On April 26, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported encouraging safety data from the Phase 1 dose-escalation study for UGN-301 (zalifrelimab) intravesical solution, an investigational drug in development for the treatment of recurrent non-muscle invasive bladder cancer (NMIBC) (Press release, UroGen Pharma, APR 26, 2025, View Source [SID1234652194]).

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"The early safety profile and clinical activity results from this study are encouraging," said Jay Raman, M.D., Professor and Chair of Urology, and Professor of Surgery, Penn State Cancer Institute, PA. "This innovative approach of localized drug delivery combined with immune modulation merits additional investigation in the treatment of non-muscle invasive bladder cancer."

The multi-part clinical study included up to 30 patients per arm, aimed to assess safety and determine the recommended Phase 2 dose of UGN-301 as monotherapy and in combination with other agents. In the monotherapy arm, dose escalation continued to the maximum feasible dose. No dose-limiting toxicities and no treatment-emergent adverse events leading to treatment discontinuation were observed. This study also demonstrated that local delivery of UGN-301 formulated in our proprietary reverse thermal gel (RTGel) allowed sustained exposure of zalifrelimab in the bladder with limited systemic exposure, which mitigated the risk of systemic immune-related toxicities associated with CTLA-4 inhibition.

With respect to clinical activity observed in the trial, among evaluable patients who received UGN-301, 46% (6 of 13) of those with Ta/T1 disease and 33% (2 of 6) of those with carcinoma in situ (CIS) ± Ta/T1 disease were recurrence-free or had achieved a complete response at week 12. Notably, 60% (3 of 5) of patients with Ta/T1 disease treated with 300 mg continued to remain recurrence-free at the 15-month disease assessment, including one patient with high-grade T1 disease. In the 500 mg cohort, 25% (1 of 4) of patients with CIS disease and 33% (1 of 3) of patients with Ta/T1 disease remained disease-free at six months, both of whom are still active participants in the study.

These findings highlight the potential of UGN-301 as a targeted treatment for NMIBC with an acceptable safety profile. Presentation of data from the combination arms is planned for later this year.

"Our hypothesis is that UGN-301’s unique formulation could potentially offer the dual benefits of maximizing therapeutic activity while minimizing systemic side effects, a key challenge in cancer immunotherapy," said Mark Schoenberg, Chief Medical Officer, UroGen. "Although this requires additional clinical investigation, we are encouraged by the potential of UGN-301 as an investigational treatment for patients with recurrent NMIBC."

About Non-Muscle Invasive Bladder Cancer and High-Grade Disease

In the U.S., bladder cancer is the second most common urologic cancer in men. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. High-grade non-muscle invasive bladder cancer (HG-NMIBC) is a serious and potentially life-threatening form of bladder cancer that remains confined to the inner layers of the bladder wall but exhibits aggressive behavior and a higher risk of progression. In the U.S., HG-NMIBC accounts for approximately 30–40% of all newly diagnosed NMIBC cases. Patients with HG-NMIBC face a significantly elevated risk of recurrence and progression to muscle-invasive disease, necessitating close surveillance and aggressive treatment. The standard of care includes complete transurethral resection of bladder tumor, often followed by intravesical therapy such as Bacillus Calmette-Guérin (BCG). However, BCG has a treatment failure rate of approximately 40-50%, leaving patients with limited treatment options short of radical cystectomy. Given the high recurrence and progression rates, HG-NMIBC presents a substantial clinical and quality-of-life burden. Upon recurrence, which occurs in approximately 70% of patients, the patients undergo another round of BCG therapy with a response rate of approximately 30%.

About UGN-301

UGN-301 is an anti-CTLA-4 monoclonal antibody (zalifrelimab), originally licensed from Agenus Inc. in 2019. It is formulated with RTGel, our proprietary reverse-thermal hydrogel, for intravesical administration into the bladder. Intravesical administration of UGN-301 is designed to increase drug concentrations in the bladder without significant systemic exposure, potentially diminishing the systemic toxicity associated with CTLA-4 blockade. UroGen is evaluating UGN-301 in a multi-arm Phase 1 study of UGN-301 as monotherapy and in combination with other agents. The safety of UGN-301 is being evaluated in the monotherapy arm of the study as combination therapy for HG-NMIBC.

On April 26, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported an updated 18-month DOR of 80.6% (95% CI: 74.0, 85.7), by Kaplan-Meier estimate, from the Phase 3 ENVISION trial of UGN-102 (mitomycin) for intravesical solution, an investigational treatment for recurrent LG-IR-NMIBC (Press release, UroGen Pharma, APR 26, 2025, View Source [SID1234652195]). These data were featured today in an Oral Presentation Session (Abstract ID: PD12) at the AUA 2025 Annual Meeting in Las Vegas, Nevada.

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"This new update from the pivotal ENVISION trial of UGN-102 demonstrated a compelling probability of remaining in complete response of 80.6% at 18 months in patients who achieved a complete response (CR) at three months (79.6%)," said Sandip Prasad M.D., M.Phil., Director of Genitourinary Surgical Oncology, Vice Chair of Urology at Morristown Medical Center/Atlantic Health System, NJ, and Principal Investigator of the ENVISION trial. "Low-grade bladder cancer is a persistent cancer that frequently recurs and comes with its own risks. There is a significant unmet need in finding treatment options for patients with recurrent low-grade bladder cancer."

The existing standard of care for LG-IR-NMIBC is an invasive surgical procedure requiring anesthesia called transurethral resection of bladder tumor (TURBT). Repeated TURBT procedures can impact patients’ physical health and quality of life and are even associated with an increased risk in mortality. Due to high recurrence rates, LG-IR-NMIBC patients, who are typically elderly with comorbidities, will likely need multiple TURBTs under general anesthesia over the course of their lifetime. An estimated 59,000 patients with LG-IR-NMIBC recur annually and face the burden and risks of repeat surgeries that often provide limited value.

Mark Schoenberg, M.D., Chief Medical Officer of UroGen, stated, "The duration of response data from the ENVISION trial further underscores UGN-102’s potential to positively impact the treatment landscape for patients with recurrent LG-IR-NMIBC. Many of these patients are elderly and face the burden of repeated surgeries under general anesthesia, highlighting the urgent need for innovative treatment options. If approved, we believe UGN-102’s potential to deliver durable complete responses, reduce recurrence rates, and extend treatment-free intervals would represent a significant advancement in the management of recurrent LG-IR-NMIBC."

The most common treatment-emergent adverse events (TEAEs) in the ENVISION trial were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. The TEAEs were typically mild-to-moderate in severity and either resolved or were resolving. The ENVISION trial demonstrated a similar safety profile to that observed in other studies of UGN‑102. Median follow-up time at 18 months was 18.7 months after the three-month CR.

UroGen completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment for LG-IR-NMIBC ahead of schedule, and the FDA accepted the NDA for UGN-102 with a Prescription Drug User Free Act (PDUFA) goal date of June 13, 2025.

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 recurrent 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 by a trained healthcare professional. UroGen completed the submission of the rolling NDA for UGN-102 in August 2024, ahead of schedule. The FDA accepted the NDA for UGN-102 and assigned a PDUFA goal date of June 13, 2025.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

LG-IR-NMIBC affects around 82,000 people in the U.S. every year and of those, an estimated 59,000 are recurrent. Bladder cancer primarily affects older populations with increased risk of comorbidities, with the median age of diagnosis being 73 years. Guideline recommendations for the management of NMIBC include TURBT as the standard of care. Up to 70 percent of NMIBC patients experience at least one recurrence and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures.

About ENVISION

The Phase 3 ENVISION trial is a single-arm, multinational, multicenter pivotal study evaluating the efficacy and safety of UGN-102 (mitomycin) for intravesical solution as a chemoablative therapy in patients with LG-IR-NMIBC. The Phase 3 ENVISION trial completed target enrollment with 240 patients across 56 sites. Study participants received six once-weekly intravesical instillations of UGN-102. The primary endpoint evaluated the CR rate at the three-month assessment after the first instillation, and the key secondary endpoint evaluated durability over time in patients who achieved a CR at the three-month assessment. Learn more about the Phase 3 ENVISION trial at www.clinicaltrials.gov (NCT05243550).

On April 25, 2025 Bantam Pharmaceutical, a drug discovery and development company targeting selective modulation of mitochondrial dynamics in cancer, reported solid tumor regression data from Bantam’s lead product candidate, BTM-3566 (Press release, Bantam Pharmaceutical, APR 25, 2025, View Source [SID1234652160]). These preclinical data will be shared in a poster presentation during the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held from April 25-30, 2025 at the McCormick Place Convention Center in Chicago, Illinois. The poster highlights evidence of robust anti-tumor activity in a broad range of solid tumor models, as well as introduces FAM210B, a mitochondrial protein, as a potential biomarker for response.

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BTM-3566 is a first-in-class, small molecule cancer therapeutic which targets difficult-to-treat, aggressive tumors by activating OMA1-ATF4 Integrated Stress Response (ISR), a newly described mitochondrial homeostasis pathway. Previously, BTM-3566 was shown to have strong single-agent activity in both cell line and patient-derived xenograft (PDX) models of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL), regardless of cell of origin (COO) or genotype. The new data extend these findings to solid tumors and demonstrate that BTM-3566 has in vitro and in vivo activity across tumor types.

Key findings include:

BTM-3566 exhibits in vitro and in vivo activity in a broad range of solid tumor models
BTM-3566 drives tumor regression in models with low FAM210B RNA expression, supporting the use of FAM210B as a potential biomarker for response
Ectopic expression of FAM210B blocks drug activity in multiple models, suggesting a mechanistic role for the protein in mediating response
BTM-3566 demonstrates additive and synergistic activity in combination with other agents from multiple classes in preclinical models, including BH3 mimetics, supporting future combination strategies
"These findings provide important insight into the unique mechanism of our lead compound and support the potential for future patient selection using FAM210B expression," said Michael Stocum, President & CEO of Bantam Pharmaceutical. "We believe BTM-3566 holds promise not only as a monotherapy but also in combination with numerous approved anti-cancer agents, potentially expanding treatment options for patients with aggressive, hard-to-treat tumors. We intend to further explore these relationships as product development progresses."

Poster Presentation Details

Title: Selective pharmacological activation of the mitochondrial protease OMA1 inhibits tumor growth and induces regression in tumors expressing low levels of FAM210B
Presenter: Matthew Kostura, PhD, Chief Scientific Officer, Bantam Pharmaceutical
Session: Experimental and Molecular Therapeutics
Date/Time: Monday, April 28th at 3 p.m. to 6 p.m. ET
Abstract Number: 3032

The poster presentation will be available under the News & Resources section of the company’s website shortly after the event.

About BTM-3566

BTM-3566 is a novel, orally available small molecule designed to target a wide range of cancers, including both hematologic and solid tumors. Its initial clinical focus is on mature B-cell lymphomas, such as mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL). In preclinical studies, BTM-3566 demonstrated potent anti-cancer activity, driving significant tumor regression – and in many cases, complete tumor elimination – in models resistant to standard treatments, including CAR-T cell therapy. BTM-3566 works by disrupting the mitochondrial function in tumor cells, triggering their natural cell death process (apoptosis). With its unique mechanism of action and strong preclinical data, Bantam also plans to expand clinical development into solid tumors, broadening its potential impact for patients with limited treatment options.

Currently, Bantam is conducting an ongoing Phase 1 clinical trial in both the U.S. and Canada evaluating BTM-3566 in relapsed/refractory mature B-cell lymphomas. For more information about the U.S. trial, visit ClinicalTrials.gov and search NCT06792734.

On April 25, 2025 Incyte (Nasdaq:INCY) reported that the Company will present new early-stage data from its oncology portfolio at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago, IL, from April 25–30 (Press release, Incyte, APR 25, 2025, View Source [SID1234652177]).

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"At AACR (Free AACR Whitepaper) we will be presenting data from early-stage programs across our oncology portfolio, including for patients with myeloproliferative neoplasms, ovarian cancer and other solid tumors," said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. "These data will guide our approach as we advance our pipeline and seek to transform the treatment landscape for patients with cancer and myeloproliferative neoplasms."

Abstracts accepted for presentation at AACR (Free AACR Whitepaper) include:

Mini Symposium

INCB177054

INCB177054: A Novel, Potent, Orally Bioavailable DGKα/ζ Dual Inhibitor Enhances T-Cell Function and Demonstrates Potent Antitumor Activity
(Session Title: Novel Antitumor Agents. April 28, 4:50 p.m. – 5:05 p.m. ET (3:50 p.m. – 4:05 p.m. CT). Abstract #3789.))

Poster Presentations

INCA33890

INCA33890 Increases CD8+ T-Cell Effector Function Compared with pembrolizumab as Assessed by Single-Cell RNA Sequencing in Human PD-1xTGFβR2 Knock-In Mouse Model (Session Title: Immune Fitness and Metabolic Regulation of Cancer Immunity​. April 29, 10:00 a.m. – 1:00 p.m. ET (9:00 a.m. – 12:00 p.m. CT). Abstract #4861.))

INCA33890, a Bispecific Antibody Targeting PD-1 and TGFβR2, Shows Enhanced Immune Responses in Models of Ovarian Cancer
(Session Title: Antibodies 3: Multi-Target Checkpoint Inhibitors and Immune Activators. April 29, 3:00 p.m. – 6:00 p.m. ET (2:00 – 5:00 p.m. CT). Abstract #6074.))

PD-1xTGFβR2 Bispecific Biclonics Antibody INCA33890 Augments Human T-Cell Effector Functions In Vitro and Ex Vivo
(Session Title: Antibodies 3: Multi-Target Checkpoint Inhibitors and Immune Activators​. April 29, 3:00 p.m. – 6:00 p.m. ET (2:00 – 5:00 p.m. CT). Abstract #6071.))

INCB057643

INCB057643, a Bromodomain and Extra-Terminal (BET) Protein Inhibitor, Improved Bone Marrow Function and Shifted Megakaryopoiesis to Erythropoiesis in Patients with Myeloproliferative Neoplasms (MPNs)
(Session Title: Molecular Genetics and Epigenetics of Tumors​. April 30, 10:00 a.m. – 1:00 p.m. ET (9:00 a.m. – 12:00 p.m. CT). Abstract #7188.))

Novel Role of INCB057643, a Bromodomain and Extra-Terminal (BET) Protein Inhibitor, in Myeloid Cell Regulation and Immunosuppressive Tumor Environment Remodeling in Myelofibrosis (MF)
(Session Title: Molecular Genetics and Epigenetics of Tumors​. April 30, 10:00 a.m. – 1:00 p.m. ET (9:00 a.m. – 12:00 p.m. CT). Abstract #7184.))

Association of Cyclin E1 Expression with Genomic Instability in Ovarian Cancer
(Session Title: Origins and Mechanisms of Genomic Instability​. April 28, 3:00 p.m. – 6:00 p.m. ET (2:00 – 5:00 p.m. CT). Abstract #2846.))

On April 25, 2025 Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "the Company") reported the financial results for fiscal year 2024 ending March 31, 2025 (FY2024) (Press release, Astellas, APR 25, 2025, View Source [SID1234653926]).

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