On November 2, 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 ended September 30, 2022 and provided a corporate update for the year (Press release, Ultragenyx Pharmaceutical, NOV 2, 2022, View Source [SID1234622866]).
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"We continue to initiate treatment globally for more patients with Crysvita, Dojolvi and Mepsevii and are further expanding our markets with approvals of Crysvita in Argentina and Dojolvi in Mexico. We are seeing significant enthusiasm for the Evkeeza launch in Europe as we initiate reimbursement steps in member countries and are receiving many urgent calls for access for pediatric cases of HoFH," said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx. "At the same time, we are focusing on our priority clinical programs and in the next few months anticipate completing enrollment in the pivotal study for DTX401 for GSDIa, the important setrusumab Phase 2 stage for osteogenesis imperfecta, and the dose escalation cohorts of the GTX-102 program for Angelman syndrome."
Third Quarter 2022 Financial Results
Net Revenues
For the third quarter of 2022, Ultragenyx reported $90.7 million in total revenue. Ultragenyx recognized $64.5 million in Crysvita (burosumab) revenue in the Ultragenyx territories, which includes $51.3 million in collaboration revenue in the North American profit share territory and net product sales in other regions of $13.2 million. Total royalty revenue related to European Crysvita sales was $5.4 million. Dojolvi (triheptanoin) product sales in the third quarter of 2022 were $13.3 million. Mepsevii (vestronidase alfa) product sales for the third quarter of 2022 were $6.0 million.
Total revenue for the third quarter of 2022 also includes $1.5 million related to technical assistance following the successful completion of technology transfer activities with Daiichi Sankyo. This compares to total revenue in the third quarter of 2021, which includes $12.1 million related to the technology transfer services which were ongoing at the time.
Operating Expenses
Total operating expenses for the third quarter of 2022 were $315.8 million, which includes research and development expenses of $237.3 million, selling, general and administrative expenses of $69.8 million, and cost of sales of $8.6 million. Operating expenses for the quarter include $75.2 million in research and development expense to acquire GeneTx and non-cash stock-based compensation of $35.8 million.
Net Loss
For the third quarter of 2022, Ultragenyx reported net loss of $245.1 million, or $3.50 per share basic and diluted, which includes $75.2 million in research and development expense related to the acquisition of GeneTx. This compares with a net loss for the third quarter of 2021 of $73.0 million, or $1.08 per share, basic and diluted.
Net Cash Used in Operations
Net cash used in operations for the nine months ended September 30, 2022 was $290.1 million.
Cash, Cash Equivalents and Marketable Debt Securities
As of September 30, 2022, cash, cash equivalents, and marketable debt securities were $996.2 million, which includes $491.0 million in net proceeds that was received in July 2022 from OMERS through the sale of a portion of our Crysvita royalty in the profit share territory. Total payments to OMERS are capped at $725 million, which is 1.45 times the purchase price.
2022 Financial Guidance
The Company continues to expect 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.
Corporate and Program Updates
Crysvita for X-Linked Hypophosphatemia and Tumor Induced Osteomalacia: Amendment to collaboration agreement increases field support after April 2023
In September 2022, we entered into an amendment to our collaboration agreement with Kyowa Kirin Co. Ltd. (KKC) related to the transition of commercialization responsibilities from Ultragenyx to KKC on the transition date in April 2023. Under the terms of the amendment, Kyowa Kirin North America (KKNA) recently began field operations in the U.S. to further support the transition between the two companies and provide additional resources to support commercialization activities ahead of the transition. In addition, the amendment allows Ultragenyx to continue promoting and supporting the Crysvita program in the field in the U.S. until April 2024, which is one additional year after the transition date. During this period, Ultragenyx will continue to share costs of the Crysvita commercial operating expenses with KKC. The amendment strengthens our partnership in driving Crysvita forward with a substantial increase in the total commercial effort after the transition date to optimally support Crysvita’s growth while also allowing more overlap time to assure a smooth and productive transition of responsibilities.
GTX-102 for Angelman Syndrome: Enrollment and dosing in the Phase 1/2 ongoing; dosing in expansion cohorts expected in the first half of 2023
Based on encouraging interim clinical data and scientific confirmation of their technology, we exercised our option to acquire GeneTx and closed on the acquisition for $75.4 million, net of cash acquired from GeneTx, in July 2022. We are required to make milestone payments based on certain achievements and royalty payments on net sales.
In July 2022, we also provided an interim data update on patients treated in Canada, the U.K, and the U.S. under each region’s amended protocol for the Phase 1/2 study of GTX-102. As of the data cut-off for that update, a total of 11 patients had reached at least the Day 128 evaluation, with three patients reaching the Day 170 Pre-Maintenance Dose (PMD) evaluation. We evaluated patients across various clinical measurements and found encouraging signs of clinical activity including some changes in quantitative measures such as the Bayley-4 expressive and receptive communication that were statistically significantly different from normal variation, even starting at the lowest doses of the titration ramp. The quantitative data also appear to show a dose-dependent effect and that some patients did improve further with longer follow up.
At this time, 13 patients have received cumulative doses of 20 mg or higher, and 14 patients have over 132 days of exposure to treatment, which was the minimum cumulative dose and maximum exposure after the first dose that led to the lower extremity weakness that was seen in the originally treated five patients. There have been no treatment-related SAEs of any type nor adverse events related to lower extremity weakness observed in these patients. No clinically significant or persistent elevations of cerebrospinal fluid protein level have been observed to date.
Redosing of patients originally treated in 2020 under the original protocol has begun outside the U.S. Two of the original five patients treated in the U.S. have now restarted treatment at a Canadian site and, since restarting, have received two or more doses with no treatment-related SAEs of any type nor adverse events related to lower extremity weakness observed in these patients to date.
Dosing in the U.K. and Canada is ongoing with patients continuing to initiate treatment at higher loading doses and to receive treatment in the maintenance phase. Discussions with the FDA to harmonize the U.S. with the Canada/U.K. protocol are ongoing. We expect to begin enrollment of the expansion cohorts in the first half of 2023. We also expect to provide the next data update when we have substantive data on a larger number of patients in the program.
UX143 (setrusumab) for Osteogenesis Imperfecta (OI): Phase 2/3 study dosing patients; Phase 2 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 under a recently amended protocol. The updated protocol removes placebo in the dose finding stage to enable more efficient real-time data analyses for the same two dose levels of setrusumab as in the original protocol. We expect to complete enrollment in early 2023 and will have data from the Phase 2 portion of the study in mid-2023, including two-month changes in bone biomarkers response that will be used to establish the optimal dosing algorithm for the Phase 3 portion of the study.
In addition, Ultragenyx intends to initiate an additional randomized study in children with OI under age five in the first half of 2023 with severe bone disease comparing bisphosphates to setrusumab with total fractures as the primary endpoint.
DTX401 for Glycogen Storage Disease Type Ia (GSDIa): Phase 3 study randomizing patients, last patient to be randomized around the end of the year
In September 2022, DTX401 was accepted into the EMA’s Priority Medicines program (PRIME), enabling more frequent interactions with the EMA and the potential for an accelerated approval.
The Phase 3 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 or placebo. The primary endpoint is the reduction in oral glucose replacement with cornstarch while maintaining glucose control. The last patient to be enrolled in the baseline screening phase of the Phase 3 study of DTX401 is expected to occur around the end of the year.
UX701 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 Cyprus2+ study of UX701 under a recently amended protocol that removes placebo from the dose finding stage and sets 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. The design should allow more real-time assessment of the gene therapy. Completion of Stage 1 enrollment is expected in mid-2023 with data on safety and initial signs of clinical activity expected around the end of 2023 or early 2024.
DTX301 for Ornithine Transcarbamylase (OTC) Deficiency: Phase 3 study expected to initiate around the end of the year
Ultragenyx expects to initiate the Phase 3 study of DTX301 in patients with OTC around the end 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 removal of ammonia-scavenger medications and protein-restricted diet and change in 24-hour ammonia levels.
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 are 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, Wednesday, November 2, 2022, at 2 p.m. PT/ 5 p.m. ET to discuss the third quarter 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/BI6b6d0f4fec0e415597e9e3890c1f67fd), and you will be provided with dial in details. The replay of the call will be available for one year.