Ultragenyx Pharmaceutical Inc. FDA announcement

FDA approval of FAYUVI, the first-ever treatment for Sanfilippo syndrome type A. We appreciate all of you making time to join us this afternoon to discuss this important milestone. A press release with details on this announcement is available on our website, along with an updated corporate presentation. Joining me today are Emil Kakkis, Chief Executive Officer and President, Eric Crombez, Chief Medical Officer, and Erik Harris, Chief Commercial Officer. Howard Horn, Chief Financial Officer, is also on the line for Q&A. Before we begin, I would like to remind everyone that today's discussion will include forward-looking statements. These statements involve risks and uncertainties, and actual results may differ materially. Please refer to the risk factors described in our SEC filings. With that, I will turn the call to Emil.

Thank you, Josh, and good afternoon, everyone. Earlier today, the FDA approved FAYUVI, the first-ever treatment for Sanfilippo syndrome type A and our second gene therapy approval in less than a month. This milestone represents our sixth FDA approval overall and further establishes Ultragenyx as a leader in both rare disease medicine and gene therapy. Before we discuss in detail the significance of this achievement for our company and the MPS community, I want to briefly acknowledge the recent outcome from our phase III ASPIRE study for GTX-102 for Angelman syndrome. This was truly disappointing for the company and for the Angelman community. We expect to provide a more comprehensive update by our next quarterly financial results call. We will address your questions on the Angelman results and our expense management plans in greater detail at that time.

For today, we are going to focus on the FAYUVI approval and what it means for children and families with Sanfilippo syndrome type A. Sanfilippo syndrome type A is one of the most heartbreaking diseases I have encountered in my career. These children often appear healthy early in life. Then by age 2 to 6 years old, as the disease progresses, they gradually lose their ability to learn, to communicate, and to engage with the world around them. After a period of hyperactivity and altered behavior, the children slow down. As family watch, skills disappear one by one, leading to a bedridden state. The children eventually die from this devastating disease, usually as teenagers. Until now, families and clinicians have had to face this diagnosis without any approved treatment with the potential to stop or slow this inevitable decline.

We're here today because parents, advocates, clinicians, researchers, and organizations across the broader MPS community refused to accept that reality. They raised awareness, funded research, participated in clinical studies, and never stopped fighting for their children. Now, thanks to their perseverance, families receiving a diagnosis of Sanfilippo syndrome type A can have hope that their children's future may look different. Ultragenyx was founded to pursue diseases that others overlooked and deliver treatments where none existed before. In less than 1 month, we've now achieved our consecutive gene therapy approvals for 2 severe rare diseases, demonstrating not only the strength of our science, but our ability to translate innovation into approved medicines for patients. Even though Ultragenyx was not originally working on Sanfilippo syndrome, we received a call from Abeona CEO, Vish Seshadri.

When funding constraints arose despite positive clinical data, Abeona made the pivotal decision to out-license the asset to Ultragenyx, ensuring this vital treatment reached the finish line for patients. When we picked up the program, our team found a way to make it work relentlessly and courageously, taking on the task, making sure the product on hand was able to treat kids and getting the program to a BLA filing. It has not been an easy road for us either, but we are gratified that all of this work has enabled us to bring forth the first approved treatment for Sanfilippo type A. Developing new therapies is only one part of our mission. We've also believed that approval only matters if patients can actually obtain treatment, and we are committed to helping eligible families within the U.S. access Fayuvi as quickly as possible.

We also know and have gotten urgent calls for treatment from families elsewhere in the world, also in great need, and we will work on finding a way to treat some patients globally while we seek approval in other regions. I'll now turn it to Eric Crombez to review the clinical data and Erik Harris to discuss our commercial launch preparations.

Thank you, Emil. Fayuvi is indicated for the treatment of neurologic manifestations of mucopolysaccharidosis type IIIA or Sanfilippo syndrome type A in pediatric patients with preserved neurodevelopmental function. As Emil noted, this is a rare and fatal lysosomal storage disease that primarily affects the brain and is marked by neurodegeneration beginning in early childhood. The disease is caused by an enzymatic deficiency, which results in the accumulation of heparan sulfate and progressive damage to the central nervous system. Fayuvi is a single-dose AAV9 gene therapy designed to directly address this underlying enzymatic deficiency. Conceptually, this gene therapy provides the ability to produce fully functioning enzyme in some cells in the brain to break down heparan sulfate. These cells will then secrete the enzyme that can cross-correct other brain cells, resulting in a decrease in heparan sulfate substrate levels throughout the brain.

The BLA was based on data from the phase I, II, III Transpher A study and long-term follow-up demonstrating improvements in key developmental domains compared with natural history, along with substantial and durable reductions in CSF heparan sulfate. Clinical data now extend to nearly 8 years of follow-up. FAYUVI was generally well-tolerated and maintained a favorable safety profile. The most frequently reported treatment emergent adverse events were elevation in liver enzymes, which were mostly mild or moderate. While we originally submitted FAYUVI for accelerated approval, the agency recognized the robustness of our clinical data package during the review and granted standard full approval rather than accelerated approval. Importantly, this approval covers the entire pediatric age range and reflects the deep understanding by the FDA of the unmet need for children and families affected by this disease.

Over time, we expect that children will be diagnosed earlier through newborn screening, enabling the option for early treatment prior to the accumulation of heparan sulfate and irreversible damage to the central nervous system. As with all of our therapies, we will monitor clinical trial patients and an additional cohort of commercially treated patients in our disease monitoring program through 10 years of follow-up. The totality of evidence generated throughout development gives us confidence in the potential of FAYUVI to meaningfully alter the course of this devastating disease. With that, I'll turn the call over to Erik.

Thanks, Erik. First, I'd like to acknowledge what a rare privilege it is to have the opportunity to launch two drugs in a month, impacting the lives of patients with significant unmet needs. The approach you heard me reference a few weeks ago, understanding the need of patients and caregivers first, remains our guiding principle for this second launch. Families with children that live with Sanfilippo syndrome type A understand that this disease is progressive and relentless. Every day matters to preserve precious neurologic function, and each day without treatment risks the potential loss of critical skills and abilities. That understanding has shaped our preparation. We are fortunate that both GENGLYCOS and FAYUVI fall within our inborn errors of metabolism franchise. So there are significant synergies between our preparations for both gene therapy launches.

Based on extensive pre-approval engagement with both Medicaid programs and leading commercial plans, it is clear that payers understand the devastating nature of Sanfilippo syndrome type A and the importance of treating as soon as possible. Beyond the clinical impact, payers recognize that the lifetime cost of care for a child with Sanfilippo syndrome type A, who can spend years in a bedridden state, can exceed $8 million, and that this burden grows as the disease advances. We set the U.S. per patient wholesale acquisition cost of FAYUVI at $3.95 million as the first and only one-time gene therapy treatment for this ultra-rare, progressive, and fatal neurodegenerative disease with the potential to slow or stop its irreversible decline. Consistent with our expectations for GENGLYCOS, we expect that access in the initial phase of launch for FAYUVI will flow through single-case agreements.

Our UltraCare program has a proven history of helping patients and families navigate access to therapies and overcome potential barriers to care. As I shared at the approval of GENGLYCOS, we have expanded that offering to include dedicated gene therapy guides who will help families navigate insurance coverage, assist in obtaining treatment support, and answer questions about treatment process. Treatment will be provided through a national network of qualified treatment centers selected for clinical expertise and experience in gene therapy administration. The network is highly synergistic with our footprint for GENGLYCOS, with many centers planning to offer both treatments. A list of QTCs will be available on fayuvi.com once that website is live in the coming days. As with GENGLYCOS, we have established relationships with the treating community.

Like families, providers understand that time is of the essence for these patients and approach treatment decisions with a strong sense of urgency. We are expecting fairly rapid requests for treatment. FAYUVI is manufactured entirely within the U.S. at our gene therapy manufacturing facility in Bedford, Massachusetts, and at Andelyn Biosciences in Columbus, Ohio. We believe we have adequate commercial supply to meet initial demand and will continue our efforts to scale manufacturing over time. We expect that the commercial product will be ready to ship to QTCs in approximately 30-60 days, consistent with the expectations we shared for GENGLYCOS. This is now our sixth commercial approval and second gene therapy launch. The infrastructure, capabilities, and experience we have built in commercializing rare disease therapies are highly applicable across our entire portfolio of approved medicines, with purposeful alignment built into our approach for FAYUVI.