Material Event Form 8 K

Item 8.01 Other Events.

On July 17, 2024, Ultragenyx Pharmaceutical Inc. (the "Company") announced the successful completion of an end-of-Phase 2 ("EoP2") meeting with the U.S. Food and Drug Administration ("FDA"), supporting its Phase 3 study plans for GTX-102, an antisense oligonucleotide for Angelman syndrome.

Phase 3 design and next steps

The EoP2 meeting focused on discussion of the Company's interim Phase 1/2 data and resulted in alignment with the FDA on the Phase 3 study design and endpoints. The pivotal Phase 3, will be a global, randomized, double-blind, sham-controlled trial and will include a 48-week primary efficacy analysis period enrolling approximately 120 patients with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. The primary endpoint will be improvement in cognition assessed by Bayley-4 cognitive raw score. Control patients completing the study will be eligible to roll over onto treatment after the double-blind period is over.

Previously disclosed results from the Phase 1/2 study showed that UBE3A gene deletion patients treated with GTX-102 experienced rapid, progressive and clinically significant improvement in cognition, as assessed by Bayley-4, that was far greater than the minimal change observed in Natural History data(1)in deletion patients. UBE3A gene deletion patients are at the severe end of the clinical spectrum, with lower Bayley scores at baseline, and demonstrate a much slower rate of skill attainment compared to, for example, UBE3A missense mutation patients, who demonstrate higher Bayley cognition improvement in Natural History data(2). In the Phase 1/2 study, GTX-102 treated patients also demonstrated meaningful improvements in other domains of communication, motor function, sleep problems, and behavior.

The Phase 3 study will include the key secondary endpoint of the Multi-domain Responder Index (MDRI) across all five domains of cognition, receptive communication, behavior, gross motor function, and sleep. Individual secondary endpoints were also discussed and aligned on with the FDA for the domains of communication, behavior, motor function and sleep. Additional feedback on the conduct and analysis of these endpoints may be received from the FDA's Division of Clinical Outcomes Assessment.

Global regulatory progress

The Company has also participated in a PRIME meeting with the European Medicines Agency, receiving acceptance of the overall Phase 3 study design, dosing and evaluations. The Company expects to meet with Japan's Pharmaceuticals and Medical Devices Agency in the coming weeks to inform and discuss the Phase 3 study design.

Additional genotypes and ages to be studied in Phase 3

In addition to the randomized, controlled Phase 3 study, the Company discussed with the FDA its plans to initiate an open-label clinical study to evaluate the safety and efficacy of GTX-102 for the treatment of patients with other Angelman syndrome genotypes and in other age groups. The goal of this additional study would be to enable treatment across a broad array of Angelman patient types.

1) https://clinicaltrials.gov/study/NCT00296764

2) https://pubmed.ncbi.nlm.nih.gov/33517526/

Cautionary Note Regarding Forward-Looking Statements

This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of words such as, but not limited to, "anticipates," "continue," "will," or other similar terms or expressions that concern the Company's expectations, plans and intentions. Forward-looking statements include, without limitation, statements regarding the clinical benefit, tolerability and safety of GTX-102 and the corresponding impact on patients, the anticipated dosing of the Phase 2 study for GTX-102, the timing for initiation of a Phase 3 study for GTX-102 and associated regulatory meetings and the Company's plans to initiate other studies evaluating GTX-102 with other Angelman syndrome genotypes and in other age groups. Such forward-looking statements involve substantial risks and uncertainties that could cause the Company's clinical development programs, collaboration with third parties, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainty of clinical drug development and unpredictability and lengthy process for obtaining regulatory approvals, the ability of the Company to successfully develop GTX-102, the Company's ability to achieve its projected development goals in its expected timeframes, the risk that results from earlier studies may not be predictive of future study results, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the Company's behalf, smaller than anticipated market opportunities for the Company's products and product candidates, manufacturing risks, competition from other therapies or products, and other matters that could affect the sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the Company's future operating results and financial performance, the timing of clinical trial activities and reporting results from same, and the availability or commercial potential of the Company's products and drug candidates. The Company undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the business of the Company in general, see the Company's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 3, 2024, and its subsequent periodic reports filed with the SEC.

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