Transitional cell cancer of the renal pelvis and ureter recurrent

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 highlights results from the first and largest post-commercial utilization review of JELMYTO ® (mitomycin) for pyelocalyceal solution. This study evaluated 132 patients treated with JELMYTO from 15 high-volume academic and community centers and characterizes the manner in which urologists are now using JELMYTO in their practices. The study titled, “Early Experience with UGN-101 for the Treatment of Upper Tract Urothelial Cancer – A Multi-Center Evaluation of Practice Patterns and Outcomes,” is published in Urologic Oncology: Seminars and Original Investigations. The authors describe several trends in JELMYTO use that differ from the pivotal Olympus study that led to drug approval. Doctors are using JELMYTO for the treatment of large tumors (>3cm in 15% of cases), high grade tumors (9% of cases), and ureteral tumors (35% of cases). In addition, the report documents the use of JELMYTO as a valuable multimodal adjunct following complete laser tumor ablation. JELMYTO is indicated for the treatment of adult patients with low-grade upper tract urothelial cancer (LG-UTUC). Primary chemoablation resulted in a 70% complete response (CR) rate for patients with tumors less than 1cm (CR rates following primary therapy were lower for larger tumors consistent with previous reporting) while 69% achieved CR when JELMYTO was combined with laser ablation. CR in the Olympus trial was 59%. Almost half of the patients in the review were treated by antegrade administration of JELMYTO through a nephrostomy tube. The Olympus cohort was treated exclusively by retrograde catheter passed into the upper tract through the bladder. The authors of a recent single-center retrospective review observed that antegrade administration of JELMYTO was associated with a lower rate of ureteric stenosis than the retrograde approach as observed in OLYMPUS, and this larger multi-center review supports that earlier observation. The rate of ureteric stenosis in the Olympus trial was 44%. In this multi-center study it was 23%. The limitations of this study include the retrospective design, lack of a control group, 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 longitudinal follow-up. “This study provides valuable insights into how physicians are utilizing JELMYTO in the real-world and reinforces the genuine clinical value of this therapy for patients with LG-UTUC,” said Mark Schoenberg, M.D., Chief Medical Officer, UroGen. “We look forward to additional analyses from this retrospective study as well as prospective and retrospective data from the uTRACT Patient Registry.” About UTUC Approximately 5-7% of urothelial cancer occurs in the upper lining of the kidney, called the calyx and renal pelvis. It could also occur in one or both of the ureter(s), the tubes that lead from the kidneys to the bladder. Cancer in the renal pelvis or ureter(s) is called upper tract. LG-UTUC is usually not very aggressive and is slow to spread but has a high recurrence rate. High-grade UTUC can be more aggressive. It may spread to other parts of the urinary tract, or to other parts of the body. JELMYTO is approved for the treatment of adults with LG-UTUC. LG-UTUC is a rare disease managed by endoscopic methods and radical nephroureterectomy. Endoscopic resection and laser ablation attempt to preserve the kidney, though there is a high risk of recurrence that may eventually necessitate removal of the kidney. Although kidney removal is the gold standard for treatment of high-grade UTUC, it may be over-treatment in LG-UTUC, as kidney removal offers similar five-year survival as kidney-sparing procedures but is associated with significant morbidity. JELMYTO is efficacious as a primary chemoablative therapy in patients with LG-UTUC. About JELMYTO ® JELMYTO ® (mitomycin) for pyelocalyceal solution is a mitomycin-containing reverse thermal gel containing 4 mg mitomycin per mL gel indicated for primary chemoablative treatment of LG-UTUC in adults. It is recommended for primary treatment of biopsy-proven LG-UTUC in patients deemed appropriate candidates for renal-sparing therapy. 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 U.S. Food and Drug Administration. Visit www.fda.gov/medwatch or call 1800FDA1088. You may also report side effects to UroGen Pharma at 1-855-987-6436. Please click here for JELMYTO Full Prescribing Information, including the Patient Information, for additional information and here for the Nephrostomy Administration Guide. About UroGen Pharma Ltd. UroGen is 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 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. UroGen’s first commercial product JELMYTO (mitomycin) for pyelocalyceal solution, 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 www.urogen.com to learn more or follow us on 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 additional analysis from the retrospective study of JELMYTO as well as prospective and retrospective data from the uTRACT Patient Registry; 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 initial reports from the retrospective study evaluating post-commercial utilization of JELMYTO in the publication 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; potential safety and other complications from JELMYTO use in diverse UTUC patient types; and our RTGel technology may not perform as expected and we may not successfully develop and receive regulatory approval of any other product that incorporates our 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 Form 10-Q filed with the United States Securities and Exchange Commission (SEC) on November 10, 2022 and other filings that UroGen makes with the SEC from time to time (which are available at http://www.sec.gov ), 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.

June 22, 2022 12:00 UTC SAN DIEGO & REHOVOT, Israel--(BUSINESS WIRE)-- Nucleix a liquid biopsy company revolutionizing cancer treatment by detecting the disease earlier, today announced that the company has expanded the European Union (EU) label indication of its Bladder EpiCheck® test. Bladder EpiCheck detects DNA methylation patterns in urine that are associated with urothelial cancer. The technology was initially indicated for use as a non-invasive method for the monitoring of tumor recurrence in conjunction with cystoscopy in patients previously diagnosed with bladder cancer. The current update expands the label indication to also include aiding in the detection of primary bladder cancer and upper tract urothelial carcinoma (UTUC) in patients presenting with hematuria and/or other urinary tract symptoms and/or findings with a suspicion of malignancy, and the detection of recurrent UTUC, in conjunction with standard diagnostic procedures. Bladder cancer is the fifth most common cancer in Europe with more than 200,000 new cases of the disease diagnosed annually.1 With bladder cancer, patients typically experience symptoms of traces of blood in the urine, called hematuria, though this is not usually visible to the naked eye.2 Up to 30% of adults will experience hematuria at some point in their life, so it is crucial to quickly and non-invasively determine if the symptom is associated with bladder cancer, to ensure a urological workup is conducted immediately.2 Bladder EpiCheck demonstrated 88% sensitivity in detecting the primary high-risk bladder cancer, with a specificity of 98% or more. “The current workup of hematuria is invasive, costly and usually performed too late, due to delayed referrals to urologists, all the while symptoms can worsen and diagnosis of the disease is delayed when treatment is critical,” said Eli Frydman, Ph.D. MBA, President EMEA of Nucleix. “With this expanded label indication and high specificity of Bladder EpiCheck in this population, we’re able to offer a cost-effective, non-invasive approach to triage hematuria patients and help identify bladder cancer early.” Two recently published studies evaluated the performance of Bladder EpiCheck in the detection of primary and recurrent UTUC including 220 patients.3,4 Bladder Epicheck showed high-grade sensitivity of 96-98% and specificity of 81-100% in urine collected from the ureter. One of the studies also reported high-grade sensitivity of 71% and specificity of 81% in bladder urine. In both studies, test sensitivity was higher than cytology. “Identifying patients with high-grade UTUC early is critical – if missed, the disease can progress to metastases very quickly and the standard treatment, which is the removal of ureter and kidney, can lead to considerable morbidity,” said Aharona Shuali, M.D., Vice President of Medical Affairs at Nucleix. “We are encouraged by this expanded label indication because of its potential impact on patients. Bladder EpiCheck delivers highly accurate results in a non-invasive way and could play an important role in the diagnosis and follow-up of this disease, particularly in ruling-out high-grade disease.” About Bladder EpiCheck® Bladder EpiCheck® provides patients and clinicians with a simple, objective urine test to detect primary and recurrent bladder and upper urinary tract cancers. The test analyzes subtle disease-specific changes in DNA methylation markers, with sensitivity of 91-96% of high-grade cancers. Bladder EpiCheck® demonstrated negative predictive value (NPV) of 99% for high-grade cancer, meaning that when receiving a negative Bladder EpiCheck® result, there is 99% chance that no high-grade cancer is present.5 Overall specificity of Bladder EpiCheck® is 84%, 81% and 98% for recurrent bladder cancer, UTUC and primary cancers, respectively, ensuring a low rate of false positive results. Bladder EpiCheck® is intended for use as a non-invasive method for detection of urinary tract cancers in conjunction with standard methods. Bladder EpiCheck® is CE-marked and commercially available in Europe. The test is not available for sale in the United States. About Nucleix Nucleix is a liquid biopsy company revolutionizing cancer treatment with earlier disease detection at a time when intervention can bring the greatest impact for patients. Leveraging NGS and PCR-based epigenetics, the Company’s pioneering testing approach uses methylation-based identification for early-stage and recurring cancer detection. The Company’s non-invasive EpiCheck® platform delivers highly accurate and sensitive results, all while providing a seamless testing option for patients and the healthcare system. The Company is building an EpiCheck franchise, beginning with the Bladder EpiCheck® testing kit, marketed in Europe for the detection of primary and recurrent bladder cancer and Upper Tract Urinary Cancer. The Company is advancing a Lung EpiCheck test toward commercialization for high-risk individuals, while advancing additional tests for high-risk diseases. For more information, please visit: . _____________________________ 1 The International Agency for Research on Cancer (IARC). (n.d.). Global Cancer Observatory. Global Cancer Observatory. Retrieved June 9, 2022, from 2 Matulewicz, R. S., MD. (2016, October 11). Blood in the Urine (Hematuria). Nephrology | JAMA | JAMA Network. 3 Territo, A., et al. (2022). DNA methylation urine biomarkers test in the diagnosis of Upper Tract urothelial carcinoma: Results from a single-center prospective clinical trial. Journal of Urology. 4 Pierconti, F., et al. (2021). Upper Urothelial Tract High-grade carcinoma: Comparison of urine cytology and DNA methylation analysis in urinary samples. Human Pathology. 5 Laukhtina, E., et al. (2022). Corrigendum to “Diagnostic Accuracy of Novel Urinary Biomarker Tests in Non–muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis” [Eur Urol Oncol 2021;4:927–42]. European Urology Oncology.

Pivotal Phase 3 trial recruiting 100 patients, and examining complete response of tumors as the primary endpoint. Consists of induction and maintenance phases, with follow up 12 months post treatment The activation of ENLIGHTED marks a significant milestone for Steba’s ambitious development program LUXEMBOURG, April 20, 2021 (GLOBE NEWSWIRE) -- Steba Biotech, the pioneering Im mune P hoto A ctivate C ancer T reatment (ImPACT) specialist, today announces the treatment of the first patient in ENLIGHTED, its pivotal Phase 3 trial of Padeliporfin ImPACT for the treatment of Low Grade Upper Tract Urothelial Cancer (UTUC). David Perry, Head of Research and Development, said, “The successful initiation of the pivotal trial for padeliporfin ImPACT is an important milestone in our ambitious new development program. Our aim is to unlock the potential of our novel oncology platform, Padeliporfin ImPACT, on solid tumors with high unmet medical need. Targeting diseases such as UTUC, where surgery is either impossible or clinically undesirable could be very beneficial for patients living with these conditions. The ENLIGHTED trial is one of two clinical and five pre-clinical programs that we are advancing this year.” The International, multi-center ENLIGHTED study aims to recruit 100 patients with low-grade UTUC in either the kidney or the ureter. The patients will be treated with Padeliporfin ImPACT in two phases, induction treatment and maintenance treatment, and will be followed up for 1-5 years post treatment. The primary efficacy endpoint is the absence of UTUC tumors in the entire ipsilateral calyces’ renal pelvis and ureter which will be evaluated endoscopically and determined as either failure or success in achieving complete response. Primary endpoint data is expected in 2022 and submission is expected in 2023. Jonathan Coleman, MD, Principal Investigator of ENLIGHTED and urologic surgeon at Memorial Sloan Kettering Cancer Center, said, “The treatment of UTUC remains a clinical challenge with limited options available to effectively help our patients while avoiding the risk of significant morbidity. This study will work closely with investigators in the U.S., Europe and Israel with the goal of confirming the safety and efficacy of Padeliporfin ImPACT as a promising new therapy for treating patients with urothelial cancers involving the upper urinary tract.” Steba is focusing on the development of Padeliporfin ImPACT as an innovative oncology platform with the potential to offer surgery-like efficacy, combined with organ preservation in UTUC and other solid tumors for high-risk surgical patients with unmet needs – either because surgery is not the preferred clinical option (e.g. to delay the loss of a kidney) or the risk of surgery is too high. The U.S. Food and Drug Administration has granted Orphan Drug Designation (ODD) and Fast Track designation to Padeliporfin ImPACT for the treatment of adult patients with low-grade UTUC. About Padeliporfin ImPACT Padeliporfin ImPACT (Immune Photo Activated Cancer Therapy) offers surgery-like efficacy combined with organ preservation. ImPACT is Steba's oncology platform comprising the intravenous delivery of an inactive drug, Padeliporfin activated by non-thermal laser light. Upon activation, the drug rapidly triggers the constriction of the blood supply in the illuminated area only, resulting in targeted tumor necrosis that activates anti-tumor immunity which enhances cancer cell eradication. About UTUC Upper tract urothelial carcinoma (UTUC) is a type of cancer that grows from the urothelium, a thin, continuous, protective layer of cells which line the urine collecting system from kidney to bladder [1]. UTUC obstructs the flow of urine from the kidney causing severe flank pain and blood to appear in urine, which may not be visible with the naked eye and delays diagnosis [2]. It currently accounts for 5-10 percent of urinary tract cancers [3], with the prognosis worse than bladder cancer and worsening over time, increasing the strain on healthcare services[4]. About Steba Biotech Steba Biotech is a Luxembourg based biotech company founded in 1996. It is focused on developing a novel potential cancer therapy, Padeliporfin ImPACT, considered a potential new chemical entity by FDA/EMA. Padeliporfin ImPACT offers surgery-like efficacy combined with organ preservation. The activation of Padeliporfin in the tumor has been shown in patients to lead to immediate occlusion of the tumor blood supply followed by self-propagating necrosis of the entire tumor with minimal collateral damage to surrounding normal tissue. We are focusing our new Padeliporfin ImPACT development on de-risked indications where surgery is most needed but overly debilitating or ineligible. Thus far, Padeliporfin ImPACT has proven to be safe and efficacious in Phase 3 localized prostate cancer and is approved in Europe in that indication. U.S. ODAC recommended against TOOKAD VTP (brand name for Padeliporfin ImPACT in prostate cancer) approval in early prostate cancer, citing concerns that it might be used too broadly, i.e. in patients that might not need it, where a wait and see approach might be better. Our U.S. development strategy now focused on indications where surgery would be required but comes with overly debilitating consequences or cannot be conducted in patients. Contacts Disclaimer This press release contains certain forward-looking statements concerning Steba Biotech and its business. Such forward looking statements are based on assumptions that Steba considers to be reasonable. However, there can be no assurance that such forward-looking statements will be verified, which statements are subject to numerous risks and to the development of economic conditions, financial markets and the markets in which Steba operates. The forward-looking statements contained in this press release are also subject to risks not yet known to Steba or not currently considered material by Steba. The occurrence of all or part of such risks could cause actual results, financial conditions, performance, or achievements of Steba to be materially different from such forward-looking statements. This press release and the information that it contains do not constitute an offer to sell or subscribe for, or a solicitation of an offer to purchase or subscribe for, Steba shares in any country. The communication of this press release in certain countries may constitute a violation of local laws and regulations. Any recipient of this press release must inform oneself of any such local restrictions and comply therewith. 1. Upper Tract Urothelial Carcinoma. (n.d.). Accessed January 8, 2021; . 2. Taylor, W. S. (2019). Delays to Diagnosis and Management of Upper Tract Urothelial Carcinoma. Journal of Endoluminal Endourology, 2(3), e5–e11. . 3. Soria, F., Shariat, S. F., Lerner, S. P., Fritsche, H.-M., Rink, M., Kassouf, W., Thalmann, G. N. (2016). Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC). World Journal of Urology, 35(3), 379–387. doi: 10.1007/s00345-016-1928-x. 4. Eylert, M., Hounsome, L., Verne, J., Bahl, A., Jefferies, E., & Persad, R. (2013). Prognosis is deteriorating for upper tract urothelial cancer: data for England 1985-2010. BJU International, 112(2), E107-E113. doi: 10.1111/bju.12025.