Glut1 Deficiency Syndrome

Green light from HAS to facilitate reimbursement of METAglut1TM test in France Decision paves the way for adoption and reimbursement of the test in Europe and the U.S. PARIS--(BUSINESS WIRE)-- METAFORA biosystems, today announces that the Haute Autorité de Santé (HAS), the French Health Technology Agency, has issued a recommendation for insurance coverage of METAglut1TM, a test for the early diagnosis of De Vivo disease (or GLUT1 deficiency syndrome), a rare neurometabolic disorder. The HAS conducted a thorough evaluation of METAglut1TM, which included an assessment of its clinical performance and clinical utility. The evaluation concluded that METAglut1 is a valuable addition to the diagnostic arsenal for Glut1 DS, and was ascribed a high clinical added value. Vincent Petit, CEO of Metafora, said, “We are extremely proud to obtain HAS approval for METAglut1, a true milestone for the company and our partners, and not least for GLUT1 deficient patients. This rare neurometabolic disease is highly underdiagnosed, and we expect that METAglut1’s availability will increase awareness and help physicians to diagnose the disease earlier. We are grateful for the Forfait Innovation of the French Ministry of Health, which has allowed us to bring a multi-year prospective study to its successful conclusion. We look forward to making METAglut1 available to patients and clinicians in France and other large European countries, while we are actively exploring ways to launch the test in the U.S. as well.” Principal Investigator Prof. Fanny Mochel, Head of the Reference Centre for Adult Neurometabolic Diseases at AP-HP Pitié-Salpêtrière Hospital said, “METAglut1 quickly and accurately diagnoses GLUT1 deficiency syndrome. Its reimbursement will be of major benefit to physicians, pediatricians and neurologists, but especially to patients with this rare disease, as its early diagnosis is essential for targeted therapeutic management that can significantly improve the symptoms and daily lives of patients and their families.” About De Vivo disease & METAglut1TM – diagnose to cure De Vivo disease, or GLUT1 deficiency syndrome, is a rare and debilitating neurological disease. An estimated 30,000 people suffer from the GLUT1 deficiency syndrome in Europe and the USA, of which less than 2,000 are currently diagnosed. GLUT1-deficient patients suffer from an impaired glucose uptake by brain cells, leading to epileptic seizures, ataxia and often developmental delay. Uniquely, unlike for many genetic diseases, treatment is relatively straightforward, requiring a high-fat diet (known as a ketogenic diet), which significantly improves symptoms in patients. Early diagnosis is therefore of the essence. A multicenter validation study supported by the French Society of Neuropediatrics (SFNP) and the French Society for the Study of Innate Metabolic Diseases (SFEIM), was presented at the 3rd European GLUT1D Conference in 2021 and is accepted for a forthcoming publication in a leading scientific journal. It demonstrated that METAglut1 resulted in almost 100% specificity and a sensitivity of approximately 80%. METAglut1 identifies affected children and adults within 48 hours, unlike current diagnostic tests which rely on a lumbar puncture, an invasive procedure, and complex genetic analysis. METAglut1 is the result of a collaboration between METAFORA biosystems, the teams at Greater Paris University Hospitals (AP-HP), over 30 clinical trial sites, Cerba HealthCare, a clinical testing laboratory responsible for supporting the rollout of METAglut1 in France, and CNRS. METAglut1 is the first product to receive a recommendation through the Forfait Innovation program supported by the French Ministry of Solidarity and Health. The Forfait Innovation was critical in supporting a 30-month study in over 60 pediatric and adult neurology centers in France to demonstrate the efficacy of METAglut1 for the early detection of the GLUT1 deficiency syndrome. About METAFORA biosystems Metafora biosystems is a health-tech company based in Paris with 30 employees, developing a single-cell analysis platform. This platform allows to measure changes in single-cell metabolism, and determine “cell metabolic fitness” or lack thereof, which is a telltale sign of disease, especially in neurology, cancer and inflammatory diseases. METAglut1 is a first diagnostic test for the early diagnosis of De Vivo disease, a rare pediatric neurometabolic disorder. The company has forged key partnerships, notably with Sebia, a leading player in in vitro diagnostics, for the development of new diagnostic tests in oncology, and of a solution to increase the clinical efficacy of cell therapies and reduce manufacturing costs. Metafora has also developed METAflowTM, a cytometry data analysis software with unmatched robustness and a user-friendly interface that yields objective, reproducible, and actionable results from the increasingly large and unwieldy data sets generated by conventional, mass or spectral cytometry. A first research use only version will be launched by mid-2023, and developments are ongoing to turn METAflow into a clinical grade solution. Metafora has received grants to develop its technology platform from Bpifrance and funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 806038, and is laureate of the EIC Accelerator program from the European Commission. View source version on businesswire.com: Contacts For further information: Vincent Petit, CEO Phone: +33 6 76 71 61 14 Email: vincent.petit@metafora-biosystems.com Source: METAFORA biosystems View this news release online at:

Launch in Europe & U.S. for limited number of RUO licensees Global launch expected later in spring PARIS & CHICAGO--(BUSINESS WIRE)-- METAFORA biosystems, today announces the launch of METAflow, its digital flow cytometry platform, into the RUO market. METAflow offers the power of a highly advanced unsupervised algorithm suite through a simple, elegant workflow accessible to any user, from beginners to advanced users. A cloud-based software enabling automated multidimensional clustering of flow cytometry data, METAflow marks a dramatic advance over existing, suboptimal solutions, regardless of data processing skills. Vincent Petit, CEO of Metafora, said, “Scientists and biologists today analyze flow cytometry data either manually, through a so-called gating strategy, or through a mix of manual data preprocessing and the implementation of a series of algorithms. Multiple trial and error runs are required before finding the right settings, and getting relevant results. In contrast, METAflow offers a faster, more robust and intuitive way to reach the desired populations. We look forward to rolling out METAflow to at first a limited number of RUO licensees, and setting the stage for accessing the research community at large later this spring.” Starting today, a limited number of licensees from Europe and the U.S. will start working with METAflow. The feedback of these first customers will serve to prepare for the global roll-out of METAflow in spring, while simultaneously scaling the support team of application and digital specialists and the opening a U.S. office. About METAflow METAflow is a flow cytometry data analysis software with unmatched robustness and a seamless, comprehensive, user-friendly interface. Metafora believes that METAflow will allow hundreds of thousands of flow cytometrists to move from cumbersome sequential manual gating to automated multidimensional clustering to obtain more objective data in a much shorter timeframe. METAflow provides objective, reproducible, traceable results, all in a collaborative digital platform that empowers users to mine and retrieve the best from increasing data sets generated by conventional, mass or spectral cytometry. After a successful features’ showcase during CYTO22 and ESSCA conferences, and a year of continuous development through an early access program, METAflow is now ready to enter the RUO market. To go beyond the RUO market, Metafora is developing, partly financed through the EIC Accelerator Program, a clinical grade version for use in clinical research and in routine settings. About Metafora METAFORA biosystems has developed METAflow, a flow cytometry data analysis software with unmatched robustness and a user-friendly interface that yields objective, reproducible, and actionable results from the increasingly large and unwieldy data sets generated by conventional, mass or spectral cytometry. METAflow in combination with Metafora’s proprietary reagents underpins METAbolism, the company’s IVD activity. METAglut1 is a first diagnostic test for the early diagnosis of De Vivo disease, a rare pediatric neurometabolic disorder. The company is developing a number of oncology diagnostics as well as a solution to increase the clinical efficacy of cell therapies and reduce manufacturing costs.

Ultragenyx Pharmaceutical Inc. today reported its financial results and corporate update for the quarter ended September 30, 2018. NOVATO, Calif., Nov. 05, 2018 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc.(NASDAQ: RARE), a biopharmaceutical company focused on the development of novel products for serious rare and ultra-rare genetic diseases, today reported its financial results and corporate update for the quarter ended September 30, 2018. “We’re encouraged by the growing demand for Crysvita from both children and adults with XLH in the United States, and we are making significant progress reaching doctors and helping them get patients on commercially available therapy in this early launch phase,” said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. “Next year, we expect to potential approval of our third therapy, UX007 in fatty acid oxidation disorders, and we continue to advance our two gene therapy clinical programs with additional data expected around the end of this year and in 2019.” Financial Results For the third quarter of 2018, Ultragenyx reported a net loss of $87.3 million, or $1.74 per share, basic and diluted, compared with a net loss for the third quarter of 2017 of $79.2 million, or $1.87 per share, basic and diluted. For the nine months ended September 30, 2018, net loss was $109.8 million, or $2.22 per share, basic and diluted, compared with a net loss for the same period in 2017 of $220.4 million, or $5.22 per share, basic and diluted. The loss from the first nine months was reduced by the sale of the Mepsevii™ (vestronidase alfa) priority review voucher (PRV) in January 2018 for net proceeds of $130.0 million and a $40.3 million gain from Ultragenyx’s portion of the sales of the PRV received with the Crysvita® (burosumab) approval. The net loss for the first nine months of 2018 reflected cash used in operations of $234.7 million compared to $172.0 million for the same period in 2017. Net Revenues For the third quarter of 2018, Ultragenyx reported $11.8 million in total revenue. For Crysvita, Ultragenyx recognized $5.4 million in profit sharing and royalty revenue from its collaboration and license agreement with Kyowa Hakko Kirin. This includes $4.4 million in collaboration revenue in the U.S. profit share territory and $1.0 million in royalty revenue in the European territory. Net product sales for Crysvita in other regions were nominal. Mepsevii product revenue for the third quarter of 2018 was $2.1 million, and UX007 named patient revenue was $0.4 million. Ultragenyx recognized $3.6 million in revenue from its research agreement with Bayer. Operating Expenses Total operating expenses for the third quarter of 2018 were $101.4 million compared with $83.9 million for the same period in 2017, including non-cash stock-based compensation of $20.7 million and $17.2 million in the third quarter of 2018 and 2017, respectively. Total operating expenses for the nine months ended September 30, 2018, were $316.3 millioncompared with $232.3 million for the same period in 2017, including non-cash stock-based compensation of $59.0 million and $48.5 million in the first nine months of 2018 and 2017, respectively. The increase in total operating expenses is due to the increase in commercial, development, and general and administrative costs as the company commercializes, grows and advances its pipeline. Cash, Cash Equivalents and Investments Cash, cash equivalents and investments were $503.1 million as of September 30, 2018. Recent Updates Crysvita in X-Linked Hypophosphatemia (XLH) Ultragenyx submitted regulatory filings in Canada, Brazil and Colombia. We anticipate regulatory decisions in these markets over the course of 2019. Reimbursed named patient treatment has already begun in Argentina in response to physician requests for multiple patients. Crysvita in Tumor-Induced Osteomalacia (TIO) Positive longer-term 48-week and 72-week data from the Phase 2 study of Crysvita in adults with TIO were presented at the American Society for Bone and Mineral Research (ASBMR) 2018 Annual Meeting in Montreal . In adults with TIO, Crysvita was associated with increases in serum phosphorus and serum 1,25 dihydroxy vitamin D levels; improvements in osteomalacia, mobility and vitality; and reductions in fatigue. Adverse events (AE) generally reflected the patients’ underlying diseases, and there were no serious treatment-related AEs during the study. Discussions with the U.S. Food and Drug Administration (FDA) regarding the regulatory pathway are ongoing. Mepsevii in Mucopolysaccharidosis VII (MPS VII) The European Commission (EC) approved the Marketing Authorization Application (MAA) for Mepsevii under exceptional circumstances for the treatment of non-neurological manifestations of MPS VII. Mepsevii is now approved for use in all 28 EU countries as well as in Iceland, Liechtenstein and Norway, and has launched in Germany. Brazil’s National Health Surveillance Agency approved Mepsevii for the treatment of MPS VII for patients of all ages. Additional regulatory decisions for patients in Columbia and Chile are anticipated over the course of 2019. UX007 in Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) and Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) The FDA accepted Ultragenyx’s proposal to submit a New Drug Application (NDA) for UX007 for the treatment of LC-FAOD based on currently available data. Further details will be forthcoming following a pre-NDA meeting, which is scheduled to take place by the end of 2018. Additionally, discussions are progressing with the European Medicines Agency regarding a potential conditional marketing authorization in Europe. In October 2018, Ultragenyx announced that the Phase 3 study evaluating UX007 in patients with Glut1 DS did not achieve its primary endpoint compared to placebo. The safety pro in this study was consistent with what has been previously reported with UX007. Ultragenyx plans to discontinue further Glut1 DS clinical development for UX007, and expects no impact on plans for the LC-FAOD indication. DTX301 Gene Therapy in Ornithine Transcarbamylase (OTC) Deficiency Positive topline data from the first two dose cohorts of the Phase 1/2 study demonstrate normalization of ureagenesis in two patients and further support proof-of-concept. The first responder (Cohort 1) showed a further increased level of ureagenesis at 52 weeks and has been clinically stable for more than eight months after discontinuing alternate pathway medications and also after liberalizing a protein-restricted diet near the 52 week time point. The second responder (Cohort 2) achieved normalization of ureagenesis at 24 weeks, and has been clinically stable for more than one month after also discontinuing all alternate pathway medications. The remaining four patients in Cohorts 1 and 2 continue to demonstrate no clinically meaningful change in rate of ureagenesis. All patients have remained clinically and metabolically stable, with only modest rises in ALT well treated by a reactive, tapering steroid regimen. The first patient in cohort 3 has been dosed. Data from higher dose Cohort 3 are expected in mid-2019. DTX401 Gene Therapy in Glycogen Storage Disease Type Ia (GSDIa) All three patients in the lowest-dose Cohort 1 of the Phase 1/2 study have been dosed. Data from this cohort are expected around the end of 2018. CDKL5 Deficiency Disorder (CDD) Ultragenyx exercised its option with REGENXBIO Inc. to develop a gene therapy to treat patients with CDD using REGENXBIO’s adeno-associated virus (AAV) vectors, including AAV9. CDD is a severe and debilitating neurological disorder that shares many features of Rett Syndrome. It was commonly identified as an atypical Rett Syndrome until improved genetic testing led to more accurate diagnosis and an increasing prevalence of diagnosed CDD-affected patients. Corporate Ultragenyx appointed a Chief Operating Officer, Wladimir (Vlad) Hogenhuis, M.D., on September 28, 2018. In this newly created role, Dr. Hogenhuis oversees the Global Commercial, Business Development, and Manufacturing organizations. Conference Call and Webcast Information Ultragenyx will host a conference call today, Monday, November 5, 2018, at 2 p.m. PT/ 5 p.m. ET to discuss third quarter 2018 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at . To participate in the live call by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (international) and enter the passcode 1290627. The replay of the call will be available for one year. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing to patients novel products 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 no approved therapies. Crysvita® (burosumab) is approved by the U.S. FDA for the treatment of XLH in adult and pediatric patients one year of age and older, and has received conditional marketing authorization in Europe for the treatment of XLH with radiographic evidence of bone disease in children 1 year of age and older and adolescents with growing skeletons. Mepsevii™ (vestronidase alfa) is approved in the United States for the treatment of children and adults with MPS VII. In Europe, Mepsevii is approved under exceptional circumstances for the treatment of non-neurological manifestations of MPS VII. In addition to the approved treatments for XLH and MPS VII, Ultragenyx has four clinical development programs. Crysvita is being studied for the treatment of TIO, a rare disease that impairs bone mineralization. UX007 is being studied in patients severely affected by LC-FAOD, a genetic disorder in which the body is unable to convert long chain fatty acids into energy. The company has two gene therapy pipeline candidates: DTX 301 is an AAV8 gene therapy product candidate in development for the treatment of patients with OTC deficiency, the most common urea cycle disorder; and DTX 401 is an AAV8 gene therapy product candidate for the treatment of patients with GSDIa. 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 Except for the historical information contained herein, the matters set forth in this press release, including statements relating to Ultragenyx’s plans for its clinical programs and future regulatory filings and interactions, 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, 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 uncertainties inherent in the clinical drug development process, such as the regulatory approval process, the timing of regulatory filings, and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations and the availability or commercial potential of our 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 on August 3, 2018, and its subsequent periodic reports filed with the Securities and Exchange Commission. Contact Ultragenyx Pharmaceutical Inc. Investors & Media Danielle Keatley 415-475-6876 Ultragenyx Pharmaceutical Inc. Selected Statement of Operations Financial Data (in thousands, except share and per share amounts) (unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2018 2017 2018 2017 Statement of Operations Data: Revenues: Collaboration and license $ 9,015 $ — $ 28,896 $ — Product sales 2,748 198 6,338 198 Total revenues 11,763 198 35,234 198 Operating expenses: Cost of sales 273 — 639 — Research and development 70,041 60,412 222,380 170,117 Selling, general and administrative 31,095 23,499 93,248 62,189 Total operating expenses 101,409 83,911 316,267 232,306 Loss from operations (89,646 ) (83,713 ) (281,033 ) (232,108 ) Gain from sale of priority review vouchers — — 170,322 — Other income (expense), net 2,583 4,490 1,314 11,718 Loss before income taxes (87,063 ) (79,223 ) (109,397 ) (220,390 ) Provision for income taxes (247 ) (4 ) (388 ) (18 ) Net loss $ (87,310 ) $ (79,227 ) $ (109,785 ) $ (220,408 ) Net loss per share, basic and diluted $ (1.74 ) $ (1.87 ) $ (2.22 ) $ (5.22 ) Shares used in computing net loss per share, basic and diluted 50,319,772 42,471,606 49,447,889 42,222,413 Ultragenyx Pharmaceutical Inc. Selected Balance Sheet Financial Data (in thousands) (unaudited) September 30, December 31, 2018 2017 Balance Sheet Data: Cash, cash equivalents and investments $ 503,098 $ 244,468 Working capital 500,799 198,569 Total assets 765,145 490,753 Total stockholders’ equity 662,596 383,454 Source: Ultragenyx Pharmaceutical Inc.