CD200AR-L / OX2 Therap - LARVOL DELTA

CD200AR-L and Allogeneic Tumor Lysate Vaccine Immunotherapy for Recurrent HGG and Newly Diagnosed DMG/DIPG in Children and Young Adults (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: OX2 Therapeutics

New P1 trial • Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Orphan Designation: Treatment of malignant glioma (FDA) - Date Designated: 08/29/2023

Orphan drug • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Trap and ambush therapy using sequential primary and tumor escape-selective oncolytic viruses. (PubMed, Mol Ther Oncolytics) - "This also facilitated the priming of anti-tumor T cell responses, which could be further exploited using immune checkpoint blockade with the CD200 activation receptor ligand (CD200AR-L) peptide. Our findings here are significant in that they offer the possibility to develop oncolytic viruses as highly specific, escape-targeting viro-immunotherapeutic agents to be used in conjunction with recurrence of tumors following multiple different types of frontline cancer therapies."

IO biomarker • Journal • Oncolytic virus • Immune Modulation • Melanoma • Oncology • Solid Tumor • CD200 • IFNB1

Circulating immune biomarkers in peripheral blood reflect the effect of a CD200 immune checkpoint targeted immunotherapy in pet dogs with high-grade glioma (AACR 2022) - P1 | "This therapy consists of an alternative checkpoint inhibitor peptide (CD200AR-L) that modulates the CD200 immune checkpoint, currently being used in an adult phase I safety trial for recurrent glioblastoma trial (NCT04642937) and a canine high-grade spontaneous glioma trial (U01CA224160-01)...These data showed that peripheral immune cell phenotypes were linked to the outcome of the immunotherapy, thus dogs with better immune cell profiles, including increased cytotoxic differentiation, had a better prognosis and longer overall survival rates. Taken together, these results suggest that variation in patient responsiveness can be explained by differences in peripheral immune cell proliferation and differentiation soon after the initiation of immunotherapy."

Biomarker • IO biomarker • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CD200

Study of CD200 Activation Receptor Ligand (CD200AR-L) and Allogeneic Tumor Lysate Vaccine Immunotherapy for Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: OX2 Therapeutics | Trial completion date: Nov 2023 ➔ Nov 2024 | Trial primary completion date: Nov 2022 ➔ Nov 2023

Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

First in human CD200 activation receptor ligand and tumor lysate vaccine immunotherapy for recurrent glioblastoma in adults (AACR 2022) - P1 | "CD200AR-L is administered on days 1 and 2 by suprascapular intradermal injection following the application of topical imiquimod. Patients are monitored for adverse events, including immune-mediated intracranial edema and other immune-related complications, and their neurological function is scored per NANO criteria. Correlative studies include immune monitoring (including expression of CD200R1, PD1/PD-L1, and CTLA-4) and MRI imaging assessment per iRANO criteria."

Clinical • IO biomarker • P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CD200

CD200AR-L: mechanism of action and preclinical and clinical insights for treating high-grade brain tumors. (PubMed, Expert Opin Investig Drugs) - No abstract available

Journal • Preclinical • Brain Cancer • Glioblastoma • Immune Modulation • Inflammation • Oncology • Solid Tumor • CD200

First-in-human phase 1 study of CD200 Activation Receptor-Ligand(CD200AR-L) and Allogeneic Tumor Lysate Vaccine Immunotherapy for Recurrent Glioblastoma: Initial results from an ongoing clinical trial (SNO 2021) - P1 | "METHODS Single-center, first-in-human, dose-escalation phase 1 clinical trial (NCT04642937) utilizing a 3 + 3 design initiated accrual in 12/2020 at dose level-1; CD200AR-L 3.75micrograms/kg/dose administered on days 1 and 2 by intradermal injection after topical imiquimod...RESULTS Between 12/2020 to 3/2021, 6 patients were enrolled on dose level-1; aged 37-65 years, 4 men, all with KPS >/= 80, and 3 patients on daily dexamethasone (4mg (n=2), 2mg (n=1))...IrICE symptoms were temporarily mitigated with ‘bevacizumab rescue protocol.’ No patients had local injection site reactions...CONCLUSION Initial dosing of CD200AR-L was well tolerated with early positive signal of immunological effect. Enrollment continues, now at dose level-2; CD200AR-L at 5micrograms/kg/dose."

Clinical • IO biomarker • P1 data • Brain Cancer • CNS Disorders • Glioblastoma • Hematological Disorders • Immunology • Oncology • Solid Tumor • CD14 • CD200 • CTLA4 • MGMT

Unique glioblastoma treatment sees encouraging early results during phase 1 clinical trials - P1, N=24; NCT04642937; Sponsor: OX2 Therapeutics; “OX2 Therapeutics, Inc….encouraging early results from phase 1 human trials of their new cancer treatment. Developed to combat recurrent high-grade brain tumors, the treatment utilizes a newly developed peptide inhibitor. ‘OX2 works to explore the therapeutic potential of the new immune checkpoint agent, CD200AR-L’…‘Our team of doctors developed the new peptide inhibitor with high binding affinity to the immune activation receptor. This activates an anti-tumor response and simultaneously downregulates the inhibitory PD-1/PD-L1 and CTLA-4 and a major immune checkpoint CD200 inhibitory receptor’.…This new mechanism is especially important in combating high grade brain tumors that typically evade the immune system and traditional treatments….CD200AR-L, is a single peptide that has the potential to replace the toxic antibody therapies that are currently used to block immune checkpoints.”

P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology

Study of CD200 Activation Receptor Ligand (CD200AR-L) and Allogeneic Tumor Lysate Vaccine Immunotherapy for Recurrent Glioblastoma (clinicaltrials.gov) - P1; N=24; Active, not recruiting; Sponsor: OX2 Therapeutics; Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

[VIRTUAL] Circulating immune cell phenotype dynamics reflect the effect of a CD200 immune checkpoint targeted immunotherapy in pet dogs with high-grade glioma (IMMUNOLOGY 2021) - P1 | "This therapy consists of an alternative checkpoint inhibitor peptide (CD200AR-L) that modulates the CD200 immune checkpoint, currently being used in an adult phase I safety trial for recurrent glioblastoma trial (NCT04642937) and a canine high-grade spontaneous glioma trial (U01CA224160-01)...These data showed that peripheral immune cell phenotypes were linked to the outcome of the immunotherapy, thus dogs with better immune cell profiles, including increased cytotoxic differentiation, had a better prognosis and longer overall survival rates. Taken together, these results suggest that variation in patient responsiveness can be explained by differences in peripheral immune cell proliferation and differentiation soon after the initiation of immunotherapy."

Brain Cancer • Glioblastoma • Glioma • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • CD200

CD200 Immune-Checkpoint Peptide Elicits an Anti-glioma Response Through the DAP10 Signaling Pathway. (PubMed, Neurotherapeutics) - "When we combined CD200AR-L with an immune-stimulatory gene therapy, in an intracranial GBM model in vivo, we observed increased median survival, and long-term survivors. These studies are the first to characterize the signaling pathway used by the CD200AR, demonstrating a novel strategy for modulating immune checkpoints for immunotherapy currently being analyzed in a phase I adult trial."

IO biomarker • Journal • Brain Cancer • Gene Therapies • Glioblastoma • Glioma • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • CD8 • PD-L1

New Treatment for Central Nervous System Tumors Enters Phase I Clinical Trials (Businesswire) - “OX2 Therapeutics, Inc…announces today that they treated their first patient in a phase one human trial of a new treatment developed to combat recurrent high-grade brain tumors…..OX2 Therapeutics treated their 1st patient January 6th in a phase one single center, open-label, dose-escalation clinical trial for recurrent glioblastoma under the direction of Elizabeth Neil, MD at the University of Minnesota.”

Trial status • Brain Cancer • Glioblastoma • Oncology

Study of CD200 Activation Receptor Ligand (CD200AR-L) and Allogeneic Tumor Lysate Vaccine Immunotherapy for Recurrent Glioblastoma (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: OX2 Therapeutics

New P1 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

[VIRTUAL] Use of A novel peptide ligand targeting multiple immune checkpoints: A novel approach to immunotherapy against Central Nervous System Tumors (SITC 2020) - "Moreover, CD200AR-L overpowers the suppressive effects of CD200 and PD-L1, which are both shed by tumors, by downregulating the inhibitory CD200R1 and PD-1 on both antigen-presenting cells (APC) and T-cells (figure 1), In addition, CD200AR-L downregulates PD-1 on APCs and inhibits the upregulation of PD-L1 and CTLA4.Download figure Open in new tab Download powerpoint Abstract 213 Figure 1 Mechanism of the CD200 Checkpoint Ligand Conclusions These studies led to the discovery that this novel peptide modulates the CD200, PD-1/PD-L1 and CTLA-4 pathways, providing the basis for the translatable development of a novel CD200 peptide inhibitor for clinical use against multiple tumors, including gliomas. These studies led to the FDA approval for the first in human peptide checkpoint inhibitor to initiate a phase I single center, open-label, dose-escalation clinical trial in adult patients with recurrent glioblastoma, to be followed by a clinical trial for children with recurrent..."

IO Biomarker • CNS Tumor • Glioblastoma • Glioma • Oncology • ITGAM

[VIRTUAL] USE OF A SINGLE PEPTIDE CHECKPOINT INHIBITOR FOR TREATMENT OF CENTRAL NERVOUS SYSTEM TUMORS (SNO 2020) - "We demonstrated that targeting the CD200AR with a checkpoint peptide ligand (CD200AR-L) activates the immune system and renders it impervious to the inhibitory effects of CD200...These studies led to the discovery that the novel peptide modulates the CD200, PD-1/PD-L1 and CTLA-4 pathways, providing the basis for the translatable development of a CD200-directed peptide for clinical use against multiple tumors including gliomas. These studies led to FDA approval of this peptide for the first in human phase I single center, open-label, dose-escalation clinical trial in adult and pediatric trial for children with recurrent malignant brain tumors."

Checkpoint inhibition • CNS Tumor • Glioma • Immune Modulation • Inflammation • Oncology • Pediatrics • Solid Tumor

[VIRTUAL] Use of A novel peptide ligand targeting multiple immune checkpoints: A novel approach to immunotherapy against Central Nervous System Tumors (SITC 2020) - "Moreover, CD200AR-L overpowers the suppressive effects of CD200 and PD-L1, which are both shed by tumors, by downregulating the inhibitory CD200R1 and PD-1 on both antigen-presenting cells (APC) and T-cells (figure 1), In addition, CD200AR-L downregulates PD-1 on APCs and inhibits the upregulation of PD-L1 and CTLA4.Download figure Open in new tab Download powerpoint Abstract 213 Figure 1 Mechanism of the CD200 Checkpoint Ligand Conclusions These studies led to the discovery that this novel peptide modulates the CD200, PD-1/PD-L1 and CTLA-4 pathways, providing the basis for the translatable development of a novel CD200 peptide inhibitor for clinical use against multiple tumors, including gliomas. These studies led to the FDA approval for the first in human peptide checkpoint inhibitor to initiate a phase I single center, open-label, dose-escalation clinical trial in adult patients with recurrent glioblastoma, to be followed by a clinical trial for children with recurrent..."

IO Biomarker • CNS Tumor • Glioblastoma • Glioma • Oncology • ITGAM

CD200 Checkpoint Reversal:A Novel Approach to Immunotherapy. (PubMed, Clin Cancer Res) - "These results support consideration of a CD200AR-L as a novel platform for immunotherapy against multiple cancers including glioblastoma multiforme."

IO Biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor