Apocept (asunercept) / Apogenix, CANbridge Pharma - LARVOL DELTA

Final results from N2M2/NOA-20 (SNO 2024) - "Background: MGMT promoter methylation determines benefit from temozolomide (TMZ)...In five subtrials (alectinib, idasanutlin, palbociclib, vismogedib and temsirolimus) patients were included according to the best matching molecular alteration... There is clinical activity of temsirolimus in patients with tumors harboring an activated mTOR pathway although this is not positively prognostic without mTOR inhibition; there is no clinical activity for asunercept and atezolizumab in not molecularly selected patients nor palbociclib in molecularly selected patients. Potential biomarkers will be discussed."

Clinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDK4 • CDKN2A • CDKN2B • MGMT

The role of CD95 in modulating CAR T-cell therapy: Challenges and therapeutic opportunities in oncology. (PubMed, Int Immunopharmacol) - "Furthermore, we characterize the therapeutic potential of CD95 targeted approaches, including CD95L inhibition (APG101) and alterations in CAR T cell manufacturing (tyrosine kinase inhibitors to mitigate fratricide). In this review, we highlight the importance of multi-path way strategies combining CD95 modulation with CAR T cell engineering to overcome resistance, specifically to target tumor cells better and sustain CAR T cell persistence to enhance treatment efficacy in solid tumors."

CAR T-Cell Therapy • Journal • Review • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • CASP8 • CFLAR • FAS

Efficacy and safety of asunercept, a CD95L-selective inhibitor, in hospitalised patients with moderate-to-severe COVID-19: ASUNCTIS, a multicentre, randomised, open-label, controlled, phase 2 trial. (PubMed, EClinicalMedicine) - P2 | "The compound was safe and well tolerated. Apogenix GmbH, Heidelberg, Germany."

Journal • P2 data • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • FAS

N2M2/NOA-20: Phase I/IIa umbrella trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation. (ASCO 2024) - P1/2 | "Background: Patients with glioblastoma without MGMT promoter hypermethylation are unlikely to benefit from temozolomide (TMZ)...The alectinib and vismodegib subtrials were closed since no molecularly matching patients were accrued; the idasanutlin subtrial was closed prior to the optimal dose at nine patients at discretion of the company providing the drug... N 2 M 2 allows for elaborate molecular testing being integrated into the treatment decision and efficient determination of treatment activity for patients with newly diagnosed glioblastoma. There is clinical activity of temsirolimus in patients with tumors harboring an activated mTOR pathway although this is not positively prognostic without mTOR inhibition; there is no clinical activity for asunercept and atezolizumab in not molecularly selected patients and also palbociclib in molecularly selected patients."

Clinical • P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • CDK4 • CDKN2A • CDKN2B

Letter to Editor: Treatment with the apoptosis inhibitor asunercept reduces clone sizes in patients with lower risk myelodysplastic neoplasms. (PubMed, Ann Hematol) - No abstract available

Journal • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms. (PubMed, Ann Hematol) - P1 | "Particularly early and pronounced reductions of clone sizes were found in subclones driven by mutations in genes involved in regulation of methylation (n = 1 DNMT3A, n = 1 IDH2, n = 1 TET2). Our results suggest that APG101 could be efficacious in reducing clone sizes of mutated hematopoietic cells in the bone marrow of Myelodysplastic Neoplasms, which warrants further investigation."

Journal • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • DNMT3A • FAS • FASLG • IDH2 • TET2 • TNFA

NCT Neuro Master Match - N²M² (NOA-20) (clinicaltrials.gov) - P1/2 | N=228 | Completed | Sponsor: University Hospital Heidelberg | Recruiting ➔ Completed | N=350 ➔ 228 | Trial completion date: Sep 2024 ➔ Feb 2023 | Trial primary completion date: Sep 2023 ➔ Feb 2023

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

CAN008 prolongs overall survival in patients with newly diagnosed GBM characterized by high tumor mutational burden. (PubMed, Biomed J) - "CAN008 combined with standard CCRT treatment prolonged the PFS and OS of newly diagnosed GBM patients compared to standard therapy alone. Higher treatment efficacy was associated with higher TMB."

Journal • Tumor mutational burden • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • TMB

ASUCOV: Asunercept for the Treatment of Patients With Moderate to Severe COVID-19 Disease (clinicaltrials.gov) - P3 | N=34 | Terminated | Sponsor: Apogenix GmbH | N=636 ➔ 34 | Trial completion date: Nov 2023 ➔ Aug 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2023 ➔ Aug 2023; Lack of patients

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease

ASUCOV: Asunercept for the Treatment of Patients With Moderate to Severe COVID-19 Disease (clinicaltrials.gov) - P3 | N=636 | Active, not recruiting | Sponsor: Apogenix AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

CANbridge to Continue CAN008 Phase 2 Trial in Glioblastoma Multiforme (GBM) in China Based on Interim Analysis of Independent Data Monitoring Committee (Businesswire) - "CANbridge Pharmaceuticals, Inc...announced that, based on the interim analysis recommendation of the independent data monitoring committee, it plans to continue the ongoing Phase 2 study of CAN008 in patients with newly diagnosed glioblastoma multiforme (GBM) in China to completion."

DSMB • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

BLOCKADE OF CD95/CD95L PATHWAY ENHANCES CAR T CELL PERSISTENCE AND ANTI-TUMOR EFFICACY IN VITRO AND IN VIVO (EBMT 2023) - "NSG mice were inoculated with CD19+ Nalm6 cells 0.5 x 105/mouse and an equal number of CD19.CART cells, followed by treatment of mice by APG101: 1mg/mouse, twice a weeks, i.v. Significant AICD of CAR T cells was observed after repeated antigenic stimulation, accompanied by an increased CD95L expression. Upregulation of CD95L after repeated antigen stimulation was reversed by APG101. CD95L blockade enhanced CAR T cell survival and promoted killing of tumor cells in vitro. Combining CAR T cell therapy with CD95L inhibitor improved CAR T cell persistence in vivo and thus enhanced the effect of CAR T cell therapy."

CAR T-Cell Therapy • IO biomarker • Preclinical • Oncology • CD19 • CD4 • CD8 • FAS • HAVCR2 • LAG3 • PD-1

CANbridge Announces Financial Results and Corporate Updates for Twelve Months Ended December 31, 2022 (Businesswire) - "Upcoming Milestones:...CAN008 - Anticipate interim read out from the Phase 2 trial for glioblastoma (GBM) in the second half of 2023."

P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

CANbridge Pharmaceuticals CAN008 Phase 2 Trial for Treatment of Glioblastoma Multiforme (GBM) in China Reaches Full Enrollment (Businesswire) - "CANbridge Pharmaceuticals...announced that the CAN008 (asunercept) Phase 2 trial for the treatment of glioblastoma multiforme (GBM) in China is fully enrolled, with a total of 117 patients. The multi-center, randomized, double-blind, placebo-controlled study is evaluating the efficacy and safety of CAN008 plus temozolomide (TMZ) during and after radiation therapy in newly diagnosed patients and is a potentially registrational trial....Interim data from the CAN008 Phase 2 GBM China trial is expected in mid-2023."

Enrollment closed • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Long-term follow-up to the phase I/II study of CAN008 plus standard chemoradiotherapy treatment in patients with newly diagnosed glioblastoma multiforme (Sarcoma-RC 2023) - P1 | "In 2016, a phase I/II open-label, dose-escalation trial of CAN008 as an add-on treatment to standard temozolomide/radiotherapy (TMZ/RT) treatment in newly-diagnosed GBM patients indicated that it was well-tolerated and showed promising efficacy. Higher tumor mutation burden and a higher frequency of DNAH family gene mutations may be predictors of a favorable response to CAN008 treatment. Legal entity responsible for the study Hong-Chieh Tsai, Department of Neurosurgery, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan."

Clinical • P1/2 data • Tumor mutational burden • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • FAS • TMB

CANbridge Pharmaceuticals Announces CAN008 Phase 1/2 Glioblastoma Multiforme Abstract Accepted by the ESMO Sarcoma and Rare Cancers Congress (Market Screener) - "CANbridge Pharmaceuticals, Inc...announced that an abstract on the long-term follow up data from the CAN008 Phase 1/2 trial in glioblastoma multiforme has been accepted for a poster presentation by the European Society for Medical Oncology (ESMO) Sarcoma and Rare Cancers Annual Congress, taking place March 20-22, in Lugano, Switzerland."

P1/2 data • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Long-Term Data from CANbridge Pharmaceuticals CAN008 Phase 1/2 Trial in Glioblastoma Multiforme Shows 67% Five-Year Overall Survival Rate Compared to 8.2% in Institutional Database (Businesswire) - P1/2 | N=NA | "CANbridge Pharmaceuticals...announced that long-term follow up data from the Phase 1/2 study of CAN008 (asunercept) plus temozolomide/radiotherapy (TMZ/RT) in newly diagnosed glioblastoma multiforme (GBM) showed a long-term survival rate of 67% at five years, three years after the trial ended. The data will be presented as a poster at the...ESMO Sarcoma and Rare Cancers Annual Congress, March 20-22, in Lugano, Switzerland....All four of the surviving patients were in the high-dose cohort of the trial, which received 400 mg of CAN008 in addition to standard temozolomide/radiotherapy (TMZ/RT). The overall survival rate of the high-dose CAN008 group was 83% at two years and 67% at three, four and five years....In addition, the high-dose CAN008 cohort saw a median progression-free survival of 17.95 months....CAN008 is currently in an ongoing Phase 2 trial in glioblastoma multiforme (GBM) in China. An interim data analysis is expected in mid-2023."

P1/2 data • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

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

ASUCOV: Asunercept for the Treatment of Patients With Moderate to Severe COVID-19 Disease (clinicaltrials.gov) - P3 | N=636 | Recruiting | Sponsor: Apogenix AG

New P3 trial • Infectious Disease • Novel Coronavirus Disease

CANbridge Announces Financial Results and Corporate Updates for Six Months Ended June 30, 2022 (Businesswire) - "Upcoming Milestones: CAN008 – Expects to complete enrollment in the Phase 2 clinical trial of CAN008 for the treatment of GBM in 2022, with a potential interim data read out in the second half of 2023."

Enrollment status • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Phase 2 Study of CAN008 in Subjects With GBM (clinicaltrials.gov) - P2 | N=117 | Recruiting | Sponsor: CANbridge Life Sciences Ltd.

New P2 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

CANbridge Announces Financial Results and Corporate Updates for the Twelve Months Ended December 31, 2021 (Businesswire) - "Upcoming Milestones: CAN008 - Continue to enroll patients in the Phase 2 clinical trial of CAN008 for the treatment of glioblastoma multiforme (GBM). Expect to have CAN008 Phase 2 interim readout in 2023."

Enrollment status • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

ASUNCTIS: Asunercept in Patients With Severe COVID-19 (clinicaltrials.gov) - P2; N=438; Completed; Sponsor: Apogenix AG; Recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Safety and tolerability of asunercept plus standard radiotherapy/temozolomide in Asian patients with newly-diagnosed glioblastoma: a phase I study. (PubMed, Sci Rep) - P1 | "Patients in Cohort 2 maintained a PFS rate of 57.1% at Month 12. Adding asunercept to standard RT/TMZ was safe and well tolerated in patients with newly-diagnosed glioblastoma and 400 mg/week resulted in encouraging efficacy.Trial registration NCT02853565, August 3, 2016."

Clinical • Journal • P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

First Patient Dosed in CANbridge Pharmaceuticals CAN008 Phase 2 Trial for Treatment of Glioblastoma Multiforme (GBM) in China (Businesswire) - "CANbridge Pharmaceuticals, Inc...announced that it has dosed the first patient in the CAN008 Phase 2 clinical trial to treat glioblastoma multiforme (GBM) in Mainland China."

Trial status • Glioblastoma • Oncology