Immunic, Inc. Reports Positive Top-line Data From Phase 2 EMPhASIS Trial

Immunic, Inc. recently announced positive top-line data from its phase 2 EMPhASIS trial of lead asset, IMU-838, the company’s selective oral DHODH inhibitor, in patients with relapsing-remitting multiple sclerosis (RRMS). The study achieved all primary and key secondary endpoints, indicating activity in RRMS patients. In particular, the study met its primary endpoint, demonstrating a statistically significant reduction in the cumulative number of combined unique active (CUA) magnetic resonance imaging (MRI) lesions up to week 24 in patients receiving 45 mg of IMU-838 once daily, by 62% (p=0.0002), as compared to placebo. The study also met its key secondary endpoint, showing a statistically significant reduction in the cumulative number of CUA MRI lesions for the 30 mg once daily dose, by 70% (p<0.0001), as compared to placebo.

All other secondary endpoints, including those based on other MRI parameters and on clinical endpoints, such as relapse events, also provided a noticeable signal and numerical benefit for the IMU-838 treatment groups, as compared to placebo. Given the study’s design, sample size, and the patient’s follow-up duration, full statistical analysis of these secondary endpoints was not deemed appropriate or included in the analysis plan. Nonetheless, we believe data on these endpoints provides useful information for the further development path toward potential approval.

Consistent with prior data sets in other patient populations, administration of IMU-838 in this trial was observed to be safe and well-tolerated, thereby providing evidence of an attractive target product profile for IMU-838 in the RRMS patient population. The rate of treatment-emergent adverse events was 42.9% of IMU-838-treated patients compared with 43.5% of patients on placebo. Likewise, serious treatment-emergent adverse events were rare and only observed in 3 out of 140 IMU-838-treated patients, and in 1 out of 69 patients on placebo. The rate of treatment withdrawals in the 24-week blinded treatment period was only 5% in the pooled IMU-838 treatment arms versus 7.2% in the placebo group. In addition, the rate of discontinuations due to adverse events or protocol-specified discontinuation criteria were equivalent between the pooled IMU-838 treatment arms and placebo. There was no increase in liver or renal events for the IMU-838 treatment arms versus placebo. Analysis of the full EMPhASIS data is ongoing and will be presented at an upcoming scientific meeting.

“Patients in the EMPhASIS trial exhibited robust responses across all study endpoints included in the top-line analysis. In addition to showing consistent activity by IMU-838 in RRMS using different measures, the study data also supports the previously observed favorable safety and tolerability profile of IMU-838 in RRMS patients,” commented Andreas Muehler, MD, Chief Medical Officer of Immunic. “We believe this data strongly supports our goal of developing IMU-838 as an easy, safe, and convenient oral treatment option for patients with RRMS and other autoimmune diseases. We are extremely encouraged by these results and intend to now focus on the development plan with the goal of eventually making IMU-838 available as a best-in-class, once-daily oral therapy for RRMS.”

The Phase 2 EMPhASIS trial was an international, multicenter, double-blind, placebo-controlled, randomized, parallel-group study, designed to assess the efficacy and safety of IMU-838 in patients with RRMS. Of the 210 patients randomized in 36 centers across four European countries, 209 patients received at least one dose of IMU-838 or placebo(placebo n=69, 30mg IMU-838 n=71, 45mg IMU-838 n=69), and 197 patients completed the blinded 24-week treatment period. All enrolled patients were required to have shown disease activity based on clinical evidence of relapse and additional MRI criteria. The primary and key secondary endpoints were the cumulative number of CUA MRI lesions, up to week 24, for 45 mg and 30 mg of IMU-838, respectively. MRI was performed at baseline and at weeks 6, 12, 18, and 24, and was evaluated centrally by an independent, blinded MRI reader. The study includes an optional, extended treatment period for up to 9.5 years to evaluate long-term safety and tolerability of IMU-838.

“These positive Phase 2 results impressively show the robust activity of IMU-838 in RRMS and provide further evidence of the favorable safety profile already observed in other patient populations, representing more than 650 human subjects and patients, to date,” stated Daniel Vitt, PhD, Chief Executive Officer and President of Immunic. “We believe that these phase 2 data of IMU-838 speak volumes about its potential to provide a new, convenient, once daily oral front-line treatment option to patients suffering from RRMS, bolstered by a unique combination of potential efficacy, safety and tolerability. Given the strength of these top-line results, we will continue to prepare a clinical Phase 3 program for IMU-838 in RRMS and, after a full review of the data, anticipate providing a further update on development strategy. We are also looking forward to reading out clinical data from the other ongoing Phase 2 trials of IMU-838 in COVID-19, primary sclerosing cholangitis and ulcerative colitis in the upcoming months.”

Multiple sclerosis (MS) is an autoimmune disease that affects the brain, spinal cord and optic nerve. In MS, myelin, the coating that protects the nerves, is attacked and damaged by the immune system. Thus, MS is considered an immune-mediated demyelinating disease of the central nervous system. Relapsing-remitting MS (RRMS) is the most common form of the disease. Approximately 85% of patients with MS are expected to develop RRMS, with some of these patients later developing more progressive forms of the disease. RRMS is characterized by clearly defined attacks of new or increasing neurologic symptoms. These relapses are followed by periods of remission, or partial or complete recovery. During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. MS is a progressive disease which, without effective treatment, leads to severe disability. MS affects more than 700,000 people in the United States, and more than 2.2 million people worldwide. The disease mainly affects young adults of prime working age, although MS can occur at any age. MS is at least two to three times more common in women than in men.

 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, eg, 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 COVID-19, relapsing-remitting multiple sclerosis and ulcerative colitis. 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. IMU-838 is not yet licensed or approved in any country and has not been demonstrated to be safe or effective for any use.

Immunic, Inc. is a clinical-stage biopharmaceutical company with a pipeline of selective oral immunology therapies aimed at treating chronic inflammatory and autoimmune diseases, including relapsing-remitting multiple sclerosis, ulcerative colitis, Crohn’s disease, and psoriasis. The company is developing three small molecule products: lead development program, IMU-838, is a selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme DHODH and exhibits a host-based antiviral effect; IMU-935 is an inverse agonist of RORγt; and IMU-856 targets the restoration of the intestinal barrier function. IMU-838 is in Phase 2 clinical development for COVID-19, relapsing-remitting multiple sclerosis and ulcerative colitis, with an additional Phase 2 trial considered in Crohn’s disease. An investigator-sponsored proof-of-concept clinical trial for IMU-838 in primary sclerosing cholangitis is ongoing at the Mayo Clinic. For more information, visit www.imux.com.