Lu AG22515 / Lundbeck, AprilBio - LARVOL DELTA

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

Lundbeck “April Bio’s ‘APB-A1’, safety and efficacy confirmed” [Google translation] (eDaily) - P1 | N=58 | NCT05136053 | Sponsor: H. Lundbeck A/S | "On the 8th (localtime), Lundbeck released a summary of the phase 1 clinical trial results of APB-A...while announcing earnings for the third quarter of this year. Lundbeck explained, 'It was safe at all administered doses, and CDL was found to be strongly and consistently reduced depending on the administered dose.' In other words, the higher the dosage, the higher the efficacy, and there were no side effects. Lundbeck reports that phase 1 clinical trials have been successfully completed and plans to enter phase 2 clinical trials in the second quarter of next year."

New P2 trial • P1 data • Trial completion • CNS Disorders • Immunology

AprilBio Announces US Patent Registration for APB-A1 (Business Korea) - "AprilBio revealed...that they have obtained a U.S. patent for their candidate drug for autoimmune disease treatment, known as 'APB-A1' (development code name, partner company Lundbeck code name Lu-AG22515)....'We have been granted the patent by claiming rights to the sequence and structure of the anti-CD40L antibody fusion protein binding to CD40L.'"

Patent • CNS Disorders • Immunology • Inflammation

A Study Investigating Lu AG22515 in Healthy Adults (clinicaltrials.gov) - P1 | N=58 | Completed | Sponsor: H. Lundbeck A/S | Active, not recruiting ➔ Completed

Trial completion

Will Aprilbio get new wing with Lundbeck’s follow-up clinical trials? (Korea Biomedical Review) - "Through a conference call for the first half-year on Wednesday (local time), Lundbeck announced it plans to start the phase 2 trial of the candidate, Lu AG22515, in 2024....In addition, Lundbeck hinted at the possibility of expanding the indications for Lu AG22515 through the phase 2 trial next year."

New indication • New P2 trial • Immunology • Inflammation

Exploration and validation of m7G-related genes as signatures in the immune microenvironment and prognostic indicators in low-grade glioma. (PubMed, Am J Transl Res) - "The identified m7G-related genes may provide new insight into the treatment and prognosis of LGG."

Biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • GRIN2B • XBP1

Evaluation of the Genetic Diversity, Population Structure and Selection Signatures of Three Native Chinese Pig Populations. (PubMed, Animals (Basel)) - "A total of 359 candidate genes were identified, and some genes may affect characteristics such as immunity (IL-2, IL-21 and ZFYVE16), adaptability (APBA1), reproduction (FGF2, RNF17, ADAD1 and HIPK4), meat quality (ABCA1, ADIG, TLE4 and IRX5), and heat tolerance (VPS13A, HSPA4). Overall, the findings of this study will provide some valuable insights for the future breeding, conservation and utilization of these three Chinese indigenous pig populations."

Journal • ABCA1 • FGF2 • HSPA4 • IL2 • IL21 • IRX5 • TLE4

A Study Investigating Lu AG22515 in Healthy Adults (clinicaltrials.gov) - P1 | N=58 | Active, not recruiting | Sponsor: H. Lundbeck A/S | Recruiting ➔ Active, not recruiting | N=43 ➔ 58

Enrollment change • Enrollment closed

A Study Investigating Lu AG22515 in Healthy Adults (clinicaltrials.gov) - P1 | N=43 | Recruiting | Sponsor: H. Lundbeck A/S | Trial completion date: Jan 2023 ➔ Jun 2023 | Trial primary completion date: Dec 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date

Insights on the pathogenesis of type 2 diabetes as revealed by signature genomic classifiers in an African American population in the Washington DC area. (PubMed, Diabetes Metab Res Rev) - "Tobacco smoking and gender were significantly associated with case-control differences of expression of the APBA1 and APOE genes (connected with Alzheimer's disease), and INSR and CYP2D6 (associated with metabolic disorders). The results highlight the needs for more effective management of T2DM and for tobacco smoking cessation interventions in this community, and further research on the associations of T2DM with other disease processes, including cancer and neurobehavioral pathways."

IO biomarker • Journal • Alzheimer's Disease • Behavior Disorders • CNS Disorders • Diabetes • Mental Retardation • Metabolic Disorders • Oncology • Psychiatry • Tobacco Cessation • Type 2 Diabetes Mellitus • APOE • BCL2 • IL6 • IR • SOD2 • TP53

A Study Investigating Lu AG22515 in Healthy Adults (clinicaltrials.gov) - P1 | N=43 | Recruiting | Sponsor: H. Lundbeck A/S | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2021 ➔ Mar 2022

Enrollment open • Trial initiation date

A Study Investigating Lu AG22515 in Healthy Adults (clinicaltrials.gov) - P1 | N=43 | Recruiting | Sponsor: H. Lundbeck A/S

New P1 trial