Mereo's Partner Ultragenyx Announces First Patient Dosed in Pivotal Phase 2/3 Clinical Study of Setrusumab (UX143) for the Treatment of Osteogenesis Imperfecta

Global study will evaluate UX143 in pediatric and young adult patients ages 5 to <26 years of age

NOVATO, Calif. — April 20, 2022 — Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, today announced the first patient has been dosed in a clinical study for the treatment of Osteogenesis Imperfecta (OI) in patients ages 5 to <26 years of age. The pivotal Orbit study is a seamless Phase 2/3 study of setrusumab (UX143), an investigational anti-sclerostin fully human monoclonal antibody in development for the treatment of OI in children and adults with OI sub-types I, III and IV. Ultragenyx is leading the clinical development of setrusumab as part of a collaboration and license agreement with Mereo BioPharma Group plc (MREO), a clinical-stage biopharmaceutical company focused on oncology and rare diseases. “The Orbit study builds on the findings of the 12-month Phase 2b ASTEROID study, which demonstrated that treatment with setrusumab resulted in a clear, dose-dependent and statistically significant effect on bone formation and bone density at multiple anatomical sites among adult participants with OI,” said Camille Bedrosian, M.D., chief medical officer at Ultragenyx. “The Orbit Phase 2/3 study is designed to study fracture risk reduction in a younger population, where the risk of fracture is higher and where we can potentially have the greatest impact on their future health.” Tracy Hart, CEO of the Osteogenesis Imperfecta Foundation commented, “The OI Foundation is excited about the potential for new treatments for our community and are encouraged that they will potentially have an impact on the overall quality of life for our community.” Ultragenyx is planning additional studies for setrusumab, including an open-label, randomized Phase 3 study in patients aged 2 to <5 years evaluating setrusumab versus bisphosphonates for the treatment of OI over a period of 12 to 24 months that is anticipated to start in the second half of 2022. The company also plans to continue to study setrusumab in adult patients over the age of 25 with OI.

Orbit Study Design
The global, seamless Phase 2/3 Orbit study will evaluate the effect of setrusumab versus placebo on fracture rate in patients aged 5 to <26 years with OI sub-types I, III, and IV. In the Phase 2 portion, 36 patients will be randomized 1:1:1 to receive setrusumab at one of two doses or placebo to determine the optimal dosing strategy for Phase 3. The Phase 3 dosing strategy will be developed based on initial Phase 2 safety, pharmacokinetic, and bone biomarker data. The pivotal Phase 3 portion of the study will include approximately 195 participants, randomized 2:1 to receive setrusumab or placebo, with a primary endpoint of fracture rate reduction. All participants will transition to an extension period and receive open-label setrusumab after the Phase 3 primary analysis is complete, or once a participant has completed 24 months in the double-blind period, whichever is sooner. Further details can be referenced here: https://clinicaltrials.gov/ct2/show/NCT05125809

About Osteogenesis Imperfecta
Osteogenesis Imperfecta (OI) includes a group of genetic disorders impacting bone metabolism. Approximately 85% to 90% of OI cases are caused by mutations in the COL1A1 or COL1A2 genes, leading to either reduced or abnormal collagen and changes in bone metabolism. The collagen mutations in OI can result in increased bone brittleness, which contributes to a high rate of fractures, including at atypical sites. Patients with OI also exhibit increased bone resorption (breakdown of old bone) and inadequate production of new bone, which leads to decreased bone mass, bone fragility and weakness. OI can also lead to bone deformities including abnormal spine curvature, pain, decreased mobility, and short stature. No treatments are approved for OI, which affects approximately 60,000 people in the developed world.

About Setrusumab (UX143)
Setrusumab is a fully human monoclonal antibody that inhibits sclerostin, a protein that acts on a key bone-signaling pathway that inhibits the activity of bone-forming cells. The goal of blocking inhibitory effects of sclerostin is to increase new bone formation, bone mineral density, and bone strength. Sclerostin inhibition also reduces excessive bone resorption, further enhancing its impact on bone density. In various mouse models of OI, the use of anti-sclerostin antibodies was shown to stimulate bone formation, improve bone mass and density, and reduce bone fragility as reflected in increased long bone strength and reduced the number of fractures.  Mereo BioPharma’s Phase 2b study (ASTEROID) treatment phase of the dose-finding study of setrusumab for the treatment of OI in 112 adults was concluded in 2019. The ASTEROID study demonstrated treatment with setrusumab resulted in a clear, dose-dependent and statistically significant effect on bone formation and bone density at multiple anatomical sites among adult participants with OI. Off-treatment results were followed.  Ultragenyx and Mereo BioPharma are collaborating on the development of setrusumab globally based on the collaboration and license agreement between the parties. The companies are planning a comprehensive late-stage program to continue development of setrusumab in pediatric and young adult patients across OI sub-types I, III and IV.

About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare 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 the company's website at: www.ultragenyx.com.

About Mereo BioPharma
Mereo BioPharma is a biopharmaceutical company focused on the development of innovative therapeutics that aim to improve outcomes for oncology and rare diseases and plans to commercialize selected rare disease programs. The Company has developed a portfolio of six clinical stage product candidates. Mereo’s lead oncology product candidate, etigilimab (anti-TIGIT), has advanced into an open label Phase 1b/2 basket study evaluating anti-TIGIT in combination with an anti-PD-1 in a range of tumor types including three rare tumors and three gynecological carcinomas, cervical, ovarian, and endometrial carcinomas. The Company’s second oncology product, navicixizumab, for the treatment of late line ovarian cancer, has completed a Phase 1 study and has been partnered with OncXerna Therapeutics, Inc., formerly Oncologie, Inc. The Company has two rare disease product candidates, alvelestat for the treatment of severe Alpha-1 antitrypsin deficiency (AATD) and Bronchiolitis Obliterans Syndrome (BOS), and setrusumab for the treatment of osteogenesis imperfecta (OI). Alvelestat has recently received U.S. Orphan Drug Designation for the treatment of AATD and is being investigated in an ongoing Phase 2 proof-of-concept study in the U.S. and Europe, with top-line data expected in early Q2 2022. The Company’s partner, Ultragenyx Pharmaceutical, Inc., is expected to initiate a pivotal Phase 2/3 pediatric study and young adult study (5-25 years old) for setrusumab in OI in H1 2022.

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 business plans and objectives for UX143, the therapeutic potential and clinical benefits of UX143, expectations regarding the safety and tolerability of UX143, and future clinical developments for UX143 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 ability of the company and Mereo BioPharma to successfully develop UX143, the effects of the COVID-19 pandemic on the company’s clinical activities, business and operating results, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, uncertainty and potential delays related to clinical drug development, the company’s ability to achieve its projected development goals in its expected timeframes, risks and uncertainties related to the regulatory approval process, 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 Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 15, 2022, and its subsequent periodic reports filed with the Securities and Exchange Commission.  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/).