RARγ

SPRING, Texas, July 08, 2024 (GLOBE NEWSWIRE) --Io Therapeutics Inc., presented today results from studies done in breast, lung, colorectal, and prostate cancer models with the company’s newest anti-cancer compound IRX5010, an agonist of retinoic acid nuclear receptor gamma which was discovered in the company’s oncology drug program. The presentation titled “RAR Gamma Agonist Compounds Promote Effector Memory Tumor Infiltrating T-cells and are Effective in Multiple Cancer Models”, which was delivered at the Federation of American Societies for Experimental Biology (FASEB) Seventh International Conference on Retinoids, being held in St. Paul, Minnesota, USA; was authored by Vidyasagar Vuligonda, Ph.D., Chief Science Officer of the company and inventor of the compound; and Martin E. Sanders, M.D., the company’s Chief Executive Officer. The presented studies showed that oral treatment with IRX5010 resulted in suppression of growth in mouse models of each of five types of the most prevalent and deadly cancers in humans, i.e. triple negative breast, Her-2 positive breast, non-small cell lung, colorectal, and prostate cancers. In all five models, treatment with IRX5010 induced tumor infiltrating effector memory phenotype T-lymphocytes associated with reduction in tumor growth. Treatment with IRX5010 did not directly impact growth of cancers cells in tissue cultures, indicating that the compound is not significantly directly toxic to cancer cells. The data support that the compound’s mechanism of anti-tumor activity is induction of cancer suppressive tumor-infiltrating T-lymphocytes, so called TILs, rather than direct toxic effects on the cancer cells. Orally administered drugs which induce TILs as a mechanism of action for treatment of cancers are being widely sought in the pharmaceutical industry. Dr. Vuligonda stated, “These results disclose a new approach to potentially improving treatment of multiple types of serious cancers in humans using IRX5010 as monotherapy, or potentially in combination with other agents such as biologic checkpoint inhibitors, which also induce anti-cancer TIL responses. We are currently conducting preclinical combination studies of IRX5010 with other agents. We anticipate advancing IRX5010 as monotherapy, and as combination therapy other already available treatments, into clinical trials in multiple types of cancers.” Dr. Sanders stated, “IRX5010 has potential to be a new effective oral immunotherapeutic treatment for many types of currently inadequately treated human cancers, including the most common types of mortal cancers. In addition to IRX5010, Io Therapeutics has discovered multiple families of compounds targeting other retinoic acid nuclear receptors, which the company is developing as potential treatments for cancers, neurodegenerative, and autoimmune 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: Forward Looking Statements: This new 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

SPRING, Texas, Sept. 12, 2023 (GLOBE NEWSWIRE) -- Io Therapeutics, Inc., announced today the publication in Scientific Reports – Nature Publishing Group, of results from studies done with the company’s novel anti-cancer compound IRX4647, an agonist of the retinoic acid nuclear receptor gamma, discovered in the company’s oncology drug program. The paper, titled “A novel retinoic acid receptor-gamma agonist antagonizes immune checkpoint resistance in lung cancers by altering the tumor immune microenvironment,” authored by Cheng-Hsin Wei, Ph.D., et al., reports studies done in the laboratory of the Molecular Pharmacology Program at the Frederick National Laboratory for Cancer Research (FNLCR), supervised by Xi Liu, Ph.D., Senior Principal Scientist; and Ethan Dmitrovsky, M.D., president of Leidos Biomedical Research and Director of the Frederick National Laboratory for Cancer Research. The studies showed that oral treatment with IRX4647 in combination with an immune checkpoint inhibitor (anti-PD-L1) resulted in suppression of a typically checkpoint inhibitor treatment-resistant syngeneic lung cancer in mice. IRX4647 did not appreciably impact growth of the lung tumor cells in cultures, indicating that the compound alone is not directly toxic to lung cancer cells. Studies in other syngeneic mouse cancer models implicated the tumor microenvironment in these anti-cancer effects since T cell depletion antagonized those effects. Notably, treatment of mice with IRX4647 in combination with the checkpoint inhibitor increased the presence of CD-4 T-lymphocytes in the tumors, indicating that the compound’s anti-cancer effects were mediated through promotion of anti-cancer immune responses in combination with the checkpoint inhibitor. Dr. Dmitrovsky stated, “These results reveal an approach to potentially improve treatment of cancers in humans using combinations of retinoic acid nuclear receptor gamma agonists with checkpoint inhibitors. Future clinical trials could address this possibility.” Martin Sanders, M.D., Chief Executive Officer of Io Therapeutics noted that “Scientific Reports – Nature Publishing Group” is the fifth most highly cited scientific journal in the world. “That these results were published so prominently in the literature indicates their importance to the future of cancer therapeutics.” Sagar Vuligonda, Ph.D, Chief Scientific Officer of Io Therapeutics stated “The company has designed, synthesized, and patented multiple structural families of compounds which bind selectively to the retinoic acid nuclear receptor gamma, and to various other retinoic acid nuclear receptor targets, which we are pursuing as potential treatments for diverse cancers, and also for treatment of neurodegenerative and autoimmune diseases such as Parkinson’s disease and psoriasis.” About Io Therapeutics: Io Therapeutics, Inc. is a privately held company headquartered in Spring, Texas, focused on the development of novel retinoic acid-based compounds for treatment of cancers, neurodegenerative diseases, and autoimmune diseases. More information on Io Therapeutics is available on the company’s web site: Forward Looking Statements: This new 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

Ipsen considered palovarotene "de-risked" and ready for approval when it acquired the drug in a 2019 deal for $1 billion. Four years later, after clearing many hurdles, the French company has won FDA approval for the rare disease drug. When Ipsen ponied up $1 billion in 2019 to acquire Clementia Pharmaceuticals for its rare disease drug palovarotene, the Paris-based company referred to the asset as “largely de-risked.” Four years, two clinical trial holds, a complete response letter, a European Commission rejection, a scrapped trial in another indication and multiple safety flags, resubmissions and delays later, Ipsen finally has gotten checkered palovarotene across the FDA finish line. Wednesday, the U.S. regulator signed off on Sohonos, an oral medication to treat the ultra-rare bone disease fibrodysplasia ossificans progressive (FOP) in females ages 8 and older and males ages 10 and older. Sohonos is a retinoic acid receptor gamma agonist that curbs progression of the genetic disease by reducing the volume of new, abnormal bone growth. FOP, which affects roughly 400 people in the U.S., causes loss of mobility, leaving most patients in a wheelchair by age 30 and reducing life expectancy to age 56. Many die from respiratory failure caused by excessive bone formation around the rib cage, Ipsen’s R&D chief Howard Mayer, M.D., said in an interview. “This is a really important moment in that it actually provides the first therapy available for patients with FOP,” Mayer said. Paving the way for approval were data from a phase 3 trial that showed Sohonos reduced new bone growth by 54%. The treatment will carry a boxed warning for children outlining the risk of premature closure of growth plates, which can cause bone deformities and stunted growth. There also is a warning for embryo-fetal toxicity. Ipsen will charge $624,000 annually for a 5-mg daily dose, the company told Reuters, though dosage will depend on disease severity and the weight of a patient, Mayer said. The company could eventually face competition in the indication from Regeneron. That company's pipeline drug is set up for an FDA submission next year. Along with the approval, Ipsen receives a priority review voucher, which it can sell or use to speed the processing of a subsequent FDA application. Roche developed palovarotene but sold its worldwide rights to Canadian company Clementia in 2013 after the treatment flunked a phase 2 trial in emphysema. The fortunes of palovarotene changed when a phase 2 trial in FOP set it up for an FDA submission in 2019. But soon after Ipsen acquired Clementia, the FDA put two clinical trials of palovarotene on partial clinical holds because of safety concerns. The situation went from bad to worse in the first quarter of 2020, when an interim analysis found the phase 3 trial in FOP was unlikely to meet its primary endpoint.  Two months later, Ipsen scrapped a pivotal trial in a second, potentially more lucrative indication because the pause in dosing under the clinical hold may have compromised the integrity of the data. Between the setbacks, Ipsen recorded a 669 million euro impairment charge. But through post hoc analysis in the FOP trial, Ipsen found a potential route to approval. While the new approach won over regulators in Canada in 2022, it got a final thumbs-down in Europe last month. In October of last year, the FDA was set to assemble an advisory committee to discuss palovarotene but canceled the meeting and asked Ipsen for additional data. Two months later, the regulator rejected Ipsen’s application for approval. Early this year, Ipsen provided the needed data, and a lengthy June advisory committee meeting produced a 10-4 vote in favor of approval. “There were many surprises,” Mayer said of Ipsen’s initial struggles with palovarotene. “It’s been an obstacle course. But we really followed the science for the benefit of patients and worked collaboratively with FDA.”