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Good day and thank you for standing by. Welcome to the second quarter 2026 Financial Results and Business Highlights. At this time all participants are in a listen only mode. After the speaker's presentation there will be a question and answer session. To ask a question during this session you will need to press star 1 1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Laura Hansen. Please go ahead. Good afternoon, everyone, and thank you for joining us today to discuss Anality Therapeutics' second quarter, 2026, financial results and business highlights. Earlier today, we issued our earnings press release and filed our quarterly report. The press release, financial tables, and today's presentation are available in the investor relations section of our website. Before we begin, I would like to remind everyone that today's discussion will include forward-looking statements. These statements are based on our current expectations and are subject to risks and uncertainties that could cause actual results to differ materially. Please refer to our SEC filings and the questionnaire language in today's press release and presentation for discussion of these risks. Finale undertakes no obligation to update these four lifting statements, except as required by law. Joining me today are Ryan Watts, our Chief Executive Officer, Katie Pang, our chief commercial officer, Alexander Shuth, our cheap operating and financial officer, and Peter Chin, our chief medical officer in head of development. Ryan will begin with opening remarks. Katie will then provide an update on the U.S. launch of Avalaya. Ryan will return to discuss pipeline highlights, and Alex will review our financial results. Peter will join the team for the question and answer session. Ryan? Thanks, Laura, and thank you, everyone, for joining us today. We will begin on slide five. This was a transformative quarter for Denali. We completed the first full quarter of the Avalaia launch, advanced two transport vehicle-enabled Alzheimer's disease programs into clinical development and further strengthened our financial position. Before I discuss those highlights, I want to begin with why we are here. At Denali, our purpose is to transform life for people living with serious diseases. That includes children and adults with rare genetic diseases such as Hunter syndrome, San Felipe syndrome, FTD granulin, and Pompe disease, as well as the millions of people living with common neurodegenerative diseases such alzheimer's disease and parkinson's disease across both groups our mission is the same to bring the power of biologic medicines to the brain slide six the common challenge across many of these diseases is the blood-brain barrier for over a decade we have built the transport vehicle platform to address that challenge by engineering biologic medicine to cross the brain barrier through receptor-mediated transport earlier this year that work reached an important milestone slide seven. With FDA approval of Avalaya, Denali became a commercial company and began delivering our first medicine to patients. For the Hunter Syndrome community, Avalay is the first new FDA approved therapy in nearly 20 years and a new treatment option designed to reach both the body and the brain. Importantly, Abalaya became the first approved medicine developed using our transport vehicle platform and the first FDA approved biologics specifically designed to across the blood-brain barrier. For Denali, Ablea is much more than a product. It is the first proof that our platform can progress from scientific concept to an approved medicine for patients. Slide eight. We believe Denali today represents a powerful and differentiated combination to create significant value for patients, the healthcare system and investors in the near and long-term. We have a commercial product in Ableia and an encouraging early launch. We have a broad clinical pipeline spanning rare genetic diseases and common neurodegenerative diseases, each with substantial market potential. We have the validated and scalable transport vehicle platform and scientific leadership in the field of BBB transport. We have operational capabilities and financial strength to execute from discovery through development, manufacturing, and commercialization. Together these attributes positions in OLLI to create near-term growth and sustainable long-term value slide nine turning to the quarter avalea generated 3.6 million in net product revenue in its first full commercial quarter the positive response from the hunter syndrome community and the physicians caring for these individuals reflects years of partnership with patients families advocacy organizations and clinicians we cannot have achieved this milestone without their unwavering commitment to advancing new treatment options i also want to recognize THE OUTSTANDING EXECUTION BY OUR COMMERCIAL TEAM IN THE EARLY STAGES OF THIS LAUNCH. IN THE PIPELINE, DNL 628 TARGETING TAU AND DNL 921 TARgeting A-BETA BOTH ADVANCED INTO CLINICAL DEVELOPMENT FOR ALZHEIMER'S DISEASE WITH INITIAL CLINCAL DATA EXPECTED IN 2027. AND FOLLOWING THE SELL OF OUR PRIORITY REVIEW VOUCHER IN JULY, OUR PRO FORMA CASH, CASH EQUIVALENCE AND MARKETABLE SECURITIES EXCEEDED 1.1 BILLION. slide 10. A key focus of today's call will be the Avalaya launch. Katie will walk through the early commercial indicators, what we are learning, and how we are building the foundation for continued growth. Thank you, Ryan. On slide 12, I'd like to start by reinforcing why we believe Avalya is setting a new bar for the treatment of MPS2. For the first time, a therapy is designed to reach the whole body, including the brain, and can normalize key disease biomarkers, both in the CNS and peripherally. These data continue to reinforce physician confidence and resonate with families, supporting the strong momentum we are seeing in the launch. Slide 12. Hunter syndrome represents one of the more prevalent mucopolysaccharide doses, and affects a meaningful patient population within the rare disease community. The U.S. opportunity is highly concentrated with most eligible patients already identified and receiving conventional IDS enzyme replacement therapy at a relatively small number of specialized treatment centers. These are pediatric patients with pre-symptomatic or symptomatic neurologic manifestations who have not progressed to advanced neurologic impairment. We estimate that there are approximately 2,000 patients worldwide in the addressable market, including approximately 500 prevalent patients with Hunter syndrome in the United States. Based on the FDA-approved indication, approximately 75% of the U.S. prevalent population, or roughly 375 patients, are currently eligible for Ablea. In addition, about 30 children are born each year with Hunter syndrome, providing an ongoing opportunity to initiate treatment early. Our ongoing phase 3 COMPASS study is an important next step in advancing Ableya, with the goal of supporting full approval and expansion of the label to include adults. Ultimately, our goal is to reach all eligible patients worldwide. Slide 13. Our launch is being executed against four core strategies. First, partnering closely with the Hunter Syndrome community through a high-touch community-centered approach. In rare diseases, families often learn from and support one another. We believe that positive experience with both Ablea and the Denali team helps build trust, increase awareness, and encourage additional families to seek treatment. Second, helping physicians evaluate Ableia and supporting treatment centers as they prepare to initiate therapy. Strong clinical conviction is creating urgency amongst physicians to switch eligible patients and engage payers to accelerate access. Third, helping each patient and family navigate the steps from prescription through their first infusion. And fourth, driving fast label-aligned coverage decisions that help remove payer roadblocks. After our first full quarter of launch, what has been particularly encouraging is how these four strategies have reinforced one another. Strong clinical conviction has driven physicians and patient demand. That demand has accelerated payer coverage, and together, these dynamics are enabling more patients to begin therapy. Slide 14. Beginning with physicians, we entered the launch with a strong foundation. Before approval, more than 80 percent of physicians surveyed were already aware of Ablea. Ninety percent viewed the biomarker and clinical data as motivating to prescribe. Since approval, we have reached approximately 80 percent of targeted healthcare organizations with Ablea's launch information through our field engagements, scientific exchange, educational webinars, and treatment center support. These activities have been highly impactful and are driving strong engagement across a significant number of treating physicians. Physicians constantly tell us that the ability to address neurologic manifestations is highly meaningful and that most patients experience neurologic symptoms at some point during the course of their disease. That belief is translating into action, as many treatment centers with eligible patients are working with families to navigate reimbursement and transition patients to Ablea. Slide 15. We have seen equally strong engagement from patients and caregivers. Through our launch webinars focused on clinical data and access, as well as with Denali patient services, we reached more than 100 families. That represents greater than one quarter of the eligible U.S. patients. This high level of engagement reflects both unmet need in Hunter Syndrome and the extent to which families have followed the development of Ablea. We are also seeing families share their experiences through advocacy networks and local media, helping other members of the community learn about the availability of a new treatment option. Slide 16. One of the most powerful aspects of LAUNCH has been hearing directly from families and advocates about their experience with Ablea and Denali. They have described the opportunity to begin Ableas as a source of hope, and in some cases as the possibility of gaining more meaningful time with their children. We are careful not to draw clinical conclusions from individual experiences, however these stories illustrate how much the approval of Ableha means to this community, and that has waited many years for a therapy designed to reach both the brain and the body. We are also hearing very positive feedback about the way the Denali team is supporting families and healthcare organizations. For many patients, initiating a new therapy involves coordinating physicians, infusion centers, insurers, specialty distributors, and patient services. Our team works closely with each family and treatment center to help them navigate those steps. The feedback from families and advocacy organizations has consistently highlighted the responsiveness, compassion, and partnership of the Denali team. That experience matters. It builds confidence in treatment, helps patients move through the access process, and supports continuity once treatment begins. Slide 17. Now, turning to payer access. We have made exceptional progress during the first quarter of launch. Commercial policies covering more than 50% of lives have already been established. As with many rare diseases, a significant portion of MPS II patients is covered by Medicaid. Recognizing that not every state will publish a product-specific policy, 14 state Medicaid programs publicly listed Ablea as covered. Separately, we are also seeing managed Medicaid policy align their coverage with commercial plans. These results compare favorably with early coverage achieved by analogous rare disease launches. Importantly, the absence of published policy does not mean a patient cannot obtain access. To date, physicians and families have successfully used prior authorizations, appeals, and medical exceptions while formal policies are being developed. The willingness of physicians to initiate these requests reflects their conviction in Ablea, and our payer and patient access teams are working closely with them to move eligible patients towards treatment. Slide 18. are extremely pleased with the trajectory of the U.S. launch. In our first full commercial quarter, we generated $3.6 million in net product revenue and secured commercial coverage for more than 50% of covered lives. Before discussing the outlook, I want to briefly address our approach to communicating launch dynamics and metrics. We understand that visibility is important to our investors, and we are committed to maintaining an open dialogue. There are many factors that influence the trajectory of Avalaya adoption, and every patient journey is unique, from the initial expression of interest through reimbursement approval and ultimately dosing. In addition, because Avalya is weight-based, the number of vials used can vary meaningfully between a newly diagnosed infant and a 16-year-old adolescent. For the first two quarters of launch, we therefore plan to provide guidance on expected net product revenue for the following quarter. We believe that this approach together with the prior quarter's reported net product revenue will provide the clearest view of the launch trajectory during this early period. Before launch, we described an adoption curve that would build over time. We expected the earliest patients to be highly engaged families who are waiting for Ablea and were prepared to move quickly through the medical exceptions process. That initial demand has been stronger than we anticipated, reflecting both the high awareness of Ablea and the significant unmet need in the Hunter Syndrome community. While many patients have already started therapies, others continue to move through the reimbursement and treatment journey. As payer coverage expands and treatment centers gain experience with Ableya, we expect the patient journey from prescription to infusion to become increasingly efficient, enabling more eligible patients to begin treatment. Given the pace of adoption, expanding access, and continued strong execution, we expect Q3 net product revenue to be in the range of $10 to $12 million. Most importantly, families continue to tell us that Ablea and the support they receive from the Denali team is making a meaningful difference in their lives. Slide 19. The Ableia launch also has significance beyond a single product. It establishes the first commercial foundation for our enzyme transport vehicle franchise across lysosomal storage disorders. The ETV platform is designed to reach the whole body, including the brain, and it provides opportunities across Hunter syndrome, Sanfilippo syndrome, FTD granulin, Pompe's disease, Gaucher's disease and Herla syndrome. The ERT market alone represents more than a $9 billion opportunity. community. Across these diseases, we expect to benefit from shared scientific expertise, established relationships with treatment centers and advocacy organizations, and commercial capabilities that could be leveraged across future launches. Each patient we support and each treatment center we activate strengthens the infrastructure that can serve the broader ETV franchise. Avleya is therefore both an important medicine for Hunter Syndrome community and an early demonstration of our ability to discover, develop, manufacture, and commercialize innovative therapies efficiently and successfully. We are proud of the start while recognizing that this is still the beginning of the launch. Our priorities remain expanding access, supporting a positive treatment experience, reaching additional eligible patients, and preparing for the international expansion. With that, I'll turn it back to you, Ryan, to discuss the broader pipeline. Thanks, Katie. Slide 21. Earlier, I described Avalaya as the commercial foundation for Denali and the first proof that the transport vehicle platform can enable medicines for patients. I would now like to provide an update on the broader pipeline and then spend most of my time on our Alzheimer's disease programs. Our D3 by 3 strategy remains unchanged, deliver, develop, and discover. Over the 2026 to 2028 period, our goals are to build two growing commercial brands, generate five clinical proofs of concept, and advance four to six additional programs into the clinic through continued leadership and invention in blood-brain barrier technologies. Slide 22. Next, I would like to briefly update you on DNL-593. DNL 593 is a direct progranulin replacement therapy designed to deliver progranulin across the blood-brain barrier and restore the missing protein to key cell types in the brain, including the lysosome where progranolin normally functions. Earlier this year, we regained full ownership and control of the program from Takeda. That provides us with greater flexibility over the development strategy and timing of the data analysis. We have decided to allow for a longer period of observation in the open-label extension portion of the ongoing Phase I and II study. We now expect data in first half 2027, updated from our prior expectation of results by the end of the year. The additional follow-up will allow us to better characterize treatment effects across multiple biomarkers, including neurofilament light chain, or NFL, which may change gradually following treatment. Pending the totality of the data, we also plan to explore whether a biomarker-driven accelerated approval path may be appropriate. NFL has regulatory precedent in the related neurodegenerative disease, ALS, although any potential path for DNL-593 would require discussion and alignment with regulators. We are excited about DNL 593 because it directly addresses the genetic cause of FTD granulin by replacing progranulin. This week, the FDA granted orphan drug designation to DNL 593 for FTD granulin, underscoring the significant unmet need facing individuals affected by this disease and the potentially promising rationale of our approach with PTV progranulin. Earlier, healthy volunteer data demonstrated dose-dependent increases in cerebral spinal fluid progranuline following intravenous administration, providing evidence of brain delivery and further validation of the transport vehicle platform. Slide 23. I will now turn to what we believe is one of the most exciting areas of our pipeline, Alzheimer's disease. A few weeks ago, I had the privilege of delivering a plenary presentation at the Alzheimer's Association International Conference in London. After working in Alzheimer's disease for more than 20 years, I believe the field has entered a transformative period because of extraordinary progress in three historically challenging areas, biology, biomarkers, and the blood-brain barrier. Human genetics and pharmacology are sharpening our understanding of the multifaceted biology of disease. imaging and blood-based biomarkers are enabling earlier diagnosis and increasingly precise measurements of disease progression and treatment response. And brain transport technologies are creating the potential to deliver biologic medicines broadly throughout the brain. Together, these advances create new opportunities for the next generation of Alzheimer's therapies. Slide 24. We believe the next advances in Alzheimer's disease may depend on delivering therapies more effectively throughout the brain. Amyloid plaque clearance is now clinically validated, but currently available antibodies are limited by modest efficacy and the risk of amyloid-related imaging abnormalities or ARIA. Cal reduction has also shown encouraging clinical signals, but current antisense approaches rely on intrathecal administration and may not achieve uniform distribution throughout the brand and have other limitations. Our two clinical programs are designed to address these limitations through better brain delivery. DNL921 is a potential best-in-class BBB-crossing anti-amyloid antibody designed to improve plaque engagement while reducing ARIA potential and peripheral immune activation. DNL628 is a potentially first-in class BBB crossing tau antisense oligonucleotide designed for intravenous administration and broad uniform distribution throughout the capillary network. Slide 25, starting with DNL921, one of the important features of transport vehicle-enabled delivery is the route of entry into the brain. When conventional anti-amyloid antibodies enter the brain, they concentrate around larger arteries and arterioles where a vascular amyloid is present. We believe that localization contributes to ARIA risk. By engaging the transfer receptor, antibody transport vehicle enabled antibodies enter the brain through the extensive capillary network and distribute more evenly throughout the brain In preclinical models, this route of entry was associated with substantially fewer MRI lesions than a conventional anti-amyloid antibody, including at dose levels that achieved strong target engagement. These data support our hypothesis that improved brain delivery and biodistribution may enhance plaque engagement while reducing ARIA potential. Slide 26. We've also engineered DL921 to address the broader attributes required for a successful medicine. Unlike fusion approaches that append a transfer receptor binding arm to an antibody, our transport vehicle binding is embedded directly into the FC. DNL921 is designed to achieve robust brain concentrations while remaining intact and minimizing effects on immature reticulocytes. With the goal of preserving activity at amyloid plaques while reducing peripheral immune activation, DNL 921 incorporates conditional effector function through our CISLALA design. Slide 29. Turning to BNL628, the central opportunity is to improve both distribution and convenience for antisense therapy. Intrathecally administered antisense oligonucleotides distribute from cerebral spinal fluid and can produce uneven exposure across brain regions with greater treatment burden for patients. By contrast, intravenous oligonucolytide transport vehicle, OTV delivery, uses a capillary network to distribute the antisense oligo broadly across the brain and spinal cord. This distribution includes key cell types involved in neurodegeneration, including neurons, astrocytes, and microglia. Slide 28. In mice expressing human tau and the human transferrin receptor, DNL628 produced robust reductions in MAP-T RNA and tau protein. Importantly, tau protein reduction persisted for more than 12 weeks after dosing, supporting the the potential for a practical dosing interval. These data support the design of the ongoing Phase 1b study where we are evaluating safety dose selection effects on tau levels and imaging measures in people with biomarker-confirmed early Alzheimer's disease, slide 29. Both Alzheimer's Disease programs are now in clinical development. DNO 628 Phase 1B study is ongoing and we expect initial clinical biomarkers data in the first half of 2027. BNL921, the clinical trial application was submitted in the first half of this year, and we expect initial safety and clinical proof of concept data in 2027. These readouts will be important not only for individual programs, but also for the broader validation of our oligonucleotide and antibody transport vehicle platforms in common neurodegenerative disease. Taken together, our progress this quarter demonstrates the breadth of Denali, a growing commercial business, broad clinical pipeline, and a repeatable platform capable of supporting multiple therapeutic modalities, all focused on delivering meaningful medicines to patients and families. Slide 30. With that, I will turn the call over to Alex to review our financial results. Thank you, Ryan. Slide 31. I will close our prepared remarks today with a at our portfolio, capital allocation priorities, and second quarter financial results. We have built a broad portfolio based on the transport vehicle platform, which is now clinically and commercially validated through AVLEA. This portfolio has the potential to create significant value in the near and long term, with each program designed to offer first or best-in-class potential in its respective indication, and we are well capitalized to execute against it. Our portfolio has two key components. First, we have a pipeline of next-generation enzyme and protein replacement therapies designed to treat the whole body, including the brain. Across these programs, we can apply the clinical and regulatory learnings from AdLayer and leverage our existing capabilities in development, manufacturing, and commercialization. We estimate that each program represents a potential market opportunity ranging from approximately $500 million to more than $1 billion, creating a multi-billion dollar opportunity across the franchise. These programs benefit from a well-established therapeutic modality, measurable biomarkers, and in certain diseases, the potential for biomarker-based accelerated development paths. In addition, and shown on the right, is our portfolio targeting common neurodegenerative diseases. This includes two clinical stage blood-brain barrier-enabled molecules targeting tau and amyloid beta for Alzheimer's disease with first and or best-in-class potential. If successful, these programs could reach millions of patients and represent substantial multi-billion-dollar market opportunities. Slide 32, turning to the financials and capital allocation. We ended the second quarter with approximately $940 million in cash, cash equivalents, and marketable securities. In July, we received $195 million in proceeds from the sale of the Rare Pediatric Disease Priority Review Voucher awarded following the approval of Ablea. Together, this brings our pro forma cash, cash equivalents, and marketable security to more than $1.1 billion. This gives us flexibility to pursue three priorities with discipline. First, it allows us to invest in the execution of our portfolio, including the commercial activities for Avlea as outlined by Katie, preparations for the potential launch of DL-126 or Safinofasb-Alpha in 2027, and advancement of clinical programs. Second, we can continue to build capabilities and infrastructure for efficiency. In particular, our internal manufacturing facility in Salt Lake City provides opportunities for speed and development and attractive cogs as we bring additional products forward. Third, our balance sheet provides strategic flexibility with respect to potential future partnerships and diversified sources of capital. Slide 33. The complete details of our financial results are included in today's press release in Form 10-Q, so I will focus only on the key items. Avalaya generated $3.6 million in net product revenues during the first full quarter of commercial availability. Research and development expenses were $97 million, compared with $102.7 million for the same period in 2025. The decrease primarily reflected the timing of Ablea commercial supply manufacturing in the prior year period and lower external spending on small molecule programs. Selling general and administrative expenses were $36.3 million compared to $32.3 million in the second quarter 2025. The increase primarily reflected investments to support the Ableia commercial launch. As noted, we ended the quarter with approximately $940 million in cash, cash equivalents, and marketable securities before receipt of the $195 million in PRV proceeds in July. In closing, we believe Denali is entering this exciting next phase from a position of strength with a commercial product, a broad pipeline, a validated platform, and the capabilities and capital to deliver value for patients and investors. With that, I will turn the call back to the operator to begin the Q&A session. Thank you. Thank you, we will now begin the question and answer session. If you wish to ask a question, you will need to press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. We will take our first question, and the question comes from the line of Jessica Fry from J.P. Morgan. Please go ahead. Your line is open. Hello. This is Adam on for Jess. Thanks for taking our question. I just was curious, what in the launch so far has helped you come up with the next quarter's guidance? Can we assume that growth trajectory to continue through the end of the year? And could we see maybe op-ex guidance in the future? Thank you. Thanks, Adam. Thanks, Adam. Thanks for your question. So, what's giving us confidence is all of the leading indicators are moving in a very positive direction. As you saw from the presentation, physician awareness is extremely high of the Ablea data, and they're highly motivated to switch patients. In addition, we've seen tremendous engagement from families as well, And we've also had great success moving patients through reimbursement with the medical exceptions process. And as you can see, also, we've had success with payer access, and we have now greater than 50% of commercial lives covered as of the end of Q2. So given all the dynamics are moving in the right direction, we feel very confident that the momentum will continue. I can take the second part of this, Alex. I can take the second part on OPEX. So capital efficiency is very important to us, and we're pleased that we're able to keep OPEx flat in Q2 of 26 versus Q2 of 25, and actually slightly lower on a six-month basis, while at the same time preparing for the launch and advancing important new programs into the clinic. With respect to an outlook, we generally provide an outlook for the full year at the beginning of the year. So please stay tuned for that. Thank you. Thank you. We will take our next question. And the question comes from Salveen Richler from Goldman Sachs. Please go ahead. Your line is open. Good afternoon, Mrs. Lydia. I'm for Salveem. Congrats on the progress and on your first earnings call. Could you just speak to the patient profile of the initial patients on therapy and kind of the breakdown between the newly diagnosed versus switched patients. Thanks so much. Great. Thanks for that question, Lydia. So, as you know, with this patient population, majority of the patients are already treated on Idar cell phase. So, we expect 90% of patients, prevalent patients, would be then switching. So the majority of that, of course, we are seeing as well newly diagnosed patients being put on Ablea, but the majority will come from patients that are switching. In terms of patient profiles, we initially believe that patients may skew to the younger population because those are the families that were most engaged and have been following the development of Ableia. But we've been really pleased to see that what we can gather today is that it's very broad. In fact, patients across the different age groups within the pediatric population have demonstrated interest in being prescribed Avlea. Thanks so much. Thank you. We will take our next question. And the question comes from Andrew Tsai from Jefferies. Please go ahead. Your line is open. Hey, good afternoon. Thanks for sharing all these positive updates. So maybe one more on Hunter. You're guiding to a strong sales number for Q3, and then I think in your prepared remarks, the original guidance for an S-shaped curve still seems to hold. So to me, that would mean that come next year, could we be talking about a quarterly revenue number that's significantly larger than 10 million. Is that the right way to think about it? And then secondly, Biogen just shared their phase two tau data set. So I'd be curious to gauge your thoughts on the degree of efficacy they're seeing. How much do you think that is attributed to too much tau lowering or is it the mode of administration or something else? It'd be nice to gauge your views on these possibilities or variables around efficacy. Thank you. Thanks, Andrew. I'll start with the first part of your question. And yes, we still believe that this year is a foundational year. We talked about getting as many patients on therapy as possible, and we are definitely at the beginning stages of that S-curve. But of course, our goal is to tighten that S shape curve and bring in the inflection point as soon as possible. And that's why our focus on, you know, driving awareness, making sure the experience on Avalaya is very positive so that the community can further share that and drive the momentum that will drive, as well as with payer access, that will drive that inflection point. I'm happy to take the second question, Andrew. As you know we spoke before the data was shared at AIC in London and then of course a lot came out after the data presentation. And I think, you know, our response is that, in general, it's the first data set to show that tau lowering may lead to a clinical benefit. And I Think what's probably the most compelling is you look across not just ADAS-COG, or sorry, CDR sum of boxes, but also ADAS, COG, and MMSC, and you're seeing consistency in potential clinical benefit, I think the challenge is you, as you have highlighted, is a question around why was there not a dose response? Why did the higher doses not lead to more efficacy? And I think just a couple points without going into too much detail, you know, obviously there were more discontinuations and adverse events in the higher dosages. I think it's well understood with intrathecal administration that this is not uncommonly seen, including, you knows, transient confusion. So, I think we, like others, look forward to seeing more details and the differences between the doses and that may this actually be masking you know some of the efficacy but in general you know first data set showing power lowering and potential clinical benefit thank you thank you we will take our next question and the question comes from tazim ahmed from banks america please go ahead your line is open Hi, guys. Thanks so much for taking my questions. I wanted to just focus on 593 for a second. I'm sorry if I missed this in your prepared remarks, but can you share any color on what level of data you plan to share when you release it? And what, in your view, would be good data? And then can you just clarify why you want to wait for NFL data? I think in the the past, you mentioned the focus was going to be on lysosomal function. Thanks. Yeah, thanks, Zazina. I'm happy to take that. I think the most important point here is that, you know, as we've regained full rights to this program, we're now in a position where we can essentially drive the strategy on this program. And I think in our experience, I think point number one is that longer-term data is often needed when looking at biomarkers like NFL. And I think what's unique about FTD granulin from, let's say, some of our other lysosomal storage disease programs, that this is a haploinsufficiency in terms of the underlying disease. And as a result, as we look at some of the lysosoma biomarkers historically, there's elevation, but it's modest, not like what you see with heparin sulfate in Hunter syndrome. And so, what we've decided to do is we're trying to find an accelerated path. As you may have also noted, we received orphan disease designation for this program just recently as well. And so we think we have the best chance of seeing robust data specifically on the distal biomarkers such as NFL and more broadly, and just looking at the entire biomarker set, including lysosomal biomarkers as well. So, I think the key here is just giving this program the best chance of a potential accelerated path. Obviously, with data in hand, then we'd have to address that with regulators. Thank you. We will take our next question, and the question comes from Michael Yee from UBS. Please go ahead. Your line is open. Hi, this is Madeline on for Michael. I just wanted to ask a couple more on the launch. Congratulations on such a strong number right out of the gate. Just wondering, given your comments around stronger than expected early demand and the fact that we sort of know the number of hunter patients that are out there, do you expect a sort of bolus effect in the U.S. of these patients who are covered on the label now coming on? And then for these patients that are having to go through sort of medical exceptions and fire-offs, do you have any sense of what the time is from getting the script to actually getting infused? Thank you. Thank you for that question. So in terms of what we expected, we definitely expected that pool of patients who have been following Ablaa's development very closely. And that pool of highly interested families is bigger than we initially had expected. But we are working through, with the early experience with these early families, though, we are seeing expansion into the broader patient population, as I described earlier. And so we're very excited about the fact that it's going beyond just those early families and we're going to expect to see continued growth into the broader population. And as you stated, the total eligible population is around 375 that are considered pediatric patients in the U.S. In terms of, I think your question was starting the interest to infusion and what's the timeline for that. As you know, with this early in launch and without payer coverage initially, although, of course, that's expanding now, there is huge variability in the time between patients expressing interest to when they actually get infused. So, it's really hard to comment on that this early in launch. However, you know, with payer coverage improving over time, that timeline should get more straightforward, more efficient. Thank you. We will take our next question. And the question comes from Sean Lauman from Morgan Stanley. Please go ahead. Your line is open. Hi, this is Mike Riad on for Sean. Thank you for taking our questions and congratulations on the strong start. Can you remind us how is progress going on for the adult confirmatory study? And given what you've learned so far, acknowledging it's only one quarter into the launch, is there anything that has changed your excitement or views as to how that adult study could influence launch trajectory or pricing? So what we're hearing today, certainly there are adult patients that are very much interested in getting treated with Avalaya. I think that's That's your question. I don't think launch price will change since we've already gone into market, even when we hopefully will get the label expansion. And I'll let Peter comment on the study. Yeah, and in terms of the Compass Phase 2-3 study, we're excited about reading out the study, which is set to end at the end of next year. It is going to be the basis for expanding the label both in the U.S. as a confirmatory study and for potential global launches. Thank you. That's very helpful. And then just thinking about the 2Q to 3Q revenue guidance and RAMP, can you walk us through any key drivers of that acceleration? How much of it is coming from new patient starts versus patients converting to reimbursement? So I think it's a combination of all those factors. So we're seeing, as I stated earlier, all of the leading indicators, the high level of engagement from physicians and families, the conviction that physicians have in going for a medical exceptions process, and then the fact that our payer coverage is getting better every day. I think all of those things are going to be contributing to the growth over the next quarter. Thank you. Grant, again. Thank you, we will take our next question, and the question comes from the line of Paul Matisse from Stifel. Please go ahead. Your line is open. Great. Thanks very much, and congrats on the early launch progress. I guess taking a step back, given everything you kind of understand around this patient population, the degree to which families are plugged in and we're waiting for Avalaya, do you think you're seeing a bolus right now, and might we see some attenuation in the ad rate later this year, or do you feel like this is actually, you know, potentially sustainable? And then as it relates to tau and the upcoming data next year, you know, Ryan, I think you've talked about CSF tau data being an interesting early biomarker, given that pet changes can take some time. I'm wondering, though, that do you think your CSF tao data for the shuttle will be comparable to the CSF Tao data for an intrathecal drug, given the fact that it's not that IT-administered drugs can maybe bias CSF biomarkers, given sort of the site of administration? Thanks so much. Thanks. I will take the bolus question first. And certainly, you're correct that we expected this bolus. The bolus is bigger than we expected. But I think the key thing that we're seeing is that this early experience from this initial patient population is translating to the broader population. And over time, especially as physicians gain more experience and the stories are shared more broadly through the patient community, we expect the growth to continue into the full eligible population. Thanks, Katie. Paul, fantastic question. Obviously, very mechanistic. You know, obviously, my kind of question. I think you're exactly right. It's really difficult to compare CSF tau in an intrathecally delivered molecule versus one that's delivered through, you know, capillaries through the transport vehicle, through transferrin receptor. And the experience we have related to this is actually with, you know,, early days of ETB-IDS, now Avalaya, and its comparison with intrathecal delivery of iduronate to sulfatase, where, you know., there's a regional, very high concentrations of enzyme. In this case, it would be high concentration of the antisense oligo. And so, I think it's really apples to oranges in terms of like percent reduction and what we would correlate ultimately with clinical benefit. But what we can say is that our biodistribution is even and robust. So when we look at different cell types throughout the brain and brain regions, we get basically roughly the same knockdown of gene expression across these various cell types. So, when we measure CSF levels of tau, we're confident that that's the level of knockdown we're getting throughout the brain. And I think if you then relate that to maybe some disappointment in the maximal efficacy seen with intrathecal delivery, that may be simply because you're not penetrating deeper brain regions that may Be impacted by tau and tau pathology. And then to the sort of first half of your question around CSF tau and taupet, I think what's really remarkable, and we mentioned this at AAIC, the intrathecal data has essentially proven that tau PET can be reversed. That was actually a fundamental question, and many mouse models actually had never really necessarily shown that. So, in other words, if you reduce the expression of MAPT, which codes for tau, and then you reducethe expression of tau protein, over time, you start to see a reduction in the tau PET signal. And if you look at the totality of the data, including the new data that's been presented, it seems like the shortest window is about a year from when they see tau PET reduction. The early data set didn't really show much reduction at six months, and then they looked later. It was either 18 months or two years. This data set shows that in a year, they're seeing, albeit variable, from patient to patient. And actually, if you Look at the data sets carefully, they've been published, some patients get no tau reduction by PET and others get robust. We think this is actually heterogeneity in intrathecal delivery. And so the take-home is, you know, biodistribution is going to be, you Know, critically important and different with the transport vehicle technology. And CSF tau will still be very informative, just like heparin sulfate. CSF was informative for our um hunter program but we're not comparing percent reductions because of exactly the point you made these are fundamentally different delivery approaches great thanks ryan thank you we will take our next question and the question comes from the line of mayank mamtani from b riley securities please go ahead your line is open Good afternoon. Thanks for taking my question, and congrats on a strong LL launch. Maybe right on the prior point on the OTD MAPT strategy, are there any genetic thymopathy you could potentially look at? And just taking the logic that you're applying to the GRN program, you know, there are FTD MAPP thymopathies also that could be looked at. And then maybe just a high-level question is, a lot still we need to see from a biomarker standpoint in the CVR study. What are sort of the right things to kind of look out for as you obviously think about the biomarkers you want to look at in your six to eight cohort leading up next year? Yeah, great. Thanks, Neil. Again, great questions. My take is, I think with MAPT, the key point here is really focusing on tau reduction, showing that the OTV works, that you can deliver medicine systemically and get tau reduction. We're definitely interested in these genetic subpopulations, but our experience actually with FTD granulin is that initially it was very, very difficult to enroll these more rare cases. And the tauopathies are not unlike FTD, and in fact, there are FTD sort of tauopathes, so sort of rare, hard to diagnose initially, and then you have to genetically diagnose them. So we're interested in that. I just don't think that it's the fastest path to really proving the platform and then subsequently driving for the first approval. In terms of what to look for, we're essentially looking for tau reduction in CSF, not really hitting a target. The genetic data in mice suggests that, you know, the haploinsufficiency loss of one copy of tau is highly protective in the Alzheimer's models. And so, you could imagine somewhere between 25 and 70% reduction. But I think that fundamentally, what's actually very interesting about the data set that has recently been presented is that there was a non-dose proportional reduction in tau. So as you go up 2x in dose and 4x in dos, there's only really about a 20% difference in overall tau reduction in that range. And yet there is sort of a different, obviously, AE profile for those higher doses. And so we feel like the CSF data for intrathecal is apples to oranges. but we look at our own data and our own preclinical data and what's sort of been published to set the tone that, you know, we really need to see CSF tau reduction as really a proof of the platform. I don't know, Peter, if you want to add anything there. No, I think you covered it well. I think we're really focused on executing the program, generating the data that Ryan alluded to, and I think other potential indications is something that we can consider in the future. thank you thank you we will take our next question the question comes from the line of Ananda gosh from HC Wayne writing co please go ahead your line is open hi thanks guys and comrades on the great quarter I have actually two questions you know in 2025 seat at barge and presented some data using this zirconium dye where they try to show their intrathecal you know, the tau modality, like how well they kind of distribute throughout the CNS. And you would see that, you know—you know, it's a very poor distribution. Now, the question is that, despite such a poor distribution, they do see, you know, as you rightly mentioned, some—you know, that they can move the clinical endpoints at least, you know, in a trend way, trend setting. And so, just wanted to get your thoughts on that aspect of it, that how did—you know, even with such a poor distribution, how can they see, you know, some efficacy with respect to both as a biomarker as well as from clinical endpoints? The second question is, you Know, there are also these ideas that, and especially from the Donanemab trial, that, you Now, in patients where you have low tau, there you can see, you Know. Those patients are much more amenable to either both anti-abeta therapy or anti-tau therapy. So, you know, as you are thinking about your phase 1b, is there a way to enrich patients with low tau in your phase one b patient, you know, the trial population? Thanks. Yeah, good questions. I'll try to be brief because we have a number of other questions. I think, you know, let's look at additional data that hopefully will be presented on BID-80 to really understand that dynamic. But you're right, there's enormous heterogeneity. There is, and we've published this already in Monkey, and so I think the positive clinical signal across, you know, three different endpoints, ADAS, COG, CDR, sum of boxes, and MMSC is really encouraging, and there are some patients that get, you Know, really decent biodistribution in the particular study that you're referencing, andso I think that, you that's I think the the main point great thanks thank you we will take our next question and the question comes from Joseph Thorne from TD Cohen please go ahead your line is open hi this is Jacob on the line for Joe thanks for taking our question kind of going along with you know patient enrichment or kind of patient selection I was curious how you're thinking about some of these co-pathologies that often come along with AD, like alpha-synuclein and TDP-43, and how those can play a role in patient selection or kind of pre-specified subgroup analyses. So, and then just additionally, looking farther ahead, how you're thinking about, you know, what a bar might look like given some of the currently approved amyloid beta therapies on things like CDR-SB. Thanks. I'll address the first one on the copathologies. And then Peter, why don't you address the bar on, I'm assuming what you're asking is the bar for approval or for like clear differentiation with the anti-amyloids. Yeah. So I think with copathology, the two, obviously the most common copathogy, which is actually in some ways defines Alzheimer's is A-beta plaque or amyloid plaque and tau neuroflag rate tangles. I think what you're referencing is also it's been shown like, you know, you see Lewy bodies and other sort of vascular pathologies. The challenge with those type of co-pathologies, there aren't imaging biomarkers yet that allow you to look at the level of, let's say, Lewy body that can also be observed with amyli plaque or tau. And so at this point, our focus is on the two most common and prevalent. I'll add that there's, by the way, a fourth one, TDP43 pathology, which I think represents roughly 30% of Alzheimer's. All of this being said, amyloid appears to be at the top of the cascade. So, amnyloid eventually drives the formation of tau pathology and then tau pathology correlates with cognitive decline. And so, we're keen on targeting both amylloid and tau. And I think as biomarkers improve, you'll be able to see, hopefully we'll be allowed to identify patients that have other pathologies, which, you know, in some ways is probably complicating the clinical picture. With that in mind, I'll hand it to Peter to talk about what the bar might be for anti-amyloid approvals. Yeah, thank you, Ryan, and thanks for the question. I mean, I think I'll start by saying this is a very exciting time for Alzheimer's, and coming off the vast amount of data that was presented at AAIC, there's a lot that's being learned about different aspects of the patient populations. I think it's premature to say exactly where we're headed, but I do think that with all the data that's being generated and understanding both progression rates and response of different types of therapies, this is something that we'll definitely pay attention to both with targeting tau as well as with amyloid. I mean, from an amyloc perspective, we're very excited about the differentiating potential of DNL921, and I think our goal is really to generate proof of concept with that first. Great. Thank you. Thank you, we will take our next question. The question comes from the line of Laura Chico from Wedbush. Please go ahead. Your line is open. Hey, thanks very much for taking the question. Congrats, guys, on the quarter. one for Katie. I'm wondering if you could expand a little bit further. What capacity do the centers have for switch patients? Just wondering if there's any additional considerations that the physicians need to work through for a switch patient versus perhaps somebody that's new to treatment. You indicated in the webinars that you encompass or encountered over 100 families or greater than 25% of the eligible patient pool. So I guess I'm just trying to understand if there are any capacity considerations that we should be making as you're progressing here. Thanks very much. Thank you, Laura. That's a great, great question. And you're exactly right. There are definitely dynamics, both for the newly diagnosed patients and for the switchers. As you remember, majority of the idosarphorase patients are treated at home. And so these are patients coming back to the clinic. And definitely infusion scheduling is one of the steps that families have to work through. And so, with all the families coming back, there is a sequencing, depending on the center, you know, depending if you're at a center that has specialized centers of care, they are going to have a little bit more capacity than other centers. So, that is the dynamic that has significant variability that we're going to be working through. But what we've seen is the sense of urgency and the motivation from families have been very strong. Thanks very much. Thank you. We will take our next question, and the question comes from Mark Goodman from Nearing Partners. Please go ahead. Your line is open. Hi. Good evening, everyone. This is Alyssa. I'm for Mark. Thank you for taking our question. I was wondering if you could help us think about the average price per patient for Avlyia given the weight-based dosing and titration schedule. Since many patients will initially be up titrating over the course of the first few months, when should we expect pricing to reach a steady state run rate? And then secondly, on the manufacturing facility in Salt Lake City, do you have any plans to use that facility to manufacture commercial batches of Avlea, or will that be used only for clinical manufacturing? Thank you. Great, thanks. I'll address the pricing question. So, at maintenance for a 10-kilogram patient, it's roughly around $270,000 per year, and up to a 30-kg patient, which is about $800,000 per year. And as you described, there is a dose escalation described in our label. And what's been provided to physicians, and this is ultimately a physician's decision on how quickly to do the escalation, is that we expect the escalation to be about four weeks at each step before they get to maintenance dose. And there may be variability as patients' dose escalates, depending, and it'll be very individualized and physician-sided. And then I'll answer the second question. We do not have plans to manufacture in Salt Lake City for Avalaia. In fact, our plans are to go to larger scale with Lonza and onshore to Portsmouth to go to 6,000 liter. Okay. Thank you very much. Thank you. We will take our next question. The question comes from Michael DeFoe from Evercore ISI. Please go ahead. Your line is open. Hi, guys. Thanks so much for taking my question and congrats on the progress so far. Two for me, now that you have a full commercial quarter under your belt, at this juncture, could you give us the number of patients on drug as well as the number of cumulative start forms? And if not, when might you be able to share this information? And second question is, as patients switch off of Eliprase, have you seen any competitive response from Takeda, either on contracting pricing, or account-level pushback, for that matter. Thank you. Okay, let me see if I can address all the questions. So your first question was on start forms and patient numbers. So at this stage, we intentionally focus on communicating the overall trajectory rather than providing individual operational metrics. So I shared earlier why we have confidence is we're seeing all of the progress with the various stakeholders within the ecosystems, with physicians, being highly aware and engaged, families highly engaged, and driving towards switching, as well as centers working through reimbursement and payer access. With regard to start forms, we also feel that at this point, start forms are not predictive of revenue. And it's because each individual patient journey is very unique. And the time, depending on what their insurance plan is, which centers they're getting treatment at, that is highly variable at this point. And we haven't provided guidance as to when in the future we may provide patient or start form information. But for now, we really want our investor to rely on the revenue guidance because we feel like it's the most clear, quantitative indicator of how our launch is progressing. I think those were, oh, did you have one more question? Yeah, I did. Just regarding the switch off from LRAs, any competitive response from Takeda that you've seen? Yeah. So in terms of competitive response, you know, we've been very much focused on making sure that the clinical value and the biomarker data is well recognized. so I think we haven't seen a ton of pushback because it's very well recognized that Ella praise does not address neurologic manifestations and we haven't seemed the other activities that you've described which is contracting and I think you've describe another one but we haven we haven' seen any activity related to that thank you we will take our next question the next question comes from Miles Minter from William Blair. Please go ahead. Your line is open. Hey, team. This is John. I'm from Miles. Congrats on a strong first launch quarter, and thanks so much for taking our question. So for Avleya, wondering if any of your commercial patients have previously been clinical trial participants, and wondering if you can give us any color on the cadence you expect for clinical trial patients to transition over to commercial therapy yeah so the majority of patients that have started today are are not actually our clinical trial patients we expect all of our clinical trial patient to be able to convert to commercial patients by the end of this year thank you thank you we will take our next question and the question comes from David Hong from Deutsche Bank. Please go ahead. Your line is open. Hi, this is Rosemary on for David. Thank you so much for taking my question and congrats on the quarter. I was just wondering how you might be thinking about the competitive landscape evolution for Avalaya as there's some competitor resubmission happening this year and JCR Farmers as Cargo may be having a global phase three readout next year. Thank you. Yes. Thanks for that question. Of course, we're always very encouraged to see continued innovation in Hunter syndrome, but we are very confident in our biomarker and clinical evidence. As you know, we've shown normalization for the first time in this disease area for key disease biomarkers, and our focus is on executing on our launch and driving the momentum that we're seeing today. Thank you. We will take our next question. Your next question comes from the line of Charles Moore from Baird. Please go ahead. Your line is open. Hey, guys. Thanks for taking the question, and congrats on the great quarter. Just kind of following up on the last question, I recall your analogous trial for Avlea included patients who had been treated with gene therapy. So, looking toward the DNL-126 trial, are there any patients there who have been treated with a gene therapy previously, considering that there's the possibility for a Sanfilippo gene therapy to be approved ahead of DNL 126? Thank you. Peter, maybe I'll have you take that. I'll just make one comment. We haven't gone into great detail on the 1, 2, 6 patient population, but, you know, obviously presented new data earlier this year at World and very excited about that program, but great question around the competitive landscape. Peter, do you want to add anything to that? I just don't think we've gone into much detail onthe nature of those patients. Yeah, thanks, Ryan. Yeah. I would just say we haven't presented the baseline characteristics of the full cohort yet, but we do intend to present the data early next year at the World Symposium. And I'll just add, you know, great memory. We did have both gene therapy and cell therapy patients in the Hunter data set and where we saw, you Know, robust normalization in those patients' data in terms of CSF heparin sulfate. But I think the key here is really focused on the sustained biomarker response across our ETB franchise. thanks for the question yep thank you very much thank you this concludes today's question and answer session i'll now hand the call back to ryan watts for closing remarks we thank everyone for joining the call today we're very excited about where we are and look forward to continued momentum thanks everyone this concludes tonight's call conference call thank you for participating you may now disconnect