RedHill Biopharma Ltd., a specialty biopharmaceutical company,  announced that the first patient was dosed in its U.S. Phase 2/3 study of orally-administered RHB-107 (upamostat)[1], an investigational new drug for patients with symptomatic COVID-19 who do not require hospital care.

Dror Ben-Asher, RedHill's CEO said: "RedHill is rapidly advancing two Phase 3-stage, orally-administered, novel molecules for the treatment of COVID-19: RHB-107 for outpatient use and opaganib for hospitalized patients. With these two promising and complementary shots on goal across the disease severity spectrum, RedHill is positioned at the very forefront of COVID-19 therapeutic research, aiming to address both existing and emerging mutations."

The U.S. Phase 2/3 study (NCT04723527) 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.

RHB-107 is a novel, potent inhibitor of serine proteases, that targets human cell factors involved in preparing the spike protein for viral entry into target cells and is therefore expected to be effective against emerging viral variants with mutations in the spike protein. RHB-107 demonstrated strong inhibition of SARS-CoV-2 viral replication in an in vitro human bronchial epithelial cell model and previous preclinical work demonstrated potential tissue-protective action. Previous clinical studies of RHB-107 included several Phase 1 and Phase 2 studies in different indications, demonstrating its clinical safety profile in approximately 200 patients.

"Dosing of the first patient in the Phase 2/3 study of RHB-107 in patients with symptoms but not needing hospital care, the largest COVID-19 patient group, is a key step forward in RedHill's efforts to help combat the widespread effects of this pandemic. Together with opaganib, we now have two novel, orally-administered compounds, with unique mechanisms of action, in advanced development for treating patients at different stages of COVID-19 disease," said Terry F. Plasse MD, Medical Director at RedHill. "The ability to treat patients early in the course of COVID-19 disease, with an oral therapy designed to be used outside the hospital, and with a compound expected to be effective against emerging viral variants, has the potential to be a game-changer in managing this disease. The ground-breaking design of the study allows us to collect data at a level previously possible only in hospital while enabling patients to stay in the comfort of their homes and decreasing exposure risk of this highly contagious disease."

This study is a 2-part, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of RHB-107. 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 and will evaluate time to sustained recovery from illness as the primary endpoint. Each patient will be tested for specific viral strain.

The study is unique in a COVID-19 trial setting in its extensive use of telemetry and electronic patient-reported outcome (ePRO) data collection and is based on the latest FDA guidance for symptom monitoring. Following the patients' initial visit to a medical facility, a research-trained nurse will make periodic home visits to study patients to collect samples for safety and virology monitoring. This innovative use of home-based safety and efficacy monitoring technologies, together with home nursing support, enables patients to participate in the study from home with the benefit of hospital-level monitoring, enhancing patient comfort and markedly decreasing the risk of SARS-CoV-2 exposure to medical staff and other members of the public.

In parallel, the late-stage development program for RedHill's second COVID-19 drug candidate, opaganib[2] in patients hospitalized with severe COVID-19, is progressing rapidly. Recently announced top-line results from the U.S. Phase 2 study of opaganib demonstrated safety and positive efficacy data across key primary and secondary endpoints. The global Phase 2/3 study continues to enroll, having recently received a positive DSMB futility review, with top-line data and potential subsequent global emergency use authorization applications expected in the second quarter of 2021.

About RHB-107 (upamostat)

RHB-107 is a proprietary, first-in-class, orally-administered potent inhibitor of several serine proteases, with demonstrated antiviral and potential tissue-protective effects. RHB-107 targets human cell factors involved in preparing the spike protein for viral entry into target cells and is therefore expected to be effective against emerging viral variants with mutations in the spike protein. RHB-107 is being evaluated in a U.S. Phase 2/3 study for treatment of patients with symptomatic COVID-19 who do not require inpatient care. In addition, RHB-107 has potential in targeting cancer, inflammatory lung diseases and gastrointestinal diseases. RHB-107 has undergone several Phase 1 studies and two Phase 2 studies, demonstrating its clinical safety profile in approximately 200 patients. RedHill acquired the exclusive worldwide rights to RHB-107, excluding Mainland China, Hong Kong, S.A.R., China Region of China, Taiwan, China Region of China and Macau, S.A.R., China Region of China, from Germany's Heidelberg Pharmaceuticals (FSE: HPHA) (formerly WILEX AG) for all indications.

About RedHill Biopharma

RedHill Biopharma Ltd. (Nasdaq: RDHL) is a specialty biopharmaceutical company primarily focused on gastrointestinal and infectious diseases. RedHill promotes the gastrointestinal drugs, Movantik? for opioid-induced constipation in adults[3], Talicia? for the treatment of Helicobacter pylori (H. pylori) infection in adults[4], and Aemcolo? for the treatment of travelers' diarrhea in adults[5]. RedHill's key clinical late-stage development programs include: (i) RHB-204, with an ongoing Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) disease; (ii) opaganib (Yeliva?, ABC294640), a first-in-class SK2 selective inhibitor targeting multiple indications with a 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; (iv) RHB-104, with positive results from a first Phase 3 study for Crohn's disease; (v) RHB-102 (Bekinda?), with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; and (vi) RHB-106, an encapsulated bowel preparation. 

1. RHB-107 (upamostat) is an investigational new drug, not available for commercial distribution in the United States.
2. Opaganib (Yeliva?, ABC294640) is an investigational new drug, not available for commercial distribution in the United States.
3. Full prescribing information for Movantik? (naloxegol) is available at: www.Movantik.com.
4. Full prescribing information for Talicia? (omeprazole magnesium, amoxicillin and rifabutin) is available at: www.Talicia.com. 
5. Full prescribing information for Aemcolo? (rifamycin) is available at: www.Aemcolo.com.