niclosamide (FW-1022) / Entero Therap - LARVOL DELTA

RESERVOIR: Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection (clinicaltrials.gov) - P2 | N=166 | Active, not recruiting | Sponsor: First Wave Bio, Inc. | Trial completion date: Dec 2022 ➔ Mar 2023

Trial completion date • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

RESERVOIR: Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection (clinicaltrials.gov) - P2 | N=166 | Active, not recruiting | Sponsor: First Wave Bio, Inc. | Trial completion date: Jul 2022 ➔ Oct 2022

Trial completion date • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

RESERVOIR: Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection (clinicaltrials.gov) - P2 | N=166 | Active, not recruiting | Sponsor: First Wave Bio, Inc. | Trial completion date: Mar 2022 ➔ Jul 2022

Trial completion date • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

Niclosamide In Moderate COVID-19 (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: First Wave Bio, Inc. | N=100 ➔ 0 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Aug 2021 ➔ Jan 2022

Enrollment change • Trial primary completion date • Trial withdrawal • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

Niclosamide in COVID-19 (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: First Wave Bio, Inc. | N=148 ➔ 0 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Oct 2021 ➔ Jan 2022

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

RESERVOIR: Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection (clinicaltrials.gov) - P2 | N=166 | Active, not recruiting | Sponsor: First Wave Bio, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

AzurRx BioPharma Submits an Investigational New Drug Application for Niclosamide as Treatment for Grade 1 and Grade 2 Immune Checkpoint Inhibitor-Associated Colitis (GlobeNewswire) - "AzurRx BioPharma, Inc...announced today the submission of an Investigational New Drug (IND) Application seeking permission from the U.S. Food and Drug Administration (FDA) to begin a clinical trial evaluating proprietary formulations of niclosamide for Grade 1 and Grade 2 colitis and diarrhea in oncology patients receiving treatment with immune checkpoint inhibitors (ICIs). The planned Phase 1b/2a clinical trial, now known as PASSPORT, is designed to determine the safety and potential efficacy of niclosamide, also known as FW-420, administered as an oral, immediate-release tablet and a topical rectal enema foam formulation."

New P1/2 trial • Inflammatory Bowel Disease • Ulcerative Colitis

[VIRTUAL] AzurRx BioPharma (BIO 2021) - "The lead therapeutic candidate is MS1819, a recombinant lipase for the treatment of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis and chronic pancreatitis, currently in two Phase 2 clinical trials. AzurRx is launching two clinical programs using proprietary formulations of niclosamide, a pro-inflammatory pathway inhibitor; FW-420, for grade 1 Immune Checkpoint Inhibitor-Associated Colitis and diarrhea in oncology patients and FW-1022, for COVID-19 gastrointestinal infections. The Company is headquartered in Delray Beach, Florida with clinical operations in Hayward, California."

Cystic Fibrosis • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology • Pancreatitis • Pulmonary Disease • Respiratory Diseases

AzurRx BioPharma Doses First Patient In Phase 2 Clinical Trial of Niclosamide for the Treatment of COVID-19 Gastrointestinal Infections (GlobeNewswire) - "AzurRx BioPharma, Inc....announced today the administration of the first dose of FW-1022 to a volunteer in the ongoing Phase 2 RESERVOIR clinical trial....Topline results from the trial are expected in the first quarter of 2022....The RESERVOIR clinical trial is designed as a two-part, two-arm, placebo-controlled Phase 2 study. The trial’s primary objectives are to confirm the safety of FW-1022 in the treatment of patients with COVID-19-related GI infections and to evaluate its efficacy in clearing SARS-CoV-2 from the GI tract."

Trial status • Infectious Disease • Novel Coronavirus Disease

RESERVOIR: Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection (clinicaltrials.gov) - P2; N=148; Recruiting; Sponsor: AzurRx BioPharma, Inc.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

RESERVOIR: Safety and Efficacy of Niclosamide in Patients With COVID-19 With Gastrointestinal Infection (clinicaltrials.gov) - P2; N=148; Not yet recruiting; Sponsor: AzurRx BioPharma, Inc.

Clinical • New P2 trial • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

AzurRx BioPharma Initiates Phase 2 Clinical Trial of Niclosamide for the Treatment of COVID-19 Gastrointestinal Infections (GlobeNewswire) - "AzurRx BioPharma, Inc....has initiated its Phase 2 RESERVOIR clinical trial of a proprietary oral formulation of micronized niclosamide (FW-1022) for the treatment of COVID-19 related gastrointestinal (GI) infections. Patient enrollment is expected to begin in April 2021 with topline data anticipated in Q1 2022. The Phase 2 RESERVOIR clinical trial is a two-part, two-arm, placebo-controlled study examining the safety and efficacy of micronized oral niclosamide tablets, known as FW-1022, in patients with COVID-19 GI infection....The trial will be managed by PPD, Inc...."

P2 data • Trial status • Infectious Disease • Novel Coronavirus Disease

Niclosamide in COVID-19 (clinicaltrials.gov) - P2; N=148; Not yet recruiting; Sponsor: First Wave Bio, Inc.; Trial completion date: May 2021 ➔ Dec 2021; Initiation date: Nov 2020 ➔ Jun 2021; Trial primary completion date: May 2021 ➔ Oct 2021

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Niclosamide In Moderate COVID-19 (clinicaltrials.gov) - P2; N=100; Not yet recruiting; Sponsor: First Wave Bio, Inc.; Trial completion date: Apr 2021 ➔ Dec 2021; Initiation date: Dec 2020 ➔ Jun 2021; Trial primary completion date: Apr 2021 ➔ Aug 2021

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

AzurRx BioPharma Engages PPD to Manage Clinical Trial for Niclosamide as Treatment for COVID-19 Gastrointestinal Infections (GlobeNewswire) - "AzurRx BioPharma, Inc....has entered into an agreement with PPD, Inc....for its planned Phase 2 clinical trial evaluating a proprietary formulation of micronized niclosamide as a treatment for COVID-19-associated gastrointestinal (GI) infections. Under the terms of the agreement, PPD will manage the Phase 2 clinical trial for an immediate-release capsule formulation of micronized oral niclosamide...AzurRx anticipates initiating the trial in the first half of 2021."

Licensing / partnership • New P2 trial • Infectious Disease • Novel Coronavirus Disease

AzurRx BioPharma Announces Exclusive Worldwide License Agreement with First Wave Bio for Use of Proprietary Niclosamide Formulations to Treat Immune Checkpoint Inhibitor-Associated Colitis and COVID-19 Gastrointestinal Infections (GlobeNewswire) - "Cinical trials to initiate in 1H’21, with potential for expedited FDA 505(b)(2) pathway for IND-approved COVID-19...AzurRx BioPharma, Inc....today announced that it has signed an exclusive worldwide licensing agreement with First Wave Bio, Inc. ('First Wave') for the use of their patented and proprietary oral and rectal formulations of niclosamide for the treatment of immune checkpoint inhibitor-associated colitis (ICI-AC) and COVID-19 GI infections....Anticipates initiating both the Phase 2 COVID-19 GI Infection trial'....AzurRx is granted a worldwide, exclusive right to develop, manufacture, and commercialize First Wave’s proprietary immediate release oral and enema formulations of niclosamide..."

Licensing / partnership • Trial initiation date • Infectious Disease • Novel Coronavirus Disease

ND ND (clinicaltrialsregister.eu) - P1/2; N=51; Ongoing; Sponsor: FIRST WAVE BIOPHARMA INCORPORATION

Clinical • New P1/2 trial • Gastroenterology • Inflammatory Bowel Disease

Niclosamide in COVID-19 (clinicaltrials.gov) - P2; N=148; Not yet recruiting; Sponsor: First Wave Bio, Inc.

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

Niclosamide In Moderate COVID-19 (clinicaltrials.gov) - P2; N=100; Not yet recruiting; Sponsor: First Wave Bio, Inc.; Trial primary completion date: Jan 2021 ➔ Apr 2021

Clinical • Trial primary completion date • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease

A Study of Niclosamide Enemas in Subjects With Active Ulcerative Proctitis or Ulcerative Proctosigmoiditis (clinicaltrials.gov) - P1/2; N=51; Recruiting; Sponsor: First Wave Bio, Inc.; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Dec 2020 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

[VIRTUAL] SELECTIVE KILLING MULTIPLE MYELOMA CELLS BY TARGETING FREE LIGHT CHAIN SECRETION, ENDOPLASMIC RETICULUM STRESS AND UNFOLDED PROTEIN RESPONSE USING THE COMBINATION OF VALPROATE AND NICLOSAMIDE (VAN) (EHA 2020) - "Background Multiple Myeloma (MM) is a malignancy of differentiated B cells characterised by >10% neoplastic plasma cells in the bone marrow, monoclonal immunoglobulin (whole and/or free light chain; FLC) in serum/urine, lytic bone lesions and fractures, anaemia and immunodeficiency. As expected of activators of the UPR, VaN combined with proteasome inhibitors bortezomib or carfilzomib induced greater MM killing at low doses of PI. Combined together, these data have identified an oral drug-combination with anti-MM activity which rapidly reduces FLC secretion and has activity against PI-resistant MM cells."

Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Musculoskeletal Diseases • Oncology

Stress Conditions Induced by Locoregional Therapies Stimulate Enrichment and Proliferation of Liver Cancer Stem Cells. (PubMed, J Vasc Interv Radiol) - "Stress conditions induced by locoregional therapies stimulated hCSC enrichment and proliferation, which could be suppressed by niclosamide and inhibitors of pathways important for hCSC renewal. Future studies will determine whether combining locoregional therapies with adjuvant hCSC inhibitors reduces HCC recurrence."

Cancer stem cells • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Practice considerations on the use of investigational anti-COVID-19 medications: Dosage, administration and monitoring. (PubMed, J Clin Pharm Ther) - "Effective therapies are urgently needed to manage COVID-19, and existing drugs such as antivirals and antimalarials are under investigation for repurposing to meet this need. This process requires up-to-date drug information to ensure optimum use, particularly safety and efficacy profiles of the medications, until convincing evidence is reported."

Journal • Infectious Disease • Novel Coronavirus Disease

Targeting Wnt/β-catenin by anthelmintic drug niclosamide overcomes paclitaxel resistance in esophageal cancer. (PubMed, Fundam Clin Pharmacol) - "Stabilization of β-catenin level by Wnt activator lithium chloride (LiCl) significantly abolishes the inhibitory effects of niclosamide in inhibiting proliferation and survival but not suppressing phosphorylation of STAT3 and 70S6K in paclitaxel-resistant esophageal cancer cells, suggesting that niclosamide sensitizes esophageal cancer cell to paclitaxel mainly through inhibiting Wnt/β-catenin. Our work demonstrates the efficacy of niclosamide and its underlying mechanism in paclitaxel-resistant esophageal cancer. Our work emphasizes that Wnt/β-catenin inhibition is a sensitizing strategy in esophageal cancer."

Journal • Esophageal Cancer • Gastrointestinal Cancer • Oncology • STAT3

Niclosamide and its derivative DK-520 inhibit RANKL-induced osteoclastogenesis. (PubMed, FEBS Open Bio) - "These results demonstrate that DK-520, like Niclosamide, effectively inhibits the early stage of osteoclastogenesis. The findings presented here, together with its increased oral plasma concentrations and bioavailability suggest that DK-520 may be a promising drug candidate for treatment of osteoclast-related diseases."

Journal • TRAP