Immunic Announces Vidofludimus Calcium Reduced Risk of Disability Worsening by 30% in Primary Progressive Multiple Sclerosis Patients from Phase 2 CALLIPER Trial - Reduced Relative Risk of 24-Week Confirmed Disability Wo

Immunic Announces Vidofludimus

Calcium Reduced Risk of Disability Worsening by 30% in Primary Progressive Multiple Sclerosis Patients from Phase 2 CALLIPER Trial

Reduced Relative Risk of 24-Week Confirmed Disability Worsening Events by 20% in Overall Study Population Compared to Placebo; Even More

Prominent 30% Reduction in High Unmet Need Population of Primary Progressive Multiple Sclerosis -

Showed Consistent Reduction of Disability Worsening in Subpopulations Without Inflammatory Lesions at Baseline in Overall Study Population;

Reduced Relative Risk of 24-Week Confirmed Disability Worsening Events in Patients Without Gadolinium-Enhancing Lesions at Baseline by

29% Compared to Placebo -

Reduced Annualized Rate of Thalamic Brain Volume Loss by 20% Compared to Placebo -

Confirmed Favorable Safety and Tolerability Observed in Previous Clinical Trials; No New Safety Signals Identified -

Webcast to be Held Today, April 30, at 8:00 am ET -

April 30, 2025 - 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 positive data from its phase

2 CALLIPER trial of nuclear receptor related 1 (Nurr1) activator, vidofludimus calcium (IMU-838), in patients with progressive multiple

In the overall PMS patient

population (n=467), vidofludimus calcium reduced the relative risk of 24-week confirmed disability worsening (24wCDW) events based on

changes in the expanded disability status scale (EDSS) by 20% compared to placebo. Further analyses by disease subtype demonstrated that

vidofludimus calcium was associated with a 30% reduction in the relative risk of 24wCDW events in the primary progressive multiple sclerosis

(PPMS) study population (n=152) compared to placebo and a respective 15% reduction in the non-active secondary progressive multiple sclerosis

(naSPMS) study population (n=268). Reduction of confirmed disability worsening is widely considered to be the most recognized regulatory

approval endpoint for registrational studies in progressive forms of multiple sclerosis (MS).

Immunic believes that

these reductions in 24wCDW events are remarkable in light of the overwhelming non-activity of the CALLIPER population. In support, the

evidence of focal inflammatory disease (gadolinium-enhancing lesions at baseline in 6.8% of naSPMS and 17.8% of PPMS patients) and the

number of on-study relapses (5.8% in the overall patient population) are lower than in most historical PMS trials.

A consistent reduction

of disability worsening was observed in the different subpopulations with or without inflammatory gadolinium-enhanced lesion activity

at baseline and during the study. Vidofludimus calcium reduced the relative risk of 24wCDW events in patients without gadolinium-enhancing

lesions at baseline by 29% compared to placebo. In historical studies, such patients were largely shown to not benefit from current anti-inflammatory

therapies. Immunic believes the substantial effect in these patients, therefore, underlines the previously observed neuroprotective effect

of Nurr1 activation by vidofludimus calcium.

Magnetic Resonance Imaging (MRI) Endpoints

While vidofludimus calcium

had a modest benefit on the exploratory primary MRI endpoint (annualized rate of percent brain volume change: 5% improvement compared

to placebo), vidofludimus calcium substantially reduced the annualized rate of thalamic brain volume loss by 20% in patients with PMS

compared to placebo. Change in thalamic volume is considered a more sensitive MRI atrophy marker. Thalamic atrophy is prevalent in PMS

and data has shown strong associations with clinical disability progression.

The total volume of new

or enlarging T2 lesions showed a substantial difference between vidofludimus calcium and placebo over time, with vidofludimus calcium

decreasing and placebo increasing (mean percent change, 3.19% benefit for vidofludimus calcium (-0.22%) over placebo (+2.97%) at month

reduction of confirmed disability worsening in PMS patients is a wonderful confirmation of the objectives of this exploratory phase 2

trial. CALLIPER was designed to evaluate the clinical efficacy, safety and tolerability of vidofludimus calcium in a broad set of PMS

patients to determine the suitability of advancing to a confirmatory phase 3 program," said Daniel Vitt, Ph.D., Chief Executive

Officer of Immunic. "We are particularly thrilled to see such a clinically meaningful effect in the PPMS population, with a 30%

reduction in the relative risk of 24-week confirmed disability worsening events, which would be the endpoint of a future phase 3 registration

study, outperforming historic trials in PPMS regarding numerical reduction of disability progression events. We believe that vidofludimus

calcium may represent a novel and exciting approach for people living with PMS, where there continues to be a huge unmet medical need

given only one approved therapy. We look forward to discussing these results with healthcare authorities to determine appropriate next

steps for vidofludimus calcium in PMS."

"The most significant

unmet need in MS continues to be the lack of safe and effective therapies that can slow or halt disease progression, especially in PPMS

and non-active SPMS. Vidofludimus calcium is the only medicine in development for MS that has been shown to be a potent activator of Nurr1,

which plays a key role in neuroprotection. With this unique mode of action, vidofludimus calcium could become the first real neuroprotective

treatment option for patients with progressive forms of MS," added Andreas Muehler, M.D., M.B.A., Chief Medical Officer of Immunic.

"In particular, the 29% reduction of 24-week confirmed disability worsening events for vidofludimus calcium over placebo in the

391 patients without gadolinium-enhancing lesions at baseline underlines the drug's breakthrough potential in addressing the high

unmet need of slowing neurodegeneration in MS patients. We believe today's exciting results of the phase 2 CALLIPER trial further

validate vidofludimus calcium's scientific rationale, specifically driven by the impressive numerical benefit in reducing disability

worsening, which deserves to be further tested in a phase 3 registration trial. Since almost all disability events in a non-active PMS

population are known to be progression independent of relapse activity (PIRA), we believe the CALLIPER results also corroborate the benefit

on disability progression expected for people suffering from relapsing forms of MS, allowing for a beneficial read-through to our ongoing

phase 3 ENSURE trials."

Safety and Tolerability

The top-line CALLIPER

data set confirmed the favorable safety and tolerability profile of vidofludimus calcium already observed in previous clinical trials.

No new safety signals were identified. The occurrence of treatment-emergent adverse events and serious adverse events showed a similar

frequency between both treatment arms. The rate of treatment-emergent adverse events was 69.4% of vidofludimus calcium-treated patients

compared with 68.5% of patients on placebo. Likewise, serious adverse events were rare and only observed in 8.1% of vidofludimus calcium-treated

patients, and in 6.5% of patients on placebo. Additionally, no Hy's law range cases regarding elevations of liver enzymes were observed

CALLIPER is an international, multicenter, randomized,

double-blind, placebo-controlled, exploratory phase 2 trial which enrolled 467 patients at more than 70 sites throughout North America

as well as Western, Central and Eastern Europe. Patients, aged 18 to 65 years and without limitation on disease duration, were randomized

to either 45 mg daily doses of vidofludimus calcium or placebo and treated for up to 120 weeks. CALLIPER enrolled mainly patients with

PPMS (n=152/467) and naSPMS (n=268/467). All patients showed no evidence of relapse in the last 24 months before randomization. For more

information, please visit: www.clinicaltrials.gov, NCT05054140.

Analysis of the full

CALLIPER data set is ongoing and will be presented at upcoming scientific meetings. The company's phase 3 clinical trial program

of vidofludimus calcium in relapsing multiple sclerosis is ongoing and expected to be completed in 2026.

Immunic will host a webcast today at 8:00 am ET

to discuss these results. To participate in the webcast, please register in advance at: https://imux.zoom.us/webinar/register/WN_tzX8otsFRAawwEmjwgCjeA

or on the "Events and Presentations" section of Immunic's website at: ir.imux.com/events-and-presentations.

Registrants will receive a confirmation email containing a link for online participation or a telephone number for dial in access.

An archived replay of the webcast will be available

approximately one hour after completion on Immunic's website at: ir.imux.com/events-and-presentations.

sclerosis (MS) in general is an autoimmune disease characterized by immune-mediated demyelination that affects the brain, spinal cord

and optic nerve, the progressive phase of the disease seems to be dominated by significant neurodegenerative mechanisms. Progressive multiple

sclerosis (PMS) is a clinical form of MS characterized by gradual accrual of disability independent of relapses over time. PMS includes

both primary progressive MS (PPMS) and secondary progressive MS (SPMS). PPMS is characterized by steadily worsening neurologic function

from the onset of symptoms without initial relapse or remissions. SPMS is identified following an initial relapsing-remitting course,

after which the disease becomes more steadily progressive, with (active SPMS) or without (non-active SPMS) MRI lesions and/or relapses

Vidofludimus calcium is an orally administered

investigational small molecule drug being developed for chronic inflammatory and autoimmune diseases, currently in late-stage clinical

trials for multiple sclerosis (MS). Uniquely, vidofludimus calcium's first-in-class, dual mode of action combines neuroprotective,

anti-inflammatory and anti-viral effects to target the complex pathophysiology of MS. As a selective immune modulator, it activates the

neuroprotective transcription factor, nuclear receptor-related 1 (Nurr1), which provides direct and indirect neuroprotective effects.

Additionally, vidofludimus calcium achieves anti-inflammatory and anti-viral effects through highly selective inhibition of the enzyme

dihydroorotate dehydrogenase (DHODH). Vidofludimus calcium is currently being evaluated in phase 3 and phase 2 clinical trials for the

treatment of relapsing and progressive MS, respectively. In a phase 2 clinical trial, it has shown therapeutic activity in patients suffering

from relapsing-remitting MS, significantly reducing MRI lesions and demonstrating encouraging results in reducing confirmed disability

worsening. Additionally, vidofludimus calcium has demonstrated clinical benefits in progressive MS patients by showing substantial reductions