Biomedicine Daily · Tuesday, 6 October 2026
CBA FRONTIER INSIGHTS
Nobel Prize in Medicine Goes to Optogenetics Pioneers
The 2026 Nobel Prize in Physiology or Medicine has been awarded to Karl Deisseroth of Stanford, Peter Hegemann of Humboldt University of Berlin and Georg Nagel of the University of Würzburg for discoveries underlying optogenetics. In the early 2000s, working at the Max Planck Institute of Biochemistry, Hegemann and Nagel discovered channelrhodopsin, a light-sensitive protein from the alga Chlamydomonas reinhardtii; Deisseroth and colleagues then showed the gene could make rat neurons fire in response to light. The technique now lets researchers control individual neurons and brain circuits with light to study effects on behavior. The day also brought major clinical and deal news: AstraZeneca's tozorakimab cut COPD exacerbations by up to 30% across all eosinophil counts, Vaxcyte's VAX-31 hit its primary endpoint and sent shares up more than 50% premarket, and Lilly's retatrutide delivered up to 25% weight loss at 80 weeks in the TRIUMPH program.
Clinical readouts and safety
COPD trial wins spur broad respiratory hopes
AstraZeneca's tozorakimab, an IL-33-targeted antibody, reduced COPD exacerbations by up to 30% in current and former smokers in two trials, with an FDA decision expected in the first quarter of 2027. Unlike dupilumab and mepolizumab, it worked across patients with all blood eosinophil counts, addressing non-eosinophilic COPD. The success, after mixed results for other IL-33 agents like itepekimab, is reviving industry interest in IL-33 and alarmin targets across respiratory disease.
Vaxcyte's 31-Valent Pneumococcal Vaccine VAX-31 Hits Primary Endpoint in OPUS-1 Trial
Vaxcyte reported positive topline results from the pivotal late-stage OPUS-1 trial of VAX-31, its 31-valent pneumococcal conjugate vaccine candidate. The company's shares rose more than 50% premarket, touching 86 dollars per share, with analysts raising target prices to 90 to 100 dollars. VAX-31 aims to compete in an 8 billion dollar adult pneumococcal conjugate vaccine market now dominated by Pfizer's Prevnar 20 and Merck's Capvaxive through broader serotype coverage.
Invivyd Conference Call Replay: Updates on LIBERTY VYD2311 Monoclonal Antibody Trials
VYD2311, a monoclonal antibody against the novel coronavirus on the same backbone as the authorized Pemgarda and the investigational adintrevimab, met the primary safety endpoint in the phase 3 LIBERTY trial of 210 healthy adults aged 18 to 49 across three arms: VYD2311 alone, with an mRNA vaccine, or vaccine alone. Tolerability was better than the mRNA vaccine and VYD2311 did not interfere with vaccine neutralizing titers. The company plans to submit a BLA to the FDA under the accelerated approval pathway as a pre-exposure prophylaxis, with key efficacy data from DECLARATION expected in October 2026.
medicalxpress.comWeekly cisplatin fails to show fewer serious side effects in p16-negative head and neck cancer
Weekly cisplatin at 40 mg/m2 with 70 Gy radiation did not reduce serious acute toxicity versus 100 mg/m2 every three weeks in 234 patients with p16-negative locally advanced head and neck squamous cell carcinoma in the phase II NRG-HN009 trial. The mean T-score ratio was 1.11 (p=0.77), with T-scores of 2.23 versus 2.48, and six-month locoregional failure was 4.6% versus 9.6%. The cohort did not advance to phase III, leaving the every-three-week schedule unchallenged on toxicity grounds.
The Lord of the Incretins: The Reign of Retatrutide... [Latest Research Update]
Retatrutide, Eli Lilly's unapproved GLP-1/GIP/glucagon triple agonist, delivered mean weight reductions of 17.6%, 23.7% and 25.0% at 4, 9 and 12 mg once weekly versus 3.9% on placebo over 80 weeks in the 2,339-adult TRIUMPH phase 3 program, with a BLA planned for Q1 2027. Clinicians on r/doctorsUK flagged the real-world challenge of moving patients from unregulated gray-market vials, with injection-site infections and toxic reactions already reported, back to regulated supply once the drug is approved.
Oral small-molecule GLP-1RA safiglipron versus dapagliflozin in type 2 diabetes: a randomized, double-blind, active-comparator-controlled phase 3 trial
Once-daily oral safiglipron, a small-molecule GLP-1RA, was non-inferior to dapagliflozin for HbA1c reduction at all tested doses and superior at 90 mg in adults with type 2 diabetes in a randomized, double-blind, active-comparator-controlled phase 3 trial. Safiglipron gave greater improvements in glycemic control, similar modest weight loss, and an acceptable safety profile. It offers an oral alternative in the GLP-1 receptor agonist class.
Biogen’s big lupus bet gets boost from new durability data for skin disease
Litifilimab cleared or almost cleared skin in 27.2% of cutaneous lupus erythematosus patients at one year in the Phase 2a AMETHYST trial, up from 19% at week 24, with 28.8% achieving at least 70% reduction in disease severity. The study covered 93 adults who had not responded to or could not tolerate antimalarials, and safety showed no new signals. The durable responses strengthen the case for litifilimab ahead of Phase 3 CLE data expected in 1H27 and SLE readouts in Q4, in a disease with no approved drugs.
Weighing the risks of CAR T in autoimmune disease as Kyverna nears market
Novartis paused several autoimmune trials of rapcabtagene autoleucel (rap-cel) after three patients died of immune effector cell-associated hemophagocytic syndrome, and Bristol Myers Squibb froze its own autoimmune CAR T trials of zola-cel after transient, reversible inflammatory events. Kyverna's mivocabtagene autoleucel (miv-cel) is moving toward the first CAR T approval in autoimmune disease: in the Phase 2 KYSA-8 trial, it improved mobility and leg function in 26 patients with stiff person syndrome at one year, with no high-grade CRS, ICANS or IEC-HS cases.
Regulatory and policy
FDA Approves Priovant's LISRAYA as First Oral Therapy for Adult Dermatomyositis
On August 27, 2026, the FDA approved Priovant Therapeutics' LISRAYA (brepocitinib) 30 mg tablets for adults with dermatomyositis. The FDA described it as the first approved oral treatment option for the indication and the first targeted therapy, being a small molecule directed at JAK/TYK2. Octagam 10%, an intravenous immunoglobulin, had been approved for adult dermatomyositis in 2021.
M15 Resource Center
The FDA has posted a resource center for ICH M15, a guidance on general principles for model-informed drug development (MIDD). The guidance describes MIDD principles, including planning, model evaluation and evidence documentation, sets a harmonized framework for assessing MIDD-derived evidence, and gives recommendations on MIDD-related regulatory interactions, reporting and submission. FDA recommends sponsors use it when preparing meeting requests, background packages and regulatory submissions.
STAT+: New Trump regulations would clean up health care pricing disclosures
The Trump administration released regulations on Monday requiring health insurers to publish cleaned-up spreadsheets of the prices they pay hospitals and doctors, removing cluttering data. Officials including Medicare and Medicaid head Mehmet Oz said work on a prescription drug price disclosure system starts next month, with a hopeful final plan by next May and enforcement by the end of 2027. The administration had punted on drug price disclosure rules last year.
Expedited Investigational New Drug Pilot Program - Application Instructions
The FDA has issued application instructions for its Expedited IND Pilot Program. Sponsors and prospective Qualified Research Institutions each complete a form, then the sponsor submits both through the FDA ESG Gateway as one package. The application window stays open for 45 days with possible extension, and FDA scientific experts will review submissions and select 8 to 10 Sponsor-QRI pairs. Participating parties must form their business relationship outside FDA, which will only confirm that an official agreement exists.
STAT+: Utah plows ahead with more health AI pilots for prescriptions, women’s health
Utah regulators announced a plan to let Nolla Health, a startup backed by $4.5 million from investors including General Catalyst, launch an AI service that assesses patients for mild-to-moderate acne treatment through structured intake and skin photo analysis. The AI may determine whether a low-risk drug from a list is appropriate; a licensed clinician will initially review and sign off on prescriptions, though Nolla may eventually prescribe without human review. The pilot expands Utah's AI sandbox program, in which the Office of Artificial Intelligence Policy can waive regulations for supervised testing of AI products.
STAT+: Judges skewer HHS arguments in hearing over Medicare Advantage audits lawsuit
A three-judge panel of the U.S. Court of Appeals for the Fifth Circuit appeared skeptical of HHS arguments in Humana v. Kennedy, Humana's 2023 lawsuit over Medicare Advantage audit rules. Humana argues the RADV rule diverged from the proposed rule without proper notice and comment; a federal judge invalidated it in September 2025, and HHS appealed in November. The panel seemed poised to toss the rule again.
Industry and deals
CSL Pays Up to $1.555 Billion to License Alentis Claudin-1 Antibody Lixudebart
CSL has struck a global partnership with Swiss biotech Alentis to develop lixudebart, an antibody targeting claudin-1, in kidney disease. The deal includes $355 million upfront plus up to $1.2 billion in commercial milestones, for a total of up to $1.555 billion. Lixudebart is designed to act on the cell-surface claudin-1 protein with both anti-inflammatory and anti-fibrotic effects.
Shionogi pays $2B to acquire a rare disease startup
Shionogi agreed on Oct. 5, 2026 to acquire Texas-based IntraBio for $2 billion in cash, gaining Aqneursa, a marketed treatment for Niemann-Pick disease type C and Ataxia-Telangiectasia. IntraBio, which will become a wholly owned subsidiary of Shionogi's U.S. division, reported $68 million in sales in 2025. Shionogi said it will review the deal's effect on its outlook for the fiscal year ending next March.
Lilly doubles down on Gate alliance to unlock new drug class with another $870M+ in biobucks
Eli Lilly has expanded its alliance with Gate Bioscience in a deal worth up to more than $870 million, adding one new target with the option of a second to their existing collaboration on Gate's Molecular Gate discovery engine for difficult-to-drug extracellular proteins. Gate, which signed an initial deal with Lilly worth up to $856 million in July 2025, will receive an undisclosed upfront payment plus payments on preclinical, clinical and commercial milestones and tiered royalties. Gate leads discovery while Lilly takes an exclusive worldwide license and handles development from later-stage preclinical work through commercialization; no indications have been disclosed.
Genentech pens $1.27B deal to access Alector’s preclinical blood-brain barrier asset
Genentech is paying $100 million upfront for exclusive development and commercialization rights to Alector's preclinical AL050, a blood-brain barrier-crossing glucocerebrosidase enzyme replacement therapy for neurodegenerative diseases including Parkinson's and Alzheimer's, with up to $1.17 billion in milestones plus tiered royalties. Genentech will handle development, regulatory, manufacturing and commercialization, while Alector retains its Alector Brain Carrier platform. The deal extends Alector's cash runway into 2029 and funds its anti-Aβ antibody AL137 and siRNA programs.
2 Massachusetts biotechs call it quits
Boston-based Adecto Pharmaceuticals, which was developing an anti-ADAM8 monoclonal antibody for cancers unresponsive to conventional immunotherapy, ceased operations Sept. 30 after running out of financial runway, CEO Nora Minerva said on LinkedIn; she has filed a provisional patent on the lead antibody and is exploring ways to advance its development. Aviceda Therapeutics is also winding down after its nanoparticle AVD-104 missed the primary endpoint in a December-announced Phase 2b trial in geographic atrophy secondary to AMD, showing no statistical difference versus Astellas's Izervay, derailing two planned Phase 3 studies expected to start this year.
Optogenetics researchers win a Nobel Prize; Roche bets on Alector brain drug
The Nobel Prize in Physiology or Medicine went to Peter Hegemann, Georg Nagel and Karl Deisseroth for optogenetics, a light-based method for studying neurons. Alector licensed its preclinical Parkinson's therapy AL050 to Roche's Genentech for $100 million in guaranteed cash and up to $1.17 billion in milestones plus royalties. Separately, the FDA approved Lilly's Jaypirca as a first-line treatment for CLL or SLL patients without a 17p deletion.
Research papers
Cell Publishes First Complete Connectome of the Adult Male Fruit Fly CNS
A team at the Howard Hughes Medical Institute's Janelia Research Campus has delivered the first complete connectome of the male fruit fly central nervous system, published in Cell. The project began in 2008 and took nearly 20 years, a pace the team achieved by iterating imaging and computational reconstruction methods. The work extends connectome mapping from the 302-neuron C. elegans wiring diagram, which itself took more than a decade, to a complex behaving brain.
youtube.comSympathetic Nerves Drive Skin CD8+ TRM Formation Through Epidermal Stem Cells, Not Immune Cells Directly
Sympathetic nerves regulate skin immunity through epithelial stem cells rather than by acting on immune cells directly. Sympathetic nerve terminals form synapse-like structures of about 200 nm facing epidermal stem cells; suppressing sympathetic signaling raises the stem cells' CXCL16, which recruits CXCR6-expressing effector and memory T cells and promotes antigen-specific CD8+ TRM formation. In a B16 melanoma skin graft model, the resulting CD8+ TRM increase strengthened local anti-tumor defense.
Once yearly cell-based therapy for sustained and dose-tunable delivery of monoclonal antibodies.
An encapsulated cell-based "biologics factory" using an immunomodulatory alginate formulation sustained stable serum titers of the HIV-neutralizing mAb 3BNC117 for 1 year in immunocompetent mice, supported by an anti-inflammatory, proresolving immune niche that attenuates fibrosis. The platform produced 13 diverse mAbs from an allogeneic cell chassis, and in a nonhuman primate subcutaneous implant maintained stable ipilimumab titers for more than 6 months with no detectable toxicity, antidrug antibodies, or adverse events across a three-dose escalation. A retrievable macrodevice allows on-demand termination and dose-proportional tuning, pointing toward replacing frequent injections with single-administration therapy.
Ubiquitin chain editing promotes p97/VCP-dependent removal of RPA from DNA.
A ubiquitin chain-editing mechanism in human cells drives extraction of replication protein A (RPA) from single-stranded DNA. RPA stimulates the deubiquitinase ZUP1, which removes K63 linkages from branched K48-K63 ubiquitin chains on RPA after DNA damage, enabling p97/VCP-dependent removal of ubiquitinated RPA from ssDNA. Loss of ZUP1 traps RPA on ssDNA and causes elevated ssDNA signaling and genome instability.
ZNFX1, an immunoregulatory RNA helicase and E3 ubiquitin ligase, assembles into pleiomorphic polymers.
Cryo-EM structures of RNA-bound and RNA-free ZNFX1 reveal how a regulatory insertion auto-inhibits the helicase-associated ATPase by occluding the RNA-binding groove. ZNFX1 acts as a bi-catalytic E3 ubiquitin ligase through an RNF213-like RZ finger and a newly identified Miz-like domain, with ubiquitin chains enhancing E3 activity. Patient mutations show the helicase/ATPase, E3 ligase, and connecting zinc-finger stalk are all required for function, and polymer assembly drives trans-auto-ubiquitylation controlling ZNFX1 stability.
Aging-associated SATB1 deficiency remodels 3D genome architecture and transcriptional programs in naive CD4+ T cells.
Aging remodels 3D genome architecture in murine naive CD4+ T cells, weakening topologically associating domain boundaries and rewiring enhancer-promoter contacts while up-regulating inflammatory and T cell activation genes. These structural changes partly trace to declining expression of the chromatin organizer SATB1, which normally constrains CTCF-mediated interactions; conditional SATB1 deletion in naive T cells recapitulates the aging-associated genomic and transcriptional changes.
Largest Gene Expression Atlas of the Human Prefrontal Cortex Published in Nature
The largest known gene expression map of the human prefrontal cortex has been produced, drawing on more than 6.3 million expression profiles from the brains of 1494 donors. Published in three Nature papers on September 23, the work clarifies how the prefrontal cortex develops across life stages. The resource is expected to aid studies of aging, cognitive decline and disease susceptibility.
SMOC-1 From Cardiomyocytes Protects Against Cardiac Rupture After Myocardial Infarction
A study published online in Circulation on September 29, 2026, by teams from Beijing Anzhen Hospital and Thomas Jefferson University identifies cardiomyocyte-derived secreted modular calcium-binding protein-1 (SMOC-1) as an endogenous cardioprotective molecule. SMOC-1 promotes reparative scar formation and reduces the risk of cardiac rupture after acute myocardial infarction. The problem is large: autopsy data indicate cardiac rupture causes about 30% of early deaths after acute myocardial infarction, with in-hospital mortality of 70% to 90%.
youtube.comDrosophila Hemocytes Combine H2O2 and C5a-like Signals to Target Wounds and Dead Cells
Will Wood, speaking in the Global Immunotalks expert lecture series, described how Drosophila hemocytes, the fly equivalent of macrophages, decide where to migrate in vivo. He outlined two parallel wound-recruitment signals: an early H2O2 gradient produced by Duox in damaged epithelium, and MCR, a functional homolog of complement C5a, forming a complement-like chemotactic axis. He also discussed how hemocytes sense apoptotic and injury signals, become primed, and clear dead cells more efficiently through efferocytosis, offering a model for the conserved logic of macrophage recruitment.
DND1-NANOS3 shapes the PGC transcriptome via a heptanucleotide sequence in mRNA 3′ UTRs
DND1 and NANOS3 form a complex that controls post-transcriptional gene regulation in primordial germ cells through a two-factor authorization mechanism. DND1 has low sequence specificity and NANOS3 has none, yet together they select target mRNAs via a unique heptanucleotide sequence in 3′ UTRs and collaboratively repress expression of cell cycle and epigenetic regulators, shaping the PGC transcriptome.
nature.comGlobal and regional reference curves for pain across the lifespan in 6.1 million individuals in 118 countries
Age- and sex-specific reference curves for 11 pain sites have been generated from 6.1 million people across 118 countries. Pain in late life was higher in the lowest Human Development Index countries. The curves offer a benchmarking tool for pain assessments in other cohorts.
In a successful gene therapy study on dogs with a rare genetic vision condition, scientists discovered that damaged nerve connections in adult retinas can physically repair and rebuild themselves.
A single dose of AAV-CaBP4 gene therapy in whippets with an inherited CaBP4 gene defect restored low-light vision and produced structural self-repair in the adult retina, including expansion of the outer plexiform layer and elongation of maturing ribbon synapses. Recovery of both structure and function was followed for up to three years. The finding, published by Beckwith-Cohen et al. in Molecular Therapy Advances, indicates that the adult mammalian retina retains plasticity.
youtube.comMedCram Explains Photometabolism: Infrared Photons May Modulate the Mitochondrial Electron Transport Chain
MedCram's Roger Seheult presents the "photometabolism" hypothesis from the preprint "Metabolism in the solar photon field": infrared photons near 0.754 eV, in an atmospheric transparency window, penetrate skin and clothing and modulate the mitochondrial electron transport chain not by supplying chemical energy but by shifting electron-transfer barrier-crossing probabilities in a Marcus-framework sense of vibrational energy levels. The argument is scaled by incident solar power tracking body mass to the 3/4 power, matching basal metabolic rate scaling, and accommodates 2018 findings that 750/950 nm light reduces complex IV activity and oxygen consumption. The speakers stress correlation, not causation, and that the hypothesis awaits independent experimental validation.
Metabolic rewiring induces a viral mimicry-mediated quiescence in glioblastoma
Inducing the polyamine-catabolic enzyme SSAT1 with the polyamine analogue DENSpm triggers a reversible, chemoprotective growth arrest in patient-derived glioblastoma stem cells, independent of stemness, differentiation or senescence. The arrest coincides with reduced eIF5A hypusination, lower global protein translation, and a rise in double-stranded RNA that activates type I interferon signalling; knocking down the mitochondrial antiviral-signalling protein partially reverses it. Single-cell and cohort analyses show susceptibility to this quiescence is set by intrinsic inflammatory tone and lysosomal dependency.
Matched primary-metastasis single-nucleus and spatial profiling of leiomyosarcoma identifies antigen-presenting fibroblasts at the tumor-organ interface
Matched primary and metastatic leiomyosarcoma samples reveal organ-specific malignant programs, with a stress- and hypoxia-associated program in lung metastases and a proliferative, matrix-remodeling program in liver metastases. Antigen-presenting cancer-associated fibroblasts were enriched in metastases (p = 0.001) and formed a band at the tumor-organ interface, unlike their sparse random distribution in primaries. Spatial profiling of 21 patients further defined three histomolecular phenotypes, including a GPNMB phenotype potentially targetable by GPNMB-directed therapies.
Methods and resources
youtube.comESMFold2 Matches MSA-Based Structure Prediction from Single Sequences
ESMFold2 predicts protein structures end to end from ESM-C 6B language-model embeddings alone, replacing MSA input with pair folding layers, PARSE recurrence in place of some recycle steps, and chain-independent encoding. Without MSAs it matches older MSA-based models on FoldBench (278 protein-protein interfaces) and beats most open and closed models on antibody-antigen docking (172 interfaces) from a single sequence, improving further with an MSA. About 8 to 16 recurrence loops saturate protein-protein prediction, while antibody-antigen cases keep improving; diffusion needs 20 to 30 steps.
youtube.comHans Clevers Reviews Adult Stem Cells and Organoids From Basics Toward the Clinic
Hans Clevers traced the organoid field from its origins in Lgr5+ intestinal stem cells, which self-organize into organoids that mimic tissue structure and function, to current immune co-culture work pairing organoids with dendritic cells and T and B cells to study epithelial-immune interactions, including goblet cells marked by mucin 2. Single-cell RNA sequencing compares organoids with primary tissue to map cell type composition, and single stem cells can be taken from organoid lines for reconstruction. The lecture positioned organoids as moving toward clinical use in disease modeling, drug screening and transplantation.
youtube.comNN-UNet Author Fabian Isensee Demonstrates nnInteractive Promptable 3D Segmentation at Janelia
NN-UNet author Fabian Isensee presented nnInteractive at Janelia, a vision-transformer-based promptable model that turns 2D prompts (points, boxes, lasso) into instant 3D segmentation masks. He compared it with general SAM foundation models, which still beat organ-specific checkpoints on some medical tasks, and demonstrated the tool on brain tumor MRI, electron microscopy neuron stacks, and insect brain micro-CT. Automated masks serve as initialization, with user interaction correcting model errors.
youtube.comPeking University Team Trains Protein Generative Model Claiming to Beat AlphaFold3 on Complexes
Peking University's Iching Gao presented a protein generative model trained from scratch on Huawei Ascend 910A hardware with MindSpore rather than PyTorch or Jax. With only 2-3 residue contact or interface restraints, the model reportedly outperforms AlphaFold2 and AlphaFold3 on complexes, though these are speaker claims needing independent validation. The talk also covered joint structure-sequence generation, illustrated with ubiquitin and SUMO, and a Chinese-language agent platform, Galileo, that orchestrates some 100 software tools for tasks like peptide drug candidate design.
Discovery and engineering of avian R2 retrotransposons for all-RNA-mediated targeted DNA integration in human cells
Avian R2 retrotransposons were discovered and engineered as an all-RNA-mediated system for targeted DNA integration in human cells. Sequencing data from the work were deposited in the Genome Sequence Archive for Human under accession HRA013312, and the analytic code is publicly available on GitHub. The approach offers an RNA-only route to site-specific DNA insertion, in contrast to existing DNA-cleavage-based integration methods.
youtube.comESM Team Describes Training ESMC and Opening Protein Language Models with Sparse Autoencoders
A Biohub webinar by the ESM team explains the motivation for protein language models and the training of ESMC, which masks single amino acids and predicts them from context with stacked transformer layers. The talk highlights sparse autoencoders from NLP as a way to extract monosemantic features from dense embeddings, with 16000 features chosen to balance specificity against cross-family generalization, enabling explicit clustering of protein space distinct from standard sequence or structure clustering.
youtube.comAnshul Kundaje on Interpretable Genomic Machine Learning as a Baseline for AlphaGenome
In a CSHL Leading Strand interview, Stanford's Anshul Kundaje argues for lightweight, interpretable sequence-to-activity models trained per assay, which learn enzyme-preference bias first and strip it away to leave latent biology, a framework that helped AlphaGenome avoid learning such bias. These models capture DNA grammar beyond GC content, such as cooperative binding of two proteins on the same side that breaks at 10bp spacing, and nucleosome-scale spacing near 150bp that drives nucleosome eviction. They also serve as strong baselines for large models and can find causal mutations in rare-disease patients, including variants visible only in early developmental or disease-specific cell contexts.
youtube.comMark Cragg on engineering agonistic antibodies: low-affinity Fab plus Fc-mediated crosslinking drives TNF receptor stimulation
Agonistic antibodies against TNF receptor superfamily members (CD40, 4-1BB, OX40, GITR) work in the opposite way to checkpoint blockers: receptors must be crosslinked to signal, and overly high Fab affinity hinders effective crosslinking and drives internalization. In a CD40 antibody series, activity rose as Fab affinity fell, peaking at one mutant. Crosslinking is largely provided by Fc binding to activating Fcγ receptors, while the inhibitory receptor FcγRIIB (CD32) restricts it, and hinge engineering offers a route to optimization.
youtube.comSingle-cell immune dynamics predict infliximab response before treatment in IBD and rheumatoid arthritis
Shai Shen-Orr argues the immune system gains new functions by rearranging interactions among existing cell types rather than adding new types, and applies single-cell dynamics to predict drug response. In an IBD cohort, fibrosis-organizing pathway genes differentially expressed in intermediate monocytes predicted infliximab response with AUC 0.78. The same gene set predicted infliximab response in rheumatoid arthritis blood across three independent datasets, suggesting non-response is conserved across diseases and specific to the therapy.
youtube.comGV20 Founder Shirley Liu on AI Rebuilt Cancer Drug Discovery and Antibody AI's Shortfalls
GV20 Therapeutics founder Shaoli (Shirley) Liu described how AI is reshaping anticancer drug discovery in an ImmuneZoom lecture. She argued antibody AI lags small-molecule AI because antibody structure prediction is hard, with 10^18 possible sequences and no experimentally validated de novo target-antibody design yet. Her STEAD platform retrospectively validated targets including EGFR, HER2, PD-L1 and PD1, predicted anti-PD1 antibodies with near-matching affinity before seeing clinical sequences, and has a molecule, IGS8, in phase 1 that turns cold tumors hot, with a phase 2B planned.
youtube.comMaria Brbic maps multimodal AI integration strategy at CSHL AI in biology symposium
At the CSHL AI in biology symposium, EPFL's Maria Brbic outlined a strategy for integrating multimodal biomedical data into unified AI representations: train strong single-modality encoders first, then bridge modalities with scarce paired data. Her lab's Luna model learns from spatial transcriptomics how tissue assembles and infers where dissociated single cells sit in tissue; a related work links single-cell transcriptomes to morphology via Iris. She also described a regularization method that makes small paired datasets trainable and warned that data diversity, not volume, plus leakage control, determines model capability.
Opinion and commentary
Medicine Nobel awarded for brain ‘switch’ that controls neurons with light
Karl Deisseroth of Stanford University, Peter Hegemann of Humboldt University of Berlin and Georg Nagel of the University of Würzburg have won the 2026 Nobel Prize in Physiology or Medicine for their discoveries in optogenetics. Working at the Max Planck Institute of Biochemistry in the early 2000s, Hegemann and Nagel discovered channelrhodopsin, a light-sensitive protein from the alga Chlamydomonas reinhardtii; Deisseroth and colleagues then showed the gene could make rat neurons fire in response to light. The technique lets researchers control individual neurons and brain circuits to study effects on behaviour.
youtube.comDavid Liu: Base Editing and Prime Editing Move from Engineered Proteins to the Clinic
David Liu described base editing and prime editing as engineered proteins that modify DNA at specified sites without double-strand breaks or donor templates. At least 23 clinical trials were using the editors by the time of the talk, with first in vivo base editing results reported at the end of 2023 and the FDA recently clearing the first prime editing trial. Cases include a 2022 CAR-T therapy carrying three base edits that produced complete remission in a T cell leukemia patient, and a bespoke prime editing therapy for KJ Mulun's urea cycle disorder caused by a premature stop codon.
youtube.comJennifer Doudna says AI accelerates nuclease design but cannot replace chance discovery
Jennifer Doudna discussed the Viper system, a new class of programmable nucleases discovered and named by her lab from studies of microbial defense systems, which can be engineered for gene editing and differs structurally from Cas proteins. She described its non-contiguous guide encoding, in which functional elements are not adjacent in sequence, making it harder for AI to learn without biological priors. She said generative and structural models can predict activity and narrow mutation search spaces, but chance observations still drive many breakthroughs.
youtube.comMedzhitov Lays Out Theoretical Framework on Innate Immunity and Inflammation at CSHL Leading Strand Lecture
Ruslan Medzhitov presented his theoretical framework for the innate immune system in a 57-minute CSHL Leading Strand expert lecture. He described efforts to model tissue homeostasis with mathematics and simple rules, and discussed inflammatory gene programs, cellular memory, and core gene sets shared across cell types such as neurons and epithelial cells. He also stressed how spatial structure and cell composition, including curved spatial models and client cells, shape immune function.
youtube.comThird Military Medical University's Lilin Ye identifies TDLN memory T cells as key responders to PD-1 checkpoint blockade
Lilin Ye of Third Military Medical University described CD8+ T cell exhaustion in chronic infection and cancer and identified tumor-specific memory T cells (TTSM) in tumor-draining lymph nodes as the responding population for PD-1 checkpoint blockade. PD-1 blockade drives TTSM in tumor-draining lymph nodes to differentiate into effector and exhausted T cells that migrate into tumors, which he says explains common tumor recurrence after PD-1 therapy. He proposes combining PD-1 blockade with inducing tumor pyroptosis via GSDMB/GSDME and engaging cDC1 to steer TTSM toward functional effector cells and secondary memory.
youtube.comExperts Discuss Sequencing of Therapies for Relapsed/Refractory Multiple Myeloma
Jesus G. Berdeja of Tennessee Oncology and Ajai Chari of UCSF discussed sequencing of T-cell redirecting therapies, including ADCs, bispecific antibodies and CAR-T, in relapsed/refractory multiple myeloma in a Decera Clinical Education session recorded before the FDA approved iberdomide plus daratumumab and dexamethasone. They said no randomized data define the optimal order, so decisions rely on prior treatment history, depth of response, comorbidities and drug access, with early use improving PFS while OS benefit awaits longer follow-up. CAR-T options such as idecabtagene vicleucel and ciltacabtagene autoleucel show deep responses but face manufacturing time and cost limits, whereas off-the-shelf bispecifics like teclistamab, talquetamab and elranatamab can be given immediately but carry CRS, ICANS and infection risks.
youtube.comRino Rappuoli traces vaccine R and D from empiricism to AI-driven design
In a Global ImmunoTalks lecture hosted by Stanford's Bali Pulendran, Rino Rappuoli, former head of R&D at GSK and Novartis and founder of reverse vaccinology, reviewed how vaccine development moved from empiricism to AI-driven design. He described reverse vaccinology's computational screening that identified 2158 genes from the meningitis B genome, the RSV vaccine approved in 2023 after decades of failure, and synthetic biology enabling vaccines built from a sequence alone, with AI as the natural next step in this computational lineage.
youtube.comCSHL Symposium on AI in Biology: Interview with Marinka Zitnik
Marinka Zitnik of Harvard tells a CSHL Leading Strand interview that AI for biology should use "skeptical reasoning" and report uncertainty rather than force conclusions when evidence conflicts or is lacking. She says literature-only models inherit heavy bias toward the most popular genes and must draw on raw perturbation data such as perturb-seq chemical screens. Her foundation model Proton, without additional training, was applied to bipolar disorder and then Alzheimer's disease, checking expression differences of approved-drug targets in relevant cell types for drug repurposing.
In brief
- Revisiting AXL as a therapeutic target in soft tissue sarcoma: dubermatinib and bemcentinib effects are largely independent of AXL inhibitionbiorxiv.org
- Mechanistic Decoding of Pharmacodynamic Intratumoral Heterogeneity: A Pan-Cancer Regulatory Frameworkbiorxiv.org
- Distinct sequence grammars of nucleosomal and linker DNA shape mutational and methylation landscapes in cancerbiorxiv.org
- A Novel ACLY Inhibitor Induces Transcriptional and Metabolic Reprogramming to Overcome Tyrosine kinase inhibitor Resistance in Lymphomabiorxiv.org
- The mammalian genome is punctuated by regularly spaced nucleosome islandsbiorxiv.org
- Rejane Rua Explains the Dual Role of Meningeal Macrophages in Neuroinflammation and Cognitionyoutube.com
- The effect of microgravity and flows on the organization and dynamics of the human genome.Sci Adv
Also today
10 events that did not make today's daily, one table per category, one row per event. Open a category to expand.
Regulatoryrebisufligene etisparvovec · Daraxonrasib · Jaypirca · Withdrawn …5 ▾▴
Filings, acceptances, designations, approvals and withdrawals at a regulator.
- rebisufligene etisparvovecUpdateThe FDA has approved Ultragenyx Pharmaceutical's gene therapy rebisufligene etisparvovec (Fayuvi) for paediatric patients with mucopolysaccharidosis type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A. It is the first FDA-approved treatment option for this rare neurodegenerative lysosomal storage disorder.FDA
- DaraxonrasibUpdateOn August 26, 2026, the FDA approved daraxonrasib (brand name RASONQUE), developed by Revolution Medicines, for adults with metastatic pancreatic ductal adenocarcinoma who have received at least one prior systemic therapy or are unsuitable for multi-drug combination systemic therapy. It is the first FDA-approved RAS(ON) inhibitor worldwide, extending direct RAS inhibition beyond a single mutation subtype to a broader molecular population.FDA
- JaypircaUpdateThe FDA has approved Eli Lilly's Jaypirca as a first-line therapy for chronic lymphocytic leukemia (CLL), according to STAT News. The approval moves Jaypirca, already known in CLL treatment discussions, into the earlier-line setting. Details of the decision are behind the STAT+ paywall, with further coverage available to subscribers.
- WithdrawnUpdateFDA
- sevabertinib/camizestrantUpdateFDA
Clinicalintismeran autogene · VAX-31 · Simultaneous immune checkpoint blockade3 ▾▴
Trial starts, early and mid-stage data, and results that did not make the daily.
- intismeran autogeneUpdateA late-stage mRNA cancer vaccine has shown it stopped the return of melanoma, boosting hopes that the approach can be turned against other cancers. Merck and Moderna reported in August that adding their vaccine, intismeran autogene, to an existing treatment slowed the return and spread of melanoma. The open questions are which cancers to target next and whether mRNA can meet the task.
- VAX-31Update
- Simultaneous immune checkpoint blockadeUpdate
OtherNovartis Bets $7.8 Billion on Abogen mRNA · Glenmark Pharmaceuticals Limited2 ▾▴
Everything else with a concrete event that did not make the daily.
- Novartis Bets $7.8 Billion on Abogen mRNAUpdateNovartis has struck a deal with Abogen Biosciences worth up to $7.2 billion centered on Abogen's mRNA-TCE platform, paying $575 million upfront with roughly $7.2 billion in potential milestone payments if all options are exercised. The deal includes Novartis developing ABO2203 and exploring wider uses of Abogen's RNA platform. Abogen CEO Bo Ying said the collaboration shows the platform extends beyond prophylactic vaccines.
- Glenmark Pharmaceuticals LimitedUpdateThe FDA issued a warning letter to Glenmark Pharmaceuticals on November 22, 2022, after inspecting its finished-drug manufacturing facility in Colvale, Goa, from May 12 to May 20, 2022, and finding significant CGMP violations. The letter cites inadequate investigation of out-of-specification results, including 14 rejected batches of desmopressin acetate tablets from 2018 to 2021 and a June 10, 2022 voluntary recall of batch 20220121, plus insufficient process validation for a gel product with five batches rejected for viscosity failures between 2020 and 2021. Glenmark must respond with independent assessments and remediation plans for its investigation and CAPA systems and its process validation program.FDA