On April 26, 2025 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported updated results from its ongoing Phase 2 open-label ADVANCED-2 trial assessing intravesical TARA-002, the Company’s investigational cell-based therapy, in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) patients with carcinoma in situ, or CIS (± Ta/T1), who are Bacillus Calmette-Guérin (BCG)-Unresponsive or BCG-Naïve (Press release, Protara Therapeutics, APR 26, 2025, View Source [SID1234652191]). The results will be featured today during an interactive poster session at the American Urological Association 2025 Annual Meeting in Las Vegas.

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"For patients with high-risk NMIBC, there are few effective and durable therapies available other than radical cystectomy, which we know is quite difficult for patients to tolerate," said Tom Jayram, M.D., Director of the Advanced Therapeutics Center at Urology Associates, and ADVANCED-2 study investigator. "TARA-002 has shown impressive efficacy, safety profile, and 12-month durability in its Phase 2 trial. In the clinic, we have seen TARA-002 become easily integrated into workflow without major hurdles for the patients or staff. This combination of clinical activity and ease of use makes me optimistic about TARA-002 having a meaningful impact in clinical practice."

Interim Results

BCG-Unresponsive Cohort

The BCG-Unresponsive dataset includes a total of five patients, all of whom were six- and nine-month evaluable, and three of whom were evaluable at 12 months as of an April 16, 2025 data cutoff.

The complete response (CR) rate at any time in BCG-Unresponsive patients was 100% (5/5).
The CR rate in BCG-Unresponsive patients was 100% (5/5) at six months, 80% (4/5) at nine months, and 67% (2/3) at 12 months.
BCG-Naïve Cohort

The BCG-Naïve dataset includes a total of 21 patients, including 16 evaluable at six months, eight at nine months, and seven at 12 months as of an April 16, 2025 data cutoff.

The CR rate at any time in BCG-Naïve patients was 76% (16/21).
The CR rate in BCG-Naïve patients was 63% (10/16) at six months, 63% (5/8) at nine months, and 43% (3/7) at 12 months.
Safety

The majority of adverse events were Grade 1 and transient with no Grade 3 or greater treatment-related adverse events (TRAEs) as assessed by study investigators. No patients discontinued treatment due to TRAEs. The most common adverse events were in line with typical responses to bacterial immunopotentiation, such as flu-like symptoms. The most common urinary symptoms reflect urinary tract instrumentation effects, such as bladder spasm, burning sensation, and urinary tract infection. Most bladder irritations resolved shortly after administration or within a few hours to a few days.

"The durable results shared today continue to support our conviction that TARA-002 has the potential to make a meaningful difference in the lives of patients with NMIBC," said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. "Notably, we are particularly pleased with the competitive 12-month CR rates observed in the registrational BCG-Unresponsive cohort as well as the BCG-Naïve cohort. We look forward to continuing to advance this important trial as we work toward our mission of bringing transformative therapies to patients."

The Company continues to expect to present an interim update with results from approximately 25 six-month evaluable BCG-Unresponsive patients by the end of 2025.

Conference Call and Webcast

Protara will host a conference call and webcast to discuss the data on Monday, April 28, 2025, at 8:30 am ET. The live call can be accessed by registering as a participant here. Upon registration, participants will receive conference call dial-in information. A live webcast of the event can be accessed by visiting the Events and Presentations section of the Company’s website: View Source The webcast will be archived for a limited time following the presentation.

About ADVANCED-2

ADVANCED-2 (NCT05951179) is a Phase 2 open-label trial assessing intravesical TARA-002 in NMIBC patients with carcinoma in situ or CIS (± Ta/T1) who are Bacillus Calmette-Guérin (BCG)-Unresponsive (n≈100) and BCG-Naïve (n=31). The BCG-Unresponsive cohort has been designed to be registrational in alignment with the U.S. Food and Drug Administration’s 2024 BCG-Unresponsive Non-muscle Invasive Bladder Cancer: Developing Drugs and Biological Products for Treatment, Draft Guidance for Industry.

About TARA-002

TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs, for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil in Japan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432.

When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a pro-inflammatory response with release of cytokines such as tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma IL-6, IL-10, IL-12. TARA-002 also directly kills tumor cells and triggers a host immune response by inducing immunogenic cell death, which further enhances the antitumor immune response.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle.

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 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported preclinical data demonstrating the anti-tumor activity of OP-3136, a novel small molecule that potently and selectively inhibits lysine acetyltransferase 6 (KAT6), in prostate, ovarian, and non-small cell lung cancer (NSCLC) models (Press release, Olema Oncology, APR 25, 2025, View Source [SID1234652148]). These findings are being presented in a late-breaking poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 25-30 in Chicago, Illinois.

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"These data showcase the potential of OP-3136 for the treatment of challenging cancers beyond breast cancer," said David C. Myles, Ph.D., Chief Discovery and Non-Clinical Development Officer of Olema Oncology. "OP-3136 has shown inhibition across all models explored, and we were excited to observe potent tumor growth inhibition and sustained tumor regression with OP-3136 as a monotherapy in ovarian cancer models. We are actively recruiting the Phase 1 trial of OP-3136 in multiple solid tumor types and will continue to explore its potential in other indications of high unmet need."

Poster Presentation Details
Title: OP-3136, a selective KAT6 inhibitor, demonstrates anti-tumor activity in prostate, ovarian, and non-small cell lung cancer preclinical models
Poster/Abstract: LB166
Session: Late-Breaking Research: Tumor Biology 2
Date/Time: April 28, 2025, from 9:00am-12:00pm CT / 10:00am-1:00pm ET
Presenter: Dr. Gopinath S. Palanisamy, DVM, Ph.D.

Key findings include:

OP-3136 showed potent anti-proliferative activity in multiple ovarian, NSCLC, and prostate cell lines in vitro.
OP-3136 showed activity that was independent of KAT6 amplification or over expression.
OP-3136 monotherapy demonstrated anti-tumor activity in in vivo xenograft models of ovarian (OVCAR3), NSCLC (LCLC-97TM1), and prostate (22Rv1) cancers.
In the OVCAR3 model, OP-3136 monotherapy demonstrated sustained tumor regression across the 28-day study period and robust tumor growth inhibition.
In the LCLC-97TM1 model, OP-3136 monotherapy demonstrated tumor growth inhibition comparable to ribociclib and, when combined with ribociclib, demonstrated synergy and enhanced anti-tumor activity.
In the 22Rv1 model, OP-3136 inhibited tumor growth in a dose-dependent manner and, when combined with docetaxel, resulted in enhanced anti-tumor activity.
These data indicate OP-3136 may be effective in treating ovarian, lung, and prostate cancer indications in addition to breast cancer.
A copy of this poster is available on the Publications page of Olema’s website. Additional information can be found on the AACR (Free AACR Whitepaper) Annual Meeting website, including abstracts.

About OP-3136
OP-3136 is a novel, orally available small molecule that potently and selectively inhibits lysine acetyltransferase 6 (KAT6), an epigenetic target that is dysregulated in breast and other cancers. In preclinical studies, OP-3136 has demonstrated significant anti-proliferative activity in ER+ breast cancer models and is combinable and synergistic with endocrine therapies, including palazestrant and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. The Investigational New Drug (IND) application for OP-3136 was cleared by the U.S. Food and Drug Administration (FDA) in December 2024 and patients are currently enrolling in the Phase 1 clinical trial.

On April 25, 2025 Precision Biologics, Inc. reported preclinical development and characterization of a novel ADC using its anti-core 2 O-glycans anti-human carcinoma mAb PB-223 will be presented in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025, on April 29th, 2025, McCormick Place Convention Center, Chicago, IL, USA (Press release, Precision Biologics, APR 25, 2025, View Source [SID1234652165]).

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Poster title: Development and characterization of an antibody-drug conjugate (ADC) utilizing PB-223, a novel monoclonal antibody (mAb) specifically targeting core 2 O-glycans on human carcinomas

The presentation of the poster will be made in person on the following date and location:

April 29th, 2025, 9am-12pm

McCormick Place Convention Center, Chicago, IL, USA

Session Title: Antibodies and Antibody-Drug Conjugates

Poster Section 36

Abstract Control Number 2878

BACKGROUND:

Antibody-drug conjugates (ADCs) represent a cutting-edge approach in cancer therapy. The three essential components of an ADC include: the mAb, the linker, and the cytotoxic payload. The mAb in current ADCs is usually designated to target specific tumor-associated antigens that are overexpressed on the surface of cancer cells.

Our ADC contains the following components:

The mAb: We used PB-223, an innovative mAb developed through affinity maturation of mAb NEO-102 (Ensituximab), a chimeric human IgG1 mAb that targets truncated core 2 O-glycans, specifically expressed by cancer cells and not by healthy tissues. The binding affinity of PB-223 for its target was improved, compared to NEO-102, by optimizing its VH and VL sequences through Fast Screening for Expression Biophysical Properties and Affinity. PB-223 demonstrated a binding affinity (KD) at least 4-fold lower than NEO-102, indicating stronger tumor binding. An immunohistochemistry analysis also revealed that PB-223 binds to a wider spectrum of tumor tissues compared to NEO-102, including not only colorectal, and pancreatic cancer, but also triple negative breast, prostate, kidney, head and neck, liver, and bladder cancer. Further experiments show PB-223 does not bind to normal tissues and that it can be internalized into human cancer cell lines expressing its target.
The payload: Monomethyl auristatin E (MMAE) was used as payload. MMAE is a potent antimitotic agent that inhibits cell division by blocking the polymerization of tubulin and is the most common ADC payload used to be linked to antibodies in clinical development for oncologic applications.
The linker: mc-vc-PABc was used as linker. PB-223 was conjugated to the linker-payload through a cysteine-based conjugation method.
STUDY PRESENTED AT AACR (Free AACR Whitepaper) 2025:

After development of the ADC we proceeded with its characterization, evaluating the following features:

DAR: The drug-to-antibody ratio (DAR) is crucial to predict the efficacy and safety of ADCs. It is generally believed that a DAR between 2 and 4 is the best choice for ADC drugs. Higher DAR may disrupt the pharmacokinetic properties of ADCs, while lower DAR significantly negatively affects the potency of ADCs. We developed three ADCs: PB-MMAE-2, PB-MMAE-5 and PB-MMAE-6. The DAR for these ADCs was 3.72, 3.92 and 4.15, respectively.
Binding of ADCs to cancer cells expressing core 2 O-glycans: flow cytometry was used for binding assessment of three ADC clones using the human ovarian cancer cell line OV-90 as the target. All three ADCs exhibit similar binding affinity to OV-90 compared to PB-223.
Killing of cancer cells: We evaluated the ability of all three ADC clones to kill OV-90 cells. All three ADCs effectively killed OV-90 cells (80% of cells were dead 5 days after treatment). We then chose one ADC clone, PB-MMAE-5, to test its ability to kill additional human cancer cell lines. Preliminary results show that PB-MMAE-5 can kill human prostate, triple positive and triple negative breast, lung, colon, pancreatic cancer cell lines.
Safety in vivo: We chose the ADC clone PB-MMAE-5 to test its toxicity in rats. The ADC PB-vcMMAE-5 in rats was administered intravenously at a concentration of 2.3 mg/kg as single dose. Animal body weight was measured at different time points until 14 days after ADC administration. The ADC PB-vcMMAE-5 was well tolerated in rats. No sign of distress nor loss of body weight were observed after administration.
Stability in human plasma: Stability of the ADC PB-vcMMAE-5 was evaluated in human plasma. PB-vcMMAE-5 ADC was incubated with male and female human plasma at concentration of 50 µg/mL and 100 µg/mL. Concentration in human plasma was detected by ELISA at 0h, 24h (1 day), 48h (2 days), 96h (4 days), 168h (7 days), 240h (10 days), 336h (14 days). The ADC was stable in human plasma (after 14 days, mean residual rate of PB-vcMMAE-5 ADC in human plasma was 23% for ADC at 100 µg/mL and 22% for ADC at 50 µg/mL).
Efficacy in vivo: The efficacy of the ADC PB-vcMMAE-5 was assessed in OV-90 subcutaneous xenograft model established in NOD-SCID mice. The ADC PB-vcMMAE-5 was administered intravenously at doses 1 mg/kg and 3 mg/kg, once per week for three weeks. Preliminary data suggest that PB-vcMMAE-5 exhibits anti-tumor activity in the NOD-SCID mice tumor model. Two days after the second dose of PB-vcMMAE-5 at 3mg/kg, treated mice showed a significant reduction in tumor volume compared to mice treated with an 1mg/kg dose of PB-vcMMAE-5, PBS or payload alone.
Findings from this study showed that PB-vcMMAE-5 can kill cancer cells expressing PB-223’s target, is not toxic, is effective in vivo, and is stable in human plasma, suggesting that PB-vcMMAE-5 has promising potential as a therapeutic option for a range of human malignancies expressing core 2 O-glycans.