Biomedicine Daily · Thursday, 1 October 2026
CBA FRONTIER INSIGHTS
Lilly's Zepbound plus eloralintide drives 23.3% weight loss in type 2 diabetes
Eli Lilly reported that combining Zepbound with eloralintide, its amylin-targeting candidate, produced 23.3% weight loss at 48 weeks at the highest dose in people with obesity and type 2 diabetes, outperforming Zepbound alone (14.8%) and eloralintide alone (11.1%) in a mid-stage trial. The result shows next-generation combination therapy can deliver greater weight loss even in patients with diabetes, who typically lose less on medications, though high discontinuation rates may raise tolerability questions. The day also brought a survival benefit for oncolytic virus VCN-01 plus chemotherapy in metastatic pancreatic cancer, cardiovascular safety for oral orforglipron in ACHIEVE-4, and FDA priority review of Roche's multiple sclerosis pill fenebrutinib despite an imbalance in deaths.
Clinical readouts and safety
Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomized phase 2b trial
Intravenous zabilugene almadenorepvec (VCN-01), a hyaluronidase-expressing oncolytic adenovirus, plus gemcitabine and nab-paclitaxel prolonged overall survival over chemotherapy alone in the randomized phase 2b VIRAGE trial in treatment-naive metastatic pancreatic cancer. The finding supports adding an oncolytic virus to standard first-line chemotherapy in this setting.
[Articles] 8 weeks versus 12 weeks of sofosbuvir–velpatasvir for treatment-naive, non-cirrhotic, chronic hepatitis C (RESOLVE): a multicentre, open-label, non-inferiority, randomised controlled trial in India
Eight weeks of sofosbuvir-velpatasvir was similar in efficacy to the standard 12-week regimen in treatment-naive, non-cirrhotic patients with chronic hepatitis C in the RESOLVE multicentre, open-label, non-inferiority, randomised controlled trial in India. The finding supports shortening treatment duration in this population.
STAT+: Eli Lilly’s Zepbound combined with amylin drug led to significant weight loss in mid-stage trial
Combining Eli Lilly's Zepbound with eloralintide, an amylin-targeting candidate, produced 23.3% weight loss at 48 weeks in people with obesity and type 2 diabetes at the highest dose, outperforming Zepbound alone (14.8%) and eloralintide alone (11.1%). High discontinuation rates may raise tolerability questions. It shows next-generation combination therapy can achieve greater weight loss even in patients with diabetes, who typically lose less on medications.
[Articles] Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial
Orforglipron was non-inferior to insulin glargine for MACE-4 in adults with type 2 diabetes at increased cardiovascular risk, establishing its cardiovascular safety in the event-driven ACHIEVE-4 trial. Gastrointestinal adverse events were the most frequent adverse event and the most common reason for orforglipron discontinuation, while clinically significant hypoglycaemia occurred less often with orforglipron than with insulin glargine. The findings support orforglipron as a once-daily oral option with established cardiovascular safety in this population.
Bristol Myers trial revisions shake confidence in new class of fibrosis drugs
Bristol Myers Squibb has amended the long-term safety extension of the Phase 3 Aloft trial of admilparant, its experimental LPA1R inhibitor for idiopathic pulmonary fibrosis, after a limited number of liver-related safety events including one participant death from liver injury. The amendment, filed for European Union sites in May, classifies liver injury as a newly classified important potential risk and requires closer monitoring of enrollees with high liver enzymes. It is unclear whether the patient who died received admilparant, and outside monitors have repeatedly recommended the study continue as planned.
Lilly builds commercial case for GLP-1 products over Novo with indirect analyses
Indirect comparisons presented at EASD show Lilly's 17.2-mg dose of oral Foundayo produced 1.5% to 2.4% greater weight loss and 0.3% to 0.6% greater HbA1c reduction than oral semaglutide, drawing on ACHIEVE-3 (nearly 1,700 patients) and PIONEER PLUS. A separate analysis found Zepbound gave up to 4.5% greater weight loss than high-dose injectable Wegovy, with patients up to three times more likely to lose at least 20% of body weight.
Regulatory and policy
FDA starts review of Roche’s multiple sclerosis pill
The FDA has accepted Roche's approval application for fenebrutinib, an experimental multiple sclerosis pill, under a priority review with a six-month timeline, covering both relapsed and primary progressive forms of the disease. The application rests on three late-stage studies that met their main objectives, but approval chances could be complicated by an imbalance in deaths, eight among fenebrutinib recipients versus one on Aubagio in two Phase 3 trials, and a case of liver enzyme elevations meeting Hy's law. Roche did not say when a decision might come.
Atara, Pierre Fabre resubmit twice-rebuffed cell therapy after FDA flips again
Atara Biotherapeutics and Pierre Fabre Pharmaceuticals have resubmitted the BLA for Ebvallo (tabelecleucel) to treat EBV-positive posttransplant lymphoproliferative disease in patients 2 years and older, after two complete response letters, the second in January. The FDA reversed course in May, agreeing a single-arm study with an appropriate historical control could support approval. The resubmission adds patients and longer follow-up from the Phase 3 ALLELE trial plus expanded access, separate study and European commercial data; a Class 2 resubmission could carry a March 29, 2027 action date, and Atara is eligible for a $31 million milestone on approval.
Industry and deals
BioNTech to close German manufacturing plants after failing to find buyers
BioNTech has ended its search for buyers for three German manufacturing sites in Idar-Oberstein, Marburg and Tübingen, set for exit by the end of 2027, after a deadline at the end of September passed without a deal. The plants became surplus as COVID-19 vaccine sales fell and Pfizer takes full responsibility for making Comirnaty from 2027. The closures, together with a Singapore site, could affect about 1,860 jobs, and BioNTech has agreed enhanced severance arrangements with its works council.
Research papers
Histone readers MLLT1 and MLLT3 concentrate AID to confer locus specificity
The paper reports that the histone readers MLLT1 and MLLT3 concentrate AID to confer locus specificity. Analyses included ChIP-seq, TT-seq, Nanopore amplicon-seq and BioID proteomics in B cell lines such as CH12F3 and Ramos, together with reanalysis of public datasets on histone acetylation, AID occupancy and aberrant somatic hypermutation in B cell lymphoma. Data and custom analysis code were deposited in public repositories.
RNA splicing factor mutations drive myeloid neoplasm oncogenesis through protein complex poisoning
Splicing factor mutations in myeloid neoplasms poison entire functional protein complexes, not just individual transcripts. Single-cell transcriptomics (10X-ONT, n = 21) and immunophenotype-resolved pauciproteomics (n = 78) across 62 patients and 20 healthy donors show that mutation-specific RNA mis-splicing decouples protein from transcript dynamics during hematopoietic differentiation, effects invisible to transcriptomics alone and validated in iPSC differentiation models.
Sugar-rich foods exacerbate antibiotic-induced microbiome disruption
In patients undergoing allogeneic haematopoietic cell transplantation, intake of sweets during antibiotic exposure predicted lower faecal microbiome α-diversity and increased Enterococcus abundance. The finding, from 9,419 meal samples and 1,009 stool samples across 173 patients, was validated in mice, where dietary sugar supplementation exacerbated and prolonged antibiotic-induced Enterococcus blooms. Short-term sugar avoidance emerges as a testable strategy during antibiotic treatment.
A two-hit mechanism triggers autoimmune hair loss
The paper reports a two-hit mechanism that triggers autoimmune hair loss, drawing on single-cell RNA-seq and bulk RNA-seq datasets generated in the study. The sequencing data have been deposited in the NCBI Gene Expression Omnibus under accession codes GSE343853 and GSE343613.
Transcription pause and elongation regulators mediate somatic hypermutation
Somatic hypermutation depends on recruitment of activation-induced deaminase to chromatin and on a stalled polymerase II substrate; the molecular factors and mechanisms mediating both have now been identified. The work names the transcription pause and elongation regulators involved, filling a mechanistic gap in how mutation targets are generated during antibody diversification.
Human genetics implicates a BACH2–NRF2 axis in fetal haemoglobin activation
A multi-ancestry GWAS of fetal haemoglobin (HbF) levels in 28,279 individuals across European, African and Asian cohorts identified 91 conditionally independent signals at 12 loci, including BACH2 as a new regulator. BACH2 restrains NRF2-mediated transcriptional activation of the γ-globin genes HBG1 and HBG2, defining a BACH2–NRF2 axis in HbF regulation. The finding adds a genetically nominated activator pathway to the known repressors and suggests therapeutic targets for sickle cell disease and β-thalassaemia.
Type 2 immune history trains lung macrophages for viral disease tolerance
Type 2 inflammation trains nerve- and airway-associated macrophages to confer disease tolerance against lethal influenza. The trained macrophages limit immunopathology and promote tissue repair without enhancing viral clearance, indicating prior type 2 immune history protects through tolerance of infection rather than control of the virus itself.
A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation
Proteomic and phosphoproteomic analyses of lysosomes uncovered a TBK1/ULK1 signalling axis that activates TFEB in response to lysosomal stress, independent of nutrient-sensing by mTORC1. This regulatory arm mediates lysosomal adaptation to stress, and its deregulation was linked to tumorigenesis in follicular lymphoma. The work adds a nutrient-independent branch to the mTORC1 signalling framework at the lysosome.
GPCR antagonism via rewiring of receptor trafficking and degradation
Bifunctional antibodies termed GTACs, which bind both a GPCR and the constitutively internalizing transferrin receptor 1, drive receptor endocytosis and lysosomal degradation, silencing signalling instead of competing with ligands. GTACs depleted and antagonized AT1R, RXFP1, CCR6 and BILF1, blocking chemotaxis in primary immune cells, suppressing angiotensin-potentiated contraction in iPSC-derived cardiomyocytes and inhibiting constitutive BILF1 signalling. GTACs showed more than 10-100-fold greater potency and improved efficacy over conventional antagonists, and the approach extended to APJ, A2AR and M3R.
Gene flux shapes diversity and evolution of the ancient 17q21.31 inversion polymorphism
The common 979-kb 17q21.31 inversion in humans, long treated as a recombination-suppressing block, in fact permits ongoing gene flux between H1 and H2 haplotypes. Single-cell sperm sequencing showed near-complete suppression of single crossovers, but two-switch events of 17-150 kb occurred throughout the inversion at rates above genome-wide estimates, and 99 H1-H2 recombinant haplotypes were found in All of Us genomes. Recombinant haplotypes showed H2 additively increases female crossover rates across chromosomes, an effect not explained by KANSL1 duplications, and gene flux dates to roughly 100-500 thousand years ago.
Prion-like transmission of human tau strains in the mouse brain
Human tau filaments from Alzheimer's disease and corticobasal degeneration retain their distinct structures when seeded in mouse brain, according to mouse experiments on templated seeding. The finding supports strain-specific tau propagation, in which prion-like tau strains transmit their conformations, and backs the use of such seeding for disease modelling.
Osteoclasts intercept meningeal lymphatic paths for dural metastasis
Osteoclast-derived angiopoietin-2 in the dura mater impairs lymphatic vessel function and weakens anti-tumour immunity against dural metastases. The work identifies osteoclasts as interceptors of meningeal lymphatic paths and points to selective osteoclast targeting as a way to restore meningeal lymphatic function and anti-tumour immunity. No numerical results are given.
Restoring hearing in people with a rare form of deafness
A gene therapy delivering a functional OTOF gene to inner-ear hair cells improved hearing in around 80% of participants within 24 weeks in the CHORD clinical trial, which enrolled 24 participants aged between 10 months and 16 years with OTOF-associated hearing impairment. Each participant received Otarmeni as a one-time infusion, either in one ear or in both ears. In April, Otarmeni became the first gene therapy for hearing loss approved by the US Food and Drug Administration.
Endothelial AMBRA1 loss contributes to vascular dysregulation facilitating metastatic progression in early-stage melanoma
Endothelial AMBRA1 loss drives vascular dysfunction and metastatic progression in early-stage melanoma. Melanoma-conditioned media or TGFβ1-3 ligands induced post-transcriptional AMBRA1 loss in endothelial cells, increasing proliferation, accelerating tubulogenesis, stabilizing Slug and Snail, and reducing Claudin-5, VE-cadherin and N-cadherin. In 121 non-ulcerated AJCC stage I/II melanomas classified AMBLor at-risk, loss of AMBRA1 in intratumoural and peritumoural blood and lymphatic vessels correlated significantly with metastatic progression.
Methods and resources
Function-preserving watermarking of AI-generated proteins
SynthIDBio embeds detectable, function-preserving watermarks directly into AI-designed proteins. SynthIDBio-sequence integrates watermarking into ProteinMPNN and produced biologically watermarked, functional binders in vitro: low nanomolar binders for the SARS-CoV-2 receptor binding domain and subnanomolar binders for VEGF-A and PD-L1, with no effect on binding affinity distributions or hit rates. SynthIDBio-structure fine-tunes AlphaFold 3 to emit watermarked structure predictions with near-perfect detectability and negligible loss of global accuracy, establishing provenance tracking for AI-generated sequences and structures without central databases.
ArchMap is a web-based platform for reference-based analysis of single-cell datasets
ArchMap is a free, no-code web tool for query-to-reference mapping of single-cell datasets onto reference atlases, compatible with Python-based mapping methods. It removes the need for coding expertise or a license that existing software often demands, making reference-based analysis accessible to bench scientists and clinicians.
Opinion and commentary
Beyond BMI: The diet-microbiome context of the obesity paradox
Desharnais et al. show in Nature that across diverse mouse models, anti-PD-1 sensitivity tracks more closely with the diet-microbiome-metabolite ecosystem than with obesity-associated metabolic dysfunction. The findings point to body mass index as an incomplete proxy for host biology and suggest strategies to improve anti-PD-1 efficacy without inducing obesity.
Also today
22 events that did not make today's daily, one table per category, one row per event. Open a category to expand.
RegulatoryCamzyos（mavacamten） · Ebvallo · Hetlioz · VertigoDx on firm ground with FDA greenlight for vertigo diagnostic system4 ▾▴
Filings, acceptances, designations, approvals and withdrawals at a regulator.
- Camzyos（mavacamten）UpdateThe FDA approved Camzyos (mavacamten) as the first treatment to improve functional capacity and symptoms in children with symptomatic obstructive hypertrophic cardiomyopathy, extending approval to pediatric patients weighing at least 30 kg, after adult approval in 2022. Efficacy was supported by the phase 3 SCOUT-HCM trial in 44 patients aged 12-18, where once-daily dosing for 28 weeks significantly reduced the Valsalva LVOT gradient versus placebo. The drug carries a boxed warning for heart failure risk and is available only through the Camzyos REMS program.FDA
- EbvalloUpdateFDA
- HetliozUpdateFDA
- VertigoDx on firm ground with FDA greenlight for vertigo diagnostic systemUpdateFDA
Clinicaltrevogrumab · petrelintide · Retatrutide · Connect’s Dupixent rival reduces COPD attacks by 85%, but misses a secondary goal …11 ▾▴
Trial starts, early and mid-stage data, and results that did not make the daily.
- trevogrumabUpdate
- petrelintideUpdate
- RetatrutideUpdateRetatrutide produced substantial improvements in bodyweight and improved glycaemic control in adults with obesity and type 2 diabetes in the phase 3 TRIUMPH-2 trial, a double-blind, randomised, placebo-controlled comparison. Its safety profile was generally consistent with other molecules with GLP-1 receptor agonism, supporting retatrutide as a possible treatment for obesity in people with type 2 diabetes.
- Connect’s Dupixent rival reduces COPD attacks by 85%, but misses a secondary goalUpdate
- acebilustatUpdate
- Amgen reveals 6Update
- Merck’s antiUpdate
- Highlight Therapeutics illuminates positive ph. 2 topline data in highUpdate
- amylin+ZepboundUpdate
- #EASD26Update
- AbbVie's eczema drug shows benefit in Phase 2; BioMarin lays off 117Update
Deals and financingBeam ← YolTech/Serapha · NorthStar · AstraZeneca buys into Summit, UniQure drops on 4 · Varda …5 ▾▴
Licensing, M&A and financing that did not make the daily.
- Beam ← YolTech/SeraphaUpdateBeam Therapeutics sued YolTech Therapeutics and its U.S. partner Serapha Bio in the U.S. District Court in Massachusetts on Sept. 25, alleging a former Beam scientist, Zi Jun "Emma" Wang, stole trade secrets to build a rival base editing therapy for alpha-1 antitrypsin deficiency. The therapy, SERP-01, targets the same mutation at the same DNA site as Beam's BEAM-302. Serapha, backed by $230 million in funding and planning a reverse merger to go public, denies the claims and aims to start a Phase 2/3 trial of SERP-01 later this year or in early 2027.
- NorthStarUpdate
- AstraZeneca buys into Summit, UniQure drops on 4Update
- VardaUpdate
- GSK ← Wave Life SciencesUpdate
OtherFresenius Kabi USA · FDA hits 2nd Fresenius site with contamination2 ▾▴
Everything else with a concrete event that did not make the daily.
- Fresenius Kabi USAUpdateFDA issued a warning letter, reference 320-26-129, to Fresenius Kabi USA CEO Pierluigi Antonelli on September 22, 2026, citing CGMP violations found at its sterile injectable manufacturing facility in Melrose Park, Illinois, inspected from January 27 to February 18, 2026. FDA says the firm failed to adequately investigate drug product failures, including bioburden action limit failures linked to adverse events with famotidine for injection, leading to a recall of three famotidine injection batches after an endotoxin failure in retained samples. FDA found the company's March 11, 2026 response inadequate and warned that failure to correct violations may result in seizure or injunction.FDA
- FDA hits 2nd Fresenius site with contaminationUpdateFDA