On February 16, 2023 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultrarare genetic diseases, reported its financial results for the quarter and full year ended December 31, 2022 and reaffirmed its financial guidance for 2023 (Press release, Ultragenyx Pharmaceutical, FEB 16, 2023, View Source [SID1234627322]).
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"In 2022, we continued to reach more patients around the world as we successfully commercialized multiple products to treat rare diseases," said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. "2023 will be a year of meaningful development progress for us as we focus on data generation from two of our key programs, UX143 in osteogenesis imperfecta and GTX-102 in Angelman syndrome, and the continued advancement of our late-stage gene therapy programs."
Fourth Quarter and Full Year 2022 Selected Financial Data Tables and Financial Results
Revenues (dollars in thousands) (unaudited)
Three Months Ended December 31, Year Ended December 31,
2022 2021 2022 2021
Crysvita Collaboration and Product Revenues:
North America Collaboration $ 66,903 $ 50,211 $ 215,024 $ 171,198
ROW Product Sales 7,698 5,272 42,678 21,422
Crysvita in Ultragenyx Territories1 74,601 55,483 257,702 192,620
EU Royalty Revenue 6,058 4,741 21,692 18,195
Total Crysvita Revenue 80,659 60,224 279,394 210,815
Dojolvi 16,412 11,825 55,612 39,560
Mepsevii 4,798 3,111 20,637 16,035
Total Collaboration and Product Revenues 101,869 75,160 355,643 266,410
Daiichi Sankyo 1,479 8,229 7,686 84,996
Total Revenue $ 103,348 $ 83,389 $ 363,329 $ 351,406
Net Revenues
For the fourth quarter of 2022, Ultragenyx reported $103.3 million in total revenue. Ultragenyx recognized $74.6 million in Crysvita (burosumab) revenue in the Ultragenyx territories1, which includes $66.9 million in collaboration revenue in the North American profit-share territory and net product sales in other regions of $7.7 million. Total royalty revenue related to European Crysvita sales was $6.1 million. Dojolvi (triheptanoin) revenue in the fourth quarter of 2022 was $16.4 million. Mepsevii (vestronidase alfa) revenue for the fourth quarter of 2022 was $4.8 million. Total revenue for the fourth quarter also includes $1.5 million of revenue related to the collaboration and license agreement with Daiichi Sankyo that was executed in March 2020.
Revenue for the year ended December 31, 2022 was $363.3 million, including $257.7 million in Crysvita revenue in the Ultragenyx territories1. Crysvita collaboration revenue in the North American profit-share territory was $215.0 million and net Crysvita product sales in other regions were $42.7 million. Total royalty revenue related to European Crysvita royalties was $21.7 million. Dojolvi product revenue for the year ended December 31, 2022 was $55.6 million. Mepsevii product revenue was $20.6 million. For the year ended December 31, 2022, revenue related to our strategic manufacturing partnership with Daiichi Sankyo was $7.7 million.
Selected Financial Data (dollars in thousands, except per share amounts) (unaudited)
Three Months Ended December 31, Year Ended December 31,
2022 2021 2022 2021
Total revenue $ 103,348 $ 83,389 $ 363,329 $ 351,406
Operating expense:
Cost of sales 5,319 3,509 28,320 16,008
Research and development 170,808 123,013 705,789 497,153
Selling, general and administrative 72,849 59,431 278,139 219,982
Total operating expense 248,976 185,953 1,012,248 733,143
Net loss $ (151,833 ) $ (122,458 ) $ (707,421 ) $ (454,025 )
Net loss per share, basic and diluted $ (2.16 ) $ (1.79 ) $ (10.12 ) $ (6.70 )
Operating Expenses
Total operating expenses for the fourth quarter of 2022 were $249.0 million, including non-cash stock-based compensation of $29.4 million. Total operating expenses for the year ended December 31, 2022 were $1,012.2 million, which includes $130.4 million of non-cash stock-based compensation and $75.0 million of in-process research and development expense associated with the acquisition of GeneTx in July 2022. In 2023, annual operating expenses are expected to decrease as the company manages headcount and increases operational leverage while executing on high value programs.
Net Loss
For the fourth quarter of 2022, Ultragenyx reported net loss of $151.8 million, or $2.16 per share basic and diluted, compared with a net loss for the fourth quarter of 2021 of $122.5 million, or $1.79 per share, basic and diluted. For the year ended December 31, 2022, net loss was $707.4 million, or $10.12 per share, basic and diluted, compared with a net loss for the same period in 2021 of $454.0 million, or $6.70 per share, basic and diluted.
Cash, Cash Equivalents and Marketable Debt Securities
Cash, cash equivalents, and marketable debt securities were approximately $896.7 million as of December 31, 2022.
2023 Financial Guidance
For the full year 2023, the company reaffirms:
Total revenue in the range of $425 million to $450 million
Crysvita revenue in the range of $325 million to $340 million. This includes all regions where Ultragenyx will recognize revenue, including the royalties in Europe, which have been ongoing, and the royalties in North America, which will begin in April 2023.
Dojolvi revenue in the range of $65 million to $75 million
Net Cash Used in Operations is expected to be less than $400 million
Recent Updates and 2023 Clinical Milestones
UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Phase 2/3 study dosing patients; Phase 2 enrollment complete, data expected in mid-2023
Ultragenyx is currently dosing patients in the Phase 2/3 Orbit study of UX143 in pediatric and adult patients with OI aged five to <26 years. Enrollment in the Phase 2 portion of the study is complete and data are expected in mid-2023. The Phase 2 data are expected to include changes in bone biomarkers response and some data on bone mineral density that will be used to establish the dosing algorithm for the Phase 3 portion of the study. Optimizing the dosing across the age range of the study is intended to support meaningful benefit in the reduction of clinically evident fractures in all age groups studied.
In addition, in the first half of 2023, Ultragenyx intends to initiate a randomized study in OI in children under age five with serious bone disease, comparing bisphosphonates to UX143. Younger pediatric patients with OI often have a much higher fracture rate than other age groups and a greater medical need, driving clinical urgency for better treatment options. Total fractures is expected to be the primary endpoint in the study.
GTX-102 antisense oligonucleotide for Angelman syndrome: Phase 1/2 continues dose exploration
As of January 2023, 23 patients had received loading doses ranging from 2 mg to 10 mg, with maintenance dosing ranging up to 10 mg to 14 mg. Ten patients have had between six and twelve months of exposure to GTX-102 and five patients have been on continuous therapy for more than one year. Based on the current protocols, the dose-finding cohorts in the U.K. and Canada will be followed by two, larger expansion cohorts with approximately 20 patients in each age range. Discussions are currently ongoing with the FDA to harmonize the three regions.
Based on the ongoing observations of encouraging clinical activity in the dose escalation cohorts, screening began for patients in expansion Cohort A (ages 4 to <8 years) and expansion Cohort B (ages 8 to <18 years) in February 2023. Each expansion cohort will enroll approximately 20 patients and will evaluate the same safety, pharmacokinetic, and efficacy measures as the dose escalating cohorts.
There continues to be dose and time dependent clinical activity seen across the study population, including three of the original U.S. patients who have been re-dosed, under the amended or expanded access protocols. The next data update, based on a larger number of patients in the program, is expected later this year.
DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): Enrollment in Phase 3 study complete
The Phase 3 study has a 48-week primary efficacy analysis period, and the company has enrolled approximately 50 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. The last patient has entered the baseline screening phase of the Phase 3 study of DTX401, with Phase 3 data expected in the first half of 2024.
DTX301 AAV gene therapy for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study enrolling patients
Ultragenyx has randomized and dosed the first patient in the Phase 3 study with additional patients in the approximate 4- to 8-week baseline screening period. The 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.
UX701 AAV gene therapy for Wilson Disease: Stage 1 of pivotal clinical study dosing patients; expect interim Stage 1 enrollment completion in mid-2023
The company is dosing patients in the first stage of the pivotal UX701 study under a recently amended protocol that removes placebo from the dose finding stage and enrolls five patients per cohort. During this stage of the study, safety and efficacy of up to three dose levels of UX701 will be evaluated and a dose will be selected for further evaluation in Stage 2. Completion of Stage 1 enrollment is expected in mid-2023 with data expected in early 2024 that would include safety and potentially initial signs of clinical activity.
UX111 AAV gene therapy for UX111 for the treatment of Sanfilippo syndrome type (MPS IIIA): Discussions ongoing with FDA to determine a plan to file for accelerated approval
In May 2022, Ultragenyx announced an exclusive license agreement with Abeona Therapeutics for UX111, formerly ABO-102. Under the terms of the agreement, Ultragenyx assumed responsibility for the UX111 program in exchange for Abeona’s right to receive tiered royalties of up to 10% on net sales, and milestone payments upon the attainment of certain commercial revenue milestones.
A meeting with the FDA to discuss a plan to file for accelerated approval is expected to occur in the first half of 2023.
UX053 mRNA for glycogen storage disease type III (GSDIII): Phase 1/2 single ascending dose cohort enrolled; data in 1H23
Dosing in the single ascending dose stage of the Phase 1/2 study of UX053 for the treatment of GSDIII has been completed. Data from this cohort are expected in the first half of 2023. Based on these analyses and other work, we will then review our plans for the next steps in the program.
1: Ultragenyx territories include the collaboration revenue from the North American profit-share territory (U.S. and Canada) and other regions where revenue from product sales is recognized by Ultragenyx (Latin America, Turkey). This excludes the European territory revenue, which is recognized as non-cash royalty revenue since the rights were sold to Royalty Pharma in December 2019.
Conference Call and Webcast Information
Ultragenyx will host a conference call today, Thursday, February 16, 2023, at 2 p.m. PT/ 5 p.m. ET to discuss the fourth quarter and full year 2022 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source To participate in the live call, please register by clicking on the following link (https://register.vevent.com/register/BI4de832f7ef8946e486c3198ed80e759f), and you will be provided with dial in details. The replay of the call will be available for one year.