Immunic Inc. (IMUX) Announces Positive Top-Line Data From Investigator-Sponsored Phase 2 Proof-of-Concept Clinical Trial of IMU-838 in Primary Sclerosing Cholangitis

Immunic, Inc. (Nasdaq: IMUX), a clinical-stage biopharmaceutical company developing a pipeline of selective oral immunology therapies aimed at treating chronic inflammatory and autoimmune diseases, today announced positive top-line data from an investigator-sponsored phase 2 proof-of-concept clinical trial of IMU-838 in primary sclerosing cholangitis (PSC). This single-arm, open-label, exploratory study was designed to investigate IMU-838's potential to improve various biochemical parameters in PSC patients and help determine whether any such activity warrants further investigation in randomized PSC trials. As previously announced, due to the COVID-19 pandemic, only 18 of the targeted 30 patients were enrolled in the study (intent-to-treat population, ITT), of whom only 11 patients completed the full IMU-838 treatment course and were evaluable over the 24-week treatment period (per-protocol population, PP).

The PP population experienced a statistically significant decrease in serum alkaline phosphatase (ALP) levels (p=0.041) after 24 weeks of treatment using 30 mg IMU-838 once daily, as compared to baseline. A consistent individual pattern of a stable decrease in ALP values was observed in the PP population between baseline and week 24, without any single patient showing an increase of more than 20% of ALP. As per the definition of the primary objective of the study, 27.3% of the patients in the PP population had a clinically relevant reduction of serum ALP higher than 25% at week 24, without an increase in liver biochemistry of more than 33%, as compared to baseline. Biochemical endpoints, such as changes in serum ALP, have been used in PSC trials performed by third parties.

Regarding the secondary objectives of the study, no changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total, direct or indirect bilirubin were observed in the ITT or PP populations, as compared to baseline. In addition, despite the limited scope of the data, encouraging results were observed regarding symptoms of inflammatory bowel disease, a common comorbidity for PSC patients, and patient assessments of health-related quality of life. The study also found that IMU-838 is a safe and well-tolerated oral drug for PSC patients and treatment-emergent adverse events were rare and generally mild.

"I am very excited about the effects we have seen in this highly underserved patient population where there is only a small number of cases worldwide and where no pharmaceutical treatment option is currently available," noted Daniel Vitt, Ph.D., Chief Executive Officer and President of Immunic. "We are also very pleased to see that IMU-838's safety and tolerability profile was confirmed in this patient group. The results from this small, open-label study suggest that IMU-838 merits further clinical testing in PSC. We are in discussions with investigators and leading clinical experts to further evaluate the data set and to explore potential next steps for this indication."

"Currently, no effective treatment options are available for PSC patients and the hepatology community is very keen to see new approaches and clinical programs for the investigation of promising new approaches. I am grateful that Mayo Clinic and Immunic are collaboratively exploring this underserved indication for which liver transplantation is often the only effective option," stated Keith Lindor, M.D., Professor of Medicine Emeritus and former President of the American Association for the Study of Liver Diseases. "Although we are mindful of the small size of this dataset, I do believe the results are noteworthy and merit further exploration. Notable in this small patient cohort is the absolute consistency with which these patients experienced decreases in serum alkaline phosphatase at the 24-week time point."

Study Background and Baseline Characteristics

The single-arm, open label, exploratory study was an investigator-sponsored trial led by Elizabeth Carey, M.D., Professor of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, who had received Investigator Investigational New Drug (IND) approval from the U.S. Food & Drug Administration (FDA) and had been granted Institutional Review Board (IRB) approval to conduct the study. The study was supported by a grant from the National Institutes of Health (NIH) and was conducted at two sites: Mayo Clinic, Phoenix, Arizona (Dr. Carey) and Mayo Clinic, Rochester, Minnesota (John E. Eaton, M.D.), both of which are tertiary referral centers for PSC patients.

The study, for which Immunic provided the study medication, planned to enroll 30 patients with PSC, aged 18 to 75 years, who received 30 mg of IMU-838 once daily for a period of 24 weeks. Enrollment for the study took place between July 2019 and September 2020, but almost all enrollment occurred in 2019 and early 2020. During the COVID-19 pandemic, recruitment for this study was hampered, as patients with PSC are at a high risk of COVID-19 infections and were advised to avoid travel and unnecessary social contacts such as those required to participate in a clinical trial. Together with the investigators, Immunic determined to readout data of the 18 patients who were enrolled prior to the COVID-19 pandemic. The ongoing COVID-19 pandemic also triggered the principal investigator's decision to terminate the study in late 2020, before the intended recruitment goal of 30 patients was reached.

A total of 18 patients started treatment of 30 mg IMU-838 once daily (intent-to-treat population, ITT, n=18). Of these 18 patients, 11 patients received the full 24-week treatment with IMU-838 (per-protocol population, PP, n=11). Due to the high number of discontinued patients during the COVID-19 pandemic and the fact that all discontinued patients in an ITT statistical analysis will be counted as treatment failures at week 24, this analysis focuses mainly on the 11-patient PP population.

Primary Objective

The primary objective of this study was to determine whether IMU-838 reduces serum ALP in adult patients diagnosed with PSC. The main analysis for the primary objective was whether patients could achieve a reduction of ALP at week 24 which is greater or equal to 25%, as compared to baseline, while the AST increase at week 24 is no more than 33%, as compared to baseline. This positive primary outcome was achieved by 3 of 11 patients in the PP population (27.3%, 95% CI: 6-61%). By virtue of inclusion criteria, patients at baseline had to have an elevated ALP value of at least 1.5 times upper limit of normal (ULN).

In addition, time from baseline was calculated as a continuous variable and treated as the primary predictor using a random intercept model which was adjusted for age at baseline and gender. For this longitudinal analysis of ALP from baseline to week 24 in the PP population, the ALP value statistically significantly (p=0.041) decreased by an average of 5.76 IU/L every 30 days (95% CI: -11.29, -0.23; statistical model). The time trend was not statistically significant in the ITT analysis (p=0.578) due to missing data following the high rate of treatment discontinuations during the COVID-19 pandemic.

Secondary Objectives

Secondary objectives were to investigate the liver biochemistry parameters, AST, ALT, and total/direct/indirect bilirubin, as well as the concentrations of proinflammatory cytokines, as compared to baseline. The longitudinal analysis of both AST and ALT as well as total, direct and indirect bilirubin values showed a stable pattern in the PP population with no statistically significant change over time and the confidence interval to include the no-change scenario (AST: average 30 day change 1.22 IU/L, 95% CI: -0.53, 2.97, p=0.170; ALT: average 30 day change 0.85 IU/L, 95% CI -1.46, 3.15, p=0.467, total bilirubin: average 30 day change 0.00 mg/dL, 95% CI -0.01, 0.02, p=0.561, direct bilirubin: average 30 day change 0.00 mg/dL, 95% CI -0.01, 0.01, p=0.861, indirect bilirubin: average 30 day change 0.00 mg/dL, 95% CI -0.01, 0.01, p=0.556). Similar results were found in the ITT population. In addition, a decrease in the Ulcerative Colitis Clinical score was observed in evaluated patients, although the number of assessed patients was limited.

"This was a feasibility study to explore activity of IMU-838 in PSC patients based on biochemical parameters. IMU-838 was found to lead to a statistically significant reduction of serum ALP over time in the PP population, while no trend for increases in ALT, AST or bilirubin was observed," commented Andreas Muehler, M.D., Chief Medical Officer of Immunic. "Despite the challenges we faced due to COVID-19, which severely hindered the enrollment at the two Mayo Clinic sites and which led to an unusually high discontinuation rate and an early termination of the study, we have seen encouraging activity signals for IMU-838 in this patient population. Based on these promising data and, in particular, the improvement in biochemical liver parameters, we will continue to evaluate the potential of IMU-838 as a treatment option for PSC patients. It may also be worthwhile to optimize dose levels of IMU-838 in PSC patients in the future."

For more information on this clinical trial, please visit: www.clinicaltrials.gov, NCT03722576.

Conference Call and Webcast Information

As previously announced, Immunic's management team will host a public conference call and webcast today, February 18, 2021 at 8:00 a.m. Eastern Time to discuss the data from the main phase 2 analysis of the CALVID-1 trial of IMU-838 in hospitalized patients with moderate COVID-19, as well as data from the investigator-sponsored phase 2 clinical trial of IMU-838 in primary sclerosing cholangitis.

To participate in the conference call, dial 1-877-870-4263 (USA) or 1-412-317-0790 (International) and ask to be joined into the Immunic, Inc. call. A live, listen-only webcast of the conference call can be accessed at https://www.webcaster4.com/Webcast/Page/2301/39950 or on the "Events and Presentations" section of Immunic's website at ir.imux.com/events-and-presentations.

An archived replay of conference call and webcast will be available approximately one hour after the completion for one year on Immunic's website at: ir.imux.com.

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