Ultragenyx Pharmaceutical Inc. Status update

Thank you, and good afternoon, everyone. We appreciate you all for making time to join us on such short notice to discuss this important day for Ultragenyx. The press release we issued announcing the approval of GENGLYCOS is available on our website at ultragenyx.com. Joining me on today's call are Emil Kakkis, Chief Executive Officer and President, Eric Crombez, Chief Medical Officer, Erik Harris, Chief Commercial Officer, and Howard Horn, Chief Financial Officer. Before we begin, I'd like to remind everyone that during today's call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. Please refer to the risk factors discussed in our SEC filings. With that, I'll turn the call over to Emil.

Thank you, Josh, and good afternoon, everyone. Today is an important day for Ultragenyx and for the GSD1A community. Earlier today, the FDA approved GENGLYCOS, marking Ultragenyx's first gene therapy approval and the fifth approved medicine in our company's history. It is also the first ever FDA-approved treatment designed to address the underlying cause of glycogen storage disease type 1A, representing exactly the type of breakthrough therapy Ultragenyx was built to deliver. This is a day that thousands of people living with GSD1A in the United States and elsewhere, and the families and clinicians who care for them, have hoped and advocated and fought for over the years. Until today, the only thing standing between a person living with GSD1A and a life-threatening episode of hypoglycemia was cornstarch taken as a slurry every 3 to 4 hours around the clock, day and night.

Now there's an additional treatment with the potential to reduce their dependence on cornstarch and ease the constant burden of care that defines their lives. We're grateful to everyone across the GSD1 community who helped make this today possible, and we want to especially thank the patients and families for participating in our clinical trials. As a reminder, our randomized placebo-controlled phase III study met its primary endpoint with a statistically significant reduction in daily cornstarch intake and was also positive in multiple secondary endpoints. Late during the review, the FDA decided to consider cornstarch reduction as a surrogate endpoint and so approved GENGLYCOS by accelerated approval pathway. The FDA requests additional evidence to confirm this reduction associated with clinical benefit and improved fasting tolerance over time.

We agreed to generate that data through enhancements to our existing disease monitoring program, or DMP, and Eric will share some additional details of our post-marketing program when he walks through our clinical data. Ultragenyx was created to lead the future of rare disease medicine, and that vision goes beyond the moment of approval and into our conduct as a commercial company. We are committed to helping patients access the treatments they need and reduce financial barriers that may stand in their way. GENGLYCOS extends that leadership into gene therapy, and it does so as a medicine we manufacture end-to-end entirely in-house at our gene therapy manufacturing facility in Bedford, Massachusetts. With that, I will turn the call over to Eric Crombez and Erik Harris to walk you through our data and launch plans, and finally Howard Horn to comment on the PRV and our expectations for launch.

Thank you, Emil. The approval of GENGLYCOS fulfills our commitment to provide the first therapy that directly targets the root cause of GSD1A. The reduced reliance on cornstarch demonstrates this liver-directed gene therapy's capability to deliver the necessary transgene to enable patients' livers to break down glycogen and to produce glucose during fasting or metabolic stress. This ability to regulate glucose levels has alleviated the disease burden and mitigated the risk of severe or life-threatening hypoglycemia for these patients. GENGLYCOS is indicated for the treatment of adult and pediatric patients 8 years of age and older with glycogen storage disease type 1A who do not have antibodies to AAV8. The BLA was based on data from our phase III randomized, double-blind, placebo-controlled study, which enrolled 46 patients aged 8 years and older.

Results from the phase III study show that patients treated with GENGLYCOS reduced daily cornstarch requirements compared to placebo while maintaining glycemic control. GENGLYCOS was well-tolerated with an acceptable safety profile. The most common treatment-related events were transient elevations in liver enzymes that were generally non-serious and managed with a prophylactic corticosteroid regimen. The results across the entirety of the clinical development program, which encompasses data on 52 treated patients over 8 years of follow-up, speaks to both the magnitude and to the durability of effect of this gene therapy. In regard to the post-marketing requirements that Emil referenced, we will collect 2 years of data from 50 commercially treated patients through enhancements to our existing disease monitoring program, evaluating daily cornstarch intake and time to hypoglycemia in a controlled fasting challenge.

We will also follow 20 untreated patients who have AAV8 antibodies over the same time period as a control group. Unlike the phase III study, this DMP evaluation will be performed in the open label setting with patients and the physicians receiving real-time glucose measurements. We believe that this will allow for greater corn starch reduction and improved metabolic control compared to what can be achieved in a blinded study without real-time glucose information available to patients. As a reminder, the use of a DMP is the strategy that we have used for 4 prior approvals as the sole and comprehensive evaluation of all of our treatments in the post-marketing setting. The GSD1A DMP will collect 10 years of treatment data across clinical study participants and new commercially treated patients.

This DMP is already active and enrolling clinical trial patients as they cross over from the phase III study to long-term follow-up. With that, I'll hand it to Eric to discuss how we are bringing GENGLYCOS to patients.

Thank you, Eric. As we have approached each launch in our portfolio, our guiding principle has been to start with understanding the needs of the patients and caregivers. The repeated success of this approach has informed our preparation. Supporting patients is at the center of our work. Our UltraCare program has an established track record of helping patients and families successfully navigate access to our approved therapy. Treatment with gene therapy is a multi-step process. So we have adapted our offering with that reality in mind. We have established a new dedicated role called UltraCare Gene Therapy Guides, who will help patients navigate insurance coverage, assist in obtaining treatment support, and answer questions about the treatment process. In coordination with providers, treatment will be delivered through a national network of qualified treatment centers, institutions with specialized expertise and training to safely administer gene therapy.

We selected our network of centers based on clinical experience with GSD1A and gene therapy administration, as well as for a geographic footprint that is right-sized for anticipated demand while minimizing travel burden for patients and their families. Our teams are being deployed immediately upon this approval to train teams at QTCs on the final label and will continue to onboard and train centers to ensure medical readiness on an enrolling basis as contracts are finalized. A list of QTCs will be available on ultragenyx.com once that website is live in the coming days. As we've mentioned previously, there is roughly 75% overlap in GSD1A providers with the treating community we know well from MEPSEVII and DOJOLVI. Our commercial organization is already in the field and able to leverage established trusted relationships with key providers. Shifting to payers. Our work to lay the foundation for quality coverage has been extensive, with numerous interactions across state Medicaids and large national payers.

Consistently, payers appreciate the severity of GSD1A and associated unmet needs. We are also encouraged that they recognize a reduction in cornstarch dependence as a clinically meaningful endpoint that represents the potential to deliver substantial impact for patients, caregivers, and their families. We have set the U.S. per-patient wholesale acquisition cost of GENGLYCOS at $2.7 million, reflecting its potential to reduce patients' reliance on cornstarch and enable better metabolic control of glucose. As Emil emphasized at the outset, we have a strong commitment and track record of supporting patients and families in helping to access our approved medicines, and that approach will extend to gene therapy.

Consistent with what's been observed for other newly approved gene therapies, we expect access will flow through single-case agreements in the initial phase of launch. We are familiar with and experienced in this pathway. We stand ready to help patients and providers in navigating the process. GENGLYCOS is manufactured entirely in-house at our gene therapy manufacturing facility in Bedford, Massachusetts. We have existing commercial inventory to meet anticipated demand and will continue to scale production as the launch continues. I'll close by reminding you this is our fifth commercial launch in rare disease. We are leaders in navigating, or in some cases building, complex paths from product to patient. Our team brings the experience, agility, and most importantly, the commitment for patients as we deliver our first gene therapy in the commercial setting. With that, I'll turn to Howard to touch on launch expectations.

Thank you, Eric. Consistent with our practice, we plan to provide revenue guidance once we have sufficient visibility into market dynamics, which historically has been approximately six quarters after launch. In the interim, we look forward to updating you on metrics such as how our TTC network is growing and ultimately the number of patients that have been treated. With clear urgency to treat supporting patient demand and our highly leveraged commercial model, we expect GENGLYCOS will make an important contribution to our profitability. Additionally, I can confirm that Ultragenyx received a priority review voucher for GENGLYCOS' approval. We plan to monetize the PRV to bolster our balance sheet and support our path to profitability. With that, I'll turn it back to Emil to close.