The Case for Smarter Neuroinflammation Clinical Trials

Xtalks had the chance to speak with David Moss, CEO of INmune Bio, about designing clinical trials for therapies that target chronic inflammation. INmune Bio is developing therapies aimed at innate immune pathways, with programs including XPro1595 for neurodegenerative disease and CORDStrom for recessive dystrophic epidermolysis bullosa (RDEB).

RDEB is a rare genetic disease marked by chronic inflammation, fragile skin, blistering and erosions after minimal trauma. Severe RDEB can also involve the mouth and esophagus, leading to eating difficulties, strictures and other complications.

David has been with INmune Bio since the company’s formation in 2015, previously serving as CFO before becoming CEO. His background gives him a perspective that sits across science, trial strategy and biotech execution.

Inflammation Without Broad Immune Suppression

David began with what he sees as a core unmet need in inflammation-driven disease.

“We’ve never had a potent anti-inflammatory drug that’s not immunosuppressive,” David said. “We think that makes all the difference in the world.”

He said INmune Bio sees neuroinflammation as a component of many central nervous system (CNS) diseases. “You need to get rid of the underlying foundation of inflammation,” he said, noting an ongoing challenge, “but you have to do it without immunosuppression so you can get the immune cells of the brain to start to function again.”

David pointed to age, genetics and lifestyle factors as contributors to inflammation, with age playing the largest role in his framing. He used macrophages and microglia as an example of how immune cells can shift between functional states.

With CORDStrom, INmune Bio is taking a systemic view of RDEB. CORDStrom is INmune Bio’s cell therapy platform made from umbilical cord-derived mesenchymal stromal cells, a type of cell being studied in inflammatory and tissue-related diseases.

Designing Studies Around the Right Patients and Measures

Patient selection has been a key lesson from INmune Bio’s own Phase II work, according to David.

“When you run a trial that no one’s ever done before, you’re making educated guesses,” he said. “And we thought we had the right patient population, and we got close, but we weren’t quite right.”

David compared this to breast cancer, where clinical development has become more biologically specific over time. Trials now commonly select patients by tumor subtype, such as HER2-positive, HER2-negative or triple-negative disease, depending on the mechanism of action, or MOA, of the drug.

David said that inflammation-focused studies also need to match the patient population to the drug’s mechanism of action.

In CNS disease, however, clinical measures may be less direct. Cancer trials may measure tumor burden, progression or survival. CNS trials often measure cognition, memory or mood, which can vary across patients and trial settings.

“The endpoints that you use in dementia trials or CNS trials are a little squishy,” David said.

Some dementia endpoints were developed for moderate-to-severe patients but are still applied to early-stage patients. For a study in earlier disease, the measure needs to be sensitive enough to capture the kind of change expected in that population.

David suggested that CNS trials could borrow more from oncology, where biomarkers are often collected early to show whether a drug is doing more than meeting safety requirements.

“We’re really good at cancer. We have all these biomarkers that we measure along the way, even in a Phase I trial where we just don’t do safety — we’re doing safety and showing some sort of efficacy,” David said. “We should try and consider doing the same in CNS trials, right?”

For CNS trials, that could mean using blood, cerebrospinal fluid and imaging biomarkers earlier in development to show whether a therapy is producing biological activity.

Measuring Benefit in RDEB and Alzheimer’s

When asked which endpoints and biomarkers are most important for showing early efficacy and proof of mechanism, David first turned to INmune Bio’s CORDStrom program in RDEB.

David said the key measures include wounds, pain, itch and quality of life.

Itch can lead to scratching, which can reopen wounds and worsen pain, sleep and daily function. If wounds affect the mouth or esophagus, eating and weight gain can also become part of the clinical picture.

The quality-of-life changes in RDEB could show up in tangible ways. “If you’re able to make a difference in that, you should see things like weight gain or the ability to do things that you weren’t able to do before,” he said. “Even simple things like just sleeping better, getting better quality sleep.”

These measures may help researchers see whether a therapy is making a broader difference.

“The more data that you can collect and the longer period of time you’re able to follow through, the better,” David said.

He also noted that ultra-rare disease trials may not always produce a perfect p-value because enrollment is limited. Regulators may consider the totality of evidence, especially when a disease is severe and treatment options are limited.

INmune Bio and Anthony Nolan recently expanded an agreement to support long-term access to umbilical cord tissue for INmune Bio’s CORDStrom mesenchymal stromal cell platform. The collaboration will support development across RDEB, oncology and inflammatory diseases. The amended agreement was effective April 29, 2026.

In Alzheimer’s disease research, INmune Bio is focusing on patients with higher levels of neuroinflammation. These patients may decline faster, which could make it easier to measure change over six months. INmune Bio enriched its Alzheimer’s trial for that population, using a shorter study design shaped in part by development cost.

For cognitive assessment, the company used the Early Mild Alzheimer’s Cognitive Composite (EMACC), a tool designed for earlier-stage Alzheimer’s disease and for detecting change over a shorter period.

“Not only does it apply to the early-stage population, which is what we want, it’s also got tests that are specific to measure changes over a shorter period of time,” David said. “It’s more sensitive.”

This is part of working in a newer area of drug development, where companies may need to discuss unfamiliar endpoints and hypotheses with regulators.

“When you’re the first to do something — you’ve got to blaze a path and you’ve got to write the playbook,” David said.

Amyloid, Neuroinflammation and Clinical Benefit

A central question in Alzheimer’s drug development is how beta-amyloid plaque reduction relates to clinical benefit.

INmune Bio views amyloid beta as a useful biomarker of Alzheimer’s disease, but not the main driver of the disease.

“We believe the light that matches the fire is neuroinflammation,” David said.

He said approved anti-amyloid therapies are effective at removing amyloid beta, but in his view, they slow decline instead of stopping the disease trajectory.

INmune Bio’s hypothesis is that treating neuroinflammation over time, without immunosuppression, could reduce amyloid beta. Animal models have shown reversal of amyloid pathology, though the company has not yet run human studies long enough to show that effect.

David also discussed tau, describing it as a structural protein that has already broken down by the time it is being targeted. He said the goal is to prevent that breakdown by slowing or stopping cell death and allowing the immune system to clear debris.

He suggested that neuroinflammation-focused treatment could affect downstream brain health by slowing cell death and supporting processes involving myelin, synapses and neurons.

What Could Accelerate Inflammation-Focused Drug Development

So what could accelerate clinical development for inflammation-focused therapies?

David said inflammation-focused drug development could move faster if regulators one day accepted inflammation as a cross-disease driver, similar to the way cholesterol is used in cardiovascular risk. He acknowledged that this is unlikely in the near term, as regulators generally evaluate therapies for specific diseases.

“If we could look at inflammation the same way and say inflammation causes a lot of bad diseases, and if we can treat inflammation without immunosuppression, let’s do a trial on that,” David said.

He also returned to age as a major contributor to inflammation. His view is that while age itself cannot be changed, inflammatory biology may be modifiable if targeted correctly.

Because CNS trials are long, expensive and complicated, broader acceptance of biomarkers could help support development in neurodegenerative diseases in the near term.

These biomarkers include p-tau217 and glial fibrillary acidic protein (GFAP) in Alzheimer’s disease, neurofilament light chain in amyotrophic lateral sclerosis (ALS) and imaging biomarkers that measure white and gray matter changes.

“The issue we have with the brain that’s different than, let’s say, a tumor is — in a tumor, I can take a live biopsy and see what’s going on,” David said. “In the brain, you can’t do that, so you have to use these other biomarkers.”

If regulators look more closely at these types of biomarkers in the future, they could shorten drug development timelines, make trials smaller and less expensive and allow more therapies to move forward in neurodegenerative disease.

For David, inflammation-focused drug development means helping create a clinical trial path where little precedent exists.

“There’s never really been drugs approved to treat neuroinflammation in these diseases,” David said. “And so we don’t have a history to go back and look upon. We have to go create that history.”