Immunic Presents Key Vidofludimus Calcium Data at the 40th Congress of ECTRIMS, Highlighting Its Therapeutic Potential in Multiple Sclerosis
Immunic Presents Key Vidofludimus Calcium Data at the 40th Congress of ECTRIMS, Highlighting Its Therapeutic Potential in Multiple Sclerosis |
| [18-September-2024] |
– Vidofludimus Calcium Consistently Reduced Neurofilament Light Chain Levels, Compared to Placebo, in the Interim Analysis of the Phase 2 CALLIPER Trial, Across Age and Disability Levels at Baseline For All Progressive Multiple Sclerosis Subtypes – – Clinical Signal Shown for Vidofludimus Calcium on Post COVID Fatigue May Be Related to Epstein-Barr Virus Reactivation; Preventing This Reactivation May Contribute to Fatigue Reduction in Multiple Sclerosis Patients – – Preclinical Data Showed Improved Neuronal Survival, Likely Driven by Vidofludimus Calcium's Induction of Nurr1 Activation, as Demonstrated by Primary Target Gene Regulation – – In Preclinical Experiments, Vidofludimus Calcium Reduced or Prevented Development of Pathogenic Peripheral T Helper Cells, Which Could be One of the Treatment Pathways in Multiple Sclerosis – NEW YORK, Sept. 18, 2024 /PRNewswire/ -- Immunic, Inc. (Nasdaq: IMUX), a biotechnology company developing a clinical pipeline of orally administered, small molecule therapies for chronic inflammatory and autoimmune diseases, today announced the presentation of key data at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), highlighting Immunic's lead asset, nuclear receptor related 1 (Nurr1) activator, vidofludimus calcium's (IMU-838) therapeutic potential in multiple sclerosis (MS). The data will be presented in an oral poster presentation and three ePosters at this conference, being held September 18-20, 2024, in Copenhagen, Denmark. Additionally, members of Immunic will be available throughout the event at booth #60. "Having four poster presentations on our lead asset, vidofludimus calcium, at the prestigious ECTRIMS Congress, illustrates the strength of the data generated for our drug candidate, to date, and its potential to become a new treatment option for MS," stated Daniel Vitt, Ph.D., Chief Executive Officer of Immunic. "We are particularly excited to have the opportunity to present data on various aspects of vidofludimus calcium's profile, including the neurofilament light chain (NfL) interim data from our phase 2 CALLIPER trial, antiviral data suggesting an effect on reducing fatigue, Nurr1 target data supporting a neuroprotective profile, and pathogenic T cell data further supporting the drug's anti-inflammatory effects." Dr. Vitt added, "As previously reported, in the interim analysis of our CALLIPER trial, we observed a clear separation from placebo in serum NfL levels among all patients with progressive multiple sclerosis (PMS) as well as its subtypes. These observations support the potential effectiveness of vidofludimus calcium in slowing disease progression in PMS and further substantiate its neuroprotective capabilities through the activation of Nurr1. Our next major data readout for this asset is the CALLIPER top-line data, which we expect to release in April of next year. We believe that, if the CALLIPER trial is successful in showing a beneficial effect of vidofludimus calcium, this data, along with that from the ENSURE program and vidofludimus calcium's already established, strong safety and tolerability profile, may allow for a meaningful clinical differentiation of vidofludimus calcium compared to other MS medications, providing potentially attractive commercial positioning." Dr. Vitt continued, "Fatigue is one of the most common and most debilitating symptoms for both post-Covid Syndrome (PCS) and MS. Third-party research has recognized Epstein-Barr virus (EBV) reactivation as a potential cause for PCS fatigue. Notably, data has demonstrated not only vidofludimus calcium's antiviral effects, but also its potential ability to prevent reactivation of EBV. We aim to confirm vidofludimus calcium's potential to reduce fatigue in MS patients in our ongoing CALLIPER and phase 3 ENSURE trials and in the recently initiated investigator-sponsored phase 2 RAPID_REVIVE trial in PCS patients. Additionally, results from an animal model suggest that vidofludimus calcium reduces or prevents the development of pathogenic peripheral T helper cells. Besides its effect on pathogenic immune cells, preclinical evidence further suggests a neuroprotective role of vidofludimus calcium via activation of Nurr1. Preclinical data support Nurr1-driven direct neuroprotective effects by vidofludimus calcium enhancing neuronal survival and indirect effects by reducing neurotoxic activation of microglia cells. The combination of neuroprotective and anti-inflammatory effects of vidofludimus calcium represents a potential beneficial profile for effective treatment of MS." Oral Poster Presentation:
In the phase 2 CALLIPER trial interim analysis of 203 patients, serum NfL levels were reduced by 22.4% (p=0.01, post hoc) after 24 weeks of vidofludimus calcium treatment compared to placebo, with consistent treatment effects across each progressive MS subtype, including primary progressive MS as well as active and non-active secondary progressive MS. The vidofludimus calcium group showed a 10% decrease in NfL versus a 20% increase for placebo among those with an Expanded Disability Status Scale (EDSS) score ≤ 5.5; and a 2% decrease for vidofludimus calcium versus a 12% increase for placebo among those with an EDSS score >5.5. Similarly, among patients aged ≤ 45 years, the reduction was 11.6% for vidofludimus calcium versus a 15% increase for placebo, while for those aged > 55 years, it was a 10% decrease versus a 13% increase, respectively. The data suggest that vidofludimus calcium treatment consistently reduces NfL levels compared to placebo across different patient subgroups based on age and disability scores at baseline. ePosters:
Analysis of the antiviral activity of vidofludimus calcium in vitro revealed a dose-dependent reduction of lytic EBV reactivation in B cells and an anti-EBV effect in epithelial cells. Results of a post-hoc analysis of PCS symptoms in the phase 2 CALVID-1 trial indicated a potential contribution of vidofludimus calcium to the prevention of long-term fatigue. 80% of patients who received placebo reported fatigue compared to 50% who received 45 mg vidofludimus calcium. Fatigue decreased in both treatment groups in the next 9-17 weeks to 33% for placebo and 17% for vidofludimus calcium. A clinical signal for vidofludimus calcium on PCS fatigue was observed which might be related to EBV reactivation. By preventing this reactivation, vidofludimus calcium may contribute to fatigue reduction in MS patients as well. This hypothesis will be further assessed by determining effects on fatigue using patient questionnaires as well as analyses of the anti-EBV effect in the ongoing CALLIPER, ENSURE, and RAPID_REVIVE clinical trials.
Vidofludimus calcium enhanced the expression of Nurr1 target genes important for neuronal survival, such as brain derived neurotrophic factor (BDNF) and superoxide dismutase 1 (SOD1), in a rat neuronal cell line. Additionally, it upregulated key Nurr1 target genes, such as tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2), in human microglial and murine neuronal cell lines, which could contribute to neuronal protection. Vidofludimus calcium protected neurons under pro-apoptotic conditions, reduced gene expression of IL-6, TNFa and IFNg in human microglia stimulated with lipopolysaccharide (LPS), and increased BDNF levels in human peripheral blood mononuclear cells (PBMCs) stimulated with LPS. Vidofludimus calcium effectively attenuated disease severity in an experimental autoimmune encephalomyelitis (EAE) model. Treatment with vidofludimus calcium led to reduced immune cell infiltration, including decreased numbers of pathogenic T cells producing IL-17A, GM-CSF, and IFNγ. Preliminary data showed that mice receiving vidofludimus calcium exhibit elevated levels of BDNF in the blood and enhanced expression of Nurr1 and its target gene TH in the central nervous system.
Vidofludimus calcium given prophylactically reduced disease severity and prevented disease development (63% and 15% symptom free in vidofludimus calcium and vehicle, respectively). This was reflected in the strong reduction of infiltrating T helper (Th) cells in the spinal cord as well as reduced numbers of proinflammatory Th cells in the periphery (draining lymph nodes, dLN). Vidofludimus calcium treatment, given after symptom onset, reduced disease progression compared to vehicle. This was supported by lower numbers of infiltrating proinflammatory Th cells into the spinal cord, while no significant difference was seen in the periphery compared to vehicle. The effect of vidofludimus calcium was assessed on myelin oligodendrocyte glycoprotein (MOG) antigen-specific Th cells (2D2) on day 7 after disease induction. Although vidofludimus calcium seems to increase MOG-specific follicular T helper (Tfh) cells in the periphery (dLN), the progression to develop into pathogenic Th cells was inhibited and the development of regulatory T cells was increased. Overall, vidofludimus calcium reduces or prevents development of pathogenic peripheral Th cells. All poster presentations will be accessible on the "Events and Presentations" section of Immunic's website at: https://ir.imux.com/events-and-presentations. About Vidofludimus Calcium (IMU-838) About Immunic, Inc. Cautionary Statement Regarding Forward-Looking Statements Contact Information Immunic, Inc. US IR Contact US Media Contact
SOURCE Immunic, Inc. | ||
Company Codes: NASDAQ-NMS:IMUX |
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