A 4-Week, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of the RXR Agonist Compound IRX4204 for the Treatment of Mild to Moderate Plaque Psoriasis

The goal of this clinical trial is to learn if IRX4204 works to treat plaque psoriasis in adults. It will also learn about the safety of IRX4204. The main questions it aims to answer are:
* Does IRX4204 treat plaque psoriasis symptoms?
* Does IRX4204 treat plaque psoriasis symptoms better than someone who is not being treated?
* What medical problems do participants have when taking IRX4204? Researchers will compare IRX4204 to a placebo (a look-alike substance that contains no drug) to see if the drug works to treat mild to moderate plaque psoriasis.
Participants will:
* Take IRX4204 every day for 28 days
* Visit the clinic once every week for checkups and tests
* Complete specific assessments about plaque psoriasis and changes to plaques

Start Date01 Mar 2025

Sponsor / Collaborator

Io Therapeutics, Inc.

NCT02991651

/ SuspendedPhase 1

A Phase I Study of IRX4204 in Combination With Erlotinib in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer

Patient selection: a) Pathological confirmation of non-small cell lung cancer without activating EGFR mutations; b) Advanced stage disease (IV or IIIB with malignant effusion) with at least two prior chemotherapy regimens; c) No available curative therapy; d) Pregnant women are excluded; e) Informed consent.
Pretreatment evaluation: a) Medical history and physical examination; b) Hepatic and renal function (bilirubin, aspartate aminotransaminase, creatinine); c) Preoperative staging evaluation including CT-chest or PET/CT scan;
Treatment plan: Three dose levels of IRX4204 and erlotinib will be studied using intra-patient dose escalation for dose levels 1 and 2. These study agents will be administered orally until progression of disease, unacceptable toxicities, activation of a phase II study of the combination, or exhaustion of the IRX4204 drug supply.
Evaluation on study: Adverse events will be graded on a scale of 0 to 5, using the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. Efficacy will be assessed using the RECIST v1.1 criteria based on CT-chest or PET/CT scan after 8 weeks of study treatment.

Start Date01 May 2016

Sponsor / Collaborator

Io Therapeutics, Inc.

[+1]

NCT02438215

/ CompletedPhase 1

An Open-Label, Single Site Study Using [123I]β-CIT Single Photon Emission Tomography (SPECT) to Evaluate Dopamine Transporter Binding Following Treatment With IRX4204 in Early Parkinson's Disease Subjects

This is a single site, open-label study designed to examine dopamine transporter density using [123I]β-CIT SPECT imaging before and following treatment with IRX4204 for a 30-day period in early Parkinson's disease patients. In addition, clinical evaluations will be performed to evaluate the effect of IRX4204 treatment on the motor and cognitive symptoms of PD.

Start Date01 Aug 2014

Sponsor / Collaborator

Io Therapeutics, Inc.

100 Clinical Results associated with IRX-4204

100 Translational Medicine associated with IRX-4204

100 Patents (Medical) associated with IRX-4204

Literatures (Medical) associated with IRX-4204

03 Jun 2024·Clinical cancer research : an official journal of the American Association for Cancer Research

IRX4204 Induces Senescence and Cell Death in HER2-positive Breast Cancer and Synergizes with Anti-HER2 Therapy

Article

Author: Coleman, Darian ; Vuligonda, Vidyasagar ; Brown, Powel H. ; Hill, Jamal ; Moyer, Cassandra L. ; Lanier, Amanda ; Mazumdar, Abhijit ; Sanders, Martin E. ; Qian, Jing

Abstract:

Purpose::

Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action.

Experimental Design::

IRX4204 effects on breast cancer cell growth and viability were determined using cell lines, syngeneic mouse models, and primary patient-derived xenograft (PDX) tumors. In vitro assays of cell cycle, apoptosis, senescence, and lipid metabolism were used to uncover a potential mechanism of action. Standard anti-HER2 therapies were screened in combination with IRX4204 on a panel of breast cancer cell lines to determine drug synergy.

Results::

IRX4204 significantly inhibits the growth of HER2-positive breast cancer cell lines, including trastuzumab and lapatinib–resistant JIMT-1 and HCC1954. Treatment with IRX4204 reduced tumor growth rate in the MMTV-ErbB2 mouse and HER2-positive PDX model by 49% and 44%, respectively. Mechanistic studies revealed IRX4204 modulates lipid metabolism and induces senescence of HER2-positive cells. In addition, IRX4204 demonstrates additivity and synergy with HER2-targeted mAbs, tyrosine kinase inhibitors, and antibody–drug conjugates.

Conclusions::

These findings identify HER2 as a biomarker for IRX4204 treatment response and demonstrate a novel use of RXR agonists to synergize with current anti-HER2 therapies. Furthermore, our results suggest that RXR agonists can be useful for the treatment of anti-HER2 resistant and metastatic HER2-positive breast cancer.

01 Jun 2024·Fitoterapia

Network analysis of microbiome and metabolome to explore the mechanism of raw rhubarb in the protection against ischemic stroke via microbiota-gut-brain axis

Article

Author: Huang, Mingmin ; Wang, Shumei ; Lin, Huiting ; Xian, Minghua ; Hu, Tao ; Liang, Jiaying ; Shen, Lin ; Ma, Zuqing ; Zhan, Sikai ; Cai, Jiale ; Li, Ting ; Liang, Shengwang

Ischemic stroke (IS) has attracted worldwide attention due to the high mortality and disability rate. Raw rhubarb (RR) is a traditional medicinal plant and whole-food that has been used in China for its various pharmacological activities, such as antioxidant and anti-inflammatory properties. Recent pharmacological research has shown the role of RR against IS, but its mechanism of action remains unclear, particularly in the context of the brain-gut axis. To address this gap in knowledge, the present study was conducted in the middle cerebral artery occlusion/reperfusion (MCAO/R) model with the aim of investigating the effects of RR on regulating the intestinal microbiota barrier and metabolism and thereby reducing inflammatory response so as to improve the IS. The results showed that pre-treatment of RR attenuated cerebral infarct area and inflammation response in MCAO rats. Furthermore, RR also improved intestinal barrier function, including the integrity and permeability of the intestinal barrier. Additionally, RR intervention significantly attenuated gut microbiota dysbiosis caused by ischemic stroke, especially the increased Firmicutes. Notably, the pseudo-germ-free (PGF) rats further demonstrated that the anti-stroke effect of RR might rely on intestinal microbiota. In addition, the UPLC/Q-Orbitrap-MS-Based metabolomics revealed the disrupted metabolic profiles caused by MCAO/R, and a total of 11 differential metabolites were modulated by RR administration, especially bile acids. Further correlation analysis and network pharmacology analysis also demonstrated a strong association between specific bacteria, such as Firmicutes and bile acids. In conclusion, our work demonstrated that RR could effectively ameliorate ischemic stroke by modulating the microbiota and metabolic disorders.

03 Aug 2023·Cells

RXR Agonists Enhance Lenalidomide Anti-Myeloma Activity and T Cell Functions while Retaining Glucose-Lowering Effect.

Article

Author: Wang, Xiaobei ; Mathews, Parker ; Zhang, Min ; Kang, Yubin ; Wu, Jian

Retinoid X receptor (RXR) heterodimerizes with the PPAR nuclear hormone receptor and regulates its downstream events. We investigated the effects of RXR agonists (LG100754, bexarotene, AGN194204, and LG101506) on lenalidomide's anti-myeloma activity, T cell functions, and the level of glucose and lipids in vivo. Genetic overexpression and CRISPR/Cas9 knockout experiments were conducted in multiple myeloma (MM) cell lines and Jurkat T cell lines to determine the roles of CRBN in RXR-agonist mediated effects. A xenograft mouse model of MM was established to determine the combination effect of LG100754 and lenalidomide. The combination of RXR agonists and lenalidomide demonstrated synergistic activity in increasing CRBN expression and killing myeloma cells. Mechanistically, the RXR agonists reduced the binding of PPARs to the CRBN promoter, thereby relieving the repressor effect of PPARs on CRBN transcription. RXR agonists downregulated the exhaustion markers and increased the activation markers of Jurkat T cells and primary human T cells. Co-administration of LG100754 and lenalidomide showed enhanced anti-tumor activity in vivo. LG100754 retained its glucose- and lipid-lowering effects. RXR agonists demonstrate potential utility in enhancing drug sensitivity and T-cell function in the treatment of myeloma.

News (Medical) associated with IRX-4204

01 Jan 2025

·www.globenewswire.com

Scientists report studies showing a novel drug repairs myelin and restores nervous system function in a model of multiple sclerosis

Dec. 23, 2024 -- Scientists at Dalhousie University in Halifax, and Io Therapeutics, Inc. in Spring Texas, announced today collaborative publication of data from studies demonstrating effectiveness of the RXR agonist compound IRX4204 in reversing demyelination, and functionally restoring movement in the paralyzed legs of mice subjected to an autoimmune-mediated demyelinating model of human multiple sclerosis (MS). The research report titled: “Selective retinoid X receptor agonism promotes functional recovery and myelin repair in experimental autoimmune encephalomyelitis”, G.D.S Kasheke, et al; was published in the December 21, 2024 edition of Acta Neuropathologica Communications. IRX4204 selectively activates the retinoid X receptor (RXR). Given compelling links between RXR activation and increased myelin repair, the collaborating scientists employed IRX4204 to investigate the impact of RXR agonism on functional recovery in mice subjected to experimental autoimmune encephalomyelitis (EAE). EAE is a commonly used model of neuroinflammation in human MS. Machine learning was used to obtain highly sensitive and reliable measurements of hindleg movements for mice walking on a treadmill. IRX4204 not only blocked progressive loss of knee and ankle movements, but also reversed joint movement impairments in EAE mice. Biochemical, transcriptional and histological measurements in spinal cord supported that these gait improvements reflected increased axon survival, remyelination, and reduced inflammation. Using microglia, astrocytes and oligodendrocyte progenitor cells, additional data was obtained suggesting that IRX4204 acts on multiple glial subtypes to orchestrate myelin repair. George S. Robertson, Ph.D. is the lead scientist for these studies. He is a Professor in the Departments of Psychiatry and Pharmacology at Dalhousie University. His laboratory is located in the Brain Repair Centre at Dalhousie University. Dr. Robertson stated “These results inform the discovery of restorative neural therapeutics for MS by demonstrating that selective RXR agonism is sufficient for effective myelin repair. Moreover, our findings support the therapeutic potential of IRX4204 to promote functional neurologic recovery in MS, a long-sought therapeutic objective in the MS research community.” Martin E. Sanders, M.D., Chief Executive Officer of Io Therapeutics stated “The ability of IRX4204 to inhibit and functionally repair brain demyelination, while also inhibiting microglia-mediated brain inflammation in an MS model opens opportunities for potentially reparative treatment of brain damage in other types of neurologic conditions in which demyelination and microglial inflammation are demonstrated to play pathologic roles. Examples of such conditions include normal aging-related neurodegeneration, Alzheimer’s disease, Parkinson’s disease, traumatic injury, stroke, and schizophrenia. The company is planning to develop IRX4204 for multiple nervous system indications.” 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. The content above comes from the network. if any infringement, please contact us to modify.

100 Deals associated with IRX-4204

External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Plaque psoriasis	Phase 2	United States	Io Therapeutics, Inc.	01 Mar 2025
Castration-Resistant Prostatic Cancer	Phase 2	United States	Io Therapeutics, Inc.	01 Aug 2011
Non-Small Cell Lung Cancer	Phase 2	United States	Io Therapeutics, Inc.	-
Prostatic Cancer	Phase 2	United States	Io Therapeutics, Inc.	-
Advanced Lung Non-Small Cell Carcinoma	Phase 1	United States	Io Therapeutics, Inc.	01 May 2016
Young onset Parkinson disease	Phase 1	United States	Io Therapeutics, Inc.	01 Aug 2014
HER2 Positive Breast Cancer	Phase 1	United States	Io Therapeutics, Inc.	-
Parkinson Disease	Phase 1	United States	Io Therapeutics, Inc.	-
Amyotrophic Lateral Sclerosis	Preclinical	United States	Io Therapeutics, Inc.	01 Dec 2024
Arthritis	Preclinical	United States	Io Therapeutics, Inc.	15 Aug 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01540071 (CTgov)	Phase 2	Castration-Resistant Prostatic Cancer	38	NRX 194204	gujsvxasvs = fqtcgnpaug xvtckivbsa (oxbyydcjno, rbfeqfjqfy - ncbdlptnvr) View more	-	14 May 2021
NCT01540071 (ASCO2014)	Phase 2	Metastatic castration-resistant prostate cancer	23	IRX4204 (20 mg/orally daily)	ylhlkrmppg(nheuvyzcmt) = ogenrgkhdh wzcrslwgwg (gnqscdixol )	Positive	20 May 2014
WPC2013	Not Applicable	Parkinson Disease	-	IRX4204	rhihplxbjt(sbggjlmtkm) = significant attenuation of PD-type motor impairments mgwidoyica (lmlztoivti ) View more	-	01 Oct 2013
WPC2013	Not Applicable	Parkinson Disease	-	Placebo		-	01 Oct 2013

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