Discovery speed is advancing faster than proof of clinical success
THEME RESEARCH
Biotech
Will better biological models improve patient outcomes and portfolio economics, not just generate more candidates?
Multi-asset clinical attrition, patient efficacy, cycle time, and licensing economics
01TOP SIGNAL
Source metadata only
Read evidence →Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL)
The takeaway: CLL
02
Sonrotoclax Plus Zanubrutinib in Patients With Relapsed/Refractory Mantle Cell Lymphoma Planned for Standard of Care CAR-T Cell Therapy
Mantle Cell Lymphoma
Source metadata only
ONC
clinicaltrials
03Lisaftoclax (APG-2575) Combined With Azacytidine (AZA) in the Treatment of Patients With Higher-risk Myelodysplastic Syndrome (GLORA-4).
Higher-risk Myelodysplastic Syndrome
Source metadata only
6855.HK
clinicaltrials
04Phase II Study of the Combination of Subcutaneous Blinatumomab and Olverembatinib in Patients With Philadelphia Chromosome (ph)-Positive and/or BCR::ABL1 Positive Acute Lymphoblastic Leukemia (ALL)
Phase II Clinical Trial; Blinatumomab; Olverembatinib; Lymphoblastic Leukemia; Philadelphia Chromosome Positive
Source metadata only
6855.HK
clinicaltrials
05A Multicenter Study of IBI343 Monotherapy Versus Placebo in Subjects With Previously Treated, Claudin (CLDN) 18.2-positive, Pancreatic Cancer(G-HOPE-002)
Pancreatic Cancer
Source metadata only
1801.HK
clinicaltrials
01TOP SIGNAL
Source metadata only
Read evidence →How LLMs Deal With Fraudulent Papers
The takeaway: Let’s take a look at a little-discussed aspect of using AI for scientific research. I will admit that these results don’t surprise me very much, but I’m glad that the authors have brought this issue out into the daylight. One of the hopes for sufficiently capable AI/ML systems is that they will be able to dig into the corpus of existing scientific literature and find connections (and gaps) that we ourselves have missed. It’s a huge job, very likely beyond any reasonable estimate of human abilities at this point, so some indefatigable software help in assessing things would be very welcome. But given the state of the literature - in all fields - there’s a question that should come up. I was able to ask it myself some years ago, as I’ve mentioned here before. That was when I heard a presenta
02
In vivo engineering of CAR natural killer cells for immunotherapy using ligand-directed lipid nanoparticles
Nature Biotechnology, Published online: 13 October 2026; doi:10.1038/s41587-026-03310-1 Chimeric antigen receptor natural killer cells to treat autoimmune disease and cancer are generated in vivo.
Source metadata only
rss:www.nature.com
03Proteomic aging clocks go to trial
Nature Biotechnology, Published online: 13 October 2026; doi:10.1038/s41587-026-03361-4 Six proteomic aging clocks are deployed in a clinical trial for the first time, revealing more about the clocks than about the drug.
Source metadata only
rss:www.nature.com
04Accelerated Reactions in an Electric Field
This paper caught my eye, but it’s in one of those categories that tends to do so. There are a number of things about chemical reactions that most of us chemists tend to sort of slide past, but which are (in theory) subject to manipulation, and this sort of thing could turn out to be very useful. Electric fields and electric field gradients are one of those, and over the years there have been several attempts to address that idea. It isn’t easy. In theory you can certainly alter the electron distributions of your reactants in such a field, and for well-chosen reaction types that could make a huge different. But the orientation of the molecules within such fields is crucial to testing their effects, and how do you get them to line up? Here’s some earlier work that uses mechanically tethered
Source metadata only
rss:www.science.org
05Genome editing
Nature Biotechnology, Published online: 12 October 2026; doi:10.1038/s41587-026-03324-9 Recent patents relating to systems, methods and compositions for use in genome editing.
Source metadata only
rss:www.nature.com
01TOP SIGNAL
Source metadata only
Read evidence →Mid-Infrared Photothermal Imaging Unveils Altered Stearoyl-CoA desaturase (SCD) Activity in Ovarian Cancer Cells
The takeaway: Stearoyl-CoA desaturase (SCD)-catalyzed fatty acid desaturation plays a key role in cancer metabolism reprogramming. While existing approaches enable quantification of SCD expression, directly monitoring in situ SCD enzymatic activity alterations remains challenging. Here, we report a strategy to measure intracellular SCD activity alterations and SCD product distributions by mid-infrared photothermal (MIP) imaging. Fully deuterated palmitic acid (PA-d31) is repurposed here as a chemical probe to report the SCD activity via a new peak at 2246 cm-1, corresponding to the stretching of D-C=C-D bonds in the SCD product. The MIP intensity ratio between the product-associated signal and the total C-D signal defines the apparent SCD activity index. By visualization of SCD-catalyzed metabolic conversion, our approach reveals altered SCD activity in cisplatin-treated ovarian cancer cells, ovarian cancer stem cells and cells fed with oleic acid. Non-uniform distributions of the SCD product are also observed. These results establish bio-orthogonal MIP microscopy as a platform for studying intracellular enzymatic reactions in living systems.
02
Spatiotemporal analysis of sporozoite maturation and infectivity
Plasmodium sporozoites must undergo tightly regulated developmental transitions to become infectious and be successfully transmitted from the mosquito vector to a mammalian host. While transcriptomic studies have revealed stage-specific changes across sporozoite populations, the functional consequences of these transitions remain unclear. Here, using P. berghei, we characterised over time the infectivity of sporozoite forms collected from the midgut, haemolymph, salivary glands and saliva. We show that salivary gland invasion is required but not sufficient for sporozoite optimal infectivity, with the acquisition of hepatocyte cell traversal and invasion progressively increasing until a plateau from 18 days post-infection onwards. Using a stage-specific fluorescent reporter to track maturation, we found that fluorescence increased over time and correlated with infectivity within each compartment, yet maximal infectivity was reached only in salivary gland sporozoites. Notably, our data suggest that salivated sporozoites, the natural transmission form, exhibit enhanced infectivity relative to gland-resident forms both in vitro and in vivo early after salivary gland invasion. This difference decreases following optimal maturation inside the glands over time. These observations show a crescent gradient of sporozoite maturation and infectiveness from the midgut to the saliva, in which pre-salivary gland forms retain limited infectivity but do not reach the competence of mature salivary gland-associated parasites.
Source metadata only
biorxiv
03AlphaFold3 and Intrinsically Disordered Proteins: Reliable Monomer Prediction, Unpredictable Multimer Performance
AlphaFold3 represents a major advance in protein structure prediction, yet its performance on intrinsically disordered proteins remains uncharacterized. We present the first systematic evaluation of AF3 on disordered systems, revealing a striking dichotomy. For monomers, AF3's pLDDT scores reliably predict disorder (MCC: 0.693), matching AlphaFold2 and rivaling dedicated predictors. This consistency across fundamentally different architectures confirms that disorder prediction emerges from training data, not model design. For multimers, the picture grows complex. Despite comparable aggregate performance (mean DockQ: 0.563 vs 0.571), AF3 and AF2 achieve these results through fundamentally different mechanisms. Conventional structural features explain 58% of AF2's variance but only 42% of AF3's. Users cannot predict when AF3 will succeed or fail from interface properties alone. On disorder-to-order transitions (MFIB benchmark), both models perform equally well, successfully predicting final folded states. Yet seed variance analysis reveals AF3's failures are deterministic: the model converges to identical structures across independent runs, whether correct or incorrect, indicating rigid structural priors override available information. Our findings establish AF3 as reliable for the prediction of monomer disorder but unpredictable for multimers. Architectural innovation alone cannot overcome training data bias. Progress demands disorder-enriched datasets and ensemble sampling, not merely novel architectures.
Source metadata only
biorxiv
04Supplementation with a Limosilactobacillus fermentum K73 synbiotic modulates gut microbiota function and behavior in gnotobiotic mice transplanted with microbiota from children diagnosed with autism spectrum disorder
Gut dysbiosis has been implicated in numerous pathological conditions, including neurodevelopmental and neurodegenerative disorders. Recently, dietary interventions targeted at restoring microbial balance have therefore gained attention as potential therapeutic strategies. We recently demonstrated that an encapsulated synbiotic containing high-oleic palm oil and Limosilactobacillus fermentum K73 can modulate the metabolic activity and composition of human-derived gut microbiota in an in vitro batch bioreactor. Here, we extended this work through an in vivo supplementation pilot study using gnotobiotic mice colonized with gut microbiota from Colombian pediatric patients diagnosed with autism spectrum disorder (ASD) or age-matched neurotypical (NT) donors. Behavioral assessments and analyses of gut microbiota composition and function were performed before and after synbiotic supplementation. First, we found that the gut microbiota from Colombian ASD patients exhibited significantly reduced richness relative to NT donors, consistent with reports from other geographical regions, and displayed distinct compositional features unique to this population. Humanization of the gnotobiotic mice with this donor microbiota was successful, with murine gut communities reflecting features of their corresponding donor microbiota. Notably, synbiotic supplementation induced significant increases in the abundance of beneficial taxa and the production of short chain fatty acids that were more pronounced in mice colonized with ASD-derived microbiota, with concurrent behavioral changes associated with beneficial modulation of gut microbiota. Overall, we provide evidence that supports synbiotic supplementation as a viable strategy to positively modulate gut microbiome in conditions of dysbiosis. Our study also expands the body of knowledge of gut microbiome to understudied populations such as Latin America.
Source metadata only
biorxiv
05BCR repertoire analysis and cloning of antibody candidates targeting native and Asp7-isomerized β-amyloid
Computational approaches are increasingly used to prioritize monoclonal antibody (mAB) candidates from BCR-seq datasets. However, the reliable identification of B cells encoding antibodies against rare antigenic epitopes remains challenging. We employed a repertoire-guided workflow combining antigen-tetramer sorting of B cells from immunized mice, followed by low-input bulk BCR-seq, which yielded informative clonal repertoires. Clustering analysis allowed us to prioritize IGH and IGK clonotypes potentially targeting {beta}-amyloid and the isoAsp7 proteoform (isoD7-A{beta}1-16), implicated in Alzheimer's disease. We observed recurrent IGHV8-12 and IGKV1-117 usage, consistent with canonical mouse anti-A{beta} responses. Focusing on isoD7-A{beta} -associated candidates, we selected fourteen candidate IGH--IGK combinations for recombinant expression including variants containing IGKV8-21, IGKV8-19, IGKV2-112 together with IGHV1-75, IGHV10-1 or IGHV8-12. Several recombinant mABs showed detectable binding activity to isoD7-A{beta}, including a candidate with preferential recognition of isoD7-A{beta}, supporting the feasibility of the approach but underscoring the challenge of accurate chain pairing. These results provide proof of principle that repertoire-guided analysis can prioritize candidate IGH and IGK chains and propose possible heavy-light chain combinations based on their co-representation across samples while experimental testing remains necessary to identify antibodies with preferential recognition of isoD7-A{beta}.
Source metadata only
biorxiv