Biomedicine Daily · Wednesday, 9 September 2026
CBA FRONTIER INSIGHTS
Gene-Edidted Pig Kidney Sustains Dialysis-Free Patient for 271 Days Before Successful Human Transplant
A first-in-human study published in The Lancet reports that a gene-edited porcine kidney (EGEN-2784) transplanted into a patient with end-stage kidney disease functioned immediately and maintained dialysis independence for 271 days. The organ failed after immunosuppression reduction, with thrombotic microangiopathy despite a negative donor-specific crossmatch; no porcine pathogen transmission or anti-HLA antibody change occurred. Eighty-two days after nephrectomy, the patient received a human kidney allotransplant that functioned immediately, with no sensitisation during 231 days of follow-up. The case demonstrates xenotransplantation can work as a bridge to allotransplantation without blocking subsequent human organ matching.
Clinical readouts and safety
Porcine kidney xenotransplantation as a bridge to allotransplantation: a first-in-human study.
A gene-edited porcine kidney (EGEN-2784) transplanted into a patient with end-stage kidney disease functioned immediately and maintained dialysis independence for 271 days before failing after immunosuppression reduction, with thrombotic microangiopathy despite negative donor-specific crossmatch. No porcine pathogen transmission or anti-HLA antibody change occurred. 82 days after nephrectomy, the patient received a human kidney allotransplant with immediate function and no sensitisation during 231 days of follow-up.
Base Editing Therapy CS-101/CS-206 Cures Beta-Hemoglobinopathy Patients Across Genetic Backgrounds
A base editing therapy developed with the transformer Base Editor (tBE), CS-101/CS-206 from Correctsequence Therapeutics, achieved clinical cure across patients with different genetic backgrounds, according to results published in Cell Stem Cell on September 7, 2026. Following 100% cure in Chinese beta-thalassemia patients, the study shows tBE is safe and effective in sickle cell disease and in Southeast and South Asian beta-thalassemia patients, supporting broad applicability across ethnicities.
STAT+: AstraZeneca’s experimental COPD treatment posts strong results in late-stage studies
AstraZeneca's injectable drug tozorakimab reduced COPD exacerbations by about 30% across all patients over a year in a pair of Phase 3 trials, with data presented at the European Respiratory Society conference and published in the New England Journal of Medicine. The trials included participants not eligible for other new COPD drugs, potentially giving the company a market segment to itself, with analysts projecting billions in annual sales if approved.
Tozorakimab to Prevent COPD Exacerbations.
Add-on tozorakimab, an interleukin-33 inhibitor, cut the annualized rate of moderate or severe COPD exacerbations by roughly 30% in two replicate phase 3 trials, OBERON and TITANIA, with no eosinophil-count eligibility criteria. Among former smokers, rates fell from 1.90 to 1.34 events per year (rate ratio 0.71) in OBERON and from 2.07 to 1.37 (rate ratio 0.66) in TITANIA. It offers a biologic option for exacerbation prevention independent of eosinophil status.
Transplanted pig kidney works for record 271 days in "bridging" study.
Novartis stock slides as centerpiece of $12B Avidity buyout flunks ‘crucial’ phase 3 test
Novartis' del-desiran missed the primary endpoint in the phase 3 Harbor trial, undermining the centerpiece asset of its $12 billion acquisition of Avidity Biosciences. The readout gives Novartis one win and two failures across its recent run of key clinical trial results.
STAT+: Roivant lung disease drug hits mid-stage study goals
Roivant's mosliciguat met all goals in a 16-week Phase 2 study in pulmonary hypertension, cutting pulmonary vascular resistance by a statistically significant 56% versus placebo. The drug also produced a 35-meter placebo-adjusted gain in six-minute walk distance and a 53% placebo-adjusted reduction in NT-proBNP, a blood marker of heart failure, supporting a new treatment approach for the lung disease.
The factors that could have contributed to Novartis’ Lp(a) miss
Pelacarsen, Novartis' antisense oligonucleotide targeting LPA, failed to improve cardiovascular outcomes in the Phase III HORIZON secondary prevention trial in patients with elevated Lp(a) levels. The miss undermines the company's first-in-class Lp(a) ambitions. Depending on the full data and on the fate of subsequent programs, the outcome could carry implications for antisense oligonucleotides, other RNA modalities and cardiovascular R&D more broadly.
STAT+: Neuromuscular drug from Novartis fails in key study, adding to pressure on company
Del-desiran, Novartis' experimental drug for myotonic dystrophy type 1, failed the Phase 3 HARBOR trial, missing its primary endpoint of outperforming placebo on video hand opening time (vHOT), a measure of the hand's ability to relax after squeezing. It is Novartis' second major trial failure within days, following a cardiovascular miss, and the stock fell as much as 10% in early Swiss trading, intensifying concern about the pipeline ahead of a patent cliff.
Boston Scientific recalls spinal cord implant in wake of more than 1k serious injuries
Boston Scientific recalled all unused Infinion CX Leads, components of a spinal cord stimulator that delivers mild electrical pulses to block pain signals, because the leads may break. The FDA classified the action as its most serious category, and as of May 27 the company reported 1,081 serious injuries and no deaths. Already implanted devices are not affected; the recall covers models SC-2317-50 and SC-2317-70.
Bristol Myers’ pivotal CAR-T multiple myeloma trial hits primary endpoint
A pivotal trial of Bristol Myers Squibb's GPRC5D-directed CAR-T cell therapy in multiple myeloma has met its primary endpoint. The result advances Bristol Myers Squibb's effort to compete with Johnson & Johnson for the post-BCMA multiple myeloma market. No outcome figures were disclosed in the announcement.
Regulatory and policy
FDA Approves Priovant's TYK2/JAK1 Inhibitor Lisraya for Adult Dermatomyositis
The FDA approved Priovant Therapeutics' Lisraya (brepocitinib), a first-in-class selective dual TYK2/JAK1 inhibitor, for adult dermatomyositis on August 27, 2026. Priovant was set up by Roivant and Pfizer, and the drug, originally coded PF-06700841, was discovered and taken through early-phase I/II trials by Pfizer. It is the only approved targeted oral therapy for dermatomyositis, received orphan drug designation and priority review, and is now available in the US.
A breakthrough pancreatic cancer drug won approval. They still struggle to access it
FDA approval of Rasonque, Revolution Medicines' pancreatic cancer drug that nearly doubles median overall survival, closed the company's expanded access program, leaving patients mid-process without coverage. Commercial insurers like Aetna and Medicare Part D plans take weeks or months to set up coverage, with one Medicare denial reversed only after OptumRx approved prior authorization. Patients such as Juan Solano, who has metastatic disease, remain caught in the gap.
Industry and deals
FDA approves Ziihera for first-line HER2-positive gastroesophageal adenocarcinoma, triggering milestones and $250 million Royalty Pharma financing
The FDA on August 25, 2026 approved Ziihera (zanidatamab-hrii) for first-line unresectable locally advanced or metastatic HER2-positive gastroesophageal adenocarcinoma: IHC 3+ and IHC 2+/ISH+ patients can receive it with tislelizumab plus chemotherapy, and IHC 3+ patients with chemotherapy alone. Under the BeOne Medicines collaboration, Zymeworks has received $81 million, with up to $144 million in further milestones and tiered royalties of up to 19.5%. The approval triggers the structure set up on March 2, 2026, when Zymeworks BC moved 30% of future Ziihera royalties into Zymeworks Royalty Limited Partnership, which borrowed $250 million in non-recourse notes from Royalty Pharma secured solely on those royalties.
GSK takes rights to Hutchmed’s KRAS-antibody conjugate: Deals Report
GSK plc is paying $110 million up front for most global rights to HMPL-A830, a dual-targeted oncology therapy from Hutchmed China that links a KRAS inhibitor payload to an anti-EGFR antibody. HMPL-A830 is the first deal from Hutchmed's Antibody-Targeted Therapy Conjugate (ATTC) platform, which has also produced two PI3K-payload programs now in Phase I testing. The same report also covers Alteogen's delivery-tech deal with Novartis and Menarini's local in-licensing of Gan & Lee's obesity program.
Research papers
Structural basis for modulation of group III mGlu receptors by transsynaptic interactions.
A cryo-electron microscopy structure of the ELFN-mGluR complex reveals a specific ELFN-binding pocket on group III metabotropic glutamate receptors, through which ELFN proteins allosterically regulate the orthosteric ligand binding site via a network of residues. mGluR activation increases association with ELFN proteins, a cooperativity that may serve as a feedback mechanism controlling synaptic strength. Disrupted mGluR-ELFN interaction emerges as a recurring mechanism underlying several neurological conditions.
Selective decay of interferon mRNAs controls antiviral immunity and innate memory.
The RNA-binding protein tristetraprolin (TTP) and the mRNA decay machinery selectively limit type I and type III interferon (IFN) mRNA levels at steady state and after stimulation. Loss of this pathway increases IFN mRNA poly(A) tail length, stability and translation, raising IFN expression enough to block SARS-CoV-2 infection in vitro and in vivo. A human TTP variant linked to autoimmunity shows reduced TTP levels and increased IFN signaling, and transient loss of mRNA decay primes innate memory for long-term antiviral protection.
Intracellular complement factor H protects neurons during CNS inflammation.
Intracellular complement factor H (CFH) protects neurons from inflammatory injury through a non-canonical role independent of complement C3. In single-nucleus RNA-sequencing of retinal ganglion cells from donors with multiple sclerosis and controls, CFH expression correlated strongly with resilience to degeneration. CFH was induced by inflammatory and oxidative stress, localized to the endoplasmic reticulum, limited reactive oxygen species accumulation and lipid peroxidation, and its protection depended on the C-terminal SCR20 domain in mice and humans.
An expanded codebook of human transcription factor DNA-binding specificity.
The Codebook project determined the sequence specificity of 332 putative and poorly characterized human transcription factors through more than 4,000 independent in vitro and in vivo experiments, yielding motifs for 177 TFs (53%) and about 130 distinct new motifs. The work reveals tens of thousands of previously unknown, conserved and direct TF-binding sites across the human genome, concentrated in promoters and predictive of gene expression. In vitro motifs were strongly enriched in cellular binding sites, addressing controversy over how well motifs reflect in vivo binding.
Structural basis of a SWI/SNF-associated transcription pre-initiation complex
Cryo-EM structures and genetic analyses identify the SWI/SNF chromatin remodeler as an integral component of the transcription pre-initiation complex. The structures show SWI/SNF stabilizes PIC organization and remodels the +1 nucleosome in a concerted way, providing a structural mechanism for how SWI/SNF facilitates transcription initiation.
EspF acts as a molecular scaffold to facilitate TRIM25-mediated NLRP3 inflammasome activation during mycobacterial infection
The mycobacterial ESX-1 effector EspF is a conserved activator of the NLRP3 inflammasome in Mycobacterium tuberculosis, M. bovis and M. marinum. EspF augments IL-1β and IL-18 release, ASC speck formation, caspase-1 activation and GSDMD-mediated pyroptosis in THP-1 cells, and acts as a scaffold bridging TRIM25 to NLRP3, promoting K63-linked ubiquitination of NLRP3. Mice infected with M. bovis BCG overexpressing EspF showed worse lung lesions and higher bacterial burdens.
Granule cells reorient cortical trajectories to separate contexts.
Cerebellar granule cells separate contexts not by expanding cortical representations but by rotating their low-dimensional trajectories apart between two skills sharing temporal structure, while premotor L5PT activity patterns generalized. Imaging both nodes in mice during parallel learning showed GrC remapping was coherent and strongest in expert animals. The work assigns cortex the role of invariant dynamic primitives and the cerebellum the reconfiguration for context-specific output.
Clinical Relevance of Genomics Defined WHO5 Subtypes of Pediatric B-ALL in the Context of Measurable Residual Disease-Directed Risk-Based Therapy.
WHO5 genomic classification identified subtype-defining abnormalities in 81.2% of 533 pediatric B-ALL patients treated on the ICiCLe-ALL-14 protocol, and a three-tier genomic risk model separated outcomes: 3-year EFS of 80.4%, 59.3%, and 45.8% for standard, intermediate, and high genomic risk (P < .0001). Genomic risk independently predicted EFS alongside postinduction MRD and ICiCLe risk on multivariable analysis, showing genomics can complement MRD-directed risk stratification.
CRISPR-Cas regulates expression of embedded anti-phage defence systems.
Type I CRISPR-Cas loci embed and transcriptionally control diverse innate defence systems, a regulatory paradigm named CRISIS. Small non-canonical crRNA-like RNAs guide the I-C Cascade effector to promoters of immune cassettes, keeping basal expression sufficient for antiviral activity while preventing fitness costs such as growth impairment and exclusion of beneficial plasmids. When CRISPR-Cas is compromised by mutation or anti-CRISPR proteins, transcription of the embedded defences surges, raising innate immunity at the expense of host fitness. This casts CRISPR-Cas as a supervisor of a layered prokaryotic defence network, an 'immunity guard' strategy.
Changes in five cerebrospinal fluid and three plasma Alzheimer's disease biomarkers across increasing brain amyloid-beta and tau pathology burden.
CSF Aβ42/Aβ40 declines earliest, dropping at the second quartile of Aβ burden (p<0.001) and detecting low/intermediate Aβ with AUC 0.984, while CSF p-tau markers rise only at the third quartile and perform best at advanced Aβ (AUCs 0.889 to 0.980) and intermediate tau stages (AUCs 0.949 to 0.995). In 250 participants with ante-mortem fluid sampled a median of 1.5 months (CSF) or 1 month (plasma) before death, p-tau217-based markers outperformed p-tau181 counterparts, and plasma p-tau217 measures identified only advanced Aβ and tau burden (AUCs 0.893 to 0.928). The findings support a sequential biomarker model and show current fluid biomarkers miss the earliest Aβ deposition.
Thioredoxin reductase-1 facilitates cellular plasticity and stemness mediated by TGF-β1 in non-small cell lung cancer
Thioredoxin reductase 1 (TXNRD1), expressed about 2-fold higher in advanced-stage NSCLC, drives epithelial-mesenchymal transition, migration, invasion, and stemness through an autocrine TGF-β1 loop. Knockdown of TXNRD1 reduced EMT-associated genes and TGF-β1 production in A549 and H226 cells, while overexpression raised EMT and stemness markers in H1299 cells. In an orthotopic mouse model, TXNRD1 deficiency or inhibition with TRi-1 suppressed metastatic tumor growth.
Learning induces activation-mechanism-dependent neural plasticity in an intracortical microstimulation task.
Detection thresholds for intracortical microstimulation (ICMS) fell as rats learned a detection task, and chronic imaging showed stimulus-evoked recruitment expanding at a fixed current while a consistent number of neurons still underlay behavioral responses. Electrophysiology separated two adaptations: pulse-locked, directly activated neurons strengthened excitability, and polysynaptically recruited neurons grew in number and predicted behavior. Learning thus reshapes cortical circuits through activation-mechanism-dependent plasticity, arguing for stimulation paradigms that track both cell-intrinsic and network dynamics.
Connectome analysis of a cerebellum-like circuit for sensory prediction.
A connectomic map of a cerebellum-like sensory prediction circuit in electric fish reveals inhibitory and disinhibitory input pathways suited to instructing synaptic plasticity, structured connectivity between stages that solves credit assignment, and recurrent wiring that speeds prediction and cancellation. A model constrained by electrophysiological recordings shows how plasticity at multiple sites cooperates to produce fast, accurate, noise-robust cancellation. It changes the field by demonstrating how distributed plasticity can be mechanistically deciphered with connectomics, cell-type-specific recordings and modelling.
AI-Designed Drug Rentosertib Lowers Biological Age in Idiopathic Pulmonary Fibrosis Trial
Rentosertib, an Insilico Medicine candidate whose target and molecular structure were derived with generative AI, has become the first AI-designed drug to complete clinical evaluation of anti-aging effects. In a 12-week trial, proteomics data from 42 patients with idiopathic pulmonary fibrosis were analyzed by six aging clocks developed independently by different teams, and all six indicated reduced biological age after rentosertib treatment.
Structural and functional analysis of LarC, a CTP-dependent cyclometallase required for nickel-pincer nucleotide cofactor biosynthesis.
Cryo-EM structures of full-length LarC from Moorella thermoacetica, the first reported, reveal a hexamer with a central LarC2 domain core and peripheral LarC1 trimers joined by flexible linkers. A conserved histidine-rich nickel-binding region and an adjacent acidic pocket in LarC1 are both essential for activity, and density for an intermediate analog maps a likely transfer site in an interdomain cleft. The work supports a model in which the CMPylated intermediate moves from LarC2 to LarC1 for nickel insertion.