#United States #Cambridge #Nona Biosciences #Pfizer #ADC drug

Pfizer's Latest Advancement in ADC Development

At the AACR Annual Meeting 2025, groundbreaking research is in the spotlight as Pfizer showcases the preclinical data on its innovative antibody-drug conjugate (ADC), PF-08052666. Developed in partnership with Nona Biosciences, this novel drug is designed specifically to target mesothelin (MSLN) and has shown promising effectiveness against various types of cancers.

Overview of PF-08052666

PF-08052666, also referred to as HBM9033 or SGN-MesoC2, represents a significant advancement in cancer treatment strategies. This ADC is the first to utilize a topoisomerase 1 inhibitor (TOP1i) to target MSLN, a tumor-associated antigen prevalent in several solid tumors, such as ovarian, lung, and colorectal cancers. The exploration into this drug marks a pivotal moment in the journey from concept to clinical application, facilitated by the advanced technology platforms of Nona Biosciences, which was granted commercialization rights by Pfizer on December 14, 2023.

Key Features of the Drug

The design of PF-08052666 integrates a human IgG1 monoclonal antibody with a potent, camptothecin-based TOP1i payload and a cleavable linker, achieving an impressive drug-to-antibody ratio (DAR) of 8. This unique composition is tailored to enhance antitumor activity while navigating the limitations of previous anti-MSLN ADCs.

Notable Preclinical Findings

1. In Vitro Efficacy: The ADC demonstrated direct cytotoxic effects by effectively delivering its toxic payload to MSLN-positive cells. Moreover, it also exhibited bystander killing capabilities on nearby MSLN-negative cells, maintaining its effectiveness even when soluble MSLN was present in significant concentrations.
2. In Vivo Performance: In various preclinical models, PF-08052666 outperformed benchmark ADCs based on DM4, effectively targeting ovarian, lung, and colorectal cancer cells. Its ability to function in heterogeneous xenograft models, which included both MSLN-positive and MSLN-negative cells, showcases its potential advantage through the increased bystander activity of its novel linker payload.

3. Support for Clinical Trials: These encouraging results bolster the ongoing Phase 1 clinical trials (NCT06466187) where PF-08052666 is currently being tested on patients with advanced solid tumors, confirming its solid foundation and readiness for further development.

Insights from Nona Biosciences

Dr. Jingsong Wang, Chairman of Nona Biosciences, expressed enthusiasm regarding the developments shared at the AACR meeting. He highlighted that the presentation of this preclinical data underscores the effectiveness of their facilities and showcases their commitment to advancing innovative therapies that could significantly change patient outcomes in oncology.

The Future of PF-08052666

As research in biotherapeutics continues to evolve, PF-08052666 positions itself as a potentially best-in-class therapeutic option against cancers where traditional treatments have faltered. The implications of this research stretch beyond mere academic interest, promising new avenues of improved patient care and novel strategies for cancer treatment.

Conclusion

The advancements shown by Pfizer and Nona Biosciences at the AACR Annual Meeting 2025 provide a glimpse into the future of cancer therapy, lending hope to patients and families affected by aggressive malignancies. The continued collaboration between these two entities is anticipated to accelerate the pace of breakthroughs aimed at addressing pressing medical needs in the fight against cancer.