Glycogen Storage Disease Type I

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

Preliminary 2023 Total Revenue of $430 million to $435 million, Crysvita® Revenue of $325 million to $330 million and Dojolvi® revenue of $70 million to $71 million 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 Year-end 2023 cash balance of approximately $776 million and 2024 guidance for net cash used in operations expected to be less than $400 million NOVATO, Calif., Jan. 07, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel products for serious rare and ultrarare genetic diseases, today reported preliminary unaudited 2023 revenue results, cash and investments at year end 2023, and provided 2024 guidance on select key financial metrics including net cash used in operations. “2024 is poised to be a year of significant momentum for Ultragenyx, with clinical catalysts across multiple value-driving programs, meaningful revenue growth from our commercial products, and continued focus on financial discipline,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “We anticipate several important milestones in the first half of the year, including completing enrollment of our Phase 3 studies in osteogenesis imperfecta, interim data on a substantive portion of patients enrolled in our Phase 1/2 study in Angelman syndrome, Stage 1 data from our pivotal Phase 1/2/3 study in Wilson disease, and topline Phase 3 data from our GSDIa gene therapy program.” Ultragenyx will present at the 42ᵗʰ annual J.P. Morgan Healthcare Conference on Monday, January 8, 2024 at 3:00 p.m. PT. The live and archived webcast of the presentation will be accessible from the company’s website at https://ir.ultragenyx.com/events-presentations. Financial Update 2023 Revenue (unaudited) and 2024 Revenue Guidance 2023 2024($ in millions)Preliminary Revenue Revenue GuidanceCrysvita$325 - $330 $375 - $400Dojolvi$70 - $71 $75 - $80Total Revenue$430 - $435 $500 - $530 2023 Ending Cash Position (unaudited) and 2024 Cash Used in Operations Guidance Cash, cash equivalents, and available-for-sale investments were approximately $776 million as of December 31, 2023. Cash uses in 2023 included the completion of construction of our gene therapy manufacturing facility. With forecasted ~20% increases in revenue and continued focus on key pipeline value drivers, 2024 net cash use is projected to be less than $400 million. The 2023 revenues and cash position included in this release are preliminary and are therefore subject to adjustment. The preliminary revenue results are based on management’s initial analysis of operations for the year ended December 31, 2023. The Company expects to issue full financial results for the fourth quarter and fiscal year 2023 in February 2024. Recent Updates and 2024 Clinical Milestones UX143 (setrusumab) monoclonal antibody for Osteogenesis Imperfecta (OI): Phase 3 portion of Orbit study expected to be fully enrolled in the first quarter of 2024 Patients are being dosed in the late-stage clinical trials, Orbit and Cosmic, which evaluate setrusumab in pediatric and young adult patients with OI. The randomized, placebo-controlled Phase 3 portion of the Orbit study is expected to be fully enrolled around the end of the first quarter of 2024. Additional longer-term Phase 2 data from the Orbit study are expected in 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 aged 2 to <5 years. Cosmic is targeting to enroll approximately 65 patients at more than 20 global sites and is expected to complete enrollment in the first half of 2024. GTX-102 an 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 patients enrolled. There are a total of 74 patients 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 cohorts plus some new evaluations. The next data update is expected in the first half of 2024 and is planned to include at least 20 expansion cohort patients with a minimum of Day 170 data. UX701 AAV gene therapy for Wilson Disease: Last patient in Cohort 3 on track to be dosed soon; expect interim Stage 1 data in the first half of 2024Four of five patients in the third of three dose escalation cohorts in the pivotal study have been dosed, with the fifth patient scheduled to be dosed soon. 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 first half of 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 to be presented at WORLDSymposiumTM in February 2024Ultragenyx will present new data from the ongoing pivotal Transfer A study evaluating the efficacy and safety of UX111 in children with MPS IIIA at the 20th Annual WORLDSymposiumTM. The presentation will show that reductions of heparan sulfate exposure in cerebrospinal fluid correlate with improved long-term cognitive function in patients with MPS IIIA following treatment with UX111. Discussions with FDA seeking an accelerated review path are ongoing. 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 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. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are 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 the Company’s clinical development programs, commercial success of its products and product candidates, continued 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 candidate. 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-/). Contacts Ultragenyx Pharmaceutical Inc.InvestorsJoshua Higair@ultragenyx.com MediaCarolyn Wang media@ultragenyx.com

Announces pipeline prioritization and corporate restructuring to focus on clinical stage AAV Therapeutic product candidates addressing large commercial opportunities and value generation Highest priority programs are ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, RGX-202 for the treatment of Duchenne, and RGX-121 for the treatment MPS II Restructuring plan, including a 15% reduction in workforce, expected to result in total savings of at least $100 million Anticipated cost savings from corporate restructuring, along with $365 million in cash, cash equivalents and marketable securities as of September 30, 2023, expected to fund operational runway into the second half of 2025 Conference call Wednesday, November 8, 2023, at 4:30 p.m. (EST) ROCKVILLE, Md., Nov. 8, 2023 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced financial results for the third quarter ended September 30, 2023, and recent operational highlights, including a strategic pipeline prioritization and corporate restructuring intended to significantly reduce operating expenses while continuing to support meaningful value generation from the Company's strong pipeline of AAV Therapeutics. "In the past two months, we reported exciting, positive clinical data from investigational treatments for diabetic retinopathy, and Duchenne, as well as had a very encouraging RMAT meeting with the FDA about expediting the BLA for our treatment for MPS II," said Kenneth T. Mills, President and Chief Executive Officer of REGENXBIO. "These milestones demonstrate how our science is supporting avenues to accelerate development, and, today, we are following the data and making necessary decisions to focus our capabilities and resources on these differentiated product candidates which represent opportunities to bring ground-breaking AAV Therapeutics to millions of patients." PIPELINE PRIORITIZATION AND CORPORATE RESTRUCTURING The following key strategic decisions support the pipeline prioritization and corporate restructuring related to product candidates that are differentiated, can be expedited, and support near-term and long-term value generation. Prioritizing investigational, one-time AAV therapeutic clinical stage programs: ABBV-RGX-314, being developed in collaboration with AbbVie, for the treatment of wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR) and other additional chronic retinal conditions RGX-202 for the treatment of Duchenne muscular dystrophy (Duchenne) RGX-121 for the treatment of Mucopolysaccharidosis Type II (MPS II) Pursuing strategic alternatives, including potential partnering, for its other rare neurodegenerative disease clinical stage programs: RGX-111 for the treatment of severe Mucopolysaccharidosis Type I, RGX-181 for the treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a form of Batten disease and RGX-381 for the treatment of the ocular manifestations of CLN2 disease. Reducing its workforce by approximately 15%, primarily in rare neurodegenerative disease development, early research, and other general and administrative areas. REGENXBIO expects to incur approximately $4 million in one-time restructuring costs in the fourth quarter of 2023. As a result of the portfolio prioritization and corporate restructuring, REGENXBIO anticipates total savings of at least $100 million over the next two years. These anticipated cost savings along with $365 million in cash, cash equivalents and marketable securities as of September 30, 2023 are now expected to fund operations into the second half of 2025. Mr. Mills added, "since our formation, REGENXBIO has been a leader in the field because of our mission to improve lives through the curative potential of gene therapy with our NAV® Technology Platform. As we refocus our capital allocation in a challenging economic environment and position the Company to meet important business goals, I want to express my gratitude for the commitment and dedication exhibited by our colleagues and partners in support of this mission." PROGRAM HIGHLIGHTS AND MILESTONES ABBV-RGX-314: ABBV-RGX-314 uses the NAV® AAV8 vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor (VEGF). ABBV-RGX-314 is currently being evaluated in nine ongoing clinical trials, including two pivotal trials, a Phase II bridging study, a Long-term Follow-up study, and a Fellow Eye treatment study in patients with wet AMD, all utilizing subretinal delivery, as well as two Phase II clinical trials in patients with wet AMD and DR, and two corresponding Long-term Follow-up studies, all utilizing in-office suprachoroidal delivery. ABBV-RGX-314 Subretinal Delivery for the Treatment of Wet AMD Enrollment continues to be on track in ATMOSPHERE® and ASCENTTM pivotal trials for the treatment of patients with wet AMD using subretinal delivery. These trials are expected to support global regulatory submissions with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in late 2025 through the first half of 2026. ABBV-RGX-314 Suprachoroidal Delivery for Treatment of Wet AMD and DR In November 2023, REGENXBIO presented data from the Phase II ALTITUDE® trial demonstrating that ABBV-RGX-314 administered using suprachoroidal delivery was well tolerated in dose levels 1 and 2. At one year, dose level 2 in non-proliferative DR patients prevented disease progression as measured by the Early Treatment Diabetic Retinopathy Study-Diabetic Retinopathy Severity Scale. Dose level 2 reduced the risk of developing vision-threatening events by 89% in these patients. REGENXBIO expects to report additional interim data from the Phase II AAVIATE® trial of ABBV-RGX-314 using suprachoroidal delivery for the treatment of wet AMD, including full six-month results from Cohorts 5 and 6, at the Hawaiian Eye and Retina meeting (January 13-19, 2024). RGX-202: RGX-202 is an investigational one-time AAV therapeutic for Duchenne, using the NAV AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne. In October 2023, REGENXBIO reported interim data from the Phase I/II AFFINITY DUCHENNE® trial, demonstrating that RGX-202 continued to be well tolerated with no drug-related serious adverse events in three patients at dose level 1. Initial biomarker data in two patients who completed three-month assessment demonstrate robust RGX-202 microdystrophin expression with localization to the muscle cell membrane. REGENXBIO plans to use RGX-202 microdystrophin expression as a surrogate endpoint to support a Biologics License Application (BLA) filing using the accelerated approval pathway. REGENXBIO reported that, based on these interim results, reported from dose level 1, the FDA has supported amending the trial protocol to accelerate development. Escalation to dose level 2 is expected by the end of 2023. REGENXBIO expects to share initial strength and functional assessment data for both dose levels in 2024. Additionally, REGENXBIO anticipates pivotal dose determination and the initiation of a pivotal program in 2024. RGX-121: RGX-121 is an investigational one-time AAV therapeutic for the treatment of MPS II, also known as Hunter syndrome, using the NAV AAV9 vector to deliver the gene that encodes the iduronate-2-sulfatase enzyme. REGENXBIO continues to follow patients in the Phase I/II/III CAMPSIITE® trial, with topline results from pivotal phase expected in the first quarter of 2024. A recent positive Regenerative Medicine Advanced Therapy (RMAT) meeting held in October with FDA confirmed alignment on manufacturing strategy, adequacy of safety database, and confirmatory study design, which are key elements for an expedited plan for BLA filing using the accelerated approval pathway in 2024. Based on an expected priority review, potential approval of the Company's planned BLA for RGX-121 could result in receipt of a Rare Pediatric Disease Priority Review Voucher in 2025. OPERATIONAL UPDATES The REGENXBIO Manufacturing Innovation Center in Maryland is using the NAVXpress™ platform process to produce GMP lots intended for upcoming regulatory submissions and initial launch supply for ABBV-RGX-314 and RGX-121. REGENXBIO is one of only a few gene therapy companies worldwide with a cGMP facility capable of production at scales up to 2,000 liters. NAV® TECHNOLOGY PLATFORM LICENSEE PROGRAM HIGHLIGHTS As of September 30, 2023, REGENXBIO's NAV Technology Platform was being applied in one marketed product and multiple clinical stage partnered programs, with the potential to impact a broad range of therapeutic areas and disease indications. Zolgensma®, a one-time AAV Therapeutic for the treatment of spinal muscular atrophy, is a marketed product utilizing REGENXBIO's NAV AAV9 vector. In October 2023, Novartis AG reported third quarter 2023 global sales of Zolgensma of $308 million. In November 2023, Rocket Pharmaceuticals announced the initiation of the Phase II pivotal trial of RP-A501 for Danon Disease. RP-A501 is being developed as a one-time gene therapy utilizing REGENXBIO's NAV AAV9 vector. In October 2023, Ultragenyx Pharmaceutical Inc. announced plans to provide preliminary Phase III DTX401 data in the first half of 2024 and that the DTX301 Phase III study is expected to complete enrollment in the first half of 2024. DTX401 for the treatment of Glycogen Storage Disease Type Ia and DTX301 for the treatment of Ornithine Transcarbamylase Deficiency are both being developed as one-time gene therapies utilizing REGENXBIO's NAV AAV8 vector. FINANCIAL RESULTS Cash Position: Cash, cash equivalents and marketable securities were $364.5 million as of September 30, 2023, compared to $565.2 million as of December 31, 2022. The decrease was primarily driven by cash used to fund operating activities during the nine months ended September 30, 2023. Revenues: Revenues were $28.9 million for the three months ended September 30, 2023, compared to $26.5 million for the three months ended September 30, 2022. The increase was primarily attributable to Zolgensma royalty revenues, which increased from $25.2 million for the third quarter of 2022 to $28.4 million for the third quarter of 2023. Research and Development Expenses: Research and development expenses were $58.2 million for the three months ended September 30, 2023, compared to $63.3 million for the three months ended September 30, 2022. The decrease was primarily attributable to clinical trial and manufacturing expenses for ABBV-RGX-314 resulting from an increase in development cost reimbursement from AbbVie under our eye care collaboration and was partially offset by an increase in clinical trial expenses for our other lead product candidates. General and Administrative Expenses: General and administrative expenses were $23.1 million for the three months ended September 30, 2023, compared to $20.9 million for the three months ended September 30, 2022. The increase was primarily attributable to personnel-related costs, expenses for professional services and other corporate overhead costs. Net Loss: Net loss was $61.9 million, or $1.41 basic and diluted net loss per share, for the three months ended September 30, 2023, compared to a net loss of $75.5 million, or $1.75 basic and diluted net loss per share, for the three months ended September 30, 2022. FINANCIAL GUIDANCE As a result of the portfolio prioritization and corporate restructuring, REGENXBIO anticipates total savings of at least $100 million over the next two years. These anticipated cost savings along with $365 million in cash, cash equivalents and marketable securities as of September 30, 2023 are now expected to fund operations into the second half of 2025. This cash runway guidance is based on the Company's current operational plans and excludes the impact of any payments that may be received from AbbVie upon the achievement of development or commercial milestones under our ABBV-RGX-314 collaboration. CONFERENCE CALL In connection with this announcement, REGENXBIO will host a conference call and webcast today at 4:30 p.m. EST. A live audio webcast will be available at HERE. Interested parties may also pre-register for the earnings conference call HERE. Once registration is completed, participants will be provided a dial-in number with a personalized conference code to access the call. Those who plan on participating are advised to dial in 15 minutes prior to the start time. ABOUT REGENXBIO Inc. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO's NAV Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8 and AAV9. REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates, including late-stage and commercial programs, in multiple therapeutic areas. REGENXBIO is committed to a '5x'25' strategy to progress five AAV Therapeutics from our internal pipeline and licensed programs into pivotal-stage or commercial products by 2025. FORWARD-LOOKING STATEMENTS This press release includes "forward-looking statements," within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements express a belief, expectation or intention and are generally accompanied by words that convey projected future events or outcomes such as "believe," "may," "will," "estimate," "continue," "anticipate," "assume," "design," "intend," "expect," "could," "plan," "potential," "predict," "seek," "should," "would" or by variations of such words or by similar expressions. The forward-looking statements include statements relating to, among other things, REGENXBIO's future operations, clinical trials, costs and cash flow. REGENXBIO has based these forward-looking statements on its current expectations and assumptions and analyses made by REGENXBIO in light of its experience and its perception of historical trends, current conditions and expected future developments, as well as other factors REGENXBIO believes are appropriate under the circumstances. However, whether actual results and developments will conform with REGENXBIO's expectations and predictions is subject to a number of risks and uncertainties, including the timing of enrollment, commencement and completion and the success of clinical trials conducted by REGENXBIO, its licensees and its partners, the timing of commencement and completion and the success of preclinical studies conducted by REGENXBIO and its development partners, the timely development and launch of new products, the ability to obtain and maintain regulatory approval of product candidates, the strategic pipeline prioritization and corporate restructuring plan or other cost-saving measures, and expected charges associated with restructuring and any future cost reduction measures, the ability to obtain and maintain intellectual property protection for product candidates and technology, trends and challenges in the business and markets in which REGENXBIO operates, the size and growth of potential markets for product candidates and the ability to serve those markets, the rate and degree of acceptance of product candidates, and other factors, many of which are beyond the control of REGENXBIO. Refer to the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of REGENXBIO's Annual Report on Form 10-K for the year ended December 31, 2022, and comparable "risk factors" sections of REGENXBIO's Quarterly Reports on Form 10-Q and other filings, which have been filed with the U.S. Securities and Exchange Commission (SEC) and are available on the SEC's website at . All of the forward-looking statements made in this press release are expressly qualified by the cautionary statements contained or referred to herein. The actual results or developments anticipated may not be realized or, even if substantially realized, they may not have the expected consequences to or effects on REGENXBIO or its businesses or operations. Such statements are not guarantees of future performance and actual results or developments may differ materially from those projected in the forward-looking statements. Readers are cautioned not to rely too heavily on the forward-looking statements contained in this press release. These forward-looking statements speak only as of the date of this press release. Except as required by law, REGENXBIO does not undertake any obligation, and specifically declines any obligation, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Zolgensma® is a registered trademark of Novartis Gene Therapies. All other trademarks referenced herein are registered trademarks of REGENXBIO. CONTACTS: Dana Cormack Corporate Communications [email protected] Chris Brinzey, ICR Westwicke 339-970-2843 [email protected] SOURCE REGENXBIO Inc.