VCAM1

On September 11, 2024, Johnson & Johnson announced that the U.S. Food and Drug Administration (FDA) has approved Tremfya (guselkumab) for the treatment of moderate to severe active ulcerative colitis (UC) in adult patients. The company claims that Tremfya is the first and only dual-acting inhibitor targeting interleukin 23 (IL-23) to be approved for this indication, solidifying Johnson & Johnson’s leadership position in the field of inflammatory bowel diseases. About GuselkumabGuselkumab is the first IL-23 inhibitor globally approved, selectively binding to the p19 subunit of IL-23 and blocking its interaction with the IL-23 receptor. This mechanism of action yields significant therapeutic effects across various autoimmune diseases. Guselkumab not only inhibits IL-23 but also interacts with the CD64 receptor on cells that produce IL-23. Tremfya has garnered approvals for treating plaque psoriasis, active psoriatic arthritis, and UC. Additionally, in June 2024, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the FDA for the treatment of moderate to severe active Crohn's disease (CD) in adults. Study Data Supporting ApprovalThe FDA's approval for UC was primarily based on data from the Phase 2b/3 QUASAR study. This study assessed the efficacy and safety of Tremfya in adult patients with moderate to severe active UC who had an inadequate response or intolerance to conventional therapies, other biologics, and/or JAK inhibitors. The results demonstrated that 50% of patients receiving Tremfya 200 mg subcutaneously (SC) every four weeks (q4w), and 45% of patients receiving Tremfya 100 mg SC every eight weeks (q8w), achieved the primary endpoint of clinical remission at Week 44, compared to 19% of those receiving placebo (p<0.001). Additionally, one year after maintenance therapy, 34% (200 mg) and 35% (100 mg) of patients achieved endoscopic remission, as opposed to 15% in the placebo group (p<0.001). During the induction treatment phase, the most common adverse reactions (>2%) for both Tremfya and placebo groups were respiratory infections. In the maintenance phase, the most frequent adverse reactions (>3%) among patients treated with Tremfya or placebo included injection site reactions, joint pain, and upper respiratory infections. About IL-23 p19 DrugsIL-23 p40 serves as a common subunit for both IL-12 and IL-23, with p40 antibodies providing a classical immunotherapy by blocking both IL-12 and IL-23 pathways. However, recent developments in IL-23 p19 antibodies, exemplified by guselkumab, have shown superior efficacy and safety profiles compared to p40 antibodies. The p19 subunit, besides forming the classical inflammatory cytokine IL-23 with p40, can also combine with EBI3 to form IL-39, which activates pathways involving IL-23R and gp130. Both IL-23 and IL-39 can trigger intracellular JAK-STAT signaling pathways, thereby stimulating the secretion of IL-17A/F. This sophisticated approach to targeting IL-23 not only reaffirms Johnson & Johnson’s innovative footprint in treating inflammatory and autoimmune diseases but also signals a promising horizon for patients battling these chronic conditions. In October 2023, Eli Lilly's Omvoh (mirikizumab) received FDA approval for the treatment of adults with moderately to severely active ulcerative colitis (UC). This marks the first IL-23p19 antagonist approved for this patient group. Additionally, AbbVie's risankizumab was the first IL-23 inhibitor to receive FDA approval for inflammatory bowel disease (IBD). It was approved for Crohn’s disease (CD) in June 2022 and for UC in June 2024. About Inflammatory Bowel Disease (IBD)IBD is a nonspecific, chronic, relapsing inflammatory condition of the intestines, commonly presenting with symptoms such as diarrhea, rectal bleeding, abdominal pain, fatigue, and weight loss. The precise cause and mechanism of IBD are not fully understood. However, the prevailing theory suggests that it involves an autoimmune dysfunction triggering an abnormal immune response, leading the immune system to attack normal cells in the digestive tract. IBD includes two main disorders: ulcerative colitis (UC) and Crohn's disease (CD).  UC causes inflammation and ulcers on the surface lining of the colon and rectum, whereas CD can affect any part of the digestive tract, typically involving deeper layers of the gut lining. In rare cases, it can also affect the colon and upper gastrointestinal tract. In 2019, the global prevalence of IBD was approximately 4.9 million, with China accounting for 910,000 patients. From 1990 to 2019, the incidence of IBD in Chinese men increased from 1.72 cases per 100,000 to 3.35 cases per 100,000, while in women, the numbers rose from 1.20 to 2.45 per 100,000. The current global market for IBD therapies has expanded to $18 billion. Research indicates that the migration of white blood cells into intestinal tissue is key to the onset and persistence of IBD. This process depends on the specific binding between adhesion molecules on endothelial cells (such as VCAM-1, MAdCAM-1) and integrins on white blood cells, composed of α and β subunits. Targeting and inhibiting these specific interactions can effectively treat intestinal inflammation in IBD. Elevated levels of cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-12/23 (IL-12/23), and leukocyte adhesion molecules are commonly seen during active disease phases of IBD. Inhibiting these cytokines can effectively disrupt downstream inflammatory responses and leukocyte chemotaxis, which lead to mucosal damage. Other targets such as the Janus kinase (JAK)/STAT pathway and gut microbiota are increasingly being recognized for their roles in IBD. Since the etiology and pathogenesis of IBD remain unclarified, it cannot be cured. Current drug therapies focus on reducing inflammation, maintaining remission, lowering relapse rates, and reducing the need for surgery. Common treatments include anti-inflammatory drugs, immunosuppressants, antibiotics, small molecule oral drugs, and biologics. Compared to traditional drugs like 5-aminosalicylic acids, steroids, and immunosuppressants, biologics are becoming the mainstream treatment for IBD due to their clearer efficacy and better safety profiles. Johnson & Johnson's Position in IBDIn the IBD sphere, Johnson & Johnson has developed TNF-α inhibitors infliximab and golimumab, each generating over $2 billion in sales in 2023. In addition to guselkumab, the company is developing the first IL-12/23 antibody Stelara (ustekinumab) and the oral IL-23 inhibitor JNJ-2113 for IBD indications. Furthermore, the company is working on a combination therapy for recurrent patients using guselkumab and golimumab (JNJ-8408). According to incomplete statistics, Johnson & Johnson currently has nearly 20 drugs in development for the treatment of inflammatory bowel disease. How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!

Data demonstrates that NKT cells are activated in airways in IPF patients and inhibition of type 1 invariant NKT (iNKT) cell activity can ameliorate bleomycin-induced pulmonary fibrosis in mice Compared to controls, mice treated with GRI-0621 showed histological improvement in fibrotic lesion in the lung; Inhibition of iNKT activity led to a decrease in fibrosis score and total lung inflammation Company advancing Phase 2a biomarker study of GRI-0621 in patients with IPF with interim data expected Q3 2024 and topline data in Q4 2024 LA JOLLA, CA, July 02, 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 the publication of positive preclinical data demonstrating its lead program GRI-0621 reduces the important inflammatory and fibrotic drivers in Idiopathic Pulmonary Fibrosis (IPF). The manuscript titled, “Type 1 invariant natural killer T cells drive lung fibrosis1,” has been published in the American Journal of Respiratory and Critical Care Medicine. “There remains a significant unmet need with no existing therapeutic solutions that halt disease progression of fibrotic diseases such as IPF. We are encouraged by our growing body of promising data demonstrating the potential of GRI-0621 for the treatment of IPF,” Marc Hertz, PhD, Chief Executive Officer of GRI Bio. “Supported by the data we’ve seen to date, our team continues to make solid progress in the advancement of our lead program, GRI-0621 and look forward to announcing interim data and topline data from our Phase 2a biomarker study in the third and fourth quarters of this year, respectively.” Natural Killer T (NKT) cells are a group of innate-like T cells which express NK cell receptors and antigen T cell receptors (TCR). NKT cells become rapidly activated following either TCR recognition of CD1d-bound lipid antigen or following inflammatory cytokine-activation. NKT cells produce type 1, 2 or 3 cytokines; NKT1 produce IFN-γ, whereas NKT2 secrete IL-4, IL-5, and IL-13, and NKT17 secrete IL-17A and IL-22. NKT cells have diverse functions bridging adaptive and innate immune responses. iNKT cells are tissue-resident and enriched in peripheral tissues, such as the lung. To investigate the role of pulmonary NKT populations in IPF, the Company utilized the murine bleomycin model of pulmonary fibrosis. Key Highlights Compared to controls, mice treated with GRI-0621 showed reduced fibrosis and immunopathology. Inhibition of iNKT activity led to a decrease in fibrosis score and total lung inflammation. GRI-0621 treated mice had reduced numbers of neutrophils and lymphocytes. Levels of the pro-fibrotic factor TGF-β were significantly decreased in GRI-0621-treated group in comparison to the untreated group. Similarly, VCAM-1 levels were also decreased in GRI-0621-treated group. IPF is a rare chronic progressive pulmonary disease with abnormal scarring of the lung blocking the movement of oxygen into the bloodstream. The architectural destruction of the lung results in breathlessness, significant decline in quality of life and an average untreated survival of 3.5 years from diagnosis. Currently available treatments for IPF are limited with only two approved drugs that come with significant side-effects, limited compliance and no impact on survival2. 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 IPF. Interim data from the Phase 2a biomarker study is expected in the third quarter of 2024 and topline results are expected in the fourth quarter of 2024. 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 Natural Killer T (“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. Type I invariant NKT (“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 potential stakeholder value and future financial performance, the Company’s beliefs about the timing and outcome of regulatory approvals and potential regulatory approval pathways, the Company’s expected milestones for 2024, and the Company’s beliefs and expectations regarding the sufficiency of its existing cash and cash equivalents to fund its operating expenses and capital expenditure requirements. 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 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 March 28, 2024 and subsequently filed reports. 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 1 2 T. M. Maher et al., Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res22, 197 (2021)

Compared to controls, mice treated with GRI-0621 showed improved fibrosis and immunopathology; Inhibition of type 1 invariant Natural Killer T (iNKT) cell activity led to a decrease in fibrosis score and total lung inflammation Company advancing Phase 2a biomarker study of GRI-0621 in patients with IPF with interim data expected Q3 2024 and topline data in Q4 2024 Data presented at the 2024 American Thoracic Society International Conference LA JOLLA, CA, May 20, 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 presented positive preclinical data demonstrating its lead program GRI-0621 reduces the important inflammatory and fibrotic drivers in Idiopathic Pulmonary Fibrosis (IPF). As part of the 2024 ATS International Conference held May 17-22, 2024 in San Diego, CA, Albert Agro, PhD, Chief Medical Officer of GRI Bio presented the poster titled “Altered NKT Cell Populations in the Airways of Patients With IPF,” which presented translational data from IPF patients as well as discussed data demonstrating that in a bleomycin-induced fibrosis model in mice, a selective inhibitor of iNKT cells, GRI-0621, can modulate the fibrotic condition and can reduce the important inflammatory and fibrotic drivers of the disease. Additionally, the design of the Phase 2a study examining the safety, tolerability, and effect on various biomarkers of GRI-0621 was presented. “We believe this data further supports GRI-0621’s potential for the treatment of IPF,” commented Dr. Agro. “Our belief in the potential of our NKT platform technology continues to build, and we remain focused on leveraging its potential to develop novel biomarkers and therapeutic targets that differentiate stages of fibrosis progression. We are focused on the advancement of our Phase 2a biomarker study of GRI-0621 and look forward to the interim and topline data readouts in the coming quarters and discovering more about its potential to provide benefit to patients.” Key Highlights Observed from GRI Preclinical & Translational Studies iNKT cells are found in increased number and activity in the BAL of patients with IPF as compared to age matched controls. iNKT cells are an early initiator of fibrotic disease effecting numerous pathways leading to fibrosis and inflammation. GRI-0621 is a small molecule RAR-βɣ inhibitor of iNKT cell activity facilitated by the binding to RAR receptors expressed to a higher level in iNKT cells compared to other T cell populations tested. In an animal model of IPF, GRI-0621 was shown to reduce the fibrotic score, inhibit the production of TGFβ and VCAM-1 and reduce the immune cell. IPF is a rare chronic progressive pulmonary disease with abnormal scarring of the lung blocking the movement of oxygen into the bloodstream. Currently available treatments for IPF are limited with only two approved drugs that come with significant side-effects, limited compliance and no impact on survival1. GRI Bio’s lead program, GRI-0621, is a small molecule RAR-βɣ dual agonist that inhibits the activity of human iNKT cells. In preliminary trials to date and previous trials with the oral formulation, GRI-0621 has been shown to improve fibrosis in multiple disease models and improve liver function tests and other markers of inflammation and injury in patients. The Company plans to leverage the 505(b)(2) regulatory pathway and has launched a Phase 2a biomarker study evaluating GRI-0621 for the treatment of IPF. For more information about the Phase 2a study, please visit clinicaltrials.gov and reference identifier NCT06331624. 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 IPF, 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 disease (SLE). 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 preclinical studies, clinical trials and availability of resulting data, the potential benefits and impact of the Company’s preclinical studies, clinical studies 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, any implication that the Company’s product candidates will perform similarly to other candidates or approved therapies, the Company’s beliefs and expectations regarding future financial performance, and the Company’s beliefs about the timing and outcome of regulatory approvals and potential regulatory approval pathways,. 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 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 March 28, 2024 and subsequently filed reports. 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 1 T. M. Maher et al., Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir Res22, 197 (2021)