RARE

It has been about a month since the last earnings report for Ultragenyx (RARE). Shares have added about 6.4% in that time frame, outperforming the S&P 500. But investors have to be wondering, will the recent positive trend continue leading up to its next earnings release, or is Ultragenyx due for a pullback? Well, first let's take a quick look at its latest earnings report in order to get a better handle on the recent drivers for Ultragenyx Pharmaceutical Inc. before we dive into how investors and analysts have reacted as of late. Ultragenyxreported second-quarter 2026 loss of 90 cents per share, which was narrower than the Zacks Consensus Estimate of a loss of $1.27. The company had incurred a loss of $1.17 per share in the year-ago quarter. Total revenues in the second quarter were $214 million, which surged 28.1% year over year due to higher product sales. The top line also beat the Zacks Consensus Estimate of $181 million. Management stated that second-quarter 2026 revenues were the highest quarterly revenues ever reported by the company. Crysvita’s total revenues were $156 million, up 28.9% year over year. Management noted that Crysvita sales were consistent with expected seasonality in the United States and Canada and ordering patterns in Latin America. Crysvita’s net product revenues in the second quarter of 2026 included $94 million from North America, $54 million from Latin America and Turkey, and $8 million from Europe. Mepsevii product revenues increased 11.1% year over year to $10 million in the reported quarter. Dojolvi product revenues were $27 million, up 17.4%, driven by strong demand. Evkeeza recorded sales of $21 million in the second quarter, up 50%, driven by increased demand from new country launches and early access. Operating expenses of $289 million in the quarter rose 5.1% year over year due to increased investments in multiple late-stage pipeline programs and marketing costs for approved drugs. Operating expenses included research and development (R&D) expenses of $167 million (up 1.2%), selling, general and administrative (SG&A) expenses of $88 million (up 1.1%) and cost of sales of $34 million (up 47.8%). Cash, cash equivalents and marketable securities amounted to $436 million as of June 30, 2026, compared with $534 million as of March 31, 2026. Ultragenyx continues to expect total revenues in 2026, excluding potential revenues from new product launches, between $730 million and $760 million. Crysvita revenues in 2026 are expected to be in the range of $500-$520 million, reflecting growing underlying global demand. Meanwhile, Dojolvi revenues are expected to be between $100 million and $110 million in 2026. It turns out, estimates revision have trended downward during the past month. The consensus estimate has shifted 25.84% due to these changes. Currently, Ultragenyx has a average Growth Score of C, however its Momentum Score is doing a lot better with an A. However, the stock was allocated a score of F on the value side, putting it in the lowest quintile for value investors. Overall, the stock has an aggregate VGM Score of C. If you aren't focused on one strategy, this score is the one you should be interested in. Estimates have been trending downward for the stock, and the magnitude of these revisions looks promising. Notably, Ultragenyx has a Zacks Rank #3 (Hold). We expect an in-line return from the stock in the next few months. Ultragenyx belongs to the Zacks Medical - Biomedical and Genetics industry. Another stock from the same industry, CRISPR Therapeutics AG (CRSP), has gained 8.5% over the past month. More than a month has passed since the company reported results for the quarter ended June 2026. CRISPR Therapeutics reported revenues of $10.18 million in the last reported quarter, representing a year-over-year change of +1043.8%. EPS of -$0.94 for the same period compares with -$1.29 a year ago. CRISPR Therapeutics is expected to post a loss of $1.06 per share for the current quarter, representing a year-over-year change of +9.4%. Over the last 30 days, the Zacks Consensus Estimate has changed +5.9%. CRISPR Therapeutics has a Zacks Rank #3 (Hold) based on the overall direction and magnitude of estimate revisions. Additionally, the stock has a VGM Score of F. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Ultragenyx Pharmaceutical Inc. (RARE) : Free Stock Analysis Report CRISPR Therapeutics AG (CRSP) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Phase 3 Aspire did not achieve the primary endpoint of change from Baseline in Bayley-4 cognitive raw score nor the key secondary endpoint of net response in Multidomain Responder Index (MDRI) NOVATO, Calif., Sept. 02, 2026 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced results from the Phase 3 Aspire study for apazunersen (GTX-102) in Angelman syndrome. The study did not achieve the primary endpoint of change from Baseline in Bayley-4 cognitive raw score nor the key secondary endpoint of net response in Multidomain Responder Index (MDRI). The safety profile observed in Aspire was consistent with Phase 1/2. “Based on everything we observed in the robust Phase 1/2 clinical development program and long-term extension study, we are disappointed by the Aspire result,” said Emil Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “Even more, we are disappointed for the global patient community who has invested so much in early-stage research, working to bring a first-ever treatment to their children.” In Aspire, the randomized groups were comparable at baseline and consistent with the patients studied in Phase 2. There were no differences between the treated and control groups that could support efficacy in the Bayley Cognition raw scores nor in the MDRI when looking at net response or mean changes of the individual five endpoints included in the MDRI. The Company will evaluate the apazunersen program in light of this outcome and make a decision on its disposition. The Company will also assess its planned operations to define and implement significant expense reductions, while supporting its growing commercial business. Dr. Kakkis continued: “We will maintain focus on our growing commercial business, which continues to create meaningful value, including new sources of revenue from the recent approval of GENGLYCOS for glycogen storage disease type Ia, the potential approval of UX111 for Sanfillipo syndrome, and the expansion of existing products to new territories. This strong commercial foundation will support our pipeline, while continuing toward profitability in 2027.” About apazunersen (GTX-102)Apazunersen (GTX-102) is an investigational antisense oligonucleotide (ASO) therapy delivered via intrathecal administration and designed to target and inhibit expression of the UBE3A-AS to prevent silencing of the paternally inherited allele of the UBE3A gene and reactivate expression of the deficient protein. Apazunersen has been granted Breakthrough Therapy Designation, Orphan Drug Designation, Rare Pediatric Disease Designation, and Fast Track Designation from the FDA and Orphan Designation and PRIME designation from the EMA. About Angelman SyndromeAngelman syndrome is a rare, neurogenetic disorder caused by loss-of-function of the maternally inherited allele of the UBE3A gene. The maternal-specific inheritance pattern of Angelman syndrome is due to genomic imprinting of UBE3A in neurons of the central nervous system (CNS), a naturally occurring phenomenon in which the maternal UBE3A allele is expressed and the paternal UBE3A is not. Silencing of the paternal UBE3A allele is regulated by the UBE3A-AS, the intended target of apazunersen. In almost all cases of Angelman syndrome, the maternal UBE3A allele is either missing or mutated, resulting in limited to no protein expression. This condition is generally not inherited but instead occurs spontaneously. It is estimated to affect approximately 60,000 people in commercially accessible geographies. Angelman syndrome is a lifelong neurodevelopmental disorder that causes cognitive impairment, motor impairment, balance issues and debilitating seizures. Some individuals with Angelman syndrome are unable to walk and most do not speak. Anxiety and disturbed sleep can be serious challenges in individuals with Angelman syndrome. Although individuals with Angelman syndrome have a normal lifespan, they require continuous care and are unable to live independently. Angelman syndrome is not a degenerative disorder, but the loss of the UBE3A protein expression in neurons results in abnormal communications between neurons. Angelman syndrome is often misdiagnosed as autism or cerebral palsy. There are no currently approved therapies for Angelman syndrome; however, several symptoms of this disorder can be reversed in adult animal models of Angelman syndrome, suggesting that improvement of symptoms can potentially be achieved at any age. About UltragenyxUltragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultra-rare 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 MediaExcept for the historical information contained herein, the matters set forth in this press release, including statements related to Ultragenyx’s plans to evaluate its operations and implement significant expense reductions, the Company’s expectations for profitability in 2027, the expected scope, timing, benefits and impact of those actions, its future operating results and financial performance, its business plans and objectives for GTX-102 following the Aspire results, the future development and regulatory path for GTX-102, the growth and importance of its commercial business, and the potential approval and commercialization of UX111 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 company’s ability to accurately analyze and interpret the Aspire results and determine an appropriate path forward for GTX-102, the uncertainty of clinical drug development and the unpredictability and lengthy process for obtaining regulatory approvals, the risk that results from earlier studies may not be predictive of future study results, the company’s ability to define and implement expense reductions and realize anticipated savings and benefits, the risk that expense reductions may disrupt the company’s operations, adversely affect its workforce or impair its ability to execute its business plans, risks related to adverse side effects, risks related to reliance on third party partners to conduct certain activities on the company’s behalf, 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 the 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 August 5, 2026 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-/). Ultragenyx Contacts InvestorsJoshua [email protected] MediaJess Rowlands [email protected]

Image source: The Motley Fool. Tuesday, Aug. 4, 2026 at 5:00 p.m. ET Chief of Staff and Vice President of Investor Relations - Joshua Higa Chief Executive Officer and President - Emil Kakkis Chief Financial Officer - Howard Horn Chief Commercial Officer - Erik Harris Chief Medical Officer - Eric Crombez Operator: Good afternoon, welcome to the Ultragenyx Second Quarter 2026 Financial Results Conference Call. At this time, all participants are in a listen-only mode. At the end of the prepared remarks, you will have an opportunity to ask questions during the Q&A portion of the call. It is now my pleasure to turn the call over to Joshua Higa, Chief of Staff and Vice President of Investor Relations. Joshua Higa: Thank you. We have issued a press release detailing our financial results, which you can find on our website at ultragenyx.com. Joining me on this call are Emil Kakkis, Chief Executive Officer and President, Howard Horn, Chief Financial Officer, Erik Harris, Chief Commercial Officer, and Eric Crombez, Chief Medical Officer. I'd like to remind everyone that during today's call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. Please refer to the risk factors discussed in our latest SEC filings. I'll now turn the call over to Emil. Emil Kakkis: Thanks, Josh, good afternoon, everyone. In the second quarter, we continued our pattern of strong execution across the development and commercial organizations. The commercial team delivered the highest quarterly revenue in the history of the company, which supports our reaffirmed full-year revenue guidance. As they have done in prior quarters, they continue to find new patients and expand access to Crysvita, DOJOLVI, Evkeeza, and MEPSEVII around the world. The commercial and field teams are also preparing for our first two potential gene therapy launches, which are anticipated in the coming months. If approved, both these therapies would represent first-ever treatments for diseases with significant unmet needs and high urgency to treat. The PDUFA date for DTX-401 for GSD 1A is just a few weeks away. Patients with GSD 1A have to drink a slurry of cornstarch every few hours around the clock, day and night, knowing that a single missed dose could lead to their death. This is a constant reminder of their disease and the severe consequence of missing a dose. In our phase I/II and phase III studies, patients treated with DTX-401 have been able to significantly reduce the amount and frequency of cornstarch doses to a pre-specified, clinically meaningful degree. More importantly, this gene therapy allows patients to have a more normal glucose metabolism, staying in the normal range a larger fraction of the day. The expression of the missing G6Pase enzyme from the DTX-401 vector should allow their liver to break down glycogen to produce glucose during times of fasting or metabolic stress. The ability to regulate glucose better has reduced the burden of disease and reduced the potential for rapid decline to dangerous glucose levels. Transitioning now to UX-111. I've been in and around the MPS community for many years, and I've seen so many Sanfilippo patients have to watch helplessly as their children decline and die. Sanfilippo syndrome type A has an urgent need to treat, yet there has been nothing for them. Sanfilippo syndrome is a horrible neurodegenerative disease, and kids are losing brain cells every day. Patients between the age of two and six years progressively lose their cognitive functions. By 10 years old or so, they're often bedridden and tube-fed and in and out of the hospital for many years. They can end up non-responsive for the last five or 10 years and often die as teenagers. Until now, families have had no option but to watch helplessly as their children decline and die. Based on our clinical data, treatment with UX-111 reduces heparan sulfate in these patients and enables them to stabilize and retain cognitive function compared to natural history. While patients across the age range in the study showed benefits following treatment with UX-111, it's also clear that treating earlier demonstrated better results by protecting their brains before they had lost too much function. With a disease like Sanfilippo syndrome, there's no greater urgency to treat. As long as you wait, the less function you may have. Our development organization under Dr. Crombez has been working with regulatory agencies around the world on BLA submissions for both DTX-401 for GSDIa and UX-111 for Sanfilippo A syndrome. These include preparing the applications, responding to information requests, and supporting facility inspections. This would be a lot for a single BLA. Our team is working simultaneously with the process for two BLAs that have PDUFA dates a month apart. We remain confident in the work our team is doing to support these applications. Shifting to GTX-102 for Angelman syndrome, where we have the most advanced clinical ASO program. In the phase III ASPIRE study, the last patient in has had their 48-week visit, and the team is in the process of cleaning and locking the database. For a global study like this, the process could take months, and we expect to unblind and share top-line results with you in September or October timeframe. With three major catalysts on the horizon, the second half of 2026 is poised to be the most significant period in our company's history. We're positioned to deliver another exciting series of potential firsts for our company, the communities we serve, and the broader field of rare disease medicine, including the first gene therapy approvals for Ultragenyx, the first FDA approvals for two devastating and intractable rare diseases, and the first late-stage clinical data in Angelman syndrome. It's a privilege to continue to lead the future of rare disease medicine, and we believe the combination of continued growth from our current products accelerated by contribution from potential upcoming launches and disciplined expense management gives a clear path to profitability in 2027. I'll now turn the call over to our Chief Commercial Officer, Erik Harris, who'll provide details on the commercial business and launch readiness activities in the second quarter. Erik Harris: Thank you, and good afternoon, everyone. As Emil mentioned, we are pleased with our steady, successful commercial execution, and we continue to see the benefit of our global infrastructure across products and regions. As we described on the last call, underlying demand for our products remains strong, but seasonal factors can cause quarter-to-quarter variability in revenue. In the second quarter, we saw the strong rebound in orders that we were expecting, reinforcing our confidence that we are on track to deliver against our full-year guidance. Starting with Crysvita in North America, where our partner, KKC, is commercializing, we continue to see steady growth in the underlying demand. Eight years post-launch, it's extremely gratifying to continue to see the steady addition of new patients starting this therapy. In Latin America, Crysvita performance was strong in the second quarter, supported by the combination of continued patient growth and timing of regional orders, including Brazil and Argentina. Approximately 50 patients began commercial therapy in the quarter, bringing the total number of patients on Crysvita to 1,000 in the region. As discussed, we expect that ordering patterns will continue to create some quarter-to-quarter variability, and we are confident that the underlying demand will continue to grow steadily. In Turkey, there are over 100 patients being treated with Crysvita through the named patient program. As has been the case in other countries, there is accelerating demand as HCPs and patients see the benefits this transformative therapy offers. Shifting now to DOJOLVI, the trend of steady growth continues. In North America, our team generated approximately 30 start forms in the quarter, and we now have approximately 675 patients on reimbursed therapy. In Europe, approximately 300 patients are being treated through named patient or early access programs, with notable growth in the MENA region following marketing authorization approval in Kuwait. We also recently began treating patients with DOJOLVI in Japan, following its listing on the National Health Insurance (NHI) Drug Price List. We are off to a strong start in demand, reinforcing our belief that this country represents another meaningful opportunity for continued growth over time. Evkeeza continues to be an important and growing contributor to our revenue base. In our territories outside of the U.S., we are responsible for commercialization. There are more than 500 patients across 25 countries receiving Evkeeza, as our teams continue to navigate country-by-country reimbursement, support early access, and convert appropriate patients to reimbursed therapy. Beyond the individual product performance, the real strength of this business is the scale, reach, and experience of our global commercial infrastructure. Rare disease commercialization requires deep market-by-market expertise to include patient finding, reimbursement navigation, and field execution. That is what our global team provides every quarter in giving us high confidence that we will be prepared for the next potential launches. I'll close briefly with a couple of comments on the team's work preparing to successfully launch DTX401 and UX111. Launching two gene therapies in parallel is a big undertaking. We are up to the task and ready to deliver for patients. We are preparing thoughtfully and deliberately to support not only patients and caregivers but clinicians and payers beginning on day one. As we prepare for these potential launches, we are actively working with Qualified Treatment Centers, or QTCs, with contracting and activities progressing as planned. We believe their strong engagement reflects their sense of urgency for patients and families impacted by GSDIa and Sanfilippo syndrome type A, and their understanding of the clinical potential of our investigational gene therapies. Our market access preparations are also progressing well, informed by extensive education and engagement efforts. Across more than 200 engagements with payers, we've been pleased that they recognize the significant unmet need associated with both diseases and understand the particular urgency to treat in Sanfilippo syndrome. The foundation necessary to support broad and timely access is set. With a focus on minimizing barriers for eligible patients following approval, we've been building toward these potential launches for years. We stand ready to add these products to our existing portfolio and expand our mission of helping patients with rare disease. I'll turn the call to Howard to share more details on our financial results and guidance. Howard Horn: Thank you, Erik, and good afternoon, everyone. I'll focus on our second quarter financial results, guidance for the year, and provide a few comments on our path to profitability. Starting with revenue, total revenue for the second quarter of 2026 was $214 million. Crysvita contributed $156 million, including $94 million from North America, $54 million from Latin America and Turkey, and $8 million from Europe, which were consistent with the anticipated quarterly timing and trends Erik just mentioned. DOJOLVI contributed $27 million, consistent with our expectation for steady demand growth. Evkeeza contributed $21 million, representing 50% growth over the second quarter of 2025 as demand continues to build following launches in our territories outside of the United States. MEPSEVII contributed $10 million as we continue to treat patients in this ultra-rare indication. Total operating expenses for the quarter were $289 million, which included cost of sales of $34 million and combined R&D and SG&A expenses of $255 million. Total operating expenses included $34 million of non-cash stock-based compensation. For the quarter, net loss was $92 million or $0.90 per share. As of June 30, we had $436 million in cash equivalents, and marketable securities. Net cash used in operations for the quarter was $97 million, a significant decrease from the first quarter and consistent with the expectations we discussed on our last call. As noted in our press release, we are reaffirming our financial guidance for revenue and combined R&D and SG&A operating expenses. Finally, I want to share a few thoughts on how we plan to achieve our path to profitability in 2027. There are three primary factors. First, continued double-digit revenue growth from our current products, plus contributions from our potential upcoming launches. Second, continued expense discipline and strategic capital allocation to support our launches, as outlined in our operating expense guidance. Third, incremental non-dilutive capital to bolster our balance sheet from monetization of the priority review vouchers associated with DTX401 and UX111, if approved. With that, I'll turn the call to our Chief Medical Officer, Eric Crombez. Eric Crombez: Thank you, Howard, and good afternoon, everyone. I'll start with GTX-102, or apazunersen, our antisense oligonucleotide for the treatment of Angelman syndrome. As Emil mentioned, and something that I am sure you are tracking closely, we are approaching the phase III ASPIRE data readout expected in the September or October timeframe. The ASPIRE study is a randomized, double-blind, sham-controlled study that enrolled patients with a full maternal UBE3A gene deletion, and our criteria for success are well-defined. In the 48-week study, the primary statistical alpha is split between the Bayley-4 cognitive raw score at 80% and the Multi-Domain Responder Index, or MDRI, at 20%. This is not a hierarchical evaluation, meaning both endpoints are tested in parallel. If the Bayley cognition endpoint reaches a P value equal or less than .04, or if the MDRI reaches a P value equal or less than .01, we will have a statistically successful phase III study. We designed and powered the study to hit both endpoints, but we do not need both endpoints to achieve statistical significance in order to have a successful study. Across the phase I/II program, patients have now been on continuous therapy for an average of three years, with the longest approaching five years, which represents the most significant and mature data set in the field. These patients continue to demonstrate meaningful improvements across multiple development domains while maintaining a consistent safety profile. The phase I/II open-label single-arm data demonstrates substantial clinical benefit well beyond what might be considered with placebo, though it is in an open-label setting. We believe that the long-term experience beyond the first year of treatment remains even more important as we evaluate the potential for GTX-102 to provide meaningful benefit with chronic dosing in the commercial setting. Shifting to UX143, or setrusumab, our monoclonal antibody for the treatment of osteogenesis imperfecta. At the end of last year, we shared the results from the phase III ORBIT and COSMIC studies. While neither study hit statistical significance for the primary endpoints of annualized fracture reductions, we did see clear signals of biologic activity, statistically meaningful improvements in bone mineral density and patient-reported outcomes, and meaningful reductions in fractures in certain bones and in patients with higher fracture frequencies. Since then, we have continued analyzing the data and have had discussions with regulators in the U.S. and U.K. Based on the discussion with the MHRA, we believe that a new randomized study may be needed before they would consider reviewing an application for approval. The FDA indicated openness to considering alternative approaches to fracture analysis, and we will need additional conversations with them to further define what additional clinical data would be needed to support a potential BLA. I'll now turn the call back to Emil to provide a reminder of our catalyst for 2026 and some closing remarks. Emil Kakkis: Thank you, Eric. I'll close with a few of the important catalysts we have later this year. A full list can be seen in the corporate deck posted to our website. Starting with DTX401 for the treatment of Glycogen Storage Disease Type Ia, where we continue to work with FDA ahead of our PDUFA action date of August 23rd. Next, UX111 for the treatment of Sanfilippo syndrome. Similar to DTX401, we continue to work with FDA ahead of the PDUFA action date of September 19th. Lastly, GTX-102 for the treatment of Angelman syndrome, where we're on track to read out top line phase III data from the ASPIRE study in the September or October timeframe. The second quarter reinforced the continued strength of our global commercial business and our expertise in developing first-ever medicines for patients with rare diseases. We are ready for potential launches, continue to execute across the portfolio, and are approaching a set of milestones that could meaningfully expand our impact for patients and accelerate the next phase of growth for Ultragenyx. With that, let's move on to your questions. Operator, please provide the Q&A instructions. Operator: Thank you. At this time, we will be conducting a question and answer session. Please limit yourselves to one question and one follow-up question for each time you enter the queue. To ask a question, press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from Kristen Kluska with Cantor Fitzgerald. Please state your question. Kristen Kluska: Hi, good afternoon. Congrats on a really strong quarter. For Angelman syndrome, was hoping you could provide a little bit more context on these endpoints. Specifically, if the FDA has signed off whether one endpoint or not would be sufficient for filing. Also understanding what's clinically meaningful. Understand that these both endpoints were powered for success, but were they also powered to show results that the community would deem clinically acceptable? Thank you. Emil Kakkis: We had our discussion with the FDA on the sharing of primary alpha, and that was agreed to in the phase III and pulse discussions on the two endpoints. Sharing of alpha means that either endpoint can be positive in their analysis. With regard to powering, we are powering based on the effects we've seen. We think a five or six-point change, for example, in the Bayley should be sufficient to achieve significance, and that would be the six-point level is considered clinically meaningful. For the MDRI, it only scores if there's clinically meaningful results. That is, each domain improvement requires a threshold of clinical meaningfulness. In that, previously, we've seen, as you remember in phase III, about two domains net positive that were in the clinically meaningful range. Because of the design, we would see MDRI would be positive only with clinically meaningful results. At this point, we feel comfortable about the two-endpoint approach, we think the powering will be positive with clinically meaningful results, based on our plan. We will see the data when they come. Thanks, operator. Let's move to the next question. Operator: Thank you. Your next question comes from Yaron Werber with TD Cowen. Please state your question. Yaron Werber: Great. Thanks so much. Maybe on the MDRI endpoint, which I think has generated some confusion from investors, as you noted, it's the first and most important secondary, but it's really a co-primary. It's not been used before in Angelman, but you've used it in some of your other MPS disorders. Can you talk about the level of sensitivity and whether it's a better endpoint in cognition, just given that it's a co-primary? Thank you so much. Emil Kakkis: Yes. The MDRI approach simply captures efficacy across multiple domains using a clinically meaningful threshold in order to capture any positive results. What we're saying is, any of, let's say, five or six endpoints, if there's a clinically meaningful change in the patient, count that and add up all those clinically meaningful changes together. We used it previously in the MEPSEVII program, which it was significant in our 12-patient trial. In our analyses published in our paper, the MDRI was, for example, tenfold more powerful to detect change in an enzyme replacement therapy trial compared to individual endpoints, right? That's what we've published before. We think it's substantially more sensitive. When you look at the Angelman phase III data, even in the 15-patient trial, we show substantial power with P values less than 001, even in small studies. It's more powerful because we capture more efficacy in it. Its sensitivity is very good, but its meaning is greater, and it's one of the reasons we want it. It's not just sensitivity. Being able to show through five important domains for family what a drug is doing, I think is a better assessment of what a drug does in a disease as complex as Angelman, as you know, since you've worked in the area. We think it's just a better way of describing. However, it is new and it's different, but we're confident in its clinical meaningfulness and its power in detecting change in diverse, complex disorders like Angelman syndrome. Operator: Thank you. Your next question comes from Yigal Nochomovitz with Citi. Please state your question. Yigal Nochomovitz: Yeah. Hi, how are you? I just wanted to ask with regard to the filing plans, are you going to file on the data coming up in September or October? The additional study and additional genotypes will also support the Angelman's filing. Can you just comment on the order of operations with regard to what data sets will be included? Thank you. Emil Kakkis: Yeah. Thank you, Yigal. We haven't discussed publicly what we're going to do about filing. It's something under consideration, and at this point, we're not going to describe what our plan is. We're collecting data in all the types in our program. Our expectation is to get approval in all the types, but we won't discuss at this point what our filing timeline is. Thank you. Yigal Nochomovitz: Okay. Operator: Your next- Yigal Nochomovitz: Thank you. Operator: Thank you. Your next question comes from Maury Raycroft with Jefferies. Please state your question. Maury Raycroft: Hi. Congrats on the quarter, thanks for taking my question. I'll ask one on Angelman as well. Wondering if there have been any cases of lower extremity weakness or neuroinflammation based on DMC feedback during the study, and how are you setting expectations on this for the top-line disclosure? I guess, what's the latest you can say on the dropout rate from the phase III? Emil Kakkis: Yeah. We usually don't describe all the details and operation of the study. Honestly, the safety and efficacy will have to get evaluated together. The study has never stopped or had any issue during its conduct. It's continued smoothly through at this point, right? There's been no safety issue to cause a problem that stops the study. I would say we're comfortable where we are. I think we don't expect to see a different safety profile from what we've seen before and going forward. Maury Raycroft: Will- Emil Kakkis: Got it. Maury Raycroft: Do you want to comment on the discontinuation rates that we saw? Emil Kakkis: Yeah. Well, we wouldn't comment on that. It's also part of study conduct at this point. If you look past it to phase III program, we've had very few, and usually it's more toward the beginning. Among patients that get, let's say, after six, eight, seven, eight months, we had a very good persistence of those patients long term. Maury Raycroft: Got it. Thank you. Operator: Your next question comes from Eliana Merle with Barclays. Please state your question. Eliana Merle: Hey, guys. Thanks for taking my question. Another two on Angelman. First, I guess, what are your latest expectations for the placebo arm performance on MDRI and the Bayley Cognition score and your confidence that there won't be a placebo effect? Second, I guess if you show a trend on both endpoints but do not reach statistical significance, curious how you would approach that with the regulators in terms of a potential filing. Thanks. Emil Kakkis: Great. We have talked about the placebo effect before. I think in the Bayley Cognition, where we have both natural history and the randomized data from another study, the effect has been one point or less in the Bayley Cognition, so it doesn't change. Honestly, placebo effects usually don't happen in things like a Bayley score because the patient is not cognitive of what the change should be. It can happen if you're using parent input. In this case, we think it's unlikely to see a placebo effect for the Bayley. In the MDRI, we're looking at multiple different endpoints. It is possible that some of those could change. However, we think that the threshold of clinical meaningful change means just a little bit of change from bias view things wouldn't score. It has to be a really pretty big change before you can score. I think that should filter out, I would call random placebo changes. At this point, we feel both. I don't think placebo effect would be an issue. It is neurology, though, I always say, and we always have to consider we learn things. We think we've designed it to manage any placebo effect and on both endpoints. Thank you. Operator: Your next question comes from- Emil Kakkis: That's it. Operator: Oh. My thanks. The next question comes from Anupam Rama with JPMorgan. Please state your question. Anupam Rama: Hey, guys. Thanks so much for taking the question. Emil, could you just clarify your comments a little bit on GTX-102 and Bayley? I think you said you needed a five- to six-point change to hit stats relative to placebo. I think that's the first time you've really quantified that. I'm assuming that's raw score, right? Using GSV, if I remember back to your phase III, you showed a similar-ish effect, right, in phase III. I was just wondering if you could clarify those comments. Thanks so much. Emil Kakkis: Yeah. I wasn't saying that's the threshold for powering. I was saying that a five, six point is a clinically meaningful change, and we are powered to detect that average change. That's what I meant to say. I didn't mean to say we're only powered for that threshold. We are well powered to detect anything that would be considered clinically meaningful in that range. In the data we put out recently, we said it was near 10 score when you combine all the data together at one year. If you look at all the various sets of the data, it's in that range that we would expect the data to be. What I'm saying is we're powered. Whatever we would detect should be a clinically meaningful change, and we are confident we can do that. Anupam Rama: Great. Thanks for the clarification. Operator: Your next question comes from Jack Allen with Baird. Please state your question. Jack Allen: Great. Thanks for taking the questions and congrats on the progress made over the course of the quarter. I'll keep the train rolling here as it relates to GTX-102. I wanted to ask a quick clarifying question around the allocation of the alpha. I understand on the call and on the more recent calls, you've been discussing how you have an 80% allocation of alpha to the Bayley-4 cognition endpoint and a 20% allocation to MDRI. I was looking at the completion of enrollment press release from July of last year, I think it was a 90/10 alpha allocation there. I'm just curious if there was a change to the statistics between the completion of enrollment and the potential readout here, and what educated that change? Emil Kakkis: Yes. Our current plan is to do 80/20. 90/10 are very similar. I don't really think they're materially different. We decided to make it 80/20. There was no particular date or other reason for it. It was just our take on the split between the two. It doesn't, I don't think, meaningfully change things, but the MDRI is very powerful. We think 10% or 20% is probably adequate for that. We had given 80%, 90% to the Bayley. In our discussion with FDA, that was the split we had, but they're comfortable with what we are proposing at this point. Jack Allen: Thanks for the reply. Emil Kakkis: Okay. Let's go to the next. Operator: Your next question comes from Allison Bratzel with Piper Sandler. Please state your question. Allison Bratzel: Hey, good afternoon, and thanks for taking the question. Just as clarification on setrusumab, I think in the prepared remarks, you said FDA had indicated openness to alternatives to the fracture analysis, but you need to further define what would be needed for a BLA. Could you just clarify that? Do you feel you have a fileable package from the existing COSMIC and ORBIT dataset? Just how important is that open-label extension data that's being generated now? Just what's the next point you would be able to update The Street on FDA interactions and the path forward in the U.S.? Thanks. Emil Kakkis: Yes. Our comments were basically around the type of fractures and type of patients that we were talking about with regard to what fracture analysis they would want. What we said, though, is that our discussions suggest some additional clinical data will be required, and we need to define what that is, which is not fully defined yet. We cannot state at this point whether extension data alone or whether there's any additional data required at this point in time. All right. We are discussing with them. I think they've been very open to a discussion and a path forward, and we just need to come up with a good plan to get us to that fileable package. Operator: Thank you. Your next question comes from Maxwell Skor with Morgan Stanley. Please state your question. Maxwell Skor: Great. Thank you very much for taking my question. Another on Angelman. With the centralized raters, have you seen a reduction in variability in the blinded baseline data compared to the phase I/II? Thank you. Emil Kakkis: We have not personally looked at the data. We're not aware. We don't look at the blinded data at the management level. The team would be doing that. We would expect that these reviewers, which are highly professional and consistent, would help reduce overall study variation. That was the importance of it, to control it, to absolutely make sure that a changing evaluator or variable in quality and experience at different locations might cause a problem. It was our attempt to control the endpoint. I can't tell you at this point that effect of that. I believe it is the kind of thing that will help assure consistency and give us the best chance for less noise in the program. Right now, we don't have any data to tell you that. Maxwell Skor: Great. Thank you. Operator: Your next question comes from Tazeen Ahmad with Bank of America. Please state your question. Tazeen Ahmad: Hi, guys. Thanks for taking my questions. On the financial front, how are you feeling about where you are with your cash balance and any potential need to do any kind of financing? Related to that, how should we be thinking about the investment needed for the upcoming launches that you have for your two programs for 401 and 111, assuming that both of them do get approved on time? Lastly, can you just remind us of what you think the market size for each of those two indications could be? Thanks. Emil Kakkis: Sure. Well, I'll let Howard go through the cash financing piece, but I'll touch on the market size first. For DTX401 GSDIa, we think there's about 6,000 in the developed approachable world, which means around 1,500-2,000 in the U.S. For Sanfilippo syndrome, there are 3,000-5,000 globally, but inside the U.S., there's probably, we think of it as 20% or 25% of that. The addressable population will depend on what label says, but we are looking at patients that are generally going to be probably more likely under 10 than over 10. Those are roughly where we are on population currently. I'll let Howard talk about the financials. Howard Horn: Yes. Thanks, Tazeen. First on the investments, I guess I'll remind folks of the guidance we gave for combined R&D and SG&A. It was all based on this year or next year versus 2025. This year was flat to down low single digits. In 2027, it's a decrease of at least 15%. Both of those were inclusive of the launch investments we're planning to make for 111 and 401. There is new money going in there. I think also important to note is that those programs fall into a sales structure or bag that we already carry. It's a highly leveraged situation, it's targeted investments. That's an answer to that part of the question. With regard to cash balance, we reported $436 million as of the end of the quarter. As it relates to fundraising plans, our focus is on monetization of PRVs. Upon approval, our intent would be to monetize our DTX401 PRV and also the UX111 PRV. Operator: Thank you. Your next question comes from Ben Burnett with Wells Fargo. Please state your question. Ben Burnett: Hey, thank you. Congrats on the quarter and congrats on the good Crysvita number. I wanted to ask about setrusumab and just follow up. I'm just curious, have any of the regulatory agencies that you've spoken with, have they indicated a willingness to use or rely on bone mineral density as sort of a determinant of efficacy? Or do they still also need to see efficacy be defined in some way in terms of fracture rate? Emil Kakkis: Thanks, Ben. That's a good question. At this point, there hasn't been the kind of proof for BMD's predictive value for fractures as there has been for osteogenesis, I'm sorry, for osteoporosis, where it has been accepted. We're still in the point of proving it. There's a question of whether the underlying bone disease creates that connection. We have evaluated, we believe it does, but at this point, we're looking at fracture endpoints of some form as the primary way to get approval and not using BMD. I think we all agree BMD demonstrates the profound activity of this drug in these patients. With a whole Z-score gain in a year is a profound improvement in their bones. It gives us confidence, and I think the regulators are also confident that the drug is doing something meaningful. Right now there's, I would say, acceptance of BMD as a primary for approval has not yet been enabled. Operator: Thank you. Your next question comes from Salveen Richter with Goldman Sachs. Please state your question. Lydia Erdman: Hi, this is Lydia on for Salveen. Thanks so much for taking our question and congrats on the progress. Just as a follow-up to a previous question on Angelman, related to the lower extremity weakness, has the FDA provided any sort of threshold on what would be acceptable on the safety front, particularly as it pertains to that lower extremity weakness? Thanks so much. Emil Kakkis: No thresholds were provided or any limits. In fact, I believe in our final conversation, I'm not sure if Eric you want to say something to this. We really have not had much concern, at least end of phase II as little at all. Eric, what's your take on the FDA? I don't think we've had any limits provided to us or how much maximum could be incurred or something. Eric Crombez: No, exactly. During our end of phase II meeting, there was no discussion on lower extremity weakness and as I said, we maintain a consistent safety profile. Emil Kakkis: I think our sense from them is that we've gotten past the issue with them, and I think we're in good shape. We've not had discussions further. Operator: Your next question comes from Luca Issi with RBC Capital Markets. Please state your question. Shelby Hill: Hi, team. This is Shelby on for Luca. Maybe on GSDIa. With the PDUFA just weeks away, could you provide any color on your level of confidence headed into that decision and talk about how the review has progressed? I guess specifically whether there's been any information requests from the FDA and are there any additional manufacturing sections that you need to clear before the decision date? Any color there much appreciated. Thanks. Emil Kakkis: Sure. Well, yes, we have obtained information requests during the review for both CMC and clinical, and we've been answering them. We can't provide an answer yet during progress. Things are underway like that. We feel the review has proceeded normally, and we feel like we're in good shape. However, we can't predict to you what the FDA's action are. They will have to do it. At this point, everything we have been doing is answer their questions and move in a normal fashion forward. Operator: Your next question comes from Laura Chico with Wedbush. Please state your question. Thomas Yip: Good afternoon, everyone. This is Thomas Yip on for Laura. One question from us. Of the 300, 400 Sanfilippo patients that are identified in the U.S., how many are likely within the age range that you would expect the label to support and are clinically appropriate to treat? Also, what's the incidence rate for new patients being captured on an annual basis? Thank you. Emil Kakkis: Are you talking for Sanfilippo syndrome? Thomas Yip: Yes, that's right. Sanfilippo. Emil Kakkis: Yeah, I thought you were mentioning Sanfilippo. Yeah. We haven't put out precise numbers yet on the prevalence, exact prevalence or diagnosed prevalence of patients. We know that the incident rate appears to be about one in 100,000 or about 30-40 new kids diagnosed per year. If you imagine that they're living until their teenage years, you can get a sense for what the number or prevalent number is like, right? Does that make sense? We have treated patients up to, I think, eight or nine years old in the trial. We don't know what age range will be in the labeling, but we've shown even in the older patients that we stabilize function with regard to ambulation, feeding, communication at the state they're in when we are able to treat them. We think there's a justification for treating patients that age, but we don't know what the label will be. There is a meaningful population of patients in that age range out there, and we have a sense it's a lot of urgency in wanting to get treated. Hopefully, that gives you at least a feel for it. Thomas Yip: Understood. Thank you so much for taking the question. Operator: Your next question comes from Joseph Schwartz with Leerink Partners. Please state your question. Erik Harris: Thanks. I have a two-part question on Angelman. In phase I/II, were there particular Bayley cognition items or skill clusters that appeared most sensitive to apazunersen? Are those the same skills you expect to drive separation in ASPIRE? Relatedly, because ASPIRE's primary endpoint removes caregiver input and requires the child to demonstrate skills during a single testing session, how should we think about the risk that meaningful home-based gains might not be fully captured by the Bayley Cognition assessment? Emil Kakkis: Good. Let's start with the last one. The Bayley Cognition has a relatively small number of caregiver assessments, and our endpoint team's assessment is that it shouldn't have a material effect on the raw scores at this point. We're not concerned about that. Regarding the MDR areas, the areas we studied and presented before in our slides have all been the same ones as we're using. The five domains are Bayley cognition with a threshold set by the Bayley people. We also have communication score, receptive communication for the Bayley. We're using a sleep score, and we have a behavior scale, ABC behavior score, and finally a motor score, which is either the ASA or the Bayley. Those are the five domains. Those domains are ones we saw some meaningful improvement in and the ones that are of importance to patients. All of them are contributing. If you look at the prior descriptions where we've shown the heat map, I think you can see all the endpoints are contributing pretty significantly. It's really not one or another that's dramatic. For sleep, for example, there are patients who have a very big effect on sleep because they're very sleep-deprived kids. Other kids who don't have sleep problems where you might not see it. If you look across those endpoints, we see contribution from all of those endpoints that are built into the MDRI. There's no one or other that's, let's say, driving the majority of what the MDRI feels. We'll see. This is why the MDRI is so powerful. If you have multiple endpoints all contributing, you gain a lot more power when you're capturing efficacy from all areas of the patient's benefit. Operator: Thank you. Your next question comes from Gavin Clark-Gartner with Evercore ISI. Please state your question. Yi Zhong: Hi, this is Yi Zhong for Gavin. Thanks for taking our question. Just a follow-up on the Angelman phase I/II study. Looks like the study originally enrolled 74 patients, and efficacy we have seen so far is based on the 40 patients cohort. The last quarter you mentioned, based on the most recent data cut-off, there are 53 patients that have reached the 12-month milestone. Can you remind us when do you plan to share those data? Also, especially for the efficacy part, if the data has been consistent with the earlier cohort? Thank you. Emil Kakkis: All right. Well, you're talking about different cohorts and time. It depends on whether you're talking about the titration group, or we're talking about the expansion group. Those are the two groups. In the most recent release, we talked about all the patients who've been on therapy, and we have a few people who left early on in the study. The combination data we presented at the last quarterly call was including all the people together. We presented on the expansion, which wasn't everything, but we mentioned the last call, which was the near 10 score on all patients together combined for the Bayley cognition was the most complete set of data that had at least a year of treatment on it. That's included in that data. We are not planning to put out more phase III data at this point, because we are where we are with the phase III program. I hope that gives you a feel for it. I would say is we presented previously, for example, A and B cohort data, that cohort is very similar to what we're seeing and we think is in the phase III. Basically, it's from the same centers that are in the international study. At this point, we feel comfortable that what we have learned from phase III, we have disclosed to you as an adequate assessment of the patients in the countries, and at the sites that we are using in phase III. Yi Zhong: Thank you. Operator: Your next question comes from Raghuram Selvaraju with H.C. Wainwright. Please state your question. Ahmed Gadelkareem: This is Ahmed on for Raghuram. Thank you for taking our questions. I was wondering if you could give some color to the launch readiness for the next two products. How do you see the timing to first patient infusions? How sensitive is the 2027 profitability target to slower-than-expected ramp for the products? Thank you. Emil Kakkis: Okay. Let me touch on it, I'll let Erik talk about launch readiness, and maybe you can talk about profitability. We're absolutely driving to assure that we can get patients treated as promptly as possible because there are a number of patients that really urgently want to be treated. We're setting up to do that. Because we already have two products in the space of inborn errors, we already have a team in the field. We already are operating, and we're going to prepare to build out with a more measured addition. Maybe, Erik, you can talk about what we're doing in the QTCs and how we're going to help assure patients get infusions as promptly as we can. Erik Harris: Yeah, just to add on something that you said, that we've been preparing now for a few years following the initial filings. There's about a 75% overlap with the DOJOLVI and MEPSEVII with the institutions and the healthcare providers that we'll be calling on. We'll be able to leverage our current infrastructure, which we expanded to meet the demands of our previous commercial products. I just want to also emphasize, this will be our fifth and sixth launches. We've successfully launched four products previously. We certainly know what we're doing, and we'll be prepared. We have a number of QTCs already under contract, and we'll be expanding that as we prepare in our final preparations for commercialization. Emil Kakkis: Should be ready to go when we get launched. Erik Harris: We'll be. Good. Howard Horn: We'll be ready. Maybe last to your question about the sensitivity of profitability to the launches. You heard my comments earlier on the call about the different factors that play into profitability. We haven't been more specific on the exact contribution from launches, but we do imagine one as part of profitability. I think the important thing to remember is that there's lots of levers to get to a profitable year, and so it's not as though every launch is a must. That's a fortunate place to be in, where we have lots of different revenue sources and lots of different ways to manage our allocation of capital. Ahmed Gadelkareem: Thank you. Operator: Thank you. At this point, we have reached the end of the question and answer session. I will now turn the call over to Joshua Higa for closing remarks. Joshua Higa: Thank you. This concludes today's call. If there are additional questions, please reach out to us by phone or at [email protected]. Thank you for joining us. Operator: Thank you. All parties may now disconnect. Have a good day. Before you buy stock in Ultragenyx Pharmaceutical, consider this: The Motley Fool Stock Advisor analyst team just identified what they believe are the 10 best stocks for investors to buy now… and Ultragenyx Pharmaceutical wasn’t one of them. The 10 stocks that made the cut could produce monster returns in the coming years. Consider when Netflix made this list on December 17, 2004... if you invested $1,000 at the time of our recommendation, you’d have $403,337!* Or when Nvidia made this list on April 15, 2005... if you invested $1,000 at the time of our recommendation, you’d have $1,334,946!* Now, it’s worth noting Stock Advisor’s total average return is 958% — a market-crushing outperformance compared to 214% for the S&P 500. Don't miss the latest top 10 list, available with Stock Advisor, and join an investing community built by individual investors for individual investors. See the 10 stocks » *Stock Advisor returns as of August 12, 2026. This article is a transcript of this conference call produced for The Motley Fool. While we strive for our Foolish Best, there may be errors, omissions, or inaccuracies in this transcript. As with all our articles, The Motley Fool does not assume any responsibility for your use of this content, and we strongly encourage you to do your own research, including listening to the call yourself and reading the company's SEC filings. Please see our Terms and Conditions for additional details, including our Obligatory Capitalized Disclaimers of Liability. The Motley Fool has no position in any of the stocks mentioned. The Motley Fool has a disclosure policy. Ultragenyx (RARE) Q2 2026 Earnings Call Transcript was originally published by The Motley Fool

Entered into option and license agreement with Sentynl Therapeutics for alvelestat, Mereo’s investigational oral therapy for Alpha-1 Antitrypsin Deficiency-Associated Lung Disease (AATD-LD) Mereo and partner Ultragenyx engaging with regulatory agencies on potential path forward for setrusumab in osteogenesis imperfecta (OI); further updates expected by year-end 2026 Cash and cash equivalents of $30.1 million at June 30, 2026, now expected to fund operations into late-2027 LONDON, Aug. 11, 2026 (GLOBE NEWSWIRE) -- Mereo BioPharma Group plc (NASDAQ: MREO) (“Mereo” or the “Company”), a clinical-stage biopharmaceutical company focused on rare diseases, today announced financial results for the second quarter ended June 30, 2026, and provided an update on recent corporate highlights. The Company is also updating its previous cash runway guidance. As of June 30, 2026, cash and cash equivalents were approximately $30 million, which are expected to fund operations into late-2027. “The partnership with Sentynl Therapeutics which we announced earlier today marks a significant milestone for our alvelestat program and for the Company as a whole. We are now working together to refine the design of the global Phase 3 study for our potential first-in-class oral therapy for AATD-LD and look forward to a continued close collaboration during the short option period. Assuming exercise of the license option by Sentynl, we plan to initiate the Phase 3 trial in early 2027,” said Denise Scots-Knight, Chief Executive Officer of Mereo BioPharma. “Additionally, alongside our partner Ultragenyx, we have had initial regulatory interactions on setrusumab with the FDA and the MHRA and we expect to be in a position to provide an update on the potential path forward by the end of this year. We finished the quarter with approximately $30 million in cash. Thanks to our careful expense management, we now expect that this cash will provide runway into late-2027, exclusive of the potential $40 million in upfront and R&D payments that we are eligible to receive on exercise of the alvelestat option by Sentynl.” Second Quarter 2026 Highlights, Recent Developments, and Anticipated Milestones Setrusumab (UX143) The Orbit and the Cosmic Phase 3 studies did not achieve statistical significance against the primary endpoints of reduction in annualized clinical fracture rate, however, both achieved high statistical significance against the key secondary endpoint of improvement in bone mineral density, as well as reductions in vertebral fractures and improvements in patient reported outcomes (PROs) associated with disease severity, pain / discomfort and daily activities, with these PRO improvements achieving statistical significance in the Orbit study. Setrusumab also achieved meaningful reductions in fractures in certain bones and in patients with higher fracture frequencies. Both studies demonstrated a safety profile consistent with that observed in previous trials. Mereo and its partner, Ultragenyx Pharmaceutical, Inc. (Ultragenyx), are engaged with regulatory agencies to determine a potential path forward for setrusumab in pediatric OI patients and, to-date, have held discussions with the regulators in the U.S. and the U.K. The FDA indicated openness to considering alternative approaches to fracture analysis, with additional conversations needed to further define what additional clinical data would be needed to support a potential BLA. In recent communications with the MHRA, they encouraged further dialogue on any future development proposal, and we plan to have further interactions following the FDA discussions. Alvelestat (MPH-966) Mereo recently announced an option and license agreement with Sentynl Therapeutics, Inc. (Sentynl), a wholly owned subsidiary of Zydus Lifesciences Limited. Sentynl has the right to acquire a license for the U.S. commercial and global manufacturing rights to alvelestat for AATD-LD. Vantictumab (OMP18R5) āshibio, Inc. (āshibio), Mereo’s development and commercial partner for vantictumab, is continuing to advance toward initiation of a Phase 2 clinical trial in autosomal dominant osteopetrosis Type 2 (ADO2). āshibio is responsible for the global clinical development of vantictumab. Mereo has retained European commercial rights to the product, with āshibio holding commercial rights for the rest of the world. Second Quarter 2026 Financial Results Total research and development (“R&D”) expenses decreased by $3.6 million, from $5.4 million in the second quarter of 2025 to $1.8 million in the second quarter of 2026. The decrease was primarily due to a reduction of $2.6 million in R&D expenses for setrusumab and $1.0 million for alvelestat. The decrease in program expenses for setrusumab was primarily driven by reduction of, and delays to, investment in manufacturing and ongoing activities, including medical affairs activities in Europe during the second quarter of 2026. The decrease in program expenses for alvelestat was primarily due to completion of activities undertaken in preparation for the potential Phase 3 study during 2025. General and administrative (“G&A”) expenses decreased by $0.3 million, from $5.5 million in the second quarter of 2025 to $5.2 million in the second quarter of 2026. The decrease was primarily due to reductions of approximately $2.2 million driven by delays to investment in pre-commercial activities to lay the foundation for the potential commercial launch of setrusumab in Europe and other realized cost savings. These decreases were partially offset by the recognition of a $1.9 million reduction in expenses in the second quarter of 2025 for amounts received from our depository to reimburse certain expenses incurred by us in respect of our ADR program, whereas the corresponding amount in the current year was recognized in the first quarter of 2026. Net loss for the second quarter of 2026 was $7.0 million, compared to $14.6 million for the second quarter of 2025, primarily reflecting reductions in R&D and G&A expenses and a lower net foreign currency translation loss. As of June 30, 2026, the Company had cash and cash equivalents of $30.1 million, compared to $41.0 million as of December 31, 2025. The Company expects, based on current operational plans, that its existing cash and cash equivalents balance will enable it to fund its currently committed clinical trials, operating expenses, and capital expenditure requirements into late 2027. This guidance does not include any future potential payments associated with business development activity around any of the Company’s programs. Total ordinary shares issued as of June 30, 2026 were 798,093,044. Total ADS equivalents as of June 30, 2026 were 159,618,608, with each ADS representing five ordinary shares of the Company. About Mereo BioPharma Mereo BioPharma is a biopharmaceutical company focused on the development of innovative therapeutics for rare diseases. The Company has three rare disease product candidates: setrusumab for the treatment of osteogenesis imperfecta (OI); alvelestat for the treatment of alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD); and vantictumab for the treatment of autosomal dominant osteopetrosis type 2 (ADO2). The Company and its partner for setrusumab, Ultragenyx Pharmaceutical Inc., have reported top-line results from two Phase 3 studies for setrusumab in OI in patients aged 2 to 25 years old. Ultragenyx is funding and leading global development and Mereo has retained EU and UK commercial rights. Mereo has entered into an exclusive option and license agreement with Sentynl Therapeutics Inc. for the U.S. rights to commercialize alvelestat, while retaining rest of the world rights and will lead the global development. The agreement also grants Sentynl global rights to manufacture alvelestat for AATD-LD. Mereo has partnered with āshibio, Inc., for vantictumab in ADO2. āshibio, Inc. is funding and leading the global development program and Mereo has retained EU and UK commercial rights. Mereo has also entered into exclusive global license agreements with ReproNovo SA, for the development and commercialization of leflutrozole for the treatment of infertility in men, and with Feng Biosciences for the development and commercialization of navicixizumab for late-stage ovarian cancer. Forward-Looking Statements This press release contains “forward-looking statements” that involve substantial risks and uncertainties, as well as assumptions that, if they never materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. All statements other than statements of historical fact contained herein are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended, and Section 21E of the United States Securities Exchange Act of 1934, as amended. Forward-looking statements reflect our current expectations, beliefs and assumptions concerning future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements. Risks and uncertainties include, among other things, the uncertainties inherent in the clinical development process; the Company’s reliance on third parties to conduct and provide funding for its clinical trials; the sufficiency of existing cash to fund operations and/or the inability to raise additional funding on favorable terms or at all; the uncertainty inherent in regulatory review processes, including varying interpretations and analyses of data from clinical trials; the Company’s dependence on enrollment of patients in its clinical trials; potentially smaller than anticipated market opportunities for the Company's product candidates; the Company’s dependence on its key executives; and the Company’s ability to maintain compliance with Nasdaq continued listing requirements. You should carefully consider the foregoing factors and the other risks and uncertainties that affect the Company’s business, including those described in the “Risk Factors” section of its Annual Report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. Forward-looking statements are often identified by the words “believe,” “expect,” “anticipate,” “plan,” “intend,” “foresee,” “should,” “would,” “could,” “may,” “estimate,” “outlook,” “will,” “continue” and similar expressions, including the negative thereof. The absence of these words, however, does not mean that the statements are not forward-looking. These forward-looking statements are based on the Company’s current expectations, beliefs and assumptions concerning future developments and business conditions and their potential effect on the Company. While management believes that these forward-looking statements are reasonable as and when made, there can be no assurance that future developments affecting the Company will be those that it anticipates. The Company wishes to caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to publicly update or revise any of our forward-looking statements after the date they are made, whether as a result of new information, future events or otherwise, except to the extent required by law.

Get insights on thousands of stocks from the global community of over 7 million individual investors at Simply Wall St. Ultragenyx Pharmaceutical (RARE) released its second quarter 2026 results on 4 August, reporting revenue of US$214 million and a net loss of US$92 million. Investors are now assessing what this means for the stock. See our latest analysis for Ultragenyx Pharmaceutical. Ultragenyx Pharmaceutical shares trade at US$25.91 after a 4.01% 7 day share price return, although the 30 day share price return is down 25.27%. Over the past year, total shareholder return has declined 5.92%, reflecting mixed sentiment around the earnings report and the company’s progress on its rare disease portfolio. If you are reassessing risk and reward after Ultragenyx Pharmaceutical's latest results, it can help to widen the lens and look at other opportunities through the 43 healthcare AI stocks Bulls point to Ultragenyx Pharmaceutical's growing rare disease portfolio. Bears focus on ongoing losses and the sharp 30 day share price decline. The key question is whether the current valuation reflects more of the upside story or the risks ahead. Ultragenyx Pharmaceutical's most followed narrative sets a fair value of $26.00 compared with the latest close at $25.91. The gap is small, but the story behind it is detailed. Read the complete narrative. Want to know what underpins that fair value for Ultragenyx Pharmaceutical? The narrative relies on a specific revenue growth path and a projected profit profile that assumes a sharp shift from current losses. Curious which margin assumptions and long term earnings multiple sit at the core of that calculation? Result: Fair Value of $26.0 (ABOUT RIGHT) Have a read of the narrative in full and understand what's behind the forecasts. However, Ultragenyx Pharmaceutical still faces key risks, including sustained net losses of US$586 million and execution challenges related to its broad rare disease and gene therapy portfolio. Find out about the key risks to this Ultragenyx Pharmaceutical narrative. That user narrative pins Ultragenyx Pharmaceutical’s fair value close to the current $25.91 share price. Our DCF model comes out very differently. It values the stock at $264.72 based on projected future cash flows, which implies a very large gap that points to serious model risk or potential opportunity. Which set of assumptions do you trust more? Look into how the SWS DCF model arrives at its fair value. With mixed signals around Ultragenyx Pharmaceutical's valuation, the smartest move is to review the data yourself and quickly form your own stance. To weigh both the potential upside and the concerns in one place, start with these 2 key rewards and 3 important warning signs. If you want a clearer view of how Ultragenyx Pharmaceutical fits into your portfolio, compare it with other opportunities using targeted stock lists on the Simply Wall St Screener. Spot potential bargains quickly by reviewing companies that currently feature in the 51 high quality undervalued stocks. Prioritise resilience by checking stocks highlighted in the 79 resilient stocks with low risk scores. Hunt for lesser known opportunities before others catch on by scanning the screener containing 19 high quality undiscovered gems. This article by Simply Wall St is general in nature. We provide commentary based on historical data and analyst forecasts only using an unbiased methodology and our articles are not intended to be financial advice. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. We aim to bring you long-term focused analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Simply Wall St has no position in any stocks mentioned. Companies discussed in this article include RARE. Have feedback on this article? Concerned about the content? Get in touch with us directly. Alternatively, email [email protected]

Interested in Ultragenyx Pharmaceutical Inc.? Here are five stocks we like better. Ultragenyx reported record Q2 revenue of $214 million, led by Crysvita’s $156 million contribution and strong Evkeeza growth. The company reaffirmed its 2026 revenue outlook and sees a potential path to profitability in 2027 through product growth, cost discipline and possible priority review voucher monetization. The company is approaching key regulatory decisions for gene therapies DTX-401 and UX-111, expected by Aug. 23 and Sept. 19, respectively. Ultragenyx has advanced launch preparations, including treatment-center readiness and more than 200 payer engagements. Ultragenyx expects Phase III Angelman syndrome data for GTX-102 in September or October, while the regulatory path for setrusumab remains uncertain after two studies missed their primary fracture-reduction endpoints. Analysts Say These 2 Mid-Cap Biotechs Have 2x Potential Ultragenyx Pharmaceutical (NASDAQ:RARE) reported second-quarter 2026 revenue of $214 million, led by growth across its commercial rare-disease portfolio, while the company prepared for potential regulatory decisions on two gene therapies and a late-stage data readout in Angelman syndrome. Chief Executive Officer and President Emil Kakkis said the quarter marked the company’s highest quarterly revenue to date and supported its reaffirmed full-year revenue guidance. He also said Ultragenyx sees a path to profitability in 2027 through continued product growth, potential contributions from upcoming launches, expense discipline and possible monetization of priority review vouchers. → SpaceX’s First Earnings Report Could Decide Whether Shorts or Bulls Have Control Chief Financial Officer Howard Horn said total second-quarter revenue reached $214 million. Crysvita generated $156 million, including $94 million in North America, $54 million in Latin America and Turkey, and $8 million in Europe. DOJOLVI contributed $27 million, while Evkeeza generated $21 million, up 50% from the second quarter of 2025. MEPSEVII revenue was $10 million. Total operating expenses were $289 million, including $34 million in cost of sales and $255 million in combined research and development and selling, general and administrative expenses. Operating expenses included $34 million of non-cash stock-based compensation. → Financials Hit Record Highs as the AI Trade Unravels—Can They Keep Leading? Ultragenyx posted a net loss of $92 million, or $0.90 per share, for the quarter. As of June 30, the company had $436 million in cash equivalents and marketable securities. Net cash used in operations was $97 million, which Horn said was significantly lower than in the first quarter and in line with prior expectations. The company reaffirmed its revenue guidance and its guidance for combined R&D and SG&A expenses. Horn said 2026 combined R&D and SG&A spending is expected to be flat to down low single digits from 2025, while 2027 spending is expected to decline by at least 15%, including planned investments for potential launches. → Why Rare Earth Processing Could Be the Real 2027 Opportunity Chief Commercial Officer Erik Harris said underlying demand remained strong despite seasonal factors that can affect quarterly ordering patterns. In Latin America, approximately 50 patients began commercial Crysvita therapy during the quarter, bringing the regional total to 1,000 patients. More than 100 patients in Turkey are receiving Crysvita through a named-patient program. For DOJOLVI, Ultragenyx generated about 30 start forms in North America and had approximately 675 patients on reimbursed treatment. About 300 patients in Europe were receiving treatment through named-patient or early-access programs. The company also began treating patients in Japan after the therapy was listed on the country’s National Health Insurance Drug Price List. Evkeeza was being provided to more than 500 patients in 25 countries outside the U.S., Harris said. He added that Ultragenyx’s commercial infrastructure is designed to support patient identification, reimbursement navigation and field execution across individual markets. Ultragenyx is awaiting FDA action on DTX-401, an investigational gene therapy for glycogen storage disease type Ia, with a Prescription Drug User Fee Act date of Aug. 23. The company’s second anticipated decision is for UX-111, a gene therapy for Sanfilippo syndrome type A, with a PDUFA date of Sept. 19. Kakkis said DTX-401 clinical studies showed that treated patients could significantly reduce the amount and frequency of cornstarch dosing to a prespecified clinically meaningful degree. He said the therapy is designed to provide expression of the missing G6Pase enzyme and improve glucose regulation during fasting or metabolic stress. For UX-111, Kakkis said clinical data showed reductions in heparan sulfate and stabilization or retention of cognitive function relative to natural history. He said earlier treatment appeared to produce better results, although patients across the age range studied showed benefits after treatment. Harris said launch preparations for the two potential gene therapies were progressing, including work with qualified treatment centers and more than 200 payer engagements. He said the company already has commercial experience in relevant treatment settings, with approximately 75% overlap between institutions and healthcare providers involved with the potential gene therapies and those serving DOJOLVI and MEPSEVII patients. During the question-and-answer session, Kakkis said the FDA review of DTX-401 had proceeded normally, with the company responding to information requests involving clinical and chemistry, manufacturing and controls matters. He said Ultragenyx could not predict the agency’s ultimate action. Ultragenyx expects to report top-line Phase III ASPIRE data for GTX-102, also known as apazunersen, in Angelman syndrome during September or October. The randomized, double-blind, sham-controlled study enrolled patients with a full maternal UBE3A gene deletion. Chief Medical Officer Eric Crombez said the study’s statistical alpha is split between the Bayley-4 cognitive raw score, which receives 80%, and the Multi-Domain Responder Index, or MDRI, which receives 20%. The endpoints are tested in parallel rather than hierarchically. A statistically successful study would require a Bayley endpoint p-value of 0.04 or less, or an MDRI p-value of 0.01 or less. Kakkis said a five- to six-point change on the Bayley assessment would be clinically meaningful and that the study was powered to detect an average change in that range. He also said the company’s Phase I/II program has shown a consistent safety profile, and the Phase III study had not been stopped because of a safety issue. Separately, Ultragenyx continues discussions with regulators regarding UX143, or setrusumab, for osteogenesis imperfecta. Crombez said neither of the Phase III ORBIT and COSMIC studies met their primary endpoints for annualized fracture reduction, though the studies showed improvements in bone mineral density and patient-reported outcomes, along with fracture reductions in certain bones and patient groups. The U.K.’s Medicines and Healthcare products Regulatory Agency indicated that a new randomized study may be required before it would consider an application, according to Crombez. The FDA has been open to discussing alternative fracture analyses, but Ultragenyx said further discussions are needed to determine the additional clinical data required for a potential biologics license application. Ultragenyx Pharmaceutical Inc is a biopharmaceutical company focused on developing and commercializing therapies for rare and ultra-rare genetic disorders. Since its founding in 2010 and headquarters in Novato, California, the company has built expertise in protein replacement therapies, small molecules and gene therapy approaches to address high-unmet medical needs. Ultragenyx applies a precision medicine model, leveraging both in-house research and strategic collaborations to advance its product pipeline from discovery through regulatory approval. The company's commercial portfolio includes Crysvita (burosumab-tmyl) for X-linked hypophosphatemia, Mepsevii (vestronidase alfa-vjbk) for mucopolysaccharidosis VII and Dojolvi (triheptanoin) for long-chain fatty acid oxidation disorders. This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to [email protected]. The article "Ultragenyx Pharmaceutical Q2 Earnings Call Highlights" was originally published by MarketBeat. View MarketBeat's top stocks for August 2026.

Our analysts just identified a stock with the potential to be the next Nvidia. Tell us how you invest and we'll show you why it's our #1 pick. Tap here. Achieved record quarterly revenue driven by strong global demand for Crysvita, DOJOLVI, and Evkeeza, reinforcing the company's established commercial infrastructure. Preparing for parallel launches of DTX-401 for GSD 1A and UX-111 for Sanfilippo syndrome type A, targeting diseases with high urgency and no existing treatments. Clinical data for DTX-401 demonstrated significant reductions in cornstarch dependence and improved glucose metabolism, addressing life-threatening metabolic risks. UX-111 development focused on stabilizing cognitive function in Sanfilippo patients, with data showing earlier treatment leads to better brain function preservation. The global commercial strategy leverages existing relationships with Qualified Treatment Centers (QTCs), with 75% overlap between upcoming launches and current product footprints. Management emphasized that the second half of 2026 represents the most significant period in company history due to three major clinical and regulatory catalysts. Reaffirmed a clear path to profitability in 2027, supported by double-digit revenue growth from current products and contributions from new gene therapy launches. Anticipating top-line Phase III ASPIRE data for GTX-102 in Angelman syndrome in the September or October 2026 timeframe. Guidance for 2027 includes a planned operating expense reduction of at least 15% compared to 2025 levels through disciplined capital allocation. Regulatory strategy for GTX-102 utilizes a split-alpha approach between Bayley-4 cognitive scores and the Multi-Domain Responder Index (MDRI) to maximize success probability. Future liquidity will be bolstered by the intended monetization of Priority Review Vouchers (PRVs) associated with potential DTX-401 and UX-111 approvals. Setrusumab (UX-143) development faces hurdles as the UK's MHRA indicated a new randomized study may be required despite biological activity signals. FDA discussions for setrusumab remain ongoing regarding alternative fracture analysis, but management noted additional clinical data will likely be necessary for a BLA. The company is managing the operational complexity of two simultaneous BLA reviews with PDUFA dates occurring only one month apart. While Phase I/II data for GTX-102 is mature, the Phase III ASPIRE study results remain the primary dependency for the Angelman syndrome filing timeline. One stock. Nvidia-level potential. 30M+ investors trust Moby to find it first. Get the pick. Tap here. Management confirmed the FDA agreed to a split-alpha design (80% Bayley-4, 20% MDRI), where significance in either endpoint constitutes a successful study. A five-to-six point change in the Bayley raw score is considered the threshold for clinical meaningfulness, which the study is powered to detect. The MDRI is described as tenfold more powerful than individual endpoints because it aggregates clinically meaningful gains across five diverse domains (cognition, communication, sleep, behavior, and motor). Management believes this approach filters out 'random placebo changes' by requiring a high threshold of improvement to score. The FDA is open to discussing alternative fracture analyses, but management clarified that extension data alone may not be sufficient for a filing. Bone Mineral Density (BMD) is not yet accepted by regulators as a primary surrogate for approval, necessitating fracture-based efficacy data. Management declined to provide specific discontinuation rates but noted that the study has proceeded smoothly without any safety-related stops. They expressed confidence that the lower extremity weakness issues seen early in development have been addressed and are no longer a primary regulatory concern.

This article first appeared on GuruFocus. Total Revenue: $214 million for the second quarter of 2026. Crysvita Revenue: $156 million, including $94 million from North America, $54 million from Latin America and Turkiye, and $8 million from Europe. Dojolvi Revenue: $27 million, consistent with steady demand growth. Evkeeza Revenue: $21 million, representing 50% growth over the second quarter of 2025. Mepsevii Revenue: $10 million. Total Operating Expenses: $289 million, including cost of sales of $34 million and combined R&D and SG&A expenses of $255 million. Net Loss: $92 million, or $0.90 per share. Cash Position: $436 million in cash, cash equivalents, and marketable securities as of June 30. Net Cash Used in Operations: $97 million for the quarter. Warning! GuruFocus has detected 5 Warning Signs with RARE. Is RARE fairly valued? Test your thesis with our free DCF calculator. Release Date: August 04, 2026 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Ultragenyx Pharmaceutical Inc (NASDAQ:RARE) reported its highest quarterly revenue in company history at $214 million, with strong performance across all products including 50% growth for Evkeeza. The company reaffirmed its full-year revenue guidance, citing strong underlying demand and a rebound in orders in Q2. Two gene therapy launches (DTX401 for GSDIa and UX111 for Sanfilippo syndrome) are on track with PDUFA dates in August and September, representing first-ever treatments for these diseases. GTX-102 for Angelman syndrome is approaching a Phase 3 data readout in September/October, with a well-defined statistical plan and strong Phase 1/2 data showing durable benefits. The company has a clear path to profitability in 2027, supported by revenue growth, expense discipline, and potential monetization of priority review vouchers. Commercial infrastructure is highly leveraged, with 75% overlap in treatment centers for upcoming launches, and the team has experience from four prior product launches. Ultragenyx Pharmaceutical Inc (NASDAQ:RARE) reported a net loss of $92 million for Q2 2026, with cash burn of $97 million in the quarter. The company faces uncertainty in the regulatory path for setrusumab (UX143) for osteogenesis imperfecta, as the MHRA indicated a new randomized study may be needed and the FDA requires further discussions on fracture analysis. The Phase 3 Aspire study for GTX-102 has a complex statistical design with alpha split between two endpoints, and there is risk of not meeting statistical significance on either. The company has not provided specific guidance on the impact of upcoming launches on profitability, and slower-than-expected ramping could affect the 2027 target. There is potential for placebo effects in the Angelman syndrome trial, particularly on the MDRI endpoint, which could dilute treatment effects. The company faces operational risks in managing two simultaneous BLA submissions and potential manufacturing inspections, which could delay approvals. Q: For Angelman syndrome, could you provide more context on the endpoints, specifically if the FDA has signed off on whether one endpoint or not would be sufficient for filing, and if the endpoints were powered to show results the community would deem clinically acceptable? A: Emil Kakkis, CEO: We had our discussion with the FDA on the sharing of primary alpha, and that was agreed to in our end of Phase 2 and follow-up discussions. Sharing alpha means either endpoint can be positive in their analysis. We are powering based on the effects we've seen, but we think a 5- or 6-point change in the Bayley should be sufficient to achieve significance, and that 6-point level is considered clinically meaningful. For the MDRI, it only scores if there are clinically meaningful results, as each domain improvement requires a threshold of clinical meaningfulness. We are comfortable about the two-endpoint approach and think the powering will be positive with clinically meaningful results. Q: On the MDRI endpoint, which has generated some confusion, can you talk about the level of sensitivity and whether it's a better endpoint than cognition, given that it's a global primary? A: Emil Kakkis, CEO: The MDRI approach captures efficacy across multiple domains using a clinically meaningful threshold. We used it previously in the Mepsevii program, where it was significant in our 12-patient trial. In our published analyses, the MDRI was tenfold more powerful to detect change in an enzyme replacement therapy trial compared to individual endpoints. In the Angelman Phase 2 data, even in the 15-patient trial, we showed substantial power with p-values less than 0.01. It's more powerful because we capture more efficacy in it. Being able to show through five important domains for Angelman what a drug is doing is a better assessment of what a drug does in a disease as complex as Angelman. Q: Could you clarify your comments on GTX-102 and Bayley? I think you said you needed a 5- to 6-point change to hit stats relative to placebo. I'm assuming that's raw score, right? But using GSV, if I remember back to your Phase 2, you showed a similar-ish effect. A: Emil Kakkis, CEO: I wasn't saying that's the threshold for powering. I was saying that a 5- to 6-point is a meaningful change, and we are powered to detect that average change. We are well-powered to detect anything that would be considered clinically meaningful in that range. In the data we put out recently, we said it was near 10 score when you combine all the data together at one year. Whatever we would detect should be a clinically meaningful change, and we are confident we can do that. Q: On the allocation of alpha, I understand you've been discussing an 80% allocation to the Bayley-4 cognition endpoint and 20% to MDRI, but I think it was a 90/10 alpha allocation in the completion of enrollment press release. Was there a change to the statistics? A: Emil Kakkis, CEO: Our current plan is to do 80/20. 90/10 are very similar, and I don't think they're materially different. We decided to make it 80/20. There was no particular data or other reason for it. The MDRI is very powerful, and we think 10% or 20% is probably adequate for that. In our discussion with FDA, that was the split we had, and they're comfortable with what we are proposing. Q: What are your latest expectations for the placebo arm performance on MDRI and the Bayley cognition score, and your confidence that there won't be a placebo effect? A: Emil Kakkis, CEO: In the Bayley cognitive, where we have both natural history and randomized data from another study, the effect is 1 point or less. Placebo effects usually don't happen in things like a Bayley score because the patient is not cognitive of what the change should be. In the MDRI, we're looking at multiple endpoints, and the threshold of clinically meaningful change means just a little bit of change from bias wouldn't score. It has to be a really big change before you can score. We think we designed it to manage any placebo effect in both endpoints. Q: On setrusumab, you said the FDA indicated openness to alternatives to the fracture analysis, but you need to further define what would be needed for a BLA. Do you feel you have a fileable package from the existing Cosmic and Orbit dataset? A: Erik Harris, CCO: Our comments were basically around the type of fractures and type of patients we were talking about regarding what fracture analysis they would want. Our discussion suggests some additional clinical data will be required, and we need to define what that is, which is not fully defined yet. We cannot state at this point whether extension data alone or whether there's any additional data required. They've been very open to a discussion and a path forward, and we just need to come up with a good plan to get us to that file package. Q: On the financial front, how are you feeling about your cash balance and any potential need to do financing? And how should we think about the investment needed for the upcoming launches for 401 and 111? A: Howard Horn, CFO: On investments, I'll remind folks of the guidance we gave for combined R&D and SG&A. This year was flat to down low-single digits, and in 2027, it's a decrease of at least 15%. Both were inclusive of the launch investments we're planning to make for 111 and 401. Those programs fall into a sales structure we already carry, so it's a highly leveraged situation. On cash balance, we reported $436 million as of the end of the quarter. As it relates to fundraising, our focus is on monetization of PRVs. Upon approval, our intent would be to monetize our DTX401 PRV and also the UX111 PRV. Q: Have any of the regulatory agencies you've spoken with indicated a willingness to use or rely on bone mineral density as a determinant of efficacy for setrusumab? A: Emil Kakkis, CEO: At this point, there hasn't been the kind of proof of BMD predictive value for fractures as there has been for osteoporosis where it has been accepted. We're still in the point of proving it. We're looking at fracture endpoints of some form as the primary way to get approval and not using BMD. We all agree BMD demonstrates the profound activity of this For the complete transcript of the earnings call, please refer to the full earnings call transcript.

Ultragenyx Pharmaceutical RARE reported second-quarter 2026 loss of 90 cents per share, which was narrower than the Zacks Consensus Estimate of a loss of $1.27. The company had incurred a loss of $1.17 per share in the year-ago quarter. Total revenues in the second quarter were $214 million, which surged 28.1% year over year due to higher product sales. The top line also beat the Zacks Consensus Estimate of $181 million. Management stated that second-quarter 2026 revenues were the highest quarterly revenues ever reported by the company. Ultragenyx markets four drugs, namely Crysvita, Mepsevii, Dojolvi and Evkeeza. Crysvita is approved for treating X-linked hypophosphatemia, an inherited disorder and tumor-induced osteomalacia, an ultra-rare disease. Mepsevii is approved to treat Mucopolysaccharidosis VII, also known as Sly syndrome. Dojolvi is approved for treating all forms of long-chain fatty acid oxidation disorders. Evkeeza is indicated for homozygous familial hypercholesterolemia (HoFH). In 2022, Ultragenyx announced a license and collaboration agreement with Regeneron Pharmaceuticals REGN for Evkeeza, which is approved in multiple geographies as a first-in-class therapy for use together with diet and other low-density lipoprotein-cholesterol-lowering therapies to treat adults and adolescents aged 12 years and older with HoFH. Per the deal, RARE has obtained the rights to develop, commercialize and distribute Evkeeza outside the United States. The regions include the European Economic Area. The collaboration with Regeneron for Evkeeza gives Ultragenyx a fourth approved product that adds to the top line. However, REGN solely commercializes Evkeeza in the United States. Year to date, shares of Ultragenyx have gained 12.2% compared with the industry’s 1.6% rise. Image Source: Zacks Investment Research Crysvita’s total revenues were $156 million, up 28.9% year over year. Management noted that Crysvita sales were consistent with expected seasonality in the United States and Canada and ordering patterns in Latin America. Crysvita’s net product revenues in the second quarter of 2026 included $94 million from North America, $54 million from Latin America and Turkey, and $8 million from Europe. Mepsevii product revenues increased 11.1% year over year to $10 million in the reported quarter. Dojolvi product revenues were $27 million, up 17.4%, driven by strong demand. Evkeeza recorded sales of $21 million in the second quarter, up 50%, driven by increased demand from new country launches and early access. Operating expenses of $289 million in the quarter rose 5.1% year over year due to increased investments in multiple late-stage pipeline programs and marketing costs for approved drugs. Operating expenses included research and development (R&D) expenses of $167 million (up 1.2%), selling, general and administrative (SG&A) expenses of $88 million (up 1.1%) and cost of sales of $34 million (up 47.8%). Cash, cash equivalents and marketable securities amounted to $436 million as of June 30, 2026, compared with $534 million as of March 31, 2026. Ultragenyx continues to expect total revenues in 2026, excluding potential revenues from new product launches, between $730 million and $760 million. Crysvita revenues in 2026 are expected to be in the range of $500-$520 million, reflecting growing underlying global demand. Meanwhile, Dojolvi revenues are expected to be between $100 million and $110 million in 2026. In April 2026, the FDA accepted the resubmitted biologics license application (BLA) seeking accelerated approval of UX111 for the treatment of MPS IIIA. The application included extensive long-term data with follow-up of up to eight years. The data showed sustained clinical benefits compared with the decline seen in natural history studies, along with durable treatment effects across multiple clinical measures and biomarkers, while maintaining an acceptable safety profile. A final decision from the regulatory body is expected on Sept. 19, 2026. The FDA has also accepted for review Ultragenyx’s BLA for its investigational AAV8 gene therapy, DTX401, to treat glycogen storage disease type Ia. A final decision from the regulatory agency is expected on Aug. 23, 2026. Ultragenyx is also evaluating UX701, an investigational AAV9 gene therapy, in a phase I/II/III Cyprus2+ study to treat Wilson disease and expects to share top-line data in the fourth quarter of 2026. Ultragenyx’s GTX-102, an investigational antisense oligonucleotide, is being developed in the pivotal phase III Aspire study for treating Angelman syndrome (AS) patients with a genetically confirmed diagnosis of UBE3A deletion. Top-line data are expected in September or October 2026. Meanwhile, enrollment in the phase II/III Aurora study is currently ongoing to evaluate the safety and efficacy of GTX-102 for treating other AS genotypes in other patient age groups. This additional study aims to enable treatment for a broader range of AS patients. The study is expected to complete enrollment in the second half of 2026. Ultragenyx Pharmaceutical Inc. price-consensus-eps-surprise-chart | Ultragenyx Pharmaceutical Inc. Quote Ultragenyx currently carries a Zacks Rank #2 (Buy). Some other top-ranked stocks in the biotech sector are Repligen RGEN and Liquidia Corporation LQDA, each currently sporting a Zacks Rank #1 (Strong Buy). You can see the complete list of today’s Zacks #1 Rank stocks here. Over the past 60 days, estimates for Repligen’s 2026 earnings per share have risen from $1.99 to $2.06, while estimates for 2027 have increased from $2.57 to $2.62 during the same time. RGEN shares have declined 8.6% year to date. Repligen’s earnings beat estimates in each of the trailing four quarters, with the average surprise being 16.80%. Over the past 60 days, estimates for Liquidia’s 2026 earnings per share have risen from $2.97 to $3.02, while estimates for 2027 have increased from $4.81 to $5.31 during the same time. LQDA shares have surged 156.3% year to date. Liquidia’s earnings beat estimates in three of the trailing four quarters, while missing the same on the remaining occasion, with the average surprise being 54.40%. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Ultragenyx Pharmaceutical Inc. (RARE) : Free Stock Analysis Report Regeneron Pharmaceuticals, Inc. (REGN) : Free Stock Analysis Report Repligen Corporation (RGEN) : Free Stock Analysis Report Liquidia Corporation (LQDA) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research

Second quarter total revenue of $214 million, Crysvita® revenue of $156 million and Dojolvi® revenue of $27 million Reaffirm 2026 financial guidance, including total revenue of $730 million to $760 million and combined R&D and SG&A expenses to be flat to slightly down versus 2025; remain on path to profitability in 2027 Catalysts in second half of 2026 include two PDUFA dates and pivotal data readout from GTX-102 Phase 3 Aspire study for Angelman syndrome NOVATO, Calif., Aug. 04, 2026 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for serious rare and ultra-rare genetic diseases, today reported its financial results for the quarter ended June 30, 2026 and reaffirmed its financial guidance for 2026. “In the second quarter we generated the highest quarterly revenue in the history of the company, supporting our full-year revenue guidance, and keeping us on track toward profitability in 2027,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “As we look to the second half of the year, we are entering a transformative period with multiple important catalysts. We are ready to launch two gene therapy products and are preparing for a pivotal Phase 3 GTX-102 data readout in Angelman syndrome. This puts us in position to broaden our patient impact with sustained growth in the years to come.” Second Quarter 2026 Revenue Highlights and 2026 Revenue Guidance Total revenue in the second quarter of 2026 was $214 million. The company reaffirms its full year 2026 total revenue guidance of $730 million to $760 million, which excludes revenue from potential new product launches. Crysvita revenue in the second quarter of 2026 was $156 million, consistent with expected seasonality in the U.S. and Canada and ordering patterns in Latin America. The company reaffirms its full year 2026 Crysvita revenue guidance of $500 million to $520 million. Dojolvi revenue in the second quarter 2026 was $27 million. The company reaffirms its full year 2026 Dojolvi revenue guidance of $100 million to $110 million. Evkeeza® revenue in the second quarter 2026 was $21 million, driven by increased demand from new country launches and early access. Mepsevii® revenue in the second quarter 2026 was $10 million. Milestones and Upcoming Catalysts Dojolvi for the treatment of LC-FAOD: In May 2026, Dojolvi was listed on the National Health Insurance (NHI) drug price list and was launched in Japan following the receipt of manufacturing and marketing approval under the Conditional Approval System for Pharmaceuticals on March 23, 2026. DTX401 (pariglasgene brecaparvovec) AAV8 gene therapy for the treatment of glycogen storage disease type Ia (GSDIa): In February 2026, the U.S. Food and Drug Administration (FDA) accepted for review the Biologics License Application (BLA) seeking approval of DTX401 as a treatment for GSDIa and assigned a Prescription Drug User Fee Act (PDUFA) action date of August 23, 2026. UX111 (rebisufligene etisparvovec) AAV9 gene therapy for the treatment of Sanfilippo syndrome type A (MPS IIIA): In April 2026, the FDA accepted for review the resubmitted BLA seeking accelerated approval for UX111 as a treatment for MPS IIIA and assigned a PDUFA action date of September 19, 2026. GTX-102 (apazunersen) antisense oligonucleotide (ASO) for the treatment of Angelman syndrome (AS): The Phase 3 Aspire study, in patients with a full maternal UBE3A gene deletion, enrolled 129 patients, randomized 1:1 to GTX-102 or sham. Data from this study are expected in the September or October timeframe.Enrollment in the open-label Phase 2/3 Aurora study, evaluating GTX-102 in other genotypes and ages, began in October 2025 and is expected to complete in the second half of 2026. UX701 (rivunatpagene miziparvovec) AAV9 gene therapy for the treatment of Wilson disease: Enrollment is complete for the fourth cohort in the ongoing, dose-finding stage of the pivotal Cyprus2+ study. Data from this stage are expected in the fourth quarter of 2026. UX016 novel prodrug for sialic acid used as a substrate replacement therapy for the treatment of GNE myopathy: The FDA cleared the Investigational New Drug (IND) application for UX016 and an externally funded Phase 1/2 study is expected to begin in the second half of 2026. DTX301 (avalotcagene ontaparvovec) AAV8 gene therapy for the treatment of Ornithine Transcarbamylase, or OTC, deficiency: The Phase 3 Enh3ance study continues with patients in both treatment and cross-over groups progressing through 64 weeks of follow-up. Data from the second primary endpoint, which evaluates reduction in treatment burden, including use of ammonia scavengers and dietary management, are expected in the first half of 2027. Summary of Second Quarter 2026 Financial ResultsSelected Financial Data (dollars in millions, except per share amounts), (unaudited) Operating Expenses Total operating expenses for the second quarter 2026 were $289 million, including $34 million of non-cash stock-based compensation. The company reaffirms its full year 2026 and 2027 guidance for combined R&D and SG&A operating expenses: compared to 2025, combined R&D and SG&A expenses in 2026 are expected to be flat to down low-single digits, and combined R&D and SG&A expenses in 2027 are expected to decrease by at least 15%.Net Loss Net loss for the second quarter 2026 was $92 million, or $0.90 per share basic and diluted, compared with a net loss for the second quarter 2025 of $115 million, or $1.17 per share basic and diluted. Cash Balance and Net Cash Used in Operations Cash, cash equivalents, and marketable securities were $436 million as of June 30, 2026. For the three months ended June 30, 2026, net cash used in operations was $97 million. Conference Call and Webcast Information Ultragenyx will host a conference call today, Tuesday, August 4, 2026, at 2 p.m. PT/5 p.m. ET to discuss the second quarter 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 three months. About Ultragenyx Ultragenyx is a biopharmaceutical company committed to bringing novel therapies to patients for the treatment of serious rare and ultra-rare 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 regarding Ultragenyx’s expectations and projections concerning its future operating results and financial performance, including its 2026 revenue guidance for total revenue, Crysvita and Dojolvi, its anticipated R&D and SG&A expenses in 2026 and 2027, anticipated benefits and savings from its strategic restructuring plan, and the timing and sustainability of profitability; the timing, progress, results and plans for its clinical programs and studies, including the anticipated timing and outcome of the Phase 3 Aspire study of GTX-102, enrollment in the Aurora study, data from the UX701 and DTX301 studies, and initiation of the UX016 study; the FDA’s review of the BLAs for DTX401 and UX111, including the anticipated PDUFA action dates, the potential approval of either product candidate, whether the FDA may require additional information, studies or manufacturing changes, and the timing and outcome of regulatory inspections; Ultragenyx’s manufacturing and commercial readiness and the timing and success of any potential launches of DTX401 and UX111, if approved; and the potential patient impact, commercial opportunity and growth associated with Ultragenyx’s products and product candidates, 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 commercialization of Crysvita in certain major markets, including the U.S. and Canada, and for our commercial supply of Crysvita in those markets, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, smaller than anticipated market opportunities for the company’s products and product candidates, manufacturing risks, our ability to successfully manage the expansion of our company, delays or unexpected costs and other adverse effects related to the strategic restructuring plan, competition from other therapies or products, regulatory scrutiny of the company’s products and product candidates, the company’s limited experience as a company in operating its own manufacturing facility, market acceptance of our products, uncertainty related to insurance coverage and reimbursement, 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 May 6, 2026, 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 [email protected] MediaJess [email protected]

Ultragenyx (RARE) reported $214 million in revenue for the quarter ended June 2026, representing a year-over-year increase of 28.5%. EPS of -$0.90 for the same period compares to -$1.17 a year ago. The reported revenue compares to the Zacks Consensus Estimate of $181.01 million, representing a surprise of +18.23%. The company delivered an EPS surprise of +29.13%, with the consensus EPS estimate being -$1.27. While investors scrutinize revenue and earnings changes year-over-year and how they compare with Wall Street expectations to determine their next move, some key metrics always offer a more accurate picture of a company's financial health. As these metrics influence top- and bottom-line performance, comparing them to the year-ago numbers and what analysts estimated helps investors project a stock's price performance more accurately. Here is how Ultragenyx performed in the just reported quarter in terms of the metrics most widely monitored and projected by Wall Street analysts: Revenues- Dojolvi: $27 million compared to the $25.61 million average estimate based on five analysts. The reported number represents a change of +16.3% year over year. Revenues- Evkeeza: $21 million versus the five-analyst average estimate of $17.43 million. The reported number represents a year-over-year change of +44.1%. Revenues- Mepsevii: $10 million compared to the $9.75 million average estimate based on five analysts. The reported number represents a change of +20.3% year over year. Revenues- Product sales: $112 million versus the four-analyst average estimate of $98.68 million. The reported number represents a year-over-year change of +38.6%. Revenues- Total Crysvita Revenue: $156 million versus the four-analyst average estimate of $128.3 million. The reported number represents a year-over-year change of +29.6%. Revenues- Royalty revenue: $102 million versus $82.1 million estimated by four analysts on average. Compared to the year-ago quarter, this number represents a +19.1% change. View all Key Company Metrics for Ultragenyx here>>> Shares of Ultragenyx have returned -25.8% over the past month versus the Zacks S&P 500 composite's +1.7% change. The stock currently has a Zacks Rank #2 (Buy), indicating that it could outperform the broader market in the near term. Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Ultragenyx Pharmaceutical Inc. (RARE) : Free Stock Analysis Report This article originally published on Zacks Investment Research (zacks.com). Zacks Investment Research