On February 10, 2022 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultra-rare genetic diseases, reported its financial results for the quarter and full year ended December 31, 2021 and reaffirmed its financial guidance for 2022 (Press release, Ultragenyx Pharmaceutical, FEB 10, 2022, View Source [SID1234607974]).
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"Over the last quarter we made significant progress across our early and late-stage clinical pipeline, including resuming the Phase 1/2 study for Angelman syndrome and initiating two pivotal gene therapy studies in GSDIa and Wilson disease. Our recently announced collaboration with Regeneron for Evkeeza gives us a fourth approved product adding to the ongoing successful launches of Crysvita, Mepsevii, and Dojolvi," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "In 2022, we will leverage our strong capital position to continue building on this momentum, enrolling patients in our six clinical programs, launching Evkeeza in Europe, expanding our global commercial efforts to Japan, and substantially complete the construction of our gene therapy manufacturing facility."
Fourth Quarter and Full Year 2021 Financial Results
Net Revenues
For the fourth quarter of 2021, Ultragenyx reported $83.4 million in total revenue. Ultragenyx recognized $55.5 million in Crysvita (burosumab) revenue in the Ultragenyx territories, which includes $50.2 million in collaboration revenue in the North American profit share territory and net product sales in other regions of $5.3 million. Total royalty revenue related to European Crysvita sales were $4.7 million. Dojolvi (triheptanoin) product sales in the fourth quarter of 2021 were $11.8 million. Mepsevii (vestronidase alfa) product sales for the fourth quarter of 2021 were $3.1 million. Total revenue for the fourth quarter also includes $8.2 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, 2021 was $351.4 million, including $192.6 million in Crysvita revenue in the Ultragenyx territories. Crysvita collaboration revenue in the North American profit share territory was $171.2 million and net Crysvita product sales in other regions were $21.4 million. Total royalty revenue related to European Crysvita royalties was $18.2 million. Dojolvi product revenue for the year ended December 31, 2021 was $39.6 million. Mepsevii product revenue was $16.0 million. For the year ended December 31, 2021, revenue related to our strategic manufacturing partnership with Daiichi Sankyo was $85.0 million.
Operating Expenses
Total operating expenses for the fourth quarter of 2021 were $186.0 million, including non-cash stock-based compensation of $26.5 million. Total operating expenses for the year ended December 31, 2021 were $733.1 million, which includes a $50.0 million expense for the upfront payment of the license and collaboration agreement with Mereo Biopharma in January 2021 and non-cash stock-based compensation of $105.0 million.
Net Loss
For the fourth quarter of 2021, Ultragenyx reported net loss of $122.5 million, or $1.79 per share basic and diluted, compared with a net loss for the fourth quarter of 2020 of $24.0 million, or $0.37 per share, basic and diluted. For the year ended December 31, 2021, net loss was $454.0 million, or $6.70 per share, basic and diluted, compared with a net loss for the same period in 2020 of $186.6 million, or $3.07 per share, basic and diluted. Net cash used in operations for the year ended December 31, 2021 was $338.7 million.
Cash, Cash Equivalents and Marketable Debt Securities
Cash, cash equivalents, and marketable debt securities were approximately $1.0 billion as of December 31, 2021.
2022 Financial Guidance
The company expects 2022 revenue for Crysvita in Ultragenyx territories to be between $250 million and $260 million and Dojolvi revenue to be between $55 million and $65 million.
Recent Updates and 2022 Milestones
Evkeeza (evinacumab) for Homozygous Familial Hypercholesterolemia (HoFH): Submission of reimbursement dossiers expected in European countries in 2022
Ultragenyx and Regeneron announced a license and collaboration agreement for Ultragenyx to commercialize and distribute Evkeeza in countries outside of the U.S. This includes the European Economic Area where Evkeeza was approved in June 2021 as a first-in-class monoclonal antibody targeting ANGPTL3 for use together with diet and other low-density lipoprotein-cholesterol (LDL-C) lowering therapies to treat adults and adolescents aged 12 years and older with HoFH.
Ultragenyx plans to submit reimbursement dossiers with national health authorities in Europe in 2022.
UX143 (setrusumab) for Osteogenesis Imperfecta (OI): Dosing in the Pivotal Phase 2/3 Orbit study is expected to begin in the first half of 2022; Phase 2 study in children under age 5 planned for second half of 2022
Ultragenyx expects to begin dosing in the seamless Phase 2/3 Orbit study of UX143 in pediatric and adult patients ages 5 to <26 in the first half of 2022. In addition, Ultragenyx intends to initiate a Phase 2 study in children under age 5 with OI in the second half of 2022 and will continue to evaluate adult patients who were previously treated in the ASTEROID study, a Phase 2b study conducted by our partner Mereo.
A dosing update on the Phase 2 portion of the Orbit study and transition to Phase 3 is expected in the second half of 2022.
DTX401 for Glycogen Storage Disease Type Ia (GSDIa): First patients dosed in Phase 3 GlucoGene study
At the 14th International Congress of Inborn Errors of Metabolism (ICIEM) that took place in November 2021, Ultragenyx presented 2 additional positive long-term safety and efficacy data from its Phase 1/2 study of DTX401 with patients demonstrating a durable response up to three years after receiving DTX401.
The first patients have been dosed in the Phase 3 study of DTX401 following an approximate 4- to 8-week baseline screening period. The Phase 3 GlucoGene study has a 48-week primary efficacy analysis period and the company plans to enroll approximately 50 patients eight years of age and older, randomized 1:1 to DTX401 (1.0 x 10^13 GC/kg dose) or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control.
DTX301 for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 eNH3ance study expected to initiate in first half of 2022
At the 14th ICIEM, Ultragenyx presented3 additional positive long-term safety and efficacy data from its Phase 1/2 study of DTX301 with patients demonstrating a durable response up to four years after receiving DTX301.
Ultragenyx expects to initiate the Phase 3 eNH3ance study of DTX301 in patients with OTC in the first half of 2022. The 64-week study will include approximately 50 patients, randomized 1:1 to DTX301 or placebo. The primary endpoints are response as measured by change in baseline disease management and change in 24-hour ammonia levels, supported by change in the rate of ureagenesis as a key secondary endpoint.
GTX-102 for Angelman Syndrome: Phase 1/2 study is titrating patients in Canada and the U.K. with data anticipated mid-year 2022; Dosing has begun in the U.S.
The first four patients in the Phase 1/2 study have received multiple doses of GTX-102 and regular assessments for safety. There have been no treatment-related serious adverse events of any type nor adverse events related to lower extremity weakness observed in these patients, and initial assessments have shown early signs of clinical activity.
The independent data safety monitoring board (DSMB) has met to discuss the assessments for the first two patients each in Cohort 4 (ages 4 to <8 years) and Cohort 5 (ages 8 to <18 years). They recommended that the study continue enrolling and dosing of the remaining planned eight patients has begun. Data on full Cohorts 4 and 5 in the Canada/U.K. arm of the study as well as available safety and efficacy data from the patients treated in the U.S. are anticipated in mid-2022.
Patients naïve to prior treatment with GTX-102 have been screened in the U.S. and dosing has begun.
UX701 for Wilson Disease: Cyprus2+ pivotal Phase 1/2/3 study currently enrolling
Ultragenyx is currently screening and enrolling patients with Wilson disease into the baseline monitoring period prior to dosing in its pivotal, seamless Phase 1/2/3 Cyprus2+ study of UX701. During the first stage of the study, the 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. In Stage 2, a new cohort of patients will be randomized 2:1 to receive the selected dose of UX701 or placebo. The primary efficacy endpoints are change in 24-hour urinary copper concentration and percent reduction in standard of care medication by Week 52.
UX053 for Glycogen Storage Disease Type III (GSDIII) Debrancher Deficiency: Phase 1/2 study currently dosing patients; Preliminary data from first part of study and initiation of second part of study anticipated in second half of 2022
Ultragenyx has begun to dose patients in the two-part Phase 1/2 clinical trial evaluating the safety, tolerability and efficacy of UX053 in adults age 18 years and older with GSDIII. Part 1 is open label and will enroll up to 10 patients who will receive a single ascending dose of UX053 administered via intravenous infusion. Part 2 is double-blind and will evaluate five repeat doses at escalating dose levels in up to 16 patients across four cohorts randomized 3:1 to UX053 or placebo. The primary endpoints are treatment-emergent adverse events (TEAEs), serious TEAEs, and related TEAEs in both parts of the study. Secondary endpoints include pharmacokinetic parameters. Tertiary endpoints include clinician- and patient-reported outcomes, muscle strength, blood sugar, and biomarkers of liver, cardiac and muscle health.
Preliminary data from the Part 1 single ascending dose phase of the study and initiation of the Part 2 repeat dosing phase of the study is anticipated in the second half of the year.
Conference Call and Webcast Information
Ultragenyx will host a conference call today, Thursday, February 10, 2022, at 2 p.m. PT/ 5 p.m. ET to discuss the fourth quarter and year 2021 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 by phone, dial (855) 797-6910 (USA) or (262) 912-6260 (international) and enter the passcode 2087696. The replay of the call will be available for one year.