Creatine Deficiency, X-Linked

NOVATO, Calif., April 12, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced that preclinical and clinical data, including new clinical efficacy and safety data from the expansion cohorts in the Phase 1/2 study of GTX-102 for the treatment of Angelman syndrome, will be presented at the 76th Annual American Academy of Neurology Meeting (AAN) being held April 13-18 in Denver and virtually. GTX-102 is an investigational antisense oligonucleotide delivered via intrathecal administration and is designed to target and inhibit expression of UBE3A antisense transcript (UBE3A-AS). Abstracts are available to view online at . The GTX-102 emerging science presentation will include data beyond what is currently available online. AAN 2024 Presentation Details: Title: Clinical Activity and Safety of GTX-102, an Investigational Antisense Oligonucleotide for the Treatment of Patients With Angelman Syndrome Format: Oral (abstract #192, presentation #008) Session: Emerging Science 2 Presenter: Kemi A. Olugemo, M.D., FAAN, Ultragenyx Date/ Time: Tuesday, April 16, 6:12-6:18 p.m. MDT Title: Proteomic Profiling of Angelman Syndrome for Disease-Associated Biomarker Discovery Format: Poster (#8.001) Session: Child Neurology and Developmental Neurology: Neurogenetics 2 Presenter: Rachael Elizabeth Hawtin, Ph.D., Ultragenyx Date/ Time: Tuesday, April 16, 5:30-6:30 p.m. MDT Title: Clinical Characteristics of Creatine Transporter Deficiency (CTD): Final Results of the Vigilan Observational Study Format: Poster (#8.002) Session: Child Neurology and Developmental Neurology: Neurogenetics 2 Presenter: Melanie Brandabur, M.D., Ultragenyx Date/ Time: Tuesday, April 16, 5:30-6:30 p.m. MDT Conference Call and Webcast Information Ultragenyx will host a conference call at 8:00 a.m. ET on Wednesday, April 17, 2024, to discuss the new efficacy and safety data from the GTX-102 Phase 1/2 clinical study being presented at the conference. The live and replayed webcast of the call will be available through the company’s website at . To participate in the live call, please register by clicking on the following link (registration link) and you will be provided with dial-in details. 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 the company's website at: . 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 GTX-102, expectations regarding the tolerability and safety of GTX-102, and future clinical and regulatory developments for GTX-102 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 GTX-102, 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 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 21, 2024, 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 ( ) and LinkedIn website ( ). Contacts Ultragenyx Pharmaceutical Inc. Investors Joshua Higa +1-415-475-6370 ir@ultragenyx.com Media Carolyn Wang +1-415-225-5050 media@ultragenyx.com

NEW YORK--( BUSINESS WIRE )-- RTW Charitable Foundation (“RTWCF”) announced today that it has awarded $900,000 in research grants to support six research studies. These studies aim to drive transformational progress in genetic therapies and align with RTWCF’s mission to power community initiatives and scientific research to improve the health of underserved communities. Grant Recipients The following studies and researchers each received $150,000 research grants from RTWCF: “ Establishing gene replacement therapy for NEDAMSS, an ultra-rare neurological disorder caused by mutations in the IRF2BPL gene” (Kathrin Meyer, Nationwide Children’s Hospital, Columbus, OH). “ Optimizing AAV-SPL gene therapy for sphingosine phosphate lyase insufficiency syndrome” (Julie Saba, University of California, San Francisco, San Francisco, CA). “Gene therapy for SURF1-related Leigh Syndrome” (Steven Gray, The University of Texas Southwestern, Dallas, TX). “ Safety and toxicity assessment of AAV-based gene therapy for creatine transporter deficiency” (Jagdeep Walia, Queen’s University, Kingston, Ontario, Canada). “Advanced therapeutics for SELENON-related myopathy” (Alan Beggs, Boston Children’s Hospital, Boston, MA). “ Preclinical studies of ASO therapy for SPTLC1-related hereditary sensory neuropathy” (Haiyan Zhou, University College London, London, UK). “ Despite considerable advancements in gene and cell therapies that deliver more targeted and effective treatments for rare diseases, a significant amount of additional research is still required to move these advances out of the lab and safely to patients,” said Juan Carlos López, PhD, Managing Director, Research Grants, RTW Charitable Foundation. “ RTW Charitable Foundation is proud to provide financial and scientific support to these six incredible researchers and their respective studies. We believe that each of these studies will help expedite the development of gene therapies for rare and ultrarare diseases, and greatly improve the lives of individuals with unmet medical needs.” Grant Recipient Commentary Julie Saba, MD, PhD, commented : “ I am honored and grateful to receive this award from RTWCF, which will support studies to optimize gene therapy for sphingosine phosphate lyase insufficiency syndrome. This newly recognized inborn error of metabolism leads to kidney failure in most of the affected children, causing more than half of them to die in their first years of life. While kidney transplantation can be lifesaving, it is invasive, costly, unavailable to many, and does not address the many other serious consequences of the disorder. Gene therapy offers a potentially lifesaving alternative treatment. The studies undertaken with RTWCF funding should improve our gene therapy potency, allowing us to advance to toxicology studies and clinical trials. I appreciate RTWCF’s dedication to advancing research in ultrarare diseases, which are overwhelmingly underfunded. Every child deserves personalized therapy!” Alan Beggs, PhD, commented: “ Our group has studied a neuromuscular condition called Multiminicore Disease or Rigid Spine Muscular Dystrophy for many years to understand how mutations of a gene called SELENON lead to weakness. We are now on the cusp of translating our laboratory experiments into a treatment that can be tested in patients. I’m thrilled that support from the RTWCF is helping us to work towards developing a next-generation gene therapy candidate designed for eventual testing in a clinical trial.” Haiyan Zhou, MD, PhD, commented: “ We are extremely grateful for the generous award from RTWCF. This grant serves as a vital catalyst in advancing our groundbreaking work on a novel nucleic acid therapy designed for an ultrarare neurodegenerative condition, currently devoid of effective treatment options. The crucial support from RTWCF will propel the preclinical development and hasten the clinical translation of this experimental therapy. Moreover, this award will play a pivotal role in elevating the impact of our translational genetic therapy program at the Great Ormond Street Institute of Child Health and NIHR GOSH Biomedical Research Centre. It also contributes to the growth of the UK platform for nucleic acid therapy in rare diseases.” To date, RTWCF has awarded over 20 research grants, totaling over $3 million in funding. In addition to delivering financial resources, RTWCF also provides grant recipients with hands-on scientific support, helping them improve or further develop their research and research tools and identify new therapeutic targets. About RTW Charitable Foundation Founded in 2018 as the charitable foundation arm of RTW Investments, LP, RTW Charitable Foundation works to power community initiatives and scientific research to improve the health of underserved communities. The Foundation is able to provide capital, manpower, and logistical support to help scientists push such projects forward. In addition, the Foundation aims to assist in advocacy, disease awareness and directly support organizations and communities in New York City. To learn more, visit www.rtwcf.org .

The University of California Los Angeles (UCLA) has published a promising study that shows gene therapy may correct a rare creatine deficiency disorder that results in intellectual disabilities, issues with speech, involuntary movements and recurrent seizures. The study utilizes gene therapy to gradually correct abnormal creatine and guanidinoacetic acid (GAA) levels in mouse subjects with an extremely rare genetic disorder that affects creatine levels. The disorder, guanidinoacetate methyltransferase (GAMT) deficiency, is standardly treated with early creatine supplementation and optional investigational therapies. The disorder is named for the deficiency in a key enzyme involved in creatine synthesis, GAMT. GAMT enzymes are responsible for the methylation of GAA to synthesize creatine, which is then circulated to bodily tissues. Without a functioning creatine synthesis pathway, GAA levels can accumulate to toxic levels while the body suffers from a lack of creatine. In the study, the research team used an existing viral vector system intended for gene therapy to deliver a non-mutated GAMT gene. With this functioning gene, the mice developed normalized creatine and GAA levels by day 30. The subjects were monitored for one year to observe the effects this had on GAMT deficiency symptoms. According to the National Organization for Rare Disorders (NORD), GAMT deficiency management requires multidisciplinary medical attention. The brain needs creatine to function, so routine neurologist visits are necessary. The hereditary nature of the disorder beckons for geneticist consultation. Dieticians are required to ensure the patient intakes creatine-rich foods and supplementation. To manage muscle weakness and movement-related symptoms, physical therapists routinely work with patients with GAMT deficiency. Additional manifestation is seen through seizures, behavioral problems and intellectual or developmental difficulties. If left untreated and unmonitored, GAMT deficiency can lead to the development of kidney disease. Globally, as of 2015, only 110 patients with GAMT deficiency were reported. The low prevalence is likely due to the autosomal recessive hereditary pattern, through which a mutated, non-functional GAMT gene must be passed down from each parent. “What we’ve been able to demonstrate is that adult mice treated with this therapy now have normal cognitive activity, which was abnormal before the gene therapy,” said Gerald S. Lipshutz, M.D., study author and an affiliate of the UCLA Department of Surgery and the Intellectual and Developmental Disabilities Research Center at the Jane and Terry Semel Institute for Neuroscience and Human Behavior. “While the human brain and learning is more complex than that of the mouse, we hope that permanently lowering GAA toxin levels in the brain will lead to correction of cognitive and behavioral abnormalities for human patients.” As described by Lipshutz, the gene therapy method corrected the GAMT deficiency and allowed bodily functions to return to normal. The next steps for this investigational therapy will be to determine whether human trials are plausible, and a lower dose might be required to ensure patient safety. The findings were published in the scientific journal Molecular Therapy: Methods and Clinical Development. While this first phase of research was funded by a grant from the U.S. National Institute of Health and the Association for Creatine Deficiencies, it is unclear how additional research will be funded.