UroGen Pharma Ltd

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 may become the first FDA-approved medicine for low-grade intermediate risk NMIBC.** **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 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 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 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 U.S. Food and Drug Administration ("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 U.S. Food and Drug Administration ("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 upper 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 standard of care included endoscopic resection(s) and radical nephroureterectomy, the latter involving 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 radical nephroureterectomy.

Current wording

Low-grade UTUC is a rare cancer that develops in the lining of the upper urinary tract, which consists of the kidneys and ureters. 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 upper urinary tract system. Prior toJelmyto, the standard of care included endoscopic resection(s) and radical nephroureterectomy, the latter involving 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 radical nephroureterectomy.

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 ("DOR") 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.

Previous wording

In 2024, we released data from a post-hoc analysis of the OLYMPUS trial assessing the long-term effects in treating low grade-UTUC withJelmyto. Of the 71 patients who enrolled in OLYMPUS, 41 achieved a CR and their health outcomes were tracked for up to 12 months. 20 of these patients remaining in CR enrolled in a 5-year rollover study. All 41 patients with an initial CR indicated a promising median duration of response of 47.8 months, based on a median follow-up of 28.1 months. In the 5-year rollover trial, 75% (N=15) showed no disease recurrence, indicating potential for extended disease-free periods.

Current wording

In 2024, we released data from a post-hoc analysis of the OLYMPUS trial assessing the long-term effects in treating low grade-UTUC withJelmyto. Of the 71 patients who enrolled in OLYMPUS, 41 achieved a CR and their health outcomes were tracked for up to 12 months. Twenty of the patients remaining in CR enrolled in a 5-year rollover study. All 41 patients with an initial CR indicated a promising median DOR of 47.8 months, based on a median follow-up of 28.1 months. In the 5-year rollover trial, 75% (N=15) showed no disease recurrence at the time of the 4-year data cutoff, indicating potential for extended disease-free periods.

Previous wording

In October 2020, a Medicare C-Code was issued forJelmyto. The Centers for Medicare & Medicaid Services ("CMS") 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 ("CMS") 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 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 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.

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 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.

Previous wording

UGN-102 is administered locally using the standard practice of intravesical instillation directly into the bladder via a catheter. The instillation into the bladder is expected to take place in a physician’s office as a non-operative outpatient treatment, in comparison with trans-urethral resection of bladder tumor ("TURBT") or similar surgical procedures, which are operations often conducted under general anesthesia and may require an overnight stay. Complete surgical tumor removal often has limited success due to the inability to properly identify, reach and resect all tumors. We believe that an effective chemoablation agent can potentially provide better eradication of tumors irrespective of the detectability and location of the tumors. In addition, by reducing the need for surgery, patients may avoid potential complications associated with surgery and anesthesia.

Current wording

UGN-102 is administered locally using the standard practice of intravesical instillation directly into the bladder via a urethral catheter. The instillation into the bladder is expected to take place in a physician’s office as a non-operative outpatient treatment, in comparison with trans-urethral resection of bladder tumor ("TURBT") or similar surgical procedures, which are operations often conducted under general anesthesia in an operating room and may require an overnight stay. Complete surgical tumor removal often has limited success due to the inability to properly identify, reach and resect all tumors. We believe that an effective chemoablation agent can potentially provide better eradication of tumors irrespective of the detectability and location of the tumors. In addition, by reducing the need for surgery, patients may avoid potential complications associated with surgery and general anesthesia.

Previous wording

In October 2021, we reported final data from the Phase 2b OPTIMA II trial. The single-arm, open label trial completed enrollment of 63 patients at clinical sites across the United States and Israel in September 2019. Patients were treated with six weekly instillations of UGN-102 and underwent assessment of CR (the primary endpoint) four to six weeks following the last instillation; 65%, or 41 out of 63 patients, treated with UGN-102 achieved a CR three months after the start of therapy. In this subset of patients, 39 (95%), 30 (73%), and 25 (61%) remained disease-free at six, nine, and 12 months after treatment initiation, respectively. The probability of durable response nine months after CR (12 months after treatment initiation) was estimated to be 72.5% by Kaplan-Meier analysis. Thirteen patients had documented recurrences. Fifty-seven of 63 (90%) patients completed all six instillations of UGN-102 according to the study protocol. Median duration of response was not reached. The most common adverse events, greater than 10%, were most often reported as mild to moderate in severity and include dysuria, hematuria, urinary frequency, fatigue, urgency and urinary tract infection. The final data was published online in The Journal of Urology in October 2021 and was included in the January 2022 print edition.

Current wording

In October 2021, we reported final data from the Phase 2b OPTIMA II trial. The single-arm, open label trial completed enrollment of 63 patients at clinical sites across the United States and Israel in September 2019. Patients were treated with six weekly instillations of UGN-102 and underwent assessment of CR rate (the primary endpoint) four to six weeks following the last instillation; 65.1%, or 41 out of 63 patients, treated with UGN-102 achieved a CR three months after the start of therapy. In this subset of patients, 39 (95%), 30 (73%), and 25 (61%) remained disease-free at six, nine, and 12 months after treatment initiation, respectively. The probability of durable response nine months after CR (12 months after treatment initiation) was estimated to be 69.9% by Kaplan-Meier analysis. Median DOR was not reached. Thirteen patients had documented recurrences. Fifty-seven of 63 (90%) patients completed all six instillations of UGN-102 according to the study protocol. The most common adverse events, occurring in greater than 10% of participants, were most often reported as mild to moderate in severity and include dysuria, hematuria, urinary frequency, fatigue, urgency and urinary tract infection. The final data were published online in The Journal of Urology in October 2021 and was included in the January 2022 print edition.

Previous wording

In December 2022 we presented new data from a follow up study to the OPTIMA II study designed to obtain long-term data on UGN-102 that shows median duration of response of 24.4 months based on available data for 15 out of 25 patients who achieved a CR in OPTIMA II. Seven patients remained in CR, six patients had recurrence of low-grade disease, one patient had progression to high-grade disease and one patient withdrew consent but remained in CR at the last evaluation prior to discontinuation. All patients were alive at the last contact, and five patients were known to have had post-study treatment with TURBT or fulguration.

Current wording

In December 2022 we presented new data from a follow up study to the OPTIMA II study designed to obtain long-term data on UGN-102 that showed median DOR of 24.4 months based on available data for 15 out of 25 patients who achieved a CR in OPTIMA II. Seven patients remained in CR, six patients had recurrence of low-grade disease, one patient had progression to high-grade disease and one patient withdrew consent but remained in CR at the last evaluation prior to discontinuation. All patients were alive at the last contact, and five patients were known to have had post-study treatment with TURBT or fulguration.

Previous wording

We initiated our Phase 3 ATLAS trial in December 2020 and until November 2021, were enrolling patients in this trial comparing UGN-102 with or without TURBT to standard of care, TURBT. In parallel, we continued to engage in discussions with the FDA and based on this dialogue, we designed a trial in order to demonstrate the efficacy and safety of UGN-102. This Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with low-grade intermediate risk NMIBC. The design of the Phase 3 ENVISION trial is similar to our Phase 2 OPTIMA II trial in that the patient population has similar clinical characteristics, receives the same investigational treatment regimen and undergoes similar efficacy and safety assessments and qualitative follow-up. Study participants receive six once-weekly intravesical instillations of UGN-102. 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.

Current wording

We initiated our Phase 3 ATLAS trial in December 2020 and until November 2021, were enrolling patients in this trial comparing UGN-102 with or without TURBT to standard of care, TURBT alone. In parallel, we continued to engage in discussions with the FDA and based on this dialogue, we designed a pivotal trial in order to demonstrate the efficacy and safety of UGN-102. This Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 as primary chemoablative therapy in patients with low-grade intermediate risk NMIBC. The design of the Phase 3 ENVISION trial is similar to our Phase 2 OPTIMA II trial in that the patient population has similar clinical characteristics, receives the same investigational treatment regimen and undergoes similar efficacy and safety assessments and qualitative follow-up. Study participants receive six once-weekly intravesical instillations of UGN-102. 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.

Previous 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. 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.

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.

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 the second quarter of 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

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 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 endpoints of the study included 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 home health professional under the supervision of a treating physician and resulted in 75% of patients achieving a CR, defined as no detectable disease three months after starting treatment. 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 home health professionals, 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 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 the third quarter of 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 response 12 months after 3-month CR 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 Oncologic Drugs 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 the third quarter of 2024, with a potential FDA acceptance in the fourth quarter of 2024 and potential FDA approval in the first quarter of 2025 (assuming priority review) or the second quarter of 2025 (assuming standard review).

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 80 mg mitomycin formulation with ourRTGel technology, which we believe will provide advantages related to production, cost, supply and product convenience. We are preparing to initiate clinical endpoint studies to support NDAs for UGN-103 and UGN-104 in low-grade intermediate risk NMIBC and low grade-UTUC, respectively. In April, we announced that the FDA has accepted our Investigational New Drug Application ("IND") for UGN-103. We anticipate dosing patients in the planned Phase 3 trial of UGN-103 by the end of this year and initiating a Phase 3 trial of UGN-104 shortly thereafter.

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 a next-generation formulation 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, we announced that the FDA has accepted our Investigational New Drug Application ("IND") for UGN-103. We have initiated a Phase 3 clinical study to support the NDA for UGN-103 in low-grade intermediate risk NMIBC, and plan to enroll approximately 87 patients. The first patients are expected to be dosed in the third quarter of 2024, with full enrollment anticipated by the first half of 2025. An NDA filing is projected for the first half of 2026, followed by a standard review period and potential approval and, if approved, the commercial launch in the first half of 2027. We also plan to initiate a Phase 3 trial of UGN-104 in low-grade UTUC early next year.

Previous 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. UGN-301 is delivered using our proprietaryRTGel 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 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 believe that these combinations 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 is actively enrolling. Safety and dosing data from the first arm evaluating UGN-301 as monotherapy are expected in late 2024.

Previous wording

During the three months ended March 31, 2024 and March 31, 2023 we recognized $18.8 million and $17.2 million of revenue, respectively from sales of our product,Jelmyto.

Current wording

During the three and six months ended June 30, 2024, we recognized $21.8 million and $40.6 million of revenue, respectively from sales of our product,Jelmyto.

Previous wording

Revenue was $18.8 million and $17.2 million for the three months ended March 31, 2024 and 2023, respectively. The increase in revenue of $1.6 million primarily reflects the increased volume of sales ofJelmyto.

Current wording

Revenue was $21.8 million and $21.1 million for the three months ended June 30, 2024 and 2023, respectively. The increase in revenue of $0.7 million primarily reflects the increased volume of sales ofJelmyto.

Previous wording

Selling and marketing expenses were $17.1 million and $14.1 million for the three months ended March 31, 2024 and 2023, respectively. The increase in selling and marketing expenses of $3.0 million is primarily attributable to UGN-102 brand marketing costs as well as an increase in overall commercial operation costs including meetings, conferences, trainings and software costs.

Current wording

Selling and marketing expenses were $18.9 million and $13.9 million for the three months ended June 30, 2024 and 2023, respectively. The increase in selling and marketing expenses of $5.0 million is primarily attributable to UGN-102 brand marketing costs as well as an increase in overall commercial operation costs including meetings, conferences, and trainings.

Previous wording

Financing on prepaid forward obligation was $5.7 million and $5.2 million for the three months ended March 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 3 to our condensed consolidated financial statements appearing elsewhere in this Quarterly 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 $0.5 million was driven primarily by changes in underlying assumptions for remeasuring the effective rate.

Current wording

Financing on prepaid forward obligation was $5.8 million and $5.3 million for the three months ended June 30, 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 3 to our condensed consolidated financial statements appearing elsewhere in this Quarterly 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 $0.5 million was driven primarily by changes in underlying assumptions for remeasuring the effective rate.

Previous wording

Interest expense was $2.4 million and $3.6 million for the three months ended March 31, 2024 and 2023, respectively. The decrease was primarily attributed to the decrease in the margin interest rate and the related impact to amortization of the discount on the Pharmakon loan as a result of the amended and restated loan agreement in March 2024.

Current wording

Interest expense was $3.5 million and $3.8 million for the three months ended June 30, 2024 and 2023, respectively. The decrease of $0.3 million was primarily attributable to the decrease in the margin interest rate and the related impact to amortization of the discount on the Pharmakon loan as a result of the amended and restated loan agreement in March 2024.

Previous wording

Interest and other income, net was $1.6 million and $0.6 million for the three months ended March 31, 2024 and 2023, 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 $1.7 million and $0.4 million for the three months ended June 30, 2024 and 2023, respectively. The increase of $1.3 million in interest and other income, net was primarily due to higher cash and investment balances.

Previous wording

Cost of revenue was $1.7 million and $2.3 million for the three months ended March 31, 2024 and 2023, respectively. The overall decrease of $0.6 million is primarily attributable to certain nonrecurring payments made in connection with our supply arrangement in the prior year, decrease in mixing fees, lower manufacturing costs, and decrease in theJelmytounit cost.

Current wording

Cost of revenue was $4.0 million and $4.7 million for the six months ended June 30, 2024 and 2023, respectively. The decrease of $0.7 million is primarily attributable to certain nonrecurring payments made in connection with our supply arrangement in the prior year, lower shipping and warehousing costs, and decrease in theJelmytounit cost.

Previous wording

Research and development expenses were $15.5 million and $12.5 million for the three months ended March 31, 2024 and 2023, respectively. The overall increase of $3.0 million is primarily attributable to higher manufacturing costs and regulatory related expenses in connection with UGN-102 as well as research and development expenses in connection with our initiation of a Phase 3 study for UGN-103, partially offset by lower UGN-102 clinical trial costs.

Current wording

Research and development expenses were $30.9 million and $24.1 million for the six months ended June 30, 2024 and 2023, respectively. The increase of $6.8 million is primarily attributable to higher manufacturing costs, which are recognized as research and development expense prior to our product candidates receiving FDA approval, and regulatory related expense in connection with UGN-102 as well as research and development expenses, in connection with our initiation of a Phase 3 study for UGN-103, partially offset by lower UGN-102 clinical trial costs and costs related to the research into ingredient scale-up and production efficiency forJelmyto.

Previous wording

General andadministrative expenses were $10.2 million and $10.3 million for the three months ended March 31, 2024 and 2023, respectively. General and administrative expenses in the three months ended March 31, 2024 reflect lower expenses related to legal and compliance activities, offset by higher advisory and ongoing managed services related to medical affairs.

Current wording

General andadministrative expenses were $21.4 million and $18.9 million for thesix months ended June 30, 2024 and 2023, respectively. The increase in general and administrative expenses of $2.5 million is primarily attributable to higher compensation expenses, legal and compliance activities, marketing communication expenses related to UGN-102, third-party advisory services, and ongoing managed services, partially offset by lower professional services.

Previous wording

As of March 31, 2024, we had $164.5 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 June 30, 2024, we had $241.3 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.

Current wording

In December 2019, we entered into the ATM Sales Agreement with TD Cowen pursuant to which we may from time to time offer and sell our ordinary shares having an aggregate offering price of up to $100.0 million.

Previous 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 the Company after deducting sales commissions to Cowen were approximately $54.7 million. The remaining capacity under the ATM Sales Agreement is approximately $27.3 million as of March 31, 2024. 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 June 30, 2024. 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.

Previous wording

We have incurred losses since our inception and negative cash flows from our operations, and as of March 31, 2024 we had an accumulated deficit of $711.6 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 June 30, 2024 we had an accumulated deficit of $744.4 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.

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. Based on our cash, cash equivalents and marketable securities as of March 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 condensed consolidated financial statements appearing elsewhere in this Quarterly Report. We will need to raise additional capital in the future. 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, or reduce our product development, commercialization efforts or other operations.

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 our ability to raise additional capital to fund our operations, produce cash inflows fromJelmyto product sales and develop UGN-102. Based on our cash, cash equivalents and marketable securities as of June 30, 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 condensed consolidated financial statements appearing elsewhere in this Quarterly Report. We may need to raise additional capital in the future. 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, or reduce our product development, commercialization efforts or other operations.

Previous wording

Accordingly, we will need to obtain additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate our research and development programs or future commercialization efforts.

Current wording

Accordingly, we may need to obtain additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate our research and development programs or future commercialization efforts.

Previous wording

Also, in November 2019, we entered into a new lease agreement, dated effective October 31, 2019, for an office in Princeton, NJ. The lease commencement date was November 29, 2019 and the lease term is 38 months. In June 2022, we signed an amendment to our November 2019 lease agreement to extend the term for an additional three years through January 31, 2026.

Current wording

In November 2019, we entered into a new lease agreement, dated effective October 31, 2019, for an office in Princeton, NJ. The lease commencement date was November 29, 2019 and the lease term is 38 months. In June 2022, we signed an amendment to our November 2019 lease agreement to extend the term for an additional three years through January 31, 2026.

Previous wording

The total obligation for future minimum lease payments under our operating leases is $1.5 million as of March 31, 2024. See Note 11 to the condensed consolidated financial statements appearing elsewhere in this Quarterly Report for further information.

Current wording

The total obligation for future minimum lease payments under our operating leases is $1.3 million as of June 30, 2024. See Note 11 to the condensed consolidated financial statements appearing elsewhere in this Quarterly Report for further information.

Previous wording

Net cash used in operating activities was $31.7 million during the three months ended March 31, 2024, compared to $25.8 million during the three months ended March 31, 2023. The $5.9 million increase was attributable primarily to higher net loss driven by increased operating expenses such as regulatory and brand marketing costs related to UGN-102, as well as timing of certain accruals and higher personnel related spend.

Current wording

Net cash used in operating activities was $55.5 million during the six months ended June 30, 2024, compared to $46.1 million during the six months ended June 30, 2023. The $9.4 million increase was attributable primarily to higher net loss driven by increased operating expenses such as regulatory and brand marketing costs related to UGN-102, as well as timing of certain accruals and higher personnel related spend.

Previous wording

Net cash provided by investing activities was $13.5 million during the three months ended March 31, 2024, compared to net cash provided by investing activities of $6.3 million during the three months ended March 31, 2023. The net change of $7.2 million is attributable primarily to less reinvestment of marketable securities in 2024 as compared to 2023.

Current wording

Net cash provided by investing activities was $25.5 million during the six months ended June 30, 2024, compared to net cash provided by investing activities of $10.0 million during the six months ended June 30, 2023. The net change of $15.5 million is attributable primarily to less reinvestment of marketable securities in 2024 as compared to 2023.

Previous wording

Net cash provided by financing activities was $54.7 million during the three months ended March 31, 2024, compared to $0.7 million during the three months ended March 31, 2023. The increase of $54.0 million is attributable primarily to proceeds from the issuance of ordinary shares under the ATM Sales Agreement.

Current wording

Net cash provided by financing activities was $155.0 million during the six months ended June 30, 2024, compared to $0.8 million during the six months ended June 30, 2023. The increase of $154.2 million is attributable primarily to proceeds from the issuance of ordinary shares under the ATM Sales Agreement and underwritten public offering.