Biomedicine Daily · Saturday, 26 September 2026
CBA FRONTIER INSIGHTS
CagriSema Outperforms Tirzepatide Head-to-Head in REIMAGINE 5 Obesity Showdown
Novo Nordisk's CagriSema (cagrilintide plus semaglutide) beat Eli Lilly's tirzepatide head-to-head in the phase 3 REIMAGINE 5 trial, delivering mean weight loss of 12.4% versus 9.1% in patients with type 2 diabetes and meeting its primary endpoint. The parallel REDEFINE 9 trial also hit its primary endpoint, with CagriSema outperforming placebo on weight loss. Safety was broadly consistent with prior trials and no new safety signals emerged, positioning CagriSema as a direct challenger to tirzepatide in the obesity market, though the result does not settle the broader rivalry between the two companies.
Clinical readouts and safety
[Articles] Iberdomide plus daratumumab and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (EXCALIBER-RRMM): an open-label, randomised, controlled, phase 3 trial
Iberdomide plus daratumumab and dexamethasone significantly improved MRD-negative complete response versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma in the phase 3 EXCALIBER-RRMM trial. The most common grade 3 or 4 adverse events were haematological events and infections, mostly manageable with standard supportive care. The findings support this combination as an efficacious option across diverse care settings.
Novo Nordisk's CagriSema Beats Tirzepatide in REIMAGINE 5 Head-to-Head Trial
Novo Nordisk announced that CagriSema (cagrilintide and semaglutide) beat tirzepatide head-to-head on the primary endpoint of the phase-three REIMAGINE 5 trial. In parallel, the REDEFINE 9 trial showed CagriSema outperformed placebo on weight loss, also meeting its primary endpoint. The results position CagriSema as a challenger to tirzepatide in the obesity drug market.
Half of RRMM Patients Progression-Free Five Years After Single CARVYKTI Infusion in CARTITUDE-2
A single infusion of CARVYKTI (cilta-cel) kept 10 of 20 patients (50%) with relapsed/refractory multiple myeloma alive and progression-free at five years without maintenance therapy. The CARTITUDE-2 cohort A data, with a median follow-up of 60.7 months, cover patients who had received 1 to 3 prior lines of therapy. The results extend the durability evidence for cilta-cel into earlier-line RRMM.
Merck's FZD4/LRP5 Bispecific Succeeds in Phase 2b/3 DME Trial
A phase 2b/3 trial of Merck's FZD4/LRP5 bispecific antibody in diabetic macular edema met success, per the company. Merck built its ophthalmology pipeline around two assets, Remigromig and MK-8748, obtained through its $3 billion acquisition of EyeBio in May 2024. In July, MK-8748, a first-in-class VEGF/Tie2 bispecific also originally developed by EyeBio, entered two phase 3 DME trials head-to-head against aflibercept.
CagriSema Beats Tirzepatide on Weight Loss in REIMAGINE 5 Head-to-Head Trial
In the head-to-head REIMAGINE 5 trial, Novo Nordisk's CagriSema produced mean weight loss of 12.4% in patients with type 2 diabetes, versus 9.1% for Eli Lilly's tirzepatide. Both studies met their primary endpoints, safety was broadly consistent with prior trials, and no new safety signals were identified. The result positions CagriSema ahead of tirzepatide on weight loss, though it does not settle the broader competition between the two companies.
Tumour extrinsic neutrophil regulation in mesothelioma correlates with responsiveness to AXL and PD1 inhibition in MIST3, a phase IIA clinical trial
AXL and PD1 inhibition with bemcentinib plus pembrolizumab met its primary endpoint in the phase IIA MIST3 trial in ICB naïve-relapsed mesothelioma, with a 12-week disease control rate of 46.2% (90% CI 29.2-63.8%); grade 3 or greater adverse events occurred in 53.9% of patients. Multiomic analyses linked response to NF2 loss, immune response signalling, epithelial mesenchymal transition, and neutrophil-related transcriptional programmes including SPI1, ETS2 and FLI1 activation. Gut microbiota composition differed between responders and non-responders and correlated with neutrophil-associated transcription programmes, IRF3 and TLR2.
[Articles] Radiotherapy versus observation following surgical resection of WHO grade 2 atypical meningioma (ROAM/EORTC-1308): an international, multicentre, open-label, phase 3, randomised controlled trial
Adjuvant radiotherapy should be considered after complete surgical resection of WHO grade 2 atypical meningioma, the ROAM/EORTC-1308 phase 3 randomised trial concludes. The international, multicentre, open-label trial compared radiotherapy with observation and found radiotherapy reduces meningioma recurrence, trading that benefit against potential delayed adverse effects. The authors recommend decisions through individual discussion with each patient.
J&J, Legend tout long-term survival benefits for Carvykti in multiple myeloma
Half of multiple myeloma patients in Cohort A of the Phase 2 CARTITUDE-2 study remained alive and progression-free after a single dose of Carvykti, with a median follow-up of 60.7 months. Of 20 patients treated after one to three prior lines of therapy, 10 were alive without progression, and overall survival at this timepoint was 69.2%. The data extend evidence for the BCMA-targeting CAR T therapy in earlier-line use, where Gilead's anito-cel awaits an FDA decision on Dec. 23.
Sequential combination of anti-PD-1 antibody and PEG-IFNα in chronic hepatitis B patients: correlates of HBsAg loss with enhanced T-cell responses
Six of ten virologically suppressed chronic hepatitis B patients with HBsAg levels ≤200 IU/mL achieved HBsAg loss on a response-guided sequential strategy of the anti-PD-1 antibody sintilimab plus PEG-IFNα add-on, with all six maintaining HBsAg negativity 24 weeks after stopping treatment. HBsAg loss correlated with increased HBV-specific IL-2 and IFN-γ T-cell responses, and week-3 IL-10 levels associated with early ALT elevation and subsequent HBsAg decline. Adverse events were mostly grade 1-2.
Regulatory and policy
FDA approves Eli Lilly's weekly insulin Efsitora alfa for type 2 diabetes
The FDA has approved Eli Lilly's once-weekly basal insulin Efsitora alfa (brand name Onswik), announced on September 24, 2026, to improve glycaemic control in adults with type 2 diabetes alongside diet and exercise. Efsitora is a fusion protein linking a novel single-chain insulin variant to a human IgG2-Fc domain, extending half-life to allow weekly subcutaneous injection instead of daily dosing.
Lilly Wins Approval in China for Once-Weekly Insulin Efsitora alfa
Lilly's once-weekly insulin Efsitora alfa has been approved for marketing in China. Efsitora alfa is an Fc-fusion single-chain insulin of 299 amino acids expressed in CHO cells, with 24 disulfide bonds and a molecular weight of 64 kDa. In the trials QWINT-1 and QWINT-2 it showed glucose-lowering effects non-inferior to insulin glargine and insulin degludec, respectively.
Industry and deals
Genentech makes $1.5B+ deal with AI heavyweight Earendil for cancer bispecifics
Genentech will pay Earendil Labs $55 million upfront to discover and develop several bispecific antibody cancer therapies, in a deal that could exceed $1.5 billion including milestones, plus tiered royalties. Earendil leads antibody discovery and early clinical research on pre-agreed target combinations, while Genentech handles global development and commercialization; oncology indications have not been named. Roche also struck a $70 million upfront deal with Atavistik Bio the same day.
bsky.appSignal or noise? > Enveda Raises $311 Million From Leading AI and Biotech Investors to Bring Pharma Into the 21st Century - Business Wire >> Comment below! #strategy #competitiveintelligence #marketing #healthcare #pharmaceutical #pharma #competitivemarketing #biotech
Enveda, a company applying artificial intelligence to drug discovery, has raised $311 million from AI and biotech investors. The financing, announced via Business Wire, is intended to support its effort to modernise pharmaceutical research and development. No trial data, pipeline specifics or timelines were disclosed alongside the raise.
STAT+: Licensing deals on generic versions of Roche flu drug aimed at preparing for pandemic
The Medicines Patent Pool, a U.N.-backed agency, has signed sub-licensing deals with 11 manufacturers to develop, make and supply generic versions of Roche's influenza treatment Xofluza in 129 countries, covering nearly all low- and middle-income nations. The manufacturers will receive technical data, reference products for bioequivalence studies and other support to help secure regulatory approval, as part of pandemic preparedness efforts.
Research papers
Photolabile oligonucleotides with topological light gradients enable spatially resolved single-cell transcriptomics and epigenomics
The material available contains no experimental results, methods description, or findings from the study itself, so the work cannot be summarized beyond its stated topic.
Cell Study Proposes Executor Protein Mechanism for Cuproptosis, Suggesting Targets in Drug-Resistant Gastric and Liver Cancer
A Cell study proposes a mechanism for an executor protein in cuproptosis, the copper-dependent form of cell death. Prior work showed copper ionophores carry copper into cells, causing lipoylated mitochondrial proteins to aggregate and iron-sulfur cluster proteins to break down, but no executor protein had been identified, unlike Gasdermin in pyroptosis, Caspases in apoptosis, and RIPK3 and MLKL in necroptosis. The work points to intervention strategies for drug-resistant gastric cancer and liver cancer.
Aurora kinase a phosphorylates and stabilizes UHRF1 to maintain DNA methylation and prostate cancer cell survival
Aurora kinase A maintains global DNA methylation in prostate cancer cells by phosphorylating the epigenetic regulator UHRF1 at Ser76, which blocks its polyubiquitination and degradation by the proteasome. Depleting AURKA lowered genomic 5methylcytosine levels, destabilized UHRF1, de-repressed p16 and p21, and impaired cell proliferation; only wild-type UHRF1, not the phospho-deficient S76A mutant, rescued these defects. The work links oncogenic kinase signaling directly to DNMT1-mediated methylation maintenance and identifies a druggable AURKA-UHRF1 axis in prostate cancer.
Single-cell analysis of chromatin accessibility in the human intestine identifies regulatory programs and clarifies genetic associations in Crohn’s disease
Single-cell ATAC-seq was used to map chromatin accessibility in intestinal mucosa from patients with Crohn's disease and healthy controls. The work characterizes regulatory programs associated with inflammation and genetic effects, clarifying genetic associations in Crohn's disease.
In-cell discovery and characterization of a non-canonical bacterial protein translocation-folding complex
In-cell cryo-electron tomography combined with proteomics, integrative structural modeling, and bioinformatics uncovered an uncharacterized protein complex in Mycoplasma pneumoniae. The complex links Sec-based protein translocation with extracellular folding and supports both co-translational and post-translational pathways, functionally annotating a previously unknown structure in a minimal bacterium.
Stroke drives glioma progression through the emergence of tumor-associated astrocytes with reduced Ca 2+ activity
Ischemic stroke generates a population of astrocytes with reduced calcium signaling, Lee and colleagues report. These astrocytes recruit tumor-associated macrophages, and this promotes glioma invasion in preclinical models. The work links stroke to glioma progression through a defined astrocyte-macrophage pathway.
A single-nuclei multiomics resource across four brain regions prioritises human neural cell types influencing brain-related traits
Single-nuclei multiomic profiling of gene expression and chromatin accessibility across ~140,000 nuclei from 40 post-mortem adult brain samples (11 donors, four regions: amygdala, hippocampus, hypothalamus, prefrontal cortex) pinpoints neural cell populations underlying brain-related traits. Integration with GWAS statistics prioritised similar neuronal populations for BMI, schizophrenia, bipolar disorder and age at menarche, and supported enhancer-gene relationships relevant to Alzheimer's disease. The resource nominates effector transcripts and cellular pathways for trait-associated variants.
Deconvolution of HIV-1 Mutational Signatures Reveals Dominant and Donor-Specific APOBEC3-Associated Mutagenesis Across Anatomical Compartments
APOBEC3-associated mutagenesis accounts for roughly half of all HIV-1 mutations across blood, spleen, gut, and brain tissues from 21 people with HIV in the Last Gift rapid autopsy program. Two APOBEC3 signatures were deconvolved from single-genome env DNA sequences, and mutational patterns tracked donor identity rather than anatomical compartment. Identical hypermutated sequences found across brain, gut, and blood indicate clonal expansion and trafficking of infected cells.
Euchromatin forms condensed domains with short active regions on the surface
Integrating micro-C and imaging data, simulations now trace chromatin organization continuously from nucleosomes to clutches to domains. The model shows that most euchromatic regions form compact condensed domains, while short regulatory elements remain highly exposed on the domain surface. This unifies two structural levels previously described separately and locates active regulatory elements at accessible positions.
Structure-based rational design and biological evaluation of a quinazoline-based EGFR exon 20 insertion inhibitor
Structure-based design of quinazoline analogues incorporating an intramolecular hydrogen bond at the 5-position yielded potent inhibitors of EGFR exon 20 insertion mutants in non-small cell lung cancer. Thirty-six compounds were synthesised and tested in biochemical kinase assays; the R-configuration of the 5-position acylpyrrolidine substituent plus specific 4-position anilines gave the best activity. The most potent analogues reached sub-nanomolar IC50 values against various EGFR exon20ins mutants.
Circadian timing of first-line chemoimmunotherapy is associated with survival in extensive-stage small cell lung cancer
Earlier infusions of first-line platinum-etoposide plus atezolizumab or durvalumab were linked to longer survival in 107 patients with extensive-stage small cell lung cancer. Those treated before the cohort median time of day of administration (11:54) had median PFS of 9.07 vs. 7.23 months and OS of 21.17 vs. 11.43 months, with adjusted HRs of 1.63 and 1.65 for later administration, and no difference in toxicity. The finding points to infusion timing as a modifiable factor that warrants prospective testing.
Methods and resources
Robustness measures for cell type classification in single-cell RNA-seq datasets of kidney organoids
Two robustness measures, the classification stability score and prediction specificity score, quantify the reliability of cell-type labels from label-transfer tools in scRNA-seq data. Applied to human fetal kidney and four iPSC-derived kidney organoid protocols with a mouse fetal kidney reference, scores were high for most fetal kidney cell types except immature epithelial structures, high for organoid cap mesenchyme, and variable for epithelial lineages depending on protocol. A cell-removal simulation confirmed the measures flag unreliable classifications.
Opinion and commentary
Chemists struggle to ditch hazardous solvents — even after decades of ‘green’ efforts
An analysis of 1.3 million chemical reactions from patents across four decades shows hazardous solvent use rose from about 60% of reactions in 1976 to above 70% by 2016. Helen Sneddon of the University of York and Maarten Dobbelaere of the Swiss Federal Institute of Technology in Lausanne used the AI system Rxn-INSIGHT on a US Patent and Trademark Office database, publishing the survey this month in Angewandte Chemie. When regulation restricts a toxic solvent, chemists tend to switch to another hazardous liquid rather than a safer alternative, and use of trifluoroacetic acid, a PFAS, has risen substantially; the database ends in 2016 and does not measure solvent quantities.
The role of fibronectin in the tumor microenvironment - implications for immunotherapy
A review in Cell Cycle examines how oncofetal fibronectin isoforms containing the EDA and EDB domains shape the tumor microenvironment in solid tumors, where they are highly expressed but absent from normal adult tissues. It covers their roles in vascular remodeling, epithelial-mesenchymal transition, pre-metastatic niches and immunosuppression, and evaluates fibronectin as a biomarker and therapeutic target in breast cancer, ovarian cancer and glioblastoma. Stromal strategies including antibody-drug conjugates and immunocytokines are discussed as ways to overcome resistance to standard immunotherapy.
Redesigning cardiovascular medicine around sex differences
A Perspective published in Nature Medicine on 25 September 2026 argues for redesigning cardiovascular medicine around sex differences. It connects evidence from preclinical and clinical domains, calls for greater understanding of sex-biased mechanisms, and urges integrating those insights into diagnostics and therapeutics, with a focus on female-predominant cardiovascular conditions.
Also today
8 events that did not make today's daily, one table per category, one row per event. Open a category to expand.
Deals and financingADARx Pharmaceuticals · Nektar prevails in legal battle with Lilly over broken rezpeg partnership · North Immunology ← Aethlon M · ADARx Pharmaceuticals4 ▾▴
Licensing, M&A and financing that did not make the daily.
OtherSTAT+ · Signal or noise? > Cell therapy weekly · A clinical study on the efficacy of a novel herbal medicine cocktail in enhancing HIFU treatment for · STAT+4 ▾▴
Everything else with a concrete event that did not make the daily.