Biomedicine Daily · Friday, 4 September 2026
CBA FRONTIER INSIGHTS
FDA Approves First RAS(ON) Inhibitor for Metastatic Pancreatic Cancer
The FDA has approved Revolution's daraxonrasib (RASONQUE), a once-daily oral RAS(ON) multi-selective inhibitor, for adults with metastatic pancreatic ductal adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multi-drug combination therapy. The 26 August approval arrived about 6.5 months ahead of the FDA's original target date. Daraxonrasib is the first approved RAS(ON) multi-selective inhibitor and the first RAS-targeted drug for metastatic PDAC that broadly inhibits multiple RAS mutations, giving a hard-to-treat cancer a new oral option. On the same day, ivonescimab from Akeso and Summit met its overall survival endpoint in a head-to-head trial against pembrolizumab, following an earlier progression-free survival win with median PFS of 11.14 versus 5.82 months (HR 0.51), though the overall survival result drew a more measured reception.
Clinical readouts and safety
YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism in Patients With Cancer: A Randomized Clinical Trial.
The YEARS algorithm was as safe as direct computed tomographic pulmonary angiography (CTPA) for ruling out acute pulmonary embolism in patients with active cancer. In the per-protocol analysis, 5 of 282 patients (1.8%) managed by YEARS vs 15 of 273 (5.5%) by CTPA only had symptomatic venous thromboembolism or possible PE-related death within 90 days (absolute risk difference, -3.7%; upper bound of 99.9% CI, 1.4%), and 22% of YEARS patients avoided CTPA entirely. This challenges guideline advice to send all cancer patients with suspected PE straight to CTPA.
Ivonescimab Beats Pembrolizumab Head-to-Head in HARMONi-2 Phase III Trial
Ivonescimab from Akesf outperformed pembrolizumab in the phase III HARMONi-2 head-to-head trial, meeting the primary endpoint of progression-free survival at interim analysis with a statistically significant result. Median PFS was 11.14 months with ivonescimab versus 5.82 months with pembrolizumab, hazard ratio 0.51. HARMONi-2 is the first phase III study to show a significant positive result against pembrolizumab.
STAT+: Ultragenyx drug to treat Angelman syndrome, a rare disease, fails late-stage trial
Ultragenyx reported that GTX-102, its experimental therapy for Angelman syndrome, showed no benefit versus sham treatment in a large Phase 3 trial. The drug had shown powerful results in early trials, raising hopes among families and advocates that it could pioneer medicines improving cognition and communication in intellectual disabilities. The failure also removes a drug investors counted on as Ultragenyx's path to profitability.
Akeso, Summit’s ivonescimab extends lives in Keytruda head-to-head trial. What now?
Ivonescimab, the PD-1xVEGF bispecific from Akeso and Summit, has met its overall survival endpoint in a head-to-head trial against Keytruda. The result follows a progression-free survival win reported about two years ago, which had positioned the drug and its class as the leading candidate to replace Keytruda. The overall survival finding, however, has drawn a far more measured reception.
Ultragenyx fails phase 3 Angelman test, plots ‘significant expense reductions’
Ultragenyx's phase 3 Aspire trial of apazunersen in Angelman syndrome missed its primary endpoint of change from baseline in Bayley-4 cognitive raw score and its secondary endpoint of net response on the Multidomain Responder Index. The company is reviewing the program's future and planning significant expense reductions. Shares fell 43% after hours; no trial figures were disclosed.
AbbVie’s bispecific T-cell engager shows promise in ph. 3 multiple myeloma trial
Etentamig, AbbVie's bispecific T-cell engager, improved response rates and progression-free survival in patients with relapsed/refractory multiple myeloma in a phase 3 trial. The positive data, released Thursday, support the candidate as a treatment option in this setting.
Regulatory and policy
FDA Approves Revolution's RAS(ON) Inhibitor Daraxonrasib for Metastatic Pancreatic Cancer
The FDA approved Revolution's RASONQUE (daraxonrasib), a once-daily oral tablet, for adults with metastatic pancreatic ductal adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multi-drug combination systemic therapy. The approval on 26 August 2026 came about 6.5 months ahead of the original FDA target date. Daraxonrasib is the first approved RAS(ON) multi-selective inhibitor and the first RAS-targeted drug for metastatic PDAC that broadly inhibits multiple RAS mutations.
FDA Approves First Drug to Treat Alexander Disease
The FDA has approved Zanvastro (zilganersen) injection from Ionis Pharmaceuticals for Alexander disease in pediatric and adult patients, the first treatment for this rare neurological disorder and the first to target the abnormal GFAP protein buildup that drives it. Efficacy rested on a 49-patient randomized controlled study plus a 4-patient open-label substudy in infants under 2, with treated patients aged 5 and older showing better walking speed at 61 weeks. The antisense oligonucleotide is injected into the spinal canal every three months.
China's NHSA Releases DRG/DIP 3.0 Grouping Scheme, Expanding Core DRG Groups to 492
China's National Healthcare Security Administration released version 3.0 of its DRG and DIP payment grouping schemes at a press conference on September 2, more than a month later than the planned July release. Core DRG groups rise from 409 in version 2.0 to 492, with detailed subgroups up from 634 to 825, while core DIP disease categories are cut from 9520 to 5125. The revision shifts weight toward complex cases such as oncology and critical illness and away from common conditions.
Trump Signs Most-Favored-Nation Pricing Deals With Nine More Drugmakers, Total Now 26
US President Trump announced new most-favored-nation drug pricing agreements with nine pharmaceutical companies on August 31, bringing the total number of manufacturers signed to 26. The deals cover 89% of the US brand-name drug market. The pacts extend the White House MFN strategy, which ties what US government insurance pays for drugs to the lowest prices paid in other developed countries, from large multinationals to smaller biotech and generic drugmakers.
NMPA Approves Sanofi BTK Inhibitor Rilzabrutinib Tablets for Adult Chronic ITP
China's NMPA has approved Sanofi's BTK inhibitor rilzabrutinib tablets for adults with persistent or chronic primary immune thrombocytopenia (ITP) who responded poorly to or cannot tolerate corticosteroids, immunoglobulin or similar treatments. Sanofi gained the drug through its $3.68 billion acquisition of Principia Biopharma in September 2020. The FDA approved rilzabrutinib for ITP in August 2025, making it the first BTK inhibitor cleared for that indication.
NMPA Approves Two Domestic Long-Acting RSV Antibodies for Infants on Same Day
On September 3, China's NMPA approved two domestic long-acting RSV monoclonal antibodies through the priority review pathway. Tai Nuo Mai Bo's antibody is indicated for newborns and infants entering or born in their first RSV season to prevent RSV lower respiratory tract infection. Rui Yang Bio's antibody covers newborns with gestational age of at least 35 weeks in the same setting, excluding children with chronic lung disease, including bronchopulmonary dysplasia, or clinically significant congenital airway abnormalities. Studies cited show RSV mortality in infants under 1 year old is about 2.5 times higher than with influenza.
China's NMPA Approves Culeivibartamab Injection to Prevent RSV Lower Respiratory Tract Infection in Infants
China's National Medical Products Administration approved Culeivibartamab Injection, brand name Yingmule, from Ruiyang (Shandong) Biopharmaceutical, via priority review. It prevents RSV lower respiratory tract infection in neonates and infants with gestational age of at least 35 weeks entering or born in their first RSV season, excluding children with chronic lung disease including bronchopulmonary dysplasia or clinically significant congenital airway abnormalities. The approval adds a new option for this population.
Industry and deals
GSK pens $1.3B Hutchmed deal for early-stage KRAS-EGFR cancer asset
GSK has licensed Hutchmed's preclinical KRAS-EGFR antibody conjugate HMPL-A830, paying $110 million upfront in a deal worth up to $1.295 billion, excluding Mainland China, Hong Kong, Macau and Taiwan. The candidate delivers a KRAS inhibitor to EGFR-expressing tumors and is slated to enter trials later this year, initially in colorectal, pancreatic and lung cancer. Hutchmed will run Phase 1 trials, after which GSK takes over R&D and commercialization outside select Asian territories.
Medtronic Invests About $700 Million in Cornerstone Robotics and Gains Overseas Distribution Rights for Sentire
Medtronic has made a strategic investment of about $700 million in Cornerstone Robotics and acquired rights to distribute the Sentire laparoscopic surgical robot in certain approved markets outside the United States. Medtronic will sell Sentire alongside its Hugo robot-assisted surgery system as a complementary dual-platform offering within its connected surgery ecosystem. The deal pairs Cornerstone's product with Medtronic's capital and channel access.
Research papers
Systematic discovery of pathogen effector functions across human pathogens and pathways.
A scalable functional genomics platform, the effector ORFeome (eORFeome), covers 3,835 effector ORFs from viruses, bacteria, and parasites. Barcoded screens across NF-κB, apoptosis, p53, cGAS-STING, and MHC class I pathways found pathway-modulating functions for hundreds of uncharacterized eORFs and unexpected activities of known ones, including HHV6A U14 as a p53 antagonist, HHV7 U21 as a dual-function STING antagonist and MHC-I inhibitor, and adenoviral 13.6K/i-leader protein as a de novo-evolved TAP inhibitor.
Thermo-sensing mechanisms of splicing control by nuclear stress bodies.
CLK1 localization to nuclear stress bodies depends on phosphorylation of its Ser341, which is removed by PP1 during thermal stress and restored by RIOK2 during recovery, timing CLK1 arrival at nSBs to the recovery phase. The work, done in HeLa cells and cell-free reconstitution, also identifies PPP1R2, an intrinsically disordered PP1 inhibitory subunit, as a reversible thermosensor that dissociates under stress to activate PP1. It explains how staged localization of SRSFs and CLK1 coordinates temperature-dependent pre-mRNA splicing.
Gene alteration in human brain suggests genetic and epigenetic roots of major depression
Molecular profiling of the adult human hippocampus finds evidence of sustained neurogenesis and identifies a stalled neurogenic process in major depressive disorder. Cell- and circuit-specific genetic, epigenetic, stress, immune, metabolic and synaptic mechanisms underlie impaired hippocampal plasticity. The work provides a framework for disease subtyping and therapeutic development.
Subnuclear genome compartmentalization controls bivalent chromatin activity.
During cortical neurogenesis, hundreds of neuronal genes relocate from the nuclear lamina to nuclear speckles, including bivalent neurodevelopmental genes marked by H3K27me3 and H3K4me3. Relocation to speckles resolves bivalent chromatin to H3K4me3 monovalency and increases transcription more than eightfold. Proximity to the nuclear periphery, not H3K27me3 itself, maintains the poised low-expression state, so gene location within the nucleus is required to understand epigenomic regulation.
LZTFL1 rewires NADPH-glutathione metabolism to amplify ferroptosis.
LZTFL1 amplifies ferroptosis by promoting oxidation of G6PD, which limits NADPH production and impairs glutathione regeneration; GSH depletion then boosts LZTFL1 translation through an AKT-mTOR-eIF4E feedforward loop. In vivo, the LZTFL1-FHOD1-G6PD axis sensitized multiple tumor models, including patient-derived xenografts, suppressing tumor growth and prolonging survival. LZTFL1 restored cisplatin sensitivity in resistant lung and ovarian cancer cells and predicted better survival in lung adenocarcinoma patients.
Adaptive model-guided protein evolution with sparse data optimizes compact eukaryotic genome editors.
A model-guided engineering strategy for sparse data, EvoMax, produced a compact eukaryotic Fanzor2 nuclease variant, FanzMAX v3-hLa, that reaches up to 97% editing efficiency at the best-performing endogenous locus and a mean of ~33% across 19 endogenous loci. It outperformed enNlovFz2 and enCnCas12f1 by more than 2.6-fold and edited hPCSK9 in humanized mice. EvoMax combines Gaussian process regression, protein language models and inverse folding with iterative experimental profiling.
Zinc finger protein 24 enhances the pro-inflammatory activities of Tc17 cells and Tc17.1 cells in mouse collagen-induced arthritis
Zinc finger protein 24 acts as a positive regulator of the pro-inflammatory activity of synovial Tc17 and Tc17.1 cells in rheumatoid arthritis. Transcriptome profiling of sorted synovial Tc17 and Tc17.1 cells from mice with collagen-induced arthritis identified ZNF24 among the differentially expressed genes; ZNF24 knockdown reduced expression of IL-17A, RORgt, GM-CSF, IL-22, perforin and granzyme B, weakened induction of pro-inflammatory mediators in synovial fibroblasts, and ameliorated the exacerbation of CIA by transferred Tc17.1 cells. The findings were also seen in RA patients and human Tc17 and Tc17.1 cells.
3D epigenome of glial cell types in developing human cortex.
A 3D epigenomic analysis of four glial populations from the mid-gestational human neocortex, integrating gene expression, chromatin accessibility, DNA methylation and 3D chromatin interactions, mapped cell-type-specific candidate cis-regulatory elements and validated their function in transgenic mouse embryos. Machine learning prioritized 112 schizophrenia risk variants within glial enhancers, and the rs4449074 risk allele was confirmed in vivo to disrupt a predicted vRG enhancer. oRG regulatory elements are enriched for human accelerated regions, some showing activity differences from chimpanzee orthologues.
METTL3 promotes cell-cycle progression via activation of transcriptional elongation.
The m6A methyltransferase METTL3 is a direct substrate of the mitotic kinase CDK1 in mammalian cells. CDK1 phosphorylates METTL3 at Ser43 at mitotic entry, driving m6A methylation of 7SK RNA and release of P-TEFb from the 7SK snRNP, which clears RNA polymerase II genome-wide; mutating Ser43 disrupts elongation, delays mitotic exit, and increases chromosome missegregation. This places RNA methylation inside the CDK1-driven mitotic program.
Conformational asymmetry of replicated human chromosomes.
Human sister chromatids are consistently misaligned in the 5'→3' direction of inherited DNA strands, revealed by sister chromatid-sensitive conformation analysis. The shift persists without cohesin-mediated loop extrusion but is lost upon disruption of cohesion, and polymer modeling shows modest directional misalignment of cohesive cohesins can explain it. The register shift has implications for homology search during DNA repair.
Tumor-derived antioxidants suppress immunity by depriving T cells of reactive oxygen species.
Tumors release the antioxidant enzyme peroxiredoxin 1 (PRDX1) into their environment, where it deprives T cells of reactive oxygen species needed for T cell receptor signaling and effector function. Prdx1 is up-regulated during cancer immunoediting, and its loss within tumors enhances antitumor immunity and responses to immunotherapy. The work identifies a redox-dependent mechanism of tumor immunosuppression that may be targetable therapeutically.
Unveiling the immune microenvironment in sinonasal intestinal type adenocarcinoma: new arguments for immunotherapy
High CD8+ T-cell density is an independent prognostic factor for better disease-free and overall survival in sinonasal intestinal-type adenocarcinoma (59 tumors analyzed by immunohistochemistry, flow cytometry and transcriptomics). Tumor-infiltrating lymphocytes expressed PD1, TIGIT and TIM-3, and TIM-3 blockade in patient-derived explants increased tumor cell apoptosis, while tumors expressed CD155 but not PDL1 on tumor cells. Transcriptomics separated hot from cold tumor clusters with different prognoses and immunotherapy response scores, giving a rationale for immunotherapy trials in this wood dust-associated cancer with limited standard options.
Microfluidic-engineered glucose-responsive microparticle depot for smart insulin delivery
Microfluidic-engineered glucose-responsive microspheres, using glucose oxidase as the sensing unit in a PLGA and acetalated dextran carrier, release insulin in response to glucose. Fabrication gave uniform, controllable microsphere size with stable batch-to-batch reproducibility. In STZ-induced diabetic mice, a single injection kept blood glucose normal for at least 20 hours, with no organ toxicity, no systemic inflammation and a low hypoglycemic index.
Metabolite buffering of labile iron governs ferroptosis.
Ferroptosis sensitivity is not governed by iron abundance alone. Sharma and colleagues identify polyamines as endogenous metabolic buffers that reduce the chemical accessibility of labile iron, assigning an unexpected function to one of the cell's most abundant metabolite classes. The finding points to new questions about how intracellular iron metabolism is organized.
Nanoemulsion adjuvanted COBRA HA vaccine enhances protective antibody titers against H1N1 and H3N2 influenza viruses
A W805EC oil-in-water nanoemulsion adjuvant (NE01) substantially improves immune responses to computationally optimized broadly reactive antigen (COBRA) HA vaccines in mice. Adjuvanted COBRA H1 and H3 HA proteins elicited higher HAI antibody titers against panels of H1N1 and H3N2 viruses and more IFN-γ-secreting splenocytes than unadjuvanted HA. After challenge, adjuvanted groups lost statistically less weight and had undetectable viral lung titers.
Methods and resources
Barcoded oligonucleotide system (BOLT) for targeted organ delivery
BOLT is a barcoded oligonucleotide platform that lets many chemically diverse ligand-oligo conjugates be evaluated simultaneously in a single animal, combining rational barcode design, modular conjugation chemistry, and NGS-based quantification. It works in mice and nonhuman primates and identified ligands with tropism for brain, lung, and muscle, addressing the low throughput of testing oligo candidates one by one in animals. It changes how tissue-specific extrahepatic delivery ligands are screened.
Opinion and commentary
Nirsevimab for respiratory syncytial virus prevention: A comprehensive product review
A product review in Hum Vaccin Immunother assesses nirsevimab (Beyfortus), a long-acting monoclonal antibody against the RSV prefusion F protein, for infant RSV prevention with a single season-long dose. It highlights the HARMONIE trial's 83.2% reduction in RSV-associated hospitalization and postlicensure effectiveness of 70-90% against hospitalization across multiple countries, with 2024-2025 data suggesting greater protection than maternal RSVpreF vaccination. The authors call for continued surveillance of effectiveness, safety and viral escape.