A Pilot Study of Intratumorally and Intraparenchymally Administered OS2966 Using Convection-enhanced Delivery in Patients With Recurrent/Progressive High-grade Glioma Undergoing a Clinically-indicated Surgical Resection

The primary goal of this Phase 1 study is to determine if a new investigational drug, OS2966, when delivered directly to the brain of adult participants with recurrent/progressive high-grade glioma (HGG) is safe and well tolerated.
OS2966 is a therapeutic antibody blocking a cell surface receptor governing fundamental biological processes that allow cancer cells to grow, spread and become resistant to cancer treatment. Despite availability of new promising cancer treatments, successful treatment of HGG has been limited by the presence of the brain's protective blood brain barrier (BBB). The BBB is made up of tightly knit cells that block entry of several substances including cancer treatments. To overcome this obstacle, a technique called convection-enhanced-delivery (CED) will be utilized to deliver OS2966 directly to the site of disease. Convection-enhanced delivery involves placement of one or more catheters into the brain tumor and tumor-infiltrated brain in order to slowly pump a therapy into the tissue.
To be eligible for this study participants must require surgical resection of their recurrent HGG.

Start Date02 Mar 2021

Sponsor / Collaborator

OncoSynergy, Inc.

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100 Clinical Results associated with OS-2966

100 Translational Medicine associated with OS-2966

100 Patents (Medical) associated with OS-2966

Literatures (Medical) associated with OS-2966

22 Jun 2021·JCI InsightQ1 · MEDICINE

Role of c-Met/β1 integrin complex in the metastatic cascade in breast cancer

Q1 · MEDICINE

ArticleOA

Author: Yagnik, Garima ; Lau, Darryl ; Shah, Sumedh S ; Nguyen, Alan T ; Chandra, Ankush ; Safaee, Michael M ; Aghi, Manish K ; Sudhir, Sweta ; Jahangiri, Arman ; Spatz, Jordan M ; Cheng, Justin ; Jain, Saket ; Pappu, Ananya ; Wadhwa, Harsh ; Chang, Alexander Chih-Chieh

Metastases cause 90% of human cancer deaths. The metastatic cascade involves local invasion, intravasation, extravasation, metastatic site colonization, and proliferation. Although individual mediators of these processes have been investigated, interactions between these mediators remain less well defined. We previously identified a complex between receptor tyrosine kinase c-Met and β1 integrin in metastases. Using cell culture and in vivo assays, we found that c-Met/β1 complex induction promoted intravasation and vessel wall adhesion in triple-negative breast cancer cells, but did not increase extravasation. These effects may have been driven by the ability of the c-Met/β1 complex to increase mesenchymal and stem cell characteristics. Multiplex transcriptomic analysis revealed upregulated Wnt and hedgehog pathways after c-Met/β1 complex induction. A β1 integrin point mutation that prevented binding to c-Met reduced intravasation. OS2966, a therapeutic antibody disrupting c-Met/β1 binding, decreased breast cancer cell invasion and mesenchymal gene expression. Bone-seeking breast cancer cells exhibited higher levels of c-Met/β1 complex than parental controls and preferentially adhered to tissue-specific matrix. Patient bone metastases demonstrated higher c-Met/β1 complex than brain metastases. Thus, the c-Met/β1 complex drove intravasation of triple-negative breast cancer cells and preferential affinity for bone-specific matrix. Pharmacological targeting of the complex may have prevented metastases, particularly osseous metastases.

01 Aug 2020·Lab AnimalQ1 · AGRICULTURAL & FORESTRY SCIENCE

Endpoint in ovarian cancer xenograft model predicted by nighttime motion metrics

Q1 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Carbonell, Anne-Marie E ; Nwagwu, Chibueze D ; Defensor, Erwin ; Carbonell, W Shawn ; Jiang, Michael Y ; Rolle-McFarland, Danelle A

Despite several therapeutics showing promise in nonclinical studies, survival from ovarian cancer remains poor. New technologies are urgently needed to optimize the translation of nonclinical studies into clinical successes. While most nonclinical settings utilize subjective measures of physiological parameters, which can hamper the accuracy of the results, this study assessed the physical activity of mice in real time using an objective, non-invasive, cloud-based, digital vivarium monitoring platform. An initial range-finding study in which varying numbers of ovarian cancer cells were inoculated in mice was conducted to characterize disease progression using digital metrics such as motion and breathing rate. Data from the range-finding study were used to establish a motion threshold (MT) that might predict terminal endpoint. Using the MT, the efficacies of cisplatin and OS2966, an anti-CD29 antibody, were assessed. Results showed that MT predicted terminal endpoint significantly earlier than traditional parameters and correlated with therapeutic efficacy. Thus, continuous motion monitoring sensitively predicts terminal endpoint in nonclinical ovarian cancer models and could be applicable for drug efficacy testing.

01 Aug 2019·Targeted OncologyQ3 · MEDICINE

A Monoclonal Antibody Against β1 Integrin Inhibits Proliferation and Increases Survival in an Orthotopic Model of High-Grade Meningioma

Q3 · MEDICINE

Article

Author: Kiyokawa, Juri ; Carbonell, W Shawn ; Gurtner, Alessandra ; Martuza, Robert L ; Rabkin, Samuel D ; Wakimoto, Hiroaki ; Kawamura, Yoichiro ; Nigim, Fares ; Kasper, Ekkehard M ; Brastianos, Priscilla K ; Cahill, Daniel P ; Hua, Lingyang

BACKGROUNDHigh-grade meningiomas (HGMs; World Health Organization [WHO] classification grade II and III) have high relapse rates and poor clinical outcomes despite surgery and radiation treatments. No effective medical therapy currently exists for HGMs, and developing novel therapeutic strategies depends on the identification of molecular drivers. In cancer, β1 integrin enhances malignant characteristics, including proliferation, invasion, and drug resistance.OBJECTIVEWe conducted this study to investigate whether β1 integrin could be a therapeutic target in HGMs.PATIENTS AND METHODSExpression of β1 integrin was examined in gene array datasets, with proteomics of clinical meningioma specimens, and in patient-derived HGM xenografts. Anti-tumor activity of OS2966, a first-in-class humanized antagonizing monoclonal antibody against β1 integrin, was tested in vitro and in vivo using an orthotopic mouse model of patient-derived malignant meningioma.RESULTSβ1 integrin was expressed in meningiomas of all WHO grades and two xenografts tested. In vitro, OS2966 suppressed the viability of NF2-deficient MN3 sphere cells and NF2-wild-type IOMM-Lee malignant meningioma cells only when plated on laminin-coated plastic. While OS2966 decreased phosphorylation of ERK1/2 in both MN3 cells and laminin-grown IOMM-Lee cells, OS2966 only affected the phosphorylation of FAK (Tyr397) in MN3, and of Akt (Ser473) in IOMM-Lee cells, respectively, indicating differential pathway inhibition. Systemic administration of OS2966 in mice bearing orthotopic MN3 HGMs inhibited HGM cell proliferation and significantly extended overall survival of the treated mice.CONCLUSIONSβ1 Integrin may be a therapeutic target in HGMs, and further preclinical and clinical development of OS2966 for HGM therapy is warranted.

100 Deals associated with OS-2966

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma	Phase 2	-	OncoSynergy, Inc.	25 Apr 2022
Acute Lymphoblastic Leukemia	IND Application	-	OncoSynergy, Inc.	25 Apr 2022
Acute Myeloid Leukemia	IND Application	-	OncoSynergy, Inc.	25 Apr 2022
Brain Injuries, Traumatic	IND Application	-	OncoSynergy, Inc.	25 Apr 2022
Psoriasis	IND Application	-	OncoSynergy, Inc.	25 Apr 2022
Ovarian Cancer	Preclinical	US	OncoSynergy, Inc.	16 May 2024
Glioblastoma Multiforme	Preclinical	US	OncoSynergy, Inc.	02 Mar 2021
High grade glioma	Preclinical	US	OncoSynergy, Inc.	02 Mar 2021
Malignant glioma of brain	Preclinical	US	OncoSynergy, Inc.	02 Mar 2021
Recurrent Malignant Glioma	Preclinical	US	OncoSynergy, Inc.	02 Mar 2021

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