Immunic, Inc. Receives First Regulatory Approval from German Health Authority BfArM to Initiate a Phase 2 Clinical Trial of its Selective Oral DHODH Inhibitor, IMU-838, in COVID-19 Patients

"Approval to begin the CALVID-1 phase 2 clinical trial in Germany is a significant achievement that will allow for the near-term investigation of the oral DHODH inhibitor, IMU-838, in COVID-19 patients," commented Prof. Maria Vehreschild, M.D., Head of Infectious Diseases at University Hospital Frankfurt and Principal Investigator of one of the clinical sites participating in the study. "Given IMU-838’s broad antiviral effect, recently confirmed preclinical activity against SARS-CoV-2 itself, as well as its selective effect against hyper-activated immune cell populations which may play a role in the potentially deadly complications of interstitial lung disease, IMU-838 represents a prospective, potential treatment option that merits urgent investigation."

Immunic recently announced that IMU-838 had successfully demonstrated preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, IMU-838 was observed to inhibit replication of clinical isolates of SARS-CoV-2 associated with COVID-19. In cellular assays, IMU-838 demonstrated this antiviral activity at concentrations which are well below the blood concentrations associated with IMU-838 dosing regimens studied in ongoing and previous clinical trials. In addition, IMU-838 has an attractive pharmacokinetic, safety and tolerability profile and, to date, has already been tested in about 650 individuals.

The aim of the CALVID-1 trial is to investigate IMU-838 as an oral treatment option for COVID-19 and to enable the use of IMU-838 as a treatment for current and potential future pandemic threats. The trial is expected to initially enroll approximately 230 patients at 10-35 centers across Europe and the United States. Patients will be randomized to receive either 22.5 mg of IMU-838 twice daily, or placebo twice daily, for 14 consecutive days. All patients are also eligible to receive investigator’s choice of standard-of-care therapy throughout the duration of the study. Inclusion criteria are hospitalized adult patients with a confirmed SARS-CoV-2 infection fulfilling clinical status category 3 or 4, as assessed with the nine-category ordinal scale proposed by the World Health Organization (WHO) COVID-19 Therapeutic Trial Synopsis, as well as certain additional clinical and laboratory conditions. The primary endpoint will be the proportion of patients free of invasive ventilation throughout the entire study period. Secondary endpoints include duration of hospitalization, duration of intensive care unit (ICU) treatment, 28-day all-cause mortality, time to clinical improvement and viral titer reduction.

The CALVID-1 study will employ an adaptive trial strategy by including interim safety and efficacy assessments. If clinical activity of IMU-838 is confirmed by the Independent Data Monitoring Committee after the first interim analysis, which is scheduled to occur after approximately 200 patients have completed the blinded treatment period, an expansion of this trial into a confirmatory phase 3 trial could be recommended.

"The speed of preparation and approval for this important phase 2 clinical trial for IMU-838 speaks to the strength of our data package, while also reflecting the urgent global need to develop useful therapies against COVID-19," stated Andreas Muehler, M.D., Chief Medical Officer of Immunic. "IMU-838’s profile, as an orally available DHODH inhibitor that employs a host-based mode of action, thereby providing broad-spectrum antiviral activity, makes it a unique, potential therapeutic option which may be applicable as either a standalone or combination therapy. All phase 2 preparatory activities have been completed and we anticipate beginning the trial in short order."

For more information on this clinical trial, please visit: www.clinicaltrials.gov, NCT04379271.

About IMU-838
IMU-838 is an orally available, next-generation selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme dihydroorotate dehydrogenase (DHODH). IMU-838 acts on activated T and B cells while leaving other immune cells largely unaffected and allows the immune system to stay functioning, e.g. in fighting infections. In previous trials, IMU-838 did not show an increased rate of infections compared to placebo. In addition, DHODH inhibitors, such as IMU-838, are known to possess a host-based antiviral effect, which is independent with respect to specific virus proteins and their structure. Therefore, DHODH inhibition may be broadly applicable against multiple viruses. IMU-838 was successfully tested in two phase 1 clinical trials in 2017 and is currently being tested in phase 2 trials in patients with relapsing-remitting multiple sclerosis and ulcerative colitis. IMU-838 is also under investigation as a potential treatment option for SARS-CoV-2 infections associated with COVID-19. Furthermore, Immunic’s collaboration partner, the Mayo Clinic, has started an investigator-sponsored proof-of-concept clinical trial testing IMU-838 activity in patients with primary sclerosing cholangitis. To date, IMU-838 has already been tested in about 650 individuals and has shown an attractive pharmacokinetic, safety and tolerability profile.

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