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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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 27, 2025 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the Company anticipates the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) will adopt an opinion on the marketing authorization application (MAA) for nirogacestat, an oral gamma secretase inhibitor, for the treatment of adults with desmoid tumors in the second quarter of 2025 (Press release, SpringWorks Therapeutics, APR 27, 2025, View Source [SID1234652193]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On April 27, 2025 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported new data from the OPTIMA II Phase 2b study of UGN‑102 (mitomycin) for intravesical solution demonstrate clinically meaningful two-year duration of response (24.2 months) by Kaplan-Meier analysis (Press release, UroGen Pharma, APR 27, 2025, View Source [SID1234652196]). UGN-102 is UroGen’s sustained-release formulation of mitomycin being developed for the treatment of recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The median duration of response of two years highlights UGN-102’s durability, even in patients with recurrent disease and multiple prior TURBT procedures," said Neal Shore, MD, Medical Director, Carolina Urologic Research Center, Myrtle Beach, South Carolina. "These long-term data provide encouraging evidence of UGN-102’s sustained impact."

The majority of patients included in OPTIMA II had recurrent disease at baseline (77.8%), with multiple prior transurethral resection of bladder tumor (TURBT) procedures. Among the 41 patients achieving a complete response (CR) at three months, 25 remained in CR at 12 months, and 17 of these patients entered long-term follow-up. The median Kaplan–Meier estimate of duration of response for the 41 patients that achieved CR was 24.2 months (95% CI 9.72, 47.18), with a median follow-up time of 33.6 months (95% CI 10.78, 42.94). Twenty patients (48.8%) experienced recurrence of low-grade disease. One patient progressed to high-grade disease and one patient died due to a cardiac disorder. Five patients remained disease-free at the time of the four-year data analysis.

"As the burden of LG-IR-NMIBC persists, the need for long-lasting treatment options becomes increasingly urgent," said Mark Schoenberg, Chief Medical Officer, UroGen. "The growing body of evidence supporting UGN-102 underscores its potential to address this unmet need. These results emphasize UGN-102’s potential to deliver meaningful and sustained responses, offering hope to patients who have long struggled with recurrence and limited treatment options."

UroGen completed the submission of the UGN-102 rolling new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 in August 2024, ahead of schedule. The FDA accepted the NDA for UGN-102 with a Prescription Drug User Free Act (PDUFA) goal date of June 13, 2025.

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.

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 OPTIMA II

OPTIMA II (OPTimized Instillation of Mitomycin for Bladder Cancer Treatment) was an open-label, single-arm, multi-center Phase 2b clinical trial of investigational drug UGN-102 to evaluate its safety and efficacy in patients with LG-IR-NMIBC.

Learn more about the Phase 2b OPTIMA II trial at www.clinicaltrials.gov (NCT03558503).