Ultragenyx Announces Initiation of Dosing in Second Cohort of Pivotal Phase 1/2/3 Cyprus2+ Trial Evaluating UX701 Gene Therapy for the Treatment of Wilson Disease

Initial data expected in first half of 2024

NOVATO, Calif., July 31, 2023 (GLOBE NEWSWIRE) — Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced it has begun dosing the second dose-escalation cohort in its pivotal Phase 1/2/3 Cyprus²⁺ study following completion of dosing and safety review in the first cohort. The company’s investigational AAV9 gene therapy is designed to deliver stable expression of the ATP7B copper transporter following a single intravenous infusion, with the goal of normalizing copper metabolism in patients with Wilson disease.

In the first dose cohort, UX701 has been well tolerated with no unexpected related treatment emergent adverse events observed as of July 11, 2023. The Data Safety Monitoring Board recommended that the company proceed with dosing patients at the higher dose of 1.0 x 10^13 GC/kg. Investigators have dosed the first patient and have identified and screened the remaining four patients for dosing in Cohort 2. The company is on track to complete enrollment in Stage 1 of the Phase 1/2/3 trial this year and expects to share initial data in the first half of 2024.

“We are encouraged by the safety data and early signals of the establishment of normal trafficking of copper observed in Cohort 1 and with acceleration of enrollment following improvements in study design and entry criteria,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “The shift to open label design and broadening of inclusion criteria allows us to enroll subjects who may not be well managed on current standard of care with chelators and/or zinc.”

U.S. residents can learn more by visiting ultraclinicaltrials.com.

Cyprus²⁺Phase 1/2/3 study design

This study evaluating UX701 for the potential treatment of Wilson disease is designed with three stages. During the first stage, the safety and efficacy of up to three dose levels of UX701 will be evaluated over the course of 52 weeks and a dose will be selected for further evaluation in Stage 2. In this first stage, 15 patients will be enrolled into three sequential dosing cohorts to evaluate doses of 5.0 x 10^12 GC/kg, 1.0 x 10^13 GC/kg, and 2.0 x 10^13 GC/kg.

In Stage 2, a new cohort of patients will be randomized 2:1 to receive the selected dose of UX701 or placebo. The primary safety and efficacy analyses will be conducted at Week 52 of Stage 2. The primary efficacy endpoints are change in 24-hour urinary copper concentration and percent reduction in standard of care (SOC) medication by Week 52. After the initial 52-week study period, all patients will have long term follow up in stage 3.

About Wilson Disease

Wilson disease is a rare inherited disorder caused by mutations in the ATP7B gene, which results in deficient production of ATP7B, a protein that transports copper. Loss of function of this copper-binding protein results in the accumulation of copper in the liver and other tissues, most notably the central nervous system, and also the failure to properly distribute copper by ceruloplasmin. Patients with Wilson disease experience hepatic, neurologic and/or psychiatric problems. Those with liver disease can experience such symptoms as fatigue, lack of appetite, abdominal pain and jaundice, and can progress to fibrosis, cirrhosis, life-threatening liver failure and death. Wilson disease can be treated by reducing copper absorption or removing excess copper from the body using life-long chelation therapy, but unmet needs exist because some treated patients experience clinical deterioration and severe side effects. Wilson disease affects more than 50,000 individuals in the developed world.

About UX701

UX701 is an investigational AAV9 gene therapy designed to deliver stable expression of the ATP7B copper transporter following a single intravenous infusion. It has been shown in preclinical studies to normalize copper trafficking and excretion from the body. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to UX701.

About Ultragenyx Pharmaceutical Inc.

Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.

The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.

For more information on Ultragenyx, please visit ultragenyx.com.

Ultragenyx Forward-Looking Statements and Use of Digital Media

Except for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx’s expectations and projections regarding its future operating results and financial performance, business plans and objectives for UX701, expectations regarding the tolerability and safety of UX701, and future clinical and regulatory developments for UX701 are forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our 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 UX701, the company’s ability to achieve its projected development goals in its expected timeframes, 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 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 Ultragenyx’s products and drug candidates. Ultragenyx 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 Ultragenyx in general, see Ultragenyx’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 5, 2023, and its subsequent periodic reports filed with the SEC.

In addition to its SEC filings, press releases and public conference calls, Ultragenyx uses its investor relations website and social media outlets to publish important information about the company, including information that may be deemed material to investors, and to comply with its disclosure obligations under Regulation FD. Financial and other information about Ultragenyx is routinely posted and is accessible on Ultragenyx’s Investor Relations website (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/mycompany/).

Contacts

Ultragenyx Pharmaceutical, Inc.
Investors
Joshua Higa
415-475-6370
IR@ultragenyx.com

Media
Jeff Blake
415-612-7784
media@ultragenyx.com