Biomedicine Daily · Wednesday, 16 September 2026
CBA FRONTIER INSIGHTS
Gotistobart Nearly Doubles Median Overall Survival in Pretreated Squamous NSCLC
The standout development of the day comes from the phase 3 PRESERVE-003 trial, where updated stage 1 data show that gotistobart, a next-generation CTLA-4 antibody from BioNTech and OncoC4, nearly doubled median overall survival in previously treated squamous non-small cell lung cancer: 18.5 months versus 10.0 months on standard-of-care chemotherapy. The results support the agent's mechanism of selectively depleting regulatory T cells in the tumor microenvironment. The day also brought a wave of regulatory news: FDA approvals for Scholar Rock's apitegromab, Telix's Pixclara and Curium's Bexlutry, priority review for Takeda's zasocitinib, and China's NMPA clearing T-DXd plus pertuzumab as a first-line HER2-positive breast cancer regimen.
Clinical readouts and safety
Gotistobart nearly doubles median overall survival in previously treated squamous NSCLC
Gotistobart, a next-generation CTLA-4 antibody from BioNTech and OncoC4, nearly doubled median overall survival in previously treated squamous non-small cell lung cancer in updated stage 1 data from the phase 3 PRESERVE-003 trial. Median overall survival was 18.5 months with gotistobart versus 10.0 months with standard-of-care chemotherapy. The data support its mechanism of selectively depleting regulatory T cells in the tumor microenvironment.
Broadly neutralizing antibodies in adult males living with HIV undergoing analytical treatment interruption: secondary and exploratory outcomes of the phase II randomized controlled RIO trial
In the phase 2 RIO trial, adult males living with HIV undergoing analytical treatment interruption showed delayed viral rebound after receiving broadly neutralizing antibodies 3BNC117-LS and 10-1074-LS, with resistance to these antibodies also observed. Initial reservoir sensitivity to autologous antibodies was associated with a longer time to rebound. The findings come from secondary and exploratory outcomes of this randomized controlled trial.
GFH375 Monotherapy Shows 59.2% ORR in Pretreated KRAS G12D-Mutant NSCLC at WCLC
GFH375 monotherapy at 600 mg once daily produced an objective response rate of 59.2% and a confirmed objective response rate of 52.1% in previously treated KRAS G12D-mutant non-small cell lung cancer, with a disease control rate of 93% among 71 evaluable patients. Nearly all enrolled patients had distant metastases and over 40% had received two or more prior lines. The updated phase 2 data were presented in an oral report at the 2026 World Conference on Lung Cancer in Seoul.
Synthetic long peptide and DNA personalized cancer vaccines induce robust neoantigen-specific T cell responses in pancreatic cancer.
Personalized cancer vaccines, delivered as synthetic long peptide or DNA formulations after resection and adjuvant chemotherapy, were safe and immunogenic in pancreatic ductal adenocarcinoma: two phase 1 trials showed no grade ≥3 adverse events and induced polyclonal neoantigen-specific T cell responses confirmed by IFN-γ ELISpot, intracellular cytokine staining, and T cell receptor clonotype reconstruction. Compared with a propensity-matched cohort, vaccine recipients showed a trend toward longer median overall survival (4.4 versus 3.5 years, log-rank P = 0.23). The results establish feasibility of neoantigen vaccination in a tumor considered unresponsive to standard immunotherapy.
STAT+: Vera kidney drug Trutakna shows strong final results in Phase 3 trial
Final two-year Phase 3 results show Trutakna, Vera Therapeutics' drug for IgA nephropathy, stabilized kidney function and reduced the risk of kidney-related death and other complications. The FDA granted Trutakna accelerated approval for IgAN in July, and Vera plans to file for full approval in the fourth quarter.
Oral KRAS G12D inhibitor GFH375 for previously treated advanced solid tumors with KRASG12D mutations: a phase 1 trial
The oral dual on-off binding KRAS G12D inhibitor GFH375 was evaluated in a phase 1 trial in patients with previously treated KRASG12D-mutated advanced solid tumors. Most treatment-related adverse events were low-grade, but there was one treatment-related death. Response rates were described as encouraging in non-small cell lung cancer and pancreatic cancer.
Regulatory and policy
China's NHSA to Trial Pre-Approval Pricing Mechanism for High-Level New Medical Technologies
On September 15, China's National Healthcare Security Administration published a notice (document Yibao Fa [2026] No. 23) establishing a trial pre-approval system for medical service pricing of high-level new technologies and products. The mechanism moves the pricing acceptance stage earlier so that regulatory approval for clinical use links directly to charging authorization, and it pairs this with constraints on consumable prices, conditional charging and value assessment to filter routine iterative products and guard against misuse. Companies will be pushed to prepare clinical and economic evidence in parallel from early development stages.
Judge blocks Trump administration plans to limit visa length for grad students, postdocs
Judge F. Dennis Saylor IV of the U.S. District Court for the District of Massachusetts issued a preliminary injunction blocking a Department of Homeland Security plan, announced in mid-July, to cap stays for foreign graduate students and postdocs on nonimmigrant visas at four years. He wrote that the rule failed to comply with the Administrative Procedure Act and found the plaintiffs, a coalition including NAFSA and the Presidents' Alliance on Higher Education and Immigration, likely to succeed. The court will hear full arguments while the injunction stays in effect.
NMPA Approves T-DXd Plus Pertuzumab as First-Line Treatment for HER2-Positive Advanced Breast Cancer
China's NMPA approved trastuzumab deruxtecan (T-DXd) combined with pertuzumab on August 11, 2026 as first-line treatment for adults with unresectable or metastatic HER2-positive breast cancer. It is the first first-line ADC regimen approved in HER2-positive metastatic breast cancer in China. The approval rests on the global DESTINY-Breast09 study, in which Chinese patients made up close to a quarter of enrolment and the Chinese subgroup showed efficacy and safety better than the global population.
FDA Approves Scholar Rock's Apitegromab (Isembyld), First Muscle-Targeted SMA Therapy
Scholar Rock's apitegromab, brand name Isembyld, received FDA approval on September 11 as the first muscle-targeted therapy for spinal muscular atrophy. It is indicated for SMA patients aged 2 and older who are receiving SMN2-targeted therapy, and works by inhibiting myostatin production to promote muscle growth. US shipments begin within days of approval.
FDA Accepts Takeda's Zasocitinib NDA With Priority Review for Plaque Psoriasis
The FDA has accepted Takeda's new drug application for Zasocitinib (TAK-279), an oral TYK2 inhibitor for adults with moderate to severe plaque psoriasis, and granted priority review, Takeda announced on September 14. The drug was originally developed by Nimbus Therapeutics and Schrödinger, and Takeda acquired it from Nimbus in 2022 for a $4 billion upfront payment in a deal worth up to $6 billion.
After rejection, FDA approves Telix’s Pixclara, the first FET-PET imaging drug for brain cancer
The FDA has approved Telix's Pixclara (floretyrosine F 18, or 18F-FET), the first FET-PET imaging drug for glioma approved in the U.S., more than a year after rejecting the application in April over a need for additional confirmatory clinical evidence. The diagnostic, used with PET to distinguish recurrent or progressive glioma from treatment-related change, is approved for adults and children one month of age and older. Gliomas account for around 80% of malignant brain tumors, with around 24,000 U.S. cases yearly.
China's NHSA Pilots Pre-Approval Pricing Track for New Technologies, Lowering Threshold to Tertiary Hospitals
On September 15, China's National Healthcare Security Administration issued a notice establishing a pilot pre-approval system for medical service price items covering high-level new technologies and new products. Compared with the earlier draft for comment, the application threshold was lowered from national medical centers and clinical key disciplines to tertiary medical institutions, a change the agency said at a September 14 symposium reflects industry input to widen participation by innovative players. Implementation follows the completion of the 40 batches of project establishment guidelines.
FDA launches pilot program to speed up sluggish phase 1 trials
The FDA has opened a pilot program for an expedited investigational new drug (IND) application process, aiming to accelerate U.S. phase 1 clinical trials. The agency wants U.S. phase 1 trial timelines to match those in China and Australia. The pilot follows an initiative to speed early-stage trials that the FDA signaled over the summer.
FDA signals tighter scrutiny of early-stage data from China
FDA is signaling tighter scrutiny of early-stage clinical data generated in China while stopping short of the outright ban sought by some members of Congress. Reps. John Moolenaar and Ben Cline asked Acting Commissioner Kyle Diamantas in an Aug. 20 letter to reject data from Chinese sites not inspected within the previous 12 months, a requirement that would effectively ban such data given FDA's inspection manpower. The agency must balance congressional pressure against multinational biopharmas' reliance on China in global drug development.
FDA approves first radioligand equivalent, Curium’s copycat of Novartis’ Lutathera
The FDA has approved Bexlutry, Curium's lutetium Lu 177 dotatate injection, as the industry's first radioligand equivalent. The approval for the Boston company follows a court ruling that cleared Curium of all patent claims brought by Novartis, whose reference product is Lutathera.
Industry and deals
Novo walks away from $285M pact to develop monthly GLP-1 obesity drug with Ascendis
Novo has walked away from a $285 million pact with Ascendis to develop a monthly GLP-1 obesity drug, ending the collaboration after less than two years. The deal had aimed to develop a longer-acting monthly weight loss treatment. The article gives no further details on what happens next.
Johnson & Johnson in Talks to Sell DePuy Synthes Orthopedics to Apollo for $20 Billion
Johnson & Johnson is in talks to sell its orthopedics business DePuy Synthes to Apollo for about $20 billion, which would shift ownership of what the report calls the world's largest orthopedic device business. As of publication, neither side has officially confirmed the negotiations and no deal is final. A breakup, a higher competing bid, or a return to a tax-free spin-off and IPO remain possible outcomes.
Research papers
PLA2G2D in tumour-draining lymph nodes regulates anti-tumour immunity.
PLA2G2D-expressing myeloid cells in tumour-draining lymph nodes form a spatial neighbourhood linked to distant metastases in melanoma, and are far more abundant in TDLNs than in primary tumours or metastases. Blocking PLA2G2D genetically or with antibodies markedly reduced tumour growth, expanded tumour-specific T cells in TDLNs, circulation and tumours, and acted as a non-redundant checkpoint with PD-1, with combination treatment showing additive or synergistic efficacy in humanized mice. It identifies a targetable, lymph-node-centred immune checkpoint distinct from PD-1.
CD55 Boosts NK Cell and CAR-NK Cell Anti-Tumor Activity Through CD97 and LCK Signaling
CD55, classically a complement regulator, acts in NK cells as a tumor immunity enhancer. Tumor contact induces NK cells to upregulate CD55, which binds CD97 on tumor cells, promotes lipid raft clustering and activates LCK signaling, increasing NK cell killing, cytokine secretion and proliferation. Sustained loss of CD55 in the tumor microenvironment impairs NK cell function, and restoring CD55 expression improves anti-tumor efficacy of NK cells and CAR-NK cells.
Depletion of an immature cord blood NK subset reverses trogocytosis-driven CAR NK dysfunction.
An immature CD16-CD161- double-negative cord blood NK subset drives CAR NK product dysfunction: after CAR engineering these cells remained hypofunctional yet showed exaggerated trogocytosis, forming a trogocytic-antigen sink that diverted CAR engagement from tumors and caused exhaustion, fratricide and death of CD16+CD161+ double-positive effectors. Depleting the DN subset before manufacturing eliminated the antigen sink and restored antitumor activity in hematologic and solid tumor models. The work converts donor heterogeneity into an actionable manufacturing step for more potent off-the-shelf CAR NK products.
Engineering suppressor tRNAs for effective treatment of Duchenne muscular dystrophy.
Engineered UAA suppressor tRNAs, delivered systemically with optimized AAV vectors and RNA polymerase III promoters, restored full-length dystrophin and recovered muscle strength and motor function in mice with nonsense mutations, at lower doses than AAV microdystrophin therapies. No adverse toxicology appeared, and proteome-wide analysis showed reversion of molecular pathophysiology. The approach targets the roughly 15% of DMD patients with nonsense mutations.
5-Azacytosine induces cytotoxicity via 5-methylcytosine depletion on chromatin-associated RNA in leukemia.
The clinically used hypomethylating agent 5-azacytidine kills leukemia cells by depleting 5-methylcytosine in chromatin-associated RNA, not only through DNA demethylation. This caRNA m5C loss disrupts MBD6-mediated H2AK119ub deubiquitination, impairs SRSF2 recruitment and p300-driven H3K27ac deposition, and represses genes for cell-cycle regulation and DNA repair. Loss of the caRNA methyltransferase NSUN2 produced a prolonged cell cycle, defective DNA repair and a shift toward erythropoiesis, mirroring 5-azaC's effects.
5-Azacytosine induces cytotoxicity via 5-methylcytosine depletion on chromatin-associated RNA in leukemia
The clinically used drug 5-azacytidine kills leukemia cells by depleting 5-methylcytosine (m5C) on chromatin-associated RNA, not only through DNA hypomethylation. Loss of m5C disrupts MBD6-mediated removal of H2AK119ub and SRSF2-mediated deposition of H3K27ac, leading to cell-cycle disruption and defective DNA repair. This reframes the drug's mechanism of action in leukemia.
Gliomas phenocopy an inborn error of metabolism to drive neuronal activity and tumor growth
Immuno-resolving nitric oxide-generating stents for coordinated vascular healing
A stent coating (C15-NOGC) that couples sustained nitric oxide generation with immobilized chemerin-15 promotes coordinated vascular healing in ApoE-/- rats. The Cu-DOTA-polydopamine coating drives physiological-level NO release while C15 shifts macrophages toward a pro-resolving phenotype with higher ChemR23 expression and phagocytosis. Stents carrying the coating enhanced early re-endothelialization and reduced neointimal area versus bare metal and drug-eluting stents.
Latent tumor killers awakened.
A single-cell atlas of bone marrow T cells from patients with bone marrow-resident malignancies reveals tumor-reactive populations in a state of latent competence. A 15-gene signature identifies this subset, which is expanded by immunotherapies and predicts clinical responses. The work pinpoints a definable T cell state that clinicians could use to gauge who will respond to immunotherapy.
Latent effector T cells mediate immunotherapy responses in the bone marrow microenvironment.
Tumor-reactive T cells in the bone marrow of patients with multiple myeloma and acute myeloid leukemia carry a conserved effector program distinct from the exhausted phenotype seen in solid cancers, and respond to noncanonical peptides. A transcriptional classifier, TFiT, identifies these cells and stratifies immunotherapy, but not chemotherapy, response across independent MM and AML cohorts. The work defines a latent, activatable anti-tumor T cell compartment in bone marrow malignancies.
Programmed ribosomal frameshifting triggers translational stress to promote viral replication
Programmed ribosomal frameshifting, used by viruses such as SARS-CoV-2, turns off host translation and thereby promotes viral replication. The work expands the known roles of this mechanism in viruses beyond producing viral proteins. It identifies frameshifting as a driver of translational stress during infection.
Distinct Anaerobic Microbial Signature Differentiates Anal Squamous Cell Carcinoma From High-Grade Squamous Intraepithelial Lesions: A Prospective Metagenomic Study
Anal squamous cell carcinoma (ASCC) carries a distinct anaerobic microbial signature that separates it from high-grade squamous intraepithelial lesions (HSIL). In shotgun metagenomic sequencing of anal swabs from 121 adults (102 HSIL, 19 treatment-naive nonmetastatic ASCC), six anaerobic species, including Fusobacterium nucleatum and Parvimonas micra, were enriched in ASCC, persisted across longitudinal sampling, and declined after treatment initiation. The finding points to microbial features that may help distinguish invasive anal cancer from precursor lesions.
Exploration of the Potential Mechanism of Clematichinenoside AR in Alleviating Hyperuricemia Based on Untargeted Metabolomics and Nrf2 Signaling Pathway
Clematichinenoside AR, a natural triterpenoid saponin, reduced serum uric acid and inhibited xanthine oxidase activity in a mouse model of hyperuricemia, while easing uric acid-induced kidney and liver injury. It lowered TNF-alpha, IL-6, IL-1beta and renal malondialdehyde, upregulated ABCG2, NRF2 and HO-1, and downregulated NLRP3 and Caspase-1. Untargeted serum metabolomics showed the effect centers on purine metabolism and the NRF2/HO-1 pathway.
STAT3 inhibition for the induction of immunogenic cell death in multiple myeloma
STAT3 inhibition eliminates multiple myeloma stem-like cells and elicits hallmarks of immunogenic cell death, Sha et al. report in Blood Science. The findings link stemness, the integrated stress response, and antitumor immunity in multiple myeloma, with in vivo validation still needed before the strategy can be considered immunogenic.
Beyond tumor volume: connectomic measures of tumor burden provide superior prognostic information across tumor compartments in glioblastoma
A tractography-derived measure of brain-wide tumor involvement, the lesion–tract density index (L-TDI), outperformed conventional tumor volume for predicting overall survival in 999 patients with newly diagnosed glioblastoma across multiple institutions. Tumor volume's prognostic value depended strongly on analytical design and was largely confined to the contrast-enhancing compartment, whereas L-TDI showed robust associations with overall survival across thresholds and tumor compartments and retained its value after adjustment for established clinical variables. The findings support assessing glioblastoma prognosis as a brain-wide disease rather than by local tumor extent.
Methods and resources
A versatile nanopore identifies four classes of analytes simultaneously
A nanopore sensor engineered from a bacterial porin can identify amino acids, nucleoside monophosphates, saccharides and peptides simultaneously, which single-molecule sensing has not previously combined in one platform. Coupled with machine learning, it reaches 98.7% classification accuracy and supports compositional analysis of native glycopeptides.
Detecting and quantifying circular RNAs in terabyte-scale RNA-seq datasets with CIRI3.
CIRI3 detects and quantifies circular RNAs in terabyte-scale RNA-seq datasets, running an order of magnitude faster than existing tools with increased accuracy through dynamic multithreaded task partitioning and a blocking search strategy for junction reads. Applied to 2,535 cancer-related samples, it identified differentially spliced circRNAs and yielded the CIRIonco database with a pretraining model and biomarker network.