temelimab (GNbAC1) / GeNeuro - LARVOL DELTA

HERV Dysregulation in a Case of Myalgic Encephalomyelitis and Multiple Sclerosis Responsive to Rituximab. (PubMed, Int J Mol Sci) - "Although the expression of endogenous retroviral proteins has been associated with autoimmunity, the patient did not show increased expression of the toxic protein HERV (human endogenous retrovirus)-W ENV, a target of the ongoing clinical trials with temelimab in MS and long COVID-19 cases. Limitations of the study include sub-optimal frequency of magnetic resonance imaging to monitor lesion progression, and similarly for reassessment of HERV profiles after rituximab. Overall, the coincidence of HERV alterations and the impactful response to rituximab presents the possibility of additional, more specific, therapeutic targets encoded by other HERV elements yet to be discovered."

Journal • CNS Disorders • Epstein-Barr Virus Infections • Fatigue • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease

Mycobacterium paratuberculosis: A HERV Turn-On for Autoimmunity, Neurodegeneration, and Cancer? (PubMed, Microorganisms) - "This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Brain Cancer • CNS Disorders • CNS Tumor • Colon Cancer • Colorectal Cancer • Crohn's disease • Diabetes • Endocrine Disorders • Eye Cancer • Gastroenterology • Gastrointestinal Cancer • Glioblastoma • Immunology • Infectious Disease • Inflammatory Arthritis • Inflammatory Bowel Disease • Melanoma • Metabolic Disorders • Movement Disorders • Multiple Sclerosis • Oncology • Parkinson's Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Sarcoidosis • Solid Tumor • Tuberculosis • Type 1 Diabetes Mellitus • Uveal Melanoma

Temelimab rescues HERV-W mediated neuroinflammatory effects in transgenic mice expressing the envelope protein (ECTRIMS 2024) - "The here presented unpublished data now provide evidence that Temelimab application in this transgenic mouse model preserves myelin integrity and rescues neuroinflammatory glial phenotypes, thus providing strong evidence that antibody mediated neutralization of HERV-W ENV constitutes a potent therapeutic option for MS patients."

Late-breaking abstract • Preclinical • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • Solid Tumor

Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome (clinicaltrials.gov) - P2 | N=203 | Completed | Sponsor: GeNeuro SA | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Psychiatry

Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome (clinicaltrials.gov) - P2 | N=200 | Active, not recruiting | Sponsor: GeNeuro SA | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Psychiatry

Etiopathogenic theories about long COVID. (PubMed, World J Virol) - "The main etiopathogenic theories of long coronavirus disease (COVID) are listed and a conjunction of them is carried out with the objective of deciphering the pathophysiology of the entity, finally the main lines of treatment existing in real life are discussed (Paxlovid, use of antibiotics in dysbiosis, triple anticoagulant therapy, temelimab)."

Journal • Review • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

CancerHERVdb: Human Endogenous Retrovirus (HERV) Expression Database for Human Cancer Accelerates Studies of the Retrovirome and Predictions for HERV-Based Therapies. (PubMed, J Virol) - "In our report, we provide examples of potential uses of the CancerHERVdb, such as identification of cancers suitable for off-target treatment with the multiple sclerosis-associated retrovirus (MSRV)-Env-targeting antibody GNbAC1 (now named temelimab) currently in phase 2b clinical trials for multiple sclerosis or the discovery of cancers overexpressing HERV-H long terminal repeat-associating 2 (HHLA2), a newly emerging immune checkpoint...Therefore, the CancerHERVdb database can aid in the identification of prognostic and risk markers, drivers of cancer, tumor-specific targets, multicancer spanning signals, and targets for immune therapies. Consequently, the CancerHERVdb database is of direct relevance for clinical as well as basic research."

Journal • Bladder Cancer • CNS Disorders • Gastrointestinal Disorder • Hematological Malignancies • Immune Modulation • Leukemia • Lymphoma • Multiple Myeloma • Multiple Sclerosis • Oncology • Uterine Cancer • HHLA2

Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: GeNeuro SA | Trial completion date: Mar 2023 ➔ Jun 2024 | Trial primary completion date: Mar 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Psychiatry

HERV-W ENV Induces Innate Immune Activation and Neuronal Apoptosis via linc01930/cGAS Axis in Recent-Onset Schizophrenia. (PubMed, Int J Mol Sci) - "The totality of these results also showed that HERV-W ENV facilitated antiviral innate immune response, resulting in neuronal apoptosis through the linc01930/cGAS/STING pathway in schizophrenia. Due to its monoclonal antibody GNbAC1 application in clinical trials, we considered HERV-W ENV might be a reliable therapeutic choice for schizophrenia."

Journal • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia • CGAS • IFNB1 • PCA3 • STING

The Karolinska Institutet’s Academic Specialist Center (ASC) to Present Results of GeNeuro’s ProTEct-MS Phase 2 Study of Temelimab at ECTRIMS 2022 (Businesswire) - P2 | N=41 | ProTEct-MS (NCT04480307) | Sponsor: GeNeuro Innovation SAS | "GeNeuro...announced it will present Phase IIb safety and efficacy data on temelimab from its ProTEct-MS study at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Amsterdam, Netherlands....The topline results of the Phase 2 ProTEct-MS study, communicated in March 2022, confirmed the excellent safety profile and tolerability of higher doses of temelimab and the synergistic potential to treat neurodegeneration in addition to anti-inflammatory therapy in multiple sclerosis. Efficacy data, obtained in patients already treated effectively for inflammation, showed that temelimab has a favorable impact on key MRI parameters measuring neurodegeneration."

P2b data • Multiple Sclerosis

"#temelimab #ProTEct-MS study at 26'55 @Lecxav1 😃" (@ForsepsOrg)

Primary analysis ofProTEct-MS, a randomised, placebo-controlled, phase 2 study of Temelimab for theprevention of neurodegenerationin rituximab-treated patients with relapsing multiple sclerosis (ECTRIMS 2022) - "RMS patients who received TML displayed a reduced rate of brain atrophy, improved cortical MTSat, and lowered levels of biomarkers linked to neuronal loss and astrocytic proliferation compared with RTX alone; however, no between group comparison was statistically significant. Nevertheless, data are congruent with results from CHANGE/ANGEL-MS using TML as RMS monotherapy. Longer and larger trials will be required to determine the clinical effects of TML in relevant RMS groups."

Clinical • IO biomarker • P2 data • CNS Disorders • Multiple Sclerosis • Solid Tumor • CSF NfL • GFAP • NEFL • TLR4

Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: GeNeuro SA | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Psychiatry

Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: GeNeuro SA

New P2 trial • Infectious Disease • Novel Coronavirus Disease • Psychiatry

A Long-term Extension of Study GNC-401 (clinicaltrials.gov) - P2 | N=33 | Terminated | Sponsor: GeNeuro Innovation SAS | Trial completion date: Feb 2023 ➔ May 2022 | Recruiting ➔ Terminated | Trial primary completion date: Feb 2023 ➔ May 2022; Drug product unavailability

Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Multiple Sclerosis • CD19

ProTEct-MS: Clinical Trial Assessing Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis (clinicaltrials.gov) - P2 | N=41 | Completed | Sponsor: GeNeuro Innovation SAS | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis

Temelimab for MS and SARS-CoV-2: Could it be a double-edged blessing? (PubMed, Mult Scler Relat Disord) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Promising role of temelimab in multiple sclerosis treatment. (PubMed, Mult Scler Relat Disord) - "Our analysis showed statistically non-significant Risk Ratio (RR) of Adverse events in Temelimab group than that in placebo group (1.01 [0.70,1.46]; p-value = 0.94; I = 0%) . Considering the effect of Temelimab on brain lesions, pooled result showed statistically significant Risk Ratio (RR) of brain lesions in placebo group than that in Temelimab group (0.75 [0.69,0.81), p-value < 0.00001, I = 0% Qualitative and quantitative analysis of the trials assessing the safety and efficacy of Temelimab demonstrate that the drug is safe as well as favourable for use in MS patients."

Journal • Review • CNS Disorders • Multiple Sclerosis

HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2/PP2A/AKT1/GSK3 for Schizophrenia Risk. (PubMed, Viruses) - "In conclusion, we uncovered a relationship between HERV-W ENV and the dopaminergic system in the DA neurons. Considering that GNbAC1, a selective monoclonal antibody to the MSRV-specific epitope, has been promised as a therapy for treating type 1 diabetes and multiple sclerosis (MS) in clinical trials, understanding the precise function of HERV-W ENV in the dopaminergic system may provide new insights into the treatment of schizophrenia."

Journal • CNS Disorders • Diabetes • Metabolic Disorders • Multiple Sclerosis • Psychiatry • Schizophrenia • Type 1 Diabetes Mellitus • AKT1 • DRD2

A Long-term Extension of Study GNC-401 (clinicaltrials.gov) - P2; N=40; Recruiting; Sponsor: GeNeuro Innovation SAS

Clinical • New P2 trial • CNS Disorders • Multiple Sclerosis • CD19 • MRI

ProTEct-MS: Clinical Trial Assessing Temelimab Following Rituximab Treatment in Patients With Relapsing Forms of Multiple Sclerosis (clinicaltrials.gov) - P2; N=41; Active, not recruiting; Sponsor: GeNeuro Innovation SAS; Recruiting ➔ Active, not recruiting; Trial completion date: Sep 2021 ➔ Jan 2022; Trial primary completion date: Sep 2021 ➔ Jan 2022

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

"Ergo temelimab isn’t focused on reducing inflammation but on stopping/ slowing neurodegeneration." (@Boaz_Spermon)

CNS Disorders • Immunology • Inflammation

"Temelimab failed to show an effect on features of acute inflammation but demonstrated preliminary radiological signs of possible anti-neurodegenerative effects. Current data support the development of temelimab for progressive MS." (@Boaz_Spermon)

CNS Disorders • Immunology • Inflammation • Multiple Sclerosis

Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study. (PubMed, Mult Scler) - P2, P2b | "Current data support the development of temelimab for progressive MS. CHANGE-MS: ClinicalTrials.gov: NCT02782858, EudraCT: 2015-004059-29; ANGEL-MS: ClinicalTrials.gov: NCT03239860, EudraCT: 2016-004935-18."

Clinical • Journal • P2b data • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • MRI

Human Endogenous Retrovirus as Therapeutic Targets in Neurologic Disease. (PubMed, Pharmaceuticals (Basel)) - "This article ends by describing new, promising therapies, targeting HERV elements, one of which, temelimab, has completed phase II trials with encouraging results in treating MS. The information gathered here may turn helpful in the design of new strategies to unveil epigenetic failures behind HERV-triggered diseases, opening new possibilities for druggable targets and/or for extending the use of temelimab to treat other associated diseases."

Journal • Review • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders • Infectious Disease • Multiple Sclerosis