UroGen Pharma Ltd

Previous wording

We are a biotechnology company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers. We have developedRTGel 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. Our approved productJelmyto (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.

Current wording

We are a biotechnology company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers. We have developedRTGel® 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. Our approved productJelmyto® (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 ofJelmyto 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 monotherapy and combination therapy.

Previous wording

We estimate that the annual treatable patient population of low-grade UTUC in the United States is approximately 6,000 to 7,000 and the annual treatable population of low-grade intermediate risk NMIBC is approximately 80,000.

Current wording

If approved, UGN-102 would become the first U.S. Food and Drug Administration ("FDA") approved medicine for low-grade intermediate risk NMIBC. 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 UGN-102 in low-grade intermediate risk NMIBC is potentially over $5.0 billion, assuming an expected pricing range of $16,000 to $19,000 per dose.

Previous wording

These characteristics ofRTGel enable sustained release of mitomycin in the urinary tract for bothJelmyto and UGN-102. 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. We believe that these characteristics ofRTGel may prove useful for the local delivery of active drugs to other bodily cavities in addition to the bladder and upper urinary tract.

Current wording

These characteristics ofRTGel enable sustained release of mitomycin in the urinary tract forJelmyto, 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. We believe that these characteristics ofRTGel may prove useful for the local delivery of active drugs to other bodily cavities in addition to the bladder and upper urinary tract.

Previous wording

On April 15, 2020, the FDA approved our NDA forJelmyto (mitomycin) for pyelocalyceal solution, formerly known as UGN-101, for the treatment of adult patients with low-grade UTUC.Jelmyto consists of mitomycin, an established chemotherapy, and sterile hydrogel, using our proprietary sustained releaseRTGel technology. It has been designed to prolong exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. New product exclusivity forJelmyto expired on April 15, 2023, however, Orphan Drug exclusivity extends until April 15, 2027. Additionally, the main patents that protectJelmyto in the United States are set to expire in January 2031. These patents were listed in the FDA's Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations).

Current wording

On April 15, 2020, the FDA approved our new drug application (“NDA”) forJelmyto (mitomycin) for pyelocalyceal solution, formerly known as UGN-101, for the treatment of adult patients with low-grade UTUC.Jelmyto consists of mitomycin, an established chemotherapy, and sterile hydrogel, using our proprietary sustained releaseRTGel technology. It has been designed to prolong exposure of urinary tract tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. New product exclusivity forJelmyto expired on April 15, 2023, however, Orphan Drug exclusivity extends until April 15, 2027. Additionally, the main patents that protectJelmyto in the United States are set to expire in January 2031. These patents were listed in the FDA's Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations).

Previous wording

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 - 7,000 new or recurrent low-grade UTUC patients annually. It is a challenging condition to treat due to the complex anatomy of the urinary tract system. Prior toJelmyto, the current standard of care included endoscopic resection(s) and RNU, the latter which involves the removal of the renal pelvis, kidney, ureter and bladder cuff. 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 may suffer further complications as a result of a major surgery. We are focused on changing the way urothelial cancers are treated, an area in which there has been no significant advancements in recent years.Jelmyto is the first drug therapy of its kind, providing an alternative to endoscopic resection(s) and/or RNU.

Current wording

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. It is a challenging condition to treat due to the complex anatomy of the urinary tract system. Prior toJelmyto, the current standard of care included endoscopic resection(s) and radical nephroureterectomy (“RNU”), the latter which involves the removal of the renal pelvis, kidney, ureter and bladder cuff. 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 may suffer further complications as a result of a major surgery. We are focused on changing the way urothelial cancers are treated, an area in which there has been no significant advancements in recent years.Jelmyto is the first drug therapy of its kind, providing an alternative to endoscopic resection(s) and/or RNU.

Previous wording

In December 2022, we presented new data from a follow up study to the OLYMPUS trial designed to obtain long‐term data onJelmyto. Based on data available for 16 of the 23 patients who had remained in CR at the end of the OLYMPUS study, the median duration of response in that subset of patients was 28.9 months. Thirteen patients remained in CR, two patients had recurrence of low grade‐UTUC on the same side as treated in OLYMPUS, and one patient underwent RNU due to ureteral stricture without evidence of UTUC at the time of surgery. No patient had progressed to high‐grade disease.

Current wording

In December 2022, we presented new data from a follow-up study to the OLYMPUS trial designed to obtain long‐term data onJelmyto. Based on data available for 16 of the 23 patients who had remained in CR at the end of the OLYMPUS study, the median duration of response in that subset of patients was 28.9 months. Thirteen patients remained in CR, two patients had recurrence of low grade‐UTUC on the same side as treated in OLYMPUS, and one patient underwent RNU due to ureteral stricture without evidence of UTUC at the time of surgery. No patient had progressed to high‐grade disease. In November 2024, we published results from a long-term follow-up study withJelmyto evaluating 20 of the 41 patients from the OLYMPUS trial who achieved a CR after primary chemoablation withJelmyto. The median duration of response in this subset of patients was 47.8 months. The study results are published online in theJournal of Urology.

Previous wording

In June 2020, we initiated our commercial launch ofJelmyto 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 aJelmytoservice 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. In total, our customer-facing team comprises approximately 80 representatives.

Current wording

In June 2020, we initiated our commercial launch ofJelmyto 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. 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 aJelmytoservice 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. In total, our customer-facing team comprises approximately 100 representatives.

Previous wording

In October 2020, a Medicare C-Code was issued forJelmyto. The Centers for Medicare & Medicaid Services established a permanent and product-specific J-code forJelmyto that took effect on January 1, 2021 and replaced the C-Code. CMS has grantedJelmyto 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 withJelmyto. The purpose of the registry is to study the use ofJelmyto in clinical practice in the United States and address specific clinical questions.

Current wording

In October 2020, a Medicare C-Code was issued forJelmyto. The Centers for Medicare & Medicaid Services established a permanent and product-specific J-code forJelmyto that took effect on January 1, 2021 and replaced the C-Code. The Centers for Medicare & Medicaid Services has grantedJelmyto a New Technology 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 who have been or will be treated withJelmyto. The purpose of the registry is to study the use ofJelmyto in clinical practice in the United States and address specific clinical questions.

Previous wording

In the first three fiscal years beginning after the initiation of our commercial launch ofJelmytoin June 2020, we have experienced a moderate decline in revenue during the third quarter from the preceding quarter. We believe this result is primarily attributable to the nature of low-grade disease, which does not require immediate treatment and therefore we believe there is an impact in the summer months. However, it is too early to say with confidence whether this seasonality trend will continue in future periods. Moreover, our futureJelmytorevenue will be impacted by various factors and we expect ourJelmyto revenue to fluctuate quarter-to-quarter for the foreseeable future.

Current wording

In each of the first three fiscal years beginning after the initiation of our commercial launch ofJelmyto in June 2020, we experienced a moderate decline in revenue during the third quarter from the preceding quarter. We believe this result was primarily attributable to the nature of low-grade disease, which does not require immediate treatment and therefore we believe there could be an impact in the summer months. However, we did not observe this trend in 2024 and therefore cannot say with confidence whether this seasonality trend will continue in future periods. Moreover, our futureJelmyto revenue will be impacted by various factors and we expect ourJelmyto revenue to fluctuate quarter-to-quarter for the foreseeable future.

Previous wording

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.

Current wording

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 without knowledge of the data. 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. ATLAS continued until the last ongoing patient completed the month 15 visit. On July 27, 2023, we announced topline data from our Phase 3 trials, ATLAS and ENVISION. 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. 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 79.6% 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.

Previous wording

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. 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. Treatment visits two to six took place at the patient's home and instillations were performed by a properly trained and qualified home health professional. The primary endpoints of the study include safety and tolerability, discontinuations from at home study treatment and feedback from patients, home health professionals and investigators via standardized questionnaires. The study completed enrollment with a total of eight patients across four centers and all study visits for these enrolled patients have been completed. 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. These standardized feasibility questionnaires highlighted that all eight patients preferred at-home to in-office treatment, and five of six patients recommended UGN-102 home instillation instead of TURBT. Home instillation was reported as feasible for visiting nurses, and three of four investigators considered at-home treatment “not different” than in-office treatment.

Current wording

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. Treatment visits two to six took place at the patient's home and instillations were performed by a properly trained and qualified home health professional. The primary endpoints of the study include safety and tolerability, discontinuations from at home study treatment and feedback from patients, home health professionals and investigators via standardized questionnaires. The study completed enrollment with a total of eight patients across four centers and all study visits for these enrolled patients have been completed. 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. These standardized feasibility questionnaires highlighted that all eight patients preferred at-home to in-office treatment, and five of six patients recommended UGN-102 home instillation instead of TURBT. Home instillation was reported as feasible for visiting nurses, and three of four investigators considered at-home treatment “not different” than in-office treatment.

Previous wording

In October 2023 we announced our agreement with the FDA on plans for submission of an NDA for UGN-102 (mitomycin) for intravesical solution. 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 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.

Current wording

In October 2023, we announced our agreement with the FDA on plans for submission of an NDA for UGN-102 (mitomycin) for intravesical solution. 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 also agreed that the UGN-102 NDA can utilize a rolling review, allowing for early submission of the CMC sections of the NDA, which we submitted in January 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.

Previous wording

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 a next-generation formulation of UGN-102 andJelmyto, respectively, that combine medac’s proprietary mitomycin formulation technology with ourRTGel 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.

Current wording

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 andJelmyto, respectively, that combine medac’s proprietary 80 mg mitomycin formulation with ourRTGel technology, which we believe will provide advantages related to production, cost, supply and product convenience. 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.

Previous wording

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. 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.

Current wording

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. 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.

Previous wording

The first combination we are investigating clinically involves the sequential use of UGN-201 (imiquimod), a 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 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. 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. UGN-301 is delivered using our proprietaryRTGeltechnology, 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 potential side effects.

Current wording

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 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. 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 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.

Previous wording

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. 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. 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.

Current wording

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. 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. 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.

Previous wording

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

Current wording

In November 2019, we entered into a license agreement with Agenus Inc. (“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. UGN-301 is a formulation of zalifrelimab administered usingRTGel technology that is in Phase 1 clinical development for high-grade NMIBC.

Previous wording

During the year ended December 31, 2023 and December 31, 2022, we recognized $ 82.7 million and $64.4 million of revenue, respectively, from sales of our product,Jelmyto.

Current wording

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.

Previous wording

Cost of revenue consists primarily of inventory and related costs associated with the manufacturing, distribution, warehousing and preparation ofJelmyto,including inventory write-downs. In periods prior to receiving FDA approval forJelmyto, we recognized inventory and related costs associated with the manufacture ofJelmyto as research and development expense.

Current wording

Cost of revenue consists primarily of inventory and related costs associated with the manufacturing, distribution, warehousing and preparation ofJelmyto,including inventory write-downs. In periods prior to receiving FDA approval forJelmyto, we recognized inventory and related costs associated with the manufacture ofJelmyto as research and development expenses.

Previous wording

We manage and prioritize our research and development expenses based on scientific data, probability of successful technical development and regulatory approval, market potential and unmet medical need, available human and capital resources and other considerations. We regularly review our research and development activities and, as necessary, reallocate resources among our program, 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.

Current wording

We manage and prioritize our research and development expenses based on scientific data, probability of successful technical development and regulatory approval, market potential and unmet medical need, available human and capital resources and other considerations. 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.

Previous wording

We expense all research and development costs as incurred. We estimate nonclinical study and clinical trial expense based on the services performed pursuant to contracts with research institutions and contract research organizations that conduct and manage nonclinical studies and clinical trials on our behalf based on actual time and expense incurred by them.

Current wording

See Note 20 to our consolidated financial statements appearing elsewhere in this Annual Report for additional disaggregation of significant research and development expenses. We expense all research and development costs as incurred. We estimate nonclinical study and clinical trial expense based on the services performed pursuant to contracts with research institutions and contract research organizations that conduct and manage nonclinical studies and clinical trials on our behalf based on actual time and expense incurred by them.

Previous wording

We are currently focused on advancing our product candidates, and our future research and development expense will depend on their clinical success. Research and development expense will continue to be significant.

Current wording

We are currently focused on advancing our product candidates, and our future research and development expenses will depend on their clinical success. Research and development expenses will continue to be significant.

Previous wording

Research and development activities are central to our business model. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We do not believe that it is possible at this time to accurately project total expenses required for us to reach commercialization of our product candidates. Due to the inherently unpredictable nature of nonclinical and clinical development, we are unable to estimate with certainty the costs we will incur and the timelines that will be required in the continued development and approval of our product candidates. Clinical and nonclinical development timelines, the probability of success and development costs can differ materially from expectations. In addition, we cannot forecast which product candidates may be subject to future collaborations, if and when such arrangements will be entered into, if at all, and to what degree such arrangements would affect our development plans and capital requirements. We expect our research and development expense to increase over the next several years as our clinical programs progress and as we seek to initiate clinical trials of additional product candidates. We also expect to incur increased research and development expense as we selectively identify and develop additional product candidates.

Current wording

Research and development activities are central to our business model. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials. We do not believe that it is possible at this time to accurately project total expenses required for us to reach commercialization of our product candidates. Due to the inherently unpredictable nature of nonclinical and clinical development, we are unable to estimate with certainty the costs we will incur and the timelines that will be required in the continued development and approval of our product candidates. Clinical and nonclinical development timelines, the probability of success and development costs can differ materially from expectations. In addition, we cannot forecast which product candidates may be subject to future collaborations, if and when such arrangements will be entered into, if at all, and to what degree such arrangements would affect our development plans and capital requirements. We expect our research and development expenses to increase over the next several years as our clinical programs progress and as we seek to initiate clinical trials of additional product candidates. We also expect to incur increased research and development expenses as we selectively identify and develop additional product candidates.

Previous wording

Other thanJelmyto, which was approved by the FDA in April 2020, we have not received approval of any of our product candidates. UGN-102 and UGN-301 are still in clinical development. As such, 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. We expect to finance our cash needs through revenue from commercial sales ofJelmytoand a combination of equity or debt financings and collaboration arrangements.

Current wording

Other thanJelmyto, which was approved by the FDA in April 2020, we have not received approval of any of our product candidates. UGN-102, UGN-103, UGN-104 and UGN-301 are still in clinical development. As such, 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 revenues from commercial sales ofJelmytoand* *a combination of equity or debt financings and collaboration arrangements.

Previous wording

To date, selling and marketing expenses consist primarily of commercial personnel costs (including share-based compensation) along with pre-commercialization and commercialization activities related toJelmyto, formerly known as UGN-101.

Current wording

To date, selling and marketing expenses consist primarily of commercial personnel costs (including share-based compensation) along with commercialization activities related toJelmyto and pre-commercialization activities related to UGN-102.

Previous wording

Financing on prepaid forward obligation is comprised of financing expense related to the RTW Transaction (see Note 9 to our consolidated financial statements appearing elsewhere in this Annual Report).

Current wording

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).

Previous wording

Interest expense is comprised of interest related to our long-term debt with Pharmakon (see Note 10 to our consolidated financial statements appearing elsewhere in this Annual Report).

Current wording

Interest expense is primarily comprised of interest related to our long-term debt with Pharmakon Advisors, L.P. (“Pharmakon”) (see Note 10 to our consolidated financial statements appearing elsewhere in this Annual Report).

Previous wording

We have yet to generate taxable income in Israel. We have historically incurred operating losses resulting in carry forward tax losses totaling approximately $452.0 million as of December 31, 2023. We anticipate that we will continue to generate tax losses for the foreseeable future 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. 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 17 to our consolidated financial statements appearing elsewhere in this Annual Report for further information.

Current wording

We have yet to generate taxable income in Israel. We have historically incurred operating losses resulting in carry forward tax losses totaling approximately $533.9 million as of December 31, 2024. We anticipate that we will continue to generate tax losses for the foreseeable future 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. 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 17 to our consolidated financial statements appearing elsewhere in this Annual Report for further information.

Previous wording

General and administrative expenses were $38.6 million and $30.9 million for the years ended December 31, 2023 and 2022, respectively. The increase in general and administrative expenses of $7.7 million resulted primarily from higher compensation expenses, third-party advisory providers, recruiting fees, certain media and meeting expenses, and ongoing managed services.

Current wording

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.

Previous wording

Financing on prepaid forward obligation was $21.6 million and $21.6 million for the years ended December 31, 2023 and 2022, respectively. The measurement of financing on prepaid forward obligation is an accounting estimate under the "imputed interest method" of accounting (see Note 9 to our consolidated financial statements appearing elsewhere in this Annual Report) which is affected by estimated future payments to RTW, which are based on a percentage of revenues.

Current wording

Financing on prepaid forward obligation was $23.4 million and $21.6 million for the years ended December 31, 2024 and 2023, respectively. The measurement of financing on prepaid forward obligation is an accounting estimate under the "imputed interest method" of accounting (see Note 9 to our consolidated financial statements appearing elsewhere in this Annual Report) which is affected by estimated future payments to RTW, which are based on a percentage of revenues. 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.

Previous wording

Interest and other income, net was $3.5 million and $1.0 million for the years ended December 31, 2023 and 2022, respectively. The increase in interest and other income, net was primarily due to higher cash and investment balance earning interest and changes in the overall interest rate environment.

Current wording

Interest and other income, net was $8.7 million and $3.5 million for the years ended December 31, 2024 and 2023, respectively. The increase of $5.2 million in interest and other income, net was primarily due to higher cash and investment balances.

Previous wording

As of December 31, 2023, we had $141.5 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.

Current wording

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.

Previous wording

In December 2019, we entered into the ATM Sales Agreement with 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. The remaining capacity under the ATM Sales Agreement was approximately $83.4 million as of December 31, 2023, and subsequent to December 31, 2023, we sold approximately $26.6 million of our ordinary shares pursuant to the ATM Sales Agreement. The shares will be offered and sold pursuant to our shelf registration statement on Form S-3 filed with the SEC on November 15, 2022, which was declared effective on November 29, 2022.

Current wording

In the first quarter of 2024, we sold 3,400,468 ordinary shares under the ATM Sales Agreement, for gross proceeds of approximately $56.1 million. The net proceeds to us after deducting sales commissions to TD Cowen were approximately $54.7 million. The remaining capacity under the ATM Sales Agreement was approximately $27.3 million as of December 31, 2024. The shares will be offered and sold, if any, pursuant to our shelf registration statement on Form S-3 filed with the SEC on November 15, 2022, which was declared effective on November 29, 2022, or a subsequent shelf registration statement.

Previous wording

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. 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.

Current wording

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. 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.

Previous wording

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 is mandatory and required to be drawn by September 30, 2024, subject to satisfaction of customary conditions. The fourth tranche of $75.0 million may be drawn at our option no later than August 29, 2025, subject to (i) having successfully drawn the immediately preceding $25.0M tranche, (ii) receiving FDA approval of an NDA for UGN-102 no later than June 30, 2025 and (iii) satisfaction of customary conditions.

Current wording

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. The fourth tranche of $75.0 million will become available at our option no later than August 29, 2025, subject to (i) receiving FDA approval of an NDA for UGN-102 no later than June 30, 2025 and (ii) the satisfaction of customary bring down conditions and deliverables.

Previous wording

We have incurred losses since our inception and negative cash flows from our operations, and as of December 31, 2023 we had an accumulated deficit of $679.3 million. We anticipate that we will continue to incur losses for the reasonably foreseeable future. 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, partially offset by proceeds from sales ofJelmyto.

Current wording

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. 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 ofJelmyto.

Previous wording

We routinely evaluate our liquidity needs, including assessment of our current financial condition, sources of liquidity including current cash and cash equivalents and marketable securities and management’s cash flow projections. Our ability to continue as a going concern is expected to be impacted by our ability to raise additional capital to fund our operations, produce cash inflows fromJelmyto product sales and develop UGN-102. We believe that absent sufficient proceeds received from equity, financing, or business development transactions, we will not have sufficient cash and cash equivalents to fund our operations beyond one year from the issuance of our consolidated financial statements included elsewhere in this Annual Report. We estimate that our existing resources and projected revenues will only be sufficient to fund our planned operations until the first quarter of 2025. Accordingly, we will, within the next 12 months, require significant additional financing to continue our operations. In addition, there can be no assurances that we will be able to secure such additional financing if at all, on terms that are satisfactory to us, and in amounts sufficient to meet our needs. These factors raise substantial doubt about our ability to continue as a going concern. Failure to successfully receive additional financing will require us to delay, limit or reduce product development and commercialization efforts.

Current wording

We routinely evaluate our liquidity needs, including assessment of our current financial condition, sources of liquidity including current cash and cash equivalents and marketable securities and management’s cash flow projections. 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. 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. 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. There can be no assurances that we will be able to secure such additional financing on terms that are satisfactory to us, in an amount sufficient to meet our needs, or at all. In the event we are not successful in obtaining sufficient funding, this could force us to delay, limit, reduce or terminate our product development, commercialization efforts or other operations.

Previous wording

Net cash used in operating activities was $76.4 million during the year ended December 31, 2023, compared to $87.6 million used in operating activities during the year ended December 31, 2022. The $11.2 million decrease was attributable primarily to timing of certain accruals and cash payments, as well as increase in net sales of our product* Jelmyto* during 2023 and higher inventory purchases, including non-current inventory, in 2022, partially offset by increase in interest on long-term debt.

Current wording

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. 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.

Previous wording

Net cash used in investing activities was $1.0 million during the year ended December 31, 2023, compared to net cash provided by investing activities of $1.1 million during the year ended December 31, 2022. The decrease of $2.1 million is attributable primarily to proportionately less maturities to purchases of marketable securities during 2023 as compared to 2022.

Current wording

Net cash used in investing activities was $20.6 million during the year ended December 31, 2024, compared to net cash used in investing activities of $1.0 million during the year ended December 31, 2023. The increase of $19.6 million is attributable primarily to additional investment in marketable securities in 2024 as compared to 2023.

Previous wording

Net cash provided by financing activities was $116.9 million during the year ended December 31, 2023, compared to net cash provided by financing activities of $97.1 million during the year ended December 31, 2022. The increase of $19.8 is attributable primarily to proceeds from the Private Placement in the current year as compared to proceeds from the Pharmakon loan in the prior year.

Current wording

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. 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.