Lu AG22515 / Lundbeck, AprilBio - LARVOL DELTA

Lundbeck pivots AprilBio's APB-A1 to neurology to revive development and value (Chosun Biz) - "The company later relisted the candidate in its pipeline with the development area changed to neurology...Lundbeck said, 'Blocking CD40L has strong potential to treat a broad range of autoimmune-related neurological diseases.'Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myasthenia gravis (MG) are cited as the main target indications."

Pipeline update • Immunology • Multiple Sclerosis • Myasthenia Gravis • Neuromyelitis Optica Spectrum Disorder

AprilBio sinks as Lundbeck halts TED path, TKG Huchems faces test in Korea (Chosun Biz) - "Earlier, Denmark-based drugmaker Lundbeck said on the 19th (local time) in its second-quarter earnings release that an analysis of phase 1b data for 'Lu AG22515 (APB-A1)' 'did not confirm the anticipated clinical effect in thyroid eye disease (TED).'..." Accordingly, it will not proceed with further development in TED, and the plan is to continue development by finding a new disease that better fits CD40L, the mechanism of action of APB-A1....Lundbeck observed positive signals such as reduced proptosis in some patients and a decrease in thyroid-stimulating hormone receptor (TSHR) autoantibodies. However, after reviewing the full dataset, it changed course because it did not confirm the level of clinical effect anticipated in TED."

Discontinued • P1 data • Immunology • Thyroid Eye Disease

AprilBio to be acquired by chemical group TKG in $225 mil. deal (Korea Biomedical Review) - "Under the terms of the offering, TKG Huchems and IMM Startup Venture Fund No. 2, a venture fund managed by IMM Investment, will receive 155 billion won in voting convertible preferred shares, giving TKG effective management control. IMM Asset Management Co. and IMM Scale-up Bio Fund No. 1 will receive 141.8 billion won in ordinary shares priced at 34,620 won each and 50 billion won in nonvoting convertible preferred shares. New shares are scheduled for issuance July 24."

M&A • Atopic Dermatitis • Immunology

AprilBio secures 430 billion won to speed R&D while keeping tech‑out model (Chosun Biz) - "A representative case is APB-A1, a thyroid eye disease treatment candidate out-licensed in 2021 to Denmark's Lundbeck for about 560 billion won. It is currently in phase 2 clinical trials. In 2024, it transferred APB-R3, a candidate for autoinflammatory diseases, to U.S.-based Evoimmune for about 650 billion won. This molecule is being developed as an atopic dermatitis treatment..."

Financing • Atopic Dermatitis • Immunology • Thyroid Eye Disease

Preclinical Pharmacokinetic and Pharmacodynamic Profile of Lu AG22515, a CD40-Ligand Blocker in Development for Thyroid Eye Disease (ENDO 2026) - P1 | "These data demonstrate that Lu AG22515, an immunomodulator that blocks CD40L, is a promising candidate with potent inhibitory activity and a PK/PD profile that supports its continued clinical development. A phase 1b trial (NCT06557850) evaluating Lu AG22515 in adults with moderate-to-severe thyroid eye disease is ongoing."

PK/PD data • Preclinical • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • CD40LG • CXCL8 • IFNG • IL6

Results from a Phase 1b Trial Evaluating CD40-Ligand Blocker Lu AG22515 in Patients with Moderate-to-Severe Thyroid Eye Disease (ENDO 2026) - P1 | "Interim analyses demonstrated clinically meaningful reduction in proptosis and pharmacodynamic response to Lu AG22515 in patients with moderate-to-severe, active TED. These data support the therapeutic potential of Lu AG22515 and the CD40/CD40L pathway as a novel therapeutic target for TED. Final efficacy, PK/PD, and partial safety results from the ongoing trial will be available and presented at ENDO 2026."

Clinical • P1 data • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • Thyroid Eye Disease • CD40LG

Protein-truncating variants in APBA1 in minors with severe, early-onset obesity: implications for genetic testing. (PubMed, Mol Cell Pediatr) - No abstract available

Journal • Genetic Disorders • Obesity

INHIBITION OF MIR-4284 COULD REDUCE APOPTOSIS AND NEUROINFLAMMATION BY TARGETING APBA1/JAK1/STAT3 SIGNALING IN ALZHEIMER'S DISEASE (ADPD 2026) - "miR-4284 inhibition confers neuroprotection by modulating APBA1 and JAK/STAT3 signaling, suggesting its potential as a therapeutic target for AD."

Alzheimer's Disease • CNS Disorders • Inflammation • JAK1

'Efficacy results in patients from the phase 2a trial of APB-R3 and the phase 1b trial of APB-A1 are expected to be announced in the first half.' (Chosun Biz)

P1 data • P2a data • Atopic Dermatitis • Immunology

A Trial Investigating Lu AG22515 in Adult Participants With Moderate-to-Severe Thyroid Eye Disease (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Recruiting ➔ Active, not recruiting

Enrollment closed • Ophthalmology • Thyroid Eye Disease

Molecular insights into electroreceptor ribbon synapses from differential gene expression in sturgeon lateral line organs. (PubMed, J Anat) - "Sterlet ampullary organs also express Otof (also expected from paddlefish, though we identified one Otof transcript variant maintained in ampullary organs but not neuromasts) and two other hair cell synapse-associated genes, Apba1 (Mint1) and Rab3a...In contrast, Cbln18, encoding a secreted trans-synaptic scaffolding protein, was only expressed in neuromasts and Tulp1, encoding tubby-related protein 1 (required for the development and function of photoreceptor ribbon synapses), was only expressed in ampullary organs. Overall, our results support electroreceptor ribbon synapses in non-teleost ray-finned bony fish being glutamatergic and suggest further commonalities, but also some differences, with hair cell ribbon synapses."

Journal • Brain Cancer • DSCAM

Inhibition of miR-4284 could reduce apoptosis and neuroinflammation by targeting APBA1/JAK1/STAT3 signaling in Alzheimer's disease. (PubMed, Cell Biosci) - "miR-4284 inhibition confers neuroprotection by modulating APBA1 and JAK/STAT3 signaling, suggesting its potential as a therapeutic target for AD."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • JAK1

Discovery of obesity genes through cross-ancestry analysis. (PubMed, Nat Commun) - "While YLPM1, MC4R, and SLTM show consistent effects, GRM7 and APBA1 show significant ancestral heterogeneity...These genes also influence cardiometabolic comorbidities, including GIGYF1 and SLTM towards type 2 diabetes with or without BMI as a mediator, and altered levels of plasma proteins, such as LECT2 and NCAN, which in turn affect BMI. Our findings provide insights into the genetic basis of obesity and its related comorbidities across ancestries and ascertainments."

Clinical • Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • LECT2 • MC4R • RIF1

Obesity and the Genome: Emerging Insights from Studies in 2024 and 2025. (PubMed, Genes (Basel)) - "At the neural level, rare variants in synaptic genes like BSN (Bassoon presynaptic cytomatrix protein), a presynaptic scaffold protein, and APBA1 (amyloid beta precursor protein binding family A member 1), a neuronal adaptor involved in vesicular trafficking, disrupt communication in feeding circuits, elevating obesity risk and illustrating how synaptic integrity influences food intake regulation...For example, genetic variants in GLP-1R (glucagon-like peptide-1 receptor) and GIPR (glucose-dependent insulinotropic polypeptide receptor) may modulate the effectiveness of incretin-based therapies, while PRS for satiation can help match individuals to the most appropriate anti-obesity medications. This review focuses on studies in the last two years that highlight how advances in obesity genetics are driving a shift toward more personalized and mechanism-based treatment strategies."

Journal • Review • Genetic Disorders • Obesity • Oncology • APP

AprilBio's key clinical trial results are expected to be announced in the first half of next year, drawing attention. "Short-term R&D momentum is evident." [Google translation] (Nate) - "Interim results are scheduled to be shared internally by the end of September, with limited external disclosure. Due to the clinical nature of the study, the degree of ocular protrusion can be visually confirmed. The plan is to announce final results from Phase 1b in the first half of next year, followed by Phase 2 for TED and additional indications....Another partner, Evomune, is conducting a Phase 2a trial of APB-R3 (IL-18BP-SAFA) in atopic dermatitis involving 60 subjects, with a target completion date of December. Results, including EASI scores and pruritus indices at week 12, are expected to be announced in the first quarter of next year."

Enrollment status • P1 data • P2a data • Atopic Dermatitis • Thyroid Eye Disease

"Stable cash flow expected due to milestone payments from partner companies' additional clinical trials." [Google translation] (Nate) - "'With the milestone receipt (KRW 20 billion) for the start of phase 2 clinical trials for APB-A1 and phase 2b for APB-R3 next year...'"

New P2 trial • Atopic Dermatitis • Immunology • Rheumatoid Arthritis • Thyroid Eye Disease

Coordinated regulation of the hypothalamic-pituitary-somatotropic axis in Chinese sea bass (Lateolabrax maculatus) under temperature and salinity changes. (PubMed, Gen Comp Endocrinol) - "Weighted gene co-expression network analysis (WGCNA) among L. maculatus tissues revealed strong co-expression of HPS genes (ssts, igf1rs, igfbps) in brains than in livers and muscles, interacting with feeding (cartpt, negr1), metabolism (grik3, drd4), and growth (apba1) functional genes...Similar co-expression of HPS genes (sstrs, igf1rbs, igfbps) were with feeding (pik3r4), metabolism (mrps, ndufa12) and growth (sulf2, peli3, apod) functions in brains, indicating that HPS axis could regulate growth through coordinated mediation of the food-intake and energy metabolism in L. maculatus under environmental stress. Our results provided comprehensive understanding about the L. maculatus HPS axis responding to environmental stimuli, which are crucial for the growth regulation and will provide important insights into fast-growing L. maculatus cultivation."

Journal • APOD • IGF1R • SULF2

April Bio, Beyond Profit with Technology Export Clinical Progress, Green Light for ‘Weight Class Increase’ [Google translation] (Money Today) - "Lundbeck is expected to secure interim data from the phase 1b clinical trial of APB-A1 for thyroid eye disease (TED) within the third quarter. Evommune is also scheduled to administer its first phase 2 patient with atopic dermatitis within the first quarter. The target completion date for the clinical trial is the fourth quarter of this year."

New P2 trial • P1 data • Atopic Dermatitis • Thyroid Eye Disease

April Bio, Achieves Profit in 2 Years Since Listing… Confident in Technology Export Performance [Google translation] (Medipana) - "Lundbeck has announced that it is seeking a global big pharma to conduct joint development for 'APB-A1' in order to expand it to various indications. Evommune plans to conduct phase 2 clinical trials for 'APB-R3' for atopic patients in February....April Bio expressed confidence through IR data that 'an increase in corporate value is theoretically possible as both 'APB-A1' and 'APB-R3' will enter clinical trials for patients in 2025.'"

Commercial • New P2 trial • Atopic Dermatitis • Immunology

A Trial Investigating Lu AG22515 in Adult Participants With Moderate-to-Severe Thyroid Eye Disease (clinicaltrials.gov) - P1 | N=19 | Recruiting | Sponsor: H. Lundbeck A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Ophthalmology • Thyroid Eye Disease

Effects of second litter syndrome on reproductive performance in sows. (PubMed, Vet World) - "Only APBA1-2 was significantly decreased by SLS...Therefore, SLS sows do not necessarily have future low reproductive performance or be culled. Future investigations should explore the mechanism of alternate decrease/increase patterns in PBA."

Journal

Replicating the Association of Variants in BSN and APBA1 with Obesity in Diverse Populations. (PubMed, medRxiv) - "Specifically, BSN pLoF variants were associated with pulmonary hypertension, atrial fibrillation, and anticoagulant use, while APBA1 pLoF variants were linked to disorders of the temporomandibular joint. These findings underscore the potential of large-scale biobanks in advancing genetic discovery."

Journal • Atrial Fibrillation • Cardiovascular • Genetic Disorders • Hypertension • Obesity • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • MC4R

A Trial Investigating Lu AG22515 in Adult Participants With Moderate-to-Severe Thyroid Eye Disease (clinicaltrials.gov) - P1 | N=19 | Not yet recruiting | Sponsor: H. Lundbeck A/S

New P1 trial • Ophthalmology • Thyroid Eye Disease

Exploring the genetic landscape of B-ALL: Upregulation of cell adhesion pathway in the high risk adult as com- pared to pediatric B-ALL patients (ICKSH 2024) - "The top upregulated adhesion genes (GO) with their fold change in MR2 adults are PCDH15(7.7),THY1(5.9),HHLA(4.5),RND3(4.2),NEXMIF(3.7),C- CL2(3.6),APBA1(3.1),BMP4(2.8),CX3CL1(2.6),COL16A1(2.6) and in MR1 adults are EDIL3(4.8),MUC4(4.6),SPP1(4.5),KRT18(4.2),FOXA1(3.5), LGALS2(3.5),NRP2(3.3), LAMB4(3.2), PCDH15(3.0), IL12B(2.9). Conclusion : Compared to the paediatric cohort, the adult cohort exhibits a higher number of MR2(Poor risk) cases. The upregulation of the cell-cell adhesion pathway in MR2 adults may contribute to the poor prognosis of adult patients compared to paediatric pa- tients."

Clinical • Acute Lymphocytic Leukemia • Pediatrics • BMP4 • CX3CL1 • EDIL3 • FOXA1 • IKZF1 • IL12B • KRT18 • KRT18 • LGALS3 • MUC4 • NRP2 • SPP1 • THY1

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease. (PubMed, Nat Genet) - "We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R...Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity."

Journal • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • MC4R