Immunic, Inc. (IMUX)

Executive Summary / Key Takeaways

• Immunic is advancing a pipeline of oral immunology therapies, led by vidofludimus calcium (IMU-838) for multiple sclerosis (MS) and IMU-856 for gastrointestinal (GI) diseases, leveraging unique mechanisms of action to address high unmet needs.
• Recent positive data from the Phase 2 CALLIPER trial in progressive MS, showing a 30% reduction in confirmed disability worsening in primary progressive MS patients and significant NfL reduction, strongly supports vidofludimus calcium's neuroprotective potential.
• The company completed enrollment for both Phase 3 ENSURE trials in relapsing MS in June 2025, following a positive interim futility analysis in October 2024, maintaining the path towards potential regulatory approval with readouts expected in Q2 and 2H 2026.
• IMU-856 demonstrated clinical proof-of-concept in Phase 1b celiac disease data, showing gut barrier restoration and potential in weight management (dose-dependent GLP-1 increase), positioning it for Phase 2 development contingent on securing dedicated funding or partnerships.
• While recent financings, including a $65 million offering in June 2025 and a $5.1 million offering in April 2025, have bolstered liquidity, the company's accumulated deficit and ongoing R&D costs necessitate further capital raises or strategic collaborations to fund operations beyond the current runway into Q3 2025 and complete development programs.

Immunic: Targeting Chronic Inflammation with Oral Innovation

Immunic, Inc. is a biotechnology company focused on developing a clinical pipeline of selective oral immunology therapies aimed at treating chronic inflammatory and autoimmune diseases. Founded in 2016, the company strategically built its foundation through the acquisition of assets and expertise, notably through the transaction with Vital Therapies in 2019, which provided a platform for advancing its lead programs. Immunic's strategy centers on identifying and developing small molecule therapies with unique mechanisms of action designed to offer differentiated benefits over existing treatments, particularly in areas of high unmet medical need like multiple sclerosis (MS) and various gastrointestinal disorders.

The company operates primarily from its main base in Gräfelfing, Germany, supported by a presence in New York City and a subsidiary in Australia, allowing it to leverage global research and clinical development capabilities. This structure facilitates relationships with international service providers, contributing to the efficient execution of its development programs. Immunic's approach is to advance its most promising candidates through clinical trials, explore additional therapeutic applications for its platform technologies, and evaluate strategic collaborations to support development and potential commercialization.

The landscape for chronic inflammatory and autoimmune diseases is highly competitive, dominated by large pharmaceutical companies with established product portfolios, particularly in MS and inflammatory bowel disease (IBD). Key players like Biogen (BIIB), AbbVie (ABBV), Novartis (NVS), Gilead Sciences (GILD), and Sanofi (SNY) command significant market share with a range of therapies, including injectable biologics and oral small molecules. Competition is intense, driven by the need for improved efficacy, safety, tolerability, and convenience. While larger competitors benefit from economies of scale in R&D, manufacturing, and distribution, Immunic aims to carve out a niche by developing oral therapies with potentially superior benefit-risk profiles and novel mechanisms that address aspects of disease pathophysiology not fully targeted by current treatments.

Technological Edge: Dual Action and Barrier Restoration

Immunic's pipeline is underpinned by differentiated technological approaches. The lead candidate, vidofludimus calcium (IMU-838), stands out due to its dual mechanism of action. It acts as a highly selective inhibitor of dihydroorotate dehydrogenase (DHODH), a key enzyme involved in the metabolism of overactive immune cells, providing potent anti-inflammatory and antiviral effects. Crucially, vidofludimus calcium is also a first-in-class activator of the nuclear receptor-related 1 (Nurr1) pathway. Preclinical data has shown that vidofludimus calcium directly binds to Nurr1 and enhances the expression of Nurr1 target genes important for neuronal survival, demonstrating an up to 500% increase in gene regulation in some studies. This Nurr1 activation is associated with direct neuroprotective properties, a critical need in progressive forms of MS.

This combined anti-inflammatory, antiviral, and neuroprotective profile is believed to be unique in the MS treatment space, offering a potential advantage over therapies that primarily target inflammation. The company's clinical data supports this differentiation; interim analysis of the Phase 2 CALLIPER trial in progressive MS showed a significant reduction in serum neurofilament light chain (NfL), a biomarker of neuronal damage, reinforcing the neuroprotective potential. More recently, topline CALLIPER data announced in April 2025 demonstrated a 30% reduction in the relative risk of 24-week confirmed disability worsening (24wCDW) events in primary progressive MS patients compared to placebo, a 20% reduction in the overall progressive MS population, and a 15% reduction in the non-active secondary progressive MS population. The trial also showed a 20% reduction in the annualized rate of thalamic brain volume loss. These clinical outcomes, particularly the impact on disability worsening in progressive MS subtypes with high unmet need, highlight the potential tangible benefits of vidofludimus calcium's unique MOA. Furthermore, the drug has shown a favorable safety and tolerability profile across trials, with no anticipated need for first-dose or on-treatment monitoring and no expected black box warnings, which could offer a significant convenience advantage over some currently available oral and injectable MS therapies.

The second key program, IMU-856, is an orally available, systemically acting small molecule modulator targeting Sirtuin 6 (SIRT6). This mechanism is designed to regenerate bowel epithelium and restore intestinal barrier function, offering a potentially novel approach to treating a range of GI diseases. Unlike many current IBD therapies that are broadly immunosuppressive, preclinical data suggests IMU-856 may maintain immune surveillance, which would be a significant advantage. Positive Phase 1b data in celiac disease patients demonstrated improvements in gut architecture, symptoms, biomarkers, and nutrient absorption. A post hoc analysis of this data also revealed a dose-dependent increase in endogenous GLP-1 levels and corresponding effects in preclinical models showing reduced body weight gain and food consumption, suggesting potential applicability in weight management. This barrier restoration mechanism represents a distinct technological approach compared to the immunosuppressive strategies common among competitors like AbbVie's Humira or other biologics in the IBD space.

Immunic is also exploring next-generation molecules like IMU-381 for GI diseases, aiming for improved tissue penetration, and continuing preclinical research leveraging its Nurr1 platform for other neurodegenerative indications like Parkinson's disease, where Nurr1 is believed to play a major role. The company has built an extensive patent portfolio around vidofludimus calcium, with protection extending into the 2040s in the US, further strengthening its competitive moat.

Financial Performance and Funding the Pipeline

As a clinical-stage biotechnology company, Immunic has not generated revenue from product sales and has consistently incurred operating losses since its inception in 2016. The accumulated deficit stood at approximately $536.9 million as of March 31, 2025. Operating expenses are primarily driven by research and development costs associated with advancing the clinical pipeline. For the three months ended March 31, 2025, R&D expenses were $21.5 million, an increase from $18.7 million in the same period of 2024, primarily due to increased external development costs for the vidofludimus calcium programs. General and administrative expenses were $5.3 million in Q1 2025, a slight increase from $5.1 million in Q1 2024. The net loss for Q1 2025 was $25.5 million, compared to a net loss of $29.6 million in Q1 2024. The change in net loss was influenced by fluctuations in other income/expense, including interest income (decreasing due to lower cash balances) and non-cash charges related to the fair value of tranche rights in 2024.

Funding operations and the costly clinical trials requires significant capital. From inception through March 31, 2025, Immunic had raised approximately $430.9 million in net cash from various offerings. As of March 31, 2025, cash and cash equivalents were approximately $14.3 million. The company explicitly stated in its Q1 2025 filing that, based on funds available as of March 31, 2025, it did not have adequate liquidity to fund operations for at least twelve months without raising additional capital, which raises substantial doubt about its ability to continue as a going concern if further funding is not secured.

Subsequent to the Q1 2025 filing date (May 15, 2025), Immunic completed further financing activities. In April 2025, the company closed a registered direct offering, raising approximately $4.6 million in net proceeds. In June 2025, Immunic announced the closing of an oversubscribed underwritten public offering, raising approximately $65 million in gross proceeds. These capital raises are critical to extending the company's cash runway and funding ongoing clinical development, particularly the Phase 3 ENSURE trials and preparations for IMU-856 Phase 2 studies. The company also has access to an At-The-Market (ATM) facility with $80 million in capacity remaining as of March 31, 2025, providing another potential source of funds. Management anticipates financing future needs through a combination of equity offerings, debt, and strategic collaborations, acknowledging that market volatility and terms of financing could pose challenges.

Outlook and Strategic Catalysts

The near-term outlook for Immunic is heavily focused on the continued progress and potential outcomes of its lead clinical programs. The topline data from the Phase 2 CALLIPER trial in progressive MS, announced in April 2025, represents a major catalyst. The positive results, particularly the significant reduction in confirmed disability worsening in PPMS patients, are expected to inform discussions with health authorities regarding the potential path forward for vidofludimus calcium in progressive MS, including the possibility of an expedited regulatory pathway, although this is not guaranteed. Management has indicated that a Phase 3 study in non-active secondary progressive MS, if pursued, might require only a single trial.

For the Phase 3 ENSURE program in relapsing MS, the positive interim futility analysis in October 2024 confirmed that the trials should continue as planned, validating the initial design assumptions. Enrollment for both ENSURE trials was completed in June 2025, a significant operational milestone. Readouts from the first ENSURE trial are anticipated in the second quarter of 2026, followed by the second trial in the second half of 2026. These readouts are critical for potential regulatory submissions and represent major value inflection points.

The IMU-856 program is also progressing, with preparations underway for a Phase 2 clinical trial in ongoing active celiac disease. The promising Phase 1b data, including the potential for weight management suggested by GLP-1 effects, opens up multiple potential indications beyond celiac disease, such as IBD and short bowel syndrome. However, advancing IMU-856 into Phase 2 is contingent on securing dedicated funding or a strategic partner capable of supporting multiple therapeutic trials, which the company is actively exploring.

Strategic collaborations remain a key part of Immunic's plan to complement its R&D capabilities and facilitate potential commercialization. The recent positive data from both the vidofludimus calcium and IMU-856 programs are expected to serve as catalysts for these partnering discussions. The company has also strengthened its leadership team and board with hires bringing expertise in MS drug launch and commercialization, signaling preparations for potential market entry if clinical success continues. Management has expressed confidence in vidofludimus calcium's potential to transform the oral MS market, citing expected peak sales ranging from $2 billion to $6 billion if approved across broad indications.

Risks and Challenges

Despite the promising clinical data and strategic progress, Immunic faces significant risks inherent in the biotechnology industry. The most prominent risks include the possibility that ongoing or future clinical trials may fail to meet their endpoints, that regulatory approvals may not be obtained even with positive data, and the critical need for additional funding to complete the development and potential commercialization of its product candidates. The "going concern" risk highlighted in the Q1 2025 filing underscores the dependency on future capital raises or partnerships.

Market volatility could impact the company's ability to raise funds on favorable terms, potentially leading to significant stockholder dilution or restrictive debt covenants if that financing route is pursued. Pursuing collaborations may require relinquishing substantial rights to its technologies or future products. Operational risks include potential delays in clinical trials and the challenges of managing a global development program. The company is also exposed to foreign currency exchange rate fluctuations, which can impact financial results and the value of assets held in foreign currencies. Furthermore, the industry is prone to litigation, particularly concerning patents and intellectual property rights, which could be costly and time-consuming.

Conclusion

Immunic stands at a potentially transformative juncture, driven by a pipeline of oral therapies with differentiated mechanisms of action targeting significant unmet needs in chronic inflammatory and autoimmune diseases. The recent positive topline data from the Phase 2 CALLIPER trial in progressive MS provides compelling evidence for vidofludimus calcium's neuroprotective potential, complementing its established anti-inflammatory and antiviral effects. Coupled with the completion of enrollment in the Phase 3 ENSURE trials for relapsing MS, the company is advancing its lead program towards critical regulatory milestones in 2026.

The IMU-856 program also holds promise with clinical proof-of-concept in celiac disease and potential in weight management, offering a novel approach to GI disorders. While recent financing activities have provided a temporary liquidity boost, securing sufficient capital remains paramount to fully realize the potential of these programs and address the going concern risk. The success of ongoing clinical trials, the ability to secure strategic partnerships, and navigating the regulatory landscape will be key determinants of Immunic's future trajectory and its ability to deliver on the promise of its innovative oral therapies.