A Phase II, Escalating Dose, Open Label Study to Evaluate the Safety of Triheptanoin for the Prevention of Hypoglycemia in Patients with Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)

This is a medical research study to test a medication in adult patients with a disease called medium-chain acyl-CoA dehydrogenase deficiency (MCADD). The medication is triheptanoin, which is currently FDA approved for the treatment of Long-Chain Fatty Acid Oxidation Disorders. Previous research suggests that triheptanoin may also be effective in the treatment MCADD. This study will investigate the safety and efficacy (how well it works) of triheptanoin in patients with MCADD.

Start Date01 Jul 2025

Sponsor / Collaborator

University of Pittsburgh

[+1]

NCT06340685

/ RecruitingPhase 1IIT

An Open Label, Exploratory, Proof-of Concept Study of Triheptanoin As Treatment for Patients with Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency

This is a medical research study to test a medication in patients with a disease called Pyruvate Dehydrogenase Complex (PDC) Deficiency. The medication is triheptanoin, which is currently FDA approved for the treatment of Long-Chain Fatty Acid Oxidation Disorders. Previous research suggests that triheptanoin may also be effective in the treatment PDC Deficiency. This study will investigate the safety and efficacy (how well it works) of triheptanoin in patients with PDC Deficiency.

Start Date11 Jul 2024

Sponsor / Collaborator

University of Pittsburgh

[+1]

NCT05933200

/ RecruitingPhase 3

A Randomized, Double-blind, Multicenter Study to Determine the Effect of Triheptanoin Compared With Even-chain, Medium-chain Triglycerides (MCT) on Major Clinical Events (MCEs) in Pediatric Patients With Long-chain Fatty Acid Oxidation Disorders (LC-FAOD)

The main goal of this study is to evaluate the effects of triheptanoin versus Medium-chain Triglycerides (MCT) on frequency of Major Clinical Events (MCEs).

Start Date28 Feb 2023

Sponsor / Collaborator

Ultragenyx Pharmaceutical, Inc.

100 Clinical Results associated with Triheptanoin

100 Translational Medicine associated with Triheptanoin

100 Patents (Medical) associated with Triheptanoin

202

Literatures (Medical) associated with Triheptanoin

01 Mar 2025·JOURNAL OF BIOLOGICAL CHEMISTRY

Anaplerosis by medium-chain fatty acids through complex interplay with glucose and glutamine metabolism

Article

Author: German, Hannah M ; Ciapaite, Jolita ; Verhoeven-Duif, Nanda M ; Jans, Judith J M

The constant replenishment of tricarboxylic acid (TCA) cycle intermediates, or anaplerosis, is crucial to ensure optimal TCA cycle activity in times of high biosynthetic demand. In inborn metabolic diseases, anaplerosis is often affected, leading to impaired TCA cycle flux and ATP production. In these cases, anaplerotic compounds can be a therapy option. Triheptanoin, a triglyceride containing three heptanoate chains, is thought to be anaplerotic through production of propionyl- and acetyl-CoA. However, the precise mechanism underlying its anaplerotic action remains poorly understood. In this study, we performed a comprehensive in vitro analysis of heptanoate metabolism and compared it to that of octanoate, an even-chain fatty acid which only provides acetyl-CoA. Using stable isotope tracing, we demonstrate that both heptanoate and octanoate contribute carbon to the TCA cycle in HEK293 T cells, confirming direct anaplerosis. Furthermore, by using labeled glucose and glutamine, we show that heptanoate and octanoate decrease the contribution of glucose-derived carbon and increase the influx of glutamine-derived carbon into the TCA cycle. Our findings also point towards a change in redox homeostasis, indicated by an increased NAD⁺/NADH ratio, accompanied by a decreased lactate/pyruvate ratio and increased de novo serine biosynthesis. Taken together, these results highlight the broad metabolic effects of heptanoate and octanoate supplementation, suggesting that therapeutic efficacy may strongly depend on specific disease pathophysiology. Furthermore, they underline the need for careful selection of fatty acid compound and concentration to optimize anaplerotic action.

28 Jan 2025·NEUROLOGY

Effect of Triheptanoin on Caudate Atrophy and Motor Scores in Patients With Early-Stage Huntington Disease

Article

Author: van der Zwaan, Kasper F. ; Hainque, Elodie ; Méneret, Aurélie ; Veldkamp, Fleur C.M. ; Atencio, Mariana ; Giron, Camille ; Mochel, Fanny ; Roos, Raymond A. ; Vicaut, Eric ; Barbier, Magali ; Durr, Alexandra ; Ottolenghi, Chris ; Diallo, Abdourahmane ; Debs, Rabab ; Coppen, Emma M. ; Adanyeguh, Isaac M. ; Luton, Marie-Pierre ; Jacobs, Milou

BACKGROUND AND OBJECTIVES:

Brain energy deficiency occurs at the early stage of Huntington disease (HD). Triheptanoin, a drug that targets the Krebs cycle, can restore a normal brain energetic profile in patients with HD. In this study, we aimed at assessing its efficacy on clinical and neuroimaging structural measures in HD.

METHODS:

We conducted a 6-month bicentric (Paris, Leiden) double-blind randomized controlled trial followed by a 6-month open-label phase, between June 2015 and December 2019. We enrolled 107 patients at the early stage of HD-total motor score (TMS) of the UHDRS between 5 and 40. Participants received triheptanoin 1 g/kg/day or placebo (ratio 1/1). The primary outcome was the rate of caudate atrophy at 6 months using the caudate boundary shift integral (cBSI) method. Main secondary outcomes were cBSI at 12 months, TMS, and diffusion imaging at 6 and 12 months. Analysis was conducted using ANOVA, and data were presented with a 95% CI. To perform a 12-month comparison, we used the placebo arm of a 12-month randomized controlled trial conducted in parallel, using the double robust propensity score method.

RESULTS:

One hundred patients were randomized (mean age 49 years, 52% women). Fourteen patients withdrew from the study, including 10 because of gastrointestinal effects. There was no difference in cBSI at 6 months between groups (mean 0.026 [0.018-0.033] vs 0.023 [0.014-0.032]). TMS at 12 months was stable in patients treated with triheptanoin for 12 months (mean 0.6 [-1.1 to 2.1]), whereas it increased in patients initially on placebo (2.5 [1.2-3.8]). Compared with the external placebo control group, caudate atrophy decreased by approximately 50% (0.038 [0.028-0.048] vs 0.070 [0.057-0.082]) and TMS stabilized (0.66 [-1.07 to 2.48] vs 2.65 [1.38-3.89]) in patients treated with triheptanoin for 12 months.

DISCUSSION:

There was no effect of triheptanoin on caudate atrophy over 6 months. Compared with the external placebo group, triheptanoin was associated with motor stability and decreased caudate atrophy in patients treated for 12 months, but the post hoc nature of these findings is a major limitation.

TRIAL REGISTRATION INFORMATION:

clinicaltrials.gov NCT02453061, May 25, 2015. First patient enrolled on June 29, 2015.

CLASSIFICATION OF EVIDENCE:

This study provides Class I evidence that triheptanoin does not slow caudate atrophy compared with placebo over 6 months in patients with early HD.

01 Jan 2025·JOURNAL OF INHERITED METABOLIC DISEASE

Circulatory response to exercise relative to oxygen uptake assessed in the follow‐up of patients with fatty acid beta‐oxidation disorders

Article

Author: de Calbiac, Hortense ; Laforêt, Pascal ; Gaignard, Pauline ; Thevenet, Elise ; Ottolenghi, Chris ; Brassier, Anaïs ; de Lonlay, Pascale ; Le Guillou, Edouard ; Acquaviva‐Bourdain, Cécile ; Tuchmann‐Durand, Caroline ; Benoist, Jean‐François ; Gobin, Stéphanie ; Lebigot, Elise ; Pontoizeau, Clément ; Schiff, Manuel ; Imbard, Apolline ; Legendre, Antoine ; Lefrère, Bertrand

Abstract:

Patients with fatty acid oxidation disorders (FAODs) experience muscle symptoms due to impaired ATP metabolism and the toxicity of accumulated mitochondrial FAO substrates or intermediates, especially during catabolic states. A major issue is the absence of specific and sensible biomarkers to evaluate metabolic equilibrium. The relationship between cardiac output (Q) and oxygen consumption (VO2) during incremental exercise (dQ/dVO2) provides an indirect surrogate of mitochondrial function. A high dQ/dVO2 slope indicates impaired oxidative phosphorylation in skeletal muscle during exercise. Our study aimed to evaluate dQ/dVO2 as a potential marker of the severity of FAODs. We retrospectively collected clinical, laboratory parameters and treatment data for FAOD patients over 6 years old, including a disease severity score, plasma acylcarnitines and cardiopulmonary exercise tests with Q measurement via thoracic bioelectrical impedance. FAO flux was measured in whole blood and in myoblasts when available. We included 27 FAOD patients followed from 2015 to 2022, with deficiencies in LCHAD (n = 10), CPT2 (n = 6), VLCAD (n = 7), or MADD (n = 4). CPT2 deficient patients with severe scores had the highest C18:1‐, C16‐, C18‐acylcarnitines, and dQ/dVO2. In these patients, dQ/dVO2 was positively correlated with C18:1, C16, and C18 acylcarnitines. In a linear multivariate regression model, dQ/dVO2 was significantly associated with the severity score (B = 0.831, p = 0.008) and triheptanoin treatment (B = −0.547, p = 0.025). dQ/dVO2 and plasma long‐chain acylcarnitines might be useful to monitor CPT2D, as these parameters associate with our clinical severity score and could reflect altered mitochondrial functions.

News (Medical) associated with Triheptanoin

01 Aug 2024

·www.globenewswire.com

Ultragenyx Reports Second Quarter 2024 Financial Results and Corporate Update

Second quarter total revenue of $147 million, Crysvita® revenue of $114 million and Dojolvi® revenue of $19 million Increased 2024 expected total revenue guidance to $530 million to $550 million NOVATO, Calif., Aug. 01, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, today reported its financial results for the quarter ended June 30, 2024. “Our strong financial performance in the second quarter was driven by growing revenue across our commercial therapies from increasing global demand, leading us to raise our total revenue guidance for this year,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “In the quarter, we also reported positive data from our Phase 1/2 study in Angelman syndrome, our Phase 2/3 study in osteogenesis imperfecta, and our Phase 3 study in GSDIa. We are in an excellent position to achieve additional key milestones in the second half of the year including initiating our Phase 3 Angelman study and filing for accelerated approval for UX111 in Sanfilippo syndrome type A.” Second Quarter 2024 Selected Financial Data Tables and Financial Results Revenues (dollars in thousands), (unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Crysvita Product sales$40,449 $16,884 $76,690 $38,118 Revenue in Profit-Share Territory 67,045 61,314 107,447 111,220 Royalty revenue in European Territory 6,176 4,816 12,118 9,698 Total Crysvita Revenue 113,670 83,014 196,255 159,036 Dojolvi 19,355 16,491 35,717 30,794 Mepsevii 6,145 8,439 12,756 16,919 Evkeeza 7,856 365 11,131 577 Daiichi Sankyo — — — 1,479 Total revenues$147,026 $108,309 $255,859 $208,805 Total RevenuesUltragenyx reported $147 million in total revenue for the second quarter of 2024, which represents 36% growth compared to the same period in 2023. Second quarter 2024 Crysvita revenue was $114 million, which represents 37% growth compared to the same period in 2023. This includes product sales of $40 million from Latin America and Turkey, which represents 140% growth compared to the same period in 2023. Dojolvi revenue in the second quarter 2024 was $19 million, which represents 17% growth compared to the same period in 2023. Evkeeza revenue in the second quarter 2024 was $8 million, as demand continues to build in the company’s territories outside of the United States. Selected Financial Data (dollars in thousands, except per share amounts), (unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Total revenues$147,026 $108,309 $255,859 $208,805 Operating expenses: Cost of sales 21,280 9,914 38,813 22,171 Research and development 161,503 164,949 339,990 330,647 Selling, general and administrative 80,604 81,403 158,764 158,049 Total operating expenses 263,387 256,266 537,567 510,867 Net loss$(131,598) $(159,828) $(302,282) $(323,800)Net loss per share, basic and diluted$(1.52) $(2.25) $(3.54) $(4.58) Operating Expenses Total operating expenses for the second quarter of 2024 were $263 million, including non-cash stock-based compensation of $39 million. In 2024, annual operating expenses are expected to be stable or to decrease as the company continues to manage its costs and focus its investment on advancing multiple Phase 3 programs and executing on commercial product launches. Net Loss For the second quarter of 2024, Ultragenyx reported net loss of $132 million, or $1.52 per share basic and diluted, compared with a net loss for the second quarter of 2023 of $160 million, or $2.25 per share basic and diluted. Net Cash Used in Operations and Cash BalanceFor the three months ended June 30, 2024, net cash used in operations was $77 million and for the six months ended June 30, 2024 it was $268 million. Cash, cash equivalents, and marketable debt securities were $874 million as of June 30, 2024, which includes $381 million of net proceeds from issuance of common stock and pre-funded warrants in connection with an underwritten public offering in June 2024. 2024 Full Year Financial Guidance Total revenue guidance increased to be in the range of $530 million to $550 million (previously $500 million to $530 million)Crysvita revenue expected to be towards the upper end of the range of $375 million to $400 million. This includes all regions where Ultragenyx will recognize revenue: product sales in Latin America and Turkey, royalties in Europe, which have been ongoing, and royalties in North America, which began in April 2023.Dojolvi revenue in the range of $75 million to $80 millionNet Cash Used in Operations less than $400 million Recent Updates and Clinical Milestones UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): 14-month data resulted in a large, sustained 67% reduction in annualized fracture rate and persistent median annualized fracture rate of 0.00 (p=0.0014)Positive 14-month results from the Phase 2 portion of the ongoing Phase 2/3 Orbit study demonstrated that, as of the May 24, 2024 data cut-off date, treatment with setrusumab continued to significantly reduce incidence of fractures in patients with OI. Treatment with setrusumab also resulted in ongoing and meaningful improvements in lumbar spine bone mineral density (BMD) at month 12 without evidence of plateau. The median annualized rate of radiologically confirmed fractures across all 24 patients in the 2 years prior to treatment was 0.72. Following a mean treatment duration period of 16 months, the median annualized fracture rate was reduced 67% to 0.00 (p=0.0014; n=24). The reduction in annualized fracture rates was associated with continued, clinically meaningful increases in BMD. Treatment with setrusumab at 12-month demonstrated a mean increase in lumbar spine BMD from baseline of 22% (p<0.0001, n=19) and an improvement of mean baseline lumbar spine BMD Z-score from -1.73 to -0.49 at 12 months. The improvements in BMD and Z-scores were significant and consistent across all OI sub-types studied. As of the data cut-off, there were no treatment-related serious adverse events observed in the study and there were no reported hypersensitivity reactions related to setrusumab. More detailed 14-month data will be presented at a future scientific meeting. GTX-102 antisense oligonucleotide for Angelman syndrome: Successful End-of-Phase 2 (EOP2) meeting with Food and Drug Administration (FDA); on track to initiate Phase 3 by the end of the yearIn July 2024, Ultragenyx completed a successful EOP2 meeting with the FDA supporting the pivotal Phase 3 Aspire study design, which 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. The key secondary endpoint will be 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. Additionally, the company plans to initiate Aurora, 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 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 and has met with Japan’s Pharmaceuticals and Medical Devices Agency to inform and discuss its Phase 3 study design. The company expects the pivotal Phase 3 Aspire study to start by the end of 2024 and the Aurora study to start in 2025. UX701 AAV gene therapy for Wilson disease: Last patient in Cohort 3 dosed; expect interim Stage 1 data in the second half of 2024All patients in the three dose-escalation cohorts of Stage 1 have been dosed. During Stage 1, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2, which is the pivotal, randomized, placebo-controlled stage of the study. Data from Stage 1 are expected in the second half of 2024, which will be followed by dose selection and initiation of Stage 2. UX111 AAV gene therapy for Sanfilippo syndrome type A (MPS IIIA): Agreement reached with FDA that cerebral spinal fluid (CSF) heparan sulfate (HS) can be used as a reasonable surrogate endpoint for accelerated approvalIn June 2024, Ultragenyx announced a successful meeting with the FDA during which the company reached agreement with the FDA that CSF HS is a reasonable surrogate endpoint that could support submission of a biologics license application, or BLA, seeking accelerated approval for UX111. As discussed with the FDA, the BLA filing will be based on the available data including from the ongoing pivotal Transpher A study evaluating the safety and efficacy of UX111 in children with MPS IIIA. The details of a BLA will be finalized with the FDA in a pre-BLA meeting that is expected to happen in the second half of 2024, with the intent to file the application late this year or early next year. DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Positive top-line results from Phase 3 Study resulted in a statistically significant reduction in daily cornstarch intake at Week 48 (p<0.0001) with maintenance of glucose control In May 2024, Ultragenyx announced positive topline results from the Phase 3 GlucoGene study for the treatment of patients aged eight years and older. The study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. The mean percent reduction was 41.3% in the DTX401 group (n=20) compared with 10.3% in the placebo group (n=24) at Week 48 (p<0.0001). Across patients treated with DTX401, the mean reduction in cornstarch continued to decline over the 48-week period. In the treatment group, all patients achieved a reduction in cornstarch, with 68% achieving ≥30% reduction and 37% achieving ≥50% reduction compared to the placebo group, which achieved the same reductions in 13% and 4% of patients, respectively, at Week 48. The study also successfully met key secondary endpoints of reduction in the number of cornstarch doses per day and maintenance of glucose control at Week 48. Full 48 Week data from the Phase 3 study will be presented at a scientific conference later this year. These results will be discussed with regulatory authorities to support a marketing application in 2025. DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients; expect enrollment to be completed in the second half of 2024Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the second half of 2024. Conference Call and Webcast Information Ultragenyx will host a conference call today, Thursday, August 1, 2024, at 2 p.m. PT/5 p.m. ET to discuss the second quarter 2024 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations. The replay of the call will be available for one year. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, 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. 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, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions 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, risks related to serious or undesirable side effects of our product candidates, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, our limited experience in generating revenue from product sales, risks related to product liability lawsuits, our dependence on Kyowa Kirin for the commercial supply of Crysvita, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, the transition back to Kyowa Kirin of our exclusive rights to promote Crysvita in the United States and Canada and unexpected costs, delays, difficulties or adverse impact to revenue related to such transition, 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 3, 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 (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/mycompany/). Contacts Ultragenyx Pharmaceutical Inc.InvestorsJoshua Higair@ultragenyx.com Ultragenyx Pharmaceutical Inc.Selected Statement of Operations Financial Data(in thousands, except share and per share amounts)(unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Statement of Operations Data: Revenues: Product sales$73,805 $42,179 $136,294 $86,408 Royalty revenue 73,221 46,331 119,565 51,213 Collaboration and license — 19,799 — 71,184 Total revenues 147,026 108,309 255,859 208,805 Operating expenses: Cost of sales 21,280 9,914 38,813 22,171 Research and development 161,503 164,949 339,990 330,647 Selling, general and administrative 80,604 81,403 158,764 158,049 Total operating expenses 263,387 256,266 537,567 510,867 Loss from operations (116,361) (147,957) (281,708) (302,062)Change in fair value of equity investments (3,991) 261 (245) (73)Non-cash interest expense on liabilities for sales of future royalties (15,960) (15,375) (31,807) (31,011)Other income, net 5,572 3,975 12,791 10,573 Loss before income taxes (130,740) (159,096) (300,969) (322,573)Provision for income taxes (858) (732) (1,313) (1,227)Net loss$(131,598) $(159,828) $(302,282) $(323,800)Net loss per share, basic and diluted$(1.52) $(2.25) $(3.54) $(4.58)Shares used in computing net loss per share, basic and diluted 86,580,516 70,897,991 85,433,443 70,639,015 Ultragenyx Pharmaceutical Inc.Selected Activity included in Operating Expenses(in thousands)(unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Non-cash stock-based compensation$39,363 $34,653 $76,297 $66,592 UX143 clinical milestone — $9,000 — $9,000 Ultragenyx Pharmaceutical Inc.Selected Balance Sheet Financial Data(in thousands)(unaudited) June 30, December 31, 2024 2023 Balance Sheet Data: Cash, cash equivalents, and marketable debt securities $874,490 $777,110 Working capital 691,774 451,747 Total assets 1,618,437 1,491,013 Total stockholders' equity 432,418 275,414

Clinical ResultPhase 3Financial StatementPhase 2Gene Therapy

02 May 2024

·www.globenewswire.com

Ultragenyx Reports First Quarter 2024 Financial Results and Corporate Update

First quarter total revenue of $109 million, Crysvita® revenue of $83 million and Dojolvi® revenue of $16 million Reaffirmed 2024 expected total revenue guidance between $500 million to $530 million, Crysvita revenue of $375 million to $400 million, and Dojolvi revenue of $75 million to $80 million Presented positive interim Phase 1/2 data from GTX-102 Angelman syndrome study demonstrating that Expansion Cohorts showed rapid, clinically meaningful improvement across multiple domains consistent with or exceeding Dose-escalation Cohort data at Day 170 NOVATO, Calif., May 02, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, today reported its financial results for the quarter ended March 31, 2024 and reaffirmed its financial guidance for 2024. “In the first quarter we continued to see rapid revenue growth in the international markets with steady progress globally across our four commercial products. We also just completed enrollment of our Phase 3 program in osteogenesis imperfecta supported by strong enthusiasm from treating physicians and the patient community,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “Last month we shared new data from the GTX-102 program for Angelman syndrome and have received an overwhelming response of excitement and support from the clinical experts and advocates in the Angelman community. We are on track to hold regulatory discussions in mid-2024 with the goal of initiating a Phase 3 trial before the end of the year.” First Quarter 2024 Selected Financial Data Tables and Financial Results Revenues (dollars in thousands), (unaudited) Three Months Ended March 31, 2024 2023Crysvita Product sales$36,241 $21,234Revenue in Profit-Share Territory 40,402 49,906Royalty revenue in European Territory 5,942 4,882Total Crysvita Revenue 82,585 76,022Dojolvi 16,362 14,303Mepsevii 6,611 8,480Evkeeza 3,275 212Daiichi Sankyo — 1,479Total revenues$108,833 $100,496 Total RevenuesUltragenyx reported $109 million in total revenue for the first quarter of 2024, which represents 8% growth compared to the same period in 2023. First quarter 2024 Crysvita revenue was $83 million, which represents 9% growth compared to the same period in 2023. This includes product sales of $36 million from Latin America and Turkey, which represents 71% growth compared to the same period in 2023. In April 2023, commercialization responsibilities in the Profit-share Territory transitioned to Kyowa Kirin Co and commensurately, revenue in that region transitioned from a profit-share to a royalty ranging from the mid-20’s to 30% calculated based on annual revenue tiers. Dojolvi revenue in the first quarter 2024 was $16 million, which represents 14% growth compared to the same period in 2023. Selected Financial Data (dollars in thousands, except per share amounts), (unaudited) Three Months Ended March 31, 2024 2023 Total revenues$108,833 $100,496 Operating expenses: Cost of sales 17,533 12,257 Research and development 178,487 165,698 Selling, general and administrative 78,160 76,646 Total operating expenses 274,180 254,601 Net loss$(170,684) $(163,972)Net loss per share, basic and diluted$(2.03) $(2.33) Operating Expenses Total operating expenses for the first quarter of 2024 were $274 million, including non-cash stock-based compensation of $37 million. In 2024, annual operating expenses are expected to be stable or to decrease as the company continues to manage its costs and focus its investment on advancing multiple Phase 3 programs and executing on commercial product launches. Net Loss For the first quarter of 2024, Ultragenyx reported net loss of $171 million, or $2.03 per share basic and diluted, compared with a net loss for the first quarter of 2023 of $164 million, or $2.33 per share, basic and diluted. Net Cash Used in Operations and Cash BalanceNet cash used in operations for the quarter ended March 31, 2024 was $191 million. Cash, cash equivalents, and marketable debt securities were $569 million as of March 31, 2024. 2024 Financial Guidance For the full year 2024, the company reaffirms: Total revenue in the range of $500 million to $530 millionCrysvita revenue in the range of $375 million to $400 million. This includes all regions where Ultragenyx will recognize revenue: product sales in Latin America and Turkey, royalties in Europe, which have been ongoing, and royalties in North America, which began in April 2023.Dojolvi revenue in the range of $75 million to $80 millionNet Cash Used in Operations to be less than $400 million Recent Updates and Clinical Milestones UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Enrollment complete for Phase 3 Orbit and Cosmic studies; expect additional Phase 2 data update in second half of 2024 The Phase 3 portion of the Orbit study has completed enrollment with 158 patients. Orbit is a randomized placebo-controlled study evaluating the effect of setrusumab compared to placebo on the rate of annualized clinical fractures in patients aged 5 to <25 years. Additional longer-term safety and efficacy data from the Phase 2 portion of the Orbit study are expected in the second half of 2024. The Phase 3 Cosmic study has also completed enrollment with 66 patients randomized or in screening. Cosmic is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients aged 2 to <7 years. GTX-102 antisense oligonucleotide for Angelman syndrome: Positive interim Phase 1/2 data shared in April; expect End of Phase 2 meeting with Food and Drug Administration (FDA) in mid-2024New interim data from the Phase 1/2 study were presented at a company presentation and at the 76th Annual American Academy of Neurology Meeting. Patients in Expansion Cohorts A & B treated with a set dose and regimen of GTX-102 showed rapid and clinically meaningful improvement across multiple domains consistent with or exceeding Dose Escalation Cohorts 4-7 data at Day 170. Treatment of the Dose Escalation Cohorts 4-7 showed long-term increasing and sustained clinical benefit far exceeding Natural History data at Day 758. As previously reported and as of the data cut-off on April 5, 2024, there were two patients who had mild or moderate lower extremity weakness across 53 patients who completed the loading phase in the Expansion Cohorts A-E. Both were in Cohorts A & B and none reported in Cohorts C–E. The lower extremity weakness resolved rapidly without sequelae and patients remain in the study without ongoing safety concerns and are expected to continue dosing. The FDA and other regulatory agencies were notified and raised no issues nor required additional actions. There were no other unexpected serious adverse events. We expect to share additional long-term safety and efficacy data from the Phase 1/2 study and plan to continue to provide routine safety updates with efficacy updates. We currently expect to have an End of Phase 2 meeting with the FDA in mid-2024 and meetings with other regulatory agencies in the second half of 2024. UX701 AAV gene therapy for Wilson disease: Last patient in Cohort 3 dosed; expect interim Stage 1 data in the second half of 2024All patients in the three dose-escalation cohorts of Stage 1 have been dosed. During Stage 1, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2, the pivotal, randomized, placebo-controlled stage of the study. Data from Stage 1 are expected in the second half of 2024, which will be followed by dose selection and initiation of Stage 2. UX111 AAV gene therapy for Sanfilippo syndrome (MPS IIIA): Discussions ongoing with FDA, seeking accelerated approval pathIn February 2024, Ultragenyx participated in a workshop hosted by the Reagan-Udall Foundation for the FDA that brought together FDA representatives, patient advocates, scientists, and industry leaders to discuss the use of CSF heparan sulfate as a relevant biomarker to enable accelerated approval in neuronopathic mucopolysaccharidoses (MPS). Discussions are ongoing with the FDA in seeking an accelerated review path for UX111. DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study complete; expect Phase 3 data readout in the second quarter of 2024In May 2023, Ultragenyx announced the last patient was dosed in the Phase 3 study. The 48-week study enrolled 49 patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 safety and efficacy data are expected in the second quarter of 2024. DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients; expect enrollment to be completed in the second half of 2024Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the second half of 2024. Conference Call and Webcast Information Ultragenyx will host a conference call today, Thursday, May 2, 2024, at 2 p.m. PT/5 p.m. ET to discuss the first quarter 2024 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations. To participate in the live call, please register by clicking on the following link (https://register.vevent.com/register/BI7c62f78f6df84941acb020e8220f4d81) and you will be provided with dial-in details. The replay of the call will be available for one year. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, 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. 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, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions 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, risks related to serious or undesirable side effects of our product candidates, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, our limited experience in generating revenue from product sales, risks related to product liability lawsuits, our dependence on Kyowa Kirin for the commercial supply of Crysvita, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, the transition back to Kyowa Kirin of our exclusive rights to promote Crysvita in the United States and Canada and unexpected costs, delays, difficulties or adverse impact to revenue related to such transition, 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 (https://ir.ultragenyx.com/) and LinkedIn website (https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/mycompany/). Contacts Ultragenyx Pharmaceutical Inc.InvestorsJoshua Higair@ultragenyx.com Ultragenyx Pharmaceutical Inc.Selected Statement of Operations Financial Data(in thousands, except share and per share amounts)(unaudited) Three Months Ended March 31, 2024 2023 Statement of Operations Data: Revenues: Product sales$62,489 $44,229 Royalty revenue 46,344 4,882 Collaboration and license — 51,385 Total revenues 108,833 100,496 Operating expenses: Cost of sales 17,533 12,257 Research and development 178,487 165,698 Selling, general and administrative 78,160 76,646 Total operating expenses 274,180 254,601 Loss from operations (165,347) (154,105)Change in fair value of equity investments 3,746 (334)Non-cash interest expense on liabilities for sales of future royalties (15,847) (15,636)Other income, net 7,219 6,598 Loss before income taxes (170,229) (163,477)Provision for income taxes (455) (495)Net loss$(170,684) $(163,972)Net loss per share, basic and diluted$(2.03) $(2.33)Shares used in computing net loss per share, basic and diluted 84,286,292 70,368,478 Ultragenyx Pharmaceutical Inc.Selected Activity included in Operating Expenses(in thousands)(unaudited) Three Months Ended March 31, 2024 2023 Non-cash stock-based compensation$36,934 $31,939 Ultragenyx Pharmaceutical Inc.Selected Balance Sheet Financial Data(in thousands)(unaudited) March 31, December 31, 2024 2023Balance Sheet Data: Cash, cash equivalents, and marketable debt securities $568,661 $777,110Working capital 350,392 451,747Total assets 1,307,080 1,491,013Total stockholders' equity 140,264 275,414

Phase 3Clinical ResultFinancial StatementPhase 2

15 Feb 2024

·www.globenewswire.com

Ultragenyx Reports Fourth Quarter and Full Year 2023 Financial Results and Corporate Update

2023 Total Revenue of $434 million, Crysvita® revenue of $328 million and Dojolvi® revenue of $71 million 2024 Financial Guidance: Total Revenue between $500 million and $530 million, Crysvita revenue of $375 million to $400 million, and Dojolvi revenue of $75 million to $80 million Year-end 2023 cash balance of $777 million and 2024 guidance for Net Cash Used in Operations expected to be less than $400 million NOVATO, Calif., Feb. 15, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultrarare genetic diseases, today reported its financial results for the quarter and full year ended December 31, 2023 and reaffirmed its financial guidance for 2024. “Last year, we made significant progress across our pipeline and look forward to multiple catalysts in 2024 with substantive data in Angelman syndrome that could enable a Phase 3 study, pivotal Phase 3 data from our GSDIa gene therapy program, dose-finding data from our seamless study in Wilson disease, and longer-term Phase 2 data in Osteogenesis Imperfecta,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “In 2023, we saw increased demand for both Crysvita and Dojolvi, and achieved multiple regulatory and reimbursement milestones for our commercial products to support continued revenue growth of approximately 20% in 2024.” Fourth Quarter and Full Year 2023 Selected Financial Data Tables and Financial Results Revenues (dollars in thousands), (unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022Crysvita Product sales$18,379 $7,698 $75,697 $42,678Revenue in Profit-Share Territory 70,124 66,903 231,574 215,024Royalty revenue in European Territory 5,612 6,058 20,783 21,692Total Crysvita Revenue 94,115 80,659 328,054 279,394Dojolvi 23,286 16,412 70,633 55,612Mepsevii 7,889 4,798 30,441 20,637Evkeeza 2,102 — 3,642 —Daiichi Sankyo — 1,479 1,479 7,686Total revenues$127,392 $103,348 $434,249 $363,329 Total RevenuesUltragenyx reported $127 million in total revenue for the fourth quarter 2023, which represents 23% growth compared to the same period in 2022. Fourth quarter 2023 Crysvita revenue was $94 million, which represents 17% growth compared to the same period in 2022. This includes product sales of $18 million from Latin America and Turkey, which represents 139% growth compared to the same period in 2022. Dojolvi revenue in the fourth quarter 2023 was $23 million, which represents 42% growth compared to the same period in 2022. Total revenue for the year ended December 31, 2023 was $434 million, which represents 20% growth compared to the prior year. Full year 2023 Crysvita revenue was $328 million, which represents 17% growth compared to the same period in 2022. This includes product sales of $76 million from Latin America and Turkey, which represents 77% growth compared to the same period in 2022. Dojolvi revenue in 2023 was $71 million, which represents 27% growth compared to the same period in 2022. Selected Financial Data (dollars in thousands, except per share amounts), (unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Total revenues$127,392 $103,348 $434,249 $363,329 Operating expenses: Cost of sales 12,051 5,319 45,209 28,320 Research and development 160,557 170,808 648,449 705,789 Selling, general and administrative 76,833 72,849 309,799 278,139 Total operating expenses 249,441 248,976 1,003,457 1,012,248 Net loss$(123,190) $(151,833) $(606,639) $(707,421)Net loss per share, basic and diluted$(1.52) $(2.16) $(8.25) $(10.12) Operating Expenses Total operating expenses for the fourth quarter of 2023 were $249 million, including non-cash stock-based compensation of $34 million. Total operating expenses for the year ended December 31, 2023 were $1,003 million, including $135 million of non-cash stock-based compensation. In 2024, annual operating expenses are expected to be stable or to decrease as the company continues to manage its costs, focus its investment on advancing multiple Phase 3 programs, and execute on commercial product launches. Net Loss For the fourth quarter of 2023, Ultragenyx reported net loss of $123 million, or $1.52 per share basic and diluted, compared with a net loss for the fourth quarter of 2022 of $152 million, or $2.16 per share, basic and diluted. For the year ended December 31, 2023, Ultragenyx reported net loss of $607 million, or $8.25 per share basic and diluted, compared with a net loss the prior year of $707 million, or $10.12 per share, basic and diluted. Net Cash Used in Operations and Cash BalanceNet cash used in operations for the year ended December 31, 2023 was $475 million. Cash, cash equivalents, and marketable debt securities were $777 million as of December 31, 2023. 2024 Financial Guidance For the full year 2024, the company reaffirms: Total revenue in the range of $500 million to $530 millionCrysvita revenue in the range of $375 million to $400 million. This includes all regions where Ultragenyx will recognize revenue: product sales in Latin America and Turkey, royalties in Europe, which have been ongoing, and royalties in North America, which began in April 2023.Dojolvi revenue in the range of $75 million to $80 millionNet Cash Used in Operations to be less than $400 million Recent Updates and Clinical Milestones UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Phase 3 portion of Orbit study expected to be fully enrolled around the end of the first quarter of 2024Patients are being dosed in the late-stage clinical trials, Orbit and Cosmic, which are evaluating setrusumab in pediatric and young adult patients with OI. The randomized, placebo-controlled Phase 3 portion of the Orbit study is expected to enroll approximately 150 patients and be fully enrolled around the end of the first quarter of 2024. Additional longer-term Phase 2 safety and efficacy data from the Orbit study are expected in the second half of 2024. The Phase 3 Cosmic study is an active-controlled study evaluating the effect of setrusumab compared to intravenous bisphosphonate (IV-BP) therapy on annualized total fracture rate in patients age 2 to <5 years. Cosmic is expected to enroll approximately 50 patients or more at more than 20 global sites and is expected to complete enrollment in the first half of 2024. GTX-102 antisense oligonucleotide for Angelman syndrome: Phase 1/2 fully enrolled; expansion data expected in the first half of 2024Enrollment in the expansion cohorts was completed in December 2023 with a total of 53 new patients enrolled. A total of 74 patients are enrolled in the Phase 1/2 study including the dose-escalation/extension study patients. The expansion cohorts will evaluate many of the same safety, pharmacokinetic, and efficacy measures as the previously enrolled dose-escalation/extension cohorts plus some new evaluations. The next safety and efficacy update is expected in the first half of 2024 and is planned to include data from at least 20 expansion cohort patients with a minimum of Day 170 data. In January 2024, GTX-102 was accepted into the Priority Medicines (PRIME) program by the European Medicines Agency (EMA). PRIME is granted by the EMA to medicines that show the potential to benefit patients with unmet needs based on early clinical data. Through PRIME, the EMA offers early and proactive support to optimize development plans and the generation of robust data on a medicine’s benefits and risks, and enables accelerated assessment of medicines applications. UX701 AAV gene therapy for Wilson disease: Last patient in Cohort 3 dosed; expect interim Stage 1 data in mid-2024All patients in the three dose-escalation cohorts of Stage 1 have been dosed. During Stage 1, the safety and efficacy of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2, the pivotal, randomized, placebo-controlled stage of the study. Data from Stage 1 are expected in mid-2024, which will be followed by dose selection and initiation of Stage 2 in the second half of 2024. UX111 AAV gene therapy for Sanfilippo syndrome (MPS IIIA): Updated data from pivotal Transfer A study presented at WORLDSymposiumTM New positive data from the ongoing pivotal Transfer A study evaluating the safety and efficacy of UX111 in children with MPS IIIA were presented at the 20th Annual WORLDSymposium™ earlier this month showing that a single infusion of UX111 can substantially correct the underlying metabolic disease and maintain cognitive function in nearly all patients. The presentation also showed that the observed reductions of heparan sulfate exposure in cerebrospinal fluid can predict improved long-term cognitive function in patients with MPS IIIA following treatment with UX111. With these data and other data, discussions are ongoing with the FDA seeking an accelerated review path for UX111. DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Dosing in Phase 3 study complete; Phase 3 data readout expected in the first half of 2024In May 2023, Ultragenyx announced the last patient had been dosed in the Phase 3 study. The 48-week study has fully enrolled patients eight years of age and older, randomized 1:1 to DTX401 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. Phase 3 safety and efficacy data are expected in the first half of 2024. DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study dosing patients; expect enrollment to be completed in the first half of 2024Ultragenyx is randomizing and dosing patients in the ongoing Phase 3 study. The pivotal, 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels. Enrollment is currently expected to be completed in the first half of 2024. Conference Call and Webcast Information Ultragenyx will host a conference call today, Thursday, February 15, 2024, at 2 p.m. PT/5 p.m. ET to discuss the fourth quarter and full year 2023 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations. To participate in the live call, please register by clicking on the following link (https://register.vevent.com/register/BI177d5c166d3045ddaa4dcd3b3ec136ba) and you will be provided with dial-in details. The replay of the call will be available for one year. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved medicines and treatment candidates aimed at addressing diseases with high unmet medical need and clear biology, 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. 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, anticipated cost or expense reductions, the timing, progress and plans for its clinical programs and clinical studies, future regulatory interactions, and the components and timing of regulatory submissions 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, risks related to serious or undesirable side effects of our product candidates, the company’s ability to achieve its projected development goals in its expected timeframes, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, our limited experience in generating revenue from product sales, risks related to product liability lawsuits, our dependence on Kyowa Kirin for the commercial supply of Crysvita, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, the transition back to Kyowa Kirin of our exclusive rights to promote Crysvita in the United States and Canada and unexpected costs, delays, difficulties or adverse impact to revenue related to such transition, 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 November 3, 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.InvestorsJoshua Higair@ultragenyx.com Ultragenyx Pharmaceutical Inc.Selected Statement of Operations Financial Data(in thousands, except share and per share amounts)(unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Statement of Operations Data: Revenues: Product sales$51,656 $28,908 $180,413 $118,927 Royalty revenue 75,736 6,058 182,652 21,692 Collaboration and license — 68,382 71,184 222,710 Total revenues 127,392 103,348 434,249 363,329 Operating expenses: Cost of sales 12,051 5,319 45,209 28,320 Research and development 160,557 170,808 648,449 705,789 Selling, general and administrative 76,833 72,849 309,799 278,139 Total operating expenses 249,441 248,976 1,003,457 1,012,248 Loss from operations (122,049) (145,628) (569,208) (648,919)Change in fair value of equity investments 1,889 1,840 397 (19,299)Non-cash interest expense on liabilities for sales of future royalties (17,328) (15,874) (66,004) (43,015)Other income, net 10,596 6,378 26,351 9,508 Loss before income taxes (126,892) (153,284) (608,464) (701,725)Benefit from (provision for) income taxes 3,702 1,451 1,825 (5,696)Net loss$(123,190) $(151,833) $(606,639) $(707,421)Net loss per share, basic and diluted$(1.52) $(2.16) $(8.25) $(10.12)Shares used in computing net loss per share, basic and diluted 81,118,873 70,152,192 73,543,862 69,914,225 Ultragenyx Pharmaceutical Inc.Selected Activity included in Operating Expenses(in thousands)(unaudited) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Non-cash stock based compensation$33,744 $29,355 $135,213 $130,368In-process research and development expense from GeneTx acquisition — $(201) — $75,033UX143 clinical milestone — — $9,000 — Ultragenyx Pharmaceutical Inc.Selected Balance Sheet Financial Data(in thousands)(unaudited) December 31, December 31, 2023 2022Balance Sheet Data: Cash, cash equivalents, and marketable debt securities $777,110 $896,732Working capital 451,747 622,689Total assets 1,491,013 1,545,444Total stockholders' equity 275,414 352,494

Phase 3Financial StatementGene Therapy

100 Deals associated with Triheptanoin

External Link

KEGG	Wiki	ATC	Drug Bank
D11465	Triheptanoin	A	DB11677

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Lipid Metabolism Disorders	Canada	Ultragenyx Pharmaceutical, Inc.	01 Apr 2021
Fatty acid oxidation disorder	United States	Ultragenyx Pharmaceutical, Inc.	30 Jun 2020

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glut1 Deficiency Syndrome	Phase 3	United States	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Glut1 Deficiency Syndrome	Phase 3	France	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Glut1 Deficiency Syndrome	Phase 3	Germany	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Glut1 Deficiency Syndrome	Phase 3	Italy	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Glut1 Deficiency Syndrome	Phase 3	Spain	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Glut1 Deficiency Syndrome	Phase 3	United Kingdom	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Movement Disorders	Phase 3	United States	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Movement Disorders	Phase 3	France	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Movement Disorders	Phase 3	Germany	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017
Movement Disorders	Phase 3	Italy	Ultragenyx Pharmaceutical, Inc.	19 Apr 2017

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03181399 (CTgov)	Phase 2	Glycogen Storage Disease Id \| Epilepsy \| GLUT1 Deficiency Syndrome 1 ... View more	45	Triheptanoin	hthstsppwi = aswnpcoivv xjaideoalt (wcbnwrpwse, bdfztdymfr - okixxrkxbo) View more	-	13 Apr 2025
NCT03041363 (Pubmed \| Sci Rep)	Phase 1	Glut1 Deficiency Syndrome	12	Triheptanoin 1g/Kg/day	cwkimiqofx(ludzqtzjck) = One dose-limiting toxicity, occurring in 1 of 6 subjects, was encountered in the middle age group in the context of frequently reduced gastrointestinal tolerance for all groups wbvggdgnct (groyqqjoep ) View more	-	01 Mar 2023
NCT01993186 (UX007G-CL201, Pubmed \| Epilepsia)	Phase 2	Glut1 Deficiency Syndrome	36	Triheptanoin	phuxhiqare(cxubrnevsv) = Common treatment‐emergent adverse events included abdominal pain, mostly mild or moderate in severity rinlhhucca (uiukhrfajh ) View more	Negative	01 Jul 2022
NCT02214160 (CTgov)	Phase 2	Carnitine palmitoyltransferase deficiency \| Trifunctional Protein Deficiency With Myopathy and Neuropathy \| Carnitine-Acylcarnitine Translocase Deficiency ... View more	94	UX007 (UX007-CL201-Rollover Cohort)	kqsgypzdqt(goowoplrva) = krpkhsjplu tfxidnudyz (shzksdfgdn, 1.64) View more	-	08 Dec 2021
NCT02214160 (CTgov)	Phase 2		94	triheptanoin (IST/Other Cohort)	zdcbbkbeva(ppnhirxtbg) = rsybdtykvq dgysqoatjy (lgmolhfann, coycdreong - iczgkzposc) View more	-	08 Dec 2021
NCT01886378 (CTgov)	Phase 2	Trifunctional Protein Deficiency With Myopathy and Neuropathy \| Fatty acid oxidation disorder \| VLCAD Deficiency ... View more	29	UX007	vpajoyhbqr(mmwbybjoww) = meqngnmmae bkdyrrqtsf (hvlhrialeo, 295.54) View more	-	11 Feb 2021
NCT02036853 (GLUT1DS, CTgov)	Phase 2	Glut1 Deficiency Syndrome	20	Triheptanoin (Schedule A)	tziwyzihzk(uekiblddrl) = eunwazqqdw myjnfxqgww (eccgvjynpi, hqwfgqzogd - oasehusjie) View more	-	28 Jan 2021
NCT02036853 (GLUT1DS, CTgov)	Phase 2	Glut1 Deficiency Syndrome	20	Triheptanoin (Schedule B)	tziwyzihzk(uekiblddrl) = edavtomohy myjnfxqgww (eccgvjynpi, ruhajbuqtp - yryeaqjcag) View more	-	28 Jan 2021
NCT01993186 (UX007G-CL201, CTgov)	Phase 2	Glut1 Deficiency Syndrome	36	UX007 (UX007)	izdgluzyot(jplngedtnm) = rxclheecuj vnhmhpwdvu (yehddxdwbh, nobekmymlo - slpqwcfcqj) View more	-	29 May 2020
NCT01993186 (UX007G-CL201, CTgov)	Phase 2	Glut1 Deficiency Syndrome	36	Placebo (Placebo)	izdgluzyot(jplngedtnm) = bjfepvshxc vnhmhpwdvu (yehddxdwbh, earqbeqczq - mrqfxseawu) View more	-	29 May 2020
NCT02599961 (CTgov)	Phase 2	Glut1 Deficiency Syndrome	15	UX007 (Triheptanoin)	fxwjtkwycq = hkwnucluug sxoqzhflxc (xljbhldaqm, qivvyaxmxb - qgrlbeyamm) View more	-	30 Apr 2020
NCT02679235 (BEAT7, CTgov)	Phase 1/2	Middle Lobe Syndrome	15	POST Triheptanoin	cmmjxybszl(zujpffxfzr) = onpkwxwxrn bjsdiylopb (wrgwetzexe, 1.7) View more	-	15 Apr 2020

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Approval

Accelerate your research with the latest regulatory approval information.

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Regulation

Understand key drug designations in just a few clicks with Synapse.

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Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

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Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis