On April 27, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported that preclinical data on multiple novel bispecific antibodies, tri-specific antibodies as well as bispecific antibody-drug-conjugates (ADCs) from its oncology pipeline will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Innovent Biologics, APR 27, 2025, View Source;innovent-presents-preclinical-data-of-multiple-novel-molecules-including-bispecific-and-tri-specific-antibodies-and-bispecific-adcs-302439078.html [SID1234652205]). The AACR (Free AACR Whitepaper) meeting will take place April 25-30, 2025, in Chicago, Illinois.

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Dr. Kaijie He, Cancer Biology and ADC Vice President of Innovent, stated: "With continuous advancement of Innovent Academy’s integrated technology platforms, our global R&D capabilities have reached new heights, further strengthening our competitive position in the international biopharmaceutical landscape. This progress has accelerated our ability to design and develop innovative therapeutic candidates with significant global impact. We are proud to showcase a batch of preclinical research findings at this year’s AACR (Free AACR Whitepaper) Annual Meeting, including multiple globally first-in-class bispecific antibodies, multi-specific antibodies, and antibody-drug conjugates (ADCs). These scientific advancements highlight our expanding research expertise and underscore our unwavering dedication to creating life-changing treatments for patients across the globe. Moving forward, we remain deeply committed to scientific innovation—advancing target selection precision and pioneering unexplored biological mechanisms—to deliver breakthrough solutions for difficult-to-treat diseases and ensure more patients worldwide can access the benefits of cutting-edge therapeutic technologies. "

Research highlights as below:

Late-Breaking Research: Immunology 2
Topic: Preclinical data of IAR037, a novel CD40/PD-L1 bispecific antibody for the treatment of advanced solid tumors resistant to immune checkpoint inhibitors
Abstract Number: LB139
Presentation Form: Poster
Presentation Time: Monday April 28, 2025, 9:00 AM – 12:00 PM
Location: Poster Section 52

IAR037 is a novel CD40/PD-L1 bispecific antibody, which simultaneously activates CD40 and blocks PD-1/L1, demonstrating potent anti-tumor efficacy in PD-1-resistant syngeneic mouse models and synergy with PD-1/IL-2α-bias fusion protein IBI363. Preclinical studies show tumor-specific immune activation with minimal systemic effects and a favorable safety profile in cynomolgus monkeys.

IAR037 presents a novel therapeutic approach for ICI-resistant advanced solid tumors and the IND-enabling study of IAR037 is ongoing.

Late-Breaking Research: Clinical Research 1
Topic: Preclinical characterization of IBI3010, a FRα targeting biparatopic antibody-drug conjugate (ADC), for the treatment of FRα expressing tumors
Abstract Number: LB222
Presentation Form: Poster
Presentation Time: Monday April 28, 2025, 2:00 PM – 5:00 PM
Location: Poster Section 53

IBI3010 is a FRα targeting biparatopic ADC with novel topoisomerase I inhibitor NT1 (DAR8). The biparatopic design enhances tumor binding/internalization.

IBI3010 shows superior cytotoxicity and bystander effect versus mirvetuximab soravtansine (IMGN853) in vitro. IBI3010 demonstrated superior antitumor activity to IMGN853 in FRα-expressing CDX models, particularly in low-FRα expression models. GLP tox studies in cynomolgus monkeys established 60 mg/kg as HNSTD with full tolerability.

These data support the clinical development of IBI3010 to evaluate its potential as an ADC therapeutic for FRα-expressing solid tumors.

Poster Session: Experimental and Molecular Therapeutics – Biochemical Modulators of Cancer / Differentiation Therapeutic Strategies
Topic: IBI3014, a TROP2xPD-L1 bi-specific ADC integrating ADC killing with checkpoint blockade within one molecule, exhibits promising efficacy and safety in preclinical models
Abstract Number: 344
Presentation Form: Poster
Presentation Time: Sunday April 27, 2025, 2:00 PM – 5:00 PM
Location: Poster Section 16
Poster Board Number: 11

IBI3014 is a bispecific ADC targeting TROP2 and PD-L1. Its dual mechanism integrates TROP2-directed tumor killing with PD-L1 immune checkpoint blockade, enhancing immunogenic cell death and T cell infiltration.

In CDX models with varying TROP2/PD-L1 expression, IBI3014 demonstrated superior cytotoxicity compared to benchmark ADCs, covering broader tumor types. It maintained stability in mice and monkeys, with a well-tolerated HNSTD of 50 mg/kg in monkeys.

IBI3014’s dual mechanism of action not only enhances therapeutic efficacy but also maintains a favorable safety profile, which provides a promising approach for cancer therapy.

Poster Session: Experimental and Molecular Therapeutics – Biochemical Modulators of Cancer / Differentiation Therapeutic Strategies
Topic: Trop2 and B7H4 bi-specific ADC with improved efficacy and safety for gynecologic cancers
Abstract Number: 345
Presentation Form: Poster
Presentation Time: Sunday April 27, 2025, 2:00 PM – 5:00 PM
Location: Poster Section 16
Poster Board Number: 12

IBI3022, a bi-specific ADC targeting Trop2 and B7H4, aims to enhance tumor antigen expression and reduce off-tumor toxicity associated with Trop2 by incorporating a single-arm Trop2 antibody and a less toxic Topoi NT3 linker payload.

In vitro studies demonstrate that IBI3022 exhibits superior cytotoxicity in HT29 cells overexpressing Trop2 and B7H4 compared to mono-specific ADC benchmarks targeting Trop2 or B7H4. In vivo, IBI3022 demonstrates enhanced tumor suppression compared to mono-specific ADC benchmarks in various tumor models with differing levels of Trop2 and B7H4 expression.

IBI3022 represents a promising bi-specific ADC for the treatment of gynecologic cancers, offering improved efficacy and safety profiles.

Poster Session: Experimental and Molecular Therapeutics – Therapeutic Approaches to Attack the Tumor Microenvironment
Topic: IBI3026, a first-in-class anti-PD-1/IL-12 fusion protein, demonstrates the potential to be a new immuno-oncology therapy by releasing the breaks in immune response and strongly activating T and NK cells in the tumor microenvironment
Abstract Number: 3118
Presentation Form: Poster
Presentation Time: Monday April 28, 2025, 2:00 PM – 5:00 PM
Location: Poster Section 24
Poster Board Number: 2

IBI3026 is a bispecific immune agonist targeting PD-1 and IL-12 receptor, designed to improve safety profile by reducing IL-12 activity while enabling tumor-targeted activation through PD-1+ T cell enrichment.

IBI3026 demonstrated potent immune activation (STAT4/IFN-γ signaling) in pre-treated human PBMCs and achieved complete tumor suppression in multiple models (EMT6, CT26, A375, BxPC-3). In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) of IBI3026 is 150 mg/kg and the calculated therapeutic index is 63.

As a first-in-class candidate, IBI3026 combines PD-1 blockade with localized IL-12 activation, offering a promising strategy for tumors resistant to current immunotherapies.

Poster Session: Immunology – T Cell Engagers
Topic: A 2+1 format MUC16 targeting T cell engager induces MUC16-dependent T cell activity and superior anti-tumor efficacy
Abstract Number: 3510
Presentation Form: Poster
Presentation Time: Monday April 28, 2025, 2:00 PM – 5:00 PM
Location: Poster Section 38
Poster Board Number: 18

We developed a 2+1 format MUC16 TCE, with improved tumor cell binding affinity, enhanced tumor cell killing potency, and MUC16-dependent T cell binding and activation.

Compared to the benchmark molecule, this MUC16 TCE showed limited T cell binding and activation without MUC16, minimizing off-target activity. This 2+1 format MUC16 TCE also showed a favorable pharmacokinetics profile in mice. Functionally, systemic administration of this MUC16 TCE showed superior anti-tumor efficacy, with undetectable toxicity, in xenograft models.

This innovative TCE shows significant potential for treating MUC16-positive cancers, particularly chemotherapy-resistant ovarian cancer.

Poster Session: Experimental and Molecular Therapeutics – New and Emerging Cancer Drug Targets
Topic: IBI3019, a first-in-class EGFR/CDH17/CD16A tri-specific antibody, demonstrated potent efficacy against CRC and an excellent safety profile in preclinical studies
Abstract Number: 4249
Presentation Form: Poster
Presentation Time: Tuesday April 29, 2025, 9:00 AM – 12:00 PM
Location: Poster Section 17
Poster Board Number: 6

IBI3019 is a novel tri-specific antibody targeting EGFR, CDH17, and CD16A for colorectal cancer treatment. It demonstrated strong tumor-specific EGFR inhibition by targeting the overexpressed CDH17 on tumors, while significantly reducing skin toxicities commonly associated with EGFR therapies.

Additionally, IBI3019 incorporates a high-affinity CD16A nanobody that showed better antibody-dependent cell cytotoxicity than those mediated by low-fucose Fc. Importantly, IBI3019 not only demonstrated superior in vitro and in vivo anti-tumor efficacy to Cetuximab and Amivantamab but was also highly tolerable in cynomolgus monkeys with HNSTD at 150 mg/kg in a pilot tox study. These promising preclinical findings warrant further clinical exploration.

Poster Session: Immunology – Modulation of Tumor Microenvironment: Modulation of Lymphocyte Influx
Topic: A PD1-IFNα fusion protein, with an attenuated IFNα fused to a clinically validated PD1 mAb, elicited PD1-dependent IFNα signaling and superior anti-tumor efficacy
Abstract Number: 4881
Presentation Form: Poster
Presentation Time: Tuesday April 29, 2025, 9:00 AM – 12:00 PM
Location: Poster Section 40
Poster Board Number: 9

We engineered a novel PD1-IFNα fusion protein that combines attenuated IFNα with Sintilimab, inducing potent PD1/PDL1 blockade while eliciting highly PD1-dependent IFNα signaling, selectively activating in PD1-high cells.

Preclinical studies demonstrate superior anti-tumor efficacy compared to PD1 mAb alone in multiple mouse syngeneic tumor models, with undetectable toxicity and a favorable pharmacokinetics profile.

This bi-functional molecule potentially benefits patients with ICB-refractory cancers including pancreatic, ovarian, and MSS colorectal cancers.

On April 27, 2025 Johnson & Johnson (NYSE: JNJ) reported new data from Cohort 2 of the pivotal Phase 2b SunRISe-1 study evaluating TAR-200—an intravesical gemcitabine releasing system—for patients with certain types of bladder cancer (Press release, Johnson & Johnson, APR 27, 2025, View Source;johnsons-tar-200-monotherapy-demonstrates-highest-complete-response-rate-with-sustained-clinical-benefits-in-patients-with-certain-types-of-bladder-cancer-302438939.html [SID1234652207]). The findings demonstrate the highest complete response rate without reinduction with more than half of responders remaining cancer-free for at least 12 months. These results highlight the potential of TAR-200 as a breakthrough for people with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC) with carcinoma in situ (CIS), with or without papillary tumors who are ineligible or refuse radical cystectomy (RC). These results were featured in the Paradigm-Shifting, Practice-Changing Clinical Trials in Urology plenary session at the 2025 American Urological Association (AUA) Annual Meeting.1

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"Treatment with TAR-200 has long-lasting effectiveness. More than 82 percent of patients achieved a complete response, and of those that initially responded to treatment, more than half showed no signs of cancer at one year," said Joseph Jacob*, M.D., MCR, Associate Professor of Urology at Upstate Medical University and presenting author. "These findings represent the highest complete response rate observed for patients with HR-NMIBC and underscore the potential of TAR-200 to provide long-lasting cancer control for patients."

"Bladder cancer is one of the ten most common cancers worldwide, yet treatment options have remained largely unchanged for over 40 years, leaving patients with few choices if initial BCG therapy does not work," said Christopher Cutie, M.D., Vice President, Disease Area Leader, Bladder Cancer, Johnson & Johnson Innovative Medicine. "TAR-200 is designed to allow for sustained delivery of medication directly into the bladder through a brief and routine procedure, which benefits patients. These data now show patients can remain cancer-free for a meaningful period of time, marking a significant step forward for those facing this challenging disease."

As of March 2025, 82.4 percent of the 85 enrolled patients in the study achieved a complete response (CR) (95 percent confidence interval [CI], 72.6-89.8), meaning their cancer was undetectable following treatment. This high response rate translated into sustained disease control, with 52.9 percent of responders maintaining complete response at one year. The median duration of response (DOR) was 25.8 months (95 percent CI, 8.3-not estimable), indicating that many patients remained cancer-free for over two years without the need for reinduction therapy. At 12 months, 86.6 percent (95 percent CI, 76.6-92.6) of responders remained cystectomy-free. Importantly, the treatment was well-tolerated, with most adverse events being mild urinary symptoms. These findings show that TAR-200 offers a highly effective and durable treatment option for patients with certain types of BCG-unresponsive HR-NMIBC.

Most treatment-related adverse events (TRAEs) were mild and manageable. Overall, 71 patients (83.5 percent) experienced TRAEs, the majority of which were low-grade urinary symptoms, such as bladder irritation or discomfort. Eleven patients (12.9 percent) experienced Grade 3 or higher TRAEs, and five patients (5.9 percent) reported serious TRAEs. Only three patients (3.5 percent) discontinued treatment due to TRAEs, and there were no treatment-related deaths.

TAR-200 is inserted directly into the bladder by a healthcare professional in a brief outpatient procedure, without the need for anesthesia. Designed to remain in the bladder, it does not interfere with daily activities and provides sustained release of treatment throughout the day. To date, TAR-200 has been placed more than 10,000 times as part of the SunRISe clinical program.

Earlier results from Cohort 2 were previously presented at the 2024 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and at the 2024 American Urological Association (AUA) Annual Meeting. In January 2025, Johnson & Johnson announced the initiation of a new drug application with the FDA for TAR-200 under the Real-Time Oncology Review (RTOR) program.

About TAR-200
TAR-200 is an investigational intravesical gemcitabine releasing system. In January 2025, Johnson & Johnson announced the initiation of a new drug application with the FDA for TAR-200 under the real-time oncology review (RTOR) program. In December 2023, the FDA granted Breakthrough Therapy Designation (BTD) to TAR-200 for the treatment of adult patients with BCG-unresponsive HR-NMIBC with CIS who are ineligible for or have elected not to undergo radical cystectomy. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with MIBC in SunRISe-4, and NMIBC in SunRISe-1, SunRISe-3 and SunRISe-5.

About SunRISe-1, Cohort 2
SunRISe-1 (NCT04640623) is an ongoing Phase 2b, randomized, open-label, multicenter study evaluating the efficacy and safety of TAR-200, an intravesical gemcitabine releasing system, in patients with BCG-unresponsive HR-NMIBC who are ineligible for, or elected not to undergo, radical cystectomy. Cohort 2 specifically enrolls patients with carcinoma in situ, with or without papillary disease, treating them with TAR-200 monotherapy. The primary endpoint for Cohort 2 is CR rate at any time point. Secondary endpoints include duration of response (DOR), overall survival (OS), pharmacokinetics, quality of life, safety and tolerability.

About High-Risk Non-Muscle-Invasive Bladder Cancer
High-risk non-muscle-invasive bladder cancer is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to muscle invasive bladder cancer compared to low-risk NMIBC.2,3 HR-NMIBC makes up 15-44 percent of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors, and CIS.4 Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.5,6 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.

On April 27, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported results from the Phase 3 KEYNOTE-689 trial evaluating KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, as a perioperative treatment regimen for patients with stage III or IVA, resected, locally advanced head and neck squamous cell carcinoma (LA-HNSCC) (Press release, Merck & Co, APR 27, 2025, View Source [SID1234652189]). Results at the first interim analysis of the trial showed KEYTRUDA significantly improved event-free survival (EFS) as part of a perioperative treatment regimen with adjuvant standard of care (SOC) radiotherapy with or without cisplatin compared to adjuvant standard of care (SOC) radiotherapy with or without cisplatin alone in patients with resectable LA-HNSCC. These data are being presented for the first time today during a Plenary Session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Abstract #CT001) and were selected for the AACR (Free AACR Whitepaper) press program.

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After a median follow-up of 38.3 months (range, 9.0-66.5), treatment with KEYTRUDA before surgery (neoadjuvant), then continued in combination with standard of care radiotherapy (with or without cisplatin) after surgery followed by KEYTRUDA alone (adjuvant), reduced the risk of EFS events by 34% (HR=0.66 [95% CI, 0.49-0.88]; p=.0022) in the combined positive score (CPS) ≥10 population, by 30% (HR=0.70 [95% CI, 0.55-0.89; p=.0014) in the CPS ≥1 population and by 27% (HR=0.73 [95% CI 0.58-0.92]; p=.0041) in the intent-to-treat (ITT) population, compared to adjuvant radiotherapy (with or without cisplatin) alone in the ITT population. Among the CPS ≥10 population, median EFS was 59.7 months in the KEYTRUDA plus SOC group (95% CI, 41.1-not reached) versus 26.9 months (95% CI, 18.3-51.5) in the SOC group. Among the CPS ≥1 population, median EFS was 59.7 months (95% CI, 37.9-not reached) in the KEYTRUDA plus SOC group versus 29.6 months (95% CI, 19.5-41.9) in the SOC group. In the ITT population, median EFS was 51.8 months (95% CI, 37.5-not reached) in the KEYTRUDA plus SOC group versus 30.4 months (95% CI, 21.8-50.1) in the SOC group. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were identified.

"As the first positive trial in over two decades for patients with resectable, locally advanced head and neck squamous cell carcinoma, the presentation of these landmark results marks an important moment for these patients and those who care for them," said Dr. Ravindra Uppaluri, the study’s co-principal investigator, director of Head and Neck Surgical Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute. "KEYNOTE-689 represents a meaningful development with a potential to provide an option that helps certain patients with LA-HNSCC reduce the risk of recurrence and disease progression earlier in their treatment journey."

"The addition of immunotherapy using KEYTRUDA to standard of care surgery and adjuvant (chemo)radiotherapy resulted in a significant reduction in the risk of event-free survival events by 27%, compared with standard of care therapy alone," said study co-principal investigator Dr. Douglas Adkins, Professor, Division of Oncology, Washington University School of Medicine in St. Louis. "These results are notable as they mark the first time an anti-PD-1 therapy has demonstrated a statistically significant and clinically meaningful improvement in event-free survival in the neoadjuvant and adjuvant setting in earlier stages of head and neck squamous cell carcinoma."

The study also showed a statistically significant improvement in major pathological response (mPR) rate, a key secondary endpoint, in patients with CPS ≥10 (difference in mPR rates: 13.7% [95% CI, 9.7-18.7]; p<0.00001), CPS ≥1 (9.8% [95% CI, 7.0-13.3]; p<0.00001) and in the ITT population (9.3% [95% CI, 6.7–12.8, P<.00001), compared to adjuvant radiotherapy alone.

A trend toward improvement in overall survival (OS), another key secondary endpoint, was observed in patients with CPS ≥10 (HR=0.72 [95% CI, 0.52-0.98]) at the time of this interim analysis for the KEYTRUDA plus standard of care regimen versus standard of care alone. The OS results did not reach statistical significance at the time of this interim analysis. Due to the statistical testing hierarchy, formal testing was not performed in the CPS ≥1 and ITT populations. OS will be evaluated at the next interim analysis.

"As the 12th positive pivotal trial for a KEYTRUDA-based regimen in earlier-stage cancers, the results from KEYNOTE-689 are a testament to our commitment to address an unmet need in this important area of research," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "These compelling results illustrate the potential of this regimen to change the landscape of care for certain patients facing this challenging disease. We are working with the FDA and other global authorities to bring this new option to patients as quickly as possible."

A supplemental Biologics License Application (sBLA) for KEYTRUDA based on data from KEYNOTE-689 is under priority review with the U.S. Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA), or target action, date of June 23, 2025.

KEYTRUDA is currently approved as monotherapy and in combination regimens for appropriate patients with metastatic or unresectable, recurrent HNSCC in the U.S., Europe, China, Japan and other countries around the world. For more information, please see the "Selected KEYTRUDA (pembrolizumab) Indications in the U.S." section below.

Study design and additional data from KEYNOTE-689

KEYNOTE-689 is a randomized, active-controlled, open-label Phase 3 trial (ClinicalTrials.gov, NCT03765918) evaluating KEYTRUDA as neoadjuvant treatment and KEYTRUDA in combination with standard of care radiotherapy (with or without cisplatin) as adjuvant treatment in treatment-naïve patients with newly diagnosed, stage III or IVA resectable, locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Efficacy outcomes are classified by programmed cell death ligand 1 (PD-L1) combined positive score (CPS) status. The primary endpoint is EFS, which is defined as the time from randomization to the first occurrence of radiographic disease progression; local or distant progression or recurrence; or death due to any cause. The secondary endpoints include OS, mPR, pathological complete response and safety. The study enrolled 714 patients who were randomized 1:1 to receive:

KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for two cycles) as neoadjuvant therapy prior to surgery, followed by either KEYTRUDA (200 mg IV Q3W for 15 cycles) plus standard of care radiotherapy with cisplatin (100 mg/m2 IV Q3W for three cycles) as adjuvant therapy following surgery for high-risk patients or KEYTRUDA (200 mg IV Q3W for 15 cycles) plus standard of care radiotherapy without cisplatin as adjuvant therapy following surgery for low-risk patients; or
No neoadjuvant therapy prior to surgery, followed by adjuvant standard of care radiotherapy with cisplatin (100 mg/m2 IV Q3W for three cycles) as adjuvant therapy following surgery for high-risk patients or standard of care radiotherapy without cisplatin as adjuvant therapy following surgery for low-risk patients.
The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 44.6% of patients receiving KEYTRUDA plus standard of care radiotherapy versus 42.9% of patients receiving standard of care radiotherapy alone. TRAEs led to death in 1.1% of patients receiving the KEYTRUDA regimen (n=4) and 0.3% of patients receiving standard of care radiotherapy (n=1). No new safety concerns were identified. Immune-mediated adverse events (AEs) of any grade occurred in 43.2% of patients receiving the KEYTRUDA regimen, most commonly hypothyroidism (24.7%).

About head and neck cancer

Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. Most head and neck cancers are squamous cell carcinomas that begin in the flat, squamous cells that make up the thin surface layer of the structures in the head and neck. Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is cancer that has grown outside the original location, but has not yet spread to distant parts of the body. There are several factors that greatly increase the risk of developing head and neck cancer, including tobacco and alcohol use and human papillomavirus (HPV). It is estimated there were more than 947,200 new cases of head and neck cancer diagnosed and over 482,400 deaths from the disease in 2022 globally. In the U.S., it is estimated there will be approximately 72,680 new cases of head and neck cancer diagnosed and more than 16,680 deaths from the disease in 2025.

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.