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What changed in UroGen Pharma Ltd.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of UroGen Pharma Ltd.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+679 added−674 removedSource: 10-K (2026-03-02) vs 10-K (2025-03-10)

Top changes in UroGen Pharma Ltd.'s 2025 10-K

679 paragraphs added · 674 removed · 497 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

125 edited+53 added−65 removed205 unchanged
Biggest changeCompetition may increase further as a result of advances in the commercial applicability of technologies and greater availability of capital for investment in this industry. Our competitors may succeed in developing, acquiring or licensing on an exclusive basis, products that are more effective, easier to administer or less costly than our product candidates.
Biggest changeOur competitors may succeed in developing, acquiring or licensing on an exclusive basis, products that are more effective, easier to administer or less costly than our product candidates. The standard of care for treating low-grade intermediate risk NMIBC is repeated TURBT procedures. While effective, patients with low-grade intermediate risk NMIBC experience frequent recurrences and repeated surgical procedures.
We believe that these characteristics promote ease of delivery into and retention of drugs in body cavities, including the bladder and the upper urinary tract, forming a transient reservoir of drug that dissolves over time while preventing rapid excretion, providing for increased dwell time. RTGel leverages the physiologic flow of urine to provide a natural exit from the body.
We believe that these characteristics promote ease of delivery into and retention of drugs in body cavities, including the bladder and the upper urinary tract, forming a transient reservoir of drug that dissolves over time while preventing rapid excretion and providing for increased dwell time. RTGel leverages the physiologic flow of urine to provide a natural exit from the body.
Our worldwide intellectual property portfolio includes patents and patent applications filed in many jurisdictions such as the US, Europe, Israel, Japan, Canada, China, Australia and Korea of which are expected to remain in effect until 2043, if allowed: • Hydrogel-based pharmaceutical compositions for optimal delivery of various therapeutic agents to internal cavities such as the bladder and/or urinary tract. • The method for treating bladder cancer, upper urinary tract cancer and urothelial cancer using hydrogel-based compositions. • Proprietary mitomycin formulation for treating bladder cancer, upper urinary tract cancer and urothelial cancer. • The method for treating overactive bladder and interstitial cystitis topically without a need for injections in the bladder wall. • Special catheters and in-dwelling ureter-catheter systems for optimal delivery of a drug into the renal cavity. • Pharmaceutical compositions comprising an imidazoquinolin-amine (specifically imiquimod) for treating bladder cancer diseases. • Composition comprising immunomodulators such as anti-CTLA4 (for example, zalifrelimab) for topical/intravesical administration as a monotherapy or a combo-therapy with immunomodulators or chemotherapy drugs. • Novel phospholipid drug analogs (new chemical entities) for treating cancer or infections. • Hydrogel for removal ureteral and renal stones.
Our worldwide intellectual property portfolio includes patents and patent applications filed in many jurisdictions such as the US, Europe, Israel, Japan, Canada, China, Australia and Korea of which are expected to remain in effect until 2046, if allowed: • Hydrogel-based pharmaceutical compositions for optimal delivery of various therapeutic agents to internal cavities such as the bladder and/or urinary tract. • The method for treating bladder cancer, upper urinary tract cancer and urothelial cancer using hydrogel-based compositions. • Proprietary mitomycin formulation for treating bladder cancer, upper urinary tract cancer and urothelial cancer. • The method for treating overactive bladder and interstitial cystitis topically without a need for injections in the bladder wall. • Special catheters and in-dwelling ureter-catheter systems for optimal delivery of a drug into the renal cavity. • Pharmaceutical compositions comprising an imidazoquinolin-amine (specifically imiquimod) for treating bladder cancer diseases. • Composition comprising immunomodulators such as anti-CTLA4 (for example, zalifrelimab) for topical/intravesical administration as a monotherapy or a combo-therapy with immunomodulators or chemotherapy drugs. • Novel phospholipid drug analogs (new chemical entities) for treating cancer or infections. • Hydrogel for removal ureteral and renal stones.
In addition, under the Pediatric Research Equity Act ("PREA"), an NDA or supplement to an NDA for a new active ingredient, indication, dosage form, dosage regimen or route of administration must contain data that are adequate to assess the safety and efficacy of the drug for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
In addition, under the Pediatric Research Equity Act, an NDA or supplement to an NDA for a new active ingredient, indication, dosage form, dosage regimen or route of administration must contain data that are adequate to assess the safety and efficacy of the drug for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
The median duration of response was not reached. • The most commonly reported adverse events (≥ 20%) were ureteric obstruction, flank pain, urinary tract infection, hematuria, abdominal pain, fatigue, renal dysfunction, nausea, dysuria and vomiting. Most adverse events were mild to moderate and manageable. No treatment-related deaths occurred.
The median duration of response ("DOR") was not reached. • The most commonly reported adverse events (≥ 20%) were ureteric obstruction, flank pain, urinary tract infection, hematuria, abdominal pain, fatigue, renal dysfunction, nausea, dysuria and vomiting. Most adverse events were mild to moderate and manageable. No treatment-related deaths occurred.
Depending on the circumstances, failure to comply with these laws can result in significant penalties, including criminal, civil and administrative penalties, damages, fines, disgorgement, debarment from government contracts, imprisonment, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, exclusion from government programs, refusal to allow us to enter into supply contracts, including government contracts, reputational harm, diminished profits and future earnings and the curtailment or restructuring of our operations, any of which could adversely affect our business. 19 Table of Contents Coverage and Reimbursement Our ability to commercialize any products successfully, including Jelmyto , UGN-102 and our other product candidates, if approved, also will depend in part on the extent to which coverage and adequate reimbursement for our products, once approved, and related treatments will be available from third-party payors, such as government health administration authorities, private health insurers and managed care organizations.
Depending on the circumstances, failure to comply with these laws can result in significant penalties, including criminal, civil and administrative penalties, damages, fines, disgorgement, debarment from government contracts, imprisonment, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, exclusion from government programs, refusal to allow us to enter into supply contracts, including government contracts, reputational harm, diminished profits and future earnings and the curtailment or restructuring of our operations, any of which could adversely affect our business. 19 Table of Contents Coverage and Reimbursement Our ability to commercialize any products successfully, including Jelmyto , Zusduri and our other product candidates, if approved, also will depend in part on the extent to which coverage and adequate reimbursement for our products, once approved, and related treatments will be available from third-party payors, such as government health administration authorities, private health insurers and managed care organizations.
Efficacy of drug treatments has historically been limited due to challenges presented by bladder physiology, specifically the fact that urine is produced and voided frequently, thus diluting the concentration of the drug almost immediately and causing the excretion of the drug from the bladder at first urine voiding.
Efficacy of other drug treatments has historically been limited due to challenges presented by bladder physiology, specifically the fact that urine is produced and voided frequently, thus diluting the concentration of the drug almost immediately and causing the excretion of the drug from the bladder at first urine voiding.
In addition, we have established a customer-facing team that includes territory business managers with deep experience in both urology and oncology. These territory business manager positions are led by eight regional business director positions, who are in turn supported by eight regional operations manager positions.
In addition, we have established a customer-facing team that includes territory business managers with deep experience in both urology and oncology. These territory business manager positions are led by regional business director positions, who are in turn supported by regional operations manager positions.
A subset of low-grade intermediate risk NMIBC patients is at risk for frequent local recurrences. Due to lack of treatment options to reduce recurrences in these patients, they are managed with repeat TURBT for each subsequent recurrence.
A subset of low-grade intermediate risk NMIBC patients is at risk for frequent local recurrences. Due to lack of treatment options to reduce recurrences in these patients, they are typically managed with repeat TURBT for each subsequent recurrence.
We currently rely on third-party contract manufacturers for all of our required raw materials, active ingredients and finished products for Jelmyto and our nonclinical research and clinical trials. We have signed commercial supply agreements for Jelmyto with third-party vendors.
We currently rely on third-party contract manufacturers for all of our required raw materials, active ingredients and finished products for Jelmyto , Zusduri and our nonclinical research and clinical trials. We have signed commercial supply agreements for Jelmyto and Zusduri with third-party vendors.
In addition to patents, we have filed applications for trademark registration with the United States Patent and Trademark Office (the "USPTO"), as well as certain other international jurisdictions for Jelmyto ®, RTGel ® and UroGen ® and for certain other tradenames and logos.
In addition to patents, we have filed applications for trademark registration with the United States Patent and Trademark Office (the "USPTO"), as well as certain other international jurisdictions for Jelmyto ®, Zusduri ™, RTGel ® and UroGen ® and for certain other tradenames and logos.
In seeking approval for a drug through an NDA, including a 505(b)(2) NDA, applicants are required to list patents with the FDA which claims cover the applicant’s product.
In seeking approval for a drug through an NDA, including a 505(b)(2) NDA, applicants are required to list patents with the FDA indicating which claims cover the applicant’s product.
Manufacturing, Supply and Production We do not own or operate manufacturing facilities for the production of Jelmyto or our product candidates, nor do we have plans to develop our own manufacturing operations in the foreseeable future.
Manufacturing, Supply and Production We do not own or operate manufacturing facilities for the production of Jelmyto and Zusduri or our product candidates, nor do we have plans to develop our own manufacturing operations in the foreseeable future.
Jelmyto was also granted Breakthrough Therapy Designation by the FDA, which was created to expedite the development and review of drugs developed for serious or life-threatening conditions with high unmet need. The FDA approval was based on results from our Phase 3 OLYMPUS trial showing Jelmyto achieved clinically significant disease eradication in adults with low-grade UTUC.
Jelmyto was also granted Breakthrough Therapy Designation by the FDA, which was created to expedite the development and review of drugs developed for serious or life-threatening conditions with high unmet need. The FDA approval was based on results from UroGen's Phase 3 Olympus trial showing Jelmyto achieved clinically significant disease eradication in adults with low-grade UTUC.
Our expertise has enabled us to develop proprietary RTGel -based formulations for previously approved drugs and drugs in clinical development, including clinical-stage proprietary formulations of mitomycin and zalifrelimab.
Our expertise has enabled us to develop proprietary RTGel -based formulations for previously approved drugs and drugs in clinical development, including clinical-stage proprietary formulations of mitomycin.
Our technology is designed to enable longer exposure of the urinary tract tissue to medications, making local therapy a potentially more effective treatment option.
Our technology is designed to enable longer exposure of urinary tract tissue to medications, making local therapy a potentially more effective treatment option.
Our sales force is focused on promoting Jelmyto, and educating potential prescribers to identify patients, activate accounts and gain formulary access, as applicable.
Our sales force is focused on promoting Jelmyto and Zusduri , and educating potential prescribers to identify patients, activate accounts and gain formulary access, as applicable.
Findings from the final study results include: • Complete response (“CR”) (primary endpoint) of 58% (41/71) in the intent-to-treat population and in the sub-population of patients who were deemed not capable of surgical removal at diagnosis. • At the 12-month time point for assessment of durability, 23 patients remained in CR of a total of 41 patients, eight had experienced recurrence of disease and 10 patients were unable to be evaluated. • Durability of response was estimated to be 81.8% at 12 months by Kaplan-Meier analysis.
Findings from the final study results include: • Complete response (“CR”) rate (primary endpoint) of 58% (41/71) in the intent-to-treat population and in the sub-population of patients who were deemed not capable of surgical removal at diagnosis. • At the 12-month time point for assessment of durability, 23 patients remained in CR of a total of 41 patients, eight had experienced recurrence of disease and ten patients were unable to be evaluated. • Durability of response was estimated to be 81.8% at 12 months by Kaplan-Meier analysis.
Up to 70% of NMIBC patients experience at least one recurrence and low-grade intermediate risk NMIBC patients are even more likely to recur and face repeated TURBT procedures. Multiplicity, or number of tumors, tumor size and prior recurrence rate are the most important variables in determining the likelihood and potential severity of recurrence.
Up to 70% of NMIBC patients experience at least one recurrence and low-grade intermediate risk NMIBC patients are even more likely to recur and face repeated TURBT procedures. Focality, or number of tumors, tumor size and prior recurrence rate are the most important variables in determining the likelihood and potential severity of recurrence.
These characteristics of RTGel enable sustained release of mitomycin in the urinary tract for Jelmyto, UGN-102, UGN-103 and UGN-104. Further, RTGel may be particularly effective in the bladder and upper urinary tract where tumor visibility and access are challenging, and where there exists a significant amount of urine flow and voiding.
These characteristics of RTGel enable sustained release of mitomycin in the urinary tract for Jelmyto, Zusduri , UGN-103 and UGN-104. Further, RTGel may be particularly effective in the bladder and upper urinary tract where tumor visibility and access are challenging, and where there exists a significant amount of urine flow and voiding.
The 18-month DOR by Kaplan-Meier estimate for patients who achieved a CR at three months after the first instillation of UGN-102 remained consistent with the 12-month DOR data: 80.6% (95% CI, 74.0%, 85.7%) at 18-months (n=101) compared to 82.5% (76.1%, 87.3%) at 12-months (n=146). Median follow-up time was 18.7 months after the 3-month CR.
The 18-month DOR by Kaplan-Meier estimate for patients who achieved a CR at three months after the first instillation of Zusduri remained consistent with the 12-month DOR data: 80.6% (95% CI, 74.0%, 85.7%) at 18-months (n=101) compared to 82.5% (76.1%, 87.3%) at 12-months (n=146). Median follow-up time was 18.7 months after the three-month CR.
Limitations of Current Therapies for High-Grade NMIBC Six drugs have been approve d for high-grade NMIBC, all used as adjuvant treatment: Thiotepa, which was approved in 1959, and is no longer used in practice; BCG, which was approved in 1989; Valstar® (valrubicin), which was approved in 1998; Keytruda® (pembrolizumab), which was approved by the FDA in 2020; Adstiladrin® (nadofaragene firadenovec-vncg), which was approved by the FDA in 2022 for BCG unresponsive carcinoma in situ ("CIS") and Anktiva® (nogapendekin alfa inbakicept-pmln) in combination with BCG, which was approved by the FDA in 2024 for BCG unresponsive CIS.
Limitations of Current Therapies for High-Grade NMIBC Seven drugs have been approve d for high-grade NMIBC, all used as adjuvant treatment: Thiotepa, which was approved in 1959, and is no longer used in practice; BCG, which was approved in 1989; Valstar® (valrubicin), which was approved in 1998; Keytruda® (pembrolizumab), which was approved by the FDA in 2020; Adstiladrin® (nadofaragene firadenovec-vncg), which was approved by the FDA in 2022 for BCG unresponsive carcinoma in situ ("CIS"), Anktiva® (nogapendekin alfa inbakicept-pmln) in combination with BCG, which was approved by the FDA in 2024 for BCG-unresponsive CIS, and INLEXZO™, which was approved by the FDA in 2025 for BCG-unresponsive NMIBC.
We believe that the resulting significantly increased dwell time of mitomycin in the bladder prolongs exposure of mitomycin to the tumor tissue and therefore has the potential to chemoablate both visible and undetectable tumors. With regard to UGN-102, we own three issued U.S. patents and two issued patents in Europe. These issued patents are expected to expire in 2031.
We believe that the resulting significantly increased dwell time of mitomycin in the bladder prolongs exposure of mitomycin to the tumor tissue and therefore has the potential to chemoablate both visible and undetectable tumors. With regard to Zusduri , we own three issued U.S. patents and two issued patents in Europe. These issued patents are expected to expire in 2031.
Moreover, we filed two new U.S. patent applications with the USPTO, that relate to compositions comprising UGN-102 and for the method of treating bladder cancer. Bladder Cancer The bladder is a hollow organ in the pelvis with flexible muscular walls. Its main function is to store urine before it leaves the body.
Moreover, we filed two new U.S. patent applications with the USPTO, that relate to compositions comprising Zusduri and for the method of treating bladder cancer. Bladder Cancer The bladder is a hollow organ in the pelvis with flexible muscular walls. Its main function is to store urine before it leaves the body.
We may negotiate additional commercial supply agreements for our product candidates UGN-102, UGN-103, UGN-104, UGN-201 and UGN-301, or other back-up supply agreements with other third-party manufacturers for the commercial production of any of our product candidates that receives regulatory approval. 21 Table of Contents Development and commercial quantities of any products that we develop will need to be manufactured in facilities, and by processes, that comply with the requirements of the FDA and the regulatory agencies of other jurisdictions in which we are seeking approval.
We may negotiate additional commercial supply agreements for our product candidates UGN-103, UGN-104 and UGN-501, or other back-up supply agreements with other third-party manufacturers for the commercial production of any of our product candidates that receives regulatory approval. 21 Table of Contents Development and commercial quantities of any products that we develop will need to be manufactured in facilities, and by processes, that comply with the requirements of the FDA and the regulatory agencies of other jurisdictions in which we are seeking approval.
This results in: • protecting our product candidates that are under development; • encouraging pharmaceutical companies to negotiate development agreements with us; and • preventing competitors from attempting to design-around our inventions. Competition We are developing products for patients with low-grade UTUC, low-grade NMIBC and high-grade NMIBC.
This results in: • protecting our product candidates that are under development; • encouraging pharmaceutical companies to negotiate development agreements with us; and • preventing competitors from attempting to design-around our inventions. Competition We are developing products for patients with low-grade UTUC, recurrent low-grade intermediate risk NMIBC and high-grade NMIBC.
Mitomycin — Our Target Active Drug for the Treatment of Low-Grade UTUC and Low-Grade Intermediate Risk NMIBC Mitomycin is a generic drug currently utilized off-label as an adjuvant chemotherapy for the treatment of low-grade NMIBC after trans-urethral resection of bladder tumor ("TURBT").
Mitomycin — Our Drugs for the Treatment of Low-Grade UTUC and Low-Grade Intermediate Risk NMIBC Mitomycin is a generic drug currently utilized off-label as an adjuvant chemotherapy for the treatment of low-grade NMIBC after trans-urethral resection of bladder tumor ("TURBT").
We estimate, based upon a review of peer-reviewed and publicly available data, an addressable population of low-grade intermediate risk NMIBC patients of approximately 82,000 in the U.S. annually. Limitations of Current Therapies for Low-Grade Non-Muscle Invasive Bladder Cancer Recurrence is the primary threat for patients with low-grade NMIBC.
We estimate, based upon a review of peer-reviewed and publicly available data, an addressable population of low-grade intermediate risk NMIBC patients of approximately 82,000 in the United States annually. Limitations of Current Therapies for Low-Grade Non-Muscle Invasive Bladder Cancer Recurrence is the primary threat for patients with low-grade NMIBC.
Adjuvant intravesical chemotherapy is used in low-grade tumors following TURBT in order to try to delay tumor recurrence but is not used as a chemoablation agent. The rationale is to expose tumors to high local drug concentrations while minimizing the systemic exposure, thereby enhancing the treatment effect and reducing the drug toxicity.
Adjuvant intravesical chemotherapy is used in low-grade tumors following TURBT in order to try to delay tumor recurrence but is not used as a primary chemoablation agent. The rationale for intravesical administration of chemotherapy is to expose tumors to high local drug concentrations while minimizing the systemic exposure, thereby enhancing the treatment effect and reducing the drug toxicity.
Each region is additionally supported by one to two clinical nurse educators to provide education and training around instillation, as well as a field reimbursement manager to help ensure access and reimbursement for appropriate patients and key account directors who engage with C-suite individuals to introduce a Jelmyto service line.
Each region is additionally supported by clinical nurse educators to provide education and training around instillation, as well as field reimbursement managers to help ensure access and reimbursement for appropriate patients and key account directors who engage with C-suite individuals to introduce a Jelmyto service line.
Streamlined development risks and efficiencies for our pipeline product candidates. Jelmyto was approved with the FDA’s 505(b)(2) regulatory pathway, which provides a streamlined, capital efficient pathway when compared to traditional drug development. We also expect to use the 505(b)(2) regulatory pathway for UGN-102, UGN-103 and UGN-104.
Streamlined development risks and efficiencies for our pipeline product candidates. Jelmyto and Zusduri were approved with the FDA’s 505(b)(2) regulatory pathway, which provides a streamlined, capital efficient pathway when compared to traditional drug development. We also expect to use the 505(b)(2) regulatory pathway for UGN-103 and UGN-104.
The ENVISION trial data was published online in The Journal of Urology in October 2024 and was included in the February 2025 print edition. In March 2025, we announced updated 18-month DOR data from the Phase 3 ENVISION trial.
The ENVISION trial data were published online in The Journal of Urology in October 2024 and were included in the February 2025 print edition. In March 2025, we announced 18-month DOR data from the Phase 3 ENVISION trial.
In addition, we have a registered trademark in the U.S. covering a stylized design of our UroGen Pharmaceutical logo. 11 Table of Contents Furthermore, we rely upon trade secrets, know-how and continuing technological innovation to develop and maintain our competitive position.
In addition, we have a registered trademark in the United States covering a stylized design of our UroGen Pharmaceutical logo. 11 Table of Contents Furthermore, we rely upon trade secrets, know-how and continuing technological innovation to develop and maintain our competitive position.
BCG was approved by the FDA in 1989, and since its approval, only four other drugs have been approved for high-grade NMIBC: Valstar, approved by the FDA in 1998; Keytruda, approved by the FDA in 2020; Adstiladrin, approved by the FDA in 2022 for BCG unresponsive CIS; and Anktiva, approved by the FDA in 2024, in combination with BCG for BCG unresponsive CIS.
BCG was approved by the FDA in 1989, and since its approval, only five other drugs have been approved for high-grade NMIBC: Valstar, approved by the FDA in 1998; Keytruda, approved by the FDA in 2020; Adstiladrin, approved by the FDA in 2022 for BCG unresponsive CIS; Anktiva, approved by the FDA in 2024, in combination with BCG for BCG-unresponsive CIS, and INLEXZO, approved by the FDA in 2025 for BCG-unresponsive NMIBC.
We focus on developing proprietary RTGel formulations of previously approved drugs and novel therapeutics which we are investigating, whose efficacy for a particular indication is limited by current formulations or routes of administration.
Expertise in developing proprietary formulations of drugs for clinical benefit. We focus on developing proprietary RTGel formulations of previously approved drugs and novel therapeutics which we are investigating, whose efficacy for a particular indication is limited by current formulations or routes of administration.
Under the goals and policies agreed to by the FDA under the PDUFA, the FDA has set the review goal of 10 months from the 60-day filing date to complete its initial review of a standard NDA for a New Molecular Entity ("NME") and make a decision on the application.
Under the goals and policies agreed to by the FDA under the Prescription Drug User Fee Act ("PDUFA"), the FDA has set the review goal of 10 months from the 60-day filing date to complete its initial review of a standard NDA for a New Molecular Entity ("NME") and make a decision on the application.
In addition, we may out-license some or all of our worldwide patent rights to more than one party to achieve the fullest development, marketing and distribution of any products we develop. Employees As of January 31, 2025, we had 235 employees worldwide, 195 in the United States and 40 in Israel, many of whom hold advanced degrees.
In addition, we may out-license some or all of our worldwide patent rights to more than one party to achieve the fullest development, marketing and distribution of any products we develop. Employees As of January 31, 2026, we had 291 employees worldwide, 251 in the United States and 40 in Israel, many of whom hold advanced degrees.
These patents were listed in the FDA's Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations). 4 Table of Contents The FDA evaluated the Jelmyto NDA under Priority Review, which is reserved for medicines that may represent significant improvements in safety or efficacy in treating serious conditions.
These patents are listed in the FDA's Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations). The FDA evaluated the Jelmyto NDA under Priority Review, which is reserved for medicines that may represent significant improvements in safety or efficacy in treating serious conditions.
We estimate based upon a review of peer-reviewed and publicly available data that there are approximately 18,700 BCG-unresponsive patients in the U.S. annually.
We estimate based upon a review of peer-reviewed and publicly available data that there are approximately 18,700 BCG-unresponsive patients in the United States annually.
It will provide more flexibility to add study arms as the trial progresses and is expected to increase efficiency and potentially reduce costs. We expect the Master Protocol will allow us to more quickly evaluate safety, tolerability and dosing of UGN-301 in combination with additional immunomodulators and chemotherapies, with the goal of developing optimized treatment regimens for patients.
It provided more flexibility to add study arms as the trial progressed to increase efficiency and potentially reduce costs. We expected the Master Protocol would allow us to more quickly evaluate safety, tolerability and dosing of UGN-301 in combination with additional immunomodulators and chemotherapies, with the goal of developing optimized treatment regimens for patients.
These patents claim methods, combination products and novel compositions for treating different diseases, especially cancer in internal cavities, in particular urinary tract cancer. Our issued patents are set to expire between 2025 and 2041, and our patent applications, if issued, are set to expire between 2031 and 2043.
These patents claim methods, combination products and novel compositions for treating different diseases, especially cancer in internal cavities, in particular urinary tract cancer. Our issued patents are set to expire between 2026 and 2044, and our patent applications, if issued, are set to expire between 2031 and 2046.
In March 2022, we announced FDA clearance of our IND to begin a novel Phase 1 clinical study of UGN-301 in patients with recurrent NMIBC. The novel study design utilizes a Master Protocol that we believe is a more efficient and streamlined approach to development.
In March 2022, we announced FDA clearance of our IND to begin a novel Phase 1 clinical study of UGN-301 in patients with recurrent NMIBC. The novel study design utilized a Master Protocol that we believed would be a more efficient and streamlined approach to development.
Increased dwell time, facilitated by our RTGel preparations Jelmyto, UGN-102, UGN-103 and UGN-104, is designed to increase cell killing in vitro when compared to aqueous solutions of mitomycin. 3 Table of Contents Our Pipeline The following chart summarizes the current status of our pipeline: Jelmyto Jelmyto is our novel sustained-release RTGel -based formulation of mitomycin that we have developed for the treatment of low-grade UTUC.
Increased dwell time, facilitated by our RTGel preparations Jelmyto, Zusduri , UGN-103 and UGN-104, is designed to increase cell killing in vitro when compared to aqueous solutions of mitomycin. 3 Table of Contents Our Approved Products Jelmyto Jelmyto is our novel sustained-release RTGel -based formulation of mitomycin that we have developed for the treatment of low-grade UTUC.
In April 2024, we announced that the FDA accepted our Investigational New Drug Application ("IND") for UGN-103 and we initiated our Phase 3 UTOPIA trial, a single-arm, multicenter study that will evaluate the efficacy and safety of UGN-103 in low-grade intermediate risk NMIBC.
In April 2024, we announced that the FDA accepted our Investigational New Drug Application (“IND”) for UGN-103 and we initiated our Phase 3 UTOPIA trial, a single-arm, multicenter study evaluating the efficacy and safety of UGN-103 in patients with recurrent low-grade intermediate risk NMIBC.
Furthermore, Jelmyto and UGN-201 have received Orphan Drug Designation from the FDA for the treatment of low-grade UTUC and CIS, respectively, which provides seven years of regulatory exclusivity following FDA approval. Leverageable proprietary formulation technology. We believe that RTGel has multiple potential applications beyond urology.
Furthermore, Jelmyto has received Orphan Drug Designation from the FDA for the treatment of low-grade UTUC, which provides seven years of regulatory exclusivity following FDA approval. Leverageable proprietary formulation technology. We believe that RTGel has multiple potential applications within urology.
Our Solution: UGN-301 (zalifrelimab) intravesical solution We are exploring the use of immunotherapy for the treatment of high-grade NMIBC and have pursued a series of nonclinical studies to determine whether our proprietary RTGel technology might provide a method for delivering highly potent immunomodulators directly to the bladder surface, thereby avoiding toxicity associated with systemic administration.
We explored the use of immunotherapy for the treatment of high-grade NMIBC, and pursued a series of nonclinical studies to determine whether our proprietary RTGel technology might provide a method for delivering highly potent immunomodulators directly to the bladder surface thereby avoiding toxicity associated with systemic administration.
In practice, in the U.S., adjuvant chemotherapy in this setting is only used in 0-30% of the eligible population. 6 Table of Contents No drugs have been approved by the FDA for the primary treatment of low-grade NMIBC. Mitomycin is the drug used most often for intravesical chemotherapy in this patient population.
In practice, in the U.S., adjuvant chemotherapy in this setting is only used in 0-30% of the eligible population. Prior to Zusduri no drugs had been approved by the FDA for the primary treatment of low-grade NMIBC. Mitomycin is the drug used most often for intravesical chemotherapy in this patient population.
In total, our IP portfolio includes 45 granted patents worldwide and more than 45 pending patent applications filed in the US, Europe, Israel, Japan, Canada, China, Australia and Korea.
In total, our IP portfolio includes 54 granted patents worldwide and more than 13 pending patent applications filed in the United States, Europe, Israel, Japan, Canada, China, Australia and Korea.
Post-operative adjuvant treatments for low-grade NMIBC, which are given to prevent reimplantation of the cancerous cells, consist primarily of chemotherapy in the case of low-grade tumors and immunotherapy in the case of high-grade tumors, and are administered intravesically via catheter.
Post-operative adjuvant treatments for low-grade NMIBC, which are given to reduce the risk of recurrence, consist primarily of chemotherapy in the case of low-grade tumors and immunotherapy in the case of high-grade tumors, and are administered intravesically via catheter.
Each region is additionally supported by one to two clinical nurse educators to provide education and training around instillation, as well as a field reimbursement manager to help ensure access and reimbursement for appropriate patients and a key account director who engages with C-suite individuals to introduce a Jelmyto service line.
Each region is additionally supported by clinical nurse educators to provide education and training around instillation, as well as field reimbursement managers to help ensure access and reimbursement for appropriate patients and key account directors who engage with C-suite individuals to introduce a Jelmyto and/or Zusduri service line.
We have implemented processes to help make Jelmyto preparation and administration seamless for practitioners and patients, including entering into agreements with various national, regional and local specialty pharmacies under which the pharmacy, following receipt of a patient prescription, prepares and dispenses the Jelmyto admixture on our behalf.
In addition to reimbursement and access, we have also implemented processes to help make Jelmyto preparation and administration seamless for practitioners and patients, including entering into agreements with various national, regional and local mixing pharmacies under which the pharmacy, following receipt of a patient prescription, prepares and dispenses the Jelmyto admixture.
Refunds are based on the discarded volume above 10% of the total allowed amount. However, in unique circumstances, CMS will increase the applicable threshold to 35%. At this time, CMS has determined that Jelmyto fits within this unique circumstance classification.
Refunds are based on the discarded volume above 10% of the total allowed amount. However, in unique circumstances, CMS will increase the applicable threshold to 35%. At this time, CMS has determined that Jelmyto and Zusduri fit within this unique circumstance classification. We do not expect Zusduri to exceed the applicable 35% threshold.
In addition, our organization currently includes several medical science liaisons who appropriately engage with physicians interested in learning more about UroGen, Jelmyto and our technology, both in person and virtually. In total, our customer-facing team comprises approximately 100 representatives.
In addition, our organization includes medical science liaisons who appropriately engage with physicians interested in learning more about UroGen, our products Jelmyto and Zusduri and our technology, both in person and virtually. In total, our customer-facing team comprises approximately 150 colleagues.
We have a robust intellectual property portfolio that includes 45 granted patents worldwide and more than 45 pending patent applications filed in the US, Europe, Israel, Japan, Canada, China, Australia and Korea.
Strong intellectual property position. We have a robust intellectual property portfolio that includes 54 granted patents worldwide and more than 13 pending patent applications filed in the United States, Europe, Israel, Japan, Canada, China, Australia and Korea.
As noted earlier, companies are required as part of the NDA submission process to list patents with the FDA whose claims cover the applicant’s product. Accordingly, we have listed two patents for Jelmyto in the FDA’s Orange Book upon approval of Jelmyto for commercial sale, as part of the NDA process.
As noted earlier, companies are required as part of the NDA submission process to list patents with the FDA whose claims cover the applicant’s product. We have listed three patents for Jelmyto in the FDA’s Orange Book. In addition, we have four patents for Zusduri in the FDA's Orange Book.
Preliminary results were reported through a press release in February 2023, finding that UGN-102 was suitable to administer at home by a visiting nurse under the supervision of a treating physician and resulted in 75% of patients achieving a CR, defined as no detectable disease three months after starting treatment. Patients, nurses and investigators also completed home instillation feasibility questionnaires.
Preliminary results were reported through a press release in February 2023, finding that Zusduri was suitable to administer at home by a home health professional under the supervision of a treating physician and resulted in 75% of patients achieving a CR, defined as no detectable disease three months after starting treatment.
(“medac”) to develop UGN-103 and UGN-104, which are intended to be next-generation formulations of UGN-102 and Jelmyto , respectively, that combine medac’s proprietary 80 mg mitomycin formulation with our RTGel technology, which we believe will provide advantages related to production, cost, supply and product convenience. Medac has intellectual property protection for its proprietary mitomycin formulation technology expected through June 2035.
(“medac”) to develop UGN-103 and UGN-104, which are intended to be next-generation investigational formulations of Zusduri and Jelmyto , respectively, that combine medac’s proprietary 80 mg mitomycin formulation with our RTGel technology, which we believe will provide advantages related to production, cost, supply and product convenience.
Loss of our New Technology APC may result in Medicare beneficiaries losing access to Jelmyto in the hospital outpatient setting and Jelmyto becoming packaged into a comprehensive APC. Additionally, coverage policies and reimbursement rates may change at any time.
Loss of our New Technology APC may result in Medicare beneficiaries losing access to Jelmyto in the hospital outpatient setting and Jelmyto becoming packaged into a comprehensive APC.
Patients with low-grade intermediate risk NMIBC have frequent recurrences of disease that can be difficult to control using contemporary standards of care. 5 Table of Contents Low Grade Intermediate Risk Non-Muscle Invasive Bladder Cancer NMIBC can be characterized as low, intermediate, or high risk, which is determined based on tumor grade and stage.
Non-muscle invasive bladder cancer ("NMIBC") can then be characterized as low, intermediate, or high risk and can also be characterized as low- or high-grade. Patients with low-grade intermediate risk NMIBC have frequent recurrences of disease that can be difficult to control using contemporary standards of care.
Our approved product Jelmyto ® (mitomycin) for pyelocalyceal solution, and our investigational candidates, UGN-102 (mitomycin) for intravesical solution, UGN-103 (mitomycin) for intravesical solution and UGN-104 (mitomycin) for pyelocalyceal solution, are designed to ablate tumors by non-surgical means and to treat several forms of non-muscle invasive urothelial cancer, including low-grade upper tract urothelial cancer (“low-grade UTUC”) in the case of Jelmyto and UGN-104 and low-grade intermediate risk non-muscle invasive bladder cancer (“low-grade intermediate risk NMIBC”) in the case of UGN-102 and UGN-103.
Our approved products Jelmyto (mitomycin) for pyelocalyceal solution and Zusduri (mitomycin) for intravesical solution are designed to ablate tumors by non-surgical means and to treat several forms of non-muscle invasive urothelial cancer, including low-grade upper tract urothelial cancer (“low-grade UTUC”) and recurrent low-grade intermediate risk non-muscle invasive bladder cancer (“low-grade intermediate risk NMIBC”), respectively.
("Agenus"), pursuant to which Agenus granted us an exclusive, worldwide (not including Argentina, Brazil, Chile, Colombia, Peru, Venezuela and their respective territories and possessions), royalty-bearing, sublicensable license under Agenus’s intellectual property rights to develop, make, use, sell, import, and otherwise commercialize products incorporating a proprietary monoclonal antibody of Agenus known as AGEN1884 (zalifrelimab), an anti-CTLA-4 antagonist, for the treatment of cancers of the urinary tract via intravesical delivery.
We do not expect to incur significant additional costs related to this program going forward. 8 Table of Contents License and Acquisition Agreements Agenus Agreement In November 2019, we entered into a license agreement with Agenus, pursuant to which Agenus granted us an exclusive, worldwide (not including Argentina, Brazil, Chile, Colombia, Peru, Venezuela and their respective territories and possessions), royalty-bearing, sublicensable license under Agenus’s intellectual property rights to develop, make, use, sell, import, and otherwise commercialize products incorporating a proprietary monoclonal antibody of Agenus known as AGEN1884 (zalifrelimab), an anti-CTLA-4 antagonist, for the treatment of cancers of the urinary tract via intravesical delivery.
Our experience to date has demonstrated coverage with CMS and commercial payors for Jelmyto , and we have established written policies with certain commercial providers. For example, in October 2020, a Medicare C-Code was issued for Jelmyto . CMS has established a permanent and product-specific J-code for Jelmyto that took effect on January 1, 2021.
Our experience to date has demonstrated coverage with CMS and commercial payors for Jelmyto , and we have established written policies with certain commercial providers. For example, in October 2025, Zusduri was assigned a unique, permanent J-code, which became effective on January 1, 2026. For Jelmyto, a Medicare C-Code was issued in October 2020.
UGN-103 (mitomycin) for intravesical solution and UGN-104 (mitomycin) for pyelocalyceal solution In January 2024, we entered into a licensing and supply agreement with medac Gesellschaft für klinische Spezialpräparate m.b.H.
Our Pipeline The following chart summarizes the current status of our pipeline: 6 Table of Contents UGN-103 (mitomycin) for intravesical solution and UGN-104 (mitomycin) for pyelocalyceal solution In January 2024, we entered into a licensing and supply agreement with medac Gesellschaft für klinische Spezialpräparate m.b.H.
Investors should contact us for any inquiries through the address and telephone number of our principal executive office. We maintain a web site at www.urogen.com. The reference to our website is an inactive textual reference only and the information contained in, or that can be accessed through, our website is not incorporated into this Annual Report.
We maintain a web site at www.urogen.com. The reference to our website is an inactive textual reference only and the information contained in, or that can be accessed through, our website is not incorporated into this Annual Report.
In addition, our organization currently includes several medical science liaisons who appropriately engage with physicians interested in learning more about UroGen, Jelmyto and our technology, both in person and virtually. In total, our customer-facing team comprises approximately 100 representatives. We are committed to helping patients access Jelmyto .
In addition, our organization includes medical science liaisons who appropriately engage with physicians interested in learning more about UroGen, Jelmyto and our technology, both in person and virtually. In total, our customer-facing team comprises approximately 150 colleagues. We are committed to helping patients access Jelmyto . Our market access teams have laid the foundation for coverage and reimbursement.
Radical cystectomy, or surgical removal of the bladder, is strongly advocated in patients with BCG-unresponsive NMIBC (i.e., patients with BCG-refractory and BCG-relapsing tumors in whom further BCG therapy is not recommended) or for patients who cannot tolerate BCG.
However, the high rates of recurrence and significant risk of progression to muscle-invasive tumors are particularly dangerous. Radical cystectomy, or surgical removal of the bladder, is strongly advocated in patients with BCG-unresponsive NMIBC (i.e., patients with BCG-refractory and BCG-relapsing tumors in whom further BCG therapy is not recommended) or for patients who cannot tolerate BCG.
For example, in March 2010, the ACA was passed, which has changed health care financing by both governmental and private insurers and significantly affected the U.S. pharmaceutical industry.
For example, in March 2010, the ACA was passed, which has changed health care financing by both governmental and private insurers and significantly affected the U.S. pharmaceutical industry. There have been judicial and Congressional challenges, as well as certain aspects of the ACA.
UGN-102 is administered locally using the standard practice of intravesical instillation directly into the bladder via a catheter. The instillation into the bladder is expected to take place in a physician’s office as a non-operative outpatient treatment, in comparison with TURBT or similar surgical procedures, which are operations often conducted under general anesthesia and may require an overnight stay.
The instillation into the bladder is expected to take place in a physician’s office as a non-operative outpatient treatment, in comparison with TURBT or similar surgical procedures, which are operations usually conducted in an operating room under general anesthesia and may require an overnight stay.
Limitations of Other Treatments for Low-Grade Upper Tract Urothelial Carcinoma Before the approval of Jelmyto in April 2020, there were no drugs approved by the FDA for the treatment of low-grade UTUC, representing a significant unmet medical need.
Limitations of Other Treatments for Low-Grade Upper Tract Urothelial Carcinoma Before the approval of Jelmyto in April 2020, there were no drugs approved by the FDA for the treatment of low-grade UTUC, representing a significant unmet medical need. Currently, low-grade UTUC is frequently managed with radical nephroureterectomy ("RNU"), which is complete kidney and upper urinary tract removal.
It is used off-label as an adjuvant treatment in the post-operative setting for low-grade tumors with high risk of recurrence. Other drugs that have been used off-label include docetaxel and gemcitabine. Our Solution: UGN-102 (Mitomycin) for Intravesical Solution UGN-102 is our sustained-release formulation of mitomycin that we are developing for the treatment of low-grade intermediate risk NMIBC.
It is used off-label as an adjuvant treatment in the post-operative setting for low-grade tumors with high risk of recurrence. Other drugs that have been used off-label include docetaxel and gemcitabine.
Certain state and local laws also require the registration of pharmaceutical sales representatives. Enforcement actions can be brought by federal or state governments or, in some cases, as “qui tam” actions brought by individual whistleblowers in the name of the government.
Enforcement actions can be brought by federal or state governments or, in some cases, as “qui tam” actions brought by individual whistleblowers in the name of the government.
RTGel ’s components are polymer-based and are inactive ingredients that are used in U.S. Food and Drug Administration (“FDA”) approved Jelmyto . We formulate RTGel with an active drug: mitomycin in the case of Jelmyto and UGN-102.
RTGel ’s components are polymer-based and are inactive ingredients that are used in our FDA approved products, Jelmyto and Zusduri . We formulate RTGel with an active drug: mitomycin in the case of Jelmyto and Zusduri .
The applicant may also elect to submit a statement certifying that its proposed label does not contain, or carves out, any language regarding the patented method-of-use rather than certify to a listed method-of-use patent. On February 25, 2024, we received a Paragraph IV Certification Notice Letter from Teva Pharmaceuticals, Inc.
The applicant may also elect to submit a statement certifying that its proposed label does not contain, or carves out, any language regarding the patented method-of-use rather than certify to a listed method-of-use patent.
We are a company organized under the laws of State of Israel. We were formed in 2004 with an indefinite duration. We are registered with the Israeli Registrar of Companies. Our principal executive offices are located at 400 Alexander Park Drive, 4 th Floor, Princeton, NJ 08540. Our telephone number is (646)768-9780.
We were formed in 2004 with an indefinite duration. We are registered with the Israeli Registrar of Companies. Our principal executive offices are located at 400 Alexander Park Drive, 4 th Floor, Princeton, NJ 08540. Our telephone number is (646)768-9780. Investors should contact us for any inquiries through the address and telephone number of our principal executive office.
Tumors are graded as low or high (approximately 70% of NMIBC patients have a tumor that is classified as low-grade). Low-grade intermediate risk NMIBC is defined as having one or two of following characteristics: a tumor larger than 3 cm, multiple tumors in the bladder and a recurrence in less than one year from the prior tumor.
Low-grade intermediate risk NMIBC is defined in the Zusduri development program as having one or two of the following characteristics: a tumor larger than 3 cm, multiple tumors in the bladder and a recurrence in less than one year from the prior tumor. The standard of care for treating low-grade intermediate risk NMIBC patients is TURBT.
CMS granted Jelmyto a New Technology APC, effective from October 1, 2023. A service is separately paid for under a New Technology APC until sufficient claims data have been collected to allow CMS to assign the procedure to a clinical APC group that is appropriate in clinical and resource terms.
A service is separately paid for under a New Technology APC until sufficient claims data have been collected to allow CMS to assign the procedure to a clinical APC group that is appropriate in clinical and resource terms. This generally occurs within two to three years from the time a new HCPCS code becomes effective.
In the United States, we currently have 18 granted unexpired patents that are directed to protect our approved product, Jelmyto and our lead product candidate, UGN-102, a proprietary RTGel technology, various local compositions comprising different active ingredients, including, inter alia, compositions comprising a Botulinum Toxin, UGN-201, UGN-301, the use of UGN-201 and UGN-301 and our other product candidates in development, including UGN-103 and UGN-104 that are under company research.
In the United States, we currently have 19 granted unexpired patents that are directed to protect our approved products, Jelmyto and Zusduri , a proprietary RTGel technology, various local compositions comprising different active ingredients, including, among others, our potential product candidates in development, UGN-103, UGN-104 and UGN-501 that are under company research.
We are aware of several pharmaceutical companies that are developing drugs in the fields of urology and uro-oncology, such as AADi LLC, Aura Biosciences, Inc., Biocancell Ltd., Bristol Myers Squibb, CG Oncology Inc., enGene Holdings, Ferring Pharmaceuticals, FKD Therapies Oy, GSK, ImmunityBio, ImPact Biotech, Johnson & Johnson, LIPAC Oncology, Merck Sharp & Dohme Corp, Pfizer, Prokarium, Protara Therapeutics, Roche, Samyang Biopharma, SURGE Therapeutics, Tyra Biosciences, Viralytics Limited and Vyriad.
We are aware of several pharmaceutical companies that are developing drugs in the general fields of urology and uro-oncology, such as AstraZeneca, Aura Biosciences., Bristol Myers Squibb, CG Oncology, enGene Holdings, Ferring Pharmaceuticals, Fidia Pharmaceuticals, GSK, ImmunityBio, ImmVira, ImPact Biotech, Johnson & Johnson, LIPAC Oncology, Merck, Pfizer, Prokarium, Protara Therapeutics, Relmada Therapeutics, Roche, Samyang Biopharma, Sustained Therapeutics, SURGE Therapeutics, Theralase Technologies, Trigone Pharma, Tyra Biosciences, and Vyriad.
The current standard of care for the treatment of low-grade UTUC is radical nephroureterectomy ("RNU"), which is complete kidney and upper urinary tract removal. Recent advances in resection instrument technology have allowed physicians to treat patients with low-grade UTUC using endoscopic tumor resection, a kidney-sparing treatment, rather than nephroureterectomy followed by adjuvant chemotherapy, typically mitomycin, treatment.
Recent advances in resection instrument technology have allowed physicians to treat patients with low-grade UTUC using endoscopic tumor resection, a kidney-sparing treatment, rather than nephroureterectomy, which may be followed by adjuvant chemotherapy, typically mitomycin, treatment.
RTGel : Our Reverse Thermal Hydrogel Technology RTGel is a novel proprietary polymeric biocompatible, reverse thermal gelation hydrogel technology, which, unlike the general characteristics of most forms of matter, is liquid at lower temperatures and converts into gel form when warmed to body temperature.
In addition, our immuno-uro-oncology pipeline includes UGN-501 (formerly known as ICVB-1042), a next-generation investigational oncolytic virus. RTGel : Our Reverse Thermal Hydrogel Technology RTGel is a novel proprietary polymeric biocompatible, reverse thermal gelation hydrogel technology, which, unlike the general characteristics of most forms of matter, is liquid at lower temperatures and converts into gel form when warmed to body temperature.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeThe success of our product candidates is subject to significant risks and uncertainties, including risks associated with successfully completing current and future clinical trials, such as: • the FDA’s acceptance of our parameters for regulatory approval relating to UGN-102 and our other product candidates, including our proposed indications, primary and secondary endpoint assessments and measurements, safety evaluations and regulatory pathways, and proposed labeling and packaging; • our ability to successfully complete the FDA requirements related to CMC, for UGN-102 and our other product candidates, and if completed, their sufficiency to support an NDA; • the FDA’s timely acceptance of our INDs, for our product candidates and our inability to commence clinical trials in the United States without such IND acceptances; • the FDA’s acceptance of the design, size, conduct and implementation of our clinical trials, our trial protocols and the interpretation of data from nonclinical studies or clinical trials; • the FDA’s acceptance of the population studied in our clinical trials being sufficiently large, broad and representative to assess efficacy and safety in the patient population for which we seek approval; • our ability to successfully complete the clinical trials of our product candidates, including timely patient enrollment and acceptable safety and efficacy data and our ability to demonstrate the safety and efficacy of the product candidates undergoing such clinical trials; • our ability to demonstrate meaningful clinical or other benefits which outweigh any safety or other perceived risks, through the completion of our clinical trials for our product candidates; • the FDA’s decision to schedule an advisory committee meeting, and to conduct such meeting, in a timely manner to evaluate and make a recommendation regarding our NDA for UGN-102; • the outcome of an advisory committee meeting remains uncertain and it is possible that the advisory committee will have an adverse or split recommendation with respect to our application to market UGN-102 or our other product candidates in the United States; • if applicable, even if FDA’s advisory committee recommends approval of our applications to market UGN-102 and our other product candidates in the United States, without limiting the approved labeling, specifications, distribution or use of the products, or imposing other restrictions, the FDA is not bound by the advisory committee’s recommendation and there are a number of instances where the FDA has voted against the recommendations of advisory committees; • the FDA’s determination of safety and efficacy of our product candidates; • the FDA’s determination that the Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act ("FDCA") regulatory pathway (“505(b)(2)”) is available for our product candidates; • the prevalence and severity of adverse events associated with our product candidates, including UGN-102, as there are no drugs and related drug administration procedures approved for the primary treatment of low-grade NMIBC, that are based on RTGel technology; • the timely and satisfactory performance by third-party contractors of their obligations in relation to our clinical trials; • our success in educating physicians and patients about the benefits, risks, administration and use of our product candidates, if approved, particularly in light of the fact that there are no drugs that have been approved by the FDA for the primary treatment of low-grade NMIBC, and only a limited number of drugs have been approved by the FDA as adjuvant treatment for high-grade NMIBC; • the availability, perceived advantages, relative cost, safety and efficacy of alternative and competing treatments for the indications addressed by our product candidates; • the effectiveness of our marketing, sales and distribution strategy, and operations, as well as that of any current and future licensees; • the FDA’s acceptance of the quality of our drug substance or drug product, formulation, labeling, packaging, or the specifications of our product candidates is sufficient for approval; • our ability to develop, validate and maintain a commercially viable manufacturing process that is compliant with cGMP; 28 Table of Contents • the FDA’s acceptance of the manufacturing processes or facilities of third-party manufacturers with which we contract; • our ability to secure supplies for our product candidates to support clinical trials and commercial use; • our ability to manufacture or secure active ingredient, RTGel hydrogel, and finished product from third-party suppliers for product candidates, including UGN-102, UGN-103, UGN-104, UGN-201 and UGN-301, if approved; • our ability to obtain, maintain, protect and enforce our intellectual property rights with respect to our product candidates; • the extent to which the costs of our products, once approved, are covered and reimbursed by third-party payors, including the availability of a physician reimbursement code for our treatments, and patients’ willingness to pay for our products; and • our ability to properly train physicians or nurses for the skillful preparation and administration of any of our product candidates that receive approval, including UGN-102, and our ability to develop a broad experiential knowledge base of aggregated clinician feedback from which we can refine appropriate procedures for product administration, without which there could be a risk of adverse events.
Biggest changeThe success of our product candidates is subject to significant risks, including risks associated with successfully completing current and future clinical trials, such as: • the FDA’s acceptance of our parameters for regulatory approval relating to our product candidates, including our proposed indications, primary and secondary endpoint assessments and measurements, safety evaluations and regulatory pathways, and proposed labeling and packaging; • our ability to successfully complete the FDA requirements related to CMC for our product candidates, and if completed, their sufficiency to support an NDA; • the FDA’s timely acceptance of our INDs, for our product candidates and our inability to commence clinical trials in the United States without such IND acceptances; • the FDA’s acceptance of the design, size, conduct and implementation of our clinical trials, our trial protocols and the interpretation of data from nonclinical studies or clinical trials; • the FDA’s acceptance of the population studied in our clinical trials being sufficiently large, broad and representative to assess efficacy and safety in the patient population for which we seek approval; • our ability to successfully complete the clinical trials of our product candidates, including timely patient enrollment and acceptable safety and efficacy data and our ability to demonstrate the safety and efficacy of the product candidates undergoing such clinical trials; • our ability to demonstrate meaningful clinical or other benefits which outweigh any safety or other perceived risks, through the completion of our clinical trials for our product candidates; • if applicable, the recommendation of the FDA’s advisory committee to approve our applications to market our product candidates in the United States, without limiting the approved labeling, specifications, distribution or use of the products, or imposing other restrictions; • the FDA’s determination of safety and efficacy of our product candidates; • the FDA’s determination that the Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act ("FDCA") regulatory pathway (“505(b)(2)”) is available for our product candidates; • the prevalence and severity of adverse events associated with our product candidates; • the timely and satisfactory performance by third-party contractors of their obligations in relation to our clinical trials; • our success in educating physicians and patients about the benefits, risks, administration and use of our product candidates, if approved; • the availability, perceived advantages, relative cost, safety and efficacy of alternative and competing treatments for the indications addressed by our product candidates; • the effectiveness of our marketing, sales and distribution strategy, and operations, as well as that of any current and future licensees; • the FDA’s acceptance of the quality of our drug substance or drug product, formulation, labeling, packaging, or the specifications of our product candidates is sufficient for approval; • our ability to develop, validate and maintain a commercially viable manufacturing process that is compliant with cGMP; 28 Table of Contents • the FDA’s acceptance of the manufacturing processes or facilities of third-party manufacturers with which we contract; • our ability to secure supplies for our product candidates to support clinical trials and commercial use; • our ability to manufacture or secure active ingredient, RTGel hydrogel, and finished product from third-party suppliers for product candidates, including UGN-103 and UGN-104, if approved; • our ability to obtain, maintain, protect and enforce our intellectual property rights with respect to our product candidates; • the extent to which the costs of our products, once approved, are covered and reimbursed by third-party payors, including the availability of a physician reimbursement code for our treatments, and patients’ willingness to pay for our products; and • our ability to properly train physicians or nurses for the skillful preparation and administration of any of our product candidates that receive approval and our ability to develop a broad experiential knowledge base of aggregated clinician feedback from which we can refine appropriate procedures for product administration, without which there could be a risk of adverse events.
Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage.
Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage.
We, our CROs and other contractors, consultants, third-party vendors, and other third parties with whom we work, depend on information technology, telecommunication systems and data processing for significant elements of our operations, including, for example, systems handling human resources, financial reporting and controls, regulatory compliance and other infrastructure operations.
We, our CROs and other contractors, consultants, third-party vendors, and third parties with whom we work depend on information technology, telecommunication systems and data processing for significant elements of our operations, including, for example, systems handling human resources, financial reporting and controls, regulatory compliance and other infrastructure operations.
The stock market in general, and the market price of our ordinary shares in particular, has been and may continue to be, subject to fluctuation, whether due to, or irrespective of, our operating results and financial condition.
The stock market in general has been, and the market price of our ordinary shares in particular has been and may continue to be, subject to fluctuation, whether due to, or irrespective of, our operating results and financial condition.
Our future capital requirements depend on many factors, including: • the timing of, and the costs involved in, clinical development and obtaining regulatory approvals for our product candidates; • changes in regulatory requirements during the development phase that can delay or force us to stop our activities related to any of our product candidates; • the cost of commercialization activities for Jelmyto and any other products approved for sale, including marketing, sales and distribution costs; • our degree of success in commercializing Jelmyto ; • the cost of third-party manufacturing of our products candidates and any approved products; • the number and characteristics of any other product candidates we develop or acquire; • our ability to establish and maintain strategic collaborations, licensing or other commercialization arrangements, and the terms and timing of such arrangements; • the extent and rate of market acceptance of any approved products; • the expenses needed to attract and retain skilled personnel; • the costs associated with being a public company; • the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing patent and other intellectual property claims, including potential litigation costs, and the outcome of such litigation; • the timing, receipt and amount of sales of, or royalties on, future approved products, if any; • the repayment of outstanding debt; • any product liability or other lawsuits related to our products or business arrangements; • scientific breakthroughs in the field of urothelial cancer treatment and diagnosis that could significantly diminish the demand for our product candidates or make them obsolete; and • changes in reimbursement or other laws, regulations or policies that could have a negative impact on our future revenue stream. 23 Table of Contents In addition, we have limited experience and have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly in the biotechnology industry.
Our future capital requirements depend on many factors, including: • the timing of, and the costs involved in, clinical development and obtaining regulatory approvals for our product candidates; • changes in regulatory requirements during the development phase that can delay or force us to stop our activities related to any of our product candidates; • the cost of commercialization activities for Jelmyto, Zusduri and any other products approved for sale, including marketing, sales and distribution costs; • our degree of success in commercializing Jelmyto and Zusduri ; • the cost of third-party manufacturing of our products candidates and any approved products; • the number and characteristics of any other product candidates we develop or acquire; • our ability to establish and maintain strategic collaborations, licensing or other commercialization arrangements, and the terms and timing of such arrangements; • the extent and rate of market acceptance of any approved products; • the expenses needed to attract and retain skilled personnel; • the costs associated with being a public company; • the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing patent and other intellectual property claims, including potential litigation costs, and the outcome of such litigation; • the timing, receipt and amount of sales of, or royalties on, future approved products, if any; • the repayment of outstanding debt; • any product liability or other lawsuits related to our products or business arrangements; • scientific breakthroughs in the field of urothelial cancer treatment and diagnosis that could significantly diminish the demand for our product candidates or make them obsolete; and • changes in reimbursement or other laws, regulations or policies that could have a negative impact on our future revenue stream. 23 Table of Contents In addition, we have limited experience and have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly in the biotechnology industry.
There have been legal challenges to aspects of the FDA’s regulations and policies concerning the exclusivity provisions of the Orphan Drug Act, and future challenges could lead to changes that affect the protections afforded to our product candidates in ways that are difficult to predict. 51 Table of Contents Jelmyto and any of our product candidates that receive regulatory approval will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expenses, limit or withdraw regulatory approval and subject us to penalties if we fail to comply with applicable regulatory requirements.
There have been legal challenges to aspects of the FDA’s regulations and policies concerning the exclusivity provisions of the Orphan Drug Act, and future challenges could lead to changes that affect the protections afforded to our product candidates in ways that are difficult to predict. 51 Table of Contents Jelmyto, Zusduri and any of our product candidates that receive regulatory approval will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expenses, limit or withdraw regulatory approval and subject us to penalties if we fail to comply with applicable regulatory requirements.
The loan agreement contains negative covenants that, among other things and subject to certain exceptions, restrict our ability to: • sell or dispose of assets, including certain intellectual property; • amend, modify or waive certain agreements or organizational documents; • consummate certain change in control transactions; • incur certain additional indebtedness; • incur any non-permitted lien or other encumbrance on the Credit Parties’ assets; • pay dividends or make any distribution or payment on or redeem, retire or purchase any equity interests; and • make payments of certain subordinated indebtedness.
The 2026 Loan Agreement contains negative covenants that, among other things and subject to certain exceptions, restrict our ability to: • sell or dispose of assets, including certain intellectual property; • amend, modify or waive certain agreements or organizational documents; • consummate certain change in control transactions; • incur certain additional indebtedness; • incur any non-permitted lien or other encumbrance on the Credit Parties’ assets; • pay dividends or make any distribution or payment on or redeem, retire or purchase any equity interests; and • make payments of certain subordinated indebtedness.
With respect to our current and future product candidates, even if we complete clinical testing and receive approval of any regulatory filing for our product candidates, the FDA or applicable foreign regulatory agency may grant approval contingent on the performance of additional costly post-approval clinical trials, risk mitigation requirements and surveillance requirements to monitor the safety or efficacy of the product, which could negatively impact us by reducing revenues or increasing expenses, and cause the approved product candidate not to be commercially viable.
With respect to our current and future product candidates, even if we complete clinical testing and receive approval of any regulatory filing for our product candidates, the FDA or applicable foreign regulatory agency may grant approval contingent on the performance of additional costly post-approval clinical trials, risk mitigation requirements and surveillance requirements to monitor the safety or efficacy of the product, which could negatively impact us by reducing revenues or increasing expenses, and cause the approved product to not be commercially viable.
If we file an infringement action against a generic drug manufacturer, that company may challenge the scope, validity or enforceability of our or our licensors’ patents, requiring us and/or our licensors to engage in complex, lengthy and costly litigation or other proceedings. 46 Table of Contents In addition, if we or one of our licensors initiate legal proceedings against a third party to enforce a patent covering our product candidates, the defendant could counterclaim that the patent covering our product candidates is invalid and/or unenforceable.
If we file an infringement action against a generic drug manufacturer, that company may challenge the scope, validity or enforceability of our or our licensors’ patents, requiring us and/or our licensors to engage in complex, lengthy and costly litigation or other proceedings. 46 Table of Contents In addition, if we or one of our licensors were to initiate legal proceedings against a third party to enforce a patent covering our product candidates, the defendant could counterclaim that the patent covering our product candidates is invalid and/or unenforceable.
Any inability to manage expansion or other significant changes to our organization could delay the execution of our development, commercialization and strategic objectives or disrupt our operations; and if we are not successful in commercializing our approved product or any of our product candidates that may receive regulatory approval, either on our own or through collaborations with one or more third parties, our revenues will suffer, and we would incur significant additional losses.
Any inability to manage expansion or other significant changes to our organization could delay the execution of our development, commercialization and strategic objectives or disrupt our operations; and if we are not successful in commercializing our approved products or any of our product candidates that may receive regulatory approval, either on our own or through collaborations with one or more third parties, our revenues will suffer, and we would incur significant additional losses.
There may also be patent applications that have been filed but not published that, when issued as patents, could be asserted against us. 47 Table of Contents Third parties making claims against us for infringement or misappropriation of their intellectual property rights may seek and obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercialize our product candidates.
There may also be patent applications that have been filed but not published that, when issued as patents, could be asserted against us. 47 Table of Contents Third parties making claims against us for infringement or misappropriation of their intellectual property rights may seek and obtain injunctive or other equitable relief, which could effectively block our ability to further commercialize or develop our products and product candidates.
If adequate funds are not available to us on a timely basis, we may be required or choose to: • delay, limit, reduce or terminate nonclinical studies, clinical trials or other development activities for our product candidates or any of our future product candidates; • delay, limit, reduce or terminate our other research and development activities; or • delay, limit, reduce or terminate our establishment or expansion of manufacturing, sales and marketing or distribution capabilities or other activities that may be necessary to commercialize Jelmyto or any of our product candidates that obtain marketing approval.
If adequate funds are not available to us on a timely basis, we may be required or choose to: • delay, limit, reduce or terminate nonclinical studies, clinical trials or other development activities for our product candidates or any of our future product candidates; • delay, limit, reduce or terminate our other research and development activities; or • delay, limit, reduce or terminate our establishment or expansion of manufacturing, sales and marketing or distribution capabilities or other activities that may be necessary to commercialize Jelmyto, Zusduri or any of our product candidates that obtain marketing approval.
If our estimates of the incidence and prevalence of low-grade UTUC are incorrect, Jelmyto ’s commercial viability may prove to be limited, which may negatively affect our financial results. Jelmyto and any of our product candidates that receive regulatory approval may fail to achieve the broad degree of physician adoption and use and market acceptance necessary for commercial success.
If our estimates of the incidence and prevalence of low-grade UTUC are incorrect, Jelmyto ’s commercial viability may prove to be limited, which may negatively affect our financial results. Jelmyto, Zusduri and any of our product candidates that receive regulatory approval may fail to achieve the broad degree of physician adoption and use and market acceptance necessary for commercial success.
If we are found to have improperly promoted off-label uses of Jelmyto or any of our product candidates that receive regulatory approval, or if physicians misuse our products, we may become subject to prohibitions on the sale or marketing of our products, significant sanctions, and product liability claims, and our image and reputation within the industry and marketplace could be harmed.
If we are found to have improperly promoted off-label uses of Jelmyto, Zusduri or any of our product candidates that receive regulatory approval, or if physicians misuse our products, we may become subject to prohibitions on the sale or marketing of our products, significant sanctions, and product liability claims, and our image and reputation within the industry and marketplace could be harmed.
Filing, prosecuting and defending patents on our approved product or product candidates in all countries throughout the world would be prohibitively expensive. The requirements for patentability may differ in certain countries, particularly developing countries. For example, unlike other countries, China has a heightened requirement for patentability, and specifically requires a detailed description of medical uses of a claimed drug.
Filing, prosecuting and defending patents on our approved products or product candidates in all countries throughout the world would be prohibitively expensive. The requirements for patentability may differ in certain countries, particularly developing countries. For example, unlike other countries, China has a heightened requirement for patentability, and specifically requires a detailed description of medical uses of a claimed drug.
The measures that may be taken by various governments in response to a pandemic, epidemic or other public health emergency could disrupt the supply chain of material needed for our product candidates and our approved product, Jelmyto , interrupt healthcare services, delay coverage decisions from Medicare and third party payors, delay ongoing and planned clinical trials involving our product candidates, curtail access to hospitals, surgery centers, clinics, healthcare providers and pharmacies by our sales force and have a material adverse effect on our business, financial condition and results of operations. 41 Table of Contents To the extent any future pandemics, epidemics or public health emergencies adversely affect our business and financial results, it may also have the effect of heightening many of the other risks described in the “Risk Factors” section of this report.
The measures that may be taken by various governments, in response to a pandemic, epidemic or other public health emergency could disrupt the supply chain of material needed for our product candidates and our approved products, Jelmyto and Zusduri , interrupt healthcare services, delay coverage decisions from Medicare and third-party payors, delay ongoing and planned clinical trials involving our product candidates, curtail access to hospitals, surgery centers, clinics, healthcare providers and pharmacies by our sales force and have a material adverse effect on our business, financial condition and results of operations. 41 Table of Contents To the extent any future pandemics, epidemics or public health emergencies adversely affect our business and financial results, it may also have the effect of heightening many of the other risks described in the “Risk Factors” section of this report.
Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions. It may be difficult for us to profitably sell our product and any product candidates that receive regulatory approval if coverage and reimbursement for these products is limited by government authorities and/or third-party payor policies.
Failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions. It may be difficult for us to profitably sell our products and product candidates that receive regulatory approval if coverage and reimbursement for these products is limited by government authorities and/or third-party payor policies.
In particular, plaintiffs have become increasingly more active in bringing privacy-related claims against companies, including class claims and mass arbitration demands. Some of these claims allow for the recovery of statutory damages on a per violation basis, and, if viable, carry the potential for monumental statutory damages, depending on the volume of data and the number of violations.
In particular, plaintiffs have become increasingly active in bringing privacy-related claims against companies, including class claims and mass arbitration demands. Some of these claims allow for the recovery of statutory damages on a per-violation basis, and, if viable, carry the potential for monumental statutory damages, depending on the volume of data and the number of violations.
In the United States, the natural expiration of a patent is generally 20 years after it is filed. Various extensions may be available; however, the life of a patent, and the protection it affords, is limited. Without patent protection for Jelmyto or our product candidates, we may be open to competition from generic versions thereof.
In the United States, the natural expiration of a patent is generally 20 years after it is filed. Various extensions may be available; however, the life of a patent, and the protection it affords, is limited. Without patent protection for Jelmyto, Zusduri or our product candidates, we may be open to competition from generic versions thereof.
There is limited case law available to assist us in understanding the nature of these duties or the implications of these provisions. These provisions may be interpreted to impose additional obligations and liabilities on holders of our ordinary shares that are not typically imposed on shareholders of U.S. companies.
There is limited case law available to assist in understanding the nature of these duties or the implications of these provisions. These provisions may be interpreted to impose additional obligations and liabilities on holders of our ordinary shares that are not typically imposed on shareholders of U.S. companies.
We must also properly educate physicians and nurses on the skillful preparation and administration of Jelmyto , and develop a broad experiential knowledge base of aggregated clinician feedback from which we can refine appropriate procedures for product administration, without which there could be a risk of adverse events.
We must also properly educate physicians and nurses on the skillful preparation and administration of Jelmyto and Zusduri , and develop a broad experiential knowledge base of aggregated clinician feedback from which we can refine appropriate procedures for product administration, without which there could be a risk of adverse events.
Because there are a limited number of suppliers for the raw materials that we use to manufacture our product candidates, we may need to engage alternate suppliers to prevent a possible disruption of the manufacture of the materials necessary to produce Jelmyto for commercial sale and our product candidates for our clinical trials and their subsequent commercial sale, if approved.
Because there are a limited number of suppliers for the raw materials that we use to manufacture our product candidates, we may need to engage alternate suppliers to prevent a possible disruption of the manufacture of the materials necessary to produce Jelmyto and Zusduri for commercial sale and our product candidates for our clinical trials and their subsequent commercial sale, if approved.
As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our activities related to our product candidates may give rise to claims of infringement of the patent rights of others. We cannot assure you that our product candidates will not infringe existing or future patents.
As the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our activities related to our products and product candidates may give rise to claims of infringement of the patent rights of others. We cannot assure you that our products and product candidates will not infringe existing or future patents.
Preparing for and complying with these obligations require us to devote significant resources, which may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf. In addition, these obligations may require us to change our business model.
Preparing for and complying with these obligations requires us to devote significant resources, which may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf. In addition, these obligations may require us to change our business model.
In addition, Israeli law limits our ability to declare and pay dividends and may subject our dividends to Israeli withholding taxes. The Loan Agreement also restricts our ability to pay dividends. If we are classified as a passive foreign investment company (" PFIC" ), our U.S. shareholders may suffer adverse tax consequences.
In addition, Israeli law limits our ability to declare and pay dividends and may subject our dividends to Israeli withholding taxes. The 2026 Loan Agreement also restricts our ability to pay dividends. If we are classified as a passive foreign investment company (" PFIC" ), our U.S. shareholders may suffer adverse tax consequences.
The market opportunities for Jelmyto and our product candidates may be smaller than we anticipate or limited to those patients who are ineligible for established therapies or for whom prior therapies have failed and may be small. Cancer therapies are sometimes characterized as first-line, second-line or third-line.
The market opportunities for Jelmyto, Zusduri and our product candidates may be smaller than we anticipate or limited to those patients who are ineligible for established therapies or for whom prior therapies have failed and may be small. Cancer therapies are sometimes characterized as first-line, second-line or third-line.
On March 7, 2022, UroGen Pharma Ltd., UroGen Pharma, Inc., as the borrower (the "Borrower"), and certain direct and indirect subsidiaries of the Company party thereto from time to time, as guarantors ("Guarantors" and, collectively with UroGen Pharma Ltd. and Borrower, "Credit Parties"), entered into a loan agreement with funds managed by Pharmakon, including BPCR Limited Partnership (as a "Lender"), BioPharma Credit Investments V (Master) LP (as a "Lender"), and BioPharma Credit PLC, as collateral agent for the Lenders (in such capacity, "Collateral Agent"), pursuant to which the Lenders agreed to make term loans to the Borrower in an aggregate principal amount of up to $100.0 million (the “Initial Term Loans”) to be funded in two tranches.
On March 7, 2022, UroGen Pharma Ltd., UroGen Pharma, Inc., as the borrower (the "Borrower"), and certain of our direct and indirect subsidiaries party thereto from time to time, as guarantors ("Guarantors" and, collectively with UroGen Pharma Ltd. and Borrower, "Credit Parties"), entered into a loan agreement (the "2022 Loan Agreement") with funds managed by Pharmakon, including BPCR Limited Partnership (as a "Lender"), BioPharma Credit Investments V (Master) LP as a Lender, and BioPharma Credit PLC, as collateral agent for the Lenders (in such capacity, "Collateral Agent"), pursuant to which the Lenders agreed to make term loans to the Borrower in an aggregate principal amount of up to $100.0 million (the “Initial Term Loans”) to be funded in two tranches.
Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for Jelmyto and our investigational product candidates we develop; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial participants or cancellation of clinical trials; • costs to defend the related litigation, which may be only partially recoverable even in the event of successful defenses; • a diversion of management’s time and our resources; • substantial monetary awards to trial participants or patients; • regulatory investigations, product recalls, withdrawals or labeling, marketing or promotional restrictions; • loss of revenues; • exhaustion of any available insurance and our capital resources; and • the inability to commercialize any product we develop.
Regardless of the merits or eventual outcome, liability claims may result in: • decreased demand for Jelmyto and/or Zusduri and our product candidates; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial participants or cancellation of clinical trials; • costs to defend the related litigation, which may be only partially recoverable even in the event of successful defenses; • a diversion of management’s time and our resources; • substantial monetary awards to trial participants or patients; • regulatory investigations, product recalls, withdrawals or labeling, marketing or promotional restrictions; • loss of revenues; • exhaustion of any available insurance and our capital resources; and • the inability to commercialize any product we develop.
Additionally, Jelmyto and any of our product candidates that receive regulatory approval will be subject to extensive and ongoing regulatory requirements, including labeling and other restrictions and market withdrawal and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products.
Additionally, Jelmyto, Zusduri and any of our product candidates that receive regulatory approval will be subject to extensive and ongoing regulatory requirements, including labeling and other restrictions and market withdrawal and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our products.
Such litigation and administrative proceedings could result in revocation of our patents or amendment of our patents such that they do not cover our product or product candidates. They may also put our pending patent applications at risk of not issuing or issuing with limited and potentially inadequate scope to cover our product candidates.
Such litigation and administrative proceedings could result in revocation of our patents or amendment of our patents such that they do not cover our products or product candidates. They may also put our pending patent applications at risk of not issuing or issuing with limited and potentially inadequate scope to cover our product candidates.
Side effects such as toxicity or other safety issues associated with the use of Jelmyto or our product candidates could require us to perform additional studies or halt development or sale of Jelmyto or our product candidates or expose us to product liability lawsuits, which will harm our business.
Side effects such as toxicity or other safety issues associated with the use of Jelmyto , Zusduri or our product candidates could require us to perform additional studies or halt development or sale of Jelmyto , Zusduri or our product candidates or expose us to product liability lawsuits, which will harm our business.
Moreover, any new export or import restrictions, new legislation or shifting approaches in the enforcement or scope of existing regulations, or in the countries, persons, or product targeted by such regulations, could result in decreased use of our product by, or in our decreased ability to export our product to existing or potential customers with international operations.
Moreover, any new export or import restrictions, new legislation or shifting approaches in the enforcement or scope of existing regulations, or in the countries, persons, or product targeted by such regulations, could result in decreased use of our products by, or in our decreased ability to export our products to existing or potential customers with international operations.
If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product or product candidates. Such a loss of patent protection could have a negative impact on our business.
If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our products or product candidates. Such a loss of patent protection could have a negative impact on our business.
We are focusing a significant portion of our activities and resources on Jelmyto , and we believe our prospects are highly dependent on, and a significant portion of the value of our company relates to, our ability to successfully commercialize Jelmyto in the United States. Successful commercialization of Jelmyto is subject to many risks.
We are focusing a significant portion of our activities and resources on Jelmyto and Zusduri , and we believe our prospects are highly dependent on, and a significant portion of the value of our company relates to, our ability to successfully commercialize Jelmyto and Zusduri in the United States. Successful commercialization of Jelmyto and Zusduri is subject to many risks.
For instance, our pivotal Phase 3 OLYMPUS clinical trial for Jelmyto was designed to evaluate the use of Jelmyto for the treatment of tumors in the renal pelvis (the funnel-like dilated part of the ureter in the kidney) and was not designed to evaluate the use of Jelmyto for the treatment of tumors in the ureter (the tube that connects the kidneys to the bladder).
For instance, our pivotal Phase 3 clinical trial for Jelmyto was designed to evaluate the use of Jelmyto for the treatment of tumors in the renal pelvis (the funnel-like dilated part of the ureter in the kidney) and was not designed to evaluate the use of Jelmyto for the treatment of tumors in the ureter (the tube that connects the kidneys to the bladder).
If our CROs or any other third parties upon which we rely for administration and conduct of our clinical trials do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements, or for other reasons, or if they otherwise perform in a substandard manner, our clinical trials may be extended, delayed, suspended or terminated, and we may not be able to complete development of, obtain regulatory approval for, or successfully commercialize UGN-102 or any of our other product candidates.
If our CROs or any other third parties upon which we rely for administration and conduct of our clinical trials do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements, or for other reasons, or if they otherwise perform in a substandard manner, our clinical trials may be extended, delayed, suspended or terminated, and we may not be able to complete development of, obtain regulatory approval for, or successfully commercialize any of our product candidates.
In addition, we are required under the loan agreement to comply with various operating covenants and default clauses that may restrict our ability to finance our operations, engage in business activities or expand or fully pursue our business strategies.
In addition, we are required under the 2026 Loan Agreement to comply with various operating covenants and default clauses that may restrict our ability to finance our operations, engage in business activities or expand or fully pursue our business strategies.
Jelmyto or any of our product candidates may produce undesirable side effects that we may not have detected in our previous nonclinical studies and clinical trials or that are not expected with mitomycin treatment or inconsistent with catheter administration procedures.
Jelmyto, Zusduri or any of our product candidates may produce undesirable side effects that we may not have detected in our previous nonclinical studies and clinical trials or that are not expected with mitomycin treatment or inconsistent with catheter administration procedures.
Additionally, on July 9, 2021, President Biden signed an executive order encouraging the Federal Trade Commission (“FTC”) to curtail unfair use of non-compete agreements and other agreements that may unfairly limit worker mobility.
Additionally, on July 9, 2021, former President Biden signed an executive order encouraging the Federal Trade Commission (“FTC”) to curtail unfair use of non-compete agreements and other agreements that may unfairly limit worker mobility.
The market price of our ordinary shares on the Nasdaq Global Market may fluctuate as a result of a number of factors, some of which are beyond our control, including, but not limited to: • the success of our ongoing commercialization of Jelmyto ; • actual or anticipated variations in our and our competitors’ results of operations and financial condition; • physician and market acceptance of Jelmyto or any other approved product; • the mix of products that we sell; • any voluntary or mandatory recall of Jelmyto or any other approved product, or the imposition of any additional labeling, marketing or promotional restrictions; • our success or failure to obtain approval for and commercialize our product candidates; • changes in the structure of healthcare payment systems; • changes in earnings estimates or recommendations by securities analysts, if our ordinary shares are covered by analysts; • development of technological innovations or new competitive products by others; • announcements of technological innovations or new products by us; • publication of the results of nonclinical or clinical trials for Jelmyto , UGN-102 or our other product candidates; • failure by us to achieve a publicly announced milestone; • delays between our expenditures to develop and market new or enhanced product candidates and the generation of sales from those products; • developments concerning intellectual property rights; • the announcement of, or developments in, any litigation matters, including any product liability claims related to Jelmyto or any of our product candidates; • regulatory developments and the decisions of regulatory authorities as to the approval or rejection of new or modified products; • changes in the amounts that we spend to develop, acquire or license new products, technologies or businesses; • changes in our expenditures to promote our products; • the sale or proposed sale, by us or our significant shareholders, of our ordinary shares or other securities in the future; • changes in key personnel; • success or failure of our research and development projects or those of our competitors; • the trading volume of our ordinary shares; and • general economic and market conditions and other factors, including factors unrelated to our operating performance.
The market price of our ordinary shares on the Nasdaq Global Market may fluctuate as a result of a number of factors, some of which are beyond our control, including, but not limited to: • the success of our commercialization of Jelmyto and Zusduri ; • the success of our ongoing commercial launch of Zusduri ; • actual or anticipated variations in our and our competitors’ results of operations and financial condition; • physician and market acceptance of Jelmyto, Zusduri or any other approved product; • the mix of products that we sell; • any voluntary or mandatory recall of Jelmyto, Zusduri or any other approved product, or the imposition of any additional labeling, marketing or promotional restrictions; • our success or failure to obtain approval for and commercialize our product candidates; • changes in the structure of healthcare payment systems; • changes in earnings estimates or recommendations by securities analysts, if our ordinary shares are covered by analysts; • development of technological innovations or new competitive products by others; • announcements of technological innovations or new products by us; • publication of the results of nonclinical or clinical trials for Jelmyto , Zusduri or our product candidates; • failure by us to achieve a publicly announced milestone; • delays between our expenditures to develop and market new or enhanced product candidates and the generation of sales from those products; • developments concerning intellectual property rights; • the announcement of, or developments in, any litigation matters, including any product liability claims related to Jelmyto, Zusduri or any of our product candidates; • regulatory developments and the decisions of regulatory authorities as to the approval or rejection of new or modified products; • changes in the amounts that we spend to develop, acquire or license new products, technologies or businesses; • changes in our expenditures to promote our products; • our sale or proposed sale, or the sale by our significant shareholders, of our ordinary shares or other securities in the future; • changes in key personnel; • success or failure of our research and development projects or those of our competitors; • the trading volume of our ordinary shares; and • general economic and market conditions and other factors, including factors unrelated to our operating performance.
In the event we are unable to effectively develop and maintain our commercial team, including our sales force, our ability to effectively commercialize Jelmyto would be limited, and we would not be able to generate product revenues successfully.
In the event we are unable to effectively develop and maintain our commercial team, including our sales force, our ability to effectively commercialize Jelmyto and Zusduri would be limited, and we would not be able to generate product revenues successfully.
Even though we are approved as a commercial supplier of Jelmyto , we have limited experience as a company in the commercial supply of drugs and may never be successful as a commercial supplier of drug products containing mitomycin.
Even though we are approved as a commercial supplier of Jelmyto and Zusduri , we have limited experience as a company in the commercial supply of drugs and may never be successful as a commercial supplier of drug products containing mitomycin.
In order to successfully commercialize Jelmyto , we must continue to develop our sales, marketing, managerial, compliance and related capabilities or make arrangements with third parties to perform these services.
In order to successfully commercialize Jelmyto and Zusduri , we must continue to develop our sales, marketing, managerial, compliance and related capabilities or make arrangements with third parties to perform these services.
If we fail to develop and successfully commercialize other product candidates, our business and future prospects may be harmed, and our business will be more vulnerable to any problems that we encounter in developing and commercializing our product candidates.
If we fail to develop and successfully commercialize our product candidates, our business and future prospects may be harmed, and our business will be more vulnerable to any problems that we encounter in developing and commercializing our product candidates.
We are assessing second-source suppliers regarding certain components of Jelmyto and are advancing these conversations as a means to ensure both a second source and potential future reductions in cost of revenues.
We are assessing second source suppliers regarding certain components of Jelmyto and Zusduri and are advancing these conversations as a means to ensure both a second source and potential future reductions in cost of revenues.
Although the FDA has granted Orphan Drug Designation to Jelmyto and UGN-201 for treatment of UTUC and CIS, respectively, we may not receive Orphan Drug Designation for any of our other product candidates.
Although the FDA has granted Orphan Drug Designation to Jelmyto and UGN-201 for treatment of UTUC and CIS, respectively, we may not receive Orphan Drug Designation for any of our product candidates.
Governmental regulation of the import or export of our product, or our failure to obtain any required import or export authorization for our product, when applicable, could harm our international sales and adversely affect our revenue.
Governmental regulation of the import or export of our product, or our failure to obtain any required import or export authorization for our products, when applicable, could harm our international sales and adversely affect our revenue.
As with most pharmaceutical products, Jelmyto and our product candidates may be associated with side effects or adverse events that can vary in severity and frequency.
As with most pharmaceutical products, Jelmyto, Zusduri and our product candidates may be associated with side effects or adverse events that can vary in severity and frequency.
However, physicians are able, in their independent medical judgment, to use Jelmyto on their patients in an off-label manner, such as for the treatment of other urology indications. If we are found to have promoted such off-label uses, we may receive warning letters and become subject to significant liability, which would harm our business.
However, physicians are able, in their independent medical judgment, to use Jelmyto or Zusduri on their patients in an off-label manner, such as for the treatment of other urology indications. If we are found to have promoted such off-label uses, we may receive warning letters and become subject to significant liability, which would harm our business.
Under the Orphan Drug Act of 1983 (the "Orphan Drug Act"), the FDA may designate a product as an orphan drug if it is intended to treat an orphan disease or condition, defined as a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.
Under the Orphan Drug Act of 1983 (the "Orphan Drug Act"), the FDA may designate a product as an orphan drug (“Orphan Drug Designation”) if it is intended to treat an orphan disease or condition, defined as a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.
Jelmyto and any of our product candidates that receive regulatory approval will be subject to continual regulatory review by the FDA and/or foreign regulatory authorities.
Jelmyto, Zusduri and any of our product candidates that receive regulatory approval will be subject to continual regulatory review by the FDA and/or foreign regulatory authorities.
The degree and rate of physician and patient adoption of Jelmyto , UGN-102 or any of our other product candidates, if approved, will depend on a number of factors, including: • the clinical indications for which the product is approved; • the safety and efficacy data from the clinical trial(s) supporting the approved clinical indications; • the approved labeling and packaging for our products, including the degree of product preparation and administration convenience and ease of use that is afforded to physicians by the approved labeling and product packaging; • the prevalence and severity of adverse side effects and the level of benefit/risk observed in our clinical trials; • sufficient patient satisfaction with the results and administration of our products and overall treatment experience, including relative convenience, ease of use and avoidance of, or reduction in, adverse side effects; • the extent to which physicians recommend our products to patients; • physicians’ and patients’ willingness to adopt new therapies in lieu of other products or treatments, including willingness to adopt Jelmyto , and our lead product candidate UGN-102 as locally-administered drug replacements to current surgical standards of care; • the cost of treatment, safety and efficacy of our products in relation to alternative treatments, including the recurrence rate of our treatments; • the extent to which the costs of our products are covered and reimbursed by third-party payors, including the availability of a physician reimbursement code for our treatments, and patients’ willingness to pay for our products; • whether treatment with our products, including the treatment of low-grade UTUC with Jelmyto and the treatment of low-grade intermediate risk NMIBC with UGN-102, if approved, will be deemed to be an elective procedure by third- party payors; if so, the cost of treatment would be borne by the patient and would be less likely to be broadly adopted; • proper education of physicians or nurses for the skillful administration of our approved product, Jelmyto , and UGN-102, if approved, and development of a broad experiential knowledge base of aggregated clinician feedback from which we can refine appropriate procedures for product administration, without which there could be a risk of adverse events; • the effectiveness of our sales and marketing efforts, especially the success of any targeted marketing efforts directed toward physicians and clinics and any direct-to-consumer marketing efforts we may initiate; and • third-party clinical practice guidelines.
The degree and rate of physician and patient adoption of Jelmyto , Zusduri, or any of our product candidates, if approved, will depend on a number of factors, including: • the clinical indications for which the product is approved; • the safety and efficacy data from the clinical trial(s) supporting the approved clinical indications; • the approved labeling and packaging for our products, including the degree of product preparation and administration convenience and ease of use that is afforded to physicians by the approved labeling and product packaging; • the prevalence and severity of adverse side effects and the level of benefit/risk observed in our clinical trials; • sufficient patient satisfaction with the results and administration of our products and overall treatment experience, including relative convenience, ease of use and avoidance of, or reduction in, adverse side effects; • the extent to which physicians recommend our products to patients; • physicians’ and patients’ willingness to adopt new therapies in lieu of other products or treatments, including willingness to adopt Jelmyto and Zusduri as locally-administered drug replacements to current surgical standards of care; • the cost of treatment, safety and efficacy of our products in relation to alternative treatments, including the recurrence rate of our treatments; • the extent to which the costs of our products are covered and reimbursed by third-party payors, including the availability of a physician reimbursement code for our treatments, and patients’ willingness to pay for our products; • whether treatment with our products, including the treatment of low-grade UTUC with Jelmyto and the treatment of adult patients with recurrent low-grade intermediate risk NMIBC with Zusduri , will be deemed to be an elective procedure by third- party payors; if so, the cost of treatment would be borne by the patient and would be less likely to be broadly adopted; • proper education of physicians or nurses for the skillful administration of our approved products, Jelmyto and Zusduri, and development of a broad experiential knowledge base of aggregated clinician feedback from which we can refine appropriate procedures for product administration, without which there could be a risk of adverse events; • the effectiveness of our sales and marketing efforts, especially the success of any targeted marketing efforts directed toward physicians and clinics and any direct-to-consumer marketing efforts we may initiate; and • third-party clinical practice guidelines.
Any such violations could include prohibitions on our ability to offer our product in one or more countries and could materially damage our reputation, our brand, our international activities and our ability to attract and retain employees and our business. 42 Table of Contents In addition, our product and activities may be subject to U.S. and foreign export controls, trade sanctions and import laws and regulations.
Any such violations could include prohibitions on our ability to offer our products in one or more countries and could materially damage our reputation, our brand, our international activities and our ability to attract and retain employees and our business. 42 Table of Contents In addition, our products and activities may be subject to U.S. and foreign export controls, trade sanctions and import laws and regulations.
Topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, topline data should be viewed with caution until the final data are available. In addition, we may report interim analyses of only certain endpoints rather than all endpoints.
Topline data also remains subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, topline data should be viewed with caution until the final data are available. In addition, we may report interim analyses of only certain endpoints rather than all endpoints.
Our pending patent applications may not issue, and the scope of the claims of patent applications that do issue may be too narrow to adequately protect our competitive advantage.
Our pending patent applications may not be issued, and the scope of the claims of patent applications that do issue may be too narrow to adequately protect our competitive advantage.
These patent applications, if issued, are set to expire between 2031 and 2043. Limitations on the scope of our intellectual property rights may limit our ability to prevent third parties from designing around such rights and competing against us. For example, our patents do not claim a new compound.
These patent applications, if issued, are set to expire between 2031 and 2046. Limitations on the scope of our intellectual property rights may limit our ability to prevent third parties from designing around such rights and competing against us. For example, our patents do not claim a new compound.
During times of war and other major conflicts, we, the third parties with whom we work, may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our goods and services.
During times of war and other major conflicts, we and the third parties with whom we work, may be vulnerable to a heightened risk of these attacks, including retaliatory cyberattacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our goods and services.
Most states also have statutes or regulations similar to these laws, which may apply to items such as pharmaceutical products and services reimbursed by private insurers. We and/or our future partners may be subject to administrative, civil and criminal sanctions for violations of any of these laws.
Most states also have statutes or regulations similar to these federal laws, which may apply to items such as pharmaceutical products and services reimbursed by private insurers. We and/or our future partners may be subject to administrative, civil and criminal sanctions for violations of any of these federal and state laws.
While we cannot predict the broader consequences, these conflicts and retaliatory and counter-retaliatory actions could materially adversely affect global trade, currency exchange rates, inflation, regional economies, and the global economy, which in turn may increase our costs, disrupt our supply chain, impair our ability to raise or access additional capital when needed on acceptable terms, if at all, or otherwise adversely affect our business, financial condition, and results of operations.
While we cannot predict the broader consequences, geo-political conflicts and retaliatory and counter-retaliatory actions could materially adversely affect global trade, currency exchange rates, inflation, regional economies, and the global economy, which in turn may increase our costs, disrupt our supply chain, impair our ability to raise or access additional capital when needed on acceptable terms, if at all, or otherwise adversely affect our business, financial condition, and results of operations.
We have entered into collaboration and licensing agreements and in the future may enter into collaboration and licensing arrangements with other third parties for the development or commercialization of our product candidates. If our collaboration and licensing arrangements are not successful, we may not be able to capitalize on the market potential of these product candidates .
We have entered into collaboration and licensing agreements and in the future may enter into collaboration and licensing arrangements with other third parties for the development and commercialization of our products and product candidates. If our collaboration and licensing arrangements are not successful, we may not be able to capitalize on the market potential of these products and product candidates.
If we are unable to protect our trademarks from infringement, our business prospects may be harmed. We filed applications for trademarks ( Jelmyto ®, RTGel ®, and UroGen®) that identify our branding elements, such as Jelmyto and our unique technology in the United States, Europe, Japan and China.
If we are unable to protect our trademarks from infringement, our business prospects may be harmed. We filed applications for trademarks ( Jelmyto ®, RTGel ®, Zusduri TM and UroGen®) that identify our branding elements, such as Jelmyto and Zusduri and our unique technology in the United States, Europe, Japan and China.
Physicians treating low-grade UTUC and low-grade intermediate risk NMIBC have never had to consider treatments other than surgery.
Physicians treating low-grade UTUC and recurrent low-grade intermediate risk NMIBC have never had to consider treatments other than surgery.
We may utilize a variety of types of licensing, collaboration, distribution and other marketing arrangements with third parties to develop our product candidates and commercialize our approved product candidates, if any. We are not currently party to any such arrangement that we consider material.
We may utilize a variety of types of licensing, collaboration, distribution and other marketing arrangements with third parties to develop our product candidates and commercialize our approved products. We are not currently party to any such arrangement that we consider material.
Moreover, the law governing non-compete agreements and other forms of restrictive covenants varies from state to state within the U.S. and some states are reluctant to strictly enforce non-compete agreements. 40 Table of Contents Our employees, independent contractors, clinical investigators, CROs, consultants and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements and insider trading.
Moreover, the law governing non-compete agreements and other forms of restrictive covenants varies from state to state within the United States and some states are reluctant to strictly enforce non-compete agreements. 40 Table of Contents Our employees, independent contractors, clinical investigators, CROs, consultants and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements and insider trading.
The Drug Price Competition and Patent Term Restoration Act of 1984 (the "Hatch-Waxman Act"), added 505(b)(2) to the FDCA. 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies that were not conducted by or for the applicant, and for which the applicant has not received a right of reference, which could expedite the development program for UGN-102 and our other product candidates by potentially decreasing the amount of nonclinical and clinical data that we would need to generate in order to obtain FDA approval.
The Drug Price Competition and Patent Term Restoration Act of 1984 (the "Hatch-Waxman Act"), added 505(b)(2) to the FDCA. 505(b)(2) permits the filing of an NDA where at least some of the information required for approval comes from studies that were not conducted by or for the applicant, and for which the applicant has not received a right of reference, which could expedite the development program for certain of our product candidates by potentially decreasing the amount of nonclinical and clinical data that we would need to generate in order to obtain FDA approval.
A breach of any of these covenants or clauses could result in a default under the loan agreement, which could cause all of the outstanding indebtedness under the facility to become immediately due and payable, including a make whole amount and prepayment premium.
A breach of any of these covenants or clauses could result in a default under the 2026 Loan Agreement, which could cause all of the outstanding indebtedness under the 2026 Loan Agreement to become immediately due and payable, including a make whole amount and prepayment premium.
Remote work has become more common and has increased risks to our information technology systems and data, as more of our employees utilize network connections, computers and devices outside our premises or network, including working at home, while in transit and in public locations.
Remote work has increased risks to our information technology systems and data, as more of our employees utilize network connections, computers and devices outside our premises or network, including working at home, while in transit and in public locations.
Our other or future product candidates, including UGN-103, UGN-104, UGN-201 and UGN-301, may face similar risks. 25 Table of Contents Our projections of both the number of people who have the cancers we are targeting, as well as the subset of people with these cancers who have previously failed prior treatments, and who have the potential to benefit from treatment with our product candidates, are based on our beliefs and estimates.
Our other or future product candidates, including UGN-103, UGN-104 and UGN-501 may face similar risks. 25 Table of Contents Our projections of both the number of people who have the cancers we are targeting, as well as the subset of people with these cancers who have previously failed prior treatments, and who have the potential to benefit from treatment with our product candidates, are based on our beliefs and estimates.
These interim updates are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change as patient data become available and following a more comprehensive review of the data related to the particular study or trial.
These interim updates are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change as patient data becomes available and following a more comprehensive review of the data related to the particular study or trial.
We and the third parties with whom we work are subject to a variety of evolving threats, including, but not limited to, social-engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing attacks, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, telecommunications failures, earthquakes, fires, floods, attacks enhanced or facilitated by AI, and other similar threats.
We and the third parties with whom we work are subject to a variety of evolving threats, including, but not limited to, social engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing attacks, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, telecommunications failures, earthquakes, fires, floods, attacks enhanced or facilitated by generative artificial intelligence (“AI”), and other similar threats.
We cannot predict the impact of such changes and cannot be certain of our future compliance. Exchange rate fluctuations between the U.S. Dollar and the New Israeli Shekel may negatively affect our earnings. The U.S. dollar is our functional and reporting currency.
We cannot predict the impact of such changes and cannot be certain of our future compliance. Exchange rate fluctuations between the U.S. d ollar and the New Israeli Shekel may negatively affect our earnings. The U.S. dollar is our functional and reporting currency.
In addition, while we have established product liability insurance relating to our commercialization of Jelmyto , there can be no assurance that we will be able to maintain this insurance on commercially reasonable terms or that this insurance will be sufficient.
In addition, while we have established product liability insurance relating to our commercialization of Jelmyto and Zusduri , there can be no assurance that we will be able to maintain this insurance on commercially reasonable terms or that this insurance will be sufficient.
If any third party in our supply or distribution chain for materials or finished product is adversely impacted by restrictions resulting from pandemics, epidemics or public health emergencies or other disruptions caused by the outbreak of war, terrorist attacks or other acts of hostility, including staffing shortages, production slowdowns and disruptions in delivery systems, our supply chain may be disrupted, limiting our ability to manufacture and distribute Jelmyto and planned future commercialization of UGN-102, if approved, for commercial sales and our product candidates for our clinical trials and research and development operations. 36 Table of Contents In addition, before we can begin to commercially manufacture any product candidates that receive regulatory approval in the future, whether in a third-party facility or in our own facility, once established, we must obtain regulatory approval from the FDA for our manufacturing process and facility in order to sell such products in the United States.
If any third party in our supply or distribution chain for materials or finished product is adversely impacted by restrictions resulting from pandemics, epidemics or public health emergencies or other disruptions caused by the outbreak of war, terrorist attacks or other acts of hostility, including staffing shortages, production slowdowns and disruptions in delivery systems, our supply chain may be disrupted, limiting our ability to manufacture and distribute Jelmyto and Zusduri for commercial sales and our product candidates for our clinical trials and research and development operations. 36 Table of Contents In addition, before we can begin to commercially manufacture any product candidates that receive regulatory approval in the future whether in a third-party facility or in our own facility, once established, we must obtain regulatory approval from the FDA for our manufacturing process and facility in order to sell such products in the United States.
We may unknowingly infringe existing patents by commercialization of our product candidates. It is also possible that patents of which we are aware, but which we do not believe are relevant to our product candidates, could nevertheless be found to be infringed by our product candidates.
We may unknowingly infringe existing patents by commercialization of our products and product candidates. It is also possible that patents of which we are aware, but which we do not believe are relevant to our products and product candidates, could nevertheless be found to be infringed by our products and product candidates.
At the federal level, on November 15, 2021, the Infrastructure Investment and Jobs Act was signed into law. On January 1, 2023, manufacturers began to be required to pay quarterly refunds to the Centers for Medicare & Medicaid Services ("CMS")for discarded amounts of certain single-dose container and single-use package drugs payable under part B of the Medicare program.
At the federal level, on November 15, 2021, the Infrastructure Investment and Jobs Act was signed into law. On January 1, 2023, manufacturers began to be required to pay quarterly refunds to the CMS for discarded amounts of certain single-dose container and single-use package drugs payable under part B of the Medicare program.
We face an inherent risk of product liability as a result of the clinical testing of our product candidates and face or will face an even greater risk with the commercialization of Jelmyto and any investigational product candidates that receive marketing approval.
We face an inherent risk of product liability as a result of the clinical testing of our product candidates and face or will face an even greater risk with the commercialization of Jelmyto, Zusduri and any product candidates that receive marketing approval.
Further, any failure to effectively integrate new personnel could prevent us from successfully growing our company. 60 Table of Contents General Risk Factors If equity research analysts do not publish research or reports about us or our business or if they issue unfavorable commentary or downgrade our ordinary shares, the price of our ordinary shares could decline.
Further, any failure to effectively integrate new personnel could prevent us from successfully growing our company. 60 Table of Contents General Risk Factors If e quity research analysts do not publish research or reports about us or our business or if they issue unfavorable commentary or downgrade our ordinary shares, the price of our ordinary shares could decline.
In addition, delays in receipt of or failure to receive regulatory clearances or approvals for any future products would harm our business, financial condition, and results of operations. 53 Table of Contents We and the third parties with whom we work are subject to stringent and changing U.S. and foreign laws, regulations, and rules, contractual obligations, industry standards, self-regulatory schemes, government regulation, policies, standards, and other obligations related to data privacy and security.
In addition, delays in receipt of or failure to receive regulatory clearances or approvals for any future products would harm our business, financial condition, and results of operations. 53 Table of Contents W e and the third parties with whom we work are subject to stringent and changing U.S. and foreign laws, regulations, and rules, contractual obligations, industry standards, self-regulatory schemes, policies, and other obligations related to data privacy and security.
If we are unable to raise additional funds through other collaborations, strategic alliances or licensing arrangements, we may be required to terminate product development or future commercialization efforts or to cease operations altogether. Risks Related to Our Business and Strategy We are highly dependent on the successful commercialization of our only approved product, Jelmyto.
If we are unable to raise additional funds through other collaborations, strategic alliances or licensing arrangements, we may be required to terminate product development or future commercialization efforts or to cease operations altogether. Risks Related to Our Business and Strategy We are highly dependent on the successful commercialization of our approved products, Jelmyto and Zusduri.
There can be no assurance that our sales force will continue to have in-person access to physicians as a result of pandemics, epidemics or public health emergencies, or that digital materials and virtual engagement will be effective at growing and sustaining prescription levels of Jelmyto .
There can be no assurance that our sales force will continue to have in-person access to physicians as a result of pandemics, epidemics or public health emergencies, or that digital materials and virtual engagement will be effective at growing and sustaining prescription levels of Jelmyto and successfully launching Zusduri .

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Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeBy order dated February 27, 2025, the court approved the parties’ joint stipulation to remove the Markman hearing and any related claim-construction proceedings from the court’s calendar. This matter is scheduled for a bench trial in October 2026. From time to time, we may be involved in various claims and legal proceedings relating to claims arising out of our operations.
Biggest changeBy orders dated February 27, 2025, and June 26, 2025, the court approved the parties’ joint stipulations to remove the Markman hearing and any related claim-construction proceedings from the court’s calendar. This matter is scheduled for a bench trial in October 2026. Following certain stipulations, the case is now styled as UroGen Pharma Ltd. et al. v.
Item 3. Legal Proceedings On April 2, 2024, UroGen Pharma Ltd. filed a lawsuit in the U.S. District Court for the District of Delaware against Teva Pharmaceuticals, Inc., Teva Pharmaceuticals USA, Inc., and Teva Pharmaceutical Industries, Ltd., alleging infringement of U.S.
Item 3. Legal Proceedings On April 2, 2024, the Company filed a lawsuit in the U.S. District Court for the District of Delaware against Teva Pharmaceuticals, Inc., Teva Pharmaceuticals USA, Inc., and Teva Pharmaceutical Industries, Ltd., alleging infringement of U.S.
Patent Numbers 9,040,074 and 9,950,069 and seeking a permanent injunction preventing market entry of a generic product from Teva prior to the expiry of such patents. The Company stipulated to the dismissal of Teva Pharmaceutical Industries, Ltd. without prejudice and the action continues against the other two Teva entities.
Patent Numbers 9,040,074 and 9,950,069 and seeking a permanent injunction preventing U.S. market entry of Teva’s generic product prior to the expiry of such patents. By written stipulation dated June 11, 2024, Teva Pharmaceutical Industries, Ltd. was dismissed from the action. On May 19, 2025 the Company filed an Amended Complaint, adding U.S.
Removed
Both patents are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (commonly known as the Orange Book) for Jelmyto .
Added
Patent 12,268,745 to the litigation (the “745 Patent”). The U.S. Patent and Trademark Office issued the ‘745 Patent on April 8, 2025, and the Company subsequently added this patent to the Orange Book for JELMYTO.
Removed
The lawsuit follows an Abbreviated New Drug Application filed by Teva Pharmaceuticals, Inc., which seeks authorization from the FDA to manufacture, use or sell a generic version of mitomycin for pyelocalyceal solution, 40 mg/vial in the United States before the expiry of the two patents referenced above.
Added
Teva Pharmaceuticals, Inc. et al. By order dated January 12, 2026, the court approved the parties’ joint stipulation to dismiss counts I, II, III, and IV of the Company’s Amended Complaint alleging infringement by Teva of U.S. Patent Numbers 9,040,074 and 9,950,069, with prejudice, and to dismiss counts I and II of Teva’s counterclaims seeking declaratory judgment that U.S.
Added
Patent Numbers 9,040,074 and 9,950,069 are invalid, as moot. No ANDA may be finally approved by the FDA until the expiration of Orphan Drug Exclusivity covering JELMYTO in April 2027.
Added
If the Company is unsuccessful in securing the requested court relief, JELMYTO may be subject to immediate competition from an FDA approved generic product after regulatory exclusivity for JELMYTO expires in April 2027. From time to time, we may be involved in various claims and legal proceedings relating to claims arising out of our operations.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeHolders As of March 3, 2025, there were 10 registered holders of record of our ordinary shares. Dividend Policy We have not paid any dividends on our ordinary shares since our inception and do not expect to pay dividends on our ordinary shares in the foreseeable future. The Loan Agreement with Pharmakon restricts our ability to pay dividends.
Biggest changeHolders As of January 31, 2026, there were 8 registered holders of record of our ordinary shares. Dividend Policy We have not paid any dividends on our ordinary shares since our inception and do not expect to pay dividends on our ordinary shares in the foreseeable future. The 2026 Loan Agreement with Pharmakon restricts our ability to pay dividends.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeATM Sales Agreement In December 2019, we entered into the ATM Sales Agreement with TD Securities (USA) LLC (f/k/a Cowen and Company, LLC) (“TD Cowen”) pursuant to which we may from time to time offer and sell our ordinary shares having an aggregate offering price of up to $100.0 million.
Biggest changeATM Sales Agreement In December 2019, we entered into a sales agreement (the “ATM Sales Agreement”) with TD Securities (USA) LLC (f/k/a Cowen and Company, LLC) (“TD Cowen”), pursuant to which we were able to from time to time offer and sell our ordinary shares having an aggregate offering price of up to $100.0 million, to or through TD Cowen, acting as sales agent or principal, in any manner deemed to be an “at-the-market offering.” During the first quarter of 2024, we sold 3,400,468 ordinary shares under the ATM Sales Agreement for net proceeds to us of approximately $54.7 million after deducting sales commissions to TD Cowen of up to 3%.
We have developed RTGel ® reverse-thermal hydrogel, a proprietary sustained release, hydrogel-based technology that has the potential to improve therapeutic profiles of existing drugs. Our technology is designed to enable longer exposure of the urinary tract tissue to medications, making local therapy a potentially more effective treatment option.
We have developed RTGel reverse-thermal hydrogel, a proprietary sustained release, hydrogel-based technology that has the potential to improve therapeutic profiles of existing drugs. Our technology is designed to enable longer exposure of urinary tract tissue to medications, making local therapy a potentially more effective treatment option.
On March 7, 2022, we entered into the Loan Agreement with Pharmakon for a senior secured term loan of up to $100.0 million in two tranches.
On March 7, 2022, we entered into the 2022 Loan Agreement with Pharmakon for a senior secured term loan of up to $100.0 million in two tranches.
These patents were listed in the FDA's Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations). Low-grade UTUC is a rare cancer that develops in the lining of the upper urinary tract, ureters and kidneys. In the United States, there are approximately 6,000 to 7,000 new or recurrent low-grade UTUC patients annually.
These patents are listed in the FDA's Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations). Low-grade UTUC is a rare cancer that develops in the lining of the upper urinary tract, ureters and kidneys. In the United States, there are approximately 6,000 to 7,000 new or recurrent low-grade UTUC patients annually.
In June 2020, we initiated our commercial launch of Jelmyto in the United States. We have staffed, trained and prepared a customer-facing team that includes territory business managers with deep experience in both urology and oncology. These territory business manager positions are led by eight regional business director positions, who are in turn supported by eight regional operations manager positions.
In June 2020, we initiated our commercial launch of Jelmyto in the United States. We have staffed, trained and prepared a customer-facing team that includes territory business managers with deep experience in both urology and oncology. These territory business manager positions are led by regional business director positions, who are in turn supported by regional operations manager positions.
However, the high rates of recurrence and significant risk of progression to muscle-invasive tumors are particularly dangerous. Radical cystectomy, or surgical removal of the bladder, is strongly advocated in patients with BCG-unresponsive NMIBC (i.e., patients with BCG-refractory and BCG-relapsing tumors in whom further BCG therapy is not recommended) or for patients who cannot tolerate BCG.
However, the high rates of recurrence and significant risk of progression to muscle-invasive tumors are particularly dangerous. Radical cystectomy, or bladder removal is strongly advocated in patients with BCG-unresponsive NMIBC (i.e., patients with BCG-refractory and BCG-relapsing tumors in whom further BCG therapy is not recommended) or for patients who cannot tolerate BCG.
Debt financing, if available, may involve agreements that include covenants that further limit or restrict our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. In addition, the terms of the Forward Contract with RTW and the Loan Agreement limit our ability to take certain actions, including incurring additional indebtedness.
Debt financing, if available, may involve agreements that include covenants that further limit or restrict our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. In addition, the terms of the Forward Contract with RTW and the 2026 Loan Agreement limit our ability to take certain actions, including incurring additional indebtedness.
We regularly review our research and development activities and, as necessary, reallocate resources among our programs, product candidates and external opportunities that we believe will best support the long-term growth of our business. We do not track total research and development expenses by program, product candidates, or development phase.
We regularly review our research and development activities and, as necessary, reallocate resources among our programs, product candidates and external opportunities that we believe will best support the long-term growth of our business. We do not track total research and development expenses by program, product candidate, or development phase.
All product sales of Jelmyto are recognized through our arrangements with two customers as defined by ASC 606, both of which are third-party national specialty distributors. Payment terms with these customers are 60 days and 90 days.
All product sales of Jelmyto and Zusduri are recognized through our arrangements with two customers as defined by ASC 606, both of which are third-party national specialty distributors. Payment terms with these customers are 60 days and 90 days.
On June 29, 2023, the Loan Agreement with Pharmakon was amended to replace the benchmark governing the interest rate with a rate based on the secured overnight financing rate (“SOFR”) published by the Federal Reserve Bank of New York.
On June 29, 2023, the 2022 Loan Agreement with Pharmakon was amended to replace the benchmark governing the interest rate with a rate based on the secured overnight financing rate (“SOFR”) published by the Federal Reserve Bank of New York.
For more information as to the risks associated with our future funding needs, see “Item 1.A – Risk Factors.” We will require additional financing to achieve our goals, and a failure to obtain this capital when needed and on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development, commercialization efforts or other operations .
For more information as to the risks associated with our future funding needs, see “Item 1A – Risk Factors.” We will require additional financing to achieve our goals, and a failure to obtain this capital when needed and on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our product development, commercialization efforts or other operations .
In May 2021, following the receipt of necessary regulatory approvals, we received the $75.0 million prepaid forward payment ($72.4 million net of transaction costs) from RTW. Pharmakon Loan Agreement On March 7, 2022, we entered into a loan agreement with Pharmakon (the “Loan Agreement”) for a senior secured term loan of up to $100.0 million in two tranches.
In May 2021, following the receipt of necessary regulatory approvals, we received the $75.0 million prepaid forward payment ($72.4 million net of transaction costs) from RTW. Pharmakon Loan Agreement On March 7, 2022, we entered into a loan agreement with Pharmakon (the “2022 Loan Agreement”) for a senior secured term loan of up to $100.0 million in two tranches.
Prepaid Forward Obligation Under the RTW Transaction, we received funds to support the launch of Jelmyto and the development of UGN-102 in return for tiered, future cash payments based on net sales of Jelmyto and, subject to FDA approval, UGN-102 , UGN-103 and UGN-104. The net proceeds received under the RTW Transaction were recognized as a long-term liability.
Prepaid Forward Obligation Under the RTW Transaction, we received funds to support the launch of Jelmyto and the development of Zusduri in return for tiered, future cash payments based on net sales of Jelmyto and Zusduri , and, subject to FDA approval, UGN-103 and UGN-104. The net proceeds received under the RTW Transaction were recognized as a long-term liability.
Based on our cash, cash equivalents and marketable securities as of December 31, 2024, together with management’s cash flow projections, we believe we have sufficient cash and cash equivalents to fund our operations beyond one year from the issuance of our consolidated financial statements appearing elsewhere in this Annual Report.
Based on our cash, cash equivalents and marketable securities as of December 31, 2025, together with management’s cash flow projections, we believe we have sufficient cash and cash equivalents to fund our operations beyond one year from the issuance of our consolidated financial statements appearing elsewhere in this Annual Report.
While our significant accounting policies are more fully described in Note 3 to our consolidated financial statements appearing elsewhere in this Annual Report, we believe the following are the critical accounting policies used in the preparation of our financial statements. 71 Table of Contents Revenue Net revenue from product sales is recognized at the transaction price when the specialty distributors obtain control of our products, which occurs at a point in time, typically upon delivery of the product to the treating physician.
While our significant accounting policies are more fully described in Note 3 to our consolidated financial statements appearing elsewhere in this Annual Report, we believe the following are the critical accounting policies used in the preparation of our financial statements. 71 Table of Contents Revenue Net revenue from product sales is recognized at the transaction price when the specialty distributors obtain control of our products, which occurs at a point in time, typically upon delivery of the product to the treating physician or mixing pharmacy.
License fees and development milestone payments related to in-licensed products and technology are expensed as incurred, or achieved in the case of milestones, if it is determined at that point that they have no established alternative future use.
License fees and development milestone payments related to in-licensed products and technology are expensed as incurred, or probable of being achieved in the case of milestones, if it is determined at that point that they have no established alternative future use.
The Centers for Medicare & Medicaid Services established a permanent and product-specific J-code for Jelmyto that took effect on January 1, 2021 and replaced the C-Code. The Centers for Medicare & Medicaid Services has granted Jelmyto a New Technology Ambulatory Payment Classification, effective from October 1, 2023.
The Centers for Medicare & Medicaid Services ("CMS") established a permanent and product-specific J-code for Jelmyto that took effect on January 1, 2021 and replaced the C-Code. CMS has granted Jelmyto a New Technology Ambulatory Payment Classification ("APC"), effective from October 1, 2023.
The 18-month DOR by Kaplan-Meier estimate for patients who achieved a CR at three months after the first instillation of UGN-102 remained consistent with the 12-month DOR data: 80.6% (95% CI, 74.0%, 85.7%) at 18-months (n=101) compared to 82.5% (76.1%, 87.3%) at 12-months (n=146). Median follow-up time was 18.7 months after the 3-month CR.
The 18-month DOR by Kaplan-Meier estimate for patients who achieved a CR at three months after the first instillation of Zusduri remained consistent with the 12-month DOR data: 80.6% (95% CI, 74.0%, 85.7%) at 18-months (n=101) compared to 82.5% (76.1%, 87.3%) at 12-months (n=146). Median follow-up time was 18.7 months after the three-month CR.
(“medac”) to develop UGN-103 and UGN-104, which are intended to be next-generation formulations of UGN-102 and Jelmyto , respectively, that combine medac’s proprietary 80 mg mitomycin formulation with our RTGel technology, which we believe will provide advantages related to production, cost, supply and product convenience.
(“medac”) to develop UGN-103 and UGN-104, which are intended to be next-generation investigational formulations of Zusduri and Jelmyto , respectively, that combine medac’s proprietary 80 mg mitomycin formulation with our RTGel technology, which we believe will provide advantages related to production, cost, supply and product convenience.
These characteristics of RTGel enable sustained release of mitomycin in the urinary tract for Jelmyto, UGN-102, UGN-103 and UGN-104. Further, RTGel may be particularly effective in the bladder and upper urinary tract where tumor visibility and access are challenging, and where there exists a significant amount of urine flow and voiding.
These characteristics of RTGel enable sustained release of mitomycin in the urinary tract for both Jelmyto, Zusduri, UGN-103 and UGN-104. Further, RTGel may be particularly effective in the bladder and upper urinary tract where tumor visibility and access are challenging, and where there exists a significant amount of urine flow and voiding.
The ENVISION trial met its primary endpoint by demonstrating that patients treated with UGN-102 had a 79.6% rate of CR at three-months following the initial instillation. In both trials, the safety profile of UGN-102 was acceptable, and comparable to that observed in previous clinical trials of UGN-102.
The ENVISION trial met its primary endpoint by demonstrating that patients treated with Zusduri had a 79.6% rate of CR at three-months following the initial instillation. In both trials, the safety profile of Zusduri was acceptable, and comparable to that observed in previous clinical trials of Zusduri .
The FDA approval was based on results from our Phase 3 OLYMPUS trial showing Jelmyto achieved clinically significant disease eradication in adults with low-grade UTUC.
The FDA approval was based on results from UroGen's Phase 3 Olympus trial showing Jelmyto achieved clinically significant disease eradication in adults with low-grade UTUC.
Funding and Material Cash Requirements Our present and future funding and material cash requirements will depend on many factors, including, among other things: • the progress, timing and completion of clinical trials for UGN-301, UGN-103 and UGN-104; • nonclinical studies and clinical trials for any of our other product candidates; • the costs related to obtaining regulatory approval UGN-102, UGN-301, UGN-103, UGN-104 and any of our other product candidates, and any delays we may encounter as a result of regulatory requirements or adverse clinical trial results with respect to any of these product candidates; • selling, marketing and patent-related activities undertaken in connection with the commercialization of Jelmyto and, if approved, UGN-102 and any of our other product candidates, and costs involved in the continued development of an effective sales and marketing organization; • the costs involved in filing and prosecuting patent applications and obtaining, maintaining and enforcing patents or defending against claims or infringements raised by third parties, and license royalties or other amounts we may be required to pay to obtain rights to third party intellectual property rights; • potential new product candidates we identify and attempt to develop; • revenues we may derive either directly or in the form of royalty payments from future sales of Jelmyto , UGN-102, UGN-103, UGN-104, UGN-301, RTGel reverse thermal hydrogel technology and any other product candidates; and • the repayment of outstanding debt.
Funding and Material Cash Requirements Our present and future funding and material cash requirements will depend on many factors, including, among other things: • the progress, timing and completion of clinical trials for UGN-103, UGN-104 and UGN-501; • nonclinical studies and clinical trials for any of our other product candidates; • the costs related to obtaining regulatory approval for UGN-103, UGN-104, UGN-501 and any other product candidates, and any delays we may encounter as a result of regulatory requirements or adverse clinical trial results with respect to any of our product candidates; • selling, marketing and patent-related activities undertaken in connection with the commercialization of Jelmyto , Zusduri and any of our product candidates, if approved, and costs involved in the continued development of an effective sales and marketing organization; • the costs involved in filing and prosecuting patent applications and obtaining, maintaining and enforcing patents or defending against claims or infringements raised by third parties, and license royalties or other amounts we may be required to pay to obtain rights to third-party intellectual property rights; • potential new product candidates we identify and attempt to develop; • revenues we may derive either directly or in the form of royalty payments from future sales of Jelmyto , Zusduri , and, if approved, UGN-103, UGN-104, UGN-501, RTGel reverse thermal hydrogel technology and any other product candidates; • the timing of any milestone, net sales or royalty payments owed by us from the commercialization of our products or product candidates; and • the repayment of outstanding debt.
The ENVISION trial data was published online in The Journal of Urology in October 2024 and was included in the February 2025 print edition. In March 2025, we announced updated 18-month DOR data from the Phase 3 ENVISION trial.
The ENVISION trial data were published online in The Journal of Urology in October 2024 and were included in the February 2025 print edition. In March 2025, we announced 18-month DOR data from the Phase 3 ENVISION trial.
In the ATLAS trial, UGN-102 with or without TURBT met its primary endpoint of disease-free survival, reducing risk of recurrence, progression, or death by 55% compared to TURBT alone.
In the ATLAS trial, Zusduri with or without TURBT met its primary endpoint of disease-free survival, reducing risk of recurrence, progression, or death by 55% compared to TURBT alone.
UGN-301 is delivered using our proprietary RTGel technology, which has been designed to significantly improve the effectiveness of certain intravesical therapies. High-grade NMIBC is a highly aggressive form of bladder cancer. TURBT followed by adjuvant intravesical immunotherapy with BCG is the current standard of care therapy for high-grade NMIBC.
UGN-301 was delivered using our proprietary RTGel technology, which has been designed to significantly improve the effectiveness of certain intravesical therapies. High-grade NMIBC is a highly aggressive form of bladder cancer. TURBT followed by adjuvant intravesical immunotherapy with Bacillus of Calmette and Guerin ("BCG") is the current standard of care therapy for high-grade NMIBC.
Results of Operations Comparison of the Years Ended December 31, 2024 and 2023 The following table sets forth our results of operations for the years ended December 31, 2024 and 2023.
Results of Operations Comparison of the Years Ended December 31, 2025 and 2024 The following table sets forth our results of operations for the years ended December 31, 2025 and 2024.
Results of the ATLAS trial also showed a 64.8% CR rate at three months for patients who only received UGN-102, compared to a 63.6% CR rate at three months for patients who only received a TURBT.
Results of the ATLAS trial also showed a 64.8% CR rate at three months for patients who only received Zusduri , compared to a 63.6% CR rate at three months for patients who only received a TURBT.
We have implemented processes to help make Jelmyto preparation and administration seamless for practitioners and patients, including entering into agreements with various national, regional and local specialty pharmacies under which the pharmacy, following receipt of a patient prescription, prepares and dispenses the Jelmyto admixture on our behalf.
We have implemented processes to help make Jelmyto preparation and administration seamless for practitioners and patients, including entering into agreements with various national, regional and local mixing pharmacies under which the pharmacy, following receipt of a patient prescription, prepares and dispenses the Jelmyto admixture.
We have also launched a registry to capture data and evaluate real world outcomes in patients with low-grade UTUC who have been or will be treated with Jelmyto . The purpose of the registry is to study the use of Jelmyto in clinical practice in the United States and address specific clinical questions.
We have also launched a registry to capture data and evaluate real world outcomes in patients with low-grade UTUC treated with Jelmyto . The purpose of the registry is to study the use of Jelmyto in clinical practice in the United States and address specific clinical questions.
The second combination we are investigating clinically involves the sequential administration of gemcitabine and UGN-301 to the bladder in high-grade NMIBC. Gemcitabine is a chemotherapy that is used intravesically to treat high grade NMIBC where it is administered as a liquid formulation.
The second combination we investigated clinically involved the sequential administration of gemcitabine and UGN-301 to the bladder in high-grade NMIBC. Gemcitabine is a chemotherapy that is used intravesically to treat high grade NMIBC where it is administered as a liquid formulation.
The multi-arm Phase 1 study, which is expected to support the development of UGN-301 in high-grade NMIBC, was initiated in April 2022 and enrollment in the current arms of the study are complete. Safety and dosing data from the first arm evaluating UGN-301 as monotherapy was presented in late 2024.
The multi-arm Phase 1 study, which was expected to support the development of UGN-301 in high-grade NMIBC, was initiated in April 2022 and enrollment in the study was completed. Safety and dosing data from the first arm evaluating UGN-301 as monotherapy was presented in late 2024.
Liquidity and Capital Resources As of December 31, 2024, we had $241.7 million in cash and cash equivalents and marketable securities. Cash in excess of immediate requirements is invested in accordance with our investment policy, primarily with a view to liquidity and capital preservation, and is held primarily in U.S. dollars.
Liquidity and Capital Resources As of December 31, 2025, we had $120.5 million in cash and cash equivalents and marketable securities. Cash in excess of immediate requirements is invested in accordance with our investment policy, primarily with a view to liquidity and capital preservation, and is held primarily in U.S. dollars.
In April 2024, we announced that the FDA accepted our Investigational New Drug Application (“IND”) for UGN-103 and we initiated our Phase 3 UTOPIA trial, a single-arm, multicenter study that will evaluate the efficacy and safety of UGN-103 in low-grade intermediate risk NMIBC.
In April 2024, we announced that the FDA accepted our Investigational New Drug Application (“IND”) for UGN-103 and we initiated our Phase 3 UTOPIA trial, a single-arm, multicenter study is evaluating the efficacy and safety of UGN-103 in patients with recurrent low-grade intermediate risk NMIBC.
Effective July 2023, the loan accrued interest using a benchmark rate of 3-month SOFR plus 8.25% plus an additional adjustment of 0.26161%. On March 13, 2024, we entered into an amended and restated loan agreement with Pharmakon for an additional third and fourth tranche of senior secured loan. The third tranche of $25.0 million was funded in September 2024.
Effective July 2023, the loan accrued interest using a benchmark rate of 3-month SOFR plus 8.25% plus an additional adjustment of 0.26161%. On March 13, 2024, we entered into an amended and restated loan agreement, which replaced the 2022 Loan Agreement, with Pharmakon for an additional third and fourth tranche of senior secured loan (the "2024 Loan Agreement").
Financing Activities Net cash provided by financing activities was $194.6 million during the year ended December 31, 2024, compared to net cash provided by financing activities of $116.9 million during the year ended December 31, 2023.
Financing Activities Net cash provided by financing activities was $39.9 million during the year ended December 31, 2025, compared to net cash provided by financing activities of $194.6 million during the year ended December 31, 2024.
The first combination we are investigating clinically involves the sequential use of UGN-201 (imiquimod), a toll like receptor 7 (“TLR 7”) agonist, and UGN-301 in high-grade NMIBC. UGN-201 is a liquid formulation of imiquimod for intravesical administration that has been optimized for delivery in the urinary tract.
The first combination we investigated clinically involved the sequential use of UGN-201 (imiquimod), a toll like receptor 7 agonist, and UGN-301 in high-grade NMIBC. UGN-201 is a liquid formulation of imiquimod for intravesical administration that has been optimized for delivery in the urinary tract.
Each region is additionally supported by one to two clinical nurse educators to provide education and training around instillation, as well as a field reimbursement manager to help ensure access and reimbursement for appropriate patients and a key account director who engages with C-suite individuals to introduce a Jelmyto service line.
Each region is additionally supported by clinical nurse educators to provide education and training around instillation, as well as field reimbursement managers to help ensure access and reimbursement for appropriate patients and key account directors who engage with C-suite individuals to introduce a Jelmyto service line.
Components of Operating Results Revenue During the year ended December 31, 2024 and December 31, 2023, we recognized $90.4 million and $82.7 million of revenue, respectively, from sales of our product, Jelmyto . 65 Table of Contents Cost of Revenue Cost of revenue consists primarily of inventory and related costs associated with the manufacturing, distribution, warehousing and preparation of Jelmyto, including inventory write-downs.
Components of Operating Results Revenue During the year ended December 31, 2025 and December 31, 2024, we recognized $109.8 million and $90.4 million of revenue, respectively, from sales of our products. 65 Table of Contents Cost of Revenue Cost of revenue consists primarily of inventory and related costs associated with the manufacturing, distribution, warehousing and preparation of Jelmyto and Zusduri, including inventory write-downs.
In March 2019, we utilized the agreement extension option and extended the rent period for an additional three years until August 2022. In July 2022, we signed a lease extension agreement extending the term of the lease through September 2025.
In March 2019, we utilized the agreement extension option and extended the rent period for an additional three years until August 2022. In July 2022, we signed a lease extension agreement extending the term of the lease through September 2025 and in June 2025 we exercised our renewal option to extend the lease through September 2028.
Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of equity or debt financings and collaboration arrangements. 69 Table of Contents Cash Flows The following table sets forth the significant sources and uses of cash for the periods set forth below: Year Ended December 31, 2024 2023 (in thousands) Net cash (used in) provided by: Operating activities $ (96,766 ) $ (76,376 ) Investing activities (20,613 ) (953 ) Financing activities 194,619 116,931 Net change in cash and cash equivalents $ 77,240 $ 39,602 Operating Activities Net cash used in operating activities was $96.8 million during the year ended December 31, 2024, compared to $76.4 million used in operating activities during the year ended December 31, 2023.
Until such time, if ever, as we can generate sufficient product revenue, we expect to finance our cash needs through a combination of equity or debt financings and collaboration arrangements. 69 Table of Contents Cash Flows The following table sets forth the significant sources and uses of cash for the periods set forth below: Year Ended December 31, 2025 2024 (in thousands) Net cash (used in) provided by: Operating activities $ (162,444 ) $ (96,766 ) Investing activities 61,558 (20,613 ) Financing activities 39,918 194,619 Net change in cash and cash equivalents $ (60,968 ) $ 77,240 Operating Activities Net cash used in operating activities was $162.4 million during the year ended December 31, 2025, compared to $96.8 million used in operating activities during the year ended December 31, 2024.
Prepaid Forward Agreement In March 2021, we entered into a prepaid forward agreement with RTW, pursuant to which RTW agreed to provide us with an upfront cash payment of $75.0 million to support the launch of Jelmyto and the development of UGN-102, and we agreed to provide RTW with tiered future payments based on global annual net product sales of Jelmyto and UGN-102, if approved.
Prepaid Forward Agreement In March 2021, we entered into a prepaid forward agreement with RTW (the "Forward Contract"), pursuant to which RTW agreed to provide us with an upfront cash payment of $75.0 million to support the launch of Jelmyto and the development of Zusduri , and we agreed to provide RTW with tiered future payments based on global annual net product sales of Jelmyto and Zusduri , and, subject to FDA approval, UGN- 103 and UGN- 104 .
Our primary uses of capital are, and we expect will continue to be, commercialization activities, research and development expenses, including third-party clinical research and development services, laboratory and related supplies, clinical costs, including manufacturing costs, legal and other regulatory expense and general and administrative costs, partially offset by proceeds from sales of Jelmyto .
Our primary uses of capital are, and we expect will continue to be, commercialization activities, research and development expense, including third-party clinical research and development services, laboratory and related supplies, clinical costs, including manufacturing costs, legal and other regulatory expense and general and administrative costs.
We estimate that approximately 68% of low-grade intermediate risk NMIBC patients have two or more recurrences, with approximately 23% of recurrent patients having five or more recurrences. Repeated TURBT procedures to treat these recurrences can impact patients’ physical health and quality of life.
Due to high recurrence rates of low-grade intermediate risk NMIBC, repeat TURBTs may be necessary. We estimate that approximately 68% of low-grade intermediate risk NMIBC patients have two or more recurrences, with approximately 23% of recurrent patients having five or more recurrences. Repeated TURBT procedures to treat these recurrences can impact patients’ physical health and quality of life.
The total obligation for future minimum lease payments under our operating and finance leases are $0.8 million and $3.0 million, respectively, as of December 31, 2024. See Note 11 to the consolidated financial statements appearing elsewhere in this Annual Report for further information.
The total obligation for future minimum lease payments under our operating and finance leases are $4.1 million and $5.9 million, respectively, as of December 31, 2025. See Note 11 to the consolidated financial statements appearing elsewhere in this Annual Report for further information.
The following table provides a breakout of expenses by major cost type: (in thousands) 2024 2023 Personnel, facility and equipment, and other overhead costs $ 16,054 $ 16,245 Clinical and other development costs 41,091 29,369 Total $ 57,145 $ 45,614 See Note 20 to our consolidated financial statements appearing elsewhere in this Annual Report for additional disaggregation of significant research and development expenses.
The following table provides a breakout of expenses by major cost type: (in thousands) 2025 2024 Personnel, facility and equipment, and other overhead costs $ 18,530 $ 16,054 Clinical and other development costs 48,577 41,091 Total $ 67,107 $ 57,145 See Note 21 to our consolidated financial statements appearing elsewhere in this Annual Report for additional disaggregation of significant research and development expenses.
Research and Development Expenses Research and development expenses were $57.1 million and $45.6 million for the years ended December 31, 2024 and 2023, respectively.
Research and Development Expenses Research and development expenses were $67.1 million and $57.1 million for the years ended December 31, 2025 and 2024, respectively.
Preliminary results were reported through a press release in February 2023, finding that UGN-102 was suitable to administer at home by a visiting nurse under the supervision of a treating physician and resulted in 75% of patients achieving a CR, defined as no detectable disease three months after starting treatment. Patients, nurses and investigators also completed home instillation feasibility questionnaires.
Preliminary results were reported through a press release in February 2023, finding that Zusduri was suitable to administer at home by a home health professional under the supervision of a treating physician and resulted in 75% of patients achieving a CR, defined as no detectable disease three months after starting treatment.
Financing on Prepaid Forward Obligation Financing on prepaid forward obligation is comprised of financing expense related to the transaction with RTW Investments (the “RTW Transaction”) (see Note 9 to our consolidated financial statements appearing elsewhere in this Annual Report). Interest Expense Interest expense is primarily comprised of interest related to our long-term debt with Pharmakon Advisors, L.P.
Financing on Prepaid Forward Obligation Financing on prepaid forward obligation is comprised of financing expense related to the transaction (the "RTW Transaction") with RTW Investments (“RTW") (see Note 9 to our consolidated financial statements appearing elsewhere in this Annual Report).
Financing on Prepaid Forward Obligation Financing on prepaid forward obligation was $23.4 million and $21.6 million for the years ended December 31, 2024 and 2023, respectively.
Financing on Prepaid Forward Obligation Financing on prepaid forward obligation was $18.5 million and $23.4 million for the years ended December 31, 2025 and 2024, respectively.
We estimate that the annual treatable population of low-grade intermediate risk NMIBC in the United States is approximately 82,000, of which approximately 23,000 are estimated to be newly diagnosed and 59,000 are estimated to be recurrent patients.
We estimate that the annual treatable population of low-grade intermediate risk NMIBC in the United States is approximately 82,000, of which approximately 23,000 are estimated to be newly diagnosed and 59,000 are estimated to be recurrent patients. We estimate that the total addressable market opportunity for Zusduri in recurrent low-grade intermediate risk NMIBC is potentially over $5.0 billion.
The increase in financing on prepaid forward obligation of $1.8 million was driven primarily by changes in underlying assumptions for remeasuring the effective rate. Interest Expense on Long-term Debt Interest expense was $12.5 million and $14.7 million for the years ended December 31, 2024 and 2023, respectively.
The decrease in financing on prepaid forward obligation of $4.9 million was driven primarily by changes in underlying assumptions for remeasuring the effective rate. Interest Expense on Long-term Debt Interest expense was $15.3 million and $12.5 million for the years ended December 31, 2025 and 2024, respectively.
In periods prior to receiving FDA approval for Jelmyto , we recognized inventory and related costs associated with the manufacture of Jelmyto as research and development expenses.
In periods prior to receiving FDA approval for Jelmyto and Zusduri , we recognized inventory and related manufacturing costs as research and development expenses.
The first tranche of $75.0 million ($72.6 million of proceeds were received, $70.8 million net of additional transaction costs) was funded in March 2022, and the second tranche of $25.0 million was funded in December 2022.
The first tranche of $75.0 million ($72.6 million of proceeds were received, $70.8 million net of additional transaction costs) was funded in March 2022, and the second tranche of $25.0 million was funded in December 2022. On March 13, 2024, we entered into the 2024 Loan Agreement. The third tranche of $25.0 million was funded in September 2024.
Our approved product Jelmyto ® (mitomycin) for pyelocalyceal solution, and our investigational candidates, UGN-102 (mitomycin) for intravesical solution, UGN-103 (mitomycin) for intravesical solution and UGN-104 (mitomycin) for pyelocalyceal solution, are designed to ablate tumors by non-surgical means and to treat several forms of non-muscle invasive urothelial cancer, including low-grade upper tract urothelial cancer (“low-grade UTUC”) in the case of Jelmyto and UGN-104 and low-grade intermediate risk non-muscle invasive bladder cancer (“low-grade intermediate risk NMIBC”)in the case of UGN-102 and UGN-103.
Our approved products Jelmyto (mitomycin) for pyelocalyceal solution and Zusduri (mitomycin) for intravesical solution are designed to ablate tumors by non-surgical means and to treat several forms of non-muscle invasive urothelial cancer, including low-grade upper tract urothelial cancer (“low-grade UTUC”) and recurrent low-grade intermediate risk non-muscle invasive bladder cancer (“low-grade intermediate risk NMIBC”), respectively.
(“Agenus”), pursuant to which Agenus granted us an exclusive, worldwide (not including Argentina, Brazil, Chile, Colombia, Peru, Venezuela and their respective territories and possessions), royalty-bearing, sublicensable license under Agenus’s intellectual property rights to develop, make, use, sell, import, and otherwise commercialize products incorporating a proprietary monoclonal antibody of Agenus known as AGEN1884 (zalifrelimab), an anti-CTLA-4 antagonist, for the treatment of cancers of the urinary tract via intravesical delivery.
We do not expect to incur significant additional costs related to this program going forward. 64 Table of Contents License Agreement and Acquisition Agreement Agenus Agreement In November 2019, we entered into a license agreement with Agenus, pursuant to which Agenus granted us an exclusive, worldwide (not including Argentina, Brazil, Chile, Colombia, Peru, Venezuela and their respective territories and possessions), royalty-bearing, sublicensable license under Agenus’s intellectual property rights to develop, make, use, sell, import, and otherwise commercialize products incorporating a proprietary monoclonal antibody of Agenus known as AGEN1884 (zalifrelimab), an anti-CTLA-4 antagonist, for the treatment of cancers of the urinary tract via intravesical delivery.
In addition, our organization currently includes several medical science liaisons who appropriately engage with physicians interested in learning more about UroGen, Jelmyto and our technology, both in person and virtually. In total, our customer-facing team comprises approximately 100 representatives. We are committed to helping patients access Jelmyto .
In addition, our organization includes medical science liaisons who appropriately engage with physicians interested in learning more about UroGen, Jelmyto and our technology, both in person and virtually. In total, our customer-facing team comprises approximately 150 colleagues. We are committed to helping patients access Jelmyto . Our market access teams have laid the foundation for coverage and reimbursement.
Through December 31, 2024, we funded our operations primarily through public equity offerings, private placements of equity securities and our funding arrangements with RTW and Pharmakon.
Through December 31, 2025, we funded our operations primarily through public equity offerings, private placements of equity securities and our funding arrangements with RTW, our credit facility under the 2024 Loan Agreement with Pharmakon, and product sales.
UGN-102 is administered locally using the standard practice of intravesical instillation directly into the bladder via a catheter. The instillation into the bladder is expected to take place in a physician’s office as a non-operative outpatient treatment, in comparison with TURBT or similar surgical procedures, which are operations often conducted under general anesthesia and may require an overnight stay.
The instillation into the bladder is expected to take place in a physician’s office as a non-operative outpatient treatment, in comparison with TURBT or similar surgical procedures, which are operations usually conducted in an operating room under general anesthesia and may require an overnight stay.
The $20.4 million increase was attributable primarily to higher net loss driven by increased operating expenses such as regulatory and commercial preparation costs related to UGN-102, as well as timing of certain payments and accruals.
The $65.6 million increase was attributable primarily to higher net loss driven by increased operating expenses such as commercial costs related to Zusduri and clinical trials expenses related to UGN-103 and UGN-104, as well as timing of certain payments and accruals.
The increase in research and development expenses of $11.5 million is primarily attributable to higher manufacturing costs, which are recognized as research and development expenses prior to our product candidates receiving FDA approval, regulatory expenses in connection with UGN-102, and costs associated with the Phase 3 UTOPIA trial for UGN-103, partially offset by lower UGN-102 clinical trial costs and costs related to the research into ingredient scale-up and production efficiency for Jelmyto . 68 Table of Contents Selling and Marketing Expenses Selling and marketing expenses were $75.2 million and $54.7 million for the years ended December 31, 2024 and 2023, respectively.
The increase in research and development expenses of $10.0 million is primarily attributable to higher manufacturing costs for Zusduri , which are recognized as research and development expenses prior to our product candidates receiving FDA approval, costs associated with the Phase 3 UTOPIA trial for UGN-103 and the Phase 3 trial for UGN-104, as well as the acquisition of certain assets of IconOVir, partially offset by lower clinical trial costs and regulatory expenses in connection with Zusduri . 68 Table of Contents Selling and Marketing Expenses Selling and marketing expenses were $99.1 million and $75.2 million for the years ended December 31, 2025 and 2024, respectively.
Our ability to continue as a going concern is expected to be impacted by the advancement of UGN-102 through regulatory approval, our ability to raise additional capital to fund our operations, and produce cash inflows from Jelmyto product sales.
Our ability to continue as a going concern is expected to be impacted by our ability to produce cash inflows from Jelmyto and Zusduri product sales, the rate of physician and patient adoption of Zusduri and our ability to raise additional capital to fund our operations in the future.
If we are unable to obtain approval for UGN-102 and generate sufficient cash inflows from the sale and distribution of UGN-102, we may need to raise additional capital in the future or reduce operating expenditures.
If we are unable to generate sufficient cash inflows from Jelmyto and Zusduri product sales, we may need to raise additional capital in the future or reduce operating expenditures.
The increase of $77.7 million is attributable primarily to proceeds from the issuance of ordinary shares under the ATM Sales Agreement, the underwritten public offering and the issuance of debt related to the third tranche of the Pharmakon loan as compared to proceeds from the Private Placement in the prior year.
The decrease of $154.7 million is attributable primarily to proceeds from the issuance of ordinary shares under the ATM Sales Agreement in the first quarter of 2024, the underwritten public offering in the second quarter of 2024 and the issuance of debt related to the third tranche under the 2024 Loan Agreement with Pharmakon in the third quarter of 2024.
No treatment-related deaths occurred. 63 Table of Contents In December 2022, we presented new data from a follow-up study to the OLYMPUS trial designed to obtain long‐term data on Jelmyto .
No treatment-related deaths occurred. 63 Table of Contents In February 2025, we presented additional new data from the long-term follow-up study to UroGen’s Phase 3 Olympus trial.
Our market access teams have laid the foundation for coverage and reimbursement, meeting multiple times with payors. Medicare patients with supplemental coverage are covered and the vast majority of commercial plans have policies in place, in whole covering over 150 million lives. In addition to reimbursement and access, we have also been focused on ensuring seamless integration into physician practices.
Medicare patients with supplemental coverage are covered and the vast majority of commercial plans have policies in place to cover Jelmyto . In addition to reimbursement and access, we have also been focused on ensuring seamless integration into physician practices.
The increase in selling and marketing expenses of $20.5 million is primarily attributable to UGN-102 commercial preparation activities as well as an increase in overall commercial operation costs including compensation, advisory, meetings, conferences, trainings and software costs.
The increase in selling and marketing expenses of $23.9 million is primarily attributable to Zusduri commercial activities as well as an increase in overall commercial operation costs including the expansion of the sales force, compensation, advisory, meetings, conferences, trainings and back office support costs.
We estimate that around 35% of patients will experience an adverse event within 90 days of undergoing a TURBT, and patients who have had two to four procedures have an estimated 14% greater risk of death than patients who have only had one procedure.
Approximately 35% of patients will experience an adverse event within 90 days of undergoing a TURBT, and patients who have had two to four procedures have an estimated 14% greater risk of death than patients who have only had one procedure. On July 27, 2023, we announced topline data from our Phase 3 trials, ATLAS and ENVISION.
We also completed a Phase 3b study with the objective of demonstrating whether UGN-102 can be administered at home by a qualified home health professional, avoiding the need for repeated visits to a healthcare setting for instillation.
Results of the long-term extension study were published online in the J ournal of Clinical Genitourinary Cancer in July 2025 . We also completed a Phase 3b study with the objective of demonstrating whether Zusduri can be administered at home by a qualified home health professional, avoiding the need for repeated visits to a healthcare setting for instillation.
General and Administrative Expenses General and administrative expenses were $45.9 million and $38.6 million for the years ended December 31, 2024 and 2023, respectively. The increase in general and administrative expenses of $7.3 million is primarily attributable to higher compensation expenses, costs for announcements and communications related to UGN-102, third-party advisory services, and ongoing managed services.
General and Administrative Expenses General and administrative expenses were $56.0 million and $45.9 million for the years ended December 31, 2025 and 2024, respectively. The increase in general and administrative expenses of $10.1 million is primarily attributable to higher compensation expenses, expenses related to commercial readiness support for Zusduri , general third-party advisory services, and ongoing managed services.
We expect the Master Protocol will allow us to more quickly evaluate safety, tolerability and dosing of UGN-301 in combination with additional immunomodulators and chemotherapies, with the goal of developing optimized treatment regimens for patients.
It provided more flexibility to add study arms as the trial progressed to increase efficiency and potentially reduce costs. We expected the Master Protocol would allow us to more quickly evaluate safety, tolerability and dosing of UGN-301 in combination with additional immunomodulators and chemotherapies, with the goal of developing optimized treatment regimens for patients.
The obligations of UroGen Pharma, Inc., as the borrower under the loan agreement (the "Borrower") are guaranteed on a full and unconditional basis by UroGen Pharma Ltd. and the other guarantor parties thereto and are secured by substantially all of the respective Credit Parties’ tangible and intangible assets and property, including intellectual property, subject to certain exceptions.
The obligations of UroGen Pharma, Inc., as the borrower under the 2026 Loan Agreement, are guaranteed by UroGen Pharma Ltd., subject to customary limitations on parent guarantees under Israeli law, and are secured by substantially all of the tangible and intangible assets and property, including intellectual property, of UroGen Pharma, Inc. and UroGen Pharma Ltd., subject to certain exceptions.
Income tax expense also consists of our estimate of uncertain tax positions, and related interest and penalties. See Note 17 to our consolidated financial statements appearing elsewhere in this Annual Report for further information.
We have provided a full valuation allowance with respect to the deferred tax assets related to these carry forward losses. Income tax expense also consists of our estimate of uncertain tax positions, and related interest and penalties. See Note 18 to our consolidated financial statements appearing elsewhere in this Annual Report for further information.
We believe these two combinations could elicit both an innate and adaptive immune response, which may translate into a long-lasting acquired immune response, and potentially represent a valid post-TURBT adjuvant treatment of high-grade NMIBC.
We believed these two combinations could elicit both an innate and adaptive immune response, which may translate into a long-lasting acquired immune response, and potentially represent a valid post-TURBT adjuvant treatment of high-grade NMIBC. We investigated these combinations to determine if they could make local therapy a potentially more effective treatment option while minimizing systemic exposure and potential side effects.
In the ENVISION trial, the 12-month DOR data by Kaplan-Meier estimate for patients who achieved a CR at three months after the first instillation of UGN-102 was 82.3% (95% CI, 75.9%, 87.1%). The ENVISION trial met its primary endpoint with patients having a 79.6% (73.9%, 84.5%) CR rate at three months after the first instillation of UGN-102.
The ENVISION trial met its primary endpoint with patients having a 79.6% (73.9%, 84.5%) CR rate at three months after the first instillation of Zusduri. Among the patients in the ENVISION trial who achieved a CR at three months, 76.4% (69.8%, 82.3%) maintained a CR at 12 months.
Where at risk contingent milestone payments are due to third parties under research and development and collaboration agreements, the milestone payment obligations are expensed when such development milestone results are achieved.
Where at risk contingent milestone payments are due to third parties under research and development and collaboration agreements, the milestone payment obligations are expensed when such development milestone results are probable of being achieved. We are currently focused on advancing our product candidates, and our future research and development expenses will depend on their clinical success.
Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through revenues from commercial sales of Jelmyto and a combination of equity or debt financings and collaboration arrangements.
We cannot estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidates or whether, or when, we may achieve profitability. Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of equity or debt financings and collaboration arrangements.
We have incurred losses since our inception and negative cash flows from our operations, and as of December 31, 2024 we had an accumulated deficit of $806.2 million. We anticipate that we will continue to incur losses for the reasonably foreseeable future.
We have incurred losses since our inception and negative cash flows from our operations, and as of December 31, 2025, we had an accumulated deficit of $959.7 million.
Accordingly, we do not expect to pay taxes in Israel until we have taxable income after the full utilization of our carry forward tax losses. We have provided a full valuation allowance with respect to the deferred tax assets related to these carry forward losses.
We anticipate that we will continue to generate tax losses and that we will be able to carry forward these tax losses indefinitely to future taxable years. Accordingly, we do not expect to pay taxes in Israel until we have taxable income after the full utilization of our carry forward tax losses.
Selling and Marketing Expenses To date, selling and marketing expenses consist primarily of commercial personnel costs (including share-based compensation) along with commercialization activities related to Jelmyto and pre-commercialization activities related to UGN-102.
Selling and Marketing Expenses To date, selling and marketing expenses consist primarily of commercial personnel costs (including share-based compensation) along with commercialization activities related to Jelmyto and Zusduri . General and Administrative Expenses General and administrative expenses consist primarily of personnel costs (including share-based compensation related to directors, executives, finance, medical affairs, business development, investor relations, and human resource functions).

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeFor example, the dollar appreciated against the NIS during 2024 by a total of 1.2%. If the dollar cost of our operations in Israel increases, our dollar-measured results of operations will be adversely affected. Our operations also could be adversely affected if we are unable to effectively hedge against currency fluctuations in the future.
Biggest changeFor example, the dollar depreciated against the NIS during 2025 by approximately 12.5%. If the dollar cost of our operations in Israel increases, our dollar-measured results of operations will be adversely affected. Our operations also could be adversely affected if we are unable to effectively hedge against currency fluctuations in the future.
If a 10% change in interest rates were to have occurred on December 31, 2024, this change would not have had a material effect on the fair value of our cash and cash equivalents as of that date. Inflation Risk Inflation generally may affect us by increasing our cost of labor and clinical trial costs.
If a 10% change in interest rates were to have occurred on December 31, 2025, this change would not have had a material effect on the fair value of our cash and cash equivalents as of that date. Inflation Risk Inflation generally may affect us by increasing our cost of labor and clinical trial costs.
Inflation did not have a material effect on our business, financial condition or results of operations during the year ended December 31, 2024. Foreign Currency Exchange Risk The U.S. dollar is our functional and reporting currency. However, a significant portion of our operating expenses are incurred in NIS.
Inflation did not have a material effect on our business, financial condition or results of operations during the year ended December 31, 2025. Foreign Currency Exchange Risk The U.S. dollar is our functional and reporting currency. However, a significant portion of our operating expenses are incurred in NIS.
Financial instruments that potentially subject us to significant concentrations of credit risk consist primarily of cash and cash equivalents. As of December 31, 2024, we had approximately $241.7 million in cash, cash equivalents and marketable securities. We invest our cash primarily in money market accounts, certificates of deposit, commercial paper and debt instruments of U.S. government-sponsored agencies, the U.S.
Financial instruments that potentially subject us to significant concentrations of credit risk consist primarily of cash and cash equivalents. As of December 31, 2025, we had approximately $120.5 million in cash, cash equivalents and marketable securities. We invest our cash primarily in money market accounts, certificates of deposit, commercial paper and debt instruments of U.S. government-sponsored agencies, the U.S.

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