Precision Biologics to Present at ASCO Annual Meeting on June 1, 2024

BETHESDA, Md., May 30, 2024 – Precision Biologics, Inc. has announced new insights from their phase 2 clinical trial, which combines their monoclonal antibody NEO-201 with pembrolizumab for patients who have shown resistance to previous checkpoint inhibitor therapies. These findings are set to be showcased at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago on June 1st.

Trial Overview

The poster titled "Reduction of circulating naïve Tregs and gMDSCs and low levels of soluble MICA are prognostic for efficacy of combined NEO-201 and pembrolizumab" will be presented on June 1st, 2024, at McCormick Place Convention Center. The presentation will occur in Hall A from 9 am to 12 pm and will be part of the Developmental Therapeutics-Immunotherapy session.

Background and Rationale

Checkpoint inhibitors like pembrolizumab have revolutionized cancer immunotherapy by enhancing the immune system's ability to fight cancer. However, their efficacy is limited, with response rates for solid tumors standing at roughly 20-30% in first-line settings and even lower in cases of checkpoint refractory disease. A significant factor in this low response rate is the presence of immunosuppressive cells such as regulatory T cells (Tregs) and granulocytic myeloid-derived suppressor cells (gMDSCs) in the tumor microenvironment (TME). These cells diminish the effectiveness of the immune response against cancer.

NEO-201, a humanized IgG1 monoclonal antibody, targets specific glycan structures expressed by various cancers and mature granulocytes while sparing most normal tissues and immune cells. Previous studies indicated that NEO-201 could kill Tregs through complement-dependent cytotoxicity (CDC) and gMDSCs via antibody-dependent cellular cytotoxicity (ADCC). This dual action formed the basis for combining NEO-201 with pembrolizumab in the current phase II clinical trial aimed at treating resistant cancers, including non-small cell lung cancer (NSCLC), head and neck, cervical, and endometrial cancers.

Preliminary Findings

Initial data presented at conferences in Milan and San Diego in 2023 showed that patients receiving the combination therapy of NEO-201 and pembrolizumab experienced sustained stable disease (SD). Specifically, patients with SD for over 84 days exhibited a reduction in circulating gMDSCs and Tregs. Conversely, patients with progressive disease (PD) showed increased levels of these immunosuppressive cells. This suggests that NEO-201 may help patients overcome resistance to PD-1/PD-L1 inhibitors by reducing Tregs and gMDSCs.

ASCO 2024 Study Insights

In the study to be presented at ASCO 2024, NEO-201 employs Natural Killer (NK) cells to kill target cells through ADCC. Cancer cells can inhibit NK cell activity by releasing soluble factors like MHC class 1 chain-related protein A (MICA). High serum levels of soluble MICA (sMICA) correlate with reduced NK cell activity, cancer progression, and metastasis.

The study found that median sMICA levels before treatment were 33 times higher in patients with PD compared to those with SD. Post-treatment levels of sMICA remained high in PD patients and low in SD patients. Elevated sMICA levels impair NK cell activity, reducing the effectiveness of NEO-201 and pembrolizumab, which leads to disease progression. In contrast, low levels of sMICA allow NK cells to effectively target and kill cancer cells, Tregs, and gMDSCs, resulting in disease stabilization.

Conclusion and Future Directions

The study highlights that low sMICA levels, combined with the reduction of circulating Tregs and gMDSCs by NEO-201, are associated with durable SD in patients resistant to prior ICIs. These factors could serve as prognostic markers for the efficacy of the combined NEO-201 and pembrolizumab treatment. Continued enrollment in the clinical trial will help validate these findings in larger patient groups.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!