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.