Precision Biologics has reported promising preclinical efficacy data for its novel antibody-drug conjugate (ADC) PB-vcMMAE-5 in treating human ovarian cancer. The company announced that the ADC demonstrated measurable anti-tumor activity both in laboratory studies and animal models, with findings to be presented at the American Association for Cancer Research (AACR) Special Conference on Advances in Ovarian Cancer Research.
Targeting Truncated Core 2 O-Glycans
The ADC utilizes Precision Biologics' proprietary monoclonal antibody PB-223, which targets truncated core 2 O-glycans specifically expressed by cancer cells but not healthy tissues. PB-223 represents an improved version of the company's previous antibody NEO-102 (Ensituximab), developed through affinity maturation techniques.
"PB-223 demonstrated a binding affinity (KD) at least 4-fold lower than NEO-102, indicating stronger tumor binding," according to the company's research data. The antibody was optimized through Fast Screening for Expression Biophysical Properties and Affinity, enhancing its VH and VL sequences for improved target recognition.
The ADC combines PB-223 with monomethyl auristatin E (MMAE) as the cytotoxic payload, connected via a cleavable mc-vc-PABc linker through cysteine-based conjugation. MMAE is a potent antimitotic agent that blocks tubulin polymerization and represents the most commonly used ADC payload in clinical oncology development.
Strong In Vitro Anti-Cancer Activity
In laboratory studies, PB-vcMMAE-5 was tested against four human cancer cell lines over five days, including triple-negative breast cancer lines (HCC1937, MDA-MB-231), ER+/PR+/HER2+ breast cancer (BT474), and ovarian cancer (OV-90).
The results showed significant cytotoxic activity across all tested cell lines. At the highest concentration, PB-vcMMAE-5 achieved 52.72% cell killing in HCC1937 cells and 88.36% in MDA-MB-231 cells. In the ovarian cancer line OV-90, the ADC demonstrated 92.51% cell killing, while achieving 83.22% killing in BT474 breast cancer cells.
Importantly, the naked PB-223 antibody without the cytotoxic payload showed no killing activity in any of the tested cell lines, confirming that the therapeutic effect requires the complete ADC structure.
Promising In Vivo Efficacy and Safety Profile
Animal studies using NOD-SCID mice bearing OV-90 ovarian cancer xenografts demonstrated dose-dependent anti-tumor activity. Mice received weekly intravenous doses of PB-vcMMAE-5 at 1, 3, 6, or 9 mg/kg for five weeks, with PBS and MMAE alone serving as controls.
The efficacy results showed that while 1 mg/kg did not significantly reduce tumor volume compared to PBS controls, doses of 6 and 9 mg/kg induced robust tumor volume reduction. Analysis of tumor viability at day 45 using Ki-67 staining revealed no detectable tumor activity in mice treated with 9 mg/kg PB-vcMMAE-5.
Safety monitoring throughout the study showed that PB-vcMMAE-5 was well-tolerated across all dose levels. No signs of distress or body weight loss were observed, and no significant hematological or pathological changes were detected in the liver, spleen, brain, or heart of mice treated with efficacious doses compared to controls.
Addressing Unmet Medical Need
The research addresses a significant challenge in ovarian cancer treatment, as these cancers "remain largely unresponsive to immune checkpoint inhibitors, in part due to their ability to suppress the cytotoxic activity of immune cells infiltrating the tumor microenvironment," according to the company's background research.
Disrupted O-glycosylation pathways represent a key feature of ovarian cancer progression, metastasis, and poor prognosis, highlighting the potential therapeutic value of targeting truncated core 2 O-glycans. The company notes this "underscores the urgent need for alternative therapeutic strategies."
Previous studies presented at the AACR Annual Meeting 2025 demonstrated that PB-vcMMAE-5 remains stable in human plasma, further supporting its clinical development potential.
Clinical Development Implications
The comprehensive preclinical data package suggests PB-vcMMAE-5 has promising therapeutic potential not only for ovarian cancer but potentially for other malignancies expressing core 2 O-glycans. The combination of strong efficacy, favorable safety profile, and plasma stability positions the ADC as a candidate for clinical evaluation.
The findings will be presented in poster format at the AACR Special Conference on September 20, 2025, at the Grand Hyatt Denver, providing the scientific community with detailed methodology and results from these preclinical studies.
