Biomedicine Daily · Friday, 11 September 2026
CBA FRONTIER INSIGHTS
FDA Approves Moderna's mFlusiva, First mRNA Seasonal Flu Vaccine
The FDA has approved mFlusiva, Moderna's mRNA-based seasonal influenza vaccine, for adults aged 50-64, making it the first seasonal flu vaccine produced with mRNA technology. The shot encodes full-length hemagglutinin from three WHO-recommended strains delivered in lipid nanoparticles. In two clinical trials, mFlusiva outperformed GlaxoSmithKline's four-strain Fluarix in preventing influenza infection or eliciting antibody responses. The approval extends Moderna's mRNA franchise beyond COVID-19 into seasonal respiratory vaccines and sets a regulatory precedent for a pipeline of mRNA vaccine candidates. The day's other major regulatory news was less favorable for industry: the FDA placed an enrollment hold on Biohaven's epilepsy candidate BHV-7000 after rodent findings, days after a pending $350 million deal covering the program.
Clinical readouts and safety
Atezolizumab in early triple-negative breast cancer: the randomized phase 3 NSABP B-59/GeparDouze trial.
Adding atezolizumab to neoadjuvant taxane-carboplatin-anthracycline chemotherapy did not significantly improve event-free survival in stage II-III triple-negative breast cancer, with an HR of 0.80 (95% CI, 0.62-1.03; P = 0.083) and a 4-year EFS difference of 3.3%. Prespecified subgroup analysis suggested benefit in patients with clinical lymph node involvement (P interaction = 0.039), and an exploratory mRNA subset analysis pointed to basal-like immune-activated tumors as potential responders. Immune-related adverse events occurred in 27.6% with atezolizumab versus 11.4% with placebo.
Novartis DM1 miss raises stakes for next wave of DMPK readouts
Novartis' del-desiran (delpacibart etedesiran) missed the primary endpoint of video hand opening time (vHOT) versus placebo in the 150-patient Phase III HARBOR study in myotonic dystrophy type 1. The company reports evidence of activity in secondary and exploratory measures, including muscle strength and daily living activities, but has not disclosed numerical results or a presentation date. Four upcoming DMPK-targeting readouts will now test whether other candidates can translate molecular effects into clinical benefit.
Regulatory and policy
Moderna flu vaccine wins FDA approval
The FDA has approved Moderna's mFlusiva, an mRNA-based seasonal flu vaccine, for people aged 50–64. It is the first seasonal influenza vaccine to use mRNA production, encoding full-length hemagglutinin from three WHO-recommended strains delivered in lipid nanoparticles. In two clinical trials, mFlusiva outperformed GlaxoSmithKline's four-strain vaccine Fluarix in preventing influenza infection or eliciting antibody responses.
Biohaven epilepsy drug suffers FDA hold days after attracting $350M deal
The FDA has placed a hold on enrollment in trials of Biohaven's epilepsy drug candidate BHV-7000 after findings from rodent tests. The candidate is covered by a pending $350 million deal announced days before the hold. Biohaven has not disclosed how it will respond to the FDA.
In draft guidance, NICE rebuffs Gilead's twice-a-year PrEP med for national coverage
NICE's draft guidance recommends against NHS coverage of Gilead Sciences' twice-a-year PrEP medication lenacapavir. At least one local HIV charity called the decision profoundly disappointing. NICE's appraisal process continues before final guidance is issued.
FDA approves oncolytic virus
The FDA approved Replimune's oncolytic immunotherapy Tudriqev (vusolimogene oderparepvec), formerly RP1, in August for unresectable advanced melanoma that has progressed after PD-1 immunotherapy. The engineered HSV-1 virus encodes GM-CSF and the fusogenic GALV-GP-R glycoprotein to spread through tumours. It is the second oncolytic virus approved, after Amgen's Imlygic (talimogene laherparepvec).
STAT+: U.K. unveils recommendations for regulating AI in medicine
A U.K. commission issued 44 recommendations for regulating artificial intelligence in medicine, aiming to balance AI's potential, such as reviewing millions of diabetes eye scans each year, with safety and equitable treatment. The proposals include staged authorization of new AI models and a system for providers to report how tools perform in clinics, including malfunctions, as models adapt over time.
Research papers
Integrated signatures define mutational processes in prostate cancer.
Integrated mutational footprints (IMFs), built by combining single-base substitution, indel, copy-number and six novel complex structural variant signatures, explain the mutational processes in 85% of primary prostate cancer genomes across 959 donors from the Pan Prostate Cancer Group. Four IMFs, present in 37% of primary tumours, were linked to shorter time to metastasis, and IMFs predicted sensitivity to androgen receptor pathway inhibitors in metastatic disease, supporting their use in risk stratification and treatment selection.
A spatial single-cell transcriptomic atlas of metastatic breast cancer progression
A single-cell spatial transcriptomic atlas of metastatic breast cancer profiles 520,850 cells from 126 tumor samples of 44 patients, covering 171,766 cancer cells and 349,084 tumor microenvironment cells across primary and metastatic lesions. Multiple time points per patient revealed treatment-induced transcriptional changes driving therapy resistance, immune subpopulations predictive of hormone receptor loss, and transcriptomic features of subclones selected during progression that hold future metastatic potential.
Efficient and precise programmable DNA knock-in without double-strand breaks.
CRISPR kilobase-scale nickase-targeting (KNIT) editing inserts DNA fragments from 0.7 kb to over 10 kb without double-strand DNA cleavage by coupling a Cas9 nickase with a DNA donor recruiting system. It achieves up to 89% efficiency, cuts indel rates, translocations and off-target editing, restores gene expression in mutant cells, and enables non-viral CAR-T engineering with antitumour activity in vitro and in mice. This shifts kilobase-scale knock-in away from double-strand-break editing.
Proximity-guided graph learning reveals tumour-associated proximity antigens.
An industrialized surface protein proximity-mapping workflow produced 248 proximity maps across 12 receptor tyrosine kinases and 28 tumour cell systems, yielding MetaMap, a framework that defines spatial protein communities and the concept of tumour-associated proximity antigens (TAPAs). Applied within a multimodal prioritization framework, it identified EGFR-CDCP1 as a TAA-TAPA pair that enhances tumour cell killing across therapeutic modalities, making disease-specific membrane proximity a design principle for precision multispecific therapeutics.
Mechanism of membrane perforation in rotavirus cell entry.
Cryogenic electron tomography with subtomogram averaging, combined with live-cell fluorescence microscopy, visualizes the full course of rhesus rotavirus entry, from cell attachment and virion uptake to release of the subviral particle into the cytosol. The work outlines a mechanism for each entry step, including the membrane perforation that transfers the subviral particle. It links high-resolution virion structures to the dynamics of nonenveloped virus entry.
Sea nettle jellyfish venom targets proteoglycans to cause cell death and pain.
Sea nettle jellyfish venom kills human cells through apoptosis and necroptosis, and whole-genome CRISPR screening identifies proteoglycan biosynthesis as the key host pathway governing venom action. Heparin blocks venom cytotoxicity at a clinically relevant dose, works therapeutically even 1 hour after exposure, and in vivo reduces venom-induced acute spontaneous pain, thermal hyperalgesia, and mechanical allodynia. The findings point to repurposing heparin as a prophylactic or therapeutic against sea nettle stings, for which no rational treatments exist.
Ensemble learning of pathology foundation models for precision oncology
ELF, a framework that ensembles five pathology foundation models into unified whole-slide image representations, outperforms any individual foundation model at disease classification, biomarker detection, and prediction of response to chemotherapy, targeted therapy, and immunotherapy. It was trained on nearly 54,000 slides spanning 20 anatomical sites.
Monoclonal antibodies inhibiting MMP-9 activity alleviate peripheral neuropathy in diabetic mice.
Systemically administered monoclonal antibodies that selectively inhibit MMP-9 relieved mechanical and cold pain and restored hind paw wound healing in diabetic mice. The antibodies reduced epidermal nerve fiber degeneration by improving nerve mitochondrial function and promoting skin angiogenesis. Human relevance is supported by increased MMP-9 expression in dorsal root ganglia of patients with diabetes and by associations of MMP9 variants with neuropathic pain phenotypes.
Targeting tumor-associated macrophages using mRNA lipid nanoparticles for cytotoxic T lymphocyte-mediated cancer immunotherapy.
Antibody-coated lipid nanoparticles targeting TREM2 on tumor-associated macrophages delivered mRNA encoding CXCL9 together with a Toll-like receptor agonist, reversing immunosuppression and increasing tumor infiltration and activity of cytotoxic T lymphocytes. Adding PD-L1 and CTLA-4 checkpoint inhibitors produced a CTL-favoring immunological environment and durable memory immunity, supporting TAM reprogramming as a route to better immunotherapy response.
Oligosaccharide adjuvant-deferred antigen endocytosis promotes cross-presentation
A low-acetylated glucomannan hexasaccharide adjuvant (0.6; acOG6-L) temporally separates dendritic cell activation from antigen uptake by sequentially engaging TLR2 and CD14, deferring antigen internalization by 6 h. This promotes phagosome alkalization via NOX2 and enhances cross-presentation. OVA-acOG6 elicited stronger antigen-specific CD8+ T cell immunity against tumor cells in a subcutaneous B16-OVA melanoma model.
Platinum-based chemotherapy in childhood causes mutations that age the liver
Platinum-based chemotherapy left hundreds of mutations in the liver cells of children treated for hepatoblastoma, an average of 2,200 per liver sample, a mutation burden usually seen in adult livers. Mutation load rose with platinum exposure: children given cisplatin alone had fewer mutations than those given both cisplatin and carboplatin. Liver cells showed far more mutations than blood cells despite systemic treatment, and the authors argue these children need lifelong monitoring for secondary tumors and liver disease.
Ensemble learning of pathology foundation models for precision oncology.
ELF integrates five pretrained pathology foundation models into unified slide-level representations, trained on 53,699 whole-slide images across 20 anatomical sites. It outperformed its constituent and slide-level foundation models on disease classification, biomarker detection, and anticancer and immunotherapy response prediction across multiple cancer types. Its architecture allows data-efficient downstream evaluation, including settings with limited data such as therapeutic response prediction.
A bispecific CD3×CD19 antibody for systemic lupus erythematosus: a phase 1 trial
A next-generation CD3×CD19 bispecific T cell engager given intravenously was well tolerated in patients with active systemic lupus erythematosus in a phase 1 trial, and most patients showed improvements in disease activity scores. The findings support further testing of B cell-directed T cell engagers in systemic lupus erythematosus.
Architecture of the serotonergic projectome in the mouse brain.
The serotonergic projectome in the mouse brain is organized by functional relatedness of target regions rather than their physical proximity. Whole-brain axon tracing shows dorsal and median raphe serotonin neurons fall into five projectomic groups, each preferentially innervating the hippocampus, basal ganglia, cortex, medial interbrain, or brainstem/lateral thalamus. Spatial transcriptomics links each group to distinct transcriptomic clusters, and projection-specific serotonin depletion yields dissociable behavioral phenotypes.
Synthesis of pyrroles from isoxazoles by an O-to-C skeletal edit.
Pyrroles can now be made directly from isoxazoles by an O-to-C skeletal edit that swaps the single differing ring atom in a one-pot sequence. The key intermediate is an N-propargylic enaminone, giving a retrosynthetic disconnection orthogonal to traditional pyrrole syntheses. A predictive computational model captures the conformational features controlling the reaction outcome, enabling regioselective access to otherwise elusive pyrrole scaffolds.
Methods and resources
A clinically-oriented foundation model for intraoperative pathology
CRISP, a vision-based pathology foundation model trained exclusively on frozen section slides, outperformed current foundation models and showed extensive validation, including a prospective cohort, for supporting treatment decisions across the surgical workflow. It brings intraoperative pathology decision support closer to clinical use.
Computable longitudinal patient journeys from structured and unstructured EHR data
A suite of large pre-trained language models extracts computable clinical data from unstructured electronic health records and integrates the findings into knowledge graphs, alongside structured EHR data, to build longitudinal patient journeys. The output is intended to help understand patient trajectories and treatment responses in the real world. The work was published in Nature Medicine on 10 September 2026.
Opinion and commentary
Coroner releases details of infants who died amid growing Pennsylvania measles outbreak
Lancaster County coroner Dr. Stephen Diamantoni confirmed that two measles-related deaths in Pennsylvania last month involved infants, with measles causing one of them. Ivan Miller died Aug. 14 of a ruptured spleen shortly after birth, and Mary Stoltzfus, born with Amish lethal microcephaly, died Aug. 18 at 6 weeks old. The CDC has not said whether it will count either death as measles-associated, and Pennsylvania's outbreak has grown past 620 cases across 37 counties this year.
In brief
- COVID-19 vaccination around immune checkpoint inhibitor start and survival in a nationwide cohort of patients with cancernature.com
- Architecture of the serotonergic projectome in the mouse braincell.com
- Phenomic profiles and disease patterns of 1.9 million participants from Our Future Healthnature.com
- Teamwork makes the dream work? Ensemble learning in computational pathologycell.com