Dosing Begins in Phase 2 Trial of XPro1595, Targeting Inflammation

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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A first patient has been dosed in a Phase 2 trial of XPro1595INmune Bio’s candidate therapy for Alzheimer’s disease.

The MINDFuL trial (NCT05318976) aims to recruit around 201 people, ages 60–85, with mild Alzheimer’s and biomarkers of brain inflammation across multiple sites in the U.S., Australia, and Canada. Top-line results are expected in 2023.

For more information on enrollment, including trial sites, those interested can contact INmune at [email protected].

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Participants will be randomly assigned to XPro1595, injected subcutaneously (under the skin) once a week at a dose of 1.0 milligrams per kilogram (mg/kg), or to a weekly placebo injection for six months.

The trial will evaluate the therapy’s effectiveness in lessening neuroinflammation and, as a result, improving cognition and function.

Patients who complete the Phase 2 study will be able to participate in an extension study during which all will be treated with XPro1595. They will be monitored for biomarkers of inflammation and changes in cognition for up to an additional 12 months.

“This Phase 2 study will determine whether improvement in these biomarkers translates into a clinical benefit of improved cognition and function in patients with mild AD and biomarkers of inflammation,” C.J. Barnum, PhD, vice president of CNS development at INmune Bio, said in a press release.

The study follows early evidence from a Phase 1b clinical trial (NCT03943264) in which XPro1595 reduced white matter free water, a biomarker of neuroinflammation, in adults with mild to moderate Alzheimer’s disease with signs of inflammation.

Treatment with XPro1595 also boosted the integrity of axons, the nerve cell projections that transmit information (electrical impulses), in specific brain regions.

“The Phase 1 study data clearly showed an improvement in multiple biomarkers related to [Alzheimer’s disease] pathology, including a reduction in neuroinflammation and neurodegeneration, and an improvement in biomarkers of neurorepair and neuron communication,” Barnum said.

XPro1595 is designed to cross the blood brain barrier (BBB) and lower inflammation in the brain by targeting and blocking soluble tumor necrosis factor (sTNF), an inflammatory molecule that has been implicated in Alzheimer’s progression. Of note, the BBB is a semi-permeable membrane that shields the central nervous system (brain and spinal cord) from the general blood circulation.

“Our next-generation TNF inhibitor candidate XPro crosses the blood brain barrier to neutralize sTNF in the brain and has the ability to decrease peripheral inflammation, one of the causes of neuroinflammation in the brain,” said RJ Tesi, MD, the company’s CEO.

INmune Bio is also conducting a Phase 2 trial (NCT05321498) to test XPro1595 in people with mild cognitive impairment and markers of neuroinflammation. This trial is not yet recruiting; contact information is available on its NCT document.