Biomedicine Daily · Saturday, 12 September 2026
CBA FRONTIER INSIGHTS
FDA Grants Priority Review to First In Vivo CRISPR Therapy for Hereditary Angioedema
Intellia Therapeutics' lonvoguran ziclumeran (lonvo-z), an in vivo CRISPR therapy for hereditary angioedema, has been accepted by the FDA with priority review and a PDUFA goal date of March 10, 2027; no advisory committee meeting is planned. If approved, it would be the first approved in vivo CRISPR therapy and the only single-treatment option for HAE. The day also brought a phase 3 JAMA trial in which 10 days of intravenous loberamisal improved 90-day functional recovery after acute ischemic stroke (69.7% reaching mRS 0-1 vs 56.3% on placebo among 997 adults in China), and semaglutide approvals for MASH with F2-F3 fibrosis, based on part 1 of the ESSENCE trial in 1,197 patients, in both the US and China, where it is the first MASH indication granted.
Clinical readouts and safety
Loberamisal for Acute Ischemic Stroke: The LAIS Randomized Clinical Trial.
Intravenous loberamisal, given once daily for 10 days on top of standard care, improved functional recovery after acute ischemic stroke in the phase 3 LAIS trial. Among 997 treated adults in China with NIHSS scores of 7 to 20 within 48 hours of onset, 69.7% reached a 90-day mRS score of 0 to 1 versus 56.3% with placebo (RR, 1.24), with no increase in adverse events, serious adverse events, or mortality.
Inhaled siRNA ARO-RAGE Shows Dose-Dependent RAGE Silencing in Human Lungs
Inhaled ARO-RAGE safely and durably silenced the RAGE target in the lung in its first human trial, published in Nature Medicine by Matthias Salathe's group at the University of Kansas Medical Center with Arrowhead. In healthy volunteers and asthma patients, soluble RAGE in serum and bronchoalveolar lavage fluid fell in a dose-dependent manner. This is the first randomized controlled trial to demonstrate safe and effective pulmonary gene silencing by an inhaled siRNA in humans, though disease benefit still requires more data.
Complete Regression of Hepatoblastoma after Interleukin-15- and Interleukin-21-Coexpressing CAR T-Cell Therapy.
Oral GLP-1 Agonist Foundayo Cuts Weight Up to 12.4% at 72 Weeks in ATTAIN Trials
The oral non-peptide small-molecule GLP-1 receptor agonist Foundayo produced mean weight loss of 12.4% (27.3 pounds) at 72 weeks at the highest dose versus 0.9% (2.2 pounds) with placebo, in an on-treatment estimand counting only those who stayed on the drug, within the ATTAIN global clinical program covering both diabetic and non-diabetic populations, with results published in the New England Journal of Medicine and The Lancet. Under a treatment-policy estimand including discontinuations, the highest dose gave 11.1% (25 pounds) versus 2.1% (5.3 pounds) for placebo.
Merck, Gilead’s failed Trodelvy lung cancer trial shows better China results
GSK’s Hansoh-partnered ADC lays down marker for lung cancer scrap with Merck
GSK's risvutatug rezetecan, an antibody-drug conjugate developed with Hansoh, achieved a median overall survival of 18.5 months in a phase 3 trial. The result positions the drug as a threat to Amgen and Merck & Co. in the lung cancer field.
[Articles] Immunogenicity of fractional one-fifth and one-half doses of 17DD yellow fever vaccine compared with full dose in children aged 9–23 months in Uganda: a phase 4, single-blind, randomised clinical trial
Fractional one-fifth and one-half doses of the 17DD yellow fever vaccine were non-inferior to the full dose in inducing initial seroconversion in children aged 9-23 months in Uganda, in a phase 4, single-blind, randomised trial. The findings support fractional-dose yellow fever vaccination of young children for outbreak response during vaccine supply shortages.
Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial
Teclistamab produced higher rates of complete clinical responses than lenalidomide-dexamethasone in patients with high-risk smoldering multiple myeloma in the randomized phase 2 ImmunoPRISM trial. Longer follow-up is needed to determine whether it durably prevents progression to multiple myeloma.
BioNTech sets survival standard in hard-to-treat cancer ahead of pivotal readout
Cullinan, Taiho showcase 6-month survival benefit in phase 3 trial for advanced lung cancer
Cullinan Therapeutics and Taiho Oncology reported phase 3 data showing their therapy improved survival by more than Johnson & Johnson's Rybrevant in patients with advanced non-small cell lung cancer in the front-line setting. The comparison comes from a head-to-head context in the front-line advanced disease population.
Definium LSD drug goes 3 for 3 with another pivotal anxiety trial win
Glycocalyx-edited mesenchymal stem/stromal cell therapy in advanced osteoporosis
Intravenous glycocalyx-edited mesenchymal stem/stromal cells derived from the bone marrow of older individuals with osteoporosis proved safe and feasible in a phase 1 study of advanced osteoporosis. The cells retained clinically meaningful osteoregenerative capacity, supporting an allogeneic-style cell therapy route toward reversing bone loss rather than only slowing it.
Regulatory and policy
Novo Nordisk's Semaglutide Approved for MASH with Moderate to Severe Liver Fibrosis
Novo Nordisk's semaglutide injection (Wegovy/Novo Nordisk's brand Nuvo Ying) has been approved for MASH in patients with moderate to severe liver fibrosis. The approval is based on the primary results of part 1 of the ESSENCE outcomes trial, which enrolled 1,197 MASH patients with biopsy-confirmed F2 or F3 fibrosis. Semaglutide met both liver histology primary endpoints versus placebo.
FDA Grants Priority Review to Intellia's In Vivo CRISPR Therapy lonvo-z for HAE
The FDA has accepted Intellia Therapeutics' BLA for lonvoguran ziclumeran (lonvo-z), an in vivo CRISPR therapy for hereditary angioedema, with priority review and a PDUFA goal date of March 10, 2027. The agency does not plan to convene an advisory committee. If approved, lonvo-z would be the first approved in vivo CRISPR therapy and the only single-treatment option for HAE.
Labcorp to Offer Roche's FDA-Approved Elecsys pTau-217 Alzheimer's Blood Test in the US
Labcorp will offer Roche Diagnostics' Elecsys pTau-217 blood test in the US, the first and only FDA-approved single-biomarker blood test for Alzheimer's-related amyloid pathology. It measures pTau-217 in blood to help clinicians identify or rule out Alzheimer's-related pathology in people aged 55 and older with cognitive decline or related symptoms, in both general and specialty care settings.
Semaglutide Injection Wins China's First Approved MASH Indication
Novo Nordisk's semaglutide injection, Wegovy, has been approved in China for metabolic dysfunction-associated steatohepatitis (MASH), the first and only approval for this indication there. The decision rests on primary results from part 1 of the ESSENCE outcomes trial in semaglutide-treated MASH patients with moderate to severe hepatic fibrosis, which enrolled 1,197 patients with biopsy-confirmed MASH and F2 or F3 stage fibrosis. The approval extends the product's evidence base from weight management and cardiovascular health into liver health.
China's 7th National Consumables Tender Covers Digestive Intervention Devices for First Time
China's seventh batch of national centralized procurement of medical consumables opened bids in Tianjin on September 10, with results to be implemented from January 2027. For the first time it systematically includes digestive intervention products, spanning 23 categories such as gastrointestinal balloon dilatation catheters, esophageal, intestinal, biliary and pancreatic stents, ERCP guidewires, stone retrieval baskets, snares, endoscopic hemostatic clips and ESD knives. Of 558 products bid by 156 companies, 517 from 148 companies won selection, covering most clinically used mainstream products.
Selective oestrogen receptor degrader class grows with new cancer approval
The FDA has approved AstraZeneca's camizestrant (Etcamah), a selective oestrogen receptor degrader, as part of a combination therapy for a subset of breast cancer patients. The drug targets patients whose tumours have acquired resistance mutations to aromatase inhibitors. It expands the SERD class of therapies.
Industry and deals
With deep pockets, Solstice takes next-gen CTLA-4 into neoadjuvant treatment
Solstice Oncology has launched with a $225 million series A led by RA Capital Management, with Canaan Partners and Forbion also investing, to develop its Fc-enhanced, shorter-acting CTLA-4 antibody porustobart (HBM4003), for which it holds ex-China rights. The NewCo will test the antibody in the neoadjuvant setting to see whether giving it before surgery improves responses without toxicity delaying tumor removal. CEO Caroline Loew said the round closed at the time of the licensing deal.
Research papers
Selective RNA sequestration in biomolecular condensates directs cell fate transitions.
P-bodies selectively sequester translationally repressed, untranslated RNAs encoding cell fate regulators in a conserved, cell type-specific manner across vertebrate developmental contexts. P-body RNA contents are controlled by microRNAs and reshaped by perturbing AGO2 or polyadenylation site usage. Manipulating P-body assembly or microRNA activity directed naive mouse and human pluripotent stem cells toward totipotency and primed human embryonic cells toward the germ cell lineage.
Identification of a mechanical signaling pathway activating type 1 fimbriae via a ZraSR two-component system in neonatal meningitis-associated Escherichia coli
A mechanical signaling pathway drives blood-brain barrier invasion by neonatal meningitis-associated Escherichia coli K1. The ZraSR two-component system senses physical forces from initial attachment to human brain microvascular endothelial cells and binds fimS, flipping it to phase-ON to activate type 1 fimbriae, specifically the FimH adhesin. Disrupting the pathway attenuates meningitis progression and reduces proinflammatory factors in vivo, marking pathway components as therapeutic targets.
Dose-ranging pharmacokinetics, safety, and efficacy of a 90-day intravaginal ring delivering islatravir in pigtail macaques.
A 3D-printed intravaginal ring delivering islatravir protected macaques against repeated SHIV exposure. Rings with 15, 30, or 60 milligrams released the drug in a dose-dependent manner and were safe over 90 days. All six macaques with 60-milligram rings stayed seronegative and SHIV RNA negative after 12 weekly vaginal SHIV162p3 exposures, while two untreated controls were infected.
Complete Revascularization Guided by Functional Coronary Angiography in STEMI.
Guiding complete revascularization by functional coronary angiography rather than conventional angiography cut adverse events after STEMI. In 1823 patients with multivessel disease, the composite of death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization occurred in 8.9% versus 13.7% (hazard ratio 0.62) at a median 17.9 months, with fewer safety events (4.6% vs 7.1%). This supports physiology-based assessment for selecting nonculprit lesions to treat.
Westlake University team completes telomere-to-telomere assembly of the mouse Y chromosome in Science
The mouse genome reference is now complete: Yu Xiaochun's team at Westlake University has published a telomere-to-telomere assembly of the mouse Y chromosome in Science. Two years ago the same group assembled the 19 autosomes and the X chromosome, leaving only the structurally complex male-specific Y chromosome unresolved. The new work fills that final gap in the reference sequence.
Westlake University Team Closes Mouse Genome With Full Telomere-to-Telomere Y Chromosome
A team at Westlake University has assembled a complete telomere-to-telomere Y chromosome from C57BL/6 mice, filling the last gap in the mouse genome. The chromosome, mT2T Y, spans 95.21 Mb and closes 25 remaining gaps, most in repetitive and complex regions. The December 2024 Science paper had already completed the 19 autosomes and the X chromosome; the mouse genome is now complete.
Adaptive motility enables neutrophils to rapidly navigate confined capillaries.
Neutrophils maintain migration speed in capillaries as narrow as 2 micrometers by rapidly engaging Rho-dependent actomyosin contractility at the cell rear, offsetting the increased mechanical resistance of confinement. This adaptation was specific to neutrophils and independent of nuclear properties; disrupting it caused neutrophil jamming and occlusion of capillary-like networks. The work identifies a neutrophil-intrinsic mechanism that preserves vascular patency during inflammation.
Noncoding transcription controls the developmental dynamics of long-range gene regulation.
Noncoding RNAs transcribed from enhancers control the timing of gene activation in Drosophila embryos, according to live imaging of single alleles. Optimal gene activation required only moderate enhancer activity, and disrupting enhancer-associated ncRNAs caused precocious gene activation. Enhancer transcription also regulated long-range interactions within complex regulatory landscapes.
Engineered genomic attachment sites for site-specific recombinases enable high-efficiency integration in plants and human cells.
Rationally engineered chimeric attachment sites boost Bxb1-mediated integration efficiency in human cells and plants. The attB(V111) variant achieved 51.9% integration in HEK293T cells (1.7-fold over wild-type attB) and 35.6% in rice protoplasts (4.4-fold), and paired with a Bxb1 catalytic-domain mutant delivered 31% integration of a CD19 CAR cassette and 25% of an ornithine transcarbamylase cassette in human cells. In rice, a 5.8 kb herbicide-resistance cassette integrated in 24% of regenerated plants, with heritable transmission to T1 plants.
Mitochondrial ATP promotes T cell differentiation through chromatin accessibility
D-α-hydroxybutyrate acts as a metabolic adjuvant that drives proliferating CD8+ T cells to become cytotoxic effector cells. It links mitochondrial ATP production to chromatin remodeling and gene expression, connecting cell metabolism to the differentiation and maintenance of the effector phenotype that cell-mediated immunity requires.
Absolute Benefit of Androgen Deprivation Therapy With Radiotherapy for Localized Prostate Cancer
An integrated model combining STAR-CAP cancer-specific risk, OCCAM other-cause mortality risk, and MARCAP efficacy estimates shows wide variation in absolute benefit from androgen deprivation therapy within NCCN risk groups. Applied to 5468 PLCO prostate cancer patients, adding short-term ADT to radiotherapy in unfavorable intermediate-risk disease gave a median 10-year distant metastasis ARR of 4% (range <1% to almost 15%), while prolonging ADT in high-risk disease gave a median ARR of 9% (0.4%-17.2%). The model provides individualized estimates to support treatment discussions rather than uniform group-level recommendations.
The past and future impact of climate change on childhood malaria in Africa.
Human-caused climate change has had a small net effect on childhood malaria across sub-Saharan Africa: rising temperatures probably increased cases in East and southern Africa but averted a comparable number in West Africa, a net impact of 1 excess case per 1,000 children (95% CI -4 to 6). Projections to 2100 suggest climate change could avert 1 to 20 cases per 1,000 children continent-wide, but limiting warming from 3 °C to under 2 °C could prevent an average of 5 excess cases per 1,000 in high-elevation East Africa and southern Africa.
Clinical usability of an explainable AI decision support tool and evaluation of multimodal models in NSCLC.
In the I3LUNG study of 2,396 patients with non-small cell lung cancer, machine learning and deep learning models using clinical and blood data predicted immunotherapy outcomes with AUC up to 0.77 in the test set and surpassed PD-L1, ECOG performance status, NLR, LDH and LIPI scores. External validation gave AUC of 0.55 to 0.72. An explainable AI tool improved predictions by lung expert and nonexpert physicians, while multimodal fusion added no consistent benefit over clinical and blood data alone. Prospective validation in more than 2,000 patients is underway.
Programmable promoter editing for precise control of transgene expression.
DIAL is a modular framework for building editable promoters that tune transgene expression in fine, heritable steps. Recombinase-mediated excision of nested spacers between zinc finger transcription factor binding sites and the core promoter generates a tunable range of unimodal expression setpoints from a single promoter, with small-molecule temporal control. Lentiviral delivery produced multiple setpoints in primary cells and induced pluripotent stem cells, and enabled mapping of transgene levels to phenotype in direct conversion to induced motor neurons.
Joint impact of pathological burden and cognitive resilience on Alzheimer’s disease risk
A 15-year cohort study shows that Alzheimer's dementia risk is jointly shaped by Alzheimer's pathology and cognitive resilience. Higher resilience was linked to lower dementia risk even under greater pathology. The finding positions resilience, alongside pathological burden, as a component of risk prediction.