Ensituximab

BETHESDA, Md., Sept. 19, 2025 /PRNewswire/ -- Precision Biologics, Inc. reports that in vitro and in vivo efficacy of the novel ADC, using its anti-core 2 O-glycans anti-human carcinoma mAb PB-223 (PB-vcMMAE-5), against human ovarian cancer expressing truncated core 2 O-glycans will be presented in a poster at the American Association for Cancer Research (AACR) Special Conference in Cancer Research: Advances in Ovarian Cancer Research on September 20th, 2025, Grand Hyatt Denver, Denver, Colorado, USA. Poster title: In vitro and in vivo efficacy of the antibody-drug-conjugate (ADC) PB-vcMMAE-5 against human ovarian cancer expressing truncated core 2 O-glycans The presentation of the poster will be made in person on the following date and location: Saturday, September 20, 6:30 p.m. – 8:00 p.m. Grand Hyatt Denver, Denver, Colorado, USA Poster Section: B Abstract Control Number: B068 BACKGROUND: Ovarian 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. One of the disrupted pathways in these cancers is O-glycosylation, a feature particularly associated with ovarian cancer progression, metastasis and poor prognosis. This underscores the urgent need for alternative therapeutic strategies. We developed an ADC, designated PB-vcMMAE-5, composed of the following: The mAb: We used PB-223, an innovative mAb developed through affinity maturation of mAb NEO-102 (Ensituximab), a chimeric human IgG1 mAb that targets truncated core 2 O-glycans, specifically expressed by cancer cells and not by healthy tissues. The binding affinity of PB-223 for its target was improved, compared to NEO-102, by optimizing its VH and VL sequences through Fast Screening for Expression Biophysical Properties and Affinity. PB-223 demonstrated a binding affinity (KD) at least 4-fold lower than NEO-102, indicating stronger tumor binding. PB-223 does not bind to normal tissues and it can be internalized into human cancer cell lines expressing its target. The payload: Monomethyl auristatin E (MMAE) was used as payload. MMAE is a potent antimitotic agent that inhibits cell division by blocking the polymerization of tubulin and is the most common ADC payload used to be linked to antibodies in clinical development for oncologic applications. The linker: mc-vc-PABc was used as a cleavable linker. PB-223 was conjugated to the linker-payload through a cysteine-based conjugation method. STUDY PRESENTED AT AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research, 2025 After development of the ADC PB-vcMMAE-5, we evaluated its efficacy in vitro and in vivo In vitro efficacy: The in vitro cytotoxicity of PB-vc-MMAE-5 was tested in four human cancer cell lines: triple-negative breast cancer (HCC1937, MDA-MB-231), ER+/PR+/HER2+ breast cancer (BT474), and ovarian cancer (OV-90). Cells were treated with varying ADC concentrations for 5 days. This study shows that PB-vcMMAE-5 effectively killed all cell lines tested. At the highest concentration, the percentage of cell killing for PB-vcMMAE-5 was 52.72% in HCC1937 and 88.36% in MDA-MB-231. At the highest concentration, the percentage of cell killing for PB-vcMMAE-5 was 92.51% in OV-90 and 83.22% in BT474. In contrast, naked PB-223 mAb showed no killing in all cell lines tested In vivo safety: In a study presented in April 2025, at AACR Annual Meeting 2025, we showed that PB-vcMMAE-5 was well tolerated in rats. No sign of distress nor loss of body weight were observed after administration. In this study we confirm the same pattern in mice. NOD-SCID mice bearing OV-90 xenografts were treated with weekly doses of PBS, MMAE alone, or PB-vc-MMAE-5 (1, 3, 6, or 9 mg/kg) for five weeks. Animal body weight was monitored regularly, twice a week, as an indirect measure of toxicity. The ADC PB-vcMMAE-5 was well tolerated in mice. No sign of distress and loss of body weight were observed No significant hematological or pathological changes were detected in the liver, spleen, brain, or heart of mice treated with efficacious doses of the ADC compared with controls. In vivo efficacy: The efficacy of the ADC PB-vcMMAE-5 was assessed in OV-90 subcutaneous xenograft model established in NOD-SCID mice. The ADC PB-vcMMAE-5 was administered intravenously at doses 1, 3, 6 or 9 mg/kg, once per week for five weeks. On day 31 from first ADC infusion, most alive mice were sacrificed, and tumors were excised for histological analysis using Ki-67 staining to assess proliferating viable tumor cells. To further assess systemic toxicity and prolonged efficacy, three mice each from the 6 and 9 mg/kg groups were followed to day 45. Data presented in this study show that PB-vcMMAE-5 at 1 mg/kg did not significantly reduce tumor volume compared with PBS, whereas PB-vcMMAE-5 at 6 and 9 mg/kg induced robust reduction of tumor volume. In addition, analysis of tumor viability at day 45 (Ki67 H-score) showed no tumor activity in mice treated with PB-vcMMAE-5 at 9 mg/kg Findings from this study showed that PB-vcMMAE-5 can kill human cancer cells expressing PB-223's target, is not toxic in vivo in mice and is highly effective in vivo at 9 mg/kg in NOD-SCID mice bearing human ovarian cancer. In addition, in a poster presented at AACR Annual Meeting 2025 we reported that PB-vcMMAE-5 is stable in human plasma. All these data suggest that PB-vcMMAE-5 has promising potential as a therapeutic option for human ovarian tumors and for a range of human malignancies expressing core 2 O-glycans. The PDF of the poster will be available starting from September 19th, 2025, at the following link: SOURCE Precision Biologics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Precision Biologics will present affinity maturation and characterization of a novel core 2 O-glycan epitope targeting anti-human carcinoma mAb PB-223 at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting on November 7-8, 2024 BETHESDA, Md., Nov. 6, 2024 /PRNewswire/ -- Precision Biologics, Inc. reports that affinity maturation and characterization of its novel anti-core 2 O-glycan monoclonal antibody PB-223, will be presented in a poster at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting on November 7-8, 2024, George R. Brown Convention Center, Houston, Texas, USA, Poster title: Affinity Maturation and Characterization of a Novel O-glycan Epitope Targeting Anti-Human Carcinoma Monoclonal Antibody (mAb) PB-223 Presentation of the poster will be made in person on the following dates and locations: November 7th, 2024: SITC Immune Engineering Workshop, 3.10 p.m-5 p.m. CST, George R. Brown Convention Center, Level 3 - Grand Ballroom AB, Houston, Texas, USA November 8th, 2024: Poster Session Immuno-Engineering, abstract number 1101, 12:15–1:45 p.m. CST and 5:30-7 p.m. CST, George R. Brown Convention Center, Level 1-Exhibit Halls A B, Houston, Texas, USA BACKGROUND: PB-223 is an innovative mAb developed through immune engineering from the chimeric IgG1 NEO-102 (Ensituximab). It targets a unique core 2 O-glycan (variant of MUC5AC), Preclinical and clinical data showed that NEO-102 specifically binds to and kills colorectal and pancreatic cancer cells through ADCC. NEO-102 did not bind to healthy tissues. In a phase 2 study, NEO-102 showed promising results in heavily pretreated patients with advanced, refractory metastatic colorectal cancer. In general, the efficacy of using a monoclonal antibody as a single agent in cancer immunotherapy can be impaired not only by the resistance of cancer cells in the tumor microenvironment (TME), but also by a low binding affinity to target antigens expressed on cancer cells. One strategy to improve the therapeutic efficacy of monoclonal antibodies is to enhance their binding affinity to target antigens. STUDY PRESENTED AT SITC 2024: The objective of this study was to enhance the binding affinity of NEO-102 to its target antigen. By engineering the VH and VL sequences of NEO-102 through Fast Screening for Expression Biophysical Properties and Affinity (FASEA), while maintaining the binding specificity to the target antigen, allowed us to develop a new clone with a lower KD and markedly improved characteristics. This new biologic asset developed by affinity maturation was given the name PB-223. Binding kinetics of PB-223 and NEO-102 to the target antigen were compared by ELISA. Results show that PB-223 has a KD of 4.5-fold less than NEO-102, suggesting a higher affinity for the target antigen by PB-223 compared to NEO-102. The binding affinity of PB-223 and NEO-102 to various human tumor cell lines was also evaluated by flow cytometry. Flow cytometry analysis showed that PB-223 not only has markedly enhanced comparative binding to colorectal and pancreatic cancer cell lines recognized by NEO-102, but that PB-223 is also able to bind to many additional tumor cell lines that were not recognized by NEO-102. Further study by O-glycan array analysis showed that 1) PB-223 binds specifically to core-2 O-glycans, and that 2) core 2 O-glycans recognized by PB-223 are expressed on tumor cell lines positive for PB-223 binding in flow cytometry. Immunohistochemistry (IHC) analysis performed on human tumor tissues shows that PB-223 does not bind to healthy tissues. IHC analysis also shows that PB-223, in addition to binding to both colorectal cancer and pancreatic cancer, it also binds to additional tumor tissues not reactive with NEO-102, including triple negative breast cancer, prostate cancer, kidney cancer, head and neck cancer, liver cancer, and bladder cancer. In addition, this study demonstrated that PB-223 is internalized into human cancer cell lines expressing core 2 O-glycans. Findings from this study suggest that PB-223 has a strong binding affinity for human cancers expressing core 2 O-glycans and that PB-223 may be a potential candidate for the development of antibody-drug conjugates (ADC) for treatment of various human carcinomas. The PDF of the poster will be available starting from November 5, 2024, at the following link: SOURCE Precision Biologics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED