Good morning, and welcome to the Inozyme Pharma Interim Update Call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing star then zero on your telephone keypad. After today's presentation, there will be an opportunity to ask questions. To ask questions... To ask a question, you may press star then one on your telephone keypad. To withdraw your question, please press star then two. Please note, this event is being recorded. I would now like to turn the conference over to Stefan Riley, Director of Investor Relations. Please go ahead. Good morning, and thank you for joining us for the review of new interim data from our ongoing phase I/II clinical trials of INZ-701 in adults with ENPP1 and ABCC6 deficiencies. Today's remarks will be followed by a question-and-answer session with the management team. 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 conference over to Doug Treco, Chief Executive Officer and Chairman of the Board of Directors of Inozyme Pharma. Please go ahead. Thanks, Stefan, and thanks everyone online for being with us today. I'm joined here for this presentation by Kurt Gunter, our Chief Medical Officer, Yves Sabbagh, our Chief Scientific Officer, and Sanjay Subramanian, our CFO. At Inozyme, we're developing INZ-701, an enzyme replacement therapy for patients with genetic deficiencies of ENPP1 and ABCC6. In February, we presented interim safety pharmacokinetic and pharmacodynamic data from our phase I/II studies of INZ-701 in adult patients with these deficiencies, along with a preliminary patient-reported outcome assessment in the study of ENPP1 deficient adults. At that time, we showed that INZ-701 treatment resulted in rapid, significant, and sustained increases in pyrophosphate or PPi, and exhibited a favorable safety profile. Today, we're really excited to expand on that data and present additional long-term information on the safety, PK and PD from both studies, along with some detailed information on the potential efficacy of INZ-701 in patients with ENPP1 Deficiency. We'll also provide an update on the ABCC6 trial and provide some information on patient-reported outcome in that study. Patients with ENPP1 Deficiency present with very different symptoms, depending on their age. Babies are often born with vascular tissue calcification that impact cardiovascular function, with 50% dying within 6 months due to heart failure. Children who survive the first 6 months or who may have, have less severe symptoms at birth, will nearly uniformly present with rickets, an often severe bone abnormality that's characterized by bowed legs, soft bones and fractures, stunted growth, and bone pain, resulting in physical disability. Adults will present with permanent bone abnormalities that develop during childhood, along with soft bones and fractures and joint bone pain, again, resulting in mobility defects and physical disability. Children and adults may also experience progressive hearing loss. Based on the different symptoms observed in these different age groups, each population requires to be studied in a different clinical trial, with endpoints assessing the most important symptoms in each group. There's currently no approved therapy for ENPP1 Deficiency. As noted here, we estimate there are approximately 10,000 patients in the key markets of North America, Europe, Japan, and Brazil. Nearly one-third of the population is comprised of infants and children. We believe ENPP1 Deficiency is a severe unmet need and a substantial market opportunity. We've begun a study of INZ-701 in infants in the U.S., and we expect to begin dosing children aged 1 to less than 13 years old in a pivotal study next month. Today, we'll discuss our study in adults with ENPP1 Deficiency. Now, shown here is the design of our study in adult patients. The primary objectives of the study were to evaluate the safety, tolerability, immunogenicity, PK, and PD, as measured by change in pyrophosphate. The secondary goals were to evaluate potential endpoints appropriate for patients with ENPP1 Deficiency, to inform a future pivotal study and include exploratory biomarkers, ectopic calcification, skeletal pathology, vascular and physical function, as well as patient-reported outcomes. The study employed a dose-escalating design across three dose cohorts, where 3 patients each received 0.2, 0.6, or 1.8 milligrams per kilogram of INZ-701 via subQ injection. Patients received a single dose and then began a twice-a-week dosing 1 week later to collect PK data over a wide initial interval. There were limited subject selection criteria, but subjects were required to have documentation of biallelic ENPP1 mutations and a low pyrophosphate at screening. Patients were required to discontinue use of phosphate and active vitamin D prior to entering the study. Following a 32-day phase I portion of the study, patients could elect to enter a phase II extension for a minimum of 48 weeks. We're happy to report that all study goals have been met with regard to safety and immunogenicity and detailed characterization of the PK and PD profiles. Plasma pyrophosphate levels, which will serve as a primary endpoint in our planned pivotal studies, remained elevated for up to 18 months after initiating treatment, supporting long-term use in patients.... We've also identified potential outcome measures that we expect will inform future studies in adults and support the use of INZ-701 in infants and children, and our team will later describe the potential benefits of INZ-701 in adult patients. I'll now turn the presentation over to Kurt Gunter, our Chief Medical Officer, who will discuss the safety and tolerability of INZ-701 in ENPP1 deficient adults. Kurt? Thank you, Doug. Before we turn to the study data, I would like to begin by reviewing the patient demographics. The patients who enrolled reflected the spectrum of adult patients presenting with ENPP1 Deficiency. Patient ages ranged from 22-58 years, and the population included 6 female and 3 male patients. 5 of the patients reported a history of generalized arterial calcification of infancy, or GACI, and 4 of the patients reported onset of autosomal hypophosphatemic rickets, rickets type two, or ARHR2, later in life. Cohort 2 was skewed toward older patients and greater baseline physical impairment, as will be shown on the next slide. Based on past medical history and baseline data, the patients had a heavy lifetime disease burden. Each patient had a unique ENPP1 mutant genotype, reflecting the heterogeneity of the subjects. As expected, the most common past or current medical conditions at baseline were rickets or osteomalacia, followed by cardiovascular disease, arterial calcification or stenosis, GACI, and soft tissue or joint calcification. Interestingly, four of the patients reported arthritis or polyarthralgia at baseline, which is a finding we have also observed in X-rays in our natural history studies. All the patients had lower than predicted six-minute walk tests at baseline, with cohort two the most severely impaired. We assessed baseline health status using the Patient-Reported Outcomes Measurement Information System, or PROMIS, which demonstrated pain levels greater than observed in the patient general population. INZ-701 demonstrated a favorable safety profile, which was one of the primary goals of the study. Much of this information was presented in February, and we have not seen any safety signals since that time. 3 patients experienced mild adverse events related to INZ-701, and injection site reactions occurred in 2 of the patients. Other related adverse events observed were decreased appetite and fatigue. There were 2 serious adverse events, but they were not related to INZ-701. No patients withdrew from the phase 1 portion of the study, although 2 patients withdrew from phase 2, but not due to adverse events. 7 patients continue on INZ-701 for up to 638 days and are ongoing. All 7 of these patients remaining on study have transitioned to home self-administration. 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. We measured anti-drug antibodies, or ADA, based on dilution titers, with higher titer levels reflecting greater ADA concentration. In this figure, we are showing the ADA results for each patient by cohort in rows over time on the horizontal axis. Low ADA titers were detected but were not neutralizing, as there was no effect on PK or PPi levels. 7 of the 9 patients had detectable ADA, and the highest titers in individual patients ranged from 40-160. There was no evidence of a relationship between dose and ADA titer. There is evidence of waning of the immune response, since 3 patients with ADA titers ranging from 40-80 had no detectable ADA at last follow-up. These ADA titers are much lower than those observed with some other approved enzyme replacement therapies, as shown here. In conclusion, although ADAs were observed, they had no apparent clinical impact. Now I would like to hand the presentation over to Yves, who will present the PPi and biomarker data. Thank you, Kurt. Here, I will be showing you the PPi levels using our validated assay. We have previously shown that patients start with very low levels of PPi at baseline, as represented by the red symbol. As we noted in February, INZ-701 was able to increase plasma PPi within 6 hours after the initial dose, and the plasma PPi rose into the normal range. We are very pleased to report long-term and sustained elevation in PPi through week 48 for the first two cohorts and for at least 36 weeks in the highest dose cohort with twice-a-week dosing. I'd like to provide you with some scientific background on the key biomarkers we will be discussing. It is well established that low levels of PPi drive vascular calcification. This leads to a compensatory increase in FGF23, a key regulator of phosphate in the body, which is mainly expressed in the osteocytes in the bone. The rise of FGF23, which leads to phosphate wasting through the kidney, driving the hypophosphatemia observed, does not, however, prevent vascular calcification, but instead leads to the skeletal abnormalities such as rickets observed in children and osteomalacia in adults. It is important to note that decreasing FGF23 alone in ENPP1 Deficiency is not sufficient to address the clinical pathology and can exacerbate calcification, as an increase in PPi is also required. The use of burosumab, therefore, is contraindicated in the ENPP1 Deficiency, as it has been shown in case reports to lead to worsening of calcification in the aortic valve. Based on the role of FGF23 in bone disease, we therefore looked at the effect of raising PPi on this key mineral metabolism pathway. As we saw similar increases in PPi in our cohorts, we combined the data to measure the impact of this increase in FGF23 and phosphate, shown as Pi. As shown here, the significant and rapid increase in plasma PPi from baseline was associated with a decrease in FGF23 and an increase in serum phosphate, supporting the correction of the PPi to phosphate ratio as a key mechanism of action. Notably, the serum phosphate increases observed were seen in the absence of phosphate and active vitamin D supplementation. As we've noted previously, PPi levels increased within the first week and plateaued after long-term treatment with INZ-701. We therefore performed a correlation analysis to assess the relationship between PPi and FGF 23 levels at one week after dosing, when PPi levels were still increasing. Notably, the initial rapid increase in PPi was significantly correlated with a decrease in FGF 23 level, supporting the potential benefit in rickets and osteomalacia. Now, I would like to turn to an important biomarker that has a key role in bone mineralization, bone-specific alkaline phosphatase, or BSAP. BSAP, which is expressed in the bone, hydrolyzes PPi and increases local phosphate concentration for deposition in the matrix to maintain proper mineralization, as shown in the upper micrograph. While in the setting of hypophosphatemia, we see more undermineralized bone matrix, as shown in red in the lower panel, when compared to a healthy bone, where little to no red staining around the bone is present. As you can see on the graph on the right, at the earliest time points, we observed an increase in BSAP with INZ-701 treatment, rising at 12 weeks post-treatment in the two higher dose cohorts. This was followed by a decrease. A similar pattern of response is observed with other known treatments of rickets, such as those for X-linked hypophosphatemic rickets or vitamin D-deficient rickets. I'll now turn the presentation over to Kurt Gunter, who will discuss some of the clinical observations supporting the potential benefit of INZ-701 in patients with ENPP1 Deficiency. Kurt? Thank you, Yves. The first outcome I would like to discuss was measured using the Global Impression of Change, or GIC. 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. As shown on the bottom of the slide, the GIC is a 7-point scale rating the patient's overall, overall health, ranging from -3 to +3, with a score of +3 being very much improved. At each visit, both the patient and the clinician are asked to rate the patient's health compared to baseline using the GIC scale. Here, we have plotted the 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. In the clinical assessment, 7 of 8 evaluable patients improved, and in the patient assessment, 8 of 9 patients improved their overall health relative to baseline. Consistent with our data showing favorable changes in PPi, FGF23, and phosphate, patients in all cohorts showed the improvements in GIC scores, and improvements appear to be sustained throughout the study. No patient showed a deterioration of health, and that no negative GIC score was recorded. Importantly, both the clinician and patient independently assigned very similar GIC scores, providing further validation of the clinical outcomes revealed in this trial. To further understand the impact of INZ-701 on these patients, we employed the PROMIS system. PROMIS was developed through an NIH project to validate patient-reported outcomes for clinical research. PROMIS measures have been developed and validated with state-of-the-science methods to be psychometrically sound and to transform how life domains are measured. We utilized the PROMIS domains focusing on pain intensity, pain interference, and fatigue, and assessed patient outcomes periodically during the study. The pain intensity and fatigue domains are self-explanatory. The pain interference domain measures the self-reported consequences of pain on relevant aspects of a person's life, such as the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities.... Using all the available data, we conducted a responder analysis, where we defined responders as patients who reported improvement at greater than 50% of the time points evaluated. Overall, the majority of patients were responders across all three domains. When evaluated by cohort, the majority of patients were also responders across all domains. We also evaluated patient outcomes using a six-minute walk test. The six-minute walk test is a quantitative and objective performance measure used to assess functional capacity in a variety of diseases, and which has been used to support the approval of several drugs as an efficacy outcome measure. We collected the six-minute walk test data in meters and converted those absolute values to normalized values, in which subject age, gender, height, and weight were taken into account using a standard published method. The resulting values are presented as a% predicted of normal. As you can see in this slide, we observed a trend for improvement in the six-minute walk test during the study. The improvement in cohort two is most pronounced, as those patients had a large increase in their walk test results. It is noteworthy that the mean baseline six-minute walk test results varied across the cohorts, again, reflecting the heterogeneity of mean baseline impairment among the sub cohorts. To address this variability in baseline impairment, we performed a subset analysis, which I will discuss in the next slide. In this subset analysis, we divided patients into two groups: those with a low six-minute walk test at baseline and those with a six-minute walk test closer to normal at baseline. Here, we are showing both the% predicted abnormal result in blue and the absolute meters walked in orange. As you can see, the participants with the lower six-minute walk test at baseline had a much greater improvement compared to the participants who were greater than 70% of predicted normal at baseline. Patients with better baseline six-minute walk test showed no evidence of decline in performance. These data confirm that the unselected patient population for this study was heterogeneous and imply that it may be desirable to enrich for patients with a greater degree of physical impairment at baseline in future clinical trials. We also assessed how the six-minute walk test subset groups performed on the PROMIS PRO. As expected, the majority of participants with low baseline walk test results improved with follow-up, while only half of the patients who were closer to normal at baseline demonstrated improvement on the walk test. We also found that participants with low baseline walk test results were more likely to be responders on the PROMIS PRO compared to patients with superior baseline walk test performance. These data corroborate the other subset analysis and suggest that patients with more severe disease may be more likely to benefit from INZ-701. As mentioned earlier, 4 participants reported a history of either frank arthritis or polyarthralgia at baseline, which is consistent with preliminary findings from the radiological exams of our natural history studies. Thinking this could be an important group of patients for future study, we conducted a subset analysis on patients with or without arthritis and arthralgia. We found that all participants with arthritis or arthralgia improved on the six-minute walk test, compared to only 40% of those who did not have arthritis and arthralgia. We also conducted DEXA scans to measure bone mineral density, or BMD, and bone mineral content, or BMC. We have limited data on BMD and BMC at this point in the study, but we're able to analyze changes in these parameters in 5 participants, 3 with arthritis or arthralgia and 2 without. Based on increases in spine BMC and BMD, there was a higher responder rate in the participants with arthritis or arthralgia at baseline. This analysis suggests that patients with evidence of arthritis or arthralgia may have a better response to INZ-701. Although the data as presented so far are compelling, we would like to present two case studies to illustrate the profound impact that INZ-701 treatment had on study participants. The first patient suffered from a substantial disease burden, which included ARHR2, polyarthralgia, multiple orthopedic surgeries, and aortic valve replacement. PPi increased dramatically, as it did in all participants, and translated to the clinical improvements noted here. There was good improvement in both the GIC and PROMIS PROs. This participant was 40% as predicted in the six-minute walk test at baseline and improved dramatically with follow-up. An increase in spine BMD and BMC was also documented by DEXA. The second patient also had a substantial disease burden, suffering from GACI, rickets with leg bowing, delayed growth, and osteoarthritis. As in the previous participant, PPi increased dramatically, corresponding to the clinical improvements noted here... There was a general improvement in the GIC and PROMIS PRO outcome. This patient also had a very low six-minute walk test of 64% of normal at baseline, which dramatically improved with INZ-701 therapy. An increase in spine BMD and BMC was seen by DEXA. These are only two illustrative examples that demonstrate the therapeutic benefit of INZ-701. Overall, the clinical data from the GIC, PROMIS, and six-minute walk test, as well as these case study vignettes, support the conclusion that the rapid and sustained increase in PPi observed with INZ-701 translated into clinical benefit across all patient cohorts. And now, I'll turn the presentation back to Doug. Thanks, Kurt. As you've seen, we learned a lot and got a lot of great data from this first study in man of INZ-701 in ENPP1 Deficiency. As I said at the start of the presentation, we believe the study met all the study goals. The drug was well-tolerated with low immunogenicity, and the favorable safety profile supports studies in infants and children. The half-life of 126 hours supports a convenient weekly administration. Pyrophosphate remains significantly elevated for over 18 months and was associated with appropriate changes in phosphate and FGF23, which support the clinical hypothesis. Finally, we've observed functional improvements in the six-minute walk test, along with patient-reported outcomes. Although we've not discussed it today, we've identified locations of bone pathology that may be most useful for radiographic scoring. These clinical observations will be critical for defining endpoints and inclusion criteria for a future study in adults. Now, I'd like to move to a brief update on the study of INZ-701 in adult patients with ABCC6 Deficiency. This phase 1/2 trial design in ABCC6-deficient patients mirrored that of the previously described trial in the ENPP1 Deficiency. There were limited subset selection criteria, but subjects were required to have clinical evidence of pseudoxanthoma elasticum, or PXE, documentation of biallelic ABCC6 mutations, and a low PPi at screening. The primary objectives of the study were to evaluate the safety, tolerability, immunogenicity, PK, and PD of INZ-701. The secondary goal was to evaluate potential endpoints for a future pivotal study. Clinical outcome measures appropriate for PXE were included as exploratory objectives. The study is now fully enrolled, and I will now turn the presentation back to Kurt, who will be presenting updated results from the study. Thank you, Doug. INZ-701 demonstrated a favorable safety profile in PXE participants. All 10 patients experienced at least one adverse event, and all adverse events were mild or moderate in severity. Seven of the 10 participants experienced adverse events related to INZ-701, which were mild to moderate. These events were predominantly injection site reactions consisting of discoloration, discomfort, erythema, induration, pain, pruritus, or warmth, which occurred in seven of the 10 participants and were all mild. Other related adverse events were mild to moderate and included fatigue, night sweats, and urticaria. There were no serious or severe adverse events. One moderate adverse event, consisting of urticaria and erythema, led to the withdrawal of one participant from the 1.8 mg/kg cohort during phase 1. Eight participants continue on INZ-701, with the longest treatment now at 518 days and ongoing. Seven of the eight patients remaining on study have now transitioned to home self-administration. In conclusion, the safety profile of INZ-701 in adult patients with ABCC6 Deficiency is favorable. As in the ENPP1 study, we observed a favorable immunogenicity profile in adults with ABCC6 Deficiency. Low ADA titers were detected but were not neutralizing, as there was no effect on PK or PPi levels. Eight of the 10 participants had detectable ADA, and the titers ranged from less than 40 to 2,560. There is evidence of waning of the immune response to INZ-701, as three participants with ADA titers ranging from less than 40 to 40 had no detectable ADA at last follow-up. Notably, the participant who withdrew from phase 1 due to urticaria and erythema had no detectable ADA. The ADA titers are generally much lower than those observed with some other approved enzyme replacement therapies, as shown here. In conclusion, although ADAs were observed, they had no apparent clinical impact. Moving on to the pharmacodynamic analysis. As we noted in February, at 1.8 mg/kg twice weekly, INZ-701 was able to increase plasma PPi into the normal range. We now show that these levels remain sustained through week 36, which supports the long-term use in these patients. Finally, I am pleased to share the initial emerging clinical data from our trial in adults with ABCC6 Deficiency that links the change in PPi with important clinical outcomes. We used the GIC scale as described in the ENPP1 study. Here, we have plotted the individual GIC scores across the 3 dose cohorts, with the clinician's assessment in the top half of the slide and the participant's GIC assessment in the bottom half. In the clinical assessment, 9 of 9 patients improved, and in the participant assessment, 7 of 9 patients improved their overall health relative to baseline. Improvements in GIC appeared to be sustained throughout the study. Only 2 patients showed a decline, and these were rated as minimal. Together, these exciting data support a direct link between the increase of PPi levels and improved GIC scores in adults with ABCC6 Deficiency treated with INZ-701. Now I will ask Doug to provide some concluding remarks. Thanks, Kurt. As we saw with our ENPP1 study, the data to date from the clinical study of INZ-701 in ABCC6 patients met all of our study goals. The drug was generally well tolerated, with a favorable immunogenicity profile. The PK and PD data show the drug activity is maintained over time with a rapid increase in PPi, which was most sustained in the highest dose cohort. Analysis of the patient-reported outcome data to date show improvement in the vast majority of patients and was concordant between the patient and physician assessment. So overall, we're really pleased with the safety and immunogenicity profile of INZ-701 in patients with both ENPP1 and ABCC6 deficiencies. The ENPP1 study data showed a significant elevation of PPi maintained in all dose cohorts, with the increase in PPi linked to changes in the key biomarkers FGF23 and phosphate, providing support for potential benefit in rickets and osteomalacia and for our pivotal trial in pediatric patients, which we expect to initiate next month. We've also shown clinically meaningful outcomes that will inform the design of a pivotal study in adults. The ABCC6 study data showed a elevation of PPi maintained for over nine months in the highest dose cohort, with initial patient-reported outcome data suggesting potential clinical benefit. We expect that the current results in top-line study data, which is planned for first quarter of 2024, will inform the design of a pivotal study in adults. We look forward to presenting that data early next year. Data from both studies, that we presented today, will be presented at ASBMR in Vancouver next month. And finally, the safety data, along with the pronounced effects on bone markers, support the potential role of INZ-701 to address other disorders of pathologic mineralization and neointimal proliferation. And with that, I will conclude today's presentation and open up the line for questions. We will now begin the question-and-answer session. To ask a question, you may press star then one on your telephone keypad. If you're using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. The first question comes from Tazeen Ahmad with Bank of America. Please go ahead. Hi, good morning, and congrats on the positive data update. I wanted to ask a couple of questions. Firstly, on CC6, you have some initial data here. We're expecting to see more over time, but as it relates to using pyrophosphate as at least a potential co-primary endpoint, what are your thoughts on that? Because being able to use pyrophosphate for PP1 was heavily de-risking in our view, and we wanted to get a sense of how you're thinking about CC6. And then secondly, can you just remind us about what you think the number of patients are for both PP1 and CC6, just based on your updated market data analysis? Thanks. Yeah, this is Doug. I'll let Kurt take that, the first part of that question. Sure. Thanks for the question. Yes, just to take a step back, we're, you know, very pleased that with our ENPP1 program, regulators have accepted in the US PPi as a primary endpoint. But, you know, your question was about ABCC6. And there, you know, we think the next study will need to include clinically meaningful outcome measures as well as PPi, and that will have to be discussed with regulators in the future. I think, Tahseen, your second question was related to the market opportunity for both of these. We have Matt Winton, our COO, here, and I'll let him answer that. Sure. Hi, Tahseen. Thank you for the question. So, as we mentioned in the presentation, the patient population, at least in the markets that we are focused on, so sort of a conservative effort within North America, Brazil, Europe and Japan, is about 10,000 patients, with a global genetic prevalence of 1 in 64,000. When we move to ABCC6, we see a higher prevalence in around 1-25,000, so about 1-50,000 patients. Yeah. So maybe to follow up on that, how long do you think it'll take for you to really be able to identify those patients, in a real-world setting? Is it gonna take, you know, the drug to launch, and then you'll still be identifying patients? We're just trying to get a sense of what the opportunity might be like at the time that you launch and understanding that it would grow from there. ... Yeah, first of all, I think we're sort of out there covering the world now, looking for patients, and we've done, you know, in my view, a remarkable job building up our database into the, you know, over 500 patients, as well as another couple hundred that have been identified, that where we don't know the names of those patients. I think that every rare disease that's come before us has kind of followed the same trajectory, without a lot of education, without a drug out there, without really efficient diagnosis. A lot of patients don't get diagnosed, and we don't really know the true numbers. You know, as we move closer to launch and as we build the database, you know, patients will emerge looking for help because they know this drug is out there. I think if you look at, you know, as I said, if you look at every other rare disease out there, I think having, you know, in excess, or, you know, identified over 800 patients now, is pretty remarkable for this stage of the game. Yes, we will continue to find patients. As we move closer, we'll find patients after we launch. And, you know, we expect that, you know, we'll have a registry in, you know, a few years from now with probably several thousand patients in it and growing. So, I think this is really kind of the way, you know, all the rare disease drugs have worked in the past, and we're no different. But we're out there now, you know, getting the message out that there's a drug, there's diagnosis, and there's trials upcoming to enroll patients in. Okay. Thank you. The next question comes from Marc Frahm with TD Cowen. Please go ahead. Thanks for taking my question, and congrats on the data. So as you said, you know, the PPi levels changing in ENPP1, and that, you know, you're starting to see that translate over time into some of these more clinically hard clinical endpoints for the ENPP1 patients. Maybe turning to ABCC6, right? You're also seeing PPi increases, but maybe not quite to the same magnitude as in ENPP1. Like, how does that inform what level of change you think you might actually be able to see on these clinical endpoints as the, you know, the small data set you're going to gather matures over the next, you know, few months into next year? Yeah, I will let Yves answer that question. Yeah. So it is a good point you're making. The magnitude of change is going to be different because the baseline levels of the patients in ABCC6 also start at a higher level. So, but we are reaching the at the higher dose in the normal range, as shown in our graph. Now, one thing to point is we cannot push PPi too high up because the body also has a protective mechanism, which is driven by alkaline phosphatase, which will be able to maintain the proper homeostatic level of PPi in the normal range and not get pathological, because the main substrate of alkaline phosphatase is pyrophosphate, which will hydrolyze it to inorganic phosphate. So this is why there is a certain threshold that you cannot break through into the PPi. In terms of translating into clinical benefit, I think with the early, with the data we just showed, with the GIC data, it shows that the increase in PPi is showing some benefit. And once we report the further longer-term data with our other endpoints that we describe for ABCC6 in the 48 weeks, we will be evaluating other clinically meaningful endpoints. Yeah, and I'll also add that, you know, we have a lot of preclinical data on an animal model of ABCC6. And, you know, as you're aware, we're not giving patients with ABCC6 back the enzyme that they're missing. We're giving them the ENPP-1 enzyme. And so the clinical hypothesis is that we can take advantage of what other ATP is there, scavenge that, and ENPP-1 can use that, or sorry, INZ-701 that we administer can use that ATP. And so the benefits that we've seen in animals really de-risk this and show that this enzyme replacement therapy can work in the ABCC6 setting. You know, as we noted, pyrophosphate may not be the best endpoint. The results, you know, as it rolls out in the first quarter, as we look at that data, I think we'll find, you know, what those clinical endpoints might be to support PPi in the next study. But the animal model, I think, clearly shows that the hypothesis that INZ-701 can work in this disease is appropriate, and we expect the data to provide more information on how to conduct the next study. Okay. That, that's very helpful. And then maybe back to ENPP1 deficiency. Today, you were showing those BSAP changes, and, you know, that's kind of a leading indicator to what might happen on things like rickets score. Can you put that magnitude of change also in the BSAP into the context of what's seen with XLH therapies or, or other vitamin D rickets-dependent rickets? And just kind of how, how quickly that would potentially translate into a GIC benefit, you know, certainly since that's an important endpoint for you going forward with the adolescent trial. Great. Thanks. Yves, you want to take that question? Sure. Yeah. So if you compare to the effect of the increase in BSAP on what was observed with the other treatment, we are in the same magnitude of change that we observed, especially in XLH. There was a recent paper by Weber et al. showing the long-term effect of burosumab in XLH. And you can see that the first time point they show, I think, is 24 weeks, where you see this increase, and then it goes back down. And this is also due to the dynamic nature of the bone. In terms of how it translates to, will translate eventually to rickets, it will translate, and it will probably, you will see a very robust effect because the bone is more dynamic in children as they are actively growing and forming their bone. So you will see even a potentially stronger effect than what we saw in the adult patient population. Good. Thank you, and congrats again. Thanks. Again, to ask a question, please press star then one. Again, if you're using a speakerphone, please pick up your handset before pressing the keys. The next question comes from Chris Raymond with Piper Sandler. Please go ahead. Good morning, and congrats on the update. This is Nicole Gabreski on for Chris. Thanks for taking the question. So one, just I know in your ENPP1 study, you're also looking at a fourth cohort, for once-weekly dosing. I guess, is there any clarity there around when we could see an update from that cohort? And then, just a second question, maybe around safety. Injection site reactions seem to be a little more frequent in the ABCC6 deficiency patients. I guess, is there any underlying reason for that? And, also sorry if I missed it, but I guess, is there any just additional color that you could maybe provide around the severity of these injection site, reactions? Great. I'll take the first part of that question, which was around the fourth cohort. That cohort, you know, we started that well after the study initiated. It was really designed just to confirm that a weekly injection schedule would conform to the PK model that we developed. I can tell you that the data that we have, you know, shows that, you know, everything we expected is correct. We'll put that data out. It just wasn't mature right now with the full cohort. But the data we've collected early on confirmed the hypothesis. That data will be shown probably, you know, in the first quarter of next year, along with some of the ABCC6 update. In terms of injection site reactions, I'll let Kurt take that question. Okay, thank you, Doug, and thanks for the question. I think it's important to point out that, all the injection site reactions we've seen in both studies have been mild, i.e., grade 1. So we're not too concerned about it. And from talking to investigators, they don't seem too concerned about the injection site reactions. It is true that in the 201 study, there have been more patients who have reported injection site reactions compared to the 101 study. We think it's probably too early in the game to make any conclusions, draw conclusions about the frequency of injection site reactions in one disease state versus another. But as the data mature, we'll be able to have a better view on that in the future. Great. Thank you so much. The next question comes from David Nierengarten with Wedbush Securities. Please go ahead. Hey, thanks for taking the question. I had one on the patients who discontinued. Were they, you know, experiencing less benefit? Or to put it another way, were they maybe, you know, having a milder disease manifestation and they didn't, you know, feel personally that they improved enough, or was there any other reason? If you could give any color on that. Thanks. Great. Thanks, David. Kurt, you want to take that question? Sure, I can, I can take that question. Thank you for that one. And, yes, it's true. We've had a couple withdrawals from our studies, but none of them were related to adverse events. These studies are, you know, fairly onerous for the patients. They require them basically to remain hospitalized for the first month. And then, you know, they're coming from all over the world, in many cases, taking long journeys to get to the clinical trial site. Now, we've decided that, in the interest of patient privacy, we're not going to get into the details of why specific patients withdrew from the study. But I'll just emphasize again, nobody's had to drop out due to an adverse event. Okay. Thank you. Excuse me, at this time, this concludes our question and answer session. I would like to turn the conference back over to Douglas Treco for any closing remarks. Thanks very much. Thanks, everybody, for attending, and the event has now concluded. The conference again has now concluded. You may now disconnect your line. Thank you.