The journey toward effective therapies for patients with multiple sclerosis (MS) is marked by persistent challenges. Despite advancements in addressing relapses, the specter of disability progression looms large, leaving a significant unmet need in patient care.
Immunic Inc (NASDAQ:IMUX) is a US-listed biotechnology company dedicated to revolutionizing MS treatment. At the heart of its research is vidofludimus calcium, which could not only target relapses but also offer neuroprotective and anti-viral properties—a potential game-changer in the MS arena.
The company recently closed an up to $240 million funding round to help advance vidofludimus calcium through a twin Phase 3 relapsing MS and a Phase 2 progressive MS program.
In conversation with Proactive, CEO Dr Daniel Vitt delves into Immunic's ground-breaking efforts, exploring the significance of their approach, the pivotal role of recent interim data in shaping treatment paradigms, and the broader implications for the future of MS care.
Proactive: To start, you have a Phase 3 program ongoing in RMS and a Phase 2 trial ongoing in PMS. Can you explain the unmet need in the different forms of multiple sclerosis?
Daniel Vitt: Initially, the focus was primarily on preventing relapses, leading to the development of several highly potent molecules capable of lowering the relapse rate in MS patients. However, a somewhat problematic or overlooked issue is that despite having treatments targeting relapses, patients are still experiencing progression on the disability scale, even in the absence of any relapses or focal inflammation. This underscores the pressing medical need today. Above all, we need to know that there's an overlap between relapsing and progressive forms of MS. Both groups of patients experience worsening of disability, independent of relapses, called PIRA. This, I believe, defines the most significant medical need currently in developing new drugs for MS.
Additionally, other important factors include the necessity for easy-to-use drugs that are safer and exhibit better tolerability. There's a strong desire for neuroprotective agents that can effectively protect the brain from cell death, which may be the most significant aspect to address.
Can you explain the progress and benefits of vidofludimus calcium (IMU-838) in treating multiple sclerosis, focusing on its neuroprotective and anti-inflammatory properties?
Vidofludimus calcium is a truly unique molecule with a very special structure. Our research has revealed its dual effects, marking a significant advancement in the field. Originally, the drug was designed as a DHODH inhibitor, targeting a protein involved in immune metabolism. This makes it a promising candidate for combating autoimmune diseases like MS, where an overactive immune response is a key factor. However, what sets it apart is its additional function as a Nurr1 activator. Nurr1 is a protein that is a so-called transcription factor. It’s a nuclear receptor that plays a crucial role in protecting neurons from cell death. Notably, both neurons and immune cells in the brain express the targets affected by Nurr1, indicating its potential for influencing brain communication. Studies have demonstrated the neuroprotective effects of Nurr1 activation, a breakthrough that forms the core of our development efforts. We aim to harness this mechanism as a therapeutic target.
You recently discovered Nurr1 as vidofludimus calcium’s second target. Can you share some insights? What makes this target crucial?
Initially, we observed the neuroprotective effects in clinical settings, particularly through a detailed analysis of our Phase 2 study in relapsing MS. This EMPhASIS trial, conducted about three to four years ago, raised several questions, particularly regarding why vidofludimus calcium was so effective in preventing disability worsening as a clinical endpoint. During the study, patients were monitored for an initial 24-week treatment period and then followed up during the open-label extension phase, which we had an interim look at after two years, yielding remarkably positive data.
The challenge then became understanding the molecular mechanism behind this neuroprotective effect. To tackle this, we collaborated with academic groups, which led to the identification of vidofludimus calcium as a unique activator of a specific nuclear receptor, Nurr1. This finding was significant as it marked the first instance of such activation in the scientific landscape. Our academic partners were equally enthused by this discovery, as it represented a significant scientific advancement beyond mere clinical application.
Regarding the CALLIPER trial, could you clarify the significance of the positive interim data, especially the improvements in neurofilament light chain, NfL, levels? How does this contribute to the drug's potential in treating progressive multiple sclerosis?
One of the questions we have is whether we can demonstrate the neuroprotective potential of vidofludimus calcium in isolation. Naturally, this would entail isolating relapses from progression independent of relapses, and patients with PMS fit this criterion very well. Hence, the CALLIPER trial is ideally suited to explore the drug's neuroprotective potential. The study was designed to assess various endpoints, including brain atrophy and disability worsening after two years of treatment with the drug or placebo. However, with 467 patients randomized into the study, we needed to ascertain whether there was a signal early on.
To mitigate risk and maintain the integrity of the trial, we introduced an interim analysis limited to biomarkers. The results were highly encouraging. Both patients with primary progressive MS and those with secondary progressive MS experienced significant benefits from the treatment, with the overall NfL biomarker signal being 22% lower in treated patients compared to placebo. This result is particularly noteworthy for secondary progressive patients, as there is currently no available treatment for them. Such data, observed on such a large scale, is unprecedented and greatly excites us. We eagerly await the full readout in April 2025.
You also have the ENSURE registrational program in relapsing multiple sclerosis ongoing. How does the overall approval strategy look for vidofludimus calcium?
The ENSURE program was intentionally crafted with a highly conservative design approach to facilitate approval in relapsing MS. We essentially mirrored our Phase 2 approach from the EMPhASIS trial, aiming for a seamless transition into a Phase 3 program to corroborate our findings. Thus, we refrained from altering too many parameters, maintaining baseline characteristics similar to those in the Phase 2 trial. We also retained the 30-milligram dose, which had demonstrated efficacy in reducing lesion count in the brain, as our primary endpoint in the EMPhASIS trial.
Overall, our approach was notably conservative. The primary endpoint here is relapse prevention. While there are existing drugs for treating relapses, these are sometimes associated with severe side effects, which brings me to the second unmet medical need in MS: safety and tolerability. In relapsing MS, in addition to potential disability protection and an improved safety profile, our drug could significantly impact its practical use. This is particularly relevant when considering earlier treatment options for such a molecule. Moreover, if we can demonstrate a disability protective effect in the PMS study, we anticipate a spill-over effect into RMS patients as well. This is because these patients also experience progression independent of relapse activity, thereby potentially benefiting from our treatment.
How do you plan to use the recently secured up to $240 million from the private placement to support the development of vidofludimus calcium, IMU-856, and IMU-381? Are there specific goals or trials these funds will address?
The funds are clearly dedicated to the MS program and PMS/RMS development. When we started this discussion, it was also triggered by the interim data analysis we discussed, as investors were intrigued by the NfL data we presented. This has rendered the investment quite attractive, mitigating the perceived risks associated with the Phase 2 study. Therefore, it served as a catalyst. The utilization of proceeds is committed to the PMS Phase 2 and RMS Phase 3 studies.
Additionally, the tranche structure of the financing, with $80 million tranches, provides us with better access. The first tranche alone is sufficient to fully finance the Phase 2 PMS study, with funds extending about half a year beyond the readout. This affords us ample time, with just the initial tranche, to make decisions on the subsequent steps. For instance, we could consider partnering for further development or proceed independently, potentially banking on a conditional approval.