On May 6, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported that the first patient was enrolled on the trial studying Iomab-ACT targeted conditioning with a commercial CAR-T therapy at the University of Texas Southwestern Medical Center (UTSW) (NCT06768905) (Press release, Actinium Pharmaceuticals, MAY 6, 2025, View Source [SID1234652603]). Initial clinical data from this trial is expected in the second half of 2025. Actinium is developing Iomab-ACT as a targeted radiotherapy conditioning agent intended to replace non-targeted chemotherapeutic conditioning agents such as Fludarabine and Cyclophosphamide (Flu/Cy) to address serious CAR-T related toxicities including immune effector cell-associated neurotoxicity (ICANS) and cytokine release syndrome (CRS), to potentially improve patient access and outcomes. Currently, there are seven CAR-T therapies approved for certain leukemias and lymphomas and multiple myeloma, that over 150,000 patients are diagnosed with annually. In 2024, the seven approved CAR-T therapies generated over $4 billion in sales and CAR-T therapies are forecasted to reach $12 billion in annual sales in 2030.

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Dr. Farrukh Awan, Professor of Medicine, Division of Hematology Oncology at UTSW said, "We are thrilled to initiate patient enrollment to study Iomab-ACT targeted radiotherapy conditioning with a commercial CAR-T therapy. Iomab-ACT is supported by compelling preclinical and clinical data, and we believe it has immense potential to eliminate the need for chemotherapy-based conditioning, which is a major barrier for many patients seeking CAR-T treatment. Despite the positive impact CAR-T therapy has had on patient outcomes, there is still significant room for improvement. We are optimistic that Iomab-ACT can transform CAR-T therapy conditioning if this trial demonstrates it has the ability to increase patients access and reduce the rates and severity of ICANS and CRS and also potentially improve patient outcomes. We are excited to begin treating patients with Iomab-ACT and eager to present our preliminary findings later this year."

Iomab-ACT targets CD45, a cell surface marker expressed on immune cells relevant to CAR-T therapy including lymphocytes and is the only clinical stage conditioning agent targeting CD45. Preclinical data demonstrated that Iomab-ACT can selectively target immune cells implicated in CAR-T toxicities, while sparing bone marrow stem cells, red blood cells and platelets. Preclinical and clinical data also showed that Iomab-ACT produces transient lymphodepletion that aligns with the CAR-T treatment process. This data supported the first clinical trial of Iomab-ACT with a novel CD19 CAR-T therapy in collaboration with Memorial Sloan Kettering Cancer Center (MSK) in patients heavily pretreated with relapsed and refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) or Diffuse Large B-cell Lymphoma (DLBCL). In this study, no patients (0/4) developed ICANS of any grade, and minimal CRS. Iomab-ACT also demonstrated transient depletion of peripheral blood lymphocytes and monocytes, persistence of CAR T-cells up to 8 weeks and minimal non-hematologic toxicities. These positive findings supported the continued advancement of Iomab-ACT and the initiation of the commercial CAR-T trial at UTSW.

Sandesh Seth, Actinium’s Chairman and CEO, stated, "This is a pivotal moment for our Iomab-ACT CD45 targeted radiotherapy conditioning program. Iomab-ACT is a highly differentiated conditioning agent that has produced promising initial clinical results where multiple targeted conditioning approaches including monoclonal antibodies and antibody drug conjugates directed against a variety of targets have not achieved clinical success to date. Based on the promising initial outcomes from the pilot study of Iomab-ACT with a novel CD19 CAR-T, we are incredibly excited by the potential of this commercial CAR-T trial and future development path. With initial clinical data expected beginning in the second half of this year, we are making strong progress to achieving our goal of establishing Iomab-ACT as a universal targeted conditioning regimen for CAR-T and other cellular therapies."

Targeted Radiotherapy CAR-T Conditioning Opportunity

A multi-billion-dollar market opportunity exists for better conditioning in other areas of cellular therapy, such as CAR-T. Currently, there are seven CAR T-cell therapies targeting CD19 for lymphoma and leukemia and BCMA for multiple myeloma that are approved by the FDA with total sales of over $4.0 billion in 2024. The pipeline of CAR-T therapies in development has rapidly expanded, with the addressable patient population expected to nearly double and reach approximately 93,000 patients in the U.S. by 2030 based on the current pipeline of cellular therapies. The addressable market for Iomab-ACT is in line with the patient population for cellular therapies that is approximately150,000 patients annually across the indications in which CAR-T therapies are approved, as all patients receive conditioning of some type. We believe a potential blockbuster revenue opportunity exists for Iomab-ACT assuming it can provide clinical benefits related to adverse events related to CAR-T, longer duration of response or improved survival outcomes.

On May 6, 2025 Krystal Biotech, Inc. (the "Company") (NASDAQ: KRYS) reported financial results for the first quarter ending March 31, 2025 and provided a business update (Press release, Krystal Biotech, MAY 6, 2025, View Source [SID1234652602]).

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"We were thrilled to receive VYJUVEK approval in Europe, and with the potential expansion to Japan later in the year, we continue to make tremendous progress on our goal of delivering profound long-term benefit to DEB patients around the world," said Krish S. Krishnan, Chairman and CEO of Krystal Biotech. "With today’s announcement of our second clinical-stage ophthalmology program, the near-term initiation of our registrational study in DEB patients with eye lesions, and upcoming molecular readouts for our rare respiratory disease product candidates, KB407 and KB408, we are pushing forward a broad and expanded pipeline which we expect will ultimately demonstrate the power of HSV-1 based gene delivery in the lung, eye, and skin, and – most importantly – deliver meaningful benefit to patients."

VYJUVEK (beremagene geperpavec-svdt, or B-VEC)
for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)

In April, the European Commission approved VYJUVEK for the treatment of wounds in patients with DEB who have mutations in the collagen type VII alpha 1 chain (COL7A1) gene, starting from birth. The Company is on track for its first European launch in Germany in mid-2025.
The Company recorded $88.2 million in VYJUVEK net product revenue for the first quarter of 2025. Gross margin for the quarter was 94%.
As of April, the Company has secured over 540 reimbursement approvals for VYJUVEK in the U.S. and continues to maintain strong access nationwide including positive access determinations for 97% of lives covered under commercial and Medicaid plans.
High patient compliance with weekly treatment while on drug continued at 83% as of the end of the quarter.
The Company continues to expect a decision by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) on its Japan New Drug Application (JNDA) in 2H 2025.
In April, the British Journal of Dermatology published a case highlighting the success of VYJUVEK in promoting durable wound healing following surgical excision of a large squamous cell carcinoma (SCC) in a recessive DEB patient. The treated patient reported complete healing of their over 100 cm2 post-surgical wound after seven weeks of VYJUVEK therapy. Wound healing benefits were durable, with complete wound closure also observed upon clinical examination at four and ten month post-operative visits.
In April, the results of the Company’s open label extension (OLE) study of VYJUVEK in DEB patients were published in the American Journal of Clinical Dermatology.
Respiratory

KB407 for the treatment of cystic fibrosis (CF)

The Company continues to enroll Cohort 3 of CORAL-1, the Company’s multi-center, dose escalation study evaluating KB407 in patients with CF, regardless of their underlying genotype. The Company received full sanctioning of the study protocol by the Cystic Fibrosis Foundation Therapeutic Development Network in January and remains on track for an interim molecular data readout for Cohort 3 patients in mid-2025. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT05504837.
KB408 for the treatment of alpha-1 antitrypsin deficiency (AATD) lung disease

The Company continues to enroll in Cohort 2 and is working to enroll in Cohort 3 of SERPENTINE-1, the Company’s open label, single dose escalation study in adult patients with AATD with a Pi*ZZ or a Pi*ZNull genotype. Late last year, the Company announced successful SERPINA1 gene delivery and functional alpha-1 antitrypsin (AAT) expression reaching therapeutic levels as part of an interim clinical update for Cohorts 1 and 2 of SERPENTINE-1. Inhaled KB408 was safe and well-tolerated at both tested dose levels. The Company expects to report molecular results for the additional Cohort 2 and 3 patients later this year. Details about the study can be found at www.clinicaltrials.gov under NCT identifier: NCT06049082.
Ophthalmology

KB803 for the treatment of ocular complications of DEB

The Company continues to enroll in its ongoing natural history study to prospectively collect data on the frequency of corneal abrasions in patients with DEB and serve as a run-in period for patients who may be eligible to participate in the Company’s registrational Phase 3 study evaluating KB803’s effect on ocular complications of DEB. The Company expects to dose the first patient in the registrational KB803 Phase 3 IOLITE study later this month.
KB801 for the treatment of neurotrophic keratitis (NK)

In April, the U.S. Food and Drug Administration (FDA) cleared the Company’s investigational new drug (IND) application to evaluate KB801, the Company’s second clinical-stage ophthalmology program, for the treatment of NK. NK is a rare, degenerative corneal disease caused by nerve damage in the eye leading to corneal epithelial defects, ulcers, and perforation, with an estimated prevalence in the range of 10 to 50 cases per 100,000. KB801 was developed using the Company’s novel replication-defective, non-integrating HSV-1-based vector and is designed to deliver two transgene copies to the corneal epithelium as an eye drop to enable local nerve growth factor (NGF) production and corneal healing. Recombinant NGF eye drops have been shown to significantly improve corneal healing and are approved for the treatment of NK in multiple jurisdictions worldwide including the United States, but the short half-life of recombinant protein results in rapid clearance from the eye, thereby necessitating burdensome administration six times a day, and may lead to suboptimal treatment outcomes. Eye pain during treatment is also frequently reported.
In preclinical development, KB801 was shown to efficiently transduce corneal epithelial cells in vitro and in vivo leading to sustained NGF production in the front of the eye. By transducing the cells of the corneal epithelium to produce and secrete NGF, KB801 has the potential to significantly reduce the treatment burden for patients while also maintaining more consistent NGF levels in the front of the eye. Yesterday, the Company presented preclinical safety and efficacy data supporting the clinical development of KB801 at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting.
The Company expects to dose the first patient in EMERALD-1, the Company’s randomized, double-blind, placebo-controlled, multi-center Phase 1/2 study evaluating KB801 in moderate-to-severe NK patients, later this month.
Oncology

Inhaled KB707 for the treatment of solid tumors of the lung

Enrollment is ongoing in the Company’s KYANITE-1 study, a Phase 1/2 open label, multi-center, dose escalation and expansion study evaluating inhaled KB707, as monotherapy or in combination, in patients with locally advanced or metastatic solid tumors of the lung. Near the end of last year, the Company announced early clinical evidence of monotherapy activity in heavily pre-treated patients with advanced non-small cell lung cancer (NSCLC) treated with inhaled KB707, achieving an objective response rate of 27% and disease control rate of 73% as of data cut-off. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT06228326.
A clinical update on the monotherapy cohort from KYANITE-1 is expected to be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting next month.
Intratumoral KB707 for the treatment of injectable solid tumors

The Company continues to enroll in OPAL-1, a Phase 1/2 open label, multi-center, dose escalation and expansion study evaluating intratumoral KB707, either as monotherapy or in combination, in patients with locally advanced or metastatic solid tumor malignancies. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT05970497.
Aesthetics

KB301 for the treatment of dynamic wrinkles of the décolleté

Jeune Aesthetics is currently developing a décolleté-specific photo numeric scale for advanced clinical development of KB301. Jeune Aesthetics expects to align with the FDA on the scale and enroll the first subject in a multi-center, randomized, placebo-controlled Phase 2 study evaluating KB301 for the treatment of dynamic wrinkles of the décolleté in Q4 2025.
KB304 for the treatment of wrinkles

In February, Jeune Aesthetics completed enrollment in PEARL-2, an ongoing, randomized and placebo-controlled Phase 1 study evaluating KB304 for the treatment of wrinkles. Jeune Aesthetics expects to report top-line results from the study in 2H 2025. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT06724900.
Dermatology

KB105 for the treatment of lamellar ichthyosis

The Company expects to initiate the Phase 2 portion of its KB105 Phase 1/2 JADE-1 trial evaluating KB105 for the treatment of TGM1-deficient lamellar ichthyosis in pediatric patients in 2026.
Pipeline expansion

The Company will be presenting preclinical data at the Society for Investigative Dermatology (SID) 2025 Annual Meeting later this week on early-stage dermatology genetic medicine candidates for the treatment of Hailey-Hailey and Darier diseases.
Financial Results for the Quarter Ended March 31, 2025:

Cash, cash equivalents, and investments totaled $765.3 million as of March 31, 2025.
Product revenue, net totaled $88.2 million and $45.3 million for the quarters ended March 31, 2025 and March 31, 2024, respectively.
Cost of goods sold totaled $5.0 million and $2.4 million for the quarters ended March 31, 2025 and March 31, 2024, respectively.
Research and development expenses for the quarter ended March 31, 2025 were $14.3 million, inclusive of $2.5 million of stock-based compensation, compared to $11.0 million, inclusive of stock-based compensation of $1.9 million for the quarter ended March 31, 2024.
Selling, general, and administrative expenses for the quarter ended March 31, 2025 were $32.7 million, inclusive of stock-based compensation of $11.0 million, compared to $26.1 million, inclusive of stock-based compensation of $7.4 million, for the quarter ended March 31, 2024.
Net income for the quarter ended March 31, 2025 was $35.7 million, or $1.24 per common share (basic) and $1.20 per common share (diluted). Net income for the quarter ended March 31, 2024 was $0.9 million, or $0.03 per common share (basic) and $0.03 per common share (diluted).
Financial Guidance

($ in millions) FY 2025 Guidance
Non-GAAP Research and Development ("R&D") and Selling, General and Administrative ("SG&A") expense(1) $150.0 – $175.0

(1) Refer to Non-GAAP Financial Measures section below for additional information. Non-GAAP combined R&D and SG&A expense guidance does not include stock-based compensation as we are currently unable to confidently estimate Full Year 2025 stock-based compensation expense. As such, we have not provided a reconciliation from forecasted non-GAAP to forecasted GAAP combined R&D and SG&A Expense in the above. This could materially affect the calculation of forward-looking GAAP combined R&D and SG&A Expense as it is inherently uncertain.

Conference Call

The Company will host an investor webcast on May 6, 2025, at 8:30 am ET.

Investors and the general public can access the live webcast at:
View Source

For those unable to listen to the live conference call, a replay will be available for 30 days on the Investors section of the Company’s website at www.krystalbio.com.

On May 6, 2025 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported a business update and announced financial results for the first quarter ended March 31, 2025 (Press release, Cogent Biosciences, MAY 6, 2025, View Source [SID1234652601]).

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"The first quarter of 2025 was very productive for Cogent as our team focused on executing across our portfolio in preparation for three transformative data readouts this year. We look forward to reporting top-line results from our registration-directed SUMMIT trial with bezuclastinib in patients with nonadvanced systemic mastocytosis in July, followed later in the year with top-line results from our APEX and PEAK trials," said Andrew Robbins, the Company’s President and Chief Executive Officer. "While we are preparing for a potential launch of bezuclastinib in 2026, we are also very proud of the progress we have made with our early-stage pipeline, including presentations from four distinct programs recently at the annual AACR (Free AACR Whitepaper) conference."

Recent Business Highlights

Announced expanded clinical results from the Open Label Extension (OLE) portion of the Company’s ongoing SUMMIT trial evaluating bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM) at the 2025 American Academy of Allergy Asthma & Immunology Annual Meeting (AAAAI) meeting.
Bezuclastinib showed a 65% mean improvement in Total Symptom Score (TSS) at 48 weeks, including 88% of patients achieving at least a 50% reduction in TSS.
The safety profile for bezuclastinib remains favorable, with adverse events reported primarily as low-grade and reversible. No treatment-related bleeding or cognitive impairment was observed. The most common treatment-related adverse events were hair discoloration and transient elevations in liver transaminases. All cases of elevated transaminases were asymptomatic and fully reversible.
Presented updated preclinical data from the company’s KRAS, PI3Kα, FGFR2/3 and ErbB2 candidates at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting.
Upcoming Milestones

Announce top-line results from SUMMIT in July 2025. SUMMIT is a registration-directed, randomized, double-blind, placebo-controlled, global, multicenter, clinical trial of bezuclastinib in patients with NonAdvSM.
Announce top-line results from APEX in the second half of 2025. APEX is a registration-directed, global, open-label trial in patients with advanced systemic mastocytosis (AdvSM).
Announce top-line results from PEAK by the end of 2025. PEAK is a global, blinded, randomized Phase 3 clinical trial studying the combination of bezuclastinib and sunitinib versus sunitinib alone in patients with imatinib-resistant gastrointestinal stromal tumors (GIST).
First Quarter 2025 Financial Results

Cash and Cash Equivalents: As of March 31, 2025, cash, cash equivalents and marketable securities were $245.7 million. During the quarter, the Company sold shares under the Company’s at-the-market (ATM) stock offering for net proceeds of $24.3 million and incurred a non-recurring payment of $9.6 million related to annual performance-based bonus compensation. Based on its current plans, the Company expects its existing cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into late 2026, including through clinical readouts from ongoing SUMMIT, PEAK, and APEX registration-directed trials.

R&D Expenses: Research and development expenses were $63.0 million for the first quarter of 2025 compared to $52.7 million for the first quarter of 2024. The increase was primarily due to costs incurred to support our on-going SUMMIT, PEAK and APEX clinical trials and to the continued progression of our early stage, preclinical and discovery programs. R&D expenses include non-cash stock compensation expense of $5.3 million for the first quarter of 2025 as compared to $4.4 million for the first quarter of 2024.

G&A Expenses: General and administrative expenses were $11.9 million for the first quarter of 2025 compared to $9.7 million for the first quarter of 2024. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $4.8 million for the first quarter of 2025 as compared to $5.0 million for the first quarter of 2024.

Net Loss: Net loss was $72.0 million for the first quarter of 2025 compared to a net loss of $58.3 million for the first quarter of 2024.

On May 6, 2025 Zetagen Therapeutics, Inc., a private, clinical stage, biopharmaceutical company focused on developing breakthrough therapies, via local administration, for metastatic and primary breast cancers, reported they have successfully completed enrollment in their phase 2a study, which will evaluate ZetaMet (Zeta-BC-003) in the treatment of spinal metastatic lytic breast cancer lesions (ClinicalTrials.gov #NCT05280067) (Press release, Zetagen Therapeutics, MAY 6, 2025, View Source [SID1234652599]).

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"We are excited to reach another critical milestone in the development of ZetaMet (Zeta-BC-003), " said Joe C. Loy, Zetagen’s Chief Executive Officer. "We launched this study with stage IV breast cancer patients suffering from spinal metastases, because we recognize their severe pain and how debilitating it is, and that current treatments remain largely palliative. Our objective with ZetaMet is to eliminate cancer cells responsible for bone destruction, alleviate pain, stimulate the regeneration of bone lost to lytic lesions, enhance overall quality of life, while improving survival rates."

The 26-week study, conducted at the University of British Columbia, (UBC) Vancouver, BC, Canada, will evaluate the safety and efficacy of ZetaMet (Zeta-BC-003) in treating vertebral bone defects created by lytic metastatic breast cancer. The study will measure the reduction of skeletal related events (SRE), pain, change in vertebral body defect size, and postoperative prescribed opioid use. The Company anticipates reporting top-line results early fourth quarter of 2025.

Zetagen expects to submit an Investigation New Drug (IND) application to the U.S. Food and Drug Administration ("FDA"), leveraging its FDA’s Breakthrough designations.

About ZetaMet (Zeta-BC-003)
ZetaMet’s (Zeta-BC-003) small molecule mechanism of action (MOA) via a novel molecular pathway initiates a circuit which results in tumor cell death.

ZetaMet (Zeta-BC-003) is the first-of-its-kind, synthetic, small-molecule delivered via a proprietary controlled-release carrier intended to resolve metastatic breast cancer bone lesions, administered locoregionally, to inhibit pain while regenerating new bone, with the potential to increase survival rates.

The US Food & Drug Administration (FDA) has recognized Zetagen’s discoveries with multiple Breakthrough Designations including ZetaMet (Zeta-BC-003).

Zetagen with FDA and Health Canada (HC) approval via their Expanded Access (Compassionate Use) programs has treated several patients with ZetaMet (Zeta-BC-003) with results published in multiple peer-reviewed journals.

Peer-reviewed 2-year follow up clinical data published in 2023 on ZetaMet (Zeta-BC-003) demonstrated resolution of 7 lytic lesions (radiated and non-radiated), reduction in pain, significant reduction in opioid pain medication (4-fold), prevention of vertebral fracture, and increased survival rate in a patient living with Stage 4 breast cancer.[i] To view this publication via open access, go to: View Source

On May 6, 2025 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, reported its financial results for the quarter ended March 31, 2025 and reaffirmed its financial guidance for 2025 (Press release, Ultragenyx Pharmaceutical, MAY 6, 2025, View Source [SID1234652598]).

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"In the first quarter, our commercial team continued expanding our base of revenue around the world, while we also continued to make successful progress for our next potential launch with the review of our first gene therapy BLA for the treatment of Sanfilippo syndrome (MPS IIIA)," said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. "Patients in the UX143 Phase 3 Orbit and Cosmic studies have now been on therapy for at least 12 months and will support the interim analyses in mid-2025. We continue to hear encouraging feedback from investigators in the Phase 2 portion of Orbit, some with patients on therapy for over 2 years, who noted an excellent risk benefit profile during the open-label Phase 2 portion of the study."

First Quarter 2025 Selected Financial Data Tables and Financial Results

Revenues (dollars in thousands), (unaudited)
Three Months Ended March 31,
2025 2024
Crysvita
Product sales – Latin America and Türkiye $ 55,080 $ 36,241
Royalty revenue – U.S. and Canada 40,853 40,402
Royalty revenue – Europe 6,932 5,942
Total Crysvita Revenue 102,865 82,585
Dojolvi 17,009 16,362
Evkeeza 11,031 3,275
Mepsevii 8,387 6,611
Total revenues $ 139,292 $ 108,833

Total Revenues
Ultragenyx reported $139 million in total revenue for the first quarter of 2025, which represents 28% growth compared to the same period in 2024. First quarter 2025 Crysvita revenue was $103 million, which represents 25% growth compared to the same period in 2024. This includes product sales of $55 million from Latin America and Türkiye, which represents 52% growth compared to the same period in 2024. Dojolvi revenue in the first quarter 2025 was $17 million. Evkeeza revenue in the first quarter 2025 was $11 million as we continue to launch in the Ultragenyx territories outside of the United States.

Selected Financial Data (dollars in thousands, except per share amounts), (unaudited)
Three Months Ended March 31,
2025 2024
Total revenues $ 139,292 $ 108,833
Operating expenses:
Cost of sales 28,662 17,533
Research and development 165,772 178,487
Selling, general and administrative 87,797 78,160
Total operating expenses 282,231 274,180
Net loss $ (151,080 ) $ (170,684 )
Net loss per share, basic and diluted $ (1.57 ) $ (2.03 )

Operating Expenses
Total operating expenses for the first quarter of 2025 were $282 million, including non-cash stock-based compensation of $40 million.

Net Loss
For the first quarter of 2025, Ultragenyx reported net loss of $151 million, or $1.57 per share basic and diluted, compared with a net loss for the first quarter of 2024 of $171 million, or $2.03 per share basic and diluted.

Cash Balance and Net Cash Used in Operations
Cash, cash equivalents, and marketable debt securities were $563 million as of March 31, 2025, which reflects cash payments made during the first quarter of 2025 of $30 million for a GTX-102 Phase 3 study milestone and $15 million for an Evkeeza sales milestone, both achieved in the fourth quarter of 2024. Net cash used in operations for the quarter ended March 31, 2025 was $166 million and includes the payment of annual bonuses and a $30 million cash payment for the GTX-102 development milestone noted above.

2025 Financial Guidance
Ultragenyx reaffirmed its financial guidance for 2025. Revenues are expected to grow approximately 14-20% compared to 2024. The company will continue to prioritize expense management, focusing its investments on the execution of multiple upcoming commercial launches and advancing multiple Phase 3 programs. Together, this is expected to lead to a reduction in 2025 net cash used in operations compared to 2024.

For the full year 2025:

Total revenue to be in the range of $640 million to $670 million
Crysvita revenue to be in the range of $460 million to $480 million
Dojolvi revenue to be in the range of $90 million to $100 million
Recent Updates and Clinical Milestones

UX143 (setrusumab) monoclonal antibody for osteogenesis imperfecta (OI): Next interim analysis for Phase 3 Orbit and Cosmic studies is in mid-2025

Patients continue dosing in the ongoing Phase 3 Orbit and Cosmic clinical trials, which evaluate setrusumab in pediatric and young adult patients with OI. The randomized, placebo-controlled Phase 3 portion of the Orbit study is progressing toward a second interim analysis (IA2) in mid-2025 or a final analysis in the fourth quarter 2025. Conduct of the study is going well and patient safety in the Phase 3 is consistent with the Phase 2. Patients in the Cosmic study also are continuing to be treated with either setrusumab or intravenous bisphosphonates (IV-BP) therapy and will be evaluated in parallel with the Orbit interim analysis. If Orbit progresses to full study completion in the fourth quarter of 2025, Cosmic will also continue to a data readout, to align with the Orbit readout without spending alpha at the mid-year interim assessment.

GTX-102 an antisense oligonucleotide for Angelman syndrome: Phase 3 study is enrolling, expect completion in second half of 2025

Enrollment in the global Phase 3 Aspire study began in December 2024 and is expected to enroll approximately 120 children ages four to 17 with Angelman syndrome with a genetically confirmed diagnosis of full maternal UBE3A gene deletion. Phase 3 study site startup and enrollment are going well. Participants are randomized 1:1 to receive GTX-102 by intrathecal injection via lumbar puncture or to the sham comparator group during the 48-week primary efficacy analysis period. The primary endpoint is improvement in cognition assessed by Bayley-4 cognitive raw score, and the key secondary endpoint (with a 10% allocation of alpha) is the Multi-domain Responder Index (MDRI) across the five domains of cognition, receptive communication, behavior, gross motor function, and sleep. Enrollment in the Phase 3 Aspire study is expected to complete in the second half of 2025.

The Phase 2/3 Aurora study, which will evaluate GTX-102 in other Angelman syndrome genotypes and ages, is expected to initiate in 2025.

UX111 AAV gene therapy for Sanfilippo syndrome type A (MPS IIIA): BLA accepted; U.S. Food and Drug Administration (FDA) granted Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025

In February 2025, the FDA accepted for review the BLA seeking accelerated approval for UX111. The FDA granted the BLA Priority Review with a PDUFA action date of August 18, 2025 and also informed the company that they are not currently planning to hold an advisory committee meeting to discuss this application. The FDA review currently continues to progress as expected with a mid-cycle review recently completed and multiple clinical and manufacturing inspections scheduled and underway. Based on available information, the company continues to expect the FDA to meet its stated timeline with a PDUFA decision on August 18, 2025 that would be followed by a potential launch in the second half of 2025.

DTX401 AAV gene therapy for Glycogen Storage Disease Type Ia (GSDIa): BLA submission expected in mid-2025

As previously disclosed by Ultragenyx in May 2024, the Phase 3 GlucoGene study for the treatment of patients aged eight years and older with GSDIa achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. At Week 48, patients entered a 48-week Crossover Period where patients previously treated with placebo were treated with DTX401. During the Crossover Period, patients demonstrated even greater reductions in total daily cornstarch at their last visit compared to baseline in both the ongoing DTX401 group (-60%) and the Crossover Placebo to DTX401 group (-64%). Glycemic control was maintained in patients treated with DTX401 despite significant reductions in daily cornstarch intake. DTX401 has demonstrated a consistent and acceptable safety profile with no new safety signals identified as of the data cut-off.

Process Performance Qualification (PPQ) runs have been successfully completed in the Company’s U.S. gene therapy manufacturing facility in preparation for upcoming submissions. The latest clinical results and data from PPQ runs will be included as part of a BLA submission expected in mid-2025.

UX701 AAV gene therapy for Wilson Disease: Phase 1/2/3 study ongoing; Cohort 4 enrollment began with completion expected in second half of 2025

Enrollment has begun in the fourth cohort evaluating a 4.0e13 GC/kg dose in the ongoing, dose-finding, stage of the pivotal Cyprus2+ study of UX701 for the treatment of Wilson disease. The company expects to enroll five patients in Cohort 4 who will receive immunomodulation therapy with rituximab and tacrolimus, in addition to the prophylactic oral corticosteroid regimen patients in Cohorts 1 through 3 received, prior to being dosed with UX701. Enrollment in Cohort 4 is expected to complete in the second half of 2025.

The protocol for the pivotal, Stage 2 portion of Cyprus2+ was amended to a 52-week, randomized, open-label, active-controlled design, evaluating the safety and efficacy of UX701 following dose selection in Stage 1. The Stage 2 primary endpoints include comparisons between the UX701 and active control groups of change in 24-hour urinary copper from Baseline at Week 52 and percent reduction in SOC medication by Week 52. Enrollment in this stage is expected following dose selection in Stage 1.

Conference Call and Webcast Information

Ultragenyx will host a conference call today, Tuesday, May 6, 2025, at 2 p.m. PT/5 p.m. ET to discuss the first quarter 2025 financial results and provide a corporate update. The live and replayed webcast of the call will be available through the company’s website at View Source The replay of the call will be available for three months.