APG 101.10 / Allostera - LARVOL DELTA

ASUNERCEPT PLUS RADIOTHERAPY IN RELAPSED GLIOBLASTOMA. UPDATE ON FIVE YEARS OVERALL SURVIVAL OF STUDY NCT01071837 AND DEVELOPMENT OF A POPULATION-PK - TUMOR GROWTH INHIBITION - SURVIVAL MODEL (SNO 2018) - P2; "Asunercept (APG101) is an Fc-fusion protein consisting of the extracellular domain of human CD95 (APO-1/Fas) and the Fc domain of IgG1. A PopPK-TGI-Survival model for asunercept and radiotherapy treated patients was developed. A clear inhibitory effect of asunercept exposure was observable on tumor growth resulting in an increased survival. A recent update on OS of study NCT01071837 revealed that 7% of Asunercept+RT treated 2nd-line GB patients were alive after 5 years compared to 0% in patients treated with RT alone."

Clinical • Brain Cancer • Oncology • Solid Tumor

Clinical Response to the CD95-Ligand Inhibitor Asunercept Is Defined by a Pro-Inflammatory Serum Cytokine Profile. (PubMed, Cancers (Basel)) - "Asunercept (APG101) is a well-tolerated CD95-ligand inhibitor that showed promising efficacy in a prospective, single-arm phase I study in anemic, transfusion-dependent patients with low and intermediate risk myelodysplastic syndrome (MDS). Furthermore, non-responding patients showed a distinct, pro-inflammatory serum cytokine profile which was persistent throughout the first half of the treatment phase and appeared unaffected by asunercept. Although prospective validation is required, our post hoc analysis suggests that serum cytokine profiling based on IL-18, S100A9 and soluble p53 may represent an approach to identify and select low-risk MDS patients most likely to benefit from asunercept treatment."

Clinical • Journal • Fibrosis • Hematological Disorders • Hematological Malignancies • Immunology • Inflammation • Myelodysplastic Syndrome • Myelofibrosis • Oncology • FAS • IL18 • S100A9

N2M2 (NOA20) phase I/II trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed non-MGMT hypermethylated glioblastoma. (PubMed, Neuro Oncol) - "Patients with glioblastoma without O6-methylguanine-DNA methyltransferase (MGMT) promoter hypermethylation are unlikely to benefit from alkylating chemotherapy with temozolomide (TMZ)...Stratification for Treatment takes place in 5 subtrials, including alectinib, idasanutlin, palbociclib, vismodegib, and temsirolimus as targeted therapies, according to the best matching molecular alteration. Patients without matching alterations are randomized between subtrials without strong biomarkers using atezolizumab and asinercept (APG101) and the standard of care, TMZ...Stratification for Treatment takes place in 5 subtrials, including alectinib, idasanutlin, palbociclib, vismodegib, and temsirolimus as targeted therapies, according to the best matching molecular alteration. Patients without matching alterations are randomized between subtrials without strong biomarkers using atezolizumab and asinercept (APG101) and the standard of care, TMZ...For the phase I parts, a Bayesian..."

Biomarker • Clinical • Journal • P1/2 data • Brain Cancer • Glioblastoma

[VIRTUAL] Sequential Ganz-Exome sequencing analyzes show partial clonal response in treating MDS patients with asunercept (DGHO 2020) - "Asunercept (APG101) is a novel therapeutic fusion protein blocking the interaction between CD95 and its ligand and has previously been evaluated in a clinical phase I trial for transfusion dependent low risk MDS patients (Boch T et al. In summary, this is a successful proof of principle study showing the feasibility to perform clonal evolution analysis accompanying a clinical trial. Promising clinical activity has been observed in some patient. Our results indicate that particular subclones with molecular alterations of methylation pathways may be susceptible to treatment with Asunercept and warrant further studies, e.g. in combination with erythropoiesis stimulating agents."

Clinical • DNMT3A • FAS • IDH2 • TET2 • TNFA

[VIRTUAL] Sequential Ganz-Exome sequencing analyzes show partial clonal response in treating MDS patients with asunercept (DGHO 2020) - "Asunercept (APG101) is a novel therapeutic fusion protein blocking the interaction between CD95 and its ligand and has previously been evaluated in a clinical phase I trial for transfusion dependent low risk MDS patients (Boch T et al. In summary, this is a successful proof of principle study showing the feasibility to perform clonal evolution analysis accompanying a clinical trial. Promising clinical activity has been observed in some patient. Our results indicate that particular subclones with molecular alterations of methylation pathways may be susceptible to treatment with Asunercept and warrant further studies, e.g. in combination with erythropoiesis stimulating agents."

Clinical • DNMT3A • FAS • IDH2 • TET2 • TNFA

[VIRTUAL] Sequential Ganz-Exome sequencing analyzes show partial clonal response in treating MDS patients with asunercept (DGHO 2020) - "Asunercept (APG101) is a novel therapeutic fusion protein blocking the interaction between CD95 and its ligand and has previously been evaluated in a clinical phase I trial for transfusion dependent low risk MDS patients (Boch T et al. In summary, this is a successful proof of principle study showing the feasibility to perform clonal evolution analysis accompanying a clinical trial. Promising clinical activity has been observed in some patient. Our results indicate that particular subclones with molecular alterations of methylation pathways may be susceptible to treatment with Asunercept and warrant further studies, e.g. in combination with erythropoiesis stimulating agents."

Clinical • DNMT3A • FAS • IDH2 • TET2 • TNFA

[VIRTUAL] Sequential Ganz-Exome sequencing analyzes show partial clonal response in treating MDS patients with asunercept (DGHO 2020) - "Asunercept (APG101) is a novel therapeutic fusion protein blocking the interaction between CD95 and its ligand and has previously been evaluated in a clinical phase I trial for transfusion dependent low risk MDS patients (Boch T et al. In summary, this is a successful proof of principle study showing the feasibility to perform clonal evolution analysis accompanying a clinical trial. Promising clinical activity has been observed in some patient. Our results indicate that particular subclones with molecular alterations of methylation pathways may be susceptible to treatment with Asunercept and warrant further studies, e.g. in combination with erythropoiesis stimulating agents."

Clinical • DNMT3A • FAS • IDH2 • TET2 • TNFA

APG101 in Myelodysplastic Syndrome (clinicaltrials.gov) - P1; N=18; Active, not recruiting; Sponsor: Apogenix GmbH; Recruiting -> Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Biosimilar • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

APG101 in Myelodysplastic Syndrome (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Apogenix GmbH; Trial primary completion date: Jun 2015 ->Nov 2015

Trial primary completion date • Biosimilar • Hematological Malignancies • Inflammation • Myelodysplastic Syndrome • Oncology

SAFETY AND EFFICACY OF THE CD95-LIGAND INHIBITOR ASUNERCEPT IN TRANSFUSION-DEPENDENT PATIENTS WITH LOW AND INTERMEDIATE RISK MDS. (MDS 2017) - "...Asunercept (APG101) is a fusion protein consisting of the extracellular domain of human CD95 and the Fc domain of human IgG1...In conclusion, asunercept was very well tolerated and showed efficacy in a subset of transfusion-dependent MDS patients. It is an promising compound with a new mechanism of action that warrants for further clinical investigation, particularly in combination with erythropoiesis stimulating agents."

Clinical • Retrospective data • Biosimilar • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Blockade of CD95/CD95L Death Signaling Enhances CAR T Cell Persistence and Antitumor Efficacy (ASH 2019) - "Through specific blocking of the CD95-CD95L pathway, the CD95L inhibitor APG101 (Asunercept, Apogenix AG, Heidelberg) could prevent activated T cells from AICD. CD95L blockade enhanced CAR T cell survival and promoted killing of tumor cells in vitro. Combining CAR T cell therapy with CD95L inhibitor might improve CAR T cell persistence in vivo and thus enhance the effect of CAR T cell therapy."

CAR T-Cell Therapy • Clinical • IO Biomarker • CD8 • FAS • PD-1

Asunercept as an innovative therapeutic approach for recurrent glioblastoma and other malignancies. (PubMed, Cancer Manag Res) - "Asunercept is a first-in-class recombinant glycosylated fusion protein, which has been designed to selectively bind to CD95L and therefore disrupt CD95/CD95L signaling. The current report provides a brief overview of the role of the CD95/CD95L signaling pathway in cancer pathogenesis and discusses how asunercept was designed to bind and neutralize CD95L and disrupt signaling thereby potentially improving outcomes in glioblastoma and other malignancies."

Journal