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.
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.
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.
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."
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 (http://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.
Contact:
info@io-therapeutics.com
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