What changed in this filing

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Item 1. Business

2025-03-10 compared with 2024-03-14 · 116 added, 105 removed, 646 unchanged (25% of the section changed)

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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 approved product Jelmyto ® (mitomycin) for pyelocalyceal solution, and our investigational candidate, UGN-102 (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 low-grade intermediate risk non-muscle invasive bladder cancer (“low-grade intermediate risk NMIBC”), respectively.

In addition, our immuno-uro-oncology pipeline includes UGN-301 (zalifrelimab), an anti-CTLA-4 antibody, which we intend to study as both monotherapy and combination therapy.

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.

In addition, our immuno-uro-oncology pipeline includes UGN-301 (zalifrelimab), an anti-CTLA-4 antibody, which we are currently studying as both a monotherapy and combination therapy.

Our Reverse Thermal Hydrogel Technology

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maintaining the active drug’s molecular structure and mode of action.

These characteristics of RTGel enable sustained release of mitomycin in the urinary tract for both Jelmyto and UGN-102.

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.

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Each cancer cell goes through various phases during the cell cycle.

However, the cell cycle is not synchronized in all cancer cells, which means that at any given point in time only a portion of the cancer cells are at their S-phase, or susceptible to the instilled mitomycin in the bladder.

Increased dwell time, facilitated by our RTGel preparations Jelmyto and UGN-102, is designed to increase cell killing in vitro when compared to aqueous solutions of mitomycin.

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.

The following chart summarizes the current status of our pipeline:

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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.

However, the specific anatomy and physiology of the upper urinary tract make the performance of organ-sparing endoscopic tumor resection and instillation of adjuvant chemotherapy challenging, leading to high recurrence rates.

However, the specific anatomy and physiology of the upper urinary tract can impede the effectiveness of organ-sparing endoscopic tumor resection and instillation of adjuvant chemotherapy, leading to high recurrence rates.

Patients often undergo multiple endoscopic resection procedures, which increases the probability of potential complications of resection, including perforation and ureteral stricture, or a narrowing of the ureter.

Endoscopic tumor resection, which aims to be a kidney sparing surgical procedure, is conducted only in patients with low-grade disease and with limited tumor burden (unifocal tumor, low grade histology, less than 2 cm in greatest dimension).

Ultimately, 70% to 80% o f patients with low-grade UTUC undergo an RNU.

Treatment is further complicated by the fact that low-grade UTUC is most commonly diagnosed in patients over 70 years of age, who may already have compromised kidney function and other comorbidities such as cardiovascular disease, diabetes and pulmonary disease and may suffer further complications as a result of a major surgery.

Our Solution:

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No patient had progressed to high‐grade disease.

In November 2024, we published results from a long-term follow-up study with Jelmyto evaluating 20 of the 41 patients from the OLYMPUS trial who achieved a CR after primary chemoablation with Jelmyto.

T he median duration of response in this subset of patients was 47.8 months.

The study results are published online in the Journal of Urology .

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 seven regional business director positions, who are in turn supported by seven regional operations manager positions.

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.

These territory business manager positions are led by eight regional business director positions, who are in turn supported by eight regional operations manager positions.

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.

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.

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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 APC (Ambulatory Payment Classification), effective from October 1, 2023.

We have also launched a registry to capture data and evaluate real world outcomes in patients with low-grade UTUC that have been or will be treated with Jelmyto .

CMS has granted Jelmyto a New Technology Ambulatory Payment Classification ("APC"), effective from October 1, 2023.

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.

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These issued patents are expected to expire in 2031.

Medac has intellectual property protection for its proprietary mitomycin formulation technology expected through June 2035.

We also own three pending U.S.

applications and any patents that issue from these applications is expected to expire between 2031 and 2043.

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

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Low-grade intermediate risk NMIBC is defined as having one or two of following characteristics:

tumor larger than 3 cm, multiple tumors in the bladder and a recurrence in less than one year from the prior tumor.

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.

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Limitations of Current Therapies for Low-Grade Non-Muscle Invasive Bladder Cancer

Recurrence, which occurs in approximately 80% of patients, is the primary threat for patients with low-grade NMIBC.

Recurrence is the primary threat for patients with low-grade NMIBC.

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.

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UGN-102 (Mitomycin) for Intravesical Solution

We are evaluating the safety and efficacy of UGN-102, our novel sustained-release formulation of mitomycin for the treatment of low-grade intermediate risk NMIBC.

UGN-102 is our sustained-release formulation of mitomycin that we are developing for the treatment of low-grade intermediate risk NMIBC.

UGN-102 is administered locally using the standard practice of intravesical instillation directly into the bladder via a catheter.

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The primary endpoint is CR rate at three months after the first instillation, and the key secondary endpoint is durability of response in patients who achieve CR at the three-month assessment.

In February 2022, we announced the initiation of the Phase 3 ENVISION trial, targeting enrollment of 220 patients across 90 sites.

In December 2022 we completed our target enrollment of the Phase 3 ENVISION trial.

As a result of the FDA's acceptance of a single arm approach, we stopped enrollment of the Phase 3 ATLAS trial.

However, at the time enrollment was stopped, patients who had signed an informed consent were able to complete screening, and if eligible were randomized into the trial.

On July 27, 2023, we announced topline data from our Phase 3 trials, ATLAS and ENVISION.

In the ATLAS trial, UGN-102 met its primary endpoint of disease-free survival, reducing risk of recurrence, progression, or death by 55%.

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.

The ENVISION trial met its primary endpoint by demonstrating that patients treated with UGN-102 had a 79.2% rate of CR at three months following the initial treatment.

Additional data evaluating the secondary endpoint of duration of response from ENVISION is anticipated in 2024.

In both trials, the safety profile of UGN-102 was acceptable, with a safety profile comparable to that observed in previous clinical trials of UGN-102.

We also initiated 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.

In June 2024, we announced positive secondary endpoint duration of response (“DOR”) data from the Phase 3 ENVISION trial investigating UGN-102 for intravesical solution in patients with low-grade intermediate risk NMIBC.

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.

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.

Among all 240 patients enrolled in the ENVISION trial, 60.8% (54.3%, 67.0%) were in CR at 12 months.

In the ENVISION trial, DOR Kaplan-Meier estimates at 15 (n=43) and 18 (n=9) months were both 80.9% (95% CI, 73.9%, 86.2%) with a median follow-up time of 13.8 months after the 3-month CR.

The ENVISION trial demonstrated a similar safety profile to that observed in the OPTIMA II and ATLAS trials, with treatment-emergent adverse events typically mild-to-moderate in severity.

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 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.

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.

As per the study design, patients in this study received six once-weekly intravesical instillations of UGN-102 with the initial treatment visit occurring at the investigative site and instillation performed by a qualified physician.

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The FDA indicated that the current clinical development plan for UGN-102, which includes evaluation of duration of CR at 12 months from the pivotal ENVISION trial, will support submission of an NDA for the treatment of low-grade intermediate risk NMIBC.

The FDA indicated that it may seek the advice of the Oncology Drug Advisory Committee as part of the NDA review process.

The FDA also agreed that the UGN-102 NDA can utilize a rolling review, allowing for early submission of the Chemistry, Manufacturing and Controls ("CMC") sections of the NDA, which we submitted in January 2024.

Based on our agreement with the FDA, we expect to complete the submission of the rolling NDA for UGN-102 in September 2024.

In August 2024, we completed the submission of the rolling NDA for UGN-102.

In October 2024, the FDA accepted our NDA for UGN-102 (mitomycin) for intravesical solution and assigned a Prescription Drug User Fee Act ("PDUFA") goal date of June 13, 2025.

We anticipate, and are preparing for, an FDA advisory committee meeting.

If approved, UGN-102 would become the first FDA-approved medicine for the treatment of low-grade intermediate-risk NMIBC.

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.

(“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 mitomycin formulation technology with our RTGel technology, which we believe will provide advantages related to production, cost, supply and product convenience.

We plan to initiate a Phase 3 study in 2024 to explore the safety and efficacy of UGN-103 in low-grade intermediate risk NMIBC.

We also plan to initiate a Phase 3 study in 2024 to explore the safety and efficacy of UGN-104 in low-grade UTUC.

(“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.

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.

We plan to enroll 87 patients in the UTOPIA trial, with patients receiving 75 mg of mitomycin via intravesical instillation once a week for six weeks.

Efficacy will be assessed by the CR rate at the three-month visit.

Patients who have a CR at the three-month visit, defined as having no detectable disease in the bladder, will enter the follow-up period of the study.

Patients will remain on study until disease recurrence, disease progression, death, or the last patient completes 12 months of follow-up (i.e., 15 months after the first instillation), whichever occurs first.

In October 2024, we announced the first patient dosed in the UTOPIA trial.

An NDA submission is projected for 2026, followed by a standard review period and potential approval and, if approved, the commercial launch in 2027.

In February 2025, the FDA accepted our IND for UGN-104.

We plan to initiate a Phase 3 trial of UGN-104 in low-grade UTUC in the first half of 2025.

UGN-301 (zalifrelimab) intravesical solution

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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.

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.

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.

Limitations of Current Therapies for High-Grade NMIBC

O nly five drugs have been approve d for high-grade NMIBC, all used as adjuvant treatment:

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;

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Keytruda® (pembrolizumab), which was approved by the FDA in 2020;

and Adstiladrin® (nadofaragene firadenovec-vncg), which was approved by the FDA in 2022 for BCG unresponsive CIS.

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.

However, despite the approvals of these novel treatments, recurrence and progression rates remain high.

BCG, an immunotherapy-based drug, is used as an adjuvant treatment for patients with high-grade NMIBC.

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When administered systemically, they have led to improved outcomes in patients suffering from advanced cancers.

The completion of non-human primate toxicity studies supported the initiation of a multi-arm Phase 1 study of UGN-301 in combination with other agents.

We believe that this approach leverages our unique drug delivery technology and provides an opportunity to evaluate intravesical delivery of UGN-301 in combination with other immuno-modulators, chemotherapies, gene therapy and innate immune stimulators.

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We have obtained Orphan Drug Designation for UGN-201 for the treatment of CIS in the bladder.

We have an active Investigational New Drug Application ("IND") for UGN-201, which has been effective since 2013.

We have an active IND for UGN-201, which has been effective since 2013.

The second combination we are investigating clinically involves the sequential administration of gemcitabine and UGN-301 to the bladder in high-grade NMIBC.

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UGN-301 is delivered using our proprietary RTGel technology, which has been designed to significantly improve the effectiveness of certain intravesical therapy.

We believe that these combinations make local therapy a potentially more effective treatment option while minimizing systemic exposure and its potential side effects.

We are investigating these combinations to determine if they may make local therapy a potentially more effective treatment option while minimizing systemic exposure and potential side effects.

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.

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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.

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 is actively enrolling.

We expect safety and tolerability data from this Phase 1 study in mid-2024.

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 all three of 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.

Research and Development and License Agreements

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UGN-301 is a formulation of zalifrelimab administered using RTGel technology that is in Phase 1 clinical development for high-grade NMIBC.

MD Anderson Agreement

In January 2021, we announced that we had entered into a three-year strategic research collaboration agreement with MD Anderson focusing on the sequential use of UGN-201 and UGN-301 as an investigational treatment for high-grade NMIBC.

Pursuant to the agreement, we have made bi-annual payments totaling $2.0 million to MD Anderson to fund the collaboration, recognized evenly over the associated period through research and development expenses.

In July 2022, we determined that we had achieved the objectives that we established when the agreement was initiated, and notified MD Anderson that we were exercising our right to conclude the collaboration in 2022 as we did not foresee initiating further development activities as part of the collaboration, although we will continue to collaborate on existing joint projects.

As a result of this notification, we were not responsible for any further fixed bi-annual funding payments in 2023, although we are responsible for costs related to existing joint projects to the extent they exceed the payments already made to MD Anderson.

Our Competitive Strengths

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Strong intellectual property position.

We have a robust intellectual property portfolio that includes 43 granted patents worldwide and more than 45 pending patent applications filed in the US, Europe, Israel, Japan, Canada, China, Mexico and Australia.

In the United States, we currently have 19 granted 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, inter alia compositions comprising a Botulinum Toxin, UGN-201, UGN-302 (the sequential use of UGN-201 and UGN-301) and our future product candidates that are under company research.

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.

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.

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 2024 and 2037.

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.

Experienced and accomplished leadership team with proven track record.

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Advance our product candidate UGN-102 and establish it as the first primary non-surgical chemoablative therapy in its target indication following regulatory approval.

We submitted an IND for UGN-102 in June 2018.

On July 27, 2023, we announced topline data from our Phase 3 trials, ATLAS and ENVISION, and additional data evaluating the secondary endpoint of duration of response from ENVISION is anticipated in 2024.

We believe that UGN-102 has the potential to be a new therapeutic option for the treatment of low-grade intermediate risk NMIBC patients, if approved.

In August 2024, we completed the submission of a rolling NDA for UGN-102.

In October 2024, the FDA accepted our NDA for UGN-102 and assigned a PDUFA goal date of June 13, 2025.

We believe that UGN-102 has the potential to be the first FDA-approved therapeutic option for the treatment of low-grade intermediate risk NMIBC patients.

Expand our uro-oncology product pipeline.

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We believe that the combination treatments make local therapy a potentially more effective treatment option while minimizing systemic exposure and its potential side effects.

We also plan to initiate a Phase 3 study in 2024 to explore the safety and efficacy of UGN-103 in low-grade, intermediate risk NMIBC.

We also plan to initiate a Phase 3 study in 2024 to explore the safety and efficacy of UGN-104 in low-grade UTUC.

In October 2024, we initiated a Phase 3 study to explore the safety and efficacy of UGN-103 in low-grade, intermediate risk NMIBC.

We also plan to initiate a Phase 3 study in the first half of 2025 to explore the safety and efficacy of UGN-104 in low-grade UTUC.

UGN-103 and UGN-104 combine medac’s proprietary mitomycin formulation technology with our RTGel technology, which we believe will provide advantages related to production, cost, supply and product convenience.

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Intellectual Property

Our patent estate includes patents and patent applications with claims directed to our approved product, Jelmyto and our lead product candidate, UGN-102, a proprietary RTGel technology, various local compositions comprising different active ingredients, inter alia compositions comprising a Botulinum Toxin, UGN-201, UGN-302 (the sequential use of UGN-201 and UGN-301) and our future product candidates that are under company research.

In the United States, we currently have 19 granted 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, inter alia compositions comprising a Botulinum Toxin, UGN-201 and our future product candidates that are under company research.

Our patent estate includes patents and patent applications with claims directed to our approved product, Jelmyto and our lead product candidate, UGN-102, as well as UGN-103 and UGN-104, a proprietary RTGel technology, 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 future product candidates that are under company research.

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.

These patents claim methods, combination products and novel compositions for treating different diseases, especially cancer in internal cavities, in particular urinary tract cancer.

These issued patents are set to expire between 2024 and 2037.

In total, our IP portfolio includes 43 granted patents worldwide, and more than 45 pending patent applications filed in the US, Europe, Israel, Japan, Canada, China, Mexico and Australia that are directed to cover various methods, systems and compositions for treating cancer locally, by intravesical means, utilize various active ingredients and the combinations thereof.

These patent applications, if issued, are set to expire between 2031 and 2043.

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.

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.

Our worldwide intellectual property portfolio includes patents and patent applications filed in many jurisdictions such as the US, Europe, Israel, Japan, Canada, China and Australia of which are expected to remain in effect until 2043, if allowed:

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.

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Pharmaceutical compositions comprising an imidazoquinolin-amine (specifically imiquimod) for treating bladder cancer diseases.

Composition comprising immunomodulators such as anti-PD1 and/or anti-CTLA4 for topical/intravesical administration as a monotherapy or a combo-therapy.

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 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 ®, UroGen ® and Cystoject™ 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 ®, RTGel ® and UroGen ® and for certain other tradenames and logos.

In addition, we have a registered trademark in the U.S.

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We are developing products for patients with low-grade UTUC, low-grade NMIBC and high-grade NMIBC.

Prior to Jelmyto , there were no approved drugs used to treat the low-grade UTUC.

Prior to Jelmyto , there were no approved drugs used to treat low-grade UTUC.

Tumor resection surgeries are conducted in some cases of low-grade UTUC;

however, complete kidney and upper urinary tract removal is the standard of care for recurring UTUC.

We are aware of a company called Steba Biotech with an IND granted in December 2020 who has initiated a Phase 3 study of padeliporfin for the treatment of adult patients with low-grade and unifocal high-grade UTUC.

We are aware of a company called ImPact Biotech with an IND granted in December 2020 that has initiated a Phase 3 study of padeliporfin for the treatment of adult patients with low-grade and unifocal high-grade UTUC.

We do not know whether other competitors in the NMIBC space are already developing, or plan to develop, UTUC treatments.

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However, off-label usage as a standard of care does not change the FDA’s approval criteria and does not suggest that FDA approval is more likely than for other investigational drugs.

Companies such as Janssen and Lipac are conducting, or have recently conducted clinical trials for product candidates for the treatment of low-grade intermediate risk NMIBC.

Companies such as Johnson & Johnson, CG Oncology, Aura Biosciences and LIPAC Oncology are conducting, or have recently conducted, clinical trials for product candidates for the treatment of low-grade intermediate risk NMIBC.

The standard of care for treating high-grade NMIBC patients is the TURBT procedure for papillary tumor resection, followed by post-operative adjuvant BCG.

In the case of high-grade disease without papillary tumor (CIS), BCG is used alone as primary therapy.

BCG was approved by the FDA in 1989, since its approval, only three other drugs were approved for high-grade NMIBC:

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;

and Adstiladrin, approved by the FDA in 2022 for BCG unresponsive CIS.

Valstar is indicated for patients with CIS that do not respond to BCG treatment and is rarely used.

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.

Valstar is indicated for patients with CIS who do not respond to BCG treatment and is rarely used.

Keytruda was approved for CIS with or without papillary involvement for patients who do not respond to BCG treatment.

Additionally, in January 2025 Johnson & Johnson announced the submission of their NDA for TAR-200 for the treatment of patients with BCG unresponsive high-risk NMIBC with CIS.

It remains to be seen whether the broader urology community will adopt a systemic infused immunotherapy into their clinical management of BCG unresponsive NMIBC.

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There are several products in the development pipeline, most of which are treatments targeted for high-grade NMIBC patients who have failed BCG treatment and are facing cystectomy.

We are aware of several pharmaceutical companies that are developing drugs in the fields of urology and uro-oncology, such as AADi, LLC, Biocancell Ltd., Bristol Myers Squibb, CG Oncology Inc., enGene Holdings, Ferring Pharmaceuticals, FKD Therapies Oy, GSK, ImmunityBio, Janssen, Merck Sharp & Dohme Corp, Pfizer, Prokarium, Protara Therapeutics, Roche, Samyang Biopharma, Steba Biotech Ltd., SURGE Therapeutics, Viralytics Limited and Vyriad.

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.

In addition, we face competition from existing standards of treatment, surgical tumor resection procedures.

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Patent Numbers 9,040,074 and 9,950,069 each of which expires in January 2031, are invalid, unenforceable, or will not be infringed by Teva’s manufacture, use, or sale of the generic product described in its ANDA submission.

See Part I, Item 3.

“Legal Proceedings” for additional discussion.

The FDA provides periods of regulatory exclusivity, which provides the holder of an approved NDA limited protection from new competition in the marketplace for the innovation represented by its approved drug for a period of three or five years following the FDA’s approval of the NDA.

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During the seven-year exclusivity period, the FDA may not approve any other applications to market the same drug for the same disease, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.

Orphan drug exclusivity does not prevent FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.

Orphan drug exclusivity does not prevent the FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.

Among the other benefits of Orphan Drug Designation are tax credits for certain research and a waiver of the NDA application user fee.

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The FDA may give a priority review designation to drugs that are intended to treat serious conditions and provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions.

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.

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.

For non-NME standard applications, the FDA has set the review goal of 10 months from the submission date to complete its initial review and to make a decision on the application.

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In January 2016, CMS issued a final rule regarding the Medicaid Drug Rebate Program, effective April 1, 2016, that, among other things, revises the manner in which the AMP is to be calculated by manufacturers participating in the program and implements certain amendments to the Medicaid rebate statute created under the ACA.

On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s AMP for single source and innovator multiple source drugs beginning January 1, 2024.

On March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s AMP for single-source and innovator multiple source drugs beginning January 1, 2024.

Drugs that are approved under a biologics license application ("BLA"), or an NDA, including a 505(b)(2) NDA, are subject to an additional requirement to calculate and report the manufacturer’s best price for the drug and inflation penalties which can substantially increase rebate payments.

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CMS has established a permanent and product-specific J-code for Jelmyto that took effect on January 1, 2021.

CMS granted Jelmyto a New Technology APC (Ambulatory Payment Classification), effective from October 1, 2023.

A service is separately for paid 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.

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.

This generally occurs within two to three years from the time a new HCPCS code becomes effective.

However, if CMS are able to collect sufficient claims data in less than two years, CMS may consider reassigning the service to an appropriate APC, or, if CMS does not have sufficient data at the end of three years upon which to base its reassignment to an appropriate clinical APC, CMS may keep the service in a New Technology APC until adequate data become available.

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 ambulatory payment classification.

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.

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The ACA, among other things, subjected manufacturers to new annual fees and taxes for specified branded prescription drugs, increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program, expanded health care fraud and abuse laws, revised the methodology by which rebates owed by manufacturers to the state and federal government for covered outpatient drugs under the Medicaid Drug Rebate Program are calculated, imposed an additional rebate similar to an inflation penalty on new formulations of drugs, extended the Medicaid Drug Rebate Program to Medicaid managed care organizations, expanded the 340B program, which caps the price at which manufacturers can sell covered outpatient pharmaceuticals to specified hospitals, clinics and community health centers, and provided incentives to programs that increase the federal government’s comparative effectiveness research.

There have been judicial and Congressional challenges, as well as efforts by the Trump Administration to repeal or replace certain aspects of the ACA.

For example, on June 17, 2021, the U.S.

Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the individual mandate was repealed by Congress.

On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (“IRA”) into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

There have been judicial and Congressional challenges, as well as certain aspects of the ACA.

For example, on August 16, 2022, the Inflation Reduction Act of 2022 (“IRA”) was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a newly established manufacturer discount program.

It is possible that the ACA will be subject to judicial or Congressional challenges in the future.

It is unclear how any such challenges and the healthcare reform measures of the Biden administration will impact the ACA.

It is unclear how any such challenges and the healthcare reform measures of the current administration will impact the ACA.

Other legislative changes have been proposed and adopted in the United States since the ACA was enacted.

In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress.

A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs.

This includes aggregate reductions of Medicare payments to providers up to 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments to the statute will remain in effect until 2032 unless additional U.S.

Congressional action is taken.

In addition, in January 2013, then President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several categories of healthcare providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

These changes include aggregate reductions to Medicare payments to providers of 2% per fiscal year pursuant to the Budget Control Act of 2011, which began in 2013 and, due to subsequent legislative amendments to the statute, including the Infrastructure Investment and Jobs Act, will remain in effect until 2032 unless additional Congressional action is taken.

Further, there has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices.

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Congressional inquiries and proposed and enacted legislation at the federal and state levels designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs.

At the federal level, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

Further, on November 15, 2021, President Biden signed into law the Infrastructure Investment and Jobs Act.

Beginning on January 1, 2023, manufacturers will be required to pay quarterly refunds to 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.

Effective January 1, 2023, manufacturers will be required to pay quarterly refunds to CMS for discarded amounts of certain single-dose container and single-use package drugs payable under part B of the Medicare program.

Refunds are based on the discarded volume above 10% of the total allowed amount.

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At this time, CMS has determined that Jelmyto fits within this unique circumstance classification.

In addition, the IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics covered under Medicare and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions take effect progressively starting in fiscal year 2023.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

It is unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.

In response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

It is unclear whether the models will be utilized in any health reform measures in the future.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.

In addition, the IRA, among other things, (1) directs HHS to negotiate the price of certain high expenditure single-source drugs that have been on the market for at least 7 years covered under Medicare (the “Medicare Drug Price Negotiation Program”) and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions began to take effect progressively starting in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon prices of the first ten drugs that were subject to price negotiations, although the Medicare Drug Price Negotiation program is currently subject to legal challenges.

On January 17, 2025, HHS selected fifteen additional products covered under Part D for price negotiation in 2025.

Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.

Further, on December 7, 2023, the an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act was announced.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

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At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Additional health reform measures may continue and affect our business in unknown ways.

Additional health reform measures may continue and affect our business in unknown ways, particularly given the recent change in administration.

The current administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, CMS and related agencies.

These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

These actions may include, for example, directives to reduce agency workforce, rescinding a Biden administration executive order tasking the Center for Medicare and Medicaid Innovation (“CMMI”) to consider new payment and healthcare models to limit drug spending and eliminating the Biden administration’s executive order that directed HHS to establishing an AI task force and developing a strategic plan.

Additionally, in its June 2024 decision in Loper Bright Enterprises v.

Raimondo (“Loper Bright”), the U.S.

Supreme Court overturned the longstanding Chevron doctrine, under which courts were required to give deference to regulatory agencies’ reasonable interpretations of ambiguous federal statutes.

The Loper Bright decision could result in additional legal challenges to current regulations and guidance issued by federal agencies applicable to our operations, including those issued by the FDA.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA.

The Foreign Corrupt Practices Act

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Manufacturing, Supply and Production

We do not own or operate manufacturing facilities for the production of our product candidates, nor do we have plans to develop our own manufacturing operations in the foreseeable future.

We currently rely on third-party contract manufacturers for all of our required raw materials, active ingredients and finished products for our nonclinical research and clinical trials.

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.

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 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 approved products.

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.

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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 seven regional business director positions, who are in turn supported by three regional operations manager positions.

These territory business manager positions are led by eight regional business director positions, who are in turn supported by eight regional operations manager positions.

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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.

Of the 161 employees in the United States one was a part-time employee, and of the 40 employees in Israel, two were part-time.

None of our employees are subject to a collective bargaining agreement.

We have never experienced any employment-related work stoppages and consider our relationships with our employees are good.

We have never experienced any employment-related work stoppages and consider our relationships with our employees good.

Israeli labor laws govern the length of the workday and workweek, minimum wages for employees, procedures for hiring and dismissing employees, determination of severance pay, annual leave, sick days, advance notice of termination, payments to the National Insurance Institute, and other conditions of employment and include equal opportunity and anti-discrimination laws.

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Investors should contact us for any inquiries through the address and telephone number of our principal executive office.

We maintain a web site at http://www.urogen.com.

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.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business