Biomedicine Daily · Monday, 7 September 2026
CBA FRONTIER INSIGHTS
Roivant's Inhaled Mosliciguat Posts 56% PVR Reduction in Phase 2 PH-ILD Win
Roivant's bet on an inhaled hypertension therapy cleared its first major test. In the phase 2 PHocus trial, mosliciguat — a soluble guanylate cyclase activator licensed from Bayer for $14 million and developed through Pulmovant — cut pulmonary vascular resistance by a placebo-adjusted 56.3% at Week 16 among 135 patients with pulmonary hypertension associated with interstitial lung disease across 20 countries. Six-minute walk distance rose 35.2 meters and NT-proBNP fell 53.2%, while cough, the key inhaled-safety concern, appeared in 12.1% of drug recipients versus 18.2% on placebo. The once-daily therapy has already moved into phase 3. Elsewhere, the sham-controlled PVI-SHAM-AF trial found ablation beats sham on AF recurrence but not on disease-specific quality of life at 6 months, and Japan approved GSK's antisense drug bepirovirsen as its first functional-cure treatment for chronic hepatitis B.
Clinical readouts and safety
Roivant’s $14M bet on Bayer’s inhaled hypertension med pays off with phase 2 win
Inhaled mosliciguat, a soluble guanylate cyclase activator Roivant licensed from Bayer, hit the primary endpoint in the phase 2 PHocus trial: a placebo-adjusted 56.3% reduction in pulmonary vascular resistance at Week 16 among 135 patients with PH-ILD across 20 countries. Six-minute walk distance improved by 35.2 meters and NT-proBNP fell 53.2%, with cough in 12.1% of drug recipients versus 18.2% on placebo. Pulmovant has moved the once-daily therapy into phase 3.
PVI-SHAM-AF: Ablation Cuts AF Recurrence but Beats Sham on Quality of Life at 6 Months No
In the double-blind, sham-controlled PVI-SHAM-AF trial, real catheter ablation was more effective than sham procedure at reducing atrial fibrillation recurrence, but at 6 months it did not provide a significant additional improvement in atrial fibrillation-specific quality of life over sham. Reported by Rolf Wachter at ESC 2026, the finding separates rhythm control from symptomatic benefit in a rigorously controlled design.
[Articles] Induction and consolidation atezolizumab with stereotactic body radiation therapy versus radiation alone in high-risk, early-stage non-small-cell lung cancer (SWOG/NRG S1914): a multicentre, open-label, superiority, phase 3, randomised controlled trial
Adding induction and consolidation atezolizumab to stereotactic body radiation therapy did not improve overall survival in patients with high-risk, inoperable, early-stage non-small-cell lung cancer in the SWOG/NRG S1914 phase 3 randomised trial. This was the first fully reported phase 3 cooperative group trial of immunotherapy in this setting, and the combination produced more grade 3 or higher adverse events than radiation alone. The results argue against adding atezolizumab to SBRT in this population.
Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.
Balanced crystalloid fluid did not improve outcomes over 0.9% saline in children with septic shock. In the PRoMPT BOLUS trial, conducted at 47 emergency departments in five countries, a major adverse kidney event occurred in 3.4% of the balanced-fluid group (137 of 4235 patients) versus 3.0% of the saline group (124 of 4247 patients) (risk ratio, 1.10; 95% CI, 0.88 to 1.40). Hyperchloremia was more frequent with saline, 49.0% versus 31.4%, without affecting the primary outcome.
Regulatory and policy
Japan Approves GSK Antisense Therapy Hibsago for Functional Cure of Chronic Hepatitis B
Japan's Ministry of Health, Labour and Welfare has approved GSK's antisense oligonucleotide therapy Hibsago (bepirovirsen) as the first treatment in Japan aimed at achieving a functional cure for chronic hepatitis B. It is indicated for adults who have received at least six months of nucleos(t)ide analogue therapy and meet predefined virological marker criteria. The approval adds an ASO-based option alongside recent siRNA advances in functional cure efforts.
Research papers
Carbon ion irradiation at a clinically used dose rewires super-enhancers to drive necroptosis and systemic immunity.
A single 2 Gy fraction of carbon ion irradiation provokes antitumor immunity by switching cell death from apoptosis to MLKL-dependent necroptosis, surpassing 8 Gy x-rays in immunogenicity despite lower direct tumor cell killing. Multi-omics analyses trace the switch to clustered DNA damage-driven super-enhancer remodeling that suppresses cIAP1/2-caspase-8-mediated apoptosis and licenses an NF-κB inflammatory cascade (IL1A/B, CXCL1/2/3). In vivo, 2 Gy CIRT drives an abscopal response with increased CD8+ T cell infiltration and function, and MLKL inhibition abolishes these effects.
Mitochondrial Citrate-to-Acetyl-CoA Metabolism Drives SASP Through Epigenetic Regulation in Senescent Cells
Mitochondria act as a key regulator of the senescence-associated secretory phenotype (SASP), but activation of inflammatory transcription factors alone does not guarantee high expression of the corresponding genes. The work shows that senescent cells upregulate a mitochondrial pyruvate-citrate-acetyl-CoA metabolic axis: SLC25A1 exports citrate to the cytoplasm and ACLY generates acetyl-CoA, sustaining histone acetylation and open chromatin at SASP-related loci.
CD55 Organizes Lipid Raft-LCK Signaling to Boost NK Cell Antitumor Immunity
CD55, classically a complement regulator, acts as an immune activator in NK cells: after tumor recognition NK cells upregulate CD55, which binds CD97 on tumor cells, promotes lipid raft clustering and activates LCK signaling to strengthen antitumor killing. The work, published in Cell Research by a team from the First Hospital of Jilin University, also shows sustained loss of CD55 in the tumor microenvironment drives NK cell exhaustion, and restoring CD55 markedly enhances antitumor activity of NK and CAR-NK cells.
Recurrent patterns of TOP1-mediated neuronal genomic damage shared by major neurodegenerative disorders.
Neurons from C9ORF72 ALS, C9ORF72 FTD, and Alzheimer's disease brains share a mutational process linked to topoisomerase 1. Single-cell whole-genome sequencing of 469 neurons showed a TOP1-like sIndel signature in 22% of ALS, 76% of FTD, and 61% of AD neurons versus 2% of controls, and RADAR assays confirmed increased TOP1-DNA covalent complexes. TOP1-mediated genome damage emerges as a shared mechanism of neuronal death across TDP-43 and tau proteinopathies.
Acidic transcription factors position the genome at nuclear speckles through transcription-dependent and -independent mechanisms.
Specific DNA sequences from nuclear speckle-associated genomic regions target themselves to nuclear speckles as transgenes, without active transcription. Dissection of the COL1A1-SGCA locus identified redundant targeting cis-regulatory elements, including an ∼600-bp fragment with 17 binding motifs for 8 transcription factors. Four of these factors carry acidic activation domains conferring chromatin-context and transcription-dependent targeting, and a subset also shows transcription-independent targeting activity.
Four-dimensional molecular mapping from a spatial snapshot reveals the dynamics of hair follicle organogenesis.
A spatial transcriptomics method called 3D DNase-Enhanced Expression Profiling captures gene expression hundreds of microns deep in cleared intact tissue, and applied to neonatal mouse skin it mapped hundreds of developing hair follicles in 3D. Ordering follicles by molecularly inferred developmental age turned one snapshot into a four-dimensional map of organogenesis, revealing stem cell compartment stratification, new cell subtypes, and hair canal formation. In Foxn1-deficient nude mice, organ-wide delays and reduced coordination appeared before overt structural defects.
Regulatory roles of pyroptosis-associated lncRnas in breast cancer progression and immune microenvironment
Pyroptosis-associated long non-coding RNAs can stratify breast cancer patients into risk groups with significantly different survival outcomes, based on transcriptomic analyses. Low-risk tumors show increased infiltration of CD8+ T cells, NK cells, and B cells with elevated immune checkpoint expression, while high-risk tumors show M2 macrophage enrichment and higher tumor mutation burden. Mechanistically, these lncRNAs act through inflammasome activation, gasdermin-mediated signaling, and epigenetic modulation, marking them as candidate prognostic biomarkers and therapeutic targets.
DT56a (Femarelle) effectively manages vulvovaginal atrophy in postmenopausal women
Twelve weeks of DT56a (Femarelle), a non-hormonal oral treatment, improved vulvovaginal atrophy/genitourinary syndrome of menopause in postmenopausal women with severe VVA. All 12 patients showed a significant reduction in vaginal pH, and 11 of 12 improved on the vaginal maturation index and Utian Quality of Life scores. The findings support a non-hormonal systemic option for VVA/GSM.
Probing far-from-equilibrium dynamics of electrical double layers.
An integrated experimental-computational framework directly resolves electrical double layer dynamics during the hydrogen evolution reaction, combining time-resolved surface-enhanced infrared absorption spectroscopy on nanostructured Pt film electrodes with machine-learning molecular dynamics over nanosecond timescales. The work reveals a nonlinear, two-phase evolution of the inner layer that intensifies the local electric field, plus irreversible restructuring of interfacial water during cyclic potential modulation. It shows ions and interfacial water respond asynchronously far from equilibrium, replacing classical equilibrium EDL models with a quantitative molecular framework.
Influenza Vaccine Effectiveness and Safety for the 2026-2027 Respiratory Season.
Influenza vaccines cut influenza-related hospitalization in older adults across seasons (VE 19.0%-43.0%) and mortality (VE 29.0%-65.8%), and prevented 80.0% of laboratory-confirmed influenza-associated deaths in those aged 6 months to 17 years. A 2025 RCT showed the high-dose vaccine outperformed standard-dose against hospitalization in older adults (relative VE, 43.6%). A self-controlled case series of 9,973,703 vaccinees found no increased risk of serious adverse events, including Guillain-Barré syndrome, and none for febrile seizure 0 to 7 days after vaccination. This JAMA review of 69 studies updates the evidence base for the 2026-2027 season.
Network pharmacology, and molecular docking studies for two flavonoid compounds isolated from Dodonaea viscosa towards SARS-CoV-2 infection and loaded in lipid nanoparticles
Santin and viscosine isolated from Dodonaea viscosa, loaded into spanlastic nanovesicles, showed anti-SARS-CoV-2 activity in an MTT assay, with IC50 of 4.483 µg/ml for V1 and 9.795 µg/ml for S1. V1 inhibited virus adsorption while S1 showed 55.7% virucidal activity. Network pharmacology identified EGFR as the top annotated gene with 7 edges, and docking plus ADMET profiling supported drug-like, non-toxic behaviour.
Methods and resources
A simple, anesthesia-free infusion technique for in vivo metabolic tracing.
Isoflurane anesthesia broadly alters serum and tissue metabolism, decreasing serum acylcarnitines and fatty acids while increasing amino acid metabolites and select nucleotides, with tissue-specific remodeling such as glycolytic changes in brain and amino acid accumulation in pancreas. A nonsurgical tail vein catheterization method, done in minutes, enables multihour U-13C6-cystine infusion in awake, freely moving mice, achieving cysteine labeling comparable to jugular infusion with circulating cystine closer to physiological levels. It replaces anesthesia-based tracer delivery for in vivo stable isotope tracing.