SANTA ANA, CA, United States
SANTA ANA, CA, United States

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Patent
Io Therapeutics, Inc. and Dartmouth College | Date: 2016-11-02

The present specification provides RXR agonist compounds, compositions comprising such RXR agonists, and methods using such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection as well as use of such RXR agonists to manufacture a medicament and use of such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection.


Disclosed herein are methods of treating disease with a combination of a RXR agonist and a thyroid hormone.


Disclosed herein are methods of treating disease with a combination of a RXR agonist and a thyroid hormone.


Patent
Io Therapeutics, Inc. and Dartmouth College | Date: 2015-06-05

The present specification provides RXR agonist compounds, compositions comprising such RXR agonists, and methods using such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection as well as use of such RXR agonists to manufacture a medicament and use of such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection.


Patent
Io Therapeutics, Inc. and University of Minnesota | Date: 2014-01-08

The present specification provides RAR antagonist compounds, compositions comprising such RAR antagonists, and methods using such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection as well as use of such RAR antagonists to manufacture a medicament and use of such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection.


Patent
Io Therapeutics, Inc. and Dartmouth College | Date: 2015-02-19

The present specification provides RXR agonist compounds, compositions comprising such RXR agonists, and methods using such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection as well as use of such RXR agonists to manufacture a medicament and use of such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 225.00K | Year: 2014

DESCRIPTION (provided by applicant): Io Therapeutics is developing a novel agonist for the Retinoid X Receptors (RXR), IRX4204, to treat multiple sclerosis (MS) and other autoimmune diseases. RXR is a key nuclear receptor involved in inflammation. It has arole in regulating immunity through the enhancement of Treg activities and suppression of inflammatory Th17 activities. Because of the importance of RXR in controlling immunity, small molecule agonists and antagonists for these nuclear receptors have become attractive drug candidates. Io developed IRX4204 as a second-generation RXR specific agonist that belongs to the rexinoid class of compounds. It binds with very high affinity and selectivity to the RXRs, IRX 4204 has very limited affinity for the Retinoic Acid Receptors (RAR). In functional transactivation assays, IRX4204 is at least 2,000 fold more potent in activating RXR homodimers than RAR-RXR heterodimers and IRX4204 does not activate other heterodimers such as RXR-PPAR , RXR-LXR, and RXR-FXR.


Patent
Io Therapeutics, Inc. | Date: 2016-01-12

A method of treating cancer is disclosed comprising administering to a patient in need of such treatment a RXR agonist at a level below the RAR activating threshold and at or above the RXR effective dose.


Patent
Io Therapeutics, Inc. | Date: 2016-01-12

A method of treating cancer is disclosed comprising administering to a patient in need of such treatment a RXR agonist at a level below the RAR activating threshold and at or above the RXR effective dose.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 854.39K | Year: 2016

Multiple Sclerosis MS is a chronic progressive debilitating autoimmune disease of the CNS affecting patients in the US Acute flares of MS are treated with corticosteroids but corticosteroids are not disease modifying Although several biologics and drugs are approved in the US for chronic disease modifying treatment of MS none completely inhibits disease progression and all have significant toxicities or safety issues Thus MS remains a serious debilitating disease with significant unmet medical need for safer and more effective treatments especially for treatments with mechanisms of action other than or in addition to immunomodulatory mechanisms such as mechanisms directly effecting neuroprotection and or promoting myelin protection or repair Io Therapeutics is developing IRX to treat MS because it has substantial preclinical data indicating it has potential to be effective in the treatment of MS patients by multiple mechanisms of action including immunomodulation neuroprotection and myelin protective reparative effects IRX is a synthetic orally available compound which is a potent and highly selective agonist for the RXR nuclear receptors The compound is distinctive from the only currently approved RXR agonist bexarotene in that it is approximately fold more potent as an RXR agonist than bexarotene with RXR activation occurring at sub nanomolar nM concentrations and maximal RXR activation occurring at approximately nM for all three RXR isoforms IRX at pharmacologic concentrations is devoid of activity at RAR PPAR FXR and LXR nuclear receptors which are activated by bexarotene IRX transactivates RXR Nurr and RXR Nur heterodimers at sub nM concentrations These RXR heterodimers are implicated in its activities on immune system and CNS We have already tested IRX in humans with cancer or Parkinson s disease under two US INDs and it has been shown to be well tolerated and safe for administration to humans with chronic neurodegenerative disease The unique pharmacologic activities of IRX combined with its human clinical data demonstrating safety following chronic administration and oral pharmacokinetics consistent with once daily oral dosing has substantially diminished the risk of IRX as an advanced clinical stage therapeutic candidate for MS This application is seeking funds to advance the development of IRX into Phase randomized blinded and controlled efficacy trials in MS patients Prior to conducting chronic clinical trials in MS patients the company must perform six month GLP toxicology studies in rats and dogs These are required to meet ICH and FDA guidelines for administration of an experimental compound to humans for six months or longer Per company discussions with the FDA chronic toxicology studies of six months duration in rats and dogs are the only unmet requirements for advancing IRX into the chronic controlled phase clinical trials to provide preliminary evidence of clinical efficacy in MS patients and patients with other types of neurodegenerative diseases Project Narrative Our studies focus on the development of a novel orally available small molecule drug IRX to treat Multiple Sclerosis MS Extensive preclinical testing supports that IRX may be effective for the treatment of MS by multiple mechanisms of action including novel effects on the immune system protective effects on neurons and protective or reparative effects on the myelin sheaths surrounding neurons and IRX has already been shown to be safe and well tolerated in long term studies in humans having cancer and in a short term study in patients with early Parkinson s disease Upon completion of the proposed month toxicology studies in rats and dogs the company plans to conduct rigorous testing of the safety and efficacy of chronic administration of IRX in controlled clinical trials in both relapsing remitting and progressive MS patient populations treated with the drug for six months or longer i e studies of sufficient duration to demonstrate clinical efficacy in these MS patient populations

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