Rethinking Disease Modification Through Targeted Immunotherapy

By David Moss, CEO and cofounder, INmune Bio, Inc.

Inflammation sits at the center of many serious diseases, from ultra-rare genetic disorders like progeria and recessive dystrophic epidermolysis bullosa (RDEB), to common age-related conditions like Alzheimer’s disease. Yet most therapies still focus on managing symptoms rather than addressing the immune dysfunction that drives disease progression. As a result, patients often see limited long-term benefit, and promising science often fails to translate into durable clinical results.

Advances in immunology are beginning to change this dynamic. A new generation of therapies is emerging that aims to selectively reduce harmful inflammation while preserving the immune system’s ability to protect and repair tissue. This shift toward targeted immune modulation is influencing how preclinical programs are designed and how developers think about disease modification more broadly.

At INmune Bio, this philosophy underpins the development of two distinct therapeutic programs, CORDStrom and XPro, which address very different diseases but share a common biological focus on dysregulated inflammation and innate immune dysfunction. While the modalities and patient populations differ, the lessons from their development highlight broader considerations for drug discovery and translational research.

Why Broad Immunosuppression Falls Short

For decades, many anti-inflammatory therapies have relied on broad immunosuppression. While this approach can reduce inflammatory activity, it often introduces new risks, including increased susceptibility to infection, impaired tissue repair, and long-term safety concerns. In chronic diseases, suppressing immune function may ease symptoms temporarily but doesn’t change the underlying disease process.

This limitation frequently becomes apparent during development. A therapy may perform well in preclinical models by reducing inflammatory markers yet fail to deliver meaningful functional benefit in patients. In many inflammatory conditions, the immune system is both a contributor to pathology and a critical driver of repair, making indiscriminate suppression an imperfect solution.

INmune Bio’s approach has focused instead on precision immune modulation, reducing harmful inflammatory signaling while preserving protective immune responses. This strategy requires a deeper understanding of disease biology and careful alignment between preclinical findings and clinical trial design.

What Systemic Stromal Cell Therapies Reveal About Inflammation and Repair

Rare inflammatory diseases offer a clear view into how immune dysfunction drives progressive tissue damage. Recessive dystrophic epidermolysis bullosa (RDEB), a devastating genetic skin disorder, is caused by mutations affecting skin integrity. However, disease severity is amplified by chronic inflammation, impaired wound healing, pain, and scarring over time.

INmune Bio’s lead program, CORDStrom, is a systemic, umbilical cord–derived mesenchymal stromal cell (MSC) therapy being developed to address these upstream drivers of disease. Rather than targeting localized symptoms, CORDStrom is designed to modulate inflammatory signaling and support tissue repair at a systemic level.

Preclinical research for CORDStrom focused on models of systemic inflammation and impaired wound healing, including inflammatory injury and fibrosis models that reflect the chronic immune activation seen in RDEB. These studies consistently demonstrated that systemically administered MSCs could reduce pro-inflammatory cytokine signaling while promoting pathways associated with tissue repair and immune regulation.

One of the primary challenges in preclinical development was separating transient anti-inflammatory effects from durable biological impact. Early work highlighted that delivery route, dosing frequency, and cell manufacturing consistency all influenced persistence and therapeutic reach. This led to a development strategy that emphasized systemic administration and rigorous control of cell identity and potency, rather than relying on localized delivery or surrogate laboratory markers alone.

Experience from preclinical and clinical research in this area has highlighted several development considerations relevant beyond rare diseases:

• Systemic inflammation often requires systemic intervention; localized treatments may relieve symptoms but rarely alter disease progression.
• Delivery strategy influences biological impact, including persistence and therapeutic reach.
• Manufacturing consistency is essential for translational reliability and scalability.
• Functional outcomes, such as pain, itch, wound healing, and quality of life, can offer clearer insight into real-world benefits than laboratory markers alone.

These lessons apply broadly to any therapy intended to influence immune-driven tissue damage across multiple organ systems.

Targeting Neuroinflammation In Alzheimer’s Disease

Neurodegenerative disorders present a different but related challenge. Alzheimer’s disease has traditionally been viewed through the lens of amyloid plaques and tau tangles, which disrupt neuronal function, but growing evidence points to neuroinflammation as a key contributor to synaptic loss and cognitive decline.

INmune Bio’s XPro program reflects this evolving understanding. XPro is an anti-tumor necrosis factor (TNF) biologic designed to selectively reduce harmful inflammatory signaling without broadly suppressing immune function. This precision approach aims to address neuroinflammation while avoiding safety issues associated with more generalized immune suppression. Specifically, XPro selectively neutralizes soluble TNF while sparing transmembrane TNF activity, which is important for immune surveillance and tissue repair.

Preclinical development of XPro relied on established animal models of neuroinflammation and neurodegeneration, including models combining amyloid pathology with elevated inflammatory signaling. In these systems, selective inhibition of soluble TNF reduced microglial activation and preserved synaptic function, translating into improvements in cognitive and behavioral readouts. A central challenge was demonstrating that targeted TNF modulation could meaningfully impact neuroinflammation without introducing the safety risks associated with broad TNF suppression, which led to an early emphasis on biomarker development and the integration of imaging and inflammatory markers into the development program.

Development experience in this area reinforces several important principles:

• Inflammation varies widely across patients, making biomarker-based patient selection critical.
• Identifying subgroups with both disease pathology and heightened inflammation can improve signal detection in clinical trials.
• Safety monitoring, particularly through imaging and inflammatory biomarkers, must be incorporated early.
• Trial design should closely reflect a therapy’s mechanism of action, from inclusion criteria to endpoints.

Together, these insights suggest that success in neuroinflammatory drug development depends as much on strategic design as on scientific innovation.

Bridging Preclinical Insight And Clinical Impact

While CORDStrom and XPro differ in modality and indication, both programs are built around a shared goal: modifying disease by addressing immune dysfunction at its source. Their development highlights the importance of integrating preclinical biology, translational biomarkers, and clinical strategy from the outset.

Programs that advance successfully tend to prioritize biological relevance over technical novelty, align preclinical models with clinical decision-making, and consider manufacturing and scalability early in development. Looking across disease boundaries to identify shared inflammatory mechanisms also can unlock platform-level insights that extend beyond a single indication.

Looking Ahead

The future of immunotherapy lies in precision rather than suppression. As understanding of immune-driven disease deepens, therapies that selectively correct dysregulated inflammation have the potential to reshape treatment paradigms across both rare and common conditions.

For drug developers, the challenge is no longer simply reducing inflammation but doing so in a way that preserves the immune system’s essential role in protection and repair. By aligning preclinical insight, biomarkers, and trial design, companies like INmune Bio — and the broader industry — have an opportunity to move beyond symptom management and toward true disease modification.

About The Author

David J. Moss, CEO of INmune Bio, has been CFO since the formation of the company in September 2015. He has founded, funded, and taken public various companies in a variety of industries since 1995. Moss was a founding investor in Reliant Service Group LLC, which was acquired in 2015 by a leading private equity firm. He previously served as managing director, corporate finance for a New York-based securities firm, where he advised companies on corporate strategy, financing, and business development. Prior to that, he served as managing partner at a Seattle-based venture capital firm. Moss holds an MBA from Rice University and a BA in economics from the University of California, San Diego.