our Senior Advisor, while at Alexion, led the global launch for Strensiq, an analogous product. His excitement for the commercial potential of INZ-701 is rooted in a deep understanding of rare disease markets. We have built partnerships to engage the patient community, remove barriers to diagnosis, and drive a better understanding and awareness of these diseases in the medical community. Finally, our chief financial officer will provide you with the latest financial projections with key anticipated milestones for 2023. Importantly, we'll share our updated guidance regarding cash runway, which is anticipated to be into the fourth quarter of 2024. INZ-701 is a highly differentiated asset with broad intellectual property protection until at least 2036. We know of no approved therapies for the treatment of either ENPP1 or ABCC6 deficiency. Our goal is to bring this drug to patients as early as 2026. The patients are there. They need and deserve a therapy. Inozyme will provide it. Please now welcome Dr. Michael Levine to speak about ENPP1 deficiency, A Disease Overview. It is a pleasure to provide you with a top-level overview of the clinical features of ENPP1 deficiency. I'm Michael Levine, an endocrinologist at the Children's Hospital of Philadelphia and chair of the Clinical Advisory Board at Inozyme. My presentation today will focus on three topics: the unmet medical need for a safe and effective treatment for ENPP1 deficiency, the clinical recognition of ENPP1 deficiency as a lifelong condition that affects more than arteries, and the use of serum levels of pyrophosphate as both a biomarker for ENPP1 deficiency and a marker for treatment efficacy. There are several key takeaways from my presentation. ENPP1 deficiency is a lifelong disease. Children who survive GACI, generalized arterial calcification of infancy, will develop multiple chronic complications that affect multiple systems and which justify long-term treatment. The consequence of arterial calcification and intimal proliferation can lead to arterial occlusion and subsequently end-organ damage. Additionally, low pyrophosphate levels can lead to low phosphate levels via renal phosphate wasting, which impedes normal bone growth and maturity. Lastly, ENPP1 deficiency has been described as a heterogeneous disease presenting with a broad range of clinical outcomes, suggesting it may be difficult to identify patients. Of course, the most dramatic expression of ENPP1 deficiency is Generalized Arterial Calcification of Infancy, GACI. This condition is life-threatening and presents with heart failure, stroke, renal insufficiency, or hypertension within the first few days of life. In about 50% of cases, the diagnosis of GACI is suspected by a prenatal ultrasound that shows echo brightness within the heart or aorta. In some cases, a family history of GACI or unexplained neonatal death can heighten concern that a fetus or newborn has GACI. Overall mortality of GACI is estimated to be greater than 50%, which includes a very high number of miscarriage and stillborn deaths. About half of all affected babies will die before six months, which represents the so-called critical period shown here as the pink zone. Children who get through the critical period have a good likelihood of survival, but typically develop other later complications. Because GACI is characterized by a deficiency of pyrophosphate, early attempts at therapy focused on administration of pyrophosphate. Pyrophosphate is rapidly degraded or hydrolyzed, making it unsuitable as a therapeutic agent. By contrast, the bisphosphonates shown in the upper right panel are non-hydrolyzable analogs of pyrophosphate. The first generation bisphosphonate, etidronate, has been used most often as a treatment in GACI, given either orally or intravenously. However, as shown on the panel on the left, treatment with etidronate, EHDP, as well as other more potent bisphosphonates, has not led to a significant improvement in overall survival compared to no bisphosphonate, as shown by the black line. I would like to share a case that illustrates many of the features of ENPP1 deficiency. Patient A, denoted as the proband in this pedigree by the black arrow in the lower right corner, was diagnosed with likely GACI in utero after a second trimester fetal ultrasound revealed echo brightness in the heart. The diagnosis of GACI was supported by a striking family history, as shown here. An older sister had been born with extensive cardiac and arterial calcifications and had died at 38 days of life despite treatment with bisphosphonates, including pamidronate and etidronate. Genetic studies at that time confirmed that both parents were carriers of ENPP1 mutations. Remarkably, both the father and a heterozygous carrier cousin had married unrelated additional carriers, and both had children with GACI. The parents of our patient had lost their first baby at 49 days of age due to unexplained heart failure and had experienced seven miscarriages, which we believe were due to GACI-related intrauterine death. At birth, our patient had extensive calcification of the aortic root and the left main coronary artery, as well as calcifications and stenoses in the abdominal aorta and the iliac arteries. A CT angiogram later performed at four months of age showed extreme narrowing of the lower abdominal aorta and significant stenosis at the origin of the celiac trunk and superior mesenteric artery. These findings are consistent with the known arterial pathobiology of GACI. This slide shows a histological section from the aorta of a baby with GACI who unfortunately died from heart disease at 49 days of life. There are two main features that warrant our attention. First, there is calcification, as shown by these small black arrows along the internal elastic lamina of the aorta, as well as in the coronary arteries. Perhaps even more importantly, there is extensive proliferation of the intimal cells depicted by the white bar that leads to thickening of the lining of the blood vessel compared to a normal aorta with the intima shown by this white bar in the inset. The intimal proliferation leads to extreme narrowing of arteries and causes stenoses that markedly limit blood flow. Calcifications also occur beyond the arteries in patients with ENPP1 deficiency and can be present at birth in nearly 30% of patients with GACI. These panels are from other babies and not the particular case I'm presenting today, but serve to illustrate the process. The panel on the left is a 3D scan showing marked calcifications around the right shoulder that limited movement of the right arm, while the panel on the right shows an X-ray demonstrating extensive calcification of the elbow that limited use of that extremity. Calcifications can also occur in the earlobes as well as major organs such as the heart, liver, and kidneys. Back to our patient. We treated our patient with sodium thiosulfate IV five days per week for 12 months under a compassionate use protocol. Sodium thiosulfate has been shown in some studies to be able to remove arterial calcium deposits in patients with other conditions. We have treated several babies who have GACI with sodium thiosulfate, and at this time we are just not certain that it has any benefit. Repeat imaging at 15 months showed partial regression of coronary calcifications, but there was persistent narrowing of the lumens of the arteries that we had seen affected at birth. At 24 months of age, we noted impaired growth that we attributed to the development of hypophosphatemic rickets, which can be seen in this panel. This was represented as genu valgum or knock knees. There was also progressive hearing loss that by three years of age required the use of hearing aids. We had anticipated both hearing loss and rickets and had monitored the child closely for the development of these complications. A recent review of ENPP1 deficiency showed an average onset of hypophosphatemia in 16 affected patients by about age 1.6 years. Based on these patients, there is a 75% probability by age seven years of developing a form of rickets termed autosomal recessive Hypophosphatemic Rickets type 2 In fact, in 2010, it was discovered that patients with ENPP1 mutations can develop Hypophosphatemic Rickets even in the absence of a prior history of clinical GACI, thereby expanding the spectrum of disease associated with ENPP1 deficiency. Treatment of rickets in ARHR2 is controversial, and we try to avoid normalization of serum phosphate levels to prevent further calcification. Therefore, we use low doses of oral phosphate and active forms of V itamin D. The development of rickets in children with ENPP1 deficiency highlights the involvement of the skeleton in both younger and more mature patients. The skeletal problems that occur in patients with ENPP1 deficiency represent lifelong medical problems that include bone softening and fractures, bone deformity, dental abscesses, spinal stenosis, and accelerated osteoarthritis. Current treatments for X-linked hypophosphatemic rickets, XLH, such as burosumab, are considered risky for patients with ENPP1 deficiency and are therefore not used. Back to our patient. We have been monitoring the patient with annual CT scans, and at age eight years, we noted new calcification of the aortic arch and the origin of the right brachiocephalic artery, shown here by the yellow arrow. She continues on treatment for hypophosphatemic rickets. Her growth remains impacted. Having described many of the clinical problems caused by ENPP1 mutations, the first step to managing the condition is to increase awareness within the medical community of ENPP1 deficiency. Inozyme is taking a comprehensive approach that includes sponsoring scientific symposia and continuing medical education events, as well as distribution of physician-targeted information. Also sponsoring investigator-initiated research. Inozyme has also partnered with Prevention Genetics to provide free genetic screening for ENPP1 mutations. Another example is to encourage the use of ultrasound earlier in pregnancy or with greater eye and interpretation of images than in years past. Here one can see an ultrasound that demonstrates echo brightness in the aorta, shown by A, in the pulmonary artery, B, and C, the superior vena cava. These efforts are having a significant impact. Over the past five years, I have experienced a marked increase in the number of calls and emails from physicians seeking advice about a diagnosis of GACI or management of patients with suspected GACI. In addition to improving access to genetic testing of the ENPP1 gene, Inozyme is also leading the development of a clinical test to measure plasma levels of pyrophosphate. Measurement of plasma pyrophosphate has the ability to quickly distinguish affected patients who have two ENPP1 mutations from heterozygous carrier patients, as well as normal individuals who have two normal ENPP1 alleles. Perhaps even more importantly, this pyrophosphate test can also be used to monitor responsive affected patients to ENPP1 enzyme replacement therapy and ultimately may help guide dosing. It is key to recognize that GACI may be only the tip of the iceberg that represents ENPP1 deficiency. Other disorders may also represent undiagnosed manifestations of ENPP1 deficiency, including early-onset osteoporosis, some forms of pseudoxanthoma elasticum, or PXE, as well as unexplained hearing loss, hypophosphatemic rickets, bone deformity, and arterial disease. The lack of an effective treatment for ENPP1 deficiency is a critical unmet need, and ENPP1 enzyme replacement therapy has the potential to make a great difference in the lives of affected patients. Thank you for your attention. Thank you, Dr. Levine, for highlighting the high unmet medical need in ENPP1 deficient patients. Before we jump into the clinical data, I want to take a moment to orient you on the importance of PPI. On the left side, you can see how this key molecule functions in the normal state, where it physically blocks the interaction of calcium and phosphate. On the right, when you don't have enough PPI, calcium and phosphate have the opportunity to come together and form these crystals that get deposited in the wrong parts of the body, such as in the arteries, where they can cause cardiovascular complications, and in the bone, where they can cause the skeletal complications as highlighted by Dr. Levine. This concept of a PPI inhibiting calcification has been known since 1962, where as shown on the graph, the higher the PPI concentration, the higher calcium and phosphate product is needed to form the hydroxyapatite crystal. Another important molecule that maintains healthy blood vessels is adenosine, which is a potent inhibitor of intimal proliferation, working through the adenosine receptor as shown on the left. When adenosine levels become low, narrowing and obstruction of blood vessels occur due to abnormal growth of cells in the vessel wall, which is also known as intimal proliferation, as represented on the right side of the image. What is the main producer of PPI and adenosine in the body? Extracellular ATP is metabolized by ENPP1 to produce PPI and AMP, the precursor of adenosine. When you have mutations in ENPP1, you have extremely low levels of PPI, and you can imagine those patients have lots of calcified tissues. To address this deficiency, we designed an enzyme replacement therapy called INZ-701, where we generated a soluble form of the extracellular domain of ENPP1, which was fused with an IgG Fc fragment, which can circulate throughout the body and access ATP, restoring the missing enzymatic process. Our therapeutic objective is to use INZ-701 to replace the missing ENPP1 activity to restore PPI and adenosine levels back into the physiological range to prevent and halt further disease progression. I will now pass it on to Kurt Gunter, our Chief Medical Officer, who will go over our trial design and safety data. Thank you, y. Before we turn to the data, I would like to provide an overview of the design for our phase I-II clinical trial of INZ-701 in adults with ENPP1 deficiency. The primary objective of the study is to test the safety and tolerability of INZ-701 and establish the dosing regimen for future clinical development. This study employs a dose-escalating design across three dose cohorts, where three patients each receive 0.2, 0.6, or 1.8 mg/kg of INZ-701 via a subcutaneous injection. Patients receive a single dose and then begin twice-a-week dosing one week later. In addition to safety, other important outcome measures include pharmacokinetics or PK and plasma PPI. Following the 32-day phase I portion of the study, patients can elect to enter a phase II extension for a total of 48 weeks. Clinical outcome measures, including evaluation of ectopic calcification, vascular and skeletal function, and patient-reported outcomes serve as exploratory objectives. Today we are excited to share top-line PK and pharmacodynamic data and the first evidence of clinical effects of INZ-701. First, let's review the patient demographics and safety. The patients who enrolled reflected the spectrum of adult patients presenting with ENPP1 deficiency. Patient ages ranged from 22 to 58 years and included six female and three male patients. Two Asian and 6 white patients were enrolled, and one patient did not report their race. INZ-701 demonstrated a favorable safety profile. seven out of nine patients experienced at least one adverse event. Most adverse events were mild or moderate in severity. three out of nine patients experienced mild adverse events related to INZ-701. Injection site reactions consisting of bruising or pain occurred in two of the patients and were mild in severity. Other related adverse events included decreased appetite and fatigue. There were two serious adverse events not related to INZ-701, which included a motor vehicle accident and a surgical complication. All nine patients enrolled in the phase II portion of the study. One patient withdrew from phase II for travel-related reasons, therefore, eight patients continue in the study today. In conclusion, we are very pleased with the favorable safety profile of INZ-701 observed in adult patients with ENPP1 deficiency. We also observed a favorable immunogenicity profile in this trial. Low anti-drug antibody or ADA titers were detected but were not neutralizing as there was no effect on PK or PPI levels. Seven of the nine patients had detectable ADA, and the titers ranged from less than 40 to 160. There was no evidence of a relationship between dose and ADA titer. The earliest appearance of ADAs in the third cohort was the fifteenth day after beginning treatment. The earliest appearance of ADAs in the first and second cohorts was the seventy-ninth day. These ADA titers are much lower than those observed with approved enzyme replacement therapies, as shown on the bottom of the slide. In conclusion, although ADAs were observed, they had no apparent clinical impact. Now I would like to hand over to Yves, who will present the PK and pharmacodynamic data. Thank you, Kurt. I'm very excited to show you our data from phase I-II trial in adult ENPP1 deficient patients. Previously, we have shown the phase I portion of cohort one, which is shown on the left side of the first graph. As we have mentioned, low plasma PPI is the main driver of the disease. As can be seen in the III graphs, baseline PPI levels are significantly lower than in healthy subjects, as shown by the red symbols, where the normal range is represented by the green shading. We are delighted to see that at all 3 doses, administration of INZ-701 led to a rapid increase in PPI observed within 6 hours, which is represented by the first black symbol. This is sustained through the phase II portion with 48-week data shown in cohort I. If we break the data into phases, we can clearly see that even after the single dose shown on the graph on the left, plasma PPI reaches levels observed in healthy volunteers. This effect is sustained through the dose evaluation period shown in the middle graph, as well as through the phase II portion shown on the right. We can also see that at the lowest dose level of 0.2 mg/kg, INZ-701 raised plasma PPI levels to the target threshold, similar to the healthy volunteer range, and the PPI levels were maintained throughout the trial. In terms of pharmacokinetic or PK properties, the data showed a dose-dependent exposure in a greater than dose proportional manner when you compare across cohorts. ENPP1 activity also measured and mirrored INZ-701 PK as expected. The half-life of INZ-701 was found to be around 126 hours or just over five days, which suggests the potential for once weekly dosing. Looking back at our preclinical data and putting it in the context of the data I just shared, we can see that in both mice and humans, INZ-701 was able to significantly increase plasma PPI into the normal range with a threshold effect reached at the lowest dose of 0.2 mg/kg, highlighting the translatability of our mouse model. With that in mind, let me remind you what we had seen in our proof of concept studies in the ENPP1 deficient mouse model when we significantly raised plasma PPI. ENPP1 deficient mice have extensive calcification, as shown by the red arrow in the micro-CT of the heart. INZ-701 prevented the pathologic calcification of the heart, as seen in the micro-CT, as well as quantitative assessment done in the kidney and liver. We also saw prevention of skeletal abnormalities with improvement in trabecular number and cortical thickness, main drivers of growth. Finally, we have also shown that INZ-701 can prevent intimal proliferation in an ENPP1 deficient mouse model by the absence of cells in the lumen of the artery, as shown on the right side of the image, a process driven mainly by the generation of adenosine. Our expectation is that the similar effect of INZ-701 observed on plasma PPI in our phase I- II trials will translate into improved clinical outcomes as we have seen in our preclinical studies. I will now hand it over to David Thompson, our senior advisor, to go over some additional clinical data that we are excited to share with you. I'm delighted to share with you emerging clinical data from our trial in adults with ENPP1 deficiency that links the change in PPI that Yves has shared with important clinical outcomes independently assessed by both the study clinician and the patients themselves. When I led the Strensiq Clinical Development Program at Alexion, we carefully followed anecdotal reports from patients about how they felt on therapy. Paying attention to the patients enables the construction of effective clinical protocols and improves the assessment of clinical benefits. In our ENPP1 program, we have built into the phase I- II protocol the capture of patients' overall health since beginning therapy with INZ-701. These data come from both the clinicians and the patient's perspective. The assessment instrument utilized in this trial is called the Global Impression of Change, hereafter called GIC. The GIC was developed in 1976 and has been used in many drug trials in a variety of therapeutic areas and is included in many approved drug labels. The GIC is a 7-point scale, rating the patient's overall health on a scale from -3 to +3. At each 12-week visit, both the patient and the clinician are asked to rate the patient's health compared to baseline using the GIC scoring system. We view this as an exploratory endpoint, providing the first evidence of clinical activity of INZ-701 and indicating how patients feel. We intend to share additional exploratory clinical endpoints from the ongoing studies over the coming quarters. Here, we have plotted individual GIC scores across the 3 dose cohorts with the clinician's assessment in the top half of the slide and the patient's GIC assessment in the bottom half of the slide. Six of the eight subjects with at least 12 weeks of treatment showed improvements in their health relative to baseline. They also maintained their reported improved health over the subsequent 12-week time points. No patient showed a deterioration of health in that no negative GIC score was recorded. Importantly, both the clinician and the patient independently assigned very similar GIC scores at each 12-week time point, providing further validation of the clinical outcomes revealed in this trial. Together, these exciting data support a direct link between the increase of PPI levels and improved GIC scores in adults with ENPP1 deficiency treated with INZ-701. The rapid and sustained increase in PPI observed with INZ-701 translated into improved GIC scores. Furthermore, the duration of therapy could translate into additional clinically important endpoints that will allow us to understand the clinical improvements underpinning these GIC data. In conclusion, the results from the 1st-ever clinical trial performed in this adult population are as follows: A rapid, significant, and sustained increase in PPI level was observed in all cohorts, reaching the desired target level for pyrophosphate in all patients. INZ-701 exhibited a predictable and consistent PK profile and enzymatic activity in all patients with a long half-life, suggesting the potential for once-weekly dosing. Importantly, INZ-701 was generally well-tolerated in all patients and exhibited a favorable safety profile. We showed here the first evidence of clinical activity of INZ-701 through an improvement in the overall health as measured by the GIC score. 6 out of 8 patients showed comparable and concordant improvements from the patient's and clinician's perspective. Lastly, these observations are in line with the positive anecdotal reports we received from the investigators in the ongoing trial. I will now hand it back to Kurt, who will share our regulatory progress and late-stage clinical strategy for ENPP1 deficiency. Thank you, David. Inozyme is taking a global approach to development of INZ-701. To date, we have met with regulatory authorities at the EMA and FDA, as well as European national regulatory authorities to discuss our development plans. We have ongoing successful interactions with the EMA in development of our pediatric investigational plan. We are also meeting with the FDA this quarter and the EMA and EU national regulatory authorities later this year to discuss our plans for pivotal studies. As a result of our positive regulatory interactions, we have received an Orphan Drug Designation from the EMA, as well as Orphan Drug, Fast Track, Rare Pediatric Disease designations from the FDA. Furthermore, we intend to apply for Breakthrough Therapy designation from FDA later this year. Depending on pivotal study design, we also plan to pursue FDA Accelerated Approval. We are excited to announce the ENERGY-1 study, which we anticipate initiating in the second quarter of this year. ENERGY-1 is a phase I-B open label single arm study to evaluate the safety, tolerability, PK, and pharmacodynamics of INZ-701 in infant patients with ENPP1 deficiency and GACI. This study will enroll infants from one month to one year of age and is designed to provide safety and tolerability data as well as informed dosing of infants in a future pivotal study. In addition to the primary objectives of safety and tolerability, we will be studying PK and PPI as secondary endpoints. As already mentioned, low PPI levels are critically important in disease pathogenesis in babies with ENPP1 deficiency. We will also be assessing the patients for survival, cardiac function, growth, development, functional performance, relevant biomarkers, and healthcare utilization. We look forward to providing more updates from ENERGY-1 in the future. Because patients with ENPP1 deficiency express different disease manifestations at different ages, in advanced clinical studies, we will tailor outcome measures as appropriate for specific patient age groups. PPI is the critical pharmacodynamic marker responsible for the development of disease in all ages and is the bedrock outcome measure across all patient age groups. That said, we believe it will be important to link changes in PPI to both intermediate endpoints as well as definitive clinical outcome measures that assess how patients feel, function, and survive. Some illustrative examples of this approach are shown here. For example, in an infant study, we would want to measure survival and cardiovascular function and demonstrate a correlation of these outcomes to increases in PPI. In older pediatric patients, we want to measure skeletal abnormalities and developmental milestones and show a correlation of these outcomes to increases in PPI. We are planning to initiate pivotal studies in our ENPP1 program in Q3 of this year, subject to regulatory discussions and approvals. Now I would like to introduce Dr. Wilko Spiering, who will discuss pseudoxanthoma elasticum. Hello, my name is Wilco Spiering. I'm an internist working at the University Medical Center Utrecht, the Netherlands. I'm going to talk about pseudoxanthoma elasticum, in short, PXE. In our Dutch expertise center for PXE in the Netherlands, which was founded in 2013, we have screened so far 434 cases, including even non-Dutch patients coming from abroad. So far, we have identified 352 unique PXE patients. Depending on the prevalence, this means that somewhere between 50% and 80% of all Dutch PXE patients now have been identified. We still get referrals of 2 new patients each month, and we are hosting the Dutch PXE Natural History Study. This is a prospective study where we collect clinical data as we see patients on annual base, and we collect data of skin, eyes, the vasculature, and the quality of life. All data are collected in a research database. Let me introduce one of my patients that I recently saw in my outpatient clinic. This is a male patient of 54 years old. At the age of 42, he had a stroke. A few years later, he had complaints of wavy lines on both eyes, and he was seen by a local ophthalmologist that decided to start intraocular anti-VEGF injections. This patient was referred to our expertise center, and we confirmed the diagnosis of PXE because this patient had two pathogenic mutations in the ABCC6 gene. We did an extensive follow-up in this patient, including an extensive CT scan. We showed that there was a massive vascular calcification in almost all vascular beds. A few years later, this patient had to reduce his workload to 60%. He had difficulties handling his two children. One year later, he had a second stroke. Even one year later, he had his third stroke and now became fully incapacitated for work. Currently, he is 54 years old. He has lost his vision of his left eye. He continues to receive anti-VEGF injections in his right eye to spare this vision. In PHC, there is a pathological calcification, which is the key driver of this disease. Here on the left side, we see the cell membrane in a liver cell. Different proteins can be distinguished, and one of these proteins is the ABCC6 protein, which is a transport protein, that shuttles ATP from the inside to the outside. This ATP is then converted by the important enzyme ENPP1. This ENPP1 just then generates pyrophosphate, in short, PPI. In a normal situation, calcification needs to be there at the teeth and the bones in the body. However, at other locations, this calcification needs to be inhibited. This PPI is one of the most important inhibitors of ectopic calcification. Because of mutations in the gene coding for this protein, there is less production of PPI and therefore pathological soft tissue calcification. Mutations in ABCC6 is seen in PXE, and when mutations in the gene coding for ENPP1 are present, this may lead to almost zero production of PPI, which is seen in the GACI syndrome. In PXE, there is typical calcifications in the eye, the blood vessels, the kidney, and the skin. This leads then to the following clinical manifestations in this disease. At young age, we see this typical yellowish papules of the skin. When we do a biopsy, then we see calcium deposits that are fragmenting the elastin in the skin. With respect to the retina, we see a progressive calcification of the so-called Bruch's membrane. In young age, this calcification is seen as peau d'orange, and this then evolves into angioid streaks, choroidal neovascularizations, which can give typical bleeding complications in the eye. A part of the patients even develop macular atrophy. Above the age of 50, almost 40% of the patients have visual impairment. Even 15% of the patients are legally blind. With respect to the blood vessels, here we see the leg with typical calcification. There is calcification of mostly the peripheral and the carotid arteries. PXE patients have a prevalence of stroke and TIA of 15% compared with 5% in the general population. A 3 x higher risk for stroke and TIA. Patients also have a high prevalence of peripheral arterial disease. In 50% of the patients, we see peripheral arterial disease compared with only 7% in the general population. Recently we discovered that also osteoarthritis of the knee and the AC joints in the shoulders may be an issue in these patients. When we measure this pyrophosphate, in short, PPI, we indeed see that this is decreased in PHC compared with healthy controls. Almost 60% lower levels of PPI can be found in PHC patients. There is a tendency that male patients have a somewhat lower level of PPI compared with female patients. This is a rather complicated slide, but please note that on the X-axis we see the patients getting older. Here we have in different colors the vascular beds that we can distinguish and that we measure by doing a CT scan in these patients. Here we have the intracranial carotid arteries, the extracranial carotid arteries, the coronary arteries, the aorta, the iliac arteries, and the leg arteries. As you can see, when patients are getting older, there is increased calcification in these vascular beds. Please note that the y-axis is a lock scale. At higher ages, we see a 90%-95% of all these vascular beds that have more or less severe calcification in these patients. Because of this progressive soft tissue calcification over time, we see a decrease in visual acuity over time, and this may lead to legally blindness. We see high prevalence of peripheral arterial disease, as is seen in this picture, a recent publication of my group showing that there is increased prevalence over time. The mean prevalence is around 50%, but it goes up to 70% at higher ages. There is an increased risk of stroke in these patients. When you look at the molecule structure of pyrophosphate, you see that there is a close similarity with a drug group called bisphosphonates. Because of this similarity, we did a study where we studied etidronate, one of the examples of bisphosphonates, as being a analog of pyrophosphate. We randomized patients in this double-blind randomized controlled trial to etidronate or to placebo. After one-year treatment, you can see that in almost all vascular beds, the etidronate-treated patients in red show less calcification compared with the placebo-treated patients in blue. In conclusion, PXE is a progressive disease that is characterized by mainly ophthalmological and vascular complications. Pyrophosphate is low in PXE and causes calcification, among which vascular calcification. Etidronate is an example of the group of bisphosphonate and is similar to pyrophosphate and suggests that PPI-increasing treatments may inhibit progressive vascular calcification. Because of uncertainties on long-term safety of bisphosphonates, further exploration of PPI-increasing treatments is warranted. With this, I'd like to thank you for your attention. Thank you, Dr. Spiering, for highlighting the high unmet medical need of PXE. Just conveyed by Dr. Spiering, ABCC6 plays an important role in maintaining plasma PPI in the normal range, with PXE patients having 60% lower levels of plasma PPI due to mutations in the ABCC6 transport. Our goal is to use INZ-701 to raise the PPI levels back into the physiological range by accessing other sources of ATP that are available, as shown on the left side of the figure. I will now pass it on to Kurt, who will go over our trial design and safety data. Thank you, Yves. This phase I- II trial design mirrored that of the previously described trial in ENPP1 deficiency. The primary objective of the study is to test the safety and tolerability of INZ-701 and establish the dosing regimen for future clinical development. In addition to safety, other important outcome measures include PK and plasma PPI. Clinical outcome measures appropriate for PXE were included as exploratory objectives. The study is now fully enrolled. Today we will be presenting top-line results from the phase I portion and partial data from the phase II portion of the study. Patient demographics generally reflected the spectrum of PXE patients. Patient ages ranged from 29 to 67 years, which was slightly older than the ENPP1 population, included five female and four male patients. All the patients were white. INZ-701 demonstrated a favorable safety profile in PXE patients. All 9 patients experienced at least 1 adverse event, but all adverse events were mild or moderate in severity. Seven of the nine patients experienced adverse events related to INZ-701, which were mild to moderate. Injection site reactions consisting of discoloration, erythema, induration, pain, or pruritus occurred in four of the nine patients and were all mild. Other related adverse events were mild to moderate and included erythema, fatigue, night sweats, pruritus, and urticaria. There were no serious adverse events. one moderate adverse event consisting of urticaria and erythema led to the withdrawal of one patient from the 1.8 mg/kg cohort during phase I. Eight of nine patients enrolled in phase II and continue on INZ-701. In conclusion, the safety profile of INZ-701 in adult patients with ABCC6 deficiency is favorable. In the ENPP1 study, we observed a favorable immunogenicity profile in adults with ABCC6 deficiency. Low ADA titers were detected after INZ-701 administration, but were not neutralizing as there was no effect on PK or PPI levels. 6 of the 9 patients had detectable ADA, and the titers ranged from less than 40 to 640. There was no evidence of a relationship between dose and ADA titer. The earliest appearance of ADAs in the 3 dose cohorts ranged from 29 to 55 days after beginning treatment. The ADA titers are much lower than those observed with approved enzyme replacement therapies, as shown on the bottom of the slide. In conclusion, although ADAs were observed, they had no apparent clinical impact. Now I would like to reintroduce my colleague, Yves, who will present the PK and pharmacodynamic data. Thank you, Kurt. I'm very excited to show you our data from our phase I-II trial in ABCC6 deficient patients, also known as PXE. Previously, we have shown the phase I portion of cohort one, which is shown on the left side of the graph. As we have mentioned, low plasma PPI is the main driver of the disease. We can clearly see that administration of INZ-701 led to a rapid increase in PPI after the first administration, as shown by the first black symbols. The levels of PPI were not sustained at the 0.2 and 0.6 mg/kg dose levels shown in the first two graphs. In the 1.8 mg/ kg dose cohort, we were pleased to see that once INZ-701 dosing was initiated twice weekly from day eight, we see the plasma PPI increase into the healthy volunteer range, represented by the green shading. The levels were sustained through the phase II portion. If we break out the data into phases, we can clearly see that there is a dose response even after the single dose shown on the graph on the left. We see that at a dose of 1.8 mg/kg in both the dose evaluation period shown in the first two graphs, as well as through the phase II portion shown on the right. Plasma PPI reached the desired target levels observed in healthy volunteers. In terms of pharmacokinetic or PK properties, the data showed that INZ-701 exposure increased with dose in a greater than dose proportional manner. INZ-701 activity was also measured and correlated well with PK, as we expected. Looking back at our preclinical data and putting it in the context of the data I had just shared, we can see that in both mice and humans, INZ-701 was able to significantly increase plasma PPI into the normal range in a dose-dependent manner. If we compare the response of PPI to INZ-701 in both our preclinical models that recapitulate the clinical features of the diseases in question, we can see that while threshold effect is observed in ENPP1 deficiency, a dose response is observed in ABCC6 deficiency. This is similar to what we observed in our ongoing clinical trials, underscoring the translatability of our mouse models. With that in mind, let me remind you what we had seen in our proof of concept studies in the ABCC6 deficient mouse model when we significantly raised plasma PPI levels. INZ-701 prevented pathologic calcification in the skin, one of the key features of PXE, as shown in the histological section of the skin. In the vehicle-treated mice, the red arrows point to calcification sites where we see extensive calcification in black. INZ-701 was able to prevent the significant accumulation of calcification, which was quantified and represented in the graph. Our expectation is that the similar effect of INZ-701 on plasma PPI observed in our phase II-I trials will translate into improved clinical outcomes. In summary, we demonstrated proof of principle that INZ-701 increased PPI levels in subjects with functional ENPP1 enzyme. More importantly, INZ-701 was generally well-tolerated and exhibited a favorable safety profile. PK and INZ-701 activity remain consistent with observations from ENPP1 phase I-II trial. Administering INZ-701 to adult patients with ABCC6 deficiency at the 1.8 mg/kg dose led to a rapid and sustained increase in plasma PPI to levels comparable to those observed in healthy subjects. We also noted a dose response as predicted in the preclinical data. I will now pass it back to Kurt, who will go over the development and regulatory strategy. Thank you, Yves. To date, we have met with regulatory authorities at the EMA and FDA, as well as European national regulatory authorities to discuss our development plans. As a result of our positive regulatory interactions, we have received an orphan designation from the EMA and an Orphan Drug Designation from the FDA. We plan to apply for other expedited regulatory programs. Depending on pivotal study design, we also plan to pursue FDA Accelerated Approval. Similar to ENPP1 deficiency, patients with ABCC6 deficiency express different disease manifestations at different ages. Therefore, in advanced clinical studies, we will tailor outcome measures as appropriate for specific patient age groups. PPI is the critical pharmacodynamic marker responsible for the development of disease in all ages and is the bedrock outcome measure across all patient age groups. That said, we believe it will be important to link changes in PPI to both intermediate and clinical outcome measures as well as definitive clinical outcomes that assess how patients feel, function, and survive. Some illustrative examples of this approach are shown here. We plan to initiate advanced clinical trials in ABCC6 deficiency in 2024, subject to regulatory discussions. Following ongoing interactions with regulatory authorities, we look forward to providing you with more detail regarding the design of our advanced studies in both ENPP1 and ABCC6 programs. Now I would like to introduce Dr. Mark Kiel, who will share recent advances in our understanding of the incidence of ENPP1 deficiency. My name is Mark Kiel. I am an M.D., Ph.D. with a focus on molecular genetic pathology. I am currently the Chief Scientific Officer and founder of Genomenon. I'm here today to talk to you about updated ENPP1 deficiency incidence estimates. I'd like to begin with the end in mind. This is a worthy end. This is a common goal for multiple rare diseases. It's a very valuable goal. That is to say, we are all seeking accurate, defensible, evidence-based genetic birth incidence calculations. My goal in this 10 minutes that I'm gonna share with you is to walk through those aspects, what the need is, and how Genomenon delivers against that need. In particular, did so for ENPP1 deficiency. This is the structure of the presentation. It's to first give an overview of Genomenon, provide some background very briefly about incidence, its definition, and some considerations, go through, again, very briefly, the calculation methods that are gold standard in epidemiologic circles. Then to specifically speak to the previous incidence calculations for ENPP1 deficiency and the updates that were occasioned by the data that Genomenon has gathered for this disease. To begin, let me highlight some the aspects of Genomenon's core technology and one of the things that makes us unique as a company in this space. We have an AI capability that we've referred to as genomic language processing. It takes the disorganized, widely distributed across time and publisher information in the scientific and clinical literature, all of the different terms that are necessary to understand that literature at scale, including diseases, phenotypes, therapies, genes and specifically genetic variants, no matter how an author can describe that. Collectively, our AI capability is compelling that information to order and putting it together in what we call genomic associations. This is now every paper ever published across the decades of scientific and clinical inquiry, all indexed with our technology and put into workflow queues that allow us to curate that information. That's the second unique capability that Genomenon has. It's a unique combination of computational capability and expert curation. We integrate external database data information into this published information, as I showcased on the previous slide, to provide a gold-standard clinical-grade interpretation of that information. What results is what we refer to as a variant landscape. I'm showcasing that for ENPP1. The protein axis is on the horizontal, and on the vertical is publication levels for each of those variants that are reflected by the bars, one of which is highlighted. This is comprehensive across all variants and across all of the published information and associated database information for each one. A little bit more detail about what that looks like. We are talking now about row by row being all of those variants, a comprehensive reflection of each one, every one of the reference citations by number shown in the middle, and all of the categorization of that evidence, including enumerations and adjudication of the strength of that evidence in a clinical framework necessary to interpret the validity of those disease-causing variants. This is what that looks like for one of those variants and is a reflection of the exhaustive measures we go to when curating this with my team of expert curators. We look at every reference, we adjudicate the meaningfulness of every reference, and we record our work. We associate it with the various diseases and phenotypes and also incorporate functional evidence. This is exceedingly meticulously detailed information that we've cataloged and understood. Collectively, when you look at each one of these references and the evidence that it provides to support the pathogenicity of each individual variant, that amounts to our variant landscape. Some definitions. This may be a review for some of you in the audience, but it's important to have an idea of what the difference between prevalence and incidence is when we're talking about incidence estimation. Perhaps a more widely known term is prevalence, which is to say the number of patients per defined population. That incorporates a great deal of clinical parameters, longevity, mortality, the ability to recognize these individuals clinically, et cetera. Incidence is a slightly different but related term, which is to say, what is the rate of appearance of those affected individuals into that population? That rate of appearance is occasioned by the birth of those new individuals who have the genotypes that are appropriate for causing that disease. One colloquial way to consider this is the analogy of a bathtub. It's called the epidemiologist's bathtub, where incidence is how fast the water flows in, and prevalence is how full the bathtub is. Obviously, how full the bathtub is affected by how rapidly the water drains. Other considerations here when we're thinking about incidence is to say the difference between genetic incidence and clinical incidence. In this case, the calculations allow us to get at the genetic incidence, whereas the clinical incidence is what would be seen. What we're trying to square here is the difference between those two and using the best evidence predicate, the best data to get the most accurate reflection of what that genetic birth incidence is to give us the best opportunity to divine what the most accurate clinical incidence estimate is. Importantly, if there's a perfect correlation between the genotype and the phenotype, the genetic and the clinical presentations, then these two terms are synonymous. When we talk about incidence determination, there's two categorical ways to do that. One is to estimate, which is not an uncommon method, though it suffers from imprecision and sometimes inaccuracy. A more precise way to do it is to use calculations. You're allowed to do that. You're afforded the ability to do that when we're talking about autosomal recessive diseases. Estimate determinations of incidence have to do with gathering insight from clinical experts and primary care physicians, examining EMR, comparison with other databases, or more commonly is educated guesses. When we're talking about developing a drug program, we need more confidence in the calculation, the determination that we bring to bear as it informs strategic decisions and et cetera. When we're talking about calculating the incidence, it's important to know that these are still estimates, but they're the best way to get this information and to have confidence in the number that you've come up with. It's really important to emphasize how they're predicated on evidence. They're based on the carrier status, the number of moms and dads who have disease-causing alleles, and how they might get together to have children who have the appropriate genotype to cause this disease. Again, appropriate for autosomal recessive diseases. Estimates are particularly challenged in rare and ultra-rare disease, especially when there's clinical complexity and overlapping differential diagnoses. Obviously, with rare disease, there's a small sample size. There's a low number of patients. There's often ascertainment bias when you're going anecdotal and interviewing clinicians for their experience to provide guesstimates for the incidence. The calculations don't suffer from any of those challenges. When we're talking about the calculation, we're looking at the proportion of healthy individuals at large who may be carrying those disease-causing variants and using that carrier frequency and some standard presumptions about the way that populations grow, intermingle and grow, we can use that carrier frequency to model patient birth rate or appropriate genotype birth rates. Doing so requires accurate and sensitive knowledge of disease-causing variants. The data quality and the completeness of the data that you're using to interpret those variants is critically important because a single missing or erroneously called variant will obviously have bearing on the incidence calculation. Sometimes that consequence can be very significant. I won't belabor the point here, but this is, as I say, the gold standard for autosomal recessive diseases in calculating the incidence. It's called the Hardy-Weinberg equation. This is what we're talking about in the subsequent slides as I close here is the calculated genetic birth incidence, sometimes referred to as the genetic birth prevalence, as those two terms are synonymous. To be precise, we'll stick with calculated genetic birth incidence. Very important to state that about two years ago now, a publication came out from Carlos Ferreira, who is a clinical expert on ENPP1 deficiency, and I'm happy to say is now a compatriot of mine, a colleague. We work closely together. He and his team have published estimates of incidence for ENPP1 deficiency, and they use that methodology that I talked about. That's the gold standard methodology. They came up with a determination of 1 in 200,000 pregnancies have an ENPP1 deficiency genotype. Now we're talking about the necessity to have comprehensive and accurate information, and that's why I began describing what Genomenon produces when we put together these variant landscapes. Into that consideration, that methodology, and working with Carlos, we brought to bear our data set with more of these disease-causing variants adjudicated by the evidence according to that clinical framework and working with Carlos and others, we published a updated result that modified with evidence the previous consideration for what that calculated incidence was. The result was that using that data, the estimated genetic incidence was approximately 1 in 64,000 individuals. I wanted to end here by saying, by really emphasizing when we compare these two calculations, the former and the current, that they use the same methodology and they involve the same disease experts, the same clinical experts, Carlos Ferreira being one of the leaders in this. The difference is that we used more data, more data in terms of determining our carrier frequency. There was a superior database that was not used in the previous iteration that we used with Carlos' consideration. There was also an appropriate clinical framework by which we adjudicated the disease-causing nature of these variants. We had more of those variants afforded by the comprehensive ENPP1 landscape that Genomenon produced. We had more evidence per each individual one of those variants, which came out of our genomic language processing that is unique to Genomenon. All of these things put together, the same methodology and the same expert looking over the data and adjudicating this information with his clinical acumen. There was more data to begin with for the carrier status. There was an appropriate way to adjudicate the evidence for each of those variants. There were more of those variants and there was more evidence for each of those variants. All of those considerations put together amounted to the updated ENPP1 genetic birth incidence of one in 64,000 individuals. With that, I'll conclude. I'll be available for any questions that you may have. Let me pass it over to our next speaker. Thank you, Mark. This comprehensive work gives us confidence that there are patients out there. Our partnership with Genomenon is just one example of the innovative ways we are enhancing disease awareness. I will not be talking about ABCC6 today, as finding the patients for this disease is much more straightforward. We have already found several centers with over 400 patients each. For my part this meeting, I would like you to walk away with 3 key points. We have made major progress in identifying patients with ENPP1 deficiency. The patient and physician community is highly engaged and eager to learn more about this severe disease. The ENPP1 market is sizable commercial opportunity that can be addressed with a lean and highly focused team. In 2017, when the company was founded, the published pregnancy prevalence was 1 in 506,000. We went to work to understand the true market potential. From my experience, I knew that there would be more patients than was described, but we were surprised and encouraged since we're finding patients in so many of our interactions. The number of patients we were learning about did not seem to reflect the published incidence number. I have previously worked on the launch of three blockbusters, two of them in ultra-rare indications. I know that ensuring accurate diagnosis is critical, as many patients remain undiagnosed or misdiagnosed. We started building our diagnostic pathway early and partnered with PreventionGenetics to provide free genetic testings for physicians with suspected undiagnosed ENPP1 patients. We also started a collaboration with Ultragenyx and Invitae to find ENPP patients who were misdiagnosed, in this case with XLH, a disease that overlaps phenotypically. Another important diagnostic initiative that I'm very excited about is our collaboration with Rady Children's Institute for Genomic Medicine. Imagine how important it is to get a fast diagnosis in a disease where the mortality is over 50% in the first six months of life. Most genetic labs takes two to three weeks to generate results, which is unacceptable for us. Through our pursuit to improve the turnaround time, we came across the Rady Children's Institute for Genomic Medicine. Rady has developed the fastest whole genome sequencing test currently available in the U.S., which can be completed in just three days. For upcoming planned clinical trials, and if the drug is approved, this is a huge and critical improvement. I often get asked if ENPP1 deficiency testing is part of the newborn screening program. Today, the process to get a product onto this testing program is very time-consuming and can take up to 10 years. It's only possible for diseases with an FDA-approved therapy. Again, something we're looking to speed up. During our collaboration with Rady's, we also became one of the three founding members of a program called Beginnings. This program aims to screen all newborns for genetic disease using a whole genome sequencing approach. In 2023, the target is to have 80 U.S. network members in this program and grow from there. In addition, the consortium is starting to collaborate with other programs outside of the U.S. This newborn screening program will ensure that newborns with ENPP1 and ABCC6 deficiency receive a rapid and accurate diagnosis. We're really fortunate to have a great partnership with the ENPP1 patient advocacy group. It's called GACI Global. They are incredibly engaged, and they passionately provide education and support to patients and families affected by ENPP1 deficiency. One of the ways we partner with them is through research to understand and educate on the severity of this disease. Two examples are these peer-reviewed publications that describe the disease from a patient perspective and describe the adult phenotype, two areas that were previously not well understood at all. These diagnostic initiatives, disease awareness education, and increased physician interest coalesced with an updated calculation of birth prevalence of one in 200,000. We now knew we were on to something much bigger. Our collaboration with Genomenon started in 2020. The original goal was to include ENPP1 and ABCC6 in a database called Mastermind, a comprehensive, publicly available genetic database being used by geneticists and the broader medical community. After the extensive collection and curation of all published ENPP1 deficiency articles, we found a three-fold increase in disease-causing variants, which you heard earlier from Mark Kiel. These important results were published in two publications in the fall of 2022. When building a rare disease franchise, you must create awareness and engagement in the physician community. In other words, doctors must care about a disease. To do this, you need to be able to demonstrate that the disease is severe, how to recognize and diagnose the disease, and show that the patient population is large enough that they probably have or will see an ENPP1 patients. I remember a doctor saying at the medical meeting to hematologists when I was launching Soliris for PNH while I was at Alexion. He said, "You might never have seen a PNH patient, but they have seen you." In other words, it's worth paying attention to. A big part of our success today has been the team we have built, which has a wealth of experience and success in other similar and unique rare diseases. We have developed some key materials and a scientific story that is engaging medical professionals across several different specialties. We know where to go, we know who to see, and we know what to say. We have three highly experienced professionals in the field. Two are covering the U.S. and one covering the five major markets in Europe. They engage physicians in one-on-one discussion, cover medical meetings, and identify opportunities for symposia and special projects with key collaborators. All of their activities will help advance our efforts to raise disease awareness and continue to identify new patients. When the publication came out stating that the pregnancy estimate at 1 in 64,000 was 3x higher than previously known, it finally started to feel that we had an estimate that reflected our own experience living and breathing this disease. This should not come as a surprise and has been observed previously in many rare disease launches. My experience from PNH and HPP and other rare diseases have shown that once a therapy comes to market and awareness increases, the number of patients often surpasses previously estimated patient numbers. Using the pregnancy prevalence of 1 in 64,000, we estimate that in North America and Europe, there are about 6,900 patients. In our own database to date, we already have over 500 identified patients. Of these, 200 have both a clinical and a genetic confirmation, and 300 have a clinical diagnosis. In addition, we have identified over 200 young pediatric patients suspected to have ENPP1 deficiency using a cutting-edge AI approach. Most of these patients are located in the U.S. and the five large European markets, which is not surprising as that's where we have boots on the ground. Remember, for Inozyme, the 500 patients identified came during a global pandemic with the 3 people in the field only there for the last 2 years. In summary, we continue to identify patients. Physicians and the patient organizations are very engaged and excited about our program, and the ENPP1 opportunity is real. With that, I will hand it over to Sanjay Subramanian, our CFO. Thank you, Henrik. Good morning, everyone. You just heard about the tremendous progress we have made on the clinical, regulatory, and commercial front for both ENPP1 deficiency and ABCC6 deficiency indications. This is a testimony to the tireless work by our teams this past year. Meanwhile, we have bolstered our balance sheet to support our clinical development. We have closed an oversubscribed follow-on offering last April and also entered into a flexible venture debt facility last July. It is important to highlight that our venture debt facility has an interest rate cap of 9.6%, insulating us from the last few interest rate hikes and potential future increases by the Federal Reserve. Both financings were significant accomplishments considering the very tough capital markets environment last year when many biotech companies failed to attract investors or lenders. Internally, we have been very prudent with our use of cash. Although we have not finalized our full financial results for the fourth quarter and fiscal year ended December 31, 2022, we estimate that we have ended the year with approximately $128 million of cash equivalents, and short-term investments. This was well above our internal target and a testimony to our careful cash management as well as the productivity of our teams. This morning, we are pleased to announce that we are improving our cash runway guidance. We recently drew down the $20 million available under the first tranche of the venture debt. We expect that these funds, along with our cash equivalents, and short-term investments as of December 31, 2022, will extend our cash runway into the fourth quarter of 2024. This is roughly an improvement of two quarters over the previous cash runway guidance. The extension is enabled by managing our expenses thoughtfully, limiting our hiring, increasing productivity, and focusing on our lead program with a goal to bring our product to patients as soon as possible. Let's talk about the upcoming milestones for the company. 2023 is poised to be an important year for Inozyme. Starting with the positive and encouraging data shared today, we expect to make significant progress on the regulatory and clinical front this year. We are currently engaging with the FDA to discuss our planned pivotal trials. In the second quarter, we expect to initiate a phase I-B trial in infants with ENPP1 deficiency. This would mark the first time our drug candidate, INZ-701, is administered in infants, a patient population with the highest unmet medical need. Today, you saw a glimpse of the emerging global impression of change data from the ongoing trial in adults with ENPP1 deficiency. In the third quarter, we plan to share more detailed interim clinical data from this trial. We expect to take a deeper look into the clinical benefits of INZ-701 in adults, a critical milestone that both patients and we are eagerly waiting for. In the third quarter, we also plan to initiate a pivotal trial in pediatric patients with ENPP1 deficiency. As Hendrik mentioned earlier, we have many patients identified in this population whose parents are eager for a potential treatment option for their kids. In the fourth quarter, we plan to share interim clinical data from the ongoing phase II trial in adults with ABCC6 deficiency, another important milestone that patients and we are eagerly waiting for. As one would expect, the start of the pivotal trials mentioned earlier is subject to a satisfactory agreement with the FDA. I couldn't be more excited about this year with these important milestones ahead of us at Inozyme, presenting potential value-creating catalysts. I believe that Inozyme possesses the unique combination of experience, resources, and drive to bring our product candidate to market and serve patients in need. Through our ability to execute, along with the market potential for our drug, Inozyme presents a significant value proposition for our investors. I would now like to hand it back to Axel for his closing remarks. Thank you. Axel? Ladies and gentlemen, you have heard about the burden that patients with ENPP1 and ABCC6 deficiency carry with their disease. Dr. Levine and Dr. Spiering powerfully conveyed the unmet medical need. The Inozyme team has advanced our product candidate, INZ-701, into human trials. We now have a phase III-ready asset that could be launched as early as 2026. The observed safety profile has so far been favorable. Developing an enzyme replacement therapy, we are optimistic for regulatory approval. Our team can spot significant market opportunities because they have done so before. We are preparing for the exciting commercial opportunity in front of us. On behalf of the Inozyme team, I would like to especially thank the patients, caregivers, patient community, and investigators. Thank you all as well for attending our first investor and analyst day this morning. We will now open the lines for questions. Operator? Begin the question-and-answer session. If you would like to ask a question, please ensure that you are dialed in via telephone. To ask a question, you may press star then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause just momentarily to assemble our roster. Our first question here will come from Marc Frahm with Cowen and Company. Please go ahead. Give my questions and congratulations on all the data you presented today. Maybe just to start with the company. Given the increasing treatment effect you're seeing from the 0.6 to the 1.8 mg dose in the ABCC6 study, are you thinking about adding additional higher dose levels to see if you can maybe drive patients, you know, deeper into the normal range? Alongside that, are you seeing any other changes across the studies in kind of mineralization biomarkers, you know, like other forms of phosphate, calcium, or vitamin D metabolites? Morning, Mark. Good to have you. Thank you for your question. First, let me start by saying, how, you know, excited we are about today and the data we saw. We're paving new ground here, and it's quite gratifying. To address your particular questions, I will hand it over to our Chief Medical Officer, Kurt Gunter, to go in more detail on the potential for higher doses, different dosing schedules, as well as other biomarkers. Thank you, Mark, for the question. Yeah, we're quite pleased with the data we have in ABCC6 deficiency. We believe at the 1.8 dose that we've demonstrated that we can keep PPI in the normal level, and we're definitely pleased with that. We do believe we've bracketed the optimal dose in our phase I -II study. At this time, we're not thinking we have to go higher. We are considering potentially once-a-week dosing, and that's something we do want to explore in the future. We'll have, we can share more information about exactly what our pivotal dosing strategy will be once we complete our regulatory interactions. Okay, what about your other mineralization biomarkers? Are any of those changing? We're looking at a large number of biomarkers, more than I could probably list within the time limits of this call. We are looking at quite a few, and we'll have those data in Q3 when we come out with our interim clinical data. Okay. Good. That's helpful. Not sure if they're on the line, but, Doctors Levine and Spiering, maybe if you guys could comment on just given your experience with these diseases, you know, other related diseases like XLH and HPP and just kind of magnitude of PPI changes you're seeing, how quickly would you expect those to translate into kind of clinical effects on things like, you know, rigid scores and cardiac calcifications or other measures of cardiac function? It just- Good morning. This is... I'm sorry, go ahead. Sorry. Michael, I think you go first. That's great. Then Wilco after you. Perfect. Super. Super. Good morning. This is Michael Levine. That's a super question. You know, bone mineralization is a dynamic process, but not an acute process. I would imagine that a drug that normalized phosphate and was able to affect normal mineralization in bone in patients with hypophosphatemic rickets due to ENPP1 deficiency would demonstrate improvements in two to six months. We certainly would be able to see that on standard x-rays and biochemical responses as well. In terms of cardiac function, you know, it's a little bit trickier. That might take, you know, several months, depending upon what the issues are. The drug shows very good behavior in the rodent models and preventing progressive calcification and cardiac dysfunction within a short period of time. We would anticipate similar benefits in humans who have ENPP1 deficiency, certainly looking at weeks to months as opposed to years. If I may add to that, my name is Wilko Spiering. I'm from the University Medical Center Utrecht. I'm answering your question regarding PXE. An excellent question, I must say. Of course, we do not exactly know because we didn't do these studies so far in patients. However, we have some indirect evidence from our trial with etidronate, which is a PPI analog. At least in this one-year treatment, we could nicely see a reduction in the etidronate treated patients with respect to the calcification of the arteries. However, this is an outcome that can be measured, and that's not necessarily also a functional outcome. As PXE is a more slowly progressive disease, at least compared with PXE, and I would say that takes 6-12 months at least to have some effects, as we have learned from this trial. With respect to the PXE, I'm a little bit concerned because I think that when you are treating older patients that already have these massive calcifications of Bruch's membrane in the eye, I don't think that starting and PPI increasing treatment at later stage will reverse the vision at that age. I think that the earlier you start this treatment, the better to see real clinical benefits. Okay. That's all very helpful. Thank you. Thank you. Congrats again on the data. Our next question will come from Chris Raymond with Piper Sandler. Please go ahead. Hey, thanks, congrats from us as well on the data. Really impressive. 2 questions, if I can. Maybe first on ABCC6. Just, you know, noticing you have, you know, really solid GIC scores in ENPP1, but there's, I don't think I've seen any patient quarter outcomes data in the ABCC6 indication. Just maybe what's the plan there in terms of getting that data? Is there some other, you know, sort of measure that would be, you know, sort of needed? You know, on ENPP1, just on those 500 identified patients, can you give a little bit more color on the status of those patients? I know we've talked at Axel offline, you know, a bit about, you know, potential registry, but is there a plan to maybe put these patients in some sort of formal process to maybe prioritize or categorize them for treatment at some point? Hey, good morning, Chris, and great to have you. Thanks for the questions. Again, I'm gonna hand over the first one regarding the GIC data in ABCC6 over to Kurt, and then afterwards, on the patients and their status over to Henrik. Kurt. Well, thank you very much for the question, Chris. We're really pleased with this early indicator of clinical benefit with regard to GIC. You know, as your question points out, we don't think it's the whole story. To get to your... We want to correlate that with other clinical outcomes to establish an internal validity of the GIC and also look at other PROs. To get to your question, we obviously do have the GIC and other PROs in the ABCC6 study. As you may have seen from the PPI and PK data that Yves presented, the timelines are a bit shifted between the two trials. The ENPP1 adult study began before the ABCC6 study. We've taken the decision to show data when we have them available from all three cohorts, and we don't have the GIC data from all three cohorts of the ABCC6 study yet, but we will certainly look forward to sharing those when they become available. Regarding the patient identification, first of all, I'd like to say we're very happy with the progress we're doing. We're actually much further ahead in identifying patients than we were at a similar time when I was working at Alexion, leading the Strensiq program. We're doing really well. We are planning on starting a registry. We have started a process of getting that going, the plan is to eventually try to get as many of these identified patients into the registry to actually generate data that eventually could be used for publications and potential reimbursement negotiations, et cetera. The plan is there, that's the way we will sort of more medically characterize them, et cetera. I hope that answers your question. Great. Yep. Thanks. Congrats again. Our next question will come from Joseph Stringer with Needham and Company. Please go ahead. Hi. Thanks for taking our questions. Two from us. The first one is on the ABCC6 data, the moderate AE, the erythema urticaria that led to the withdrawal. Can you explain, provide a little bit more color around that? You know, when did that occur? Any more details around that. Our second question is on the planned ENPP1 infant trial. Do you know what the range, PPI range is for healthy volunteers? Is it similar to the adult range in which you showed it was, you know, around 1,000 to 2,000? Any additional detail on that would be helpful. Thank you. Great. Good morning, Joe. good to have you on the call. again, you know, I can hand work out to my colleagues here. Kurt, we'll start with you again, on the ABCC6 study and the comment on the adverse events. After that, on the PPI levels in healthy infants, what do we know compared to the adults? I'll hand that then afterwards to Yves. Over to you, Kurt. Okay. Thank you. Thank you, Joe, for your question. Before I get to the specifics of that patient, I think it's important to point out the overall favorable safety profile that we observed in both studies. We think this is an important milestone to allow this program to proceed, which we're anxious to do. To get to your question, as I mentioned during my presentation, the patient was withdrawn from study treatment during the phase I portion of the study, and specifically, that was at day 15. That patient was withdrawn from treatment, and then we continued to follow the patient beyond day 15 to collect additional safety data. The patient had received four doses of drug prior to his withdrawal from treatment. You know, I think it's fair to say that this patient... I'll point out first that the patient had only moderate symptoms, and those resolved quickly. Since this is a phase I study, that patient was withdrawn out of abundance of caution. In clinical practice in the future, we think that patients like this with moderate symptoms could be easily managed and stay on treatment. All right. Thanks, Joe, for your question about the PPI in infants, in healthy infants. We have done a study, which we published. It's a Bernhardt et al. paper in The Journal of Clinical Endocrinology & Metabolism, where we did look at PPI levels from newborn up to 18 years old. That paper shows, that there is no much difference, with age in the PPI levels. We expect the ranges to be the same, throughout the age spectrum. Great. Thanks for taking our questions. Our next question will come from David Nierengarten with Wedbush Securities. Please go ahead. Hey, thanks for taking the questions. I had a question on the symptom scores, and a related question from Mark earlier. First off, is there any, you know, particular symptom that resolves with the fastest? It sounds like maybe the bone mineralization scores might be the one. But if there's any other one that might resolve or improve faster than the others? On the components of the GIC, I suppose by the name generalized that they're all equal, kind of contributors to the symptom score but, or improvement, score. But if there's any one or two that dominate that, I'd be curious to know or if you could describe what components go into that score. I'd appreciate it. Thanks. Great. Good morning, David. Again, you know, over to Kurt to describe these scores, particular symptoms, and also the components of the score. Okay. Well, thank you for your question, David. We are intrigued and quite pleased with these early GIC data. It's a general impression that the physicians and the patients both provide. As David noted in his presentation, they are concordant, which we think supports the reliability of this method. It is general, and we do need to collect PROs based on other functional domains that provide more specific information about pain, function, and different modeling parts. That'll be data that we're still collecting. It's a bit more complex, but we will be sharing those other PRO data in Q3. Regarding other, early indicators, I think Michael Levine addressed that, biomarkers of bone metabolism could be quite early indicators of clinical activity, as well as measures of bone mineral content and density. I hope I answered your question. Yep, that did. Thank you. Maybe a quick follow-up, if I could. The PRO you said might be ready in Q3. Do you anticipate, you know, needing it for an FDA meeting before that? Are you... If kind of maybe walk us through, you know, that timing relative to the FDA or regulatory updates. Thanks. Okay. That's I think that one's directed to me again. This is Kurt Gunter. Yeah. We are having ongoing interactions with the FDA and the EMA. Since it's an open label trial, as data become available, we can share that information. We found the regulators to be quite interested in our product and receptive to new data as we share them. Definitely we'll be sharing PRO data as well as any other data that we develop. Okay. Thank you. Our next question will come from Eun Yang with Jefferies. Please go ahead. Hi. Good morning, congratulations on the data. I have three questions, first question is for Dr. Levine. For the ENPP1 deficiency, especially in infants, how soon do you think that those infants after birth need to be treated to have the mortality benefit? Of the incidence rate, out of 64,000 pregnancy, from your experience in the clinic, what percentage of those can be diagnosed before the six-month critical period ends if the drug is approved in a few years from now? I have follow-up. Thank you. Super. Thanks very much for your question. I think we probably, by a combination of clinical findings and genetic testing, in suspected cases, can diagnose, you know, close to 100% of cases by six months of age. In the pedigree I showed, you know, there were extensive fetal losses and other infants who were affected clinically, that raised significant suspicion of GACI. In terms of how quickly the diagnosis can be made using genetic testing, within one week, certainly at this point with the Rady whole exome sequencing platform. I would say that the best outcomes would be in babies that were treated within the first two weeks. We certainly see six months as the critical period of time. The disease is progressive most aggressively during that interval. As early as we can institute treatment, you know, it would be best. Certainly we would like to see treatment within the first two to four weeks. I see. That's really helpful. Thank you. For the team, for the pivotal trial for ENPP1 deficiency program that is starting the third quarter, are you gonna be including infants or is it gonna be just in pediatric patients? Thank you for the question, Suji. I'll hand it over to Kurt for that. Sure. Thank you for the question. As I mentioned, we have, and as Sanjay mentioned, we have ongoing interactions with the FDA. We do want to focus on pediatrics in our pivotal study. We, as I mentioned in my talk, we want to incorporate different types of endpoints, both intermediate and definitive clinical outcome measures, as well as PPI in both an infant and a pediatric study. We're having those discussions with the FDA now. We haven't reached full resolution on that. We're planning to do studies in both types of patients, but I can't really speak to which one is going to start first at this time. I see. My last question is about the PXE data. It looks like some patients in cohort three, I'm looking at the scatter plot. It looks like some patients didn't have increase in PPI level. I'm just wondering why that might be the case. Okay, Yves, can you take that question, please? Yeah. Thank you. Thank you, Suji, for your question. The response, the way it's plotted, those are scatter plots, is you're seeing earlier time points and later time points. You're seeing the rise in PPI as they're going up. This is from day 32 to 168, I think you're probably asking, and these are just the first few time points, and then we will have more consistency. Based on their baseline levels, there is an increase in PPI because there is a range in the baseline levels in these patients. I see. Great. Thank you. Our next question will come from Ed White with H.C. Wainwright. Please go ahead. Good morning. Congratulations on the data. Most of my questions have been asked and answered, but maybe I could start with a follow-up to an earlier question. When can we expect the GIC data from ABCC6, you know, when could that be released? Will that be at a medical meeting, or are you just kind of planning on doing a press release or perhaps including it in a quarterly results issuance? Morning, Ed. Axel here. As we had already alluded earlier, I think the, you know, the ABCC6 trial is tracking 2 months, you know, behind the ENPP1 trial. As Kurt has explained, our goal is really to have data from all 3 cohorts. Obviously, as you can appreciate, as we've seen these nice results in the 3rd cohort in ABCC6, we want to make sure to catch, you know, the data on GIC on the 3rd cohort as well. I don't think we're far away from it. You know, during the next 2 months, quarter or 2, we expect to have these data. The forum, we haven't really decided yet, whether we use a meeting or a press release or a call. You know, that's something we're thinking about, but obviously, want to find the best way to get that important information out there. Okay, great. Thanks. You had said you'd expect a commercial launch in 2026. How are you thinking right now about which patient population will that be? Are you looking at several patient populations, or do you expect to have due to staggered trials and results, a staggered launch for the different, you know, age groups? We believe that it will be very important to cover all age groups. Our goal is certainly, to get, you know, the infants all the way to the adults. And we are building our program, you know, our, you know, late-stage trials accordingly. Yeah, I would say. Anything to add, Henrik, or no? I think that answers it. Great. Thanks for taking my questions. Okay. Again, if you have a question, please press star then one to join our queue. This will conclude our question and answer session. I would like to turn the conference back over to Axel Bolte, Chief Executive Officer. Thank you very much to all participants in this morning's event. We're certainly very excited about, you know, what we heard, and we look forward to remaining in touch and updating you on our further progress on our program. Thank you.