On April 27, 2025 ImmVira reported the Phase I clinical results of its oncolytic Herpes Simplex Virus ("oHSV") product MVR-C5252 targeting malignant glioma through poster presentation at American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") annual meeting (Press release, Immvira, APR 27, 2025, View Source [SID1234652208]).

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According to industry data, malignant glioma, a highly aggressive and recurrent brain cancer, has a five-year survival rate of less than 5%. Developed on ImmVira’s proprietary OVPENS platform, MVR-C5252 is specifically engineered with designed attenuation to achieve on-target malignant gliocyte killing and armed with PD-1 antibody and IL-12, for the synergistic anti-tumor effects of "oncolysis + immune activation". This innovative product has obtained Investigational New Drug approval in both the U.S. and China, as well as Orphan Drug Designation from the FDA.

The Phase I trial, for which the clinical study results were released, was conducted in collaboration with Duke University, a renowned institution with expertise in oncolytic virotherapy, immunotherapy, and CNS treatments. Unlike the commonly used Ommaya reservoir, MVR-C5252 is delivered intracranially via convection-enhanced delivery ("CED"). This approach can provide slow and sustained positive pressure to the target brain area via an implanted catheter to ensure even drug distribution, enabling multiple dosing while bypassing the blood-brain barrier. To date, five patients with recurrent high-grade glioma have received MVR-C5252 treatments.

In Stage 1A of the study, three patients received 5×10⁶ PFU and completed the dose-limiting toxicity ("DLT") period. Serial cytokine analysis of cerebrospinal fluid ("CSF") showed dynamic immune responses and intended biologic activity, with measurable changes in cytokine concentrations post-infusion. In addition, no serious adverse events ("SAEs"), DLTs, or Grade 3–5 adverse events ("AEs") occurred. The only reported Grade 1–2 AEs included fatigue, flu-like symptoms, and cognitive disturbance, indicating a favorable safety profile of MVR-C5252 delivered via CED.

Dr. Grace Guoying Zhou, ImmVira’s Chairwoman and CEO, said, "We are committed to developing advanced therapies featuring novel modalities using oHSV and engineered exosomes, to address complex and challenging diseases. After years of parallel development and in-depth explorations in both the U.S. and China, we have strategically focused on malignant glioma for the development of MVR-C5252, leveraging HSV-1’s unique biological and translational medical characteristics and in line with highly unmet medical needs and substantial market potential. Our collaboration with Duke University, a global leader in glioma research and treatment, will accelerate clinical development of this innovative therapy, delivering a new solution for this type of severe life-threatening diseases."

On April 27, 2025 Nona Biosciences, a global biotechnology company providing integrated solutions from "Idea to IND" (I to ITM), reported that its partner, Pfizer, has presented preclinical data on PF-08052666 (HBM9033; SGN-MesoC2), a first-in-class topoisomerase 1 inhibitor (TOP1i)-based antibody-drug conjugate (ADC) targeting mesothelin (MSLN), at the AACR (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Nona Biosciences, APR 27, 2025, View Source [SID1234652190]). This ADC was originally developed using Nona Biosciences’ proprietary Harbour Mice and integrated ADC platforms. Pfizer acquired its global clinical development and commercialization rights on December 14, 2023.

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Poster Presentation at AACR (Free AACR Whitepaper) Annual Meeting 2025

Title: PF-08052666 (HBM9033), a first-in-class topoisomerase 1 inhibitor-based ADC targeting MSLN, demonstrates potent antitumor activity in preclinical models of ovarian, lung, and colorectal cancers

Abstract Number: 324

Poster Board Number: 16

Session Title: Antireceptors and Other Biological Therapeutic Agents

Session Date: April 27, 2025

PF-08052666 was designed to address the limitations of earlier anti-MSLN ADCs through a novel antibody, differentiated linker-payload, and a higher drug-to-antibody ratio (DAR). It consists of a human IgG1 monoclonal antibody conjugated to a potent camptothecin-based TOP1i payload with a protease-cleavable linker, achieving an average DAR of 8.

Key Preclinical Findings Presented at AACR (Free AACR Whitepaper) Annual Meeting 2025

In vitro, PF-08052666 demonstrated direct cytotoxicity through delivery of payload to MSLN-positive cells, bystander killing activity on co-cultured MSLN-negative cells, and maintained cytotoxicity even in the presence of physiologically relevant concentrations of soluble MSLN.
In vivo, PF-08052666 outperformed a DM4-based anti-MSLN benchmark ADC in both cell-line and patient-derived xenograft models across multiple tumor types, including ovarian, lung, and colorectal cancers.
PF-08052666 also outperformed the DM4-based anti-MSLN benchmark ADC in heterogeneous xenograft models consisting of ad-mixed MSLN-positive and MSLN-negative cells, demonstrating the increased bystander activity of the novel linker-payload of MesoC2.
These promising preclinical results support the ongoing first-in-human phase 1 clinical trial of PF-08052666 in patients with advanced solid tumors (NCT06466187), which is currently enrolling participants.

"The preclinical data on PF-08052666 presented by Pfizer at AACR (Free AACR Whitepaper) 2025 reflects the strength of our technology platforms and our dedication to advancing transformative therapies," said Jingsong Wang, MD, PhD, Chairman of Nona Biosciences. "By leveraging our industry-leading technology platforms, we continue to drive innovation that enables the development of next-generation biotherapeutics. We look forward to further collaboration with Pfizer to accelerate breakthroughs that address critical medical needs."

About PF-08052666 (HBM9033)

PF-08052666 is an ADC drug that targets human MSLN, a tumor-associated antigen (TAA) upregulated in various solid tumors. The fully human monoclonal antibody (mAb) in PF-08052666 is derived from the Harbour Mice platform and possesses well-tuned properties, exhibiting reduced binding to soluble MSLN while maintaining strong binding and internalization to membrane-bound MSLN. The unique design of the mAb was created to enhance potency in various preclinical tumor models with differing MSLN expression levels, positioning PF-08052666 as a potential globally best-in-class therapeutic option.

On April 27, 2025 Zoldonrasib, a RAS(ON) G12D-selective inhibitor, demonstrated acceptable tolerability and encouraging initial antitumor activity in patients with previously treated KRAS G12D mutant non-small cell lung cancer
REDWOOD CITY, Calif., April 27, 2025 (GLOBE NEWSWIRE) — Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported new clinical data for zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, as monotherapy in patients with KRAS G12D mutant non-small cell lung cancer (NSCLC) (Press release, Revolution Medicines, APR 27, 2025, View Source [SID1234652192]). Results were highlighted in the official press program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois, and will be featured in a late-breaking oral presentation on April 27, 2025, at 5:00 p.m. Central Time.

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"We are pleased to share new clinical data for zoldonrasib, our innovative, oral RAS(ON) G12D-selective inhibitor, which demonstrates acceptable safety and tolerability and encouraging initial antitumor activity in patients with non-small cell lung cancer. These data reinforce the clinical potential of zoldonrasib following the initial tolerability and antitumor activity reported late last year in patients with pancreatic ductal adenocarcinoma," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "Together these results support further evaluation of zoldonrasib as monotherapy and in combination as we continue efforts to advance innovative targeted medicines for patients living with these hard-to-treat cancers."

RMC-9805-001 is a multicenter, open-label, dose escalation and dose-expansion Phase 1 study designed to evaluate zoldonrasib in patients with advanced solid tumors harboring a KRAS G12D mutation.

As of a December 2, 2024 data cutoff date, 90 solid tumor patients were treated with 1200 mg once daily (QD), the candidate recommended Phase 2 dose. In these patients, zoldonrasib demonstrated an acceptable safety profile, that was generally consistent with previously reported data for this compound in pancreatic cancer, and was generally well tolerated. The most common treatment-related adverse events (TRAEs) occurring in at least 10% of patients were nausea (39%), diarrhea (24%), vomiting (18%), and rash (12%). TRAEs were primarily Grade 1 or 2 in severity, with two patients (2%) experiencing Grade 3 events that resolved following dose interruption. Zoldonrasib had a favorable mean dose intensity of 98% and no dose limiting toxicities were observed.

Preliminary antitumor activity was assessed in 18 efficacy-evaluable patients with NSCLC at the 1200 mg QD dose. The objective response rate (confirmed or pending confirmation) was 61% (n=11) and the disease control rate was 89% (n=16).

"There is a high unmet need for new treatments within this patient population as there are currently no targeted therapies approved for any RAS G12D mutant cancer," said Kathryn Arbour, M.D., thoracic medical oncologist at Memorial Sloan Kettering Cancer Center and principal investigator and lead author for the RMC-9805-001 presentation. "While the data are from an early, small subset of patients, it is encouraging to see this level of tolerability and antitumor activity in patients with NSCLC carrying this RAS mutation."

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).