Mesupron (upamostat) / Heidelberg Pharma, RedHill - LARVOL DELTA

PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 (clinicaltrials.gov) - P2 | N=300 | Active, not recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | Recruiting ➔ Active, not recruiting

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

PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | Trial completion date: Oct 2024 ➔ Oct 2025 | Trial primary completion date: Jun 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease (clinicaltrials.gov) - P2/3 | N=61 | Terminated | Sponsor: RedHill Biopharma Limited | N=310 ➔ 61 | Suspended ➔ Terminated; Part A complete; corporate decision made to cancel Part B.

Enrollment change • Trial termination • Infectious Disease • Novel Coronavirus Disease

Combined Antitumor Effect of the Serine Protease Urokinase Inhibitor Upamostat and the Sphingosine Kinase 2 Inhibitor Opaganib on Cholangiocarcinoma Patient-Derived Xenografts. (PubMed, Cancers (Basel)) - "Mouse weights and PAX165 tumor volumes were measured. Tumor volumes in the upamostat, opaganib, and upamostat plus opaganib groups were significantly decreased compared to the control group."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • PRSS1 • PRSS3 • SPHK1 • SPHK2

Combined Antitumor Effect of the Serine Protease Urokinase Inhibitor Upamostat and the Sphingosine Kinase 2 Inhibitor Opaganib on Cholangiocarcinoma Patient-Derived Xenografts (Multidisciplinary Digital Publishing Institute) - "Four groups of 18 mice each were treated with upamostat, opaganib, both, or vehicle. Mouse weights and PAX165 tumor volumes were measured. Tumor volumes in the upamostat, opaganib, and upamostat plus opaganib groups were significantly decreased compared to the control group."

Preclinical • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

PROTECT-APT 1: Early Treatment and Post-Exposure Prophylaxis of COVID-19 (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Upamostat: a serine protease inhibitor for antiviral, gastrointestinal and anticancer indications. (PubMed, Expert Opin Investig Drugs) - "Upamostat is an orally bioavailable prodrug of WX-UK1, which is most active against trypsins and closely related enzymes. Upamostat is an orally bioavailable serine protease inhibitor with an excellent safety profile and favorable pharmacokinetic properties. It has demonstrated preliminary evidence of efficacy against COVID-19 and nonclinical data suggest potential applicability against other viral illnesses, gastrointestinal diseases and cancer."

Journal • Review • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Infectious Disease • Novel Coronavirus Disease • Oncology • Pancreatic Cancer • Respiratory Diseases • Solid Tumor

Intrinsic Deficiency of PAI-1 in Human Pulmonary Arterial Smooth Muscle Cells From Pulmonary Artery Hypertension (PAH) Patients Drives UPA-dependent Cell Proliferation and Induces Spontaneous Pulmonary Hypertension in Mice (ATS 2023) - "Taken together, our data strongly suggest that p38MAPK-FOXO3 mediated PAI-1 down-regulation in PASMC from human PAH lungs promotes PASMC hyper-proliferation, remodeling, and spontaneous PH due to unopposed uPA activation. Further studies are needed to determine the potential benefits of targeting the PAI-1/uPA imbalance to attenuate the progression and/or reverse pulmonary vascular remodeling and PH."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Oncology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Targeted Protein Degradation • SMAD3 • TGFB1 • TP53

Randomized, placebo-controlled pilot study of upamostat, a host-directed serine protease inhibitor, for outpatient treatment of COVID-19. (PubMed, Int J Infect Dis) - "Upamostat was well tolerated, shortened recovery time, and decreased new severe symptoms and hospitalization."

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

MECHANISTIC EFFECTS OF UPAMOSTAT AND OPAGANIB IN CHOLANGIOCARCINOMA CELL LINES (AASLD 2022) - "Upamostat and its active metabolite WX-UK1 have been shown to inhibit serine proteases. Upamostat and opaganib in combination have significant inhibitory effects on both CCA cell migration and viability in vitro which may prevent tumor progression. Both drugs have an established clinical safety profile and may be effective in targeted treatment of CCA patients."

Preclinical • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • HER2 Breast Cancer • Liver Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • HER-2

Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease (clinicaltrials.gov) - P2/3 | N=310 | Suspended | Sponsor: RedHill Biopharma Limited | Trial completion date: Sep 2022 ➔ Dec 2023 | Active, not recruiting ➔ Suspended | Trial primary completion date: Sep 2022 ➔ Dec 2023

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

Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease (clinicaltrials.gov) - P2/3; N=310; Active, not recruiting; Sponsor: RedHill Biopharma Limited; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease

Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease (clinicaltrials.gov) - P2/3; N=310; Recruiting; Sponsor: RedHill Biopharma Limited; Trial completion date: Sep 2021 ➔ Sep 2022; Trial primary completion date: Sep 2021 ➔ Sep 2022

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

[VIRTUAL] RedHill Biopharma (BIO 2021) - "RedHill promotes the gastrointestinal drugs Movantik® (OIC), Talicia® (H. pylori) and Aemcolo® (travelers' diarrhea). RedHill's key clinical late-stage development programs include: (i) RHB-204, with an ongoing Phase 3 study for NTM disease; (ii) opaganib (Yeliva®, ABC294640), a first-in-class SK2 selective inhibitor targeting multiple indications with positive Phase 2 COVID-19 data and an ongoing Phase 2/3 program for COVID-19 and Phase 2 studies for prostate cancer and cholangiocarcinoma ongoing; (iii) RHB-107 (upamostat), a serine protease inhibitor in a U.S. Phase 2/3 study as treatment for symptomatic COVID-19, and targeting multiple other cancer and inflammatory gastrointestinal diseases, as well as additional late-stage asset assets. More information about the Company is available at www.redhillbio.com."

Biliary Cancer • Cholangiocarcinoma • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Oncology • Prostate Cancer • Solid Tumor

RedHill Biopharma Receives Allowances for U.S. Patent Applications Covering Opaganib and RHB-107 for COVID-19 (PRNewswire) - "RedHill Biopharma Ltd....announced receipt of two Notices of Allowance from the U.S. Patent and Trademark Office (USPTO) covering opaganib and RHB-107 (upamostat) as methods for the treatment of COVID-19 caused by the SARS-CoV-2 virus. Both opaganib and RHB-107 are novel COVID-19 therapeutic candidates, in oral pill form, with dual mechanism of action effects....Enrollment in opaganib's global Phase 2/3 study in hospitalized patients with severe COVID-19 [NCT04467840] is almost 100% complete. RHB-107's Phase 2/3 study is ongoing in non-hospitalized patients with symptomatic COVID-19 [NCT04723527] who do not require supplemental oxygen."

Enrollment status • Patent • Infectious Disease • Novel Coronavirus Disease

RedHill Biopharma Provides Fourth Quarter and Full Year 2020 Financial Results and Operational Highlights (PRNewswire) - "Research and Development Expenses were approximately $16.5 million for the year ended December 31, 2020, mainly attributable to the development of our COVID-19 therapeutics and the Phase 3 study of RHB-204 for pulmonary NTM disease, and were, in total, lower than the research and development expenses for the year ended December 31, 2019."

Commercial • Infectious Disease • Novel Coronavirus Disease

ObvioHealth and RedHill Biopharma Launch First in Kind Remote COVID-19 Therapy Trial Incorporating Highest Level of At-home Patient Monitoring to Date (PRNewswire) - "ObvioHealth...announced the launch of a hybrid clinical trial for the treatment of COVID-19, using an innovative study design with digital data capture to remotely monitor patient vitals. This U.S. Phase 2/3 study will examine the safety and efficacy of RedHill Biopharma's (Nasdaq: RDHL) RHB-107 (upamostat), using ObvioHealth's clinical trial ecosystem, including digital devices, a patient-centric smartphone application and home healthcare visits....Patients will be sent home with RHB-107 and five 510(k)-cleared devices to begin treatment."

eHealth • Infectious Disease • Novel Coronavirus Disease

Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease (clinicaltrials.gov) - P2/3; N=310; Recruiting; Sponsor: RedHill Biopharma Limited; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease

RedHill Biopharma Announces First Patient Dosed in U.S. Phase 2/3 COVID-19 Outpatient Study with RHB-107 (PRNewswire) - "RedHill Biopharma Ltd....announced that the first patient was dosed in its U.S. Phase 2/3 study of orally-administered RHB-107...The U.S. Phase 2/3 study...is aimed at evaluating treatment with RHB-107 in patients with symptomatic COVID-19 early in the course of the disease, with a simple once-daily oral treatment in an outpatient setting....The first part of the study is designed for dose selection and is planned to enroll 60 patients. The second part of the study is planned to enroll 250 patients..."

Trial status • Infectious Disease • Novel Coronavirus Disease

Upamostat, a Serine Protease Inhibitor, or Placebo for Treatment of COVID-19 Disease (clinicaltrials.gov) - P2/3; N=310; Not yet recruiting; Sponsor: RedHill Biopharma Limited

Clinical • New P2/3 trial • Infectious Disease • Novel Coronavirus Disease • ALB

New potential therapeutic applications of WX-UK1, as a specific and potent inhibitor of human trypsin-like proteases (AACR 2018) - "Several of these serine proteases are known to be associated with cancer progression and metastasis. As a compound with an established clinical safety profile, targeted use of upamostat in oncology and extension to non-oncology indications may be assessed."

Oncology

RedHill Biopharma’s Second COVID-19 Candidate, RHB-107, Cleared by FDA for Phase 2/3 Study in Symptomatic COVID-19 Disease (PRNewswire) - "RedHill Biopharma Ltd....today announced that the U.S. Food and Drug Administration (FDA) has cleared the Company's Investigational New Drug (IND) application for a Phase 2/3 study evaluating orally administered RHB-107....The randomized, parallel-group double-blind Phase 2/3 study is expected to start enrolling patients early next year....Other COVID-19 candidate, opaganib, in patients with severe COVID-19 pneumonia includes: The U.S. Phase 2 study...is now fully enrolled and expected to report topline data in the coming weeks; and the global Phase 2/3 study...which is more than 50% enrolled..."

Enrollment status • IND • Infectious Disease • Novel Coronavirus Disease

RedHill Biopharma Provides Q3/2020 Results and Highlights, Including 300% Talicia Prescription Growth (RedHill Press Release) - "Enrollment in the U.S. Phase 2 study...is over 90% complete and top-line data is expected before the end of this year....A global Phase 2/3 study...is advancing rapidly and is approaching 50% enrollment. Approved in six countries and active across 20 clinical sites to date....The studies are intended to support potential emergency use applications as early as the first quarter of 2021....COVID-19 (SARS-CoV-2) Program: RHB-107 (upamostat): The Company has submitted an Investigational New Drug (IND) application to the FDA for a U.S. Phase 2/3 study with RHB-107 in moderate COVID-19 patients treated in an outpatient setting....The study is planned to be initiated early in 2021."

Enrollment status • FDA event • IND • New P2/3 trial • Infectious Disease • Novel Coronavirus Disease

RedHill Biopharma Receives U.S. Patent Allowance Covering Opaganib and RHB-107 Combination (GlobeNewswire) - "RedHill Biopharma Ltd...today announced that it has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for a new patent application related to the use of two of RedHill’s proprietary investigational compounds, opaganib (Yeliva^®, ABC294640) and RHB-107 (upamostat), for the treatment of solid tumor cancers. The patent is expected to extend IP protection for the combination until 2036...Given the encouraging pre-clinical data, RedHill plans to add an additional cohort to the ongoing Phase 2a study in cholangiocarcinoma, evaluating opaganib in combination with RHB-107, subject to discussions with the U.S. FDA."

Patent • Trial status • Cholangiocarcinoma • Gastrointestinal Disorder • Oncology

"$RDHL RedHill Biopharma Receives U.S. Patent Allowance Covering Opaganib and RHB-107 Combination https://t.co/5Aw7HZUDhj #patent" (@stock_titan)