NEO-201 / Precision Biologics - LARVOL DELTA

QUILT-3.017: Study of NEO-201 in Solid Tumors Expansion Cohorts (clinicaltrials.gov) - P1/2 | N=121 | Active, not recruiting | Sponsor: Precision Biologics, Inc | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2029 ➔ Nov 2026 | Trial primary completion date: Jan 2028 ➔ Jun 2026

Enrollment closed • First-in-human • Trial completion date • Trial primary completion date • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer • ALK1 • BRAF • EGFR • MSI • PD-L1 • ROS1 • TMB

The O-glycan epitope targeting anti-human carcinoma monoclonal antibody (mAb) NEO-201 can also target human regulatory T cells (Tregs) (AACR 2024) - P1/2 | "The purpose of this study was to further characterize the phenotype of the specific subset of CD4+ T cells expressing the NEO-201 target antigen.Experimental Design: Human PBMCs were obtained from 7 healthy donors (HD) collected at Osaka University and 6 cancer patients from our ongoing phase II clinical trial (Clinical Trial NCT03476681) evaluating the efficiency of the combination of NEO-201 with pembrolizumab in adults with solid tumors resistant to checkpoint inhibitors. NEO-201 binds to human Tregs with significantly higher % of binding to Fr l and a greater % of Tregs expressing NEO-201 target antigen in cancer patients compared to HD. It is conceivable that naïve Tregs in cancer patients express high levels of Core 1 O-glycans. Furthermore, when subjected to TCR stimulation, naïve Tregs undergo proliferation and differentiate into eTregs."

Hematological Malignancies • Oncology • Solid Tumor • CD8 • FOXP3 • IL2RA • IL7R

NEO-201-recognized truncated Core 1 O-glycans represent a new target for CAR-NK therapy in AML (AACR 2026) - P1/2 | "This study identifies Core 1 O-glycans recognized by NEO-201 as a novel AML-associated antigen present across multiple subtypes and largely absent from early hematopoietic progenitors. The potent antileukemic activity of NEO-201CAR NK cells in preclinical systems highlights the promise of this approach and sets the stage for advancing O-glycan-directed CAR NK therapy into translational and clinical development."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • CD34 • FLT3 • IL2

IL 15 enhances preclinical efficacy of anti-core 1 O-glycans monoclonal antibody NEO-201 against human endometrial and ovarian cancer. (PubMed, Front Immunol) - "A previous study showed that IL-15 superagonist complex (N-803) enhanced ADCC activity mediated by NEO-201 in vitro against several human carcinoma cells, by modulating NK cells activation and cytotoxicity. In this study we demonstrated that IL-15 enhanced ADCC mediated by NEO-201 in vitro against human endometrial and ovarian cancer cell lines expressing NEO-201 target antigen, and that the combination of IL-15 and NEO-201, using purified human NK cells as effectors, had a modest effect in prolonging the survival of mice bearing human ovarian cancer, compared to IL-15 or NEO-201 alone. The ability of IL-15 to enhance NEO-201 efficacy, with NK cells as effectors, supports the hypothesis of combining NEO-201 and IL-15 with NK cell therapy (i.e. IL-15-secreting CAR-NK cells with a longer IL-15 in vivo half-life and stronger NK activity) for the treatment of gynecological cancers expressing O-glycans recognized by NEO-201."

Journal • Preclinical • Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • IL15

NEO-201-based CAR NK cells as a novel immunotherapeutic approach to target truncated core 1 O-glycans in AML (ASH 2025) - P1/2 | "NEO-201 targets truncated core 1 O-glycans selectively expressed on some AML cells and late-stage myeloid cells, while sparing CD34⁺ HSCs. These findings highlight the NEO-201–recognized antigen as a promising immunotherapeutic target in AML. This is the first study to characterize expression of the NEO-201–target antigen across a broad panel of AML cell lines and assess its targeting using NK-based platforms."

IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Solid Tumor • CD34 • FLT3 • IL2 • KMT2A

QUILT-3.017: Study of NEO-201 in Solid Tumors Expansion Cohorts (clinicaltrials.gov) - P1/2 | N=121 | Recruiting | Sponsor: Precision Biologics, Inc | Trial completion date: Oct 2026 ➔ Jan 2029 | Trial primary completion date: Oct 2025 ➔ Jan 2028

Trial completion date • Trial primary completion date • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer • ALK1 • BRAF • EGFR • MSI • PD-L1 • ROS1 • TMB

Generation of the therapeutic monoclonal antibody NEO-201, derived from a cancer vaccine, which targets human malignancies and immune suppressor cells. (PubMed, Expert Rev Vaccines) - "To overcome the problem of poor clinical efficacy of cancer vaccines, due to the activity of immunosuppressive cells, cancer vaccines could be combined with other immunotherapeutics able to deplete immunosuppressive cells. Results from clinical trials, employing NEO-201 alone or in combination with pembrolizumab, showed that durable stabilization of disease after treatment was due to the ability of NEO-201 to target and reduce the percentage of circulating Tregs and gMDSCs.These findings provide compelling support to combine NEO-201 with cancer vaccines to reintegrate their ability to elicit a robust and durable immune adaptive response against cancer."

Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor

Precision Biologics Announces the United States Patent and Trademark Office (USPTO) has granted a Patent for its Lead Monoclonal Antibody, NEO-201, For Methods and Compositions for Targeting Treg Cells (PRNewswire) - "Precision Biologics...announced today that on July 16, 2024, the USPTO granted another patent for its lead clinical asset, NEO-201, which is currently being tested in Phase 2 human Clinical Trials in the US....The patent granted by USPTO on July 16, 2024 (Patent No. US 12,037,410B2) describes the ability of NEO-201 to bind to Treg cells, and its use in targeting Treg cells. NEO-201 may be used for isolation and detection of Treg cells. In addition, the patent claims that NEO-201 can mediate the killing of Treg cells through complement mediated cytotoxicity (CDC) in vitro. Therapeutic methods and combination therapies using NEO-201 in combination with another anti-cancer agent are also described in the patent."

Patent • Oncology • Solid Tumor

Tregs, gMDSCs, and levels of soluble MICA as prognostic biomarkers for combined NEO-201 and pembrolizumab. (ASCO 2024) - P1/2 | "Depletion of circulating Tregs and gMDSCs may prevent their accumulation in the TME and enhance the efficacy of pembrolizumab in subjects with tumors resistant to checkpoint inhibitors. The decrease in circulating nTregs and gMDSCs after treatment with NEO-201 and pembrolizumab was associated with durable SD. High levels of sMICA can impair ADCC mediated by NEO-201, resulting in poor clinical response."

Biomarker • IO biomarker • Cervical Cancer • Head and Neck Cancer • Hematological Malignancies • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CD14 • CD33 • CEACAM8 • FOXP3

Precision Biologics to Present at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 1st, 2024 (PRNewswire) - P1/2 | N=121 | NCT03476681 | Sponsor: Precision Biologics, Inc | "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....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."

Biomarker • P2 data • Cervical Cancer • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer

QUILT-3.017: Study of NEO-201 in Solid Tumors Expansion Cohorts (clinicaltrials.gov) - P1/2 | N=121 | Recruiting | Sponsor: Precision Biologics, Inc | Trial completion date: Oct 2025 ➔ Oct 2026 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Trial completion date • Trial primary completion date • Cervical Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer • ALK1 • BRAF • EGFR • MSI • PD-L1 • ROS1 • TMB

The rationale for the combination of the monoclonal antibody NEO-201 with Immune Checkpoint Inhibitors (ICI) (FOB-USA 2024) - "What is the epitope that NEO-201 targets on cancer cellsWhat are the mechanism of actions of the NEO-201 IgG1 mabWhat are the preliminary results from clinical trials using NEO-201"

Checkpoint inhibition • Oncology

Precision Biologics to Present at the American Association for Cancer Research (AACR) Annual Meeting on April 8th, 2024 (PRNewswire) - P2 | N=121 | NCT03476681 | Sponsor: Precision Biologics, Inc | "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...on April 8^th, 2024...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....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..."

P2 data • Oncology • Solid Tumor

EXPRESSION OF NEO-201 MAY HELP IN THE DIFFERENTIAL DIAGNOSIS BETWEEN MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA (SIE 2023) - "Conclusion. Expression of NEO-201 is not found in blasts, immature cells, and monocytes of the analyzed patients, contrary a CD15+ neutrophil granulocytes where NEO-201 is positive, supporting the proposal to integrate NEO-201 as a marker in the differential diagnosis, leaving open the possibility of use as a future antitumor agent."

IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Solid Tumor • CD14 • CD34 • PTPRC • SDC1

Post-treatment neutrophil-to-lymphocyte ratio and gMDSCs as independent prognostic factors for treatment efficacy with monoclonal antibody NEO-201 and pembrolizumab (SITC 2023) - P1/2 | "In our study, patients with SD had a downtrend of circulating gMDSCs, arginase-1 levels and normal to mild NLR compared to patients with PD, suggestive of good prognosis for treatment with NEO-201 and pembrolizumab (figures 1 and 2). Ongoing enrollment in this clinical trial will validate these findings in larger cohorts."

Biomarker • Clinical • IO biomarker • Oncology • Solid Tumor • CD33 • CEACAM8

Precision Biologics to Present at the Society for Immunotherapy of Cancer (SITC) Annual Meeting on November 3rd, 2023 (PRNewswire) - P1/2 | N=121 | NCT03476681 | Sponsor: Precision Biologics, Inc | "This study demonstrates that NEO-201 binds to gMDSCs in PBMCs from cancer patients. This poster also reports that following treatment, heavily pre-treated patients with durable stable disease showed a reduction of circulating gMDSCs compared to baseline levels. Additional data from the ongoing Phase 2 trial was recently presented at CRI-ENCI-AACR 7th International Cancer Immunotherapy Conference Sept 22, 2023, Milan, Italy. This data demonstrated that NEO-201 reduces the quantity of regulatory T cells in PBMCs of cancer patients and this reduction is associated with stabilization of disease."

P2 data • Oncology • Solid Tumor

Precision Biologics Announces the United States Patent and Trademark Office (USPTO) has granted a Patent for its Lead Monoclonal Antibody, NEO-201, For the Treatment of Human Carcinomas (PRNewswire) - "Precision Biologics, Inc...announced today that on September 26, 2023, the USPTO granted a patent for its lead clinical asset, NEO-201, which is currently being tested in Phase 2 human Clinical Trials in the US."

Patent • Oncology • Solid Tumor

Precision Biologics Announces the United States Patent and Trademark Office (USPTO) has granted a Patent for its Lead Monoclonal Antibody, NEO-201, For the Treatment of Human Carcinomas (PRNewswire) - P2 | N=121 | NCT03476681 | Sponsor: Precision Biologics, Inc | "Based on the safety and activity of NEO-201 in its Phase I completed study, a Phase II study is currently enrolling patients with metastatic Non-Small Cell Lung Cancer (NSCLC), Head and Neck Cancer, Endometrial Cancer and Cervical Cancer, whose disease has previously progressed through prior checkpoint inhibitor therapy (including prior Keytruda)....Data from the ongoing Phase 2 trial was recently presented at CRI-ENCI-AACR 7th International Cancer Immunotherapy Conference Sept 22, 2023, Milan, Italy. This data demonstrated that NEO-201 reduces the quantity of regulatory T cells in PBMCs of cancer patients and this reduction is associated with stabilization of disease."

P2 data • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Uterine Cancer

EXPRESSION OF NEO-201 MAY HELP IN THE DIFFERENTIAL DIAGNOSIS BETWEEN MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID LEUKEMIA (EHA 2023) - "Expression of NEO-201 is not found in blasts, immature cells, and monocytes of the analyzed patients, contrary a CD15+ neutrophil granulocytes where NEO-201 is positive, supporting the proposal to integrate NEO-201 as amarker in the differential diagnosis between AML and MDS and in monitoring the course of patients, leaving open the possibility of use as a future antitumor agent. Flow cytometry, Monoclonal antibody, Myelodysplastic syndrome, Acute myeloid leukemia"

IO biomarker • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Psychiatry • Solid Tumor • CD14 • CD34 • KIT • PTPRC • SDC1

Phase II study combining an anti-core 1 O-glycans targeting humanized monoclonal antibody NEO-201 with pembrolizumab in adults with chemo-resistant solid tumors. (ASCO 2023) - P1/2 | "NEO-201 has demonstrated the ability to bind and kill iSCs in vitro and this phenomenon was observed in the initial first in human clinical study. This Phase II study was designed to determine if NEO-201 can reactivate the effectiveness of checkpoint inhibitor therapy in subjects who previously progressed on check point therapy. The safety of combining NEO-201 with pembrolizumab has been successfully established and all 4 disease cohorts are now open to accrual with response rate as the primary endpoint."

Clinical • P2 data • Anemia • Cervical Cancer • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Uterine Cancer

A therapeutic humanized anti-carcinoma monoclonal antibody (mAb) NEO-201 can also target human granulocytic myeloid-derived suppressor cells (gMDSCs) and regulatory T (Tregs) cells (AACR 2023) - "This study demonstrated that NEO-201 can be used to identify and kill suppressive gMDSCs in addition to Treg cells. Depletion of suppressive Tregs and gMDSCs in the TME could be an effective strategy to prevent hyperprogressive disease when anti-PD-1 is used in cancer immunotherapy. These data support the rationale for the ongoing phase II clinical trial using NEO-201 in combination with pembrolizumab in checkpoint refractory patients with metastatic solid tumors."

Myeloid-derived suppressor cells • Hematological Malignancies • Oncology • Solid Tumor • CD14 • CD33 • CEACAM1 • CEACAM5 • CEACAM8 • CSF2 • FOXP3 • IL2RA • IL6 • IL7R • ITGAM

Precision Biologics Announces Publication Of First-In-Human Phase 1 Clinical Trial With NEO-201 (Businesswire) - P1 | N=121 | NCT03476681 | Sponsor: Precision Biologics | "In the Phase I clinical trial, NEO-201 was found to reduce immune suppressive cells that may be responsible in diminishing cancer-killing activity for checkpoint inhibitors like Keytruda. This ongoing Phase 2 trial is testing to see if combining of NEO-201 with Keytruda can reactivate the effectiveness of checkpoint inhibitors when they don’t work alone."

P1 data • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

First-in-human phase 1 clinical trial of anti-core 1 O-glycans targeting monoclonal antibody NEO-201 in treatment-refractory solid tumors. (PubMed, J Exp Clin Cancer Res) - P1/2 | "NEO-201 was safe and well tolerated at the MTD of 1.5 mg/kg, with neutropenia being the most common adverse event. Furthermore, a reduction in the percentage of regulatory T cells following NEO-201 treatment supports our ongoing phase II clinical trial evaluating the efficiency of the combination of NEO-201 with the immune checkpoint inhibitor pembrolizumab in adults with treatment-resistant solid tumors."

IO biomarker • Journal • P1 data • Breast Cancer • Colorectal Cancer • Febrile Neutropenia • Gastrointestinal Cancer • Hematological Disorders • Immune Modulation • Neutropenia • Oncology • Pancreatic Cancer • Solid Tumor

A therapeutic humanized anti-carcinoma monoclonal antibody (mAb) can also identify immunosuppressive regulatory T (Tregs) cells and down regulate Treg-mediated immunosuppression (SITC 2021) - P=N/A, P1/2 | "In addition, NEO-201 mAb can kill these isolated Treg cells through CDC. Conclusions This study demonstrated that the small subset of NEO-201+CD4+ T cell in human PBMCs are highly suppressive Treg cells and NEO-201 can be used as a novel marker to identify functionally suppressive Treg cells, Furthermore, NEO-201 can kill Treg cells through CDC, presenting an opportunity for therapeutic intervention to increase anti-tumor immunity."

IO biomarker • Oncology • Solid Tumor • CD4 • CD73 • CD8 • CEACAM1 • CEACAM5 • ENTPD1 • FOXP3 • IL2RA • IL7R

[VIRTUAL] Activating innate immune response as strategy for endometrial cancer treatment (AACR-II 2020) - P1 | "NEO-201 in combination with IL15 showed promising results in activating NK cells against endometrial cancer cells in vitro. Additional in vitro and in vivo studies are ongoing to optimize the combination and to correlate its activity with cells’ biological characteristics."

Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Uterine Cancer • CTNNB1 • HER-2 • KRAS • NRAS