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Distinct groups of inflammatory proteins may contribute to the progression of heart problems in men and women with Fabry disease, a study suggests.While men exhibited a profile associated with a strong pro-inflammatory response, women had a profile that could be linked to accumulating scar tissue. The identified markers may be useful for detecting cardiac problems in Fabry patients early and the findings suggest anti-inflammatory treatments may help slow cardiac progression.The study, “Sex Differences in Circulating Inflammatory, Immune, and Tissue Growth Markers Associated with Fabry Disease-Related Cardiomyopathy,” was published in Cells.Fabry disease is caused by mutations in the GLA gene that lead to a lack of functional alpha-galactosidase A (alpha-Gal A) enzyme. Fatty molecules the enzyme would normally be responsible for breaking down accumulate to toxic levels in tissues throughout the body.Because it’s inherited on the X chromosome, Fabry tends to affect the sexes differently. Generally, men show more severe and earlier-onset symptoms, while the disease course in women is milder and with a later onset, although this can vary significantly.Heart disease is a common symptom of Fabry. Hypertrophic cardiomyopathy (HCM), where the heart muscle becomes abnormally thick and the heart has a harder time pumping blood, is particularly common. But there are sex differences in Fabry-related heart disease, with data suggesting women are typically affected at a later age than men. Moreover, while men characteristically develop progressive HCM with eventual fibrosis, women sometimes develop early fibrosis before overt HCM develops.It’s been proposed that inflammation in response to the buildup of fatty molecules may play a key role in Fabry disease progression, including contributing to cardiac damage. This raises the possibility that circulating inflammatory biomarkers could have potential in early screening for cardiac involvement in Fabry patients, said the scientists, who measured blood levels of inflammatory molecules called cytokines in adult Fabry patients and healthy people as part of an observational clinical study (NCT04724083). They also looked at certain growth factors that can drive remodeling of cardiac tissue that contributes to HCM.The analysis included 45 Fabry patients (21 men, 24 women), of whom 28 had HCM. Twenty healthy people, 10 men and 10 women, served as controls.While heart disease is generally considered to affect women at a later age, early-onset HCM was not uncommon in the study group. The youngest female with a mild form of HCM was 22 and the youngest male was 21.“Thus, the early detection of HCM in females with [Fabry disease] is crucial for effective disease management,” the researchers wrote.Biomarker analyses suggested that Fabry patients had differences in inflammatory markers from healthy controls, with distinct profiles in male and female patients. Various biomarkers were also specifically associated with HCM, again with sex-specific differences.Overall, the biomarker profile in men with HCM suggested activation of the inflammatory NFkB signaling pathway, with markers such as IL-10, IL-2, GM-CSF, and VEGF-A being implicated. This reflects that significant inflammation drives cardiac tissue remodeling that promotes HCM progression in men, said the researchers.On the other hand, women with HCM showed an inflammatory marker profile consistent with activation of the TNF-alpha, TNFR2, and TGF-beta signaling cluster, which may be related to fibrosis development. This may help explain why women with Fabry often show fibrosis early in the course of cardiac disease.“The pivotal roles these cytokines and growth factors play may render them valuable as biomarkers for the early detection and clinical staging of HCM,” the researchers wrote. “Such insights are crucial for healthcare providers to develop strategies for the effective management of [Fabry] patients with cardiac manifestations.”The findings could also inform future treatment strategies, with certain anti-inflammatory treatments having already shown promise for treating cardiovascular disease in the general population.“These findings support the role of inflammation as a therapeutic target in cardiovascular diseases, including Fabry cardiomyopathy, where adjunctive anti-inflammatory therapies may improve clinical outcomes when combined with disease-specific treatments,” they wrote.

Itolizumab demonstrated clinical efficacy after 12 weeks of treatment, achieving a clinical remission rate of 23.3% compared to 20.0% for adalimumab and 10.0% for placebo Itolizumab achieved key secondary endpoint of endoscopic remission of 16.7% compared to 16.7% for adalimumab and 6.7% for placebo Itolizumab was generally well tolerated consistent with prior clinical experience LA JOLLA, CA, USA I February 06, 2025 I Equillium, Inc. (Nasdaq: EQ), a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders, and Biocon Limited (BSE code: 532523, NSE: BIOCON), an innovation-led global biopharmaceutical company, today announced positive topline results from the Phase 2 study evaluating itolizumab in the treatment of moderate to severe ulcerative colitis (UC). The double-blinded, placebo- and active-controlled Phase 2 clinical study evaluated the safety and efficacy of itolizumab in biologic-naïve patients with moderate to severe active UC. A total of 90 patients were randomized 1:1:1 to receive itolizumab (fixed dose of 140 mg), placebo, or adalimumab (a global standard of care biologic treatment used as an active control) every two weeks for an initial 12-week treatment period. The primary endpoint of the study was clinical remission as defined by Total Mayo Score, and secondary endpoints included the proportion of participants who achieved clinical response and endoscopic remission (evaluated by central endoscopy). The study was co-sponsored by Equillium and Biocon Limited and conducted at multiple clinical trial sites in India. The design and conduct of the trial were a collaborative effort, with input from the gastroenterology community and leading global clinical and scientific experts in the field of inflammatory bowel disease (IBD). “The CD6-ALCAM pathway is elevated in gastrointestinal inflammation and is associated with severity of disease in both ulcerative colitis and Crohn’s patients. As such, we are delighted with the strength of data across the primary and secondary endpoints of this Phase 2 study in moderate to severe ulcerative colitis patients,” said Dr. Stephen Connelly, chief scientific officer at Equillium. “Itolizumab was well tolerated and achieved a clinical remission rate of 23 percent despite an imbalance of more severe patients in the itolizumab arm compared to the other arms of the study. While these positive results add to itolizumab’s critical mass of safety and efficacy data across different patient populations, we are particularly encouraged by this data in the context of our Phase 3 EQUATOR study in acute graft-versus-host disease, where lower gastrointestinal pathogenesis is a key driver of mortality, with topline data expected this quarter.” “Itolizumab demonstrated proof of concept with a meaningful effect size – comparable to biologic standard of care adalimumab – in this Phase 2 study in subjects with moderate to severe ulcerative colitis,” said Dr. Brian Feagan, Professor of Medicine at the Schulich School of Medicine & Dentistry at the University of Western Ontario. “Itolizumab represents a novel selective immune modifying mechanism of action with great potential in a treatment paradigm needing differentiation and improved outcomes for patients.” Summary of Key Study Results Baseline demographics of the study included a median age of 39 years, relatively equal proportions of male and female subjects evenly distributed among study arms, and a mean weight of 58 kilograms. Baseline disease severity of the study was greater in the itolizumab arm, where 23% of patients were classified as severe (Total Mayo Score of 11) versus 0% in the placebo and adalimumab arms, and 66% had left-sided colitis versus 30% and 43% in the placebo and adalimumab arms, respectively. The primary endpoint of the study was clinical remission, defined as Total Mayo Score of ≤ 2 with no individual sub-score greater than 1 at Week 12. Secondary endpoints included the proportion of participants who achieved clinical response (per Total Mayo Score) and endoscopic remission (evaluated by central endoscopy) at Week 12 and Week 24. Additional data is expected to be presented at a future scientific conference during 2025. * One patient from the adalimumab arm had ‘endoscopic remission,’ but was recorded as ‘not in clinical remission’ at week 12 due to missing sub-score data About Itolizumab Itolizumab is a clinical-stage, first-in-class immune-modifying monoclonal antibody that selectively targets the CD6-ALCAM signaling pathway to downregulate pathogenic T effector cells while preserving T regulatory cells critical for maintaining a balanced immune response. This pathway plays a central role in modulating the activity and trafficking of T cells that drive a number of immuno-inflammatory diseases. The blockade of CD6 with itolizumab has demonstrated a reduction in T effector cell proliferation and downregulation of several important pathways that contribute to T effector cell development. The downregulation of these pathways is accompanied by decreased secretion of the pro-inflammatory T effector cytokines IFN-γ, TNF-α, IL-6 and IL-17. Additionally, inhibiting the binding of ALCAM to CD6 modulates lymphocyte trafficking and results in reduced T effector cell infiltration into inflamed tissues. About Biocon Limited Biocon Limited, publicly listed in 2004, (BSE code: 532523, NSE Id: BIOCON, ISIN Id: INE376G01013) is an innovation-led global biopharmaceuticals company committed to enhance affordable access to complex therapies for chronic conditions like diabetes, cancer and autoimmune. It has developed and commercialized novel biologics, biosimilars, and complex small molecule APIs in India and several key global markets as well as Generic Formulations in the US, Europe & key emerging markets. It also has a pipeline of promising novel assets in immunotherapy under development. Website: www.biocon.com ; Follow-us on Twitter: @bioconlimited for company updates. About Equillium Equillium is a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need. The company’s pipeline consists of the following novel first-in-class immunomodulatory assets and product platform targeting immuno-inflammatory pathways. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells that drive a number of immuno-inflammatory diseases. It is currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and has exhibited positive data from both a Phase 2 clinical study of patients with moderate to severe ulcerative colitis and a Phase 1b clinical study of patients with lupus/lupus nephritis. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited, who also provides commercial manufacturing for the product. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15, has exhibited positive results in both a Phase 2 proof-of-concept clinical study of patients with moderate to severe alopecia areata and a Phase 1/2 proof-of-concept clinical study of patients with cutaneous T cell lymphoma (CTCL). EQ302: an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21 at pre-clinical stage. For more information, visit www.equilliumbio.com . SOURCE: Equillium

Data Presented at ESMO-IO supports the potential of personalized treatment strategies to improve clinical trial outcomesHELSINKI, Finland, Dec. 05, 2024 (GLOBE NEWSWIRE) -- TILT Biotherapeutics (TILT), a clinical-stage biotechnology company developing intravenously delivered cancer immunotherapies, announces it will be presenting data at the European Society of Medical Oncology Immuno-Oncology Congress (ESMO-IO) 2024. The oral presentation discloses the impact of different biological features on treatment efficacy in patients treated with the oncolytic virus Igrelimogene litadenorepvec or ‘TILT-123’(1). The study used single-cell sequencing analysis to identify immunological markers in peripheral blood mononuclear cells that were related with better outcomes, including higher baseline levels of cytotoxic effector cells. Additionally, TILT-123 treatment supported the formation of immunological memory. TILT will also present data relating to the fully intravenous dosing of TILT-123 (2). These findings have the potential to support future clinical development strategy. In addition, TILT is progressing its plans for international Phase II trials of TILT-123 in ovarian cancer, to be administered intravenously, and expects Phase Ib clinical results by H2 2025. TILT Biotherapeutics’ founder and CEO, Akseli Hemminki, said: “This year we’ve made significant progress in the clinical development of TILT-123, and have now treated over 60 patients in five international trials, including our first patients in leading US cancer centres. Our data, presented at ESMO-IO this month, provides further support on the mechanism of action of our oncolytic immunotherapy. Our progress in IV administration, alongside our manufacturing process scale up work, supports our mission to make TILT-123 accessible to patients with hard-to-treat solid cancers.” TILT-123, an oncolytic adenovirus armed with tumor necrosis factor alpha (TNFα) and interleukin-2 (IL-2), is designed to enhance the efficacy of T-cell therapies, including immune checkpoint blockade or adoptive cell transfer. TILT’s approach uses oncolytic viruses to selectively replicate in and lyse cancer cells, while simultaneously stimulating immune responses towards the tumor. Reference (1) ESMO-IO Abstract 353: “Single-cell profiling of peripheral blood mononuclear cells from patients treated with oncolytic adenovirus armed with TNFα and IL-2 revealed pre-existing immunity as a predictor of therapy outcomes”. (2) ESMO-IO Abstract 458: “Effect of split intravenous dosing of oncolytic adenovirus TILT-123 on normal tissue versus tumor macrophages and virus bioavailability in patients with advanced solid tumors”. Notes to Editors About TILT Biotherapeutics TILT Biotherapeutics is a clinical-stage biotechnology company developing cancer therapeutics based on its proprietary oncolytic adenoviruses armed with molecules including cytokines that can activate T cells and destroy cancer cells. The company’s patented TILT® technology can be delivered intravenously, locoregionally, or intratumorally. It modifies the tumor microenvironment and has a broader systemic effect. By making cold tumors hot, it eliminates cancer’s ability to evade immune responses, thereby enhancing T-cell therapies such as immune checkpoint inhibitors, tumor infiltrating lymphocyte (TIL) therapy, and CAR T therapies. TILT’s lead asset, TILT-123 also known as Igrelimogene litadenorepvec, is a 5/3 chimeric serotype adenovirus armed with two human cytokines: TNF alpha and IL-2. Over sixty patients have been treated in five international trials sponsored by the company with promising initial efficacy responses observed in some of the patients. The company’s pioneering approach has been recognized by industry leaders. It has two collaborations with MSD (Merck & Co., Inc., Rahway, NJ, USA) investigating TILT-123 in combination with KEYTRUDA® (pembrolizumab) in ovarian cancer (NCT05271318) and in refractory non-small cell lung cancer (NCT06125197). The company is also collaborating with Merck KGaA (Darmstadt, Germany) and investigating TILT-123 in combination with Bavencio® (avelumab). Based in Helsinki, Finland, and with an office in Boston, the company was established over a decade ago as a spin-out from the University of Helsinki. It has funding from Lifeline Ventures, Finnish Industry Investment (TESI), angel investors, Business Finland, the European Innovation Council, and the U.S. Department of Defense. Media contacts TILT BiotherapeuticsCOO Aino Kalervoaino@tiltbio.com Scius CommunicationsKatja Stout+447789435990katja@sciuscommunications.com Daniel Gooch+447747875479daniel@sciuscommunications.com