Biomedicine Daily · Monday, 5 October 2026
CBA FRONTIER INSIGHTS
Retatrutide Delivers 20.8% Weight Loss at 80 Weeks in TRIUMPH-2 Topline
Retatrutide achieved an average weight loss of 20.8% at 80 weeks in the 12 mg group of the TRIUMPH-2 trial, with topline results published in The Lancet. The trial enrolled 1152 people with type 2 diabetes across dose arms, and a subgroup with baseline BMI of 35 or higher lost 23.4%. Eli Lilly plans to file with the FDA in Q1 2027, positioning retatrutide to compete at the top of an increasingly crowded obesity market. The magnitude of weight loss in a diabetic population, approaching results typically seen only in non-diabetic trials, sets a high bar for the incretin field. Elsewhere in the day's coverage: Regeneron started the first Phase III trial of ALN-CIDEB, an siRNA targeting CIDEB, in 1500 adults with MASLD, and the OpenAI Foundation pledged $25 billion with over $250 million already committed to life science programs.
Clinical readouts and safety
Retatrutide achieves 20.8% weight loss at 80 weeks in TRIUMPH-2 topline results
Retatrutide delivered an average weight loss of 20.8% at 80 weeks in the 12 mg group of the TRIUMPH-2 trial, which enrolled 1152 people with T2D across dose arms. A subgroup with baseline BMI of 35 or higher lost 23.4%. The topline results were published in The Lancet, and Eli Lilly plans to file with the FDA in Q1 2027.
Week 54 EASI-75 Response Data Reported for Adolescents with Moderate-to-Severe Atopic Dermatitis
Long-term data presented at the 35th EADV congress in Vienna show that most adolescents with moderate-to-severe atopic dermatitis achieved an EASI-75 response at week 54 of treatment with the drug branded in China as Simuqibai. The findings, released at the European Academy of Dermatology and Venereology annual meeting, address the need for safe and effective long-term therapy in this age group.
Regeneron Starts First Phase III Trial of CIDEB-Targeting siRNA ALN-CIDEB in MASLD
Regeneron has started the first Phase III trial of ALN-CIDEB, an siRNA therapy targeting CIDEB developed with Alnylam. The randomized, double-blind, placebo-controlled trial will enroll 1500 adults with MASLD to evaluate efficacy and safety, aiming to suppress fat accumulation in liver cells for MASH and other liver diseases. Phase III entry moves this CIDEB-directed approach into late-stage testing.
clinicaltrials.govA Phase 1b Study of C-CAR168 in Participants With Systemic Sclerosis (SSc)
A Phase 1b multicenter open-label trial (NCT07854483, sponsored by AbelZeta Inc.) will test a single infusion of autologous anti-CD20/BCMA CAR T cells (C-CAR168) after fludarabine and cyclophosphamide lymphodepletion in refractory systemic sclerosis not responding to standard therapy. About 6 to 12 participants will be followed for 24 months for safety, CAR T-cell persistence, pharmacokinetics/pharmacodynamics, biomarkers and preliminary efficacy, with gene therapy safety follow-up to 15 years. The trial has not yet begun recruiting; start is planned for March 2027.
Research papers
medicalxpress.comMapping parasite mitochondria reveals ancient pathways and dozens of potential new drug targets
Mitochondrial proteomes mapped across five parasites (Giardia, Acanthamoeba, trypanosomes, Leishmania and Babesia) reveal 33 protein families shared by two or more parasites and absent from human mitochondria, candidates for drugs that hit multiple pathogens at once. Giardia's mitochondrion holds just 59 proteins, over half of unknown function, while Acanthamoeba's carry a hydrogenase backup. The work, spanning a billion years of evolution, also challenges textbook views of mitochondria and their DNA retention.
Fungus Rhizopus arrhizus promotes MASLD-associated hepatocellular carcinoma through generating kynurenic acid. Rhizopus arrhizus drives liver cancer by producing kynurenic acid that activates MAPK signaling.
The gut fungus Rhizopus arrhizus is the top enriched fungus across the progression from metabolic dysfunction-associated steatotic liver disease (MASLD) to MASLD-associated hepatocellular carcinoma, and it accelerates tumorigenesis in multiple mouse models. Conditioned medium from R. arrhizus increased proliferation and reduced cell cycle arrest and apoptosis in human MASLD-HCC cells. Mechanistically, the fungus produces kynurenic acid that binds IQGAP1 and activates MAPK signaling, identifying a host-fungus interaction that could be blocked to suppress MASLD-HCC.
Conserved and divergent mitochondrial assemblies in kinetoplastid parasites.
Mitochondrial proteomes of Leishmania tarentolae and Trypanosoma brucei contain roughly 1,700 proteins, most without homologs in higher eukaryotes. Complexome profiling plus cryo-electron microscopy structures of respiratory complexes CIII2, CIV2 and CV identified nine previously unrecognized nuclear-encoded subunits and resolved five mitochondrially encoded proteins, including products of pan-edited mRNAs. The work refines annotations and reveals lineage-specific assembly features such as a QCR8 extension plugging the vestigial MPPα/β cavity in CIII2.
Distinct brainstem circuits separate GLP-1 receptor agonist weight loss from aversion, J Clin Invest study shows
Semaglutide and tirzepatide, both GLP-1 receptor agonists, suppress food intake but also cause nausea and aversive reactions. Prior work showed that neurons expressing GLP-1 receptors in two dorsal vagal complex nuclei, the nucleus of the solitary tract and the area postrema, both suppress food intake when activated, yet only area postrema activation causes aversion. The study from Weiwei Qiu and Martin G. Myers, Jr., published in J Clin Invest, identifies the key brainstem circuit underlying this dissociation.
youtube.comMendell Links ROS-Slowed Ribosome Elongation to Selenoprotein Rise and Ferroptosis Control
Joshua Mendell's CSHL keynote reviewed his laboratory's work on non-coding RNA regulation, including microRNA control, ZSWIM8-mediated miRNA degradation, and NORAD in genome stability. He then presented CRISPR screens of the selenocysteine decoding pathway, showing that disrupting the electron transport chain generates ROS, slows ribosome elongation, and raises expression of selenoproteins such as GPX4, an enzyme that suppresses ferroptosis and a vulnerability in many tumors. The pathway links ribosome biology to cancer metabolism.
youtube.comMembrane perforation by a two-component perforin complex emerges as a unifying trigger of type 2 immunity
Mushi's group at NIBS shows that allergens and parasites trigger type 2 immunity through a shared membrane-perforation signal. Alternaria fungal extract induces ILC2 activation, IL-33 release and inflammatory gene expression in airway epithelium; a two-component perforin-family complex, AEGS plus AEGL (a roughly 60.5 kD protein identified by mass spectrometry), is required together for all three responses in vitro and in vivo. Mutant extracts lacking either component lose the ability to induce airway allergic responses, and multiple perforin proteins induce TH2 infiltration, eosinophil accumulation and serum IgE elevation.
youtube.comPersonalized DNA Neoantigen Vaccine Pipeline for Glioblastoma Enters First-in-Human Phase 1
Elaine Mardis presented a CSHL lecture on a personalized DNA neoantigen vaccine pipeline for glioblastoma: tumor-versus-normal DNA comparison, RNA expression filtering, multi-algorithm neoantigen prediction, and manufacture as a DNA vector vaccine now in a first-in-human phase 1 trial. The design sequences tumors after resection during 6 weeks of radiotherapy, with PD-1 permitted only at progression per FDA requirements. Pre-treatment biopsies from patient 9 already contained tumor-specific T cells that expanded clonally after vaccination, unlike patient 2, and GBM showed greater TCR clonality than brain metastases despite lower T-cell infiltration.
youtube.comDavid Tuveson Maps Pancreatic Cancer Biology and Stromal Targets in CSHL Lecture
David Tuveson of Cold Spring Harbor Laboratory gave a CSHL Leading Strand lecture on pancreatic cancer biology, covering how oncogenic mutations drive epigenomic and microenvironmental change. He described atypical WNT7 activation that drives fibroblast overactivation and matrix production, RAS dependence on farnesylated membrane localization, and a new target validated genetically in mitochondrial metabolism with antagonist compounds designed using cryo-EM. His group uses organoids, single-cell data and in vivo metabolite perturbations such as auxin to find and test targets.
doi.orgOral delivery of recombinant Lactococcus lactis expressing an IL-23 inhibitor as a potential therapeutic strategy for experimental colitis
Engineered Lactococcus lactis delivering the IL-23p19-binding protein ILP317 through yogurt-coated food pellets protected mice against DSS- and TNBS-induced colitis, reducing disease activity index, colon shortening, and mucosal inflammatory cell infiltration. The same protection followed intraperitoneal ILP317 or the IL-23R binder REX115 as soluble proteins, but oral L. lactis expressing REX115 was less consistent. ILP317 was the more effective oral construct, supporting non-colonizing bacteria as a delivery route for IL-23 inhibition in IBD.
youtube.comFudan Team Describes Microglia Replacement From Mechanism to Clinic in ImmuneZoom Lecture
A Fudan University team presented a lecture on microglia replacement: CSF1R inhibition with PLX compounds clears resident microglia, and mismatched bone marrow transplant introduces GFP-positive, CSF1R-normal cells that repopulate the cortex, hippocampus and corpus callosum. In ALS animal models, replacement preserved brain structure and improved function. The speaker reported 8 patients stable at 6, 12 and 24 months of follow-up after inadvertent mismatched BMT, though reported replacement efficiency varied, including 19.2%.
youtube.comCross-Species Optic Nerve Single-Cell Atlas With AI Annotation Maps Glia Subtypes in Glaucoma
A cross-species single-nucleus RNA-seq atlas of the retina and optic nerve covers about 150k nuclei across 5 species, integrating data into a shared space to identify conserved and species-specific cell types. AI-assisted annotation reached 99%, 95% and 90% accuracy at different confidence tiers, speeding manual curation. The work identifies AS1 and OPC3 glial subpopulations changed in the optic nerve and glaucoma context, pointing to glial roles in optic nerve damage.
Methods and resources
youtube.comEllen Zhong on Using Machine Learning to Map cryo-EM Conformational Heterogeneity
Machine learning can turn cryo-EM from a single static reconstruction into a distribution of protein conformations, Ellen Zhong of Princeton explains in a CSHL interview. Her cryo-DRGN methods train on each new experimental dataset to discover the conformational states present, and can map states such as translation elongation factors back to spatial positions in yeast Cryo-ET samples. Next steps include transferring trained models to new datasets, adding AlphaFold-like atomic model priors to improve resolution for large complexes, and building atomic model ensembles from the reconstructed distributions.
Opinion and commentary
OpenAI Foundation Pledges $25 Billion, Starting With Cancer Vaccine and Alzheimer's Programs
The OpenAI Foundation, the nonprofit that holds 26% of OpenAI Group PBC, has pledged $25 billion as an initial commitment, with over $1 billion in grants planned across all areas in its first year. Life science grants so far total more than $250 million, including over $100 million for the AI for Alzheimer's program across six research institutions and over $125 million for the Public Data for Health program, which funds UNC's personalized cancer vaccine effort and UCSF's OpenADMET project. All grant-funded data must be openly available to researchers worldwide, and the foundation's independence from OpenAI will be tested when another director must leave the group board by October 28, 2026.
AI use in GMP Environments
A r/biotech discussion started by u/pancak3d asked whether validated AI, especially LLM-based agents, has any workable uses that directly affect product quality or safety in GMP environments. Practitioners replied that deviation-assistant drafting, document writing and data analysis are already in use, but every output still requires human review; others argued GMP's approved-SOP requirements and mostly structured data make deterministic tools easier to validate than generative AI. One commenter cited FDA's April 2, 2026 warning letter to Purolea Cosmetics Lab, the first to cite inappropriate AI use in pharmaceutical manufacturing, as a caution against generating SOPs and master production records without quality-unit review.
Also today
3 events that did not make today's daily, one table per category, one row per event. Open a category to expand.
OtherFDA Approves Lilly's Pirtobrutinib for First · Novartis Licenses AiBo's T · Novo Nordisk pays $300 million upfront for ex3 ▾▴
Everything else with a concrete event that did not make the daily.
- FDA Approves Lilly's Pirtobrutinib for FirstUpdateThe US FDA has approved a new indication for Eli Lilly's pirtobrutinib (100 mg and 50 mg tablets), announced October 2, as first-line treatment for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have not received prior treatment and have no known 17p deletion. Pirtobrutinib is a highly selective, non-covalent BTK inhibitor, the first and only approved one, binding both wild-type and C481-mutant BTK.FDA
- Novartis Licenses AiBo's TUpdateNovartis has granted... Novartis has secured an exclusive worldwide licence from AiBo Biotech (AiBo) to ABO2203, a T-cell engager molecule and the company's lead pipeline candidate, plus options to license further projects from AiBo's proprietary RNA platform. AiBo receives an upfront payment of 3.8 billion yuan and is eligible for up to about 7.2 billion in milestone payments if all options are exercised and development, regulatory and commercialisation milestones are met, plus royalties on future sales.
- Novo Nordisk pays $300 million upfront for exUpdateNovo Nordisk has licensed HRS-1596, a GLP-1/GIP dual receptor agonist developed by Hengrui for weight loss and blood glucose control, gaining exclusive rights to develop, manufacture and commercialize it outside greater China. Hengrui receives an upfront payment of $300 million, with the deal worth up to $2.6 billion in total plus royalties on net sales. The drug has potential in obesity, type 2 diabetes and other metabolic diseases.