Hello, welcome to the Applied Therapeutics Galactosemia Program Conference 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 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 Dr. Shoshana Shendelman, Applied Therapeutics' Founder and CEO. Please go ahead. Welcome, everyone, and thank you for joining us on today's call. With me on the call are Dr. Riccardo Perfetti, our Chief Medical Officer, and Adam Hansard, our Chief Commercial Officer. Before we begin, let me remind you that during today's conference call, we will be making forward-looking statements that represent the company's intentions, expectations, or beliefs concerning future events. These forward-looking statements are qualified by important factors set forth in today's press release and the company's filings with the SEC, which could cause actual results to differ materially from those in such forward-looking statements. Information discussed on today's call is accurate as of today, and we do not intend to update unless required by law. We'll start off the call with our prepared remarks and slides, and we'll follow up with an open question and answer period. To provide background for investors, I'll start with a quick overview of Galactosemia, as well as the design of our pediatric study, ACTION-Galactosemia Kids, for which we'll be providing results today. Galactosemia is a rare genetic metabolic disease resulting in an inability to metabolize the simple sugar galactose. Galactose is found in foods but is also produced endogenously by the body. When not metabolized properly, galactose is converted to the toxic metabolite galactitol, which causes neurological complications, including deficiencies in speech, cognition, behavior, motor skills, and tremor, and also results in juvenile cataracts and ovarian insufficiency in women. There are approximately 3,000 patients with Galactosemia in the U.S. and 80 new births per year, and approximately 4,000 patients with Galactosemia in the E.U. and 120 new births per year. There are no drugs approved to date to treat Galactosemia. We have previously demonstrated a statistically significant reduction in plasma galactitol versus placebo in both adults and children with Galactosemia treated with AT-007, also now called Govorestat. Today, we're pleased to discuss the results of Govorestat treatment on long-term clinical outcomes in children with Galactosemia aged two to 17 in our ACTION-Galactosemia Kids AT-007-1002 clinical trial. The ACTION-Galactosemia Kids phase III study was designed to evaluate the impact of Govorestat treatment versus placebo on clinical outcomes over time in children aged two to seven with Classic Galactosemia. Clinical outcomes using several well-defined and validated clinical functional measures were performed at baseline prior to randomization and were performed every six months thereafter. The results of the clinical efficacy data and safety were reviewed at six-month intervals by an independent data monitoring committee. At six months, we reported that the drug was safe and well-tolerated. It was too early of a time point to see any efficacy benefit or separation between the Govorestat treated and placebo arms. At 12 months, we reported that Govorestat continued to be safe and well-tolerated and that a trend favoring Govorestat treatment versus placebo could be seen on clinical efficacy endpoints, which was not statistically significant at that time. Upon review of the 18-month efficacy data, the independent data monitoring committee suggested that in light of the clear clinical benefit demonstrated by Govorestat on many clinical outcome measures, the company should consider whether the study should continue in placebo-controlled format. The company reviewed the data and has decided to unblind the study. We are pleased today to report the 18-month clinical data publicly. Overall, Govorestat demonstrated a consistent long-term clinical outcomes benefit across a range of functional measures in the ACTION-Galactosemia Kids trial, confirming prior biomarker data. Govorestat treatment improved activities of daily living, behavior, cognition, fine motor skills, adaptive skills, and tremor versus placebo and was safe and well-tolerated. The primary endpoint of the study was a composite sum of change across multiple endpoints using a statistical methodology called the Global Statistical Test. Utilizing a sum of change across multiple different independent endpoints provides an advantage for statistical powering in rare diseases that affect many aspects of clinical function, such as Galactosemia. Briefly, the sum of change across the composite endpoints is added together using a standardized Z-score methodology and is averaged for the active treatment group and for the placebo-treated group to derive a mean sum of change in each cohort. A permutation analysis is performed to derive the potential for statistical randomness. This results in a stronger P value collectively than any of the individual endpoints of the composite might have on their own. In the ACTION-Galactosemia Kids study, the composite primary endpoint was composed of functional measures of speech, activities of daily living, behavior, cognition, and fine motor skills. Speech was measured via the OWLS-II Oral Expression and OWLS-II Listening Comprehension. Activities of daily living were measured by the Behavioral Assessment System for Children or BASC-3 test. Behavior was measured by the BASC-3 Behavioral Symptoms Index. Originally, the composite primary endpoint also included cognition as measured by NIH Toolbox Cognition Battery and fine motor skills as measured by Nine-Hole Peg Test. The company, however, recently received an advice letter from the FDA requesting that cognition and fine motor skills be removed from the primary endpoint. As a compromise, these two metrics were instead designated as pre-specified sensitivity analyses to the primary endpoint. Each component of the primary endpoint was also designated as an independent secondary endpoint, as well as other endpoints, including adaptive skills and tremor. Overall, treatment with Govorestat demonstrated consistent and sustained clinical benefit on activities of daily living, behavioral symptoms, cognition, adaptive behavior, and tremor. While statistical significance defined as a p value of less than 0.05 was not met on the primary endpoint, systemic improvement over time was demonstrated for the overall primary endpoint, with a p value at 18 months of p equals 0.1030. Similarly, for the pre-specified sensitivity analyses, the statistical separation of active versus placebo treatment strengthened over time from six to 12 to 18 months, with resulting p values at 18 months for the primary endpoint, including cognition of p = 0.0698 and the primary endpoint, including Nine-Hole Peg Test of p = 0.0937. Upon examining the effect of Govorestat versus placebo on each individual functional measure, as seen on slide seven of the presentation, it became apparent that while Govorestat treatment improved most aspects of the primary endpoint, including activities of daily living, behavior, cognition, and fine motor skills, Govorestat treatment was not positively impacting the speech endpoints. A closer examination of the data regarding speech endpoints demonstrated that both placebo and active treatment arms improved on speech over time, rather than the anticipated decline in the placebo group and stabilization or improvement in the active treatment arm. We believe this result may be due to a combination of contributing factors involving speech therapy. First, a baseline imbalance in patients receiving speech therapy existed, with more patients in the placebo group receiving speech therapy versus the active treatment arm. Many patients initiated speech therapy during the study, such that nearly all patients were receiving speech therapy as the trial progressed. This should be good news for patients and speech therapists that speech therapy helps these children which has already been published previously in multiple scientific journals. This did impact our ability to demonstrate a treatment effect of Govorestat on speech endpoints. A post-hoc analysis of the primary endpoint, including behavior and activities of daily living but excluding speech endpoints, demonstrated a highly statistically significant benefit of Govorestat versus placebo at 18 months, with a p value of 0.0205. Additionally, of note, in patients with severe speech impairments at baseline, Govorestat demonstrated a trend favoring active treatment versus placebo, suggesting that there are many patients who cannot fully benefit from speech therapy alone and require pharmacological intervention. In addition to improvement on the components of the primary endpoint, including activities of daily living, behavior, cognition, and fine motor skills, Govorestat provided a statistically significant improvement on tremor at 18 months, as measured by the Archimedes spiral test with a p value of 0.0428, and improvement in adaptive skills as measured by the BASC-3 Adaptive Skills Index with a p value of 0.0265. The results on each of the individual functional tasks can be found on slides eight through 12 of the deck. Briefly, with regard to activities of daily living, the placebo group declined over 18 months, while the Govorestat-treated group improved. The mean difference in T-score between Govorestat and placebo treatment at 18 months was 6.1, with a p value of 0.1045. With regard to behavioral symptoms, the placebo group declined substantially over 18 months, while the Govorestat-treated group was stabilized or did not worsen. The mean difference in T-score between Govorestat and placebo treatment at 18 months was 6.0, with a p value of 0.0519. With regard to cognition, both the active and placebo-treated groups showed a very mild improvement versus baseline at six months, which then remained stable, while the Govorestat-treated group improved more substantially, and improvement continued through 18 months. The mean difference in standard score between Govorestat and placebo treatment at 18 months on cognition was 4.1, with a p value of 0.2625. Perhaps the strongest individual test data demonstrating improvement with Govorestat was adaptive behavior, which declined quite substantially in the placebo arm, but improved in the Govorestat arm. The mean difference in T-score between Govorestat and placebo treatment at 18 months on adaptive behavior was 8.4, with a p value of 0.0265. Lastly, Govorestat treatment substantially improved tremor versus placebo with a mean difference in Archimedes spiral drawing test between Govorestat and placebo of 0.44, and a p value of 0.0428. Please note that tremor is scored on a different scale than the other tests, and it ranges from zero to four. Consistent with prior reported data, improvements in galactitol levels was sustained throughout the trial with no impact on Gal-1p or galactose, further establishing the causal role of galactitol in disease pathogenesis. I will now hand the call over to our Chief Medical Officer, Riccardo Perfetti, to discuss the safety findings. Thank you, Shoshana. Govorestat continued to be safe and well-tolerated in all age group. There were no treatment-related serious adverse events reported. All adverse events in the trial were mild to moderate, and adverse events, as well as lab values, were balanced between active treatment and placebo group. No serious and no severe adverse events were reported. Adverse events seen across the study were typical of those seen in any pediatric population, including gastrointestinal symptoms and viral infections, such as upper respiratory infections. These were all balanced between the active and placebo group. While ALT and AST elevation were seen in some patients, they were also always mild to moderate, asymptomatic, and reversible, with or without temporary treatment discontinuation. ALT and AST elevation were never associated with an increase in other liver enzyme and never associated with an increase in bilirubin level. While there were slightly more cases of ALT/AST elevation in the active treatment group, the opposite was seen with regard of elevation in urinary albumin-creatinine ratio, with higher incidence in the placebo group. Our belief is that the population as a whole demonstrates some abnormality and fluctuations in renal and hepatic function, perhaps related to the acute renal and liver failure often seen in the newborn phase prior diagnosis and dietary restriction. To date, this abnormality in the blood chemistry had not been seen in the phase III SOURCE study, and they appear to be specific to the Galactosemia population. The full study data will be submitted for presentation at an upcoming medical conference. The company believes that Govorestat treatment offers compelling evidence of clinical efficacy. It plans to move forward for registration of Govorestat for Galactosemia based on this data. The trial will be unblinded in the next few weeks, and placebo patients will be given the opportunity to receive active treatment. Patients who participate in the trial and were on Govorestat active treatment during the double-blind phase will be offered the ongoing Govorestat treatment under the existing Fast Track Designation Expanded Access Program, which is often referred as compassionate use. I would like to thank again the patients and caregivers who participated in the ACTION-Galactosemia Kids study, as well as the investigators in the trial, the members of the steering committee, and the members of the data monitoring committee. We could not have completed this seminal study without your help and support, and we extend our greatest appreciation. Now I'll turn it back to Shoshana. Thanks, Riccardo. In summary, we believe Govorestat has demonstrated compelling evidence of clinical benefit alongside a favorable safety profile in patients with Galactosemia. Improvement in clinical function with Govorestat on endpoints such as activities of daily living, behavior, cognition, and tremor are substantial and we believe represent a meaningful clinical benefit from both the physician and the caregiver perspective. We believe that this treatment will be transformative for the Galactosemia community. We look forward to working collaboratively with regulators to make this important treatment available to patients with Galactosemia as quickly as possible. We plan to request a pre-NDA meeting immediately with the FDA to discuss a potential NDA submission in the second half of 2023. We have already received feedback from the European Medicines Agency supportive of a submission in Europe. We plan to submit a Marketing Authorization Application or MAA with the EMA in mid-2023. Concurrent with the data this morning, we also announced a $30 million private placement led by Venrock. The proceeds from the private placement, in addition to our current cash on hand and potential milestones from the advanced European licensing partnership, are expected to fund the business through mid-2024, by which time we hope to have Govorestat approved and launched in both the U.S. and Europe. We'll now open up the line for questions. Operator, please go ahead. Thank you. 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 Colin Bristow with UBS. Please go ahead. Hey, good morning, congrats on both the data update and the financing. Two questions on my side. In terms of the speech therapy, could you speak to was there any sort of standardized component of this? Was there a correlation identified between the intensity of speech therapy and the performance that was observed on speech and language? In terms of your upcoming meeting with the agency, in prior meetings, was this type of sort of intermediary scenario discussed, and if so, what was the agency's position here? Thanks. Sure. Thanks very much, Colin. With regard to speech therapy, I think as people are aware with Galactosemia, there's two things right now that parents are able to do for this disease. They can be very careful and strict with the galactose-restricted diet, which only restricts external intake of galactose and does not stop the body from making galactose endogenously. The other thing that they can do is speech therapy with their children. You know, this is sort of the current standard of treatment in children. We found that, again, there was an imbalance at baseline between placebo and active treatment, with more children in the placebo group receiving speech therapy. We also believe that children receiving speech therapy did increase in their intensity throughout the trial as they figured out how to get more access to speech therapy. The number or percentage of children receiving speech therapy increased early in the trial as well. This is a confounding factor that we were unable to control for. I think what's important to note here is that a subgroup analysis of patients who had severe speech deficiencies at baseline did benefit from active treatment with Govorestat versus placebo. When we think about the severe patient population, really, speech therapy doesn't get them to where they need to be, and even with intensive speech therapy, they require pharmacological intervention. You know, our belief is that Govorestat does impact speech, but the measurements of speech within the context of the trial were confounded by imbalances and introduction of speech therapy to many of the children during the trial. I'm sorry, Colin, what was your regulatory question? Just in terms of prior discussions you've had with the agency, was, you know, what sort of theoretical intermediary scenarios where you missed the primary endpoint, but you know, there's clearly strong factors and trends? Yes. That indicate a benefit. Was this discussed? Yes. We have been having a discussion with the European Medicines Agency since last fall on the potential acceptance of an MAA based on even what we had at the time, which was trends in clinical benefit across these various outcomes. There was a very positive receipt of that data at the time, and we had been working over the last six months to advance our submission, and we're quite far along with that process. That was based, you know, upon data that was not even as good as what we're seeing today. We're really thrilled by this data. We feel confident that this supports an MAA approval in Europe. And we believe it will support an NDA approval in the U.S. as well, although the next step there is to meet with the FDA as soon as we can. The dialogue has been ongoing for quite some time in Europe, and they have been very receptive to the data that we even had before. We feel that the conviction there is only stronger with the data that we have today. We are on track for an MAA submission around mid-year this year and have received very positive feedback from the EMA. Great. Thank you. The next question comes from Brian Skorney with Baird. Please go ahead. Hey, good morning, everyone. Thanks for taking my question. The separation over time looks pretty good. I was wondering, can you just walk us through the number of patients with data at each time point? Do all 31 Govorestat and 16 placebo patients have evaluable data at six, 12, and 18 months? Kinda related to that, were there any discontinuations due to AEs or treatment interruptions on the study? Yeah. It's a great question. You're right, Brian, we enrolled 47 patients in this study. We did have a few patients withdraw consent within the first few months of the trial, not related to adverse events, but because it was too difficult for them to participate in the study with special needs children and traveling to and from the site. I believe it was t discontinuations due to withdrawal of consent in the placebo group, and three in the active group. The evaluable patients is 47 minus five, which is two patients. S orry, 42 patients, and that was at each time point thereafter. The withdrawals of consent, and removal from the study were very early on, such that they weren't captured in any of the time points that you're seeing at six, 12 or 18 months. Could you just walk us through what happened with the primary endpoint protocol change to exclude cognition in the analysis? What was the FDA justification for requesting that protocol change and what was the timing again on that? Yes, Brian. It was relatively recent. I cannot necessarily provide a rationale for that. We believe that cognition especially, I mean, almost, you know, above many other endpoints is very relevant and important in this population, as well as things like fine motor skills. I cannot necessarily provide a good reason for that, but we did communicate our belief in cognition and fine motor skills being an important element of the phenotype, which is why we compromised on the sensitivity analysis approach. I think that when we think about what was affected in this trial overall, I can't think of things that are more important than activities of daily living, for example. You know, the ability of these children to, you know, independently get themselves dressed, brush their teeth, feed themselves. The endpoints that were impacted individually, I think are very meaningful, not only to us, but to physicians and to caregivers with Galactosemia. I think that includes activities of daily living, behavior, cognition, tremor, the aspects that we really, you know, held firm on. I'm sorry that I can't give you a good reason for that request by the FDA, but we will certainly be discussing that with them when we request our pre-NDA meeting. Great. Thanks, Shoshana. That's helpful. This concludes our question and answer session. I would like to turn the conference back over to Dr. Shoshana Shendelman for any closing remarks. Okay. Thank you everyone for joining us today. We're very excited about our data. We think this is a very meaningful treatment option for patients with Galactosemia. Again, we want to thank all of the participants in the trial, the investigators and the physicians who have supported this program. Thank you, everyone, and have a great rest of the day. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.