avdoralimab (IPH5401) / Novo Nordisk, Innate - LARVOL DELTA

Unravelling the impact of SARS-CoV-2 on hemostatic and complement systems: a systems immunology perspective. (PubMed, Front Immunol) - "The dynamics of the components are examined under three distinct conditions: the disease state representing symptomatic COVID-19 state, an intervened disease state marked by reduced levels of regulators, and drug interventions including heparin, tranexamic acid, avdoralimab, garadacimab, and tocilizumab. In conclusion, this study explains the regulatory mechanisms of the hemostatic and complement systems and illustrates how the biopathway machinery sustains the balance between activation and inhibition. The knowledge that we have acquired could contribute to designing therapies that target the hemostatic and complement systems."

Journal • Cardiovascular • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis • A2M • IL6R

A Glimpse for the subsistence from pandemic SARS-CoV-2 infection. (PubMed, Bioorg Chem) - "Although some drug regimens and vaccines have shown safety in trials, none have been entirely successful yet. This review highlights, some of the potential antibodies (tocilizumab, Sarilumab, Avdoralimab, Lenzilumab, Interferon (alfa /beta /gamma)) screened against SARS-CoV-2 and the most promising drugs (Favipiravir, Hydroxychloroquine, Niclosamide, Ribavirin, Baricitinib, Remdesivir, Arbidol Losartan, Ritonavir, Lopinavir, Baloxavir, Nitazoxanide, Camostat) in various stages of development with their synthetic protocol and their clinical projects are discussed to counter COVID -19."

Journal • Review • Cardiovascular • Gastrointestinal Disorder • Infectious Disease • Nephrology • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Treatment of Bullous Pemphigoid with Avdoralimab: Multicenter, Randomized, Open-Labeled Phase 2 Study. (PubMed, JID Innov) - "This proof-of-concept pilot study did not show preliminary signal of additional avdoralimab efficiency compared with superpotent topical steroids alone."

Clinical • Journal • P2 data • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology

Innate Pharma presents early clinical data on IPH5401 and monalizumab at the ESMO 2019 congress (GlobeNewswire, INNATE PHARMA) - "IPH5401 dose-escalation study in combination with durvalumab in advanced solid tumors, STELLAR-001, shows manageable safety profile Initiation of two expansion cohorts in non-small cell lung cancer (NSCLC) with secondary resistance to immuno-oncology (IO) treatment and IO-naïve hepatocellular carcinoma (HCC) . Survival data of monalizumab in combination with cetuximab in head and neck cancer supports current expansion cohort in IO-pretreated and IO-naïve patients . Innate Pharma SA (the “Company” - Euronext Paris: FR0010331421 – IPH) today announced that new data on IPH5401 and monalizumab were presented at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain. Preliminary results of STELLAR-001, a Phase I dose-escalation study of IPH5401, an anti-C5aR antibody, in combination with durvalumab in advanced solid tumors;. One-year survival data of the first expansion cohort of the Phase II trial evaluating monalizumab in combination..."

Clinical data • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer

Treatment of Bullous Pemphigoid With Avdoralimab (IPH5401), an Anti-C5aR1 Monoclonal Antibody (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: Centre Hospitalier Universitaire de Nice | Active, not recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Mar 2024

Trial completion • Trial completion date • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology

Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update. (PubMed, Am J Clin Dermatol) - "Rituximab, a CD20 monoclonal antibody, depletes B-lymphocytes and has shown efficacy in severe cases. Dupilumab, targeting interleukin (IL)-4 receptor α and thus blocking IL-4 and IL-13, downregulates type 2 helper (Th2) responses and has demonstrated promising results. Targeting eosinophil-related molecules using bertilimumab and AKST4290 has yielded positive results in clinical trials. Omalizumab, an immunoglobulin (Ig) E antibody, can reduce disease severity and allows corticosteroid tapering in a number of cases. Complement inhibitors such as nomacopan and avdoralimab are being investigated. IL-17 and IL-23 inhibitors such as secukinumab and tildrakizumab have shown potential in a limited number of case reports. Neonatal Fc receptor antagonists such as efgartigimod are under investigation. Additionally, topical therapies and Janus kinase inhibitors are being explored as potential treatments for BP. These novel therapies offer promising alternatives for managing..."

Clinical • Journal • Pipeline update • Review • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology • Pruritus • IL13 • IL17A • IL23A • IL4

Treatment of Bullous Pemphigoid With Avdoralimab (IPH5401), an Anti-C5aR1 Monoclonal Antibody (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: Centre Hospitalier Universitaire de Nice | Recruiting ➔ Active, not recruiting | N=40 ➔ 15

Enrollment change • Enrollment closed • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology

IPH5401 anti-human C5aR antibody targets suppressive myeloid cells in the TME (SITC 2019) - "Altogether, these results support our ongoing multi-center, open label, dose-escalation and dose expansion Phase I/II clinical trial (STELLAR-001) evaluating the safety and efficacy of IPH5401 in combination with durvalumab, an anti-PD-L1 immune checkpoint inhibitor, as a treatment for patients with advanced solid tumors."

IO Biomarker • PD(L)-1 Biomarker

STELLAR-001: a phase 1 study of the anti-C5aR avdoralimab in combination with the anti-PD-L1 durvalumab in advanced solid tumors. (ESMO-TAT 2022) - P1 | "The combination of avdoralimab and durvalumab was well tolerated, minimal anti-tumor activity in the expansion cohorts led to early termination of the study. Further exploration of translational data is ongoing."

Combination therapy • P1 data • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8

Preliminary results of STELLAR-001, a dose escalation phase I study of the anti-C5aR, IPH5401, in combination with durvalumab in advanced solid tumours (ESMO 2019) - P1; "Preliminary results of this combination of IPH5401 plus durva suggest a manageable toxicity profile. Results of dose escalation including PK/PD data will be presented. Clinical trial identification: NCT03665129."

Combination therapy • P1 data • PD(L)-1 Biomarker

Avdoralimab (Anti-C5aR1 mAb) Versus Placebo in Patients With Severe COVID-19: Results From a Randomized Controlled Trial (FOR COVID Elimination [FORCE]). (PubMed, Crit Care Med) - P2 | "In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367)."

Journal • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

IMMUNONCOVID: Prospective Study in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 Infection (clinicaltrials.gov) - P2 | N=19 | Completed | Sponsor: Centre Leon Berard | Active, not recruiting ➔ Completed | N=219 ➔ 19

Enrollment change • Trial completion • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • IL6

First patient dosed in avdoralimab phase II clinical trial in Covid-19 patients with severe pneumonia (GlobeNewswire) - "Innate Pharma SA...today announced that the first patient was dosed in a randomized, double-blind Phase II clinical trial, evaluating the safety and efficacy of its anti-C5aR antibody, avdoralimab (IPH5401), in COVID-19 patients with severe pneumonia....The Phase II trial is supported by an exploratory translational study, EXPLORE COVID-19....The trial will be conducted in La Timone Hospital and Nord Hospital in Marseille (Hopitaux Universitaires de Marseille – AP-HM) and in the Hospital Laveran (HIA-Laveran). The trial is expected to enroll a total of 108 patients (age 18-80) between two cohorts....In each cohort, patients will receive avdoralimab or placebo."

Enrollment open • New P2 trial • Trial status • Infectious Disease • Novel Coronavirus Disease

Treatment of Bullous Pemphigoid With Avdoralimab (IPH5401), an Anti-C5aR1 Monoclonal Antibody (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Centre Hospitalier Universitaire de Nice | Trial completion date: Dec 2021 ➔ Dec 2023 | Trial primary completion date: Apr 2021 ➔ Apr 2023

Trial completion date • Trial primary completion date • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology

STELLAR-001: IPH5401 (Anti-C5aR) in Combination With Durvalumab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=73 | Terminated | Sponsor: Innate Pharma | Trial completion date: Jun 2021 ➔ Feb 2021 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2021 ➔ Feb 2021; early termination

Combination therapy • Trial completion date • Trial primary completion date • Trial termination • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

IMMUNONCOVID: Prospective Study in Patients With Advanced or Metastatic Cancer and SARS-CoV-2 Infection (clinicaltrials.gov) - P2; N=219; Active, not recruiting; Sponsor: Centre Leon Berard; Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Disorders • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor • IL6

Update on Avdoralimab Phase 2 FORCE Trial in COVID-19 Patients with Severe Pneumonia (GlobeNewswire) - P2, N=208; FORCE (NCT04371367); "...FORCE (FOR COVID-19 Elimination), the investigator-sponsored, Phase 2 clinical trial evaluating the safety and efficacy of its anti-C5aR1 antibody, avdoralimab, in COVID-19 patients with severe pneumonia, did not meet its primary endpoints in all three cohorts of the trial....Investigators and the Independent Data Monitoring Committee observed slightly higher deaths in the treatment arm compared to placebo without causality being established....Based on these results, the Company will stop exploring avdoralimab in COVID-19."

Discontinued • P2 data • Infectious Disease • Novel Coronavirus Disease

Avdoralimab an Anti-C5aR Antibody, in Patients With COVID-19 Severe Pneumonia ( FORCE ) (clinicaltrials.gov) - P2; N=208; Completed; Sponsor: Assistance Publique Hopitaux De Marseille; Active, not recruiting ➔ Completed

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

Innate Pharma First Quarter 2021 Report (GlobeNewswire) - "The investigator-sponsored Phase 2 clinical trial, FORCE (FOR COVID-19 Elimination), has completed enrollment and is ongoing for patient follow-up and data analysis."

Enrollment closed • Trial status • Infectious Disease • Novel Coronavirus Disease

Mini-review: antibody therapeutics targeting G protein-coupled receptors and ion channels. (PubMed, Antib Ther) - "Major classes of membrane-associated protein targets include G protein-coupled receptors (GPCRs) and ion channels that are linked to a wide range of disease indications across all therapeutic areas. This mini-review summarizes the antibody target landscape for both GPCRs and ion channels as well as current progress in the respective research and development pipelines with some example case studies highlighted from clinical studies, including those being evaluated for the treatment of symptoms in COVID-19 infection."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

Biologics for the Use in Chronic Spontaneous Urticaria: When and Which. (PubMed, J Allergy Clin Immunol Pract) - "Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory disease...We provide information on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab...These include IgE/ligelizumab, IgE/GI-310, thymic stromal lymphopoietin/tezepelumab, C5a receptor/avdoralimab, sialic acid-binding Ig-like lectin 8/lirentelimab, CD200R/LY3454738, and KIT/CDX-0159. Our aim is to provide updated information and guidance on the use of biologics in the treatment of patients with CSU, now and in the near future."

Journal • Cardiovascular • Chronic Spontaneous Urticaria • Dermatology • Immunology • Urticaria

Complement cascade in severe forms of COVID-19: recent advances in therapy. (PubMed, Eur J Immunol) - "No antiviral drug (hydroxychloroquine, remdesivir, lopinavir/ritonavir) has yet been shown to be effective in COVID-19...Complement blockade, mostly C5a-C5aR axis blockade (avdoralimab), may prevent acute respiratory distress syndrome (ARDS) from worsening or progression to death...Complement blockade, mostly C5a-C5aR axis blockade (avdoralimab), may prevent acute respiratory distress syndrome (ARDS) from worsening or progression to death. Clinical trials are underway."

Journal • Review • Acute Respiratory Distress Syndrome • Cardiovascular • Hematological Disorders • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Thrombosis

STELLAR-001: IPH5401 (Anti-C5aR) in Combination With Durvalumab in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=73; Active, not recruiting; Sponsor: Innate Pharma; Recruiting ➔ Active, not recruiting; N=140 ➔ 73

Clinical • Combination therapy • Enrollment change • Enrollment closed • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

"Rouge: Untomiris Bleu: Avdoralimab (récepteur) Je me dis que ce n’est pas si remis en cause que cela ... 1/n" (@Lybsoo)

Avdoralimab an Anti-C5aR Antibody, in Patients With COVID-19 Severe Pneumonia ( FORCE ) (clinicaltrials.gov) - P2; N=208; Active, not recruiting; Sponsor: Assistance Publique Hopitaux De Marseille; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases