RARγ

Company advancing an innovative pipeline of NKT cell modulators for the treatment of inflammatory, fibrotic and autoimmune diseases Ongoing efforts to build a robust global patent estate for a growing pipeline targeting high-value indications in need of innovation LA JOLLA, CA, March 14, 2024 (GLOBE NEWSWIRE) -- GRI Bio, Inc. (NASDAQ: GRI) (“GRI Bio” or the “Company”), a biotechnology company advancing an innovative pipeline of Natural Killer T (NKT) cell modulators for the treatment of inflammatory, fibrotic and autoimmune diseases, today announced that the Canadian Intellectual Property Office (CIPO) has issued a notice of allowance for Patent Application No. 3,007,970 titled, "Prevention and Treatment of Inflammatory Conditions." A patent from the recently allowed application is expected to be issued in the coming months. When issued, the patent will cover claims including compositions and methods for modulating type 2 and/or type 1 invariant NKT (iNKT) cells in the prevention and treatment of inflammatory conditions of the liver. More specifically, when issued the patent will cover the prevention and treatment of inflammatory and fibrotic conditions through the administration of a Retinoic Acid Receptor (RAR) agonist that inhibits iNKT cells and the administration of an RAR agonist that inhibits the activity of iNKT cells in a subject. “We have remained committed to bolstering our intellectual property protection across our innovative pipeline of NKT cell modulators. We are pleased to receive this notice of allowance for our Canadian patent and believe this further validates our differentiated approach to the prevention and treatment of inflammatory, fibrotic and autoimmune diseases as well as underscores the global unmet need amongst patients. Our team is focused on driving our development programs forward, generating a growing body of data and continuing to build our patent estate with the ultimate goal of bringing to market much needed treatment options,” Marc Hertz, PhD, Chief Executive Officer of GRI Bio. GRI Bio is currently advancing its lead program GRI-0621, a small molecule RAR-βɣ dual agonist candidate that inhibits the activity of human iNKT cells, in a Phase 2a, randomized, double-blind, multi-center, placebo-controlled, parallel-design, 2-arm study for the treatment of Idiopathic Pulmonary Fibrosis (IPF). IPF is a rare chronic progressive pulmonary disease with abnormal scarring of the lung blocking the movement of oxygen into the bloodstream. Interim data from the Phase 2a biomarker study is expected in the first half of 2024 and topline results are expected in the second half of 2024. For more information about the Company’s innovative pipeline of NKT cell regulators for the treatment of inflammatory, fibrotic and autoimmune diseases, visit gribio.com. About GRI Bio, Inc. GRI Bio is a clinical-stage biopharmaceutical company focused on fundamentally changing the way inflammatory, fibrotic and autoimmune diseases are treated. GRI Bio’s therapies are designed to target the activity of NKT cells, which are key regulators earlier in the inflammatory cascade, to interrupt disease progression and restore the immune system to homeostasis. NKT cells are innate-like T cells that share properties of both NK and T cells and are a functional link between the innate and adaptive immune responses. iNKT cells play a critical role in propagating the injury, inflammatory response, and fibrosis observed in inflammatory and fibrotic indications. GRI Bio’s lead program, GRI-0621, is an inhibitor of iNKT cell activity and is being developed as a novel oral therapeutic for the treatment of idiopathic pulmonary fibrosis, a serious disease with significant unmet need. The Company is also developing a pipeline of novel type 2 NKT agonists for the treatment of systemic lupus erythematosus. Additionally, with a library of over 500 proprietary compounds, GRI Bio has the ability to fuel a growing pipeline. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate,” “believe,” “contemplate,” “could,” “estimate,” “expect,” “intend,” “seek,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “target,” “aim,” “should,” “will,” “would,” or the negative of these words or other similar expressions. These forward-looking statements are based on the Company’s current beliefs and expectations. Forward-looking statements include, but are not limited to, statements regarding: the Company’s expectations with respect to development and commercialization of the Company’s product candidates, the timing of initiation or completion of clinical trials and availability of resulting data, the potential benefits and impact of the Company’s clinical trials and product candidates and any implication that the data or results observed in preclinical trials or earlier studies or trials will be indicative of results of later studies or clinical trials, the Company’s beliefs and expectations regarding and the potential of the Company’s product candidates to meet unmet treatment needs and improve patient quality of life, the Company’s beliefs and expectations about the timing, outcome and robustness of the Company’s patent applications and potential intellectual property protections. Actual results may differ from the forward-looking statements expressed by the Company in this press release and consequently, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements are subject to inherent uncertainties, risks and assumptions that are difficult to predict, including, without limitation: (1) the Company’s inability to maintain the listing of the Company’s common stock on Nasdaq and to comply with applicable listing requirements; (2) changes in applicable laws or regulations; (3) the inability of the Company to raise financing in the future; (4) the success, cost and timing of the Company’s product development activities; (5) the inability of the Company to obtain and maintain regulatory clearance or approval for its respective products, and any related restrictions and limitations of any cleared or approved product; (6) the inability of the Company to identify, in-license or acquire additional technology; (7) the inability of the Company to compete with other companies currently marketing or engaged in the development of products and services that the Company is currently developing; (8) the size and growth potential of the markets for the Company’s products and services, and their respective ability to serve those markets, either alone or in partnership with others; (9) the failure to achieve any milestones or receive any milestone payments under any agreements; (10) inaccuracy in the Company’s estimates regarding expenses, future revenue, capital requirements and needs for and the ability to obtain additional financing; (11) the Company’s ability to protect and enforce its intellectual property portfolio, including any newly issued patents; and (12) other risks and uncertainties indicated from time to time in the Company’s filings with the U.S. Securities and Exchange Commission (the “SEC”), including the risks and uncertainties described in the “Risk Factors” section of the Company’s most recent Annual Report on Form 10-K filed with the SEC on February 24, 2023 and subsequently filed reports, including our Quarterly Report on Form 10-Q filed with the SEC on May 15, 2023 and our Quarterly Report on Form 10-Q filed with the SEC on November 14, 2023. Forward-looking statements contained in this announcement are made as of this date, and the Company undertakes no duty to update such information except as required under applicable law. Investor Contact: JTC Team, LLC Jenene Thomas (833) 475-8247 GRI@jtcir.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.”