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Precision Biologics to Present ADC Findings at AACR 2025

Precision Biologics, Inc. has exciting news to share at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2025. Scheduled for April 29, 2025, at the McCormick Place Convention Center in Chicago, IL, the company will present a poster detailing the development of a novel antibody-drug conjugate (ADC) utilizing its monoclonal antibody (mAb) PB-223, specifically engineered to target core 2 O-glycans found on human carcinomas.

Antibody-Drug Conjugates: A Breakthrough in Cancer Treatment

Antibody-drug conjugates are gaining significant attention in the field of oncology for their targeted approach to cancer therapy. Unlike traditional chemotherapy, which indiscriminately affects both healthy and cancerous cells, ADCs are designed to specifically attack tumor-associated antigens that are overexpressed on the surface of cancer cells. This targeted approach aims to improve efficacy while minimizing damage to healthy tissues.

About PB-223: The Innovative Monoclonal Antibody

PB-223 is a chimeric human IgG1 mAb developed through a process known as affinity maturation, deriving from its predecessor, NEO-102 (Ensituximab). This innovative antibody has been tailored to specifically bind to truncated core 2 O-glycans, which are predominantly expressed in cancer cells, ensuring greater selective binding during treatment.

The improved binding affinity of PB-223 is noteworthy—achieving a KD value that is at least four times lower than that of NEO-102, signifying its enhanced tumor-targeting capability. Immunohistochemistry analyses demonstrate PB-223's ability to bind to a broader array of tumor tissues, including colorectal, pancreatic, triple-negative breast, prostate, kidney, head and neck, liver, and bladder cancers, while sparing normal tissues from binding.

The Components of the ADC

An ADC comprises three critical elements: the monoclonal antibody (mAb), the linker, and the cytotoxic payload. In this ADC formulation, Monomethyl auristatin E (MMAE) serves as the payload. MMAE is a highly potent antimitotic agent that disrupts cell division by inhibiting tubulin polymerization, making it a common choice amidst ADC payloads under clinical development for oncological applications.

The linker utilized in this study is mc-vc-PABc, which facilitates the attachment of the payload to the PB-223 monoclonal antibody through a cysteine-based conjugation method. This configuration enhances the effectiveness of the ADC, optimizing its potential therapeutic benefits.

Characterization and Efficacy Testing of the ADC

The development of the ADC has led to a rigorous characterization process. Parameters evaluated included the drug-to-antibody ratio (DAR), a critical factor in predicting the ADC's efficacy and safety profile. Three variations of the ADC were created: PB-MMAE-2, PB-MMAE-5, and PB-MMAE-6, with DARs of 3.72, 3.92, and 4.15, respectively.

Flow cytometry was employed to assess how well these ADCs bind to cancer cells. All three demonstrated similar binding affinities to the human ovarian cancer cell line OV-90. Additionally, when tested for cytotoxic effects, all variants exhibited the ability to kill the OV-90 cells, with 80% cell death observed five days post-treatment.

The PB-MMAE-5 variant showed the most promise, as it successfully killed an array of human cancer cell lines, including those of prostate, triple-positive and triple-negative breast, lung, colon, and pancreatic origins.

Safety and Stability Assessments in vivo

Safety was tested in vivo utilizing rat subjects, with the PB-MMAE-5 ADC administered at a concentration of 2.3 mg/kg. The results indicated excellent tolerability, as no adverse effects or weight loss were noted throughout the evaluation period.

Additionally, PB-MMAE-5's stability was confirmed in human plasma, revealing a 23% residual rate after 14 days for samples incubated at concentrations of both 100 µg/mL and 50 µg/mL.

Promising Efficacy in Tumor Models

The efficacy of PB-MMAE-5 in vivo was further established through a subcutaneous xenograft model in NOD-SCID mice. Initial data suggested significant anti-tumor activity, particularly at the 3 mg/kg dosing level, compared to lower dosages or administration of the payload alone.

In summary, findings from the study highlight PB-MMAE-5's capacity to selectively target and kill cancer cells expressing core 2 O-glycans, alongside demonstrating minimal toxicity and promising in vivo efficacy, positioning it as a potential therapeutic option for treating various malignancies. The results will be showcased in poster format at the AACR Annual Meeting 2025 and available for public access online from April 25, 2025.

For more information and to access the poster, visit: Precision Biologics AACR Poster.