ALS Association Gives INmune Bio $500K to Advance Protein Targeting Innate Immune System

The biotechnological company INmune Bio has been awarded a $500,000 grant from the ALS Association to further develop a therapy that might reprogram the innate immune system in people with amyotrophic lateral sclerosis (ALS).

The grant will fund proof-of-concept studies for INmune Bio’s XPro1595, a protein that targets the innate immune defects and chronic inflammation that occurs in ALS and in Alzheimer’s, which this protein was first developed to treat.

The innate immune system is the body’s first responder to foreign threats such as bacteria or a virus. In the brain and spinal cord, microglial cells are a key component of the innate immune system. 

Microglial are activated by a potent immune signaling molecule called soluble tumor necrosis factor (sTNF). In normal circumstances, microglial cells have an anti-inflammatory function, but as ALS progresses they shift into a pro-inflammatory and neurotoxic state.

The goal of XPro1595 is to neutralize sTNF, and so stop the activation of microglia cells and the subsequent inflammation that causes nerve cell death and loss of communication between nerve cells.

Importantly, XPro1595 is designed to bind specifically to the soluble form of TNF, without affecting its membrane form that is required for the normal functioning of the immune system. Binding to both forms of TNF has been a major setback of most therapies targeting this inflammatory signaling molecule.

“While our knowledge of ALS has increased dramatically in the past few years, there are currently no disease modifying therapies,” CJ Barnum, PhD, director of neuroscience for INmune Bio, said in a press release.

“The innate immune system plays a central role in the development and progression of ALS. We believe precision targeting of the innate immune system by targeting inflammation with XPro1595 may be an effective treatment strategy in alleviating ALS,” Barnum added.

“This award allows INmune Bio to take the first step to determine whether XPro1595 has therapeutic potential for ALS patients.” 

The ALS Association is the largest private funder of ALS research in the world. This research grant will be allocated over two years, and was awarded through the association’s The Lawrence and Isabel Barnett Drug Development Program.

The program supports preclinical testing and development of pre-investigational new drug (pre-IND) therapeutics for ALS that have a high probability of reaching the clinic within three years.

“We believe INmune is on a path to unlocking some of the mystery around the immune system and how it responds to the kinds of inflammation that we know plays a role in ALS progression,” said Kuldip Dave, PhD, vice president of research at the ALS Association.

“We are honored to receive this grant from The ALS Association, the pre-eminent organization supporting novel treatments for ALS,” said R.J. Tesi, MD, CEO of INmune Bio. “This award supports our approach and moves the company’s ALS program closer to the clinic.”

An ongoing program is testing XPro1595 in Alzheimer’s disease. The compound has been studied in three animal models of Alzheimer’s, where it was seen to normalize both innate and adaptive immune responses, largely blocking toxic amyloid buildup, and preventing the loss of neuron communication and cognitive impairment.

A recently opened Phase 1b trial (NCT03943264) is studying XPro1595’s safety, tolerability, and early efficacy in people with mild to moderate Alzheimer’s disease, who have evidence of systemic inflammation. The 12-week study is testing multiple doses of the therapy to identify an optimal dosing for future trials. Changes in inflammatory biomarkers and Alzheimer’s proteins will be assessed as secondary measures. 

This study is enrolling eligible patients at sites in Australia.