Ureteral Diseases

-Gemini administration induced statistically significant, dose dependent changes in key biomarkers of activity- -Gemini was safe and well tolerated at pharmacologically active doses- -Phase 1 results enable further development across multiple indications- SAN DIEGO--(BUSINESS WIRE)-- Revelation Biosciences, Inc. (NASDAQ: REVB) (the “Company” or “Revelation”), a clinical-stage life sciences company that is focused on harnessing the power of trained immunity for the prevention and treatment of disease, today announced safety and biomarker data for its Phase 1 clinical study (RVL-HV02). The primary endpoint to evaluate the safety and tolerability of escalating doses of Gemini was met and a maximum tolerated dose in healthy volunteers was identified. Additionally, statistically significant dose dependent upregulation of key biomarkers demonstrating the immunostimulatory preconditioning effect of Gemini were observed. The study, which enrolled 40 healthy individuals 18 to 55 years of age, was conducted in Australia and evaluated escalating doses (placebo, low, mid and high dose) of intravenously administered Gemini. This press release features multimedia. View the full release here: (Graphic: Business Wire) Administration of Gemini induced significant, dose dependent changes in key circulatory biomarkers of activity that reflect the expected pharmacology of Gemini-specific toll-like receptor 4 (TLR4) stimulation. Intravenous Gemini induced significant increases in interleukin-1RA (IL-1RA) (p<0.001 at mid and high dose, Figure 1), neutrophil gelatinase lipocalin (NGAL) (p<0.01 at mid and high dose, Figure 2), c-reactive protein (CRP) (p<0.001 at mid and high dose, Figure 3), and IL-6 (p<0.01 at high dose, Figure 4). Significant, dose dependent mobilization of innate immune cell populations was observed, specifically neutrophils (p<0.001 at mid-dose and high dose) and monocytes (p<0.001 at mid and high dose). Importantly, Gemini administration did not induce significant increases in serum TNF-α (p=0.51 at the highest dose) and IL-1β (p=0.89 at the highest dose). This attenuated pro-inflammatory activity and corresponding significant upregulation of beneficial cytokines is unique to Gemini and facilitates the reprogramming of the innate immune response for resolution of inflammation and promotion of the healing process. These changes in biomarkers are consistent with the changes observed in preclinical models in which Gemini demonstrated remarkable activity (ischemia/reperfusion model of acute kidney injury and unilateral ureteral obstruction model of kidney injury) and are highly predictive of clinical efficacy, thus demonstrating the potential for Gemini in our target indications including prevention of AKI following cardiac surgery and prevention of infection following surgery. Figures 1 through 4 illustrate the reprogramming of the innate immune response after Gemini administration in multiple biomarkers of TLR4 stimulation. IL-1RA has anti-inflammatory properties, as it binds to the IL-1 receptor, blocking IL-1α and IL-1β, major drivers of the inflammation cascade. NGAL sequesters iron and is an important defense for preventing excessive oxidative damage resulting from injury and/or ongoing inflammation. CRP plays an important role in resolving acute inflammation through increased phagocytosis, clearing cellular debris. IL-6 at low concentrations facilitates multiple activities associated with the resolution of inflammation, including stimulation of IL-1RA and IL-10. IL-10 levels trended higher with increasing dose but did not reach significance vs placebo (data not shown). While significance was not observed at the time points evaluated, IL-10 activity is inferred by the significant upregulation of IL-1RA as well as the lack of significant upregulation of TNF-α, as both activities are impacted by IL-10. Gemini administration was generally well-tolerated. The frequency and severity of adverse events corresponded with increased dose, with the mid-level dose being established as the maximum tolerated dose in healthy volunteers. Adverse events observed included transient headache, chills, body aches/pain, and vomiting, and are consistent with preclinical findings and the expected pharmacology of the drug. Gemini administration did not result in significant changes in clinical safety markers (e.g. markers of organ function including creatinine, BUN, etc.) or hematologic parameters (aside from immune cell mobilization). There were no clinically significant findings with other safety measures including vital signs, ECG, urinalysis and physical exam. These results and the maximum tolerated dose will be used to guide dose level selection in a planned randomized, placebo-controlled Phase 1b study in patients with chronic kidney disease. “We are pleased that the biomarker data generated in healthy volunteers is consistent with our preclinical studies. This confirms the potential utility of Gemini as a single-dose preconditioning therapy in our target indications.” said James Rolke, Chief Executive Officer of Revelation. “With this new data, we are excited and committed to moving rapidly into a Phase 1b study in patients late 2024.” For more information on Revelation, please visit . About Gemini Gemini is the Company’s proprietary formulation of phosphorylated hexaacyl disaccharide (PHAD®), a toll-like receptor 4 (TLR4) agonist. TLR4 stimulation with PHAD potentially preconditions the innate immune system to respond to a subsequent stress, such as ischemia (loss of blood flow) or bacterial infection. Gemini is initially being developed as a single dose preconditioning therapy for two target indications: as a pretreatment to prevent or reduce the severity of acute kidney injury due to cardiac surgery (GEMINI-AKI program) and as a pretreatment to reduce the incidence, duration, and severity of post-surgical infection (GEMINI-PSI program). In addition, Gemini has the potential to be a long-term treatment to stop or slow the progression of chronic kidney disease (GEMINI-CKD program). Revelation believes Gemini works through trained immunity, which redirects and attenuates the innate immune response to external stress (infection, trauma, etc.). Preclinical studies evaluating models of AKI or bacterial infection have demonstrated pretreatment with Gemini can reduce the severity and duration of AKI or bacterial infection, respectively. Additionally, preclinical studies evaluating a model of CKD demonstrate the potential of Gemini as a treatment to prevent kidney tissue scarring following the onset of severe inflammation. About the Phase 1 Study Data Analysis For all reported biomarkers except IL-1RA, the reported p-values were based on a two-tailed t-test assuming equal variances between data sets and an alpha of 0.05 for the peak change from baseline in treated subjects (by dose vs peak change in baseline in placebo subjects). For IL-1RA, a two-tailed t-test assuming equal variances between data sets and an alpha of 0.05 using a binary responder analysis of no change vs baseline and change vs. baseline was used. For each analysis there were 9 subjects in the placebo group, 12 subjects in the low dose group, 13 subjects in the mid dose group and 5 subjects in the high dose group. About Revelation Biosciences, Inc. Revelation Biosciences, Inc. is a clinical stage life sciences company focused on harnessing the power of trained immunity for the prevention and treatment of disease using its proprietary formulation Gemini. Revelation has multiple ongoing programs to evaluate Gemini, including as a prevention for post-surgical infection, as a prevention for acute kidney injury, and for the treatment of chronic kidney disease. For more information on Revelation, please visit . Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These forward-looking statements are generally identified by the words "anticipate", "believe", "expect", "estimate", "plan", "outlook", and "project" and other similar expressions. We caution investors that forward-looking statements are based on management’s expectations and are only predictions or statements of current expectations and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from those anticipated by the forward-looking statements. Revelation cautions readers not to place undue reliance on any such forward looking statements, which speak only as of the date they were made. The following factors, among others, could cause actual results to differ materially from those described in these forward-looking statements: the ability of Revelation to meet its financial and strategic goals, due to, among other things, competition; the ability of Revelation to grow and manage growth profitability and retain its key employees; the possibility that the Revelation may be adversely affected by other economic, business, and/or competitive factors; risks relating to the successful development of Revelation’s product candidates; the ability to successfully complete planned clinical studies of its product candidates; the risk that we may not fully enroll our clinical studies or enrollment will take longer than expected; risks relating to the occurrence of adverse safety events and/or unexpected concerns that may arise from data or analysis from our clinical studies; changes in applicable laws or regulations; expected initiation of the clinical studies, the timing of clinical data; the outcome of the clinical data, including whether the results of such study is positive or whether it can be replicated; the outcome of data collected, including whether the results of such data and/or correlation can be replicated; the timing, costs, conduct and outcome of our other clinical studies; the anticipated treatment of future clinical data by the FDA, the EMA or other regulatory authorities, including whether such data will be sufficient for approval; the success of future development activities for its product candidates; potential indications for which product candidates may be developed; the ability of Revelation to maintain the listing of its securities on NASDAQ; the expected duration over which Revelation’s balances will fund its operations; and other risks and uncertainties described herein, as well as those risks and uncertainties discussed from time to time in other reports and other public filings with the SEC by Revelation.

12-month duration of response data from ENVISION study of UGN-102 to be discussed during company sponsored virtual event on June 13, 2024 ENVISION data expected to support completion of UGN-102 NDA in Q3 2024 Post-hoc analysis of OLYMPUS study for JELMYTO shows disease-free periods more than 47.8 months in LG-UTUC JELMYTO® demonstrated continued growth with net product sales of $18.8 million in Q1, compared with $17.2 million in Q1 2023 representing ~10% YoY growth IND accepted for UGN-103, next-generation novel mitomycin-based formulation of UGN-102 to treat LG-IR-NMIBC Conference call and webcast to be held today at 10:00 AM ET PRINCETON, N.J.--(BUSINESS WIRE)-- UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, today announced financial results for the first quarter ended March 31, 2024, and provided an overview of recent developments. “In 2024 to date, UroGen has made excellent progress in both our commercial business and pipeline of innovative products designed to treat urothelial and specialty cancers,” said Liz Barrett, President, and Chief Executive Officer of UroGen. “The upcoming announcement of 12-month duration of response results from ENVISION will be a key clinical milestone and we expect the data to support completion of our NDA for UGN-102. Pre-launch activities are underway and we estimate that UGN-102 will address a more than $3 billion market opportunity. If approved, we believe this product will become the major growth driver for UroGen and could establish a new standard of care in LG-IR-NMIBC.” Q1 2024 and Recent Business Highlights: UGN-102 (mitomycin) for intravesical solution: In January 2024, UroGen initiated submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). The company plans to complete the submission in Q3 2024 with a potential FDA decision as early as the first quarter of 2025. In May 2024, a subgroup analysis from the UGN-102 ATLAS trial was featured in a podium presentation at the American Urological Association (AUA) 2024 Annual Meeting in San Antonio, Texas. The analysis showed that patients with new and recurrent LG-IR-NMIBC treated with UGN-102 ± TURBT (trans urethral resection of bladder tumor) had high probabilities of remaining event-free for disease free survival (DFS) and high probabilities of remaining in complete response. JELMYTO (mitomycin) for pyelocalyceal solution in low-grade upper tract urothelial cancer (LG-UTUC): A soon-to-be-published post-hoc analysis of the OLYMPUS trial assessed the long-term effects in treating LG-UTUC with JELMYTO. Of the 71 patients who enrolled in OLYMPUS, 41 achieved a complete-response 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. JELMYTO was featured in three presentations at the AUA 2024 Annual Meeting. Independent long-term real-world analyses explored use of the product in broad patient types and with different methods of administration. The results show that JELMYTO treatment demonstrated favorable recurrence free survival rates for patients with LG-UTUC who respond to initial induction. The results were consistent regardless of JELMYTO administration, original tumor size, multifocality or tumor location. Continued strong demand for Jelmyto with record patient enrollments forms. Generated net product revenue of $18.8 million in the first quarter of 2024, compared with $17.2 million in the first quarter of 2023, representing ~10% annual growth. Next-generation novel mitomycin-based formulation for urothelial cancers In January 2024, UroGen announced a license and supply agreement with medac GmbH to develop a next-generation novel mitomycin-based formulation for urothelial cancers. UGN-103 and UGN-104 combine UroGen’s RTGel® technology with medac’s licensed mitomycin formulation. The agreement and development program potentially offer both manufacturing efficiencies and IP protection for the Company’s next-generation urothelial cancer franchise. In April 2024, the FDA accepted the Company’s Investigational New Drug (IND) application for UGN-103. If approved, UGN-103 is expected to provide several advantages related to production, cost, supply, and product convenience. UroGen plans to initiate Phase 3 studies to explore the safety and efficacy of UGN-103 in LG-IR-NMIBC in 2024 and UGN-104 in LG-UTUC shortly thereafter. First Quarter 2024 Financial Results JELMYTO Revenue: JELMYTO net product revenues were $18.8 million and $17.2 million for the three months ended March 31, 2024 and 2023, respectively. R&D Expense: Research and development expenses for the first quarter of 2024 were $15.5 million, including non-cash share-based compensation expense of $0.5 million as compared to $12.5 million, including non-cash share-based compensation expense of $0.5 million, for the same period in 2023. SG&A Expense: Selling, general and administrative expenses for the first quarter of 2024 were $27.3 million, including non-cash share-based compensation expense of $2.2 million. This compares to $24.5 million, including non-cash share-based compensation expense of $1.8 million, for the same period in 2023. Financing on Prepaid Forward Obligation: UroGen reported non-cash financing expense related to the prepaid forward obligation to RTW Investments of $5.7 million in the first quarter of 2024, compared to $5.2 million in the same period in 2023. Interest Expense on Long-Term Debt: Interest expense related to the $100 million term loan facility with funds managed by Pharmakon Advisors was $2.4 million in the first quarter of 2024, compared to $3.6 million in the same period in 2023. Net Loss: UroGen reported a net loss of $32.3 million or ($0.97) per basic and diluted share in the first quarter of 2024 compared with a net loss of $30.2 million or ($1.30) per basic and diluted share in the same period in 2023. Cash & Cash Equivalents: As of March 31, 2024, cash, cash equivalents and marketable securities totaled $164.5 million. 2024 Revenue, Operating Expense and RTW Expense Guidance: The Company is reiterating full year 2024 net product revenues guidance from JELMYTO in the range of $95 to $102 million. Increased discounts related to Medicare refunds for discarded drugs and 340B purchases will further impact net revenues in 2024. The Company also expects full year 2024 operating expenses in the range of $175 to $185 million, including non-cash share-based compensation expense of $6 to $11 million, subject to market conditions. The Company also reiterates the anticipated full year 2024 non-cash financing expense related to the prepaid obligation to RTW Investments in the range of $21 to $26 million. Of this amount approximately $12.4 to $13.3 million is expected to be in cash. Conference Call & Webcast Information: Members of UroGen’s management team will host a live conference call and webcast today at 10:00 AM Eastern Time to review UroGen’s financial results and provide a general business update. The live webcast can be accessed by visiting the Investors section of the Company’s website at . Please connect at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. UROGEN PHARMA LTD. SELECTED CONSOLIDATED BALANCE SHEETS (U.S. dollars in thousands) (Unaudited) March 31, 2024 December 31, 2023 Cash and cash equivalents and marketable securities $ 164,525 $ 141,470 Total assets $ 200,574 $ 178,311 Total liabilities $ 240,708 $ 243,523 Total shareholders' deficit $ (40,134 ) $ (65,212 ) UROGEN PHARMA LTD. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (U.S. dollars in thousands, except share and per share data) (Unaudited) Three months ended March 31, 2024 2023 Revenue $ 18,781 $ 17,192 Cost of revenue 1,728 2,265 Gross profit 17,053 14,927 Operating expenses: Research and development expenses 15,494 12,498 Selling, general and administrative expenses 27,299 24,474 Total operating expenses 42,793 36,972 Operating loss (25,740 ) (22,045 ) Financing on prepaid forward obligation (5,660 ) (5,224 ) Interest expense on long-term debt (2,447 ) (3,553 ) Interest and other income, net 1,615 630 Loss before income taxes $ (32,232 ) $ (30,192 ) Income tax expense (54 ) (21 ) Net loss $ (32,286 ) $ (30,213 ) Net loss per ordinary share, basic and diluted $ (0.97 ) $ (1.30 ) Weighted average shares outstanding, basic and diluted 33,379,786 23,279,951 About JELMYTO JELMYTO® (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for the treatment of adult patients with LG-UTUC. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow. APPROVED USE FOR JELMYTO JELMYTO® is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC). IMPORTANT SAFETY INFORMATION You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract. Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you: are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO. Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose. Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose. are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose. Tell your healthcare provider if you take water pills (diuretic). How will I receive JELMYTO? Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment. You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses. JELMYTO is given to your kidney through a tube called a catheter. During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines. After receiving JELMYTO: JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours. To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water. Clothing that comes in contact with urine should be washed right away and washed separately from other clothing. JELMYTO may cause serious side effects, including: Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO. Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO. The most common side effects of JELMYTO include: urinary tract infection, blood in your urine, side pain, nausea, trouble with urination, kidney problems, vomiting, tiredness, stomach (abdomen) pain. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1‑800‑FDA‑1088. You may also report side effects to UroGen Pharma at 1-855-987-6436. Please see JELMYTO Full Prescribing Information, including the Patient Information, for additional information. About Upper Tract Urothelial Cancer (UTUC) Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as upper tract urothelial cancers (UTUC). In the U.S., there are approximately 6,000 - 7,000 new or recurrent low-grade UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). These treatments can lead to a high rate of recurrence and relapse. About UGN-102 UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of low-grade, intermediate-risk, non-muscle invasive bladder cancer (LG-IR-NMIBC). Utilizing UroGen’s proprietary RTGel® technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting. Assuming positive findings from the durability of response endpoint from the ENVISION Phase 3 study, UroGen anticipates completing its NDA submission for UGN-102 in September with a potential FDA decision as early as the first quarter of 2025. About UroGen Pharma Ltd. UroGen is a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers because patients deserve better options. UroGen has developed RTGel reverse-thermal hydrogel, a proprietary sustained-release, hydrogel-based platform technology that has the potential to improve the therapeutic profiles of existing drugs. UroGen’s sustained release technology is designed to enable longer exposure of the urinary tract tissue to medications, making local therapy a potentially more effective treatment option. Our first product to treat low-grade upper tract urothelial cancer and investigational treatment UGN-102 (mitomycin) for intravesical solution for patients with low-grade non-muscle invasive bladder cancer are designed to ablate tumors by non-surgical means. UroGen is headquartered in Princeton, NJ with operations in Israel. Visit to learn more or follow us on X (Twitter), @UroGenPharma. Forward-Looking Statements This press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding: the Phase 3 ENVISION trial, including the expected release of data in June 2024; the estimated addressable patient population and market and revenue opportunity for UGN-102; the expectation UGN-102 will be a significant driver of UroGen’s future growth; potential for UGN-102 to establish a new standard of care in LG-IR-NMIBC; UroGen’s plans to complete its NDA submission for UGN-102 in the third quarter of 2024, with a potential FDA decision as early as the first quarter of 2025; the potential advantages of treatment with UGN-102 ± TURBT over TURBT alone; publication of the post-hoc analysis of the OLYMPUS trial that assessed the long-term effects in treating LG-UTUC with JELMYTO; the interpretation and summary of results of ENVISION, OLYMPUS, and ATLAS trials; potential for the license and supply agreement with medac to offer both manufacturing efficiencies and IP protection; the timing for the planned Phase 3 trial of UGN-103 and the potential approval of UGN-103; the timing of the planned Phase 3 trial of UGN-104;; the potential of UroGen’s proprietary RTGel technology to improve therapeutic profiles of existing drugs; and the potential of UroGen’s sustained release technology to make local delivery more effective as compared to other treatment options. Words such as “anticipate,” “could,” “may,” “plan,” “potential,” “soon-to-be,” “will,” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. These statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: preliminary results may not be indicative of results that may be observed in the future; the timing and success of clinical trials and potential safety and other complications thereof; unforeseen delays that may impact the timing of progressing clinical trials and reporting data; findings from the durability of response endpoint from the ENVISION Phase 3 study may not be sufficient to support UroGen’s NDA; even if an NDA for UGN-102 is accepted by the FDA, there is no guarantee that such NDA will be sufficient to support approval of UGN-102 on the timeframe expected, or at all; the ability to obtain regulatory approval within the timeframe expected, or at all; the ability to obtain and maintain adequate intellectual property rights and adequately protect and enforce such rights; the ability to maintain regulatory approval; complications associated with commercialization activities; the labeling for any approved product; competition in UroGen’s industry; the scope, progress and expansion of developing and commercializing UroGen’s product candidates; the size and growth of the market(s) for UroGen’s product and product candidates and the rate and degree of market acceptance thereof vis-à-vis alternative therapies; UroGen’s ability to attract or retain key management, members of the board of directors and personnel; UroGen’s RTGel technology may not perform as expected; UroGen may not successfully develop and receive regulatory approval of any other product that incorporates RTGel technology; and UroGen’s financial condition and need for additional capital in the future. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section of UroGen’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 14, 2024, as well as in the Risk Factors section of UroGen’s Quarterly Report on Form 10-Q being filed with the SEC later today, the events and circumstances discussed in such forward-looking statements may not occur, and UroGen’s actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to UroGen as of the date of this release.

There Were No Differences in RFS Regarding Usage for Chemoablation or Post-Endoscopic Ablation, Tumor Size, Multifocality, or Tumor Location RFS Was 100% in Patients who Received Maintenance therapy vs 61% for Patients Who Did Not Receive Maintenance Therapy PRINCETON, N.J.--(BUSINESS WIRE)-- UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, today highlights the results of a sub-analysis from the first and largest real-world patient cohort review of JELMYTO (mitomycin) for pyelocalyceal solution presented at the American Urological Association Meeting 2024 in San Antonio, TX. Among patients with low-grade Ta upper tract urothelial carcinoma (UTUC) who were complete responders to induction therapy (n=53), JELMYTO was associated with an 86% recurrence-free survival rate at 24 months across diverse patient types regardless of initial disease characteristics or usage for chemoablation versus post-endoscopic ablation. Among the 30% of the complete responders who received maintenance therapy, RFS at 24 months was 100%, vs. 61% for those who did not receive maintenance therapy. “The 86% recurrence-free survival rate at the 24-month mark among low-grade UTUC patients (n=53) exhibited a favorable response to the initial induction of this new treatment,” said Adam Feldman, M.D., M.P.H., Urologic Oncologist in the Department of Urology at Massachusetts General Hospital, and Director of the Combined Harvard Urologic Oncology Fellowship. “Notably, there seems to be no discernible difference in disease recurrence based on tumor characteristics or timing of administration, including primary chemoablation or post-endoscopic ablation. These results offer additional evidence for the clinical utility of JELMYTO and may also offer hope for improved long-term outcomes for our patients.” Furthermore, a different analysis of the same patient cohort, presented by Yair Lotan, M.D., Professor of Urology and Chief of Urologic Oncology at UT Southwestern and Parkland Health and Hospital System and study investigator, reports that “maintenance therapy with JELMYTO following successful induction treatment (n = 16) yielded a RFS rate of 100%, supplying more evidence of JELMYTO’s pivotal role in treating this challenging condition,” according to Dr. Lotan. Data was collected from 15 centers on patients treated with JELMYTO for upper tract urothelial cancers (UTUC). Recurrence-free survival was calculated in 53 patients with LGTa disease at baseline who had no evidence of disease following JELMYTO induction. Chemoablative use was defined as the administration of JELMYTO treatment in the setting of known residual UTUC, while post-chemoablation use was defined as receipt of JELMYTO following visually complete endoscopic ablation. Exploratory analyses were performed to assess impact of size of tumor, presence of ureteral involvement, and multifocality of UTUC prior to JELMYTO induction on RFS at 24 months. “These findings provide additional evidence reinforcing JELMYTO's position as a valuable therapeutic option for patients with low-grade upper tract urothelial cancer and add to the growing body of real-world evidence in extending the long-term positive outcomes for patients,” said Mark Schoenberg, MD, Chief Medical Officer at UroGen. “This real-world evidence reaffirms JELMYTO's role as a valuable tool in our fight against this disease.” There were 136 cases of UTUC treated with JELMYTO with a cumulative median (IQR) follow-up of 22 (12-27) months including 107 cases of LGTa UTUC. After initial treatment, 74% of post-endoscopic ablation and 39% of chemoablative patients were disease-free totaling 53 cases with LGTa UTUC without evidence of disease following JELMYTO induction. The limitations of these sub-analyses include the sample size, retrospective design, lack of a control group, and the lack of a centralized pathology review and standardized clinicopathologic assessment. To further explore the full potential of JELMYTO for the treatment of patients with UTUC, investigators are in the process of enrolling the prospective and retrospective uTRACT Registry to capture data in a large-scale, standardized manner to report further on patient outcomes following JELMYTO treatment including long-term longitudinal follow-up. About JELMYTO JELMYTO® (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for the treatment of adult patients with low-grade-UTUC (LG-UTUC). It is approved for adult patients with LG-UTUC. JELMYTO is a viscous liquid when cooled and becomes a semi-solid gel at body temperature. The drug slowly dissolves over four to six hours after instillation and is removed from the urinary tract by normal urine flow and voiding. It is approved for administration in a retrograde manner via ureteral catheter or antegrade through nephrostomy tube. The delivery system allows the initial liquid to coat and conform to the upper urinary tract anatomy. The eventual semisolid gel allows for chemoablative therapy to remain in the collecting system for four to six hours without immediately being diluted or washed away by urine flow. About Upper Tract Urothelial Cancer (UTUC) Urothelial cancer is the ninth most common cancer globally and the eighth most lethal neoplasm in men in the U.S. Between five percent and ten percent of primary urothelial cancers originate in the ureter or renal pelvis and are collectively referred to as UTUC. In the U.S., there are approximately 6,000 - 7,000 new or recurrent LG-UTUC patients annually. Most cases are diagnosed in patients over 70 years old, and these older patients often face comorbidities. There are limited treatment options for UTUC, with the most common being endoscopic surgery or nephroureterectomy (removal of the entire kidney and ureter). Treatment with endoscopic surgery can lead to a high rate of recurrence and relapse. About UroGen Pharma Ltd. UroGen is a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers because patients deserve better options. UroGen has developed RTGel® reverse-thermal hydrogel, a proprietary sustained-release, hydrogel-based platform technology that has the potential to improve the therapeutic profiles of existing drugs. UroGen’s sustained release technology is designed to enable longer exposure of the urinary tract tissue to medications, making local therapy a potentially more effective treatment option. Our first product to treat LG-UTUC and investigational treatment UGN-102 (mitomycin) for intravesical solution for patients with low-grade non-muscle invasive bladder cancer are designed to ablate tumors by non-surgical means. UroGen is headquartered in Princeton, NJ with operations in Israel. Visit to learn more or follow us on X (Twitter), @UroGenPharma. Disclosure: Dr. Yair Lotan is a paid consultant to UroGen Pharma Ltd. APPROVED USE FOR JELMYTO JELMYTO® is a prescription medicine used to treat adults with a type of cancer of the lining of the upper urinary tract including the kidney called low-grade Upper Tract Urothelial Cancer (LG-UTUC). IMPORTANT SAFETY INFORMATION You should not receive JELMYTO if you have a hole or tear (perforation) of your bladder or upper urinary tract. Before receiving JELMYTO, tell your healthcare provider about all your medical conditions, including if you: are pregnant or plan to become pregnant. JELMYTO can harm your unborn baby. You should not become pregnant during treatment with JELMYTO. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JELMYTO. Females who are able to become pregnant: You should use effective birth control (contraception) during treatment with JELMYTO and for 6 months after the last dose. Males being treated with JELMYTO: If you have a female partner who is able to become pregnant, you should use effective birth control (contraception) during treatment with JELMYTO and for 3 months after the last dose. are breastfeeding or plan to breastfeed. It is not known if JELMYTO passes into your breast milk. Do not breastfeed during treatment with JELMYTO and for 1 week after the last dose. Tell your healthcare provider if you take water pills (diuretic). How will I receive JELMYTO? Your healthcare provider will tell you to take a medicine called sodium bicarbonate before each JELMYTO treatment. You will receive your JELMYTO dose from your healthcare provider 1 time a week for 6 weeks. It is important that you receive all 6 doses of JELMYTO according to your healthcare provider’s instructions. If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. Your healthcare provider may recommend up to an additional 11 monthly doses. JELMYTO is given to your kidney through a tube called a catheter. During treatment with JELMYTO, your healthcare provider may tell you to take additional medicines or change how you take your current medicines. After receiving JELMYTO: JELMYTO may cause your urine color to change to a violet to blue color. Avoid contact between your skin and urine for at least 6 hours. To urinate, males and females should sit on a toilet and flush the toilet several times after you use it. After going to the bathroom, wash your hands, your inner thighs, and genital area well with soap and water. Clothing that comes in contact with urine should be washed right away and washed separately from other clothing. JELMYTO may cause serious side effects, including: Swelling and narrowing of the tube that carries urine from the kidney to the bladder (ureteric obstruction). If you develop swelling and narrowing, and to protect your kidney from damage, your healthcare provider may recommend the placement of a small plastic tube (stent) in the ureter to help the kidney drain. Tell your healthcare provider right away if you develop side pain or fever during treatment with JELMYTO. Bone marrow problems. JELMYTO can affect your bone marrow and can cause a decrease in your white blood cell, red blood cell, and platelet counts. Your healthcare provider will do blood tests prior to each treatment to check your blood cell counts during treatment with JELMYTO. Your healthcare provider may need to temporarily or permanently stop JELMYTO if you develop bone marrow problems during treatment with JELMYTO. The most common side effects of JELMYTO include: urinary tract infection, blood in your urine, side pain, nausea, trouble with urination, kidney problems, vomiting, tiredness, stomach (abdomen) pain. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1800FDA1088. You may also report side effects to UroGen Pharma at 1-855-987-6436. Please see JELMYTO Full Prescribing Information, including the Patient Information, for additional information. Forward-Looking Statements This press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding the results from the real-world study of JELMYTO offering hope for improved long-term outcomes for patients; the enrollment of the prospective and retrospective data from the uTRACT Patient Registry and plans to analyze and report on such data; the potential of UroGen’s proprietary RTGel technology to improve therapeutic profiles of existing drugs; and UroGen’s sustained release technology making local delivery potentially more effective as compared to other treatment options. These statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: results from of the real-world study of JELMYTO may not be indicative of results that may be observed in future clinical practice and may differ from additional analysis of the data from the study or uTRACT Patient Registry; potential safety and other complications from JELMYTO use in diverse UTUC patient types; the ability to maintain regulatory approval; the ability to obtain and maintain adequate intellectual property rights and adequately protect and enforce such rights; complications associated with commercialization activities; UroGen’s RTGel technology may not perform as expected; and UroGen may not successfully develop and receive regulatory approval of any other product that incorporates UroGen’s RTGel technology. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section of UroGen’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 14, 2024 (which is available at ), the events and circumstances discussed in such forward-looking statements may not occur, and UroGen’s actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to UroGen as of the date of this release. View source version on businesswire.com: Contacts INVESTOR CONTACT: Vincent Perrone Senior Director, Investor Relations vincent.perrone@urogen.com 609-460-3588 ext. 1093 MEDIA CONTACT: Cindy Romano Director, Corporate Communications cindy.romano@urogen.com 609-460-3583 ext. 1083 Source: UroGen Pharma Ltd. View this news release online at: