NEO-201

BETHESDA, Md., May 30, 2024 /PRNewswire/ -- Precision Biologics, Inc. reports that novel findings from its ongoing phase 2 clinical trial, combining NEO-201 with pembrolizumab for the treatment of patients resistant to prior checkpoint inhibitor therapy, will be presented in a poster at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting, McCormick Place Convention Center, Chicago, Illinois, USA, June 1st, 2024. Poster title: Reduction of circulating naïve Tregs and gMDSCs and low levels of soluble MICA are prognostic for efficacy of combined NEO-201 and pembrolizumab Presentation of the poster in person will be made at the McCormick Place Convention Center in Chicago, Illinois, USA, on Saturday June 1st, 2024, Hall A from 9am - 12pm, Session: Developmental Therapeutics-Immunotherapy, poster board #9, poster # 2530. BACKGROUND: The employment of immune checkpoint inhibitors (ICIs), such as pembrolizumab (anti-PD-1 mAb), in cancer immunotherapy has been shown to enhance activity of the immune system against cancer cells. Although ICIs show efficacy and improved survival of certain cancer patients, the response rate of PD-1/PD-L1 blockade against solid tumors is around 20-30% in the first line setting and significantly lower in checkpoint refractory disease. One cause identified for this low response rate is the infiltration of the tumor microenvironment (TME) by immunosuppressive cells, such as regulatory T cells (Tregs) and granulocytic myeloid-derived suppressor cells (gMDSCs). The accumulation of these immunosuppressive cells in the TME impairs the antitumor immunity triggered by ICIs. A strategy to restore antitumor immunity and overcome tumor resistance to ICIs is to combine ICIs with anticancer drugs able to bind to and deplete Tregs and gMDSCs. NEO-201 is a humanized IgG1 monoclonal antibody that binds to Core 1 and/or extended Core 1 O-glycans expressed by several human solid and blood tumors, as well as mature granulocytes, but it does not bind to most normal tissues and human immune cell subsets (B cells, CD4+ T cells, CD8+ T cells, NK cells, monocytes). Previous studies showed that NEO-201 can bind and mediate the killing of Tregs via CDC. Further studies presented at AACR in 2023 showed that NEO-201 can bind and mediate the killing of gMDSCs via ADCC. The ability of NEO-201 to mediate the killing of immunosuppressive cells served as the rationale for combination of NEO-201 with pembrolizumab in the ongoing phase II clinical trial (NCT03476681) for the treatment of patients with NSCLC, head and neck, cervical and endometrial cancers who were refractory to multiple lines of standard treatment, including ICIs. Preliminary findings from this ongoing clinical trial presented at the CRI-ENCI-AACR in September 2023 in Milan, Italy and at the SITC annual meeting in November 2023 in San Diego, CA, USA, revealed that, after combination treatment with NEO-201 and pembrolizumab some patients experienced durable stable disease (SD). Patients with durable SD (>84 days) demonstrated a decreasing trend in circulating gMDSCs and Tregs. Conversely, patients with progressive disease (PD) exhibited an increasing trend of circulating gMDSCs and Tregs. This preliminary data suggests that elimination of circulating gMDSCs and Tregs mediated by NEO-201 may enable patients to overcome resistance to PD-1/PD-L1 checkpoint inhibitors, in subjects for whom pembrolizumab is currently indicated and with solid tumors resistant to prior ICIs treatment. STUDY PRESENTED AT ASCO 2024: NEO-201 uses Natural Killer (NK) cells as effector cells to mediate the killing of its target cells through ADCC. Several studies reported that cancer cells inhibit NK cell antitumor activity by releasing soluble factors into the bloodstream, such as soluble MHC class 1 chain-related protein A (MICA.) Elevated serum levels of soluble MICA (sMICA) have been correlated with impairment of NK cell activity, cancer progression and metastasis. This study reports that median serum levels of sMICA pre-treatment were 33-fold higher in patients with PD compared to patients with SD and that levels of sMICA remained elevated in patients with PD and low in patients with SD at all time points post treatment. High levels of sMICA in patients with PD can impair NK cell activity. This impairment negatively impacts the NK cell mediated ADCC triggered by NEO-201 against cancer cells, Tregs and gMDSCs. Consequently, the effectiveness of NEO-201 and pembrolizumab treatment is reduced, leading to disease progression in these patients. Conversely, low levels of sMICA pre- and post-treatment do not hinder the antitumoral activity of NK cells. This allows NEO-201 to effectively mediate the killing of its target cells, including cancer cells, Tregs and gMDSCs, through ADCC. As a result, this phenomenon can lead to the durable stabilization of the disease. This study reports that low levels of sMICA, together with the reduction of both circulating Tregs and gMDSCs mediated by NEO-201, were associated with durable SD in cancer patients refractory to prior ICIs and that they could be favorable prognostic markers for clinical benefit following combination treatment with NEO-201 and pembrolizumab. Ongoing enrollment in this clinical trial will validate these findings in larger cohorts.

BETHESDA, Md., April 5, 2024 PRNewswire/ -- Precision Biologics, Inc. reports its lead monoclonal antibody, NEO-201, targets circulating human naïve regulatory T cells (Tregs) in both healthy donors and cancer patients. A poster presentation discussing this data will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2024, at the San Diego Convention Center in San Diego, CA on April 8th, 2024. Poster title: The O-glycan epitope targeting anti-human carcinoma monoclonal antibody (mAb) NEO-201 can also target human regulatory T cells (Tregs) This study was performed by Drs. Atsushi Tanaka and Shimon Sakaguchi from Osaka University, Japan. Dr. Sakaguchi's group independently analyzed by flow cytometry the ability of NEO-201 to recognize naïve Tregs in peripheral blood mononuclear cells (PBMCs) from healthy donors, confirming findings from Precision Biologics in PBMCs from cancer patients. Previous studies performed by Precision Biologics have shown that approximately 4.6% of CD4+ T cells express NEO-201 target antigen and that those CD4+ T cells have Tregs phenotype. In addition, in a recently published phase 1 clinical study it has been observed that NEO-201 binds to CD4+/ CD25+/, CD127-/, Foxp3+/, CD15s+ cells from PBMCs from cancer patients with solid tumors. The purpose of this study performed in Dr. Sakaguchi's laboratory was to corroborate and further characterize the phenotype of the specific subset of CD4+ T cells expressing the NEO-201 target antigen. In this study, human PBMCs were collected from 7 healthy donors (HD) at Osaka University and 6 cancer patients from Precision Biologics ongoing phase II clinical trial (Clinical Trial NCT03476681) evaluating the efficacy of the combination of NEO-201 with pembrolizumab in adults with solid tumors resistant to checkpoint inhibitors. Phenotypic analysis was conducted by flow cytometry to evaluate which fraction of CD4+ T cells is recognized by NEO-201. Flow cytometry analysis revealed that NEO-201 recognizes fraction I of CD4 T cells in both healthy donors and cancer patients. Fraction I includes naïve Tregs (nTregs) with the following phenotype: CD3+/CD4+/CD45RA+/Foxp3low cells. The percentage of nTregs in cancer patients was higher than the percentage detected in healthy donors. On the other hand, this study revealed that NEO-201 does not bind to fraction II of CD4 T cells in both healthy donors and cancer patients. Fraction II includes effector Tregs (eTregs) with the following phenotype: CD3+/CD4+/CD45RA-/Foxp3high cells. When subjected to t-cell receptor (TCR) stimulation, nTregs undergo proliferation and differentiate into eTregs, which can then infiltrate into tumor microenvironment (TME) and induce suppression of anticancer immunity. Depletion of circulating NEO-201 positive nTregs in cancer patients after NEO-201 treatment may prevent the differentiation of nTregs into eTregs, thus reducing their accumulation in the TME. This study suggests therapy with NEO-201 may reduce Treg-mediated suppression of anticancer immunity. The poster will be presented in person at the San Diego Convention Center, San Diego, CA, on Monday April 8th, 2024. Please stop by poster # 2716 at Poster Section 6, Poster Board number 7 (1.30 p.m.–5.00 p.m.). About Precision Biologics Founded in 2012, Precision Biologics, Inc. is a clinical stage biotechnology corporation focused on developing therapeutic and diagnostic products for the detection and treatment of cancer. The company's antibody drug candidates and diagnostics are designed to detect and target the tumor with minimal damage to healthy cells. Precision Biologics is uniquely positioned to create innovative therapeutics through the use of proprietary cancer vaccines, several of which have demonstrated success in human trials. By marrying this platform with today's breakthrough technologies, the company is developing antibody therapeutics that could change the way we detect and treat cancer. For more information on Precision Biologics, please visit .