Io Therapeutics, Inc., presented data from studies of IRX4204, the company’s phase II clinical development stage, highly selective third generation RXR nuclear receptor agonist compound, supporting its potential use for prevention and treatment of normal aging-related neurodegeneration, Parkinson’s disease, and Alzheimer’s disease

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Published Jul 09, 2024 • 4 minute read

SPRING, Texas, July 09, 2024 (GLOBE NEWSWIRE) — Io Therapeutics, Inc., presented today results from studies done on the potential for prevention and treatment of normal aging-related neurodegeneration, Parkinson’s disease (PD), and Alzheimer’s disease (AD), with its clinical stage experimental therapeutic RXR nuclear receptor agonist compound IRX4204. IRX4204 is a highly potent and highly selective, orally available, brain penetrant, third generation RXR agonist compound which has been tested in early phase clinical trials in patients with Parkinson’s disease or cancers. The presentation titled “The highly potent and selective RXR agonist compound IRX4204 is a potential treatment for normal aging-related neurodegeneration, Parkinson’s disease (PD), and Alzheimer’s disease (AD)” was delivered at the Federation of American Societies for Experimental Biology (FASEB) Seventh International Conference on Retinoids, being held in St. Paul, Minnesota, USA. The presentation was authored by Vidyasagar Vuligonda, Ph.D., Chief Science Officer of the company and inventor of IRX4204, and Martin E. Sanders, M.D., the company’s Chief Executive Officer.

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Normal aging-related neurodegeneration has been reported to be substantially related to chronic low-grade inflammation in the brain, so called neuro-inflammaging. Neuro-inflammaging results in chronic loss of myelinated nerve fibers, causing disruption of functional neuroelectrical connections between neurons in various parts of the brain. Chronic neuro-inflammaging eventually leads to death of neurons. These neurodegenerative processes produce loss of memory and cognitive functions, and other functional disabilities in patients with normal brain aging, and in diverse types of neurological conditions including PD, and AD.

Neuro-inflammaging is related to imbalance of immunosuppressive T-regulatory cells (Treg) with pro-inflammatory cytokine interleukin-17 (IL-17) overproducing T-cells (Th17) in the brain. Neuro-inflammaging also is related to overactivity of brain microglia, which produce the pro-inflammatory cytokine interleukin-6 (IL-6), and other pro-inflammatory factors.

Parkinson’s disease (PD) and Alzheimer’s disease (AD) brains manifest similar neuro-inflammaging pathologies to those observed in normal brain aging, but also have distinct pathologies related to deposition of abnormal misfolded proteins such as alpha synuclein in PD, and beta amyloid in AD. It is generally accepted within the neurodegenerative diseases research community that neuro-inflammaging establishes an at-risk environment within the brain, that may increase vulnerability for development of PD, AD, and other neurodegenerative diseases.

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The presented studies showed that IRX4204 promotes differentiation and growth of immunosuppressive human Tregs, and inhibits differentiation of pro-inflammatory human Th17 cells, while reducing production of IL-17. IRX4204 also inhibits production by microglia of IL-6 and other pro-inflammatory factors. In addition, IRX4204 promotes differentiation and growth of myelin-producing oligodendrocytes in vitro and promotes myelinated nerve fiber protection and repair (remyelination) in mouse models of demyelination. IRX4204 demonstrated direct beneficial effects alone, and additively in combination with insulin, or thyroid hormone on cortical neurons in vitro, promoting neurite outgrowth, a neuro-reparative mechanism by which damaged neurons may re-establish function-preserving connections with other neurons. These findings support the potential for IRX4204 protecting against or even reversing neuro-inflammaging-induced chronic loss of myelinated nerve fibers and neuronal damage in normal brain aging and neurodegenerative diseases.

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Further demonstration of IRX4204 beneficial effects in neurodegeneration was provided by in vivo studies in rodent models of PD, and AD. IRX4204 effectively reduced motor deficits in a rat PD model while increasing dopaminergic neuron survival in the rat brains. In a transgenic beta amyloid mouse model of AD, IRX4204 decreased deposition of new beta amyloid in the mouse brains while preserving memory functions in the mice.

IRX4204 has demonstrated safety and tolerability of oral dosing in phase I and II clinical trials in 85 patients with various cancers and 15 patients with PD for up to 20 months of continuous treatment. In PD patients, IRX4204 demonstrated brain penetrance, and improvement of motor functions in 13 of 15 patients in open label assessments. The company is planning to initiate a placebo-controlled phase II clinical trial of IRX4204 in Parkinson’s disease patients in Q4 of 2024, to further demonstrate safety and efficacy in PD patients.

Dr. Vuligonda stated, “Our results identify a new approach to potentially slowing or reversing the neurodegeneration of normal aging, as well as treating the pathologic conditions of Parkinson’s disease and Alzheimer’s disease, which cause seriously disabling chronic decline of cognitive and other functional abilities.”

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Dr. Sanders stated, “IRX4204 has been safe and well tolerated in patients and has potential to be an effective monotherapy for prevention or treatment of debilitating neurologic manifestations associated with normal aging, Parkinson’s disease, Alzheimer’s disease and other neurologic conditions. In addition, IRX4204 provides opportunities for future development of combination treatments with even greater efficacy for these conditions, by administering IRX4204 with other generally well-tolerated and already available agents, such as insulin, GLP-1 agonists, other neurotrophic factors, thyroid hormone, or anti-beta amyloid monoclonal antibodies. We believe multi-agent combination treatments including IRX4204 will enable development of well tolerated, highly effective preventative and therapeutic interventions for diverse types of neurodegenerative diseases.”

About Io Therapeutics: Io Therapeutics, Inc. is a privately held company headquartered in Spring, Texas. More information on Io Therapeutics and its product development programs is available on the company’s web site: www.io-therapeutics.com

Forward Looking Statements: This news release contains “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995.

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