COVID-19: Immunic, Inc. Begins Phase 2 Trial of IMU-838 in fusion with Oseltamivir
By T. Chakraborty, Ph.D.
As COVID-19 continues to affect human lives, global biopharmas have initiated collaborations with research organizations to bring forth innovative drugs against it. Immunic Inc., which focuses on the development of oral therapies for the treatment of chronic inflammatory and autoimmune diseases announced the first cohort of patient enrollment for a Phase 2 clinical trial that evaluates IMU-838, the company’s proprietary DHODH inhibitor to treat coronavirus.
IMU-838 is an orally accessible investigational small molecule drug that targets dihydroorotate dehydrogenase (DHODH), an enzyme involved in pyrimidine biosynthesis in the metabolically energetic activated immune cells. Inhibition of this important cellular pathway reduces the production of key inflammatory cytokines and chemokines like Interleukin 17 and Interferon-γ. Pre-clinical studies have shown that the drug specifically inhibits activated T and B cells but does not target other immune cells.
Since the drug only targets metabolically active immune cells and not all bone marrow-derived immune cells, it has a direct antiviral effect. Further, preclinical studies have shown that viral reactivation, one of the major drawbacks of immune modulators, can also be avoided when IMU-838 is used. Besides COVID-19, the drug is currently being investigated for the treatment of multiple sclerosis, inflammatory bowel disease, and other chronic inflammatory and autoimmune diseases. Clinical trials with the active form of IMU-838, vidofludimus, as well as the drug in healthy individuals generated a safety profile and pharmacokinetic properties of the drug.
Preclinical studies and IONIC Trial
In preclinical studies, IMU-838 inhibited the replication of clinical isolates of SARS-CoV-2. This antiviral activity of the drug is below the blood concentrations of IMU-838 which are currently being used in different clinical trials. These encouraging results were the basis of the Phase 2 clinical trial announced to test the safety and efficacy of the drug in moderate to severe COVID-19 patients.
The IONIC trial is a randomized, open-label phase 2b study that aims to recruit approximately 120 adult patients who have been hospitalized. Sixty patients will receive IMU-838 and Oseltamivir, while the placebo group will be treated with Oseltamivir alone, for 14 consecutive days. Patients with clinical status categories 3 to 5 as defined by the World Health Organization are eligible to be enrolled in the study.
The clinical trial is supported by University Hospitals Coventry and Warwickshire (UHCW) NHS Trust and is the lead site of patient recruitment. After the first patients were recruited on July 27th, 2020, Prof. Ramesh Arasaradnam, Chair of the British Society of Gastroenterology (BSG) Research Committee and Chief Investigator of the IONIC trial said, “The healthcare community has never faced a more urgent need for new therapies than the unprecedented situation we currently face with the COVID-19 pandemic.
Recent third-party research has highlighted the powerful synergy between direct antiviral drugs and DHODH inhibitors in preclinical models. We believe that the combination of Oseltamivir, which is a licensed drug in the United Kingdom, and IMU-838, may offer a promising approach for the treatment of severe viral infections, including mid-to-late-stage COVID-19 patients.” 
Further, Daniel Vitt, Ph.D., CEO, and President of Immunic commented “We are honored to be collaborating with the UHCW NHS Trust on this important clinical trial, in order to find a new treatment option for COVID-19 patients. Due to its unique host-based mode of action, which avoids dependence on specific viral proteins and, therefore, offers broad-spectrum antiviral activity, as well as the attractive pharmacokinetic, safety, and tolerability profile, we believe that IMU-838 is particularly suitable for combination with other antiviral drugs such as Oseltamivir. We also believe that this trial can provide valuable insights as to whether the host cell-based antiviral mechanism of IMU-838 has a synergistic effect with a direct antiviral drug in order to provide a combination treatment approach for COVID-19.” 
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