VIR Biotechnology (United States)

We present a method for absolute quantification of deuterated metabolites in vivo at 7T. We describe acquisition protocols and an analysis pipeline compatible with 7T Terra MRIs. We apply them using a 2H/1H receive array in healthy volunteers and glioblastoma patients. B1 +/B1 - maps from multiple CSI scans in a uniform phantom were used to derive calibrated coil weights for absolute quantification. We validated this in phantoms with known deuterated compounds. 2H MRSI was performed in twelve healthy volunteers (two post-[6,6-2H2]-glucose) and five treatment-naive glioblastoma patients (all post-[6,6-2H2]-glucose). Spectra were fitted with OXSA. We compared Glx/Lac between tumor and normal-appearing brain using linear mixed-effects models. Measured B1 + maps were 0.82 ± 0.19 μT/√W across the whole phantom. Natural abundance deuterium in water was 8.96 ± 0.7 mmol/L. Absolute maps of HDO, Glc, Glx, and Lac were acquired following [6,6-2H2]glucose. Rate maps showed higher Lac production in tumors (2.3 μmol/L/min, SE = 0.87) compared with normal-appearing regions (1.0 μmol/L/min, SE = 0.36; p < 0.01) and healthy brain (0.5 μmol/L/min, SE = 0.17; p < 0.01). Glx production was lower in tumors (3.8 μmol/L/min, SE = 0.44) relative to normal-appearing contralateral regions (6.0 μmol/L/min, SE = 0.36; p < 0.001) and healthy brain (9.2 μmol/L/min, SE = 0.61; p < 0.001). We demonstrate robust absolute quantification for human 7T DMI. Glioblastoma tumors showed elevated Lac and reduced Glx labeling relative to normal brain, with inter-patient heterogeneity consistent with an existence of different metabolic subtypes.

Introducción: los síntomas de los trastornos de la interacción cerebro-intestino (TICI) tienen alta comorbilidad psiquiátrica. La personalidad, entendida como un patrón relativamente estable de cognición, emoción y conducta, podría modular la expresión y gravedad de los síntomas gastrointestinales. Objetivo: determinar la relación entre los dominios de personalidad y la presencia y gravedad de los síntomas relacionados con TICI en una muestra clínica de pacientes con trastornos mentales en Bogotá. Métodos: estudio observacional, analítico y transversal realizado en 131 pacientes mayores de 18 años atendidos en una clínica de salud mental. Para medir síntomas gastrointestinales se utilizó la escala Irritable Bowel Syndrome Severity Score (IBS-SSS) y el Personality Inventory for DSM-5 (PID-5) para medir rasgos de personalidad. Se realizaron análisis descriptivos, pruebas de correlación y comparaciones mediante Kruskal-Wallis. Resultados: el 91,2% de los participantes presentó algún síntoma de los TICI, según el puntaje obtenido en la escala IBS-SSS, con predominio de rangos moderados (42,6%) y leves (31,6%). Los dominios de afecto negativo (r = 0,176; p = 0,041), desapego (r = 0,250; p = 0,003) y psicoticismo (r = 0,177; p = 0,039) se correlacionaron significativamente con mayor gravedad de los síntomas. El dominio de desapego mostró una diferencia de mayor gravedad sintomática en IBS-SSS (χ² = 11,5; grados de libertad [gl] = 3; p = 0,009) con respecto a otros dominios de personalidad. Conclusiones: los rasgos de personalidad de desapego, afecto negativo y psicoticismo se relacionan con mayor presencia de síntomas de trastornos intestinales, lo que confirma la hipótesis de la interacción intestino-cerebro. Esto resalta la importancia de evaluar tanto los rasgos de personalidad en gastroenterología como los síntomas digestivos en salud mental.

17 Background: VIR-5500, a dual-masked, PSMA-targeted bispecific T-cell engager, is designed to be specifically activated in the tumor microenvironment where protease activity is dysregulated relative to healthy tissues, potentially expanding the safety margin and therapeutic index. Methods: VIR-5500 was administered IV weekly (QW) and every 3 weeks (Q3W) at doses of 30 - 4000 ug/kg to eligible participants (pts) with progressive mCRPC after receiving SOC. Objectives were to characterize safety, pharmacokinetics (PK) profiles, anti-tumor activity, and determine the dose(s)/regimen(s) for expansion (NCT05997615). Results: As of 23 September 2025, 51 heavily pretreated mCRPC pts (~95% post-taxane) received ≥ 1 dose of VIR-5500. No dose limiting toxicities (pre-defined toxicities occurring during cycle 1) were reported. The incidence of related Grade ≥ 3 AEs was low and CRS was mostly limited to grade 1 and 2 (see Table). PSA declines were noted in all pts dosed at ≥ 3000 ug/kg Q3W, including clinically significant and deep PSA reductions (91% PSA 50 and 55% PSA 90 ). Preliminary evidence of durable PSA responses lasting over one year was noted in select patients undergoing intrapatient dose escalation. An objective response rate of 67% was observed in 4 out of 6 RECIST-evaluable patients treated at doses ≥ 3000 µg/kg Q3W, including one confirmed partial response and three additional partial responses pending confirmation. PSMA-PET imaging confirmed anti-tumor activity, demonstrating strong concordance with PSA 90 responses. Evidence of T-cell activation and target engagement included increased on-treatment CD3+ T-cell tumor infiltration and serum IFN-γ, including minimal elevation of IL-6 levels, consistent with generally low-grade CRS. Preliminary analyses indicated PK was dose-proportional for VIR-5500, with a half-life of approximately 8-10 days and minimal systemic unmasking to the fully unmasked metabolite. Dose escalation continues with both QW and Q3W regimen, and updated data will be provided at the time of the presentation. Conclusions: Pending further clinical validation, available data are suggestive of a generally favorable safety profile, with evidence of meaningful anti-tumor activity, including RECIST responses, and preliminary evidence of durable benefit in a heavily pretreated population with substantial disease burden. Clinical trial information: NCT05997615 . All Participants(n/N, %) ≥ 3000 ug/kg Q3W(n/N, %) Gr 1 CRS 24/51, 47% 9/15, 60% Gr 2 CRS 4/51, 8% 1/15, 7% Gr ≥ 3 CRS 1/51, 2% 0/15, 0% Related Gr ≥ 3 TEAE 8/51, 16% 3/15, 20% Any PSA Decline 34/45, 76% 11/11, 100% PSA 50 24/45, 53% 10/11, 91% PSA 90 11/45, 24% 6/11, 55% Objective Response Rate 4/22, 18% 4/6, 67%

Background: The GLP-1 receptor agonist, semaglutide, was shown to be beneficial in obese (STEP HFpEF) and diabetic (STEP HFpEF DM) patients suffering from heart failure with preserved ejection fraction (HFpEF), presumably secondary to anti-obesity effects. Challenging this assumption, we observed that a low dose of semaglutide, which does not impact body weight in a rat model, ameliorates cardiac HFpEF symptoms including diastolic dysfunction, fibrosis and exercise capacity. We sought to determine whether semaglutide could rescue hepatic symptoms of HFpEF, and if so, determine the molecular underpinnings. Hypothesis: GLP-1 receptor agonism improves the hepatic phenotypes in HFpEF via transcriptional reprogramming of liver. Methods: Ten-week-old male ZSF1 obese rats (n=6/group), which spontaneously develop HFpEF by 12 weeks, received either vehicle (saline) or semaglutide (30 nmol/kg, SC, biweekly) for 16 weeks, a dose and time course that does not affect body weight. Echocardiography, exercise tolerance testing, invasive hemodynamics, and histopathology were performed. Livers were subjected to single nuclei RNA-seq. Differential gene expression analysis (Wilcoxon rank-sum test) was conducted on distinct populations of cells (significance: absolute log2 fold change &gt; 0.5 and a Bonferroni-corrected p-value &lt; 0.05). Results: GLP-1 receptor agonism significantly reduced hepatic cholesterol and triglycerides and attenuated lipid droplet accumulation in liver. Single nuclei RNA sequencing identified multiple distinct hepatocyte populations, along with mesenchymal, endothelial, immune and proliferative cells, but no adipocytes (some hepatocytes expressed adipocyte genes). In hepatocytes, semaglutide induced significant downregulation of genes that promote pathologic fibrosis (including Col4a1 , Emilin1 , Bgn ) along with the TGFβ-responsive transcription factor Klf10 (KLF motifs were enriched amongst semaglutide targeted hepatocyte genes). The master regulator of cholesterol metabolism, LXR ( Nr1h2, Nr1h3 ), was decreased following semaglutide, whereas FXR ( Nr1h4 ), which increases fatty acid oxidation, was increased. Semaglutide also upregulated genes associated with amino acid catabolism. Conclusion: Low dose semaglutide induces a transcriptional response that improves liver metabolism in a HFpEF animal model, independent of weight loss. These data have implications for treatment of metabolic dysfunction associated steatohepatitis (MASH) with GLP1 receptor agonists.

Rabbit hemorrhagic disease (RHD) is a highly contagious viral infection in rabbits that can occur in acute, subacute, chronic, or peracute forms and is not fatal. It is caused by RHD virus (RHDV), a member of the genus Lagovirus in the family Caliciviridae, with variants including RHDV1, RHDV1a, and RHDV2. First identified in 1984 in domestic rabbits (Oryctolagus cuniculus) in China, RHD has since been reported in Asia, Europe, Africa, Central America, and North America. Both innate and adaptive immune responses contribute to host defense, although rapid disease progression can limit adaptive immunity. Carcasses of affected rabbits often retain adequate fat reserves, indicating that death occurs before the development of cachexia. The liver and spleen are the most frequent gross lesions, with hepatic necrosis as the predominant finding. Diagnosis is confirmed through postmortem examination and laboratory testing, with reverse transcription polymerase chain reaction (RT-PCR) being the most sensitive method for detecting viral RNA. Transmission occurs via direct contact, aerosol inhalation, contaminated food or water ingestion, ocular exposure, and contact with fomites. The virus is shed in respiratory secretions, feces, and urine, thereby enabling its rapid spread. Mortality rates range from 70% to 90%, leading to a significant decline in wild rabbit populations. No specific antiviral treatment exists, and control relies on strict biosecurity, quarantine, environmental disinfection, and vaccination. Strain-specific and bivalent vaccines remain the most effective preventive measures, particularly in regions where RHDV2 is endemic. Continuous surveillance is essential for mitigating ecological and economic impacts.

BACKGROUND AND AIMS:Heart failure with preserved ejection fraction (HFpEF) remains a therapeutic challenge. GLP-1 receptor agonists (GLP-1RAs) show clinical promise, and the prevailing hypothesis is that their benefits are primarily driven by weight loss and the downstream benefits of improved functional status. We investigated the weight loss-independent effects of low-dose GLP-1RA therapy in a clinically relevant rodent model of severe cardiometabolic HFpEF.METHODS:Ten-week-old male ZSF1 obese rats with spontaneous HFpEF were treated with low-dose semaglutide (30 nmol/kg twice weekly, n=6) or vehicle for 16 weeks. Comprehensive assessments included body weight, 2-D echocardiography, invasive hemodynamics, exercise capacity as well as cardiac and hepatic fibrosis and lipid deposition. The study utilized advanced multi-omics approaches, including single-cell RNA sequencing of the heart and liver, as well as cardiac, hepatic and plasma proteomics, to explore underlying mechanisms.RESULTS:In ZSF1 obese rats, low-dose semaglutide in the absence of weight loss, significantly improved cardiac function, exercise tolerance, and attenuated fibrosis in the heart and liver. Interestingly, semaglutide therapy reduced cardiac and hepatic lipid content as well as lipid droplets in cardiac myocytes and hepatocytes. Mechanistically, multi-omics analyses of cardiac and hepatic tissues revealed that semaglutide exerted these benefits by improving cardiac metabolism, interfering with pro-fibrotic and pro-hypertrophic signals, and by reducing systemic inflammation.CONCLUSIONS:Low-dose semaglutide provides significant cardioprotective, hepatoprotective, and metabolic benefits in HFpEF independent of weight loss. Our findings support the investigation of lower GLP-1RA dosing in HFpEF and other cardiovascular conditions, including in non-obese patients, to expand the clinical utility of these potent drugs.

This research examines the centrality of Corporate Social Responsibility (CSR) in promoting social inclusion, in terms of minimizing prejudice and promoting education among immigrants in international business. Filling in a research gap in the current literature concerning the strategic alignment of CSR with societal needs, the study will utilize a Systematic Literature Review (SLR) method, and the thematic analysis of secondary data. Our results indicate that CSR programs are a major source of employee commitment, corporate reputation and financial performance. Most importantly, social trust is singled out as one of the major mediators, reinforcing the correlation between CSR efforts and these favorable results. Moreover, institutional investors are discovered to moderate the effectiveness of CSR, and the overall effect. The research findings conclude that CSR is not just a potent strategic instrument of organizational performance and contributing to the expectations of global stakeholders but also provides business and social payoffs in the event of matching societal interests such as reduction of prejudice and education of immigrants.

Nipah virus (NiV) is an emergent paramyxovirus that causes serious disease in humans and animals. Accurate quantification of neutralizing antibodies (nAB) against NiV is essential for vaccine development. The current standard, the plaque reduction neutralization test (PRNT), requires authentic infectious NiV and BSL-4 containment, taking 4-7 days to complete. In this study, we developed a hybrid alphavirus-Nipah virus pseudovirion (Ha-NiV) composed of a non-replicating Nipah virus virus-like particle (VLP) that encapsulates an RNA genome from a fast-expressing SFV (Semliki Forest Virus) alphaviral vector. Ha-NiV can infect NiV target cells but is replication incompetent, enabling rapid quantification of nAB (6-18 hours) in BSL-2 conditions. We validated Ha-NiV using sera from Nipah virus-infected African green monkeys and established a good correlation (R&lt;2&gt; = 0.86) with PRNT, demonstrating comparable specificity and sensitivity. These results demonstrate that the Ha-NiV assay can serve as a novel platform for convenient and rapid quantification of nAB in BSL-2 settings.