Biomedicine Daily · Thursday, 24 September 2026

Roche and Ionis Sefaxersen Hits Primary Endpoint in Phase III IgA Nephropathy Trial

Sefaxersen, an antisense oligonucleotide targeting complement factor B, met the primary endpoint in a prespecified interim analysis of the phase III MAgINATION study in IgA nephropathy. At week 37, the drug produced a statistically significant and clinically meaningful reduction in proteinuria versus placebo. It is the first RNA-targeted therapy for IgA nephropathy and the only CFB antisense therapy in development.

Macrophage therapy extends transplant-free survival in cirrhosis by 252 days

A four-year follow-up study published in Cell Stem Cell reports that macrophages, the immune system's scavenger cells, can intervene in liver cirrhosis and reverse hepatic fibrosis. Patients receiving the macrophage-based therapy gained 252 days of transplant-free survival, with reduced risk of death and liver transplantation. The work opens a non-transplant treatment path for end-stage liver disease.

Kyverna ‘resetting conversation’ with 1-year miv-cel data as autoimmune CAR-T peers hit safety snags

A single dose of miv-cel (mivocabtagene autoleucel) produced durable benefit in stiff person syndrome, with 26 patients in the Kysa-8 registrational trial showing a median 49% improvement on the timed 25-foot walk test at 12 months versus baseline, up from 46% at week 16. There were zero cases of high-grade cytokine release syndrome, ICANS or IEC-HS, and 92% of patients remained free of chronic immunotherapies. Kyverna will add the one-year data to its FDA rolling submission, on track for completion in the fourth quarter.

Phase 1 Study of Anito-cel, a d-Domain BCMA CAR T Cell for Refractory or Recurrent Myeloma

FDA Direct Final Rule Allows Non-Animal Methods to Replace Animal Safety Testing

The FDA has issued a direct final rule stating that non-animal methods can be used to assess the preclinical safety of drugs and biological products intended for humans. The change formally recognizes emerging approaches as able to supplement or replace animal testing in human drug safety evaluation. Non-animal methods may be used when they are adequately validated and appropriate for the product and regulatory question.

Boehringer adds $250M to value of Variant pact by expanding into cardiovascular disease

Boehringer Ingelheim has expanded its collaboration with Seattle-based genomics biotech Variant Bio to cover cardiovascular disease, on top of the original January deal worth $120 million for cardiorenal and kidney disease. Variant will receive an additional upfront payment and is eligible for license and milestone payments totaling more than $250 million. The partners will use Variant's AI-powered Inference platform to identify genetically supported targets for potential first-in-class cardiovascular treatments.

A design approach for bitopic kinase inhibitors

A design strategy for bitopic kinase inhibitors used systematic analysis of ligand choice, linkage vector and linker length. Applying it to ABL1 and EGFR produced bitopic inhibitors, among them an ABL1 inhibitor with enhanced activity against resistance mutations and reduced off-target toxicity. The work offers a generalizable route to bitopic inhibitor design.

Targeting ZMYND8 unleashes IL-2 signalling to override T cell exhaustion

Deleting ZMYND8 lifts the block it imposes on IL-2R–STAT5 signalling in CD8+ T cells, restoring p300-mediated transcriptional activation of Il2ra and overriding terminal exhaustion. Loss of ZMYND8 pushed the cells toward effector-like states and markedly enhanced both antiviral and antitumour immunity, identifying a druggable route to reclaim exhausted T cell function.

Persistence of mucosal CAR-T cells and inflammatory remodeling in enterocolitis associated with BCMA CAR-T cell therapy

Enterocolitis after BCMA CAR-T cell therapy in patients with multiple myeloma is driven not only by plasma cell and B cell depletion but by expansion of cytotoxic CAR-T cells and coordinated dysregulation across intestinal compartments, a multimodal analysis shows. Mucosal CAR-T cells persist at the inflammation site. The findings support JAK inhibitors as a potential treatment for this complication.

mTORC1 drives cell-autonomous astrocyte reactivity in tuberous sclerosis

Reactive astrocytes are shown to arise as a primary consequence of TSC2 loss in tuberous sclerosis complex, driven by mTORC1 in a cell-autonomous manner. The work implicates glial dysfunction as a primary driver of pathogenesis rather than a secondary response, and points to astrocytes as potential therapeutic targets for tuberous sclerosis complex-related neuropathology.

TRAM promotes Toll-like-receptor-free myddosome signal transduction

TRAM is identified as a regulator of an unconventional Toll-like receptor signalling mechanism in which activated TLRs release proto-myddosomes into the cytosol rather than signalling solely from the receptor tail. Using a flow-cytometry assay that separates myddosome-containing responder cells from bystanders in LPS-treated MyD88-tagged macrophages, RNA-seq showed 2,380 differentially expressed genes, with responders selectively inducing primary and secondary response genes and producing IL-6 and TNF while bystanders did not. A genome-wide CRISPR screen for loss of myddosomes and NF-κB activation identified TRAM, and imaging of TRAM knockout lines confirmed its role in proto-myddosome formation after LPS or LTA stimulation.

A methanogen hydrolase reveals the structure of archaeal peptidoglycan

The enzyme ArmA from the gut methanogen Methanobrevibacter smithii is a glycosyl hydrolase that specifically cleaves methanogen cell walls. Characterizing ArmA revealed an archaeal peptidoglycan with a previously unidentified sugar and an unexpected chemical structure. The finding changes the picture of methanogen cell wall chemistry in a dominant human gut archaeon.

Myeloid infiltration and epidermal dysregulation characterize cutaneous photosensitivity in systemic lupus erythematosus

Type 2 Deiodinase in Cancer-Associated Fibroblasts: A Potential Therapeutic Target in Many Types of Cancer

Type 2 deiodinase (DIO2), the enzyme converting T4 to T3, is a conserved marker of cancer-associated fibroblasts (CAF) across thyroid cancer and six additional solid tumor types, and is enriched in myofibroblastic CAF. Elevated DIO2 expression correlated with worse overall survival in pancreatic and bladder cancers, while thyroid cancer showed an inverse association linked to loss of epithelial DIO2 during dedifferentiation. In a TPO-CreERT2/BrafV600E/Trp53-deficient mouse model, Dio2 loss in the tumor microenvironment significantly reduced tumor growth, and D2 activity was suppressed by cefuroxime and lenvatinib.

Practical lessons in the global scaling of clinical AI: from one hospital to over a million patients screened

Nature Medicine published on 23 September 2026 a piece on scaling a deep learning clinical tool from a single hospital to more than a million screened patients across India, Thailand and Australia. The three distinct settings yielded cross-cutting lessons on deployment. The authors suggest these insights can inform wider global expansion of healthcare artificial intelligence.