INmune Bio Focused on Novel Clinical Trial Designs to Advance Next Generation of Alzheimer’s Disease Treatments

INmune Bio, Inc. recently participated in the 15th CTAD Conference in San Francisco November 29 to December 2.

“This year’s CTAD is showcasing a potential approvable therapy for the treatment of Alzheimer’s Disease (AD) that targets amyloid,” said RJ Tesi MD, CEO of INmune. “While anti-amyloid therapies may slow the rate of cognitive decline, we believe the goal for AD therapy should be to stop progression of the disease.  This will require the incorporation of novel biomarkers into innovative clinical trial designs.”

INMB continues an ongoing AD Phase 2 program focused on stopping the progression of AD by focusing on four unique elements, including: (i) enrichment criteria; (ii) novel, non-invasive neuroimaging biomarkers; (iii) use of EMACC as a cognitive endpoint; and (iv) strategic trial design. The following describes these four unique elements:

• Enrichment criteria are used to match the patient’s AD with the mechanism of INmune’s XPro treatment. Using a novel group of easily measured blood biomarkers, INmune identifies patients who have neuroinflammation driving their AD related cognitive decline, a group we refer to as ADi. This strategy improves the probability of the patient responding to therapy. We believe about 50% of patients with AD meet the criteria of ADi, and these patients will be eligible for XPro therapy.
• Novel, non-invasive neuroimaging biomarkers are used to demonstrate biologic effects of XPro therapy in AD patients with neuroinflammation. With our neuroimaging partners, we use sophisticated analysis of AD white matter tracts to demonstrate the severity of the disease and the ability of XPro to affect the disease process. White matter analytics demonstrate decreased white matter free water (WMFW), and improvements in apparent fiber density (AFD) and radial density (RDt), which are measures of neuroinflammation, axonal quality and myelin content, respectively.
• Early AD/Mild Cognitive Impairment Cognitive Composite (EMACC) is used as the cognitive endpoint. EMACC is a validated cognitive scale that is superior to traditional cognitive scales (CDR, ADS-Cog) used in trials of early AD (early AD = MCI plus mild AD). EMACC was developed for use in patients with early AD.

  “The EMACC is unique as a cognitive endpoint in that it was developed and validated empirically using annual cognitive testing data extending over 4 years in four independent aging studies of Amyloid-confirmed Early AD patients,” said Judith Jaeger PhD, one of the developers of EMACC. “The EMACC is made up of the combination of test measures that are most sensitive to the cognitive functions that decline in this stage of AD.  Hence, it most precisely captures the most relevant information about cognitive progression in early AD.“

• Statistical power and innovative trial design is strategically used to perform smaller, faster trials. AD patients with neuroinflammation progress more rapidly and more predictably than AD patients without neuroinflammation, such biology of neuroinflammation allowing for the design of smaller and shorter clinical trials. Our mild AD trial studies 201 patients and lasts 6 months with a 2:1 enrolment ratio (2 XPro™ treated patients for each placebo patient). Shorter/smaller trials consume less company resources and decrease “disease progression” risk to patients. In contrast, because of the pace of AD progression, a patient that participates in an 18-month trial and that receives placebo may progress to a disease state that makes them ineligible for crossover therapy. This limitation will happen less often in trials that last 6 months.

“The use of novel enrolment criteria, easily measured pharmacodynamic end-points, innovative trial design and cognitive testing strategies are needed to progress the AD field beyond traditional anti-amyloid therapies,” said CJ Barnum, VP CNS Drug Development. “We believe the use of non-invasive neuroimaging biomarkers and fit-for-purpose cognitive end-points will help develop effective therapies for AD and other forms of dementia. If the field continues to focus on the failed development strategies used for the last 20 years, little progress will be made. Our strategy is different, and it is our belief that it will ultimately be better.”

XPro is a next-generation inhibitor of tumor necrosis factor (TNF) that is currently in clinical trial and acts differently than currently available TNF inhibitors in that it neutralizes soluble TNF (sTNF), without affecting trans-membrane TNF (tmTNF) or TNF receptors. XPro™ could have potential substantial beneficial effects in patients with neurologic disease by decreasing neuroinflammation, improving axonal quality and synaptic function while promoting remyelination.

INmune Bio, Inc. is a publicly traded, clinical-stage biotechnology company focused on developing treatments that target the innate immune system to fight disease. INmune Bio has two product platforms that are both in clinical trials: The Dominant-Negative Tumor Necrosis Factor (DN-TNF) product platform utilizes dominant-negative technology to selectively neutralize soluble TNF, a key driver of innate immune dysfunction and a mechanistic driver of many diseases. DN-TNF product candidates are in clinical trials to determine if they can treat cancer (INB03), Mild Alzheimer’s disease, Mild Cognitive Impairment and treatment-resistant depression (XPro). The Natural Killer Cell Priming Platform includes INKmune developed to prime a patient’s NK cells to eliminate minimal residual disease in patients with cancer. INmune Bio’s product platforms utilize a precision medicine approach for the treatment of a wide variety of hematologic and solid tumor malignancies, and chronic inflammation. For more information, visit www.inmunebio.com.