lecanemab

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Ligands
lecanemab

GtoPdb Ligand ID: 12202

Synonyms: BAN-2401 | BAN2401 | lecanemab-irmb | Leqembi®

lecanemab is an approved drug (FDA (2023))

Compound class: Antibody

Comment: Lecanemab (BAN2401) is a humanized IgG1 monoclonal antibody that targets amyloid β protein (APP) protofibrils [5,18]. It binds more potently to amyloid β protofibrils than to monomeric amyloid β [5,16]. Lecanemab was developed by Eisai and Biogen for potential to slow neurological decline in patients in the very early stages of developing Alzheimer's disease. It is not suitable for other forms of dementia.
This blog post by Derek Lowe ('Lecanemab and Alzheimer's: More Data'; posted on Nov. 30, 2022) provides a sound review of lecanemab's reported efficacy [19], what it contributes as an Alzheimer's therapy, and the issues around potential lecanemab-mediated cerebral bleeding events.

References
1. Cho S, Gaamouch FE, Upadhyay S, Nada H, Kuncewicz K, Gabr MT. (2025) As48, a First-in-Class Dual-Function TREM2 Modulator: Receptor Activation and Shedding Inhibition. bioRxiv,. [PMID:40909719]
2. Cho S, Kaur B, Lam K, Gaamouch FE, Kuncewicz K, Doering NP, Wolber G, Gabr MT. (2025) Structure-Based Virtual Screening Identifies TREM2-Targeted Small Molecules that Enhance Microglial Phagocytosis. bioRxiv,. [PMID:40909477]
3. Cho S, Szalai TV, El Gaamouch F, Bajusz D, Keserű GM, Gabr M. (2025) AI-Assisted Discovery and Optimization of Small Molecule TREM2 Agonists with Functional Microglial Activity. bioRxiv,. [PMID:41000669]
4. Curtis D, Joseph S, Alzheimer’s Disease Neuroimaging Initiative. (2025) Analysis of whole genome sequence data shows association of Alzheimer's disease with rare coding variants in ABCA7, PSEN1, SORL1 and TREM2. J Neurogenet, 39 (4): 95-104. [PMID:40990081]
5. Gellerfors P, Lannfelt L, Sehlin D, Pettersson FE, Englund H. (2011) Protofibril selective antibodies and the use thereof. Patent number: US8025878B2. Assignee: Bioarctic Neuroscience AB. Priority date: 23/03/2006. Publication date: 27/09/2011.
6. Hoy SM. (2023) Lecanemab: First Approval. Drugs, 83 (4): 359-365. [PMID:36856953]
7. Ji KY, Kim SM, Yee SM, Kim MJ, Ban YJ, Kim EM, Lee EH, Choi HR, Yun H, Lee CW et al.. (2021) Cyclophilin A is an endogenous ligand for the triggering receptor expressed on myeloid cells-2 (TREM2). FASEB J, 35 (4): e21479. [PMID:33710680]
8. Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, Basun H, Lannfelt L. (2016) Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody. Alzheimers Res Ther, 8 (1): 14. [PMID:27048170]
9. Long H, Simmons A, Mayorga A, Burgess B, Nguyen T, Budda B, Rychkova A, Rhinn H, Tassi I, Ward M et al.. (2024) Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease. Alzheimers Res Ther, 16 (1): 235. [PMID:39444037]
10. Mummery CJ, Mayorga AJ, Simmons A, Chow TW, Burgess B, Nguyen T, Gao J, Budda B, Park LQ, Gupta R et al.. (2026) The TREM2 agonistic antibody AL002 in early Alzheimer's disease: a phase 2 randomized trial. Nat Med, 32 (5): 1708-1716. [PMID:41787076]
11. Roberts M, Sevastou I, Imaizumi Y, Mistry K, Talma S, Dey M, Gartlon J, Ochiai H, Zhou Z, Akasofu S et al.. (2020) Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer's disease. Acta Neuropathol Commun, 8 (1): 13. [PMID:32019610]
12. Saeb D, Lietzke EE, Fuchs DI, Aldrich EC, Bruce KD, Sprenger KG. (2025) The flexible stalk domain of sTREM2 modulates its interactions with brain-based phospholipids. Elife, 13. [PMID:40928206]
13. Schlepckow K, Morenas-Rodríguez E, Hong S, Haass C. (2023) Stimulation of TREM2 with agonistic antibodies-an emerging therapeutic option for Alzheimer's disease. Lancet Neurol, 22 (11): 1048-1060. [PMID:37863592]
14. Sharma C, Mazumder A. (2025) From Bench to Bedside: Cutting-Edge and Emerging Therapies for Alzheimer's Disease. Cent Nerv Syst Agents Med Chem, [Epub ahead of print]. [PMID:40993929]
15. Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, Bradley H, Rabe M, Koyama A et al.. (2022) Correction to: A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther, 14 (1): 70. [PMID:35598024]
16. Söllvander S, Nikitidou E, Gallasch L, Zyśk M, Söderberg L, Sehlin D, Lannfelt L, Erlandsson A. (2018) The Aβ protofibril selective antibody mAb158 prevents accumulation of Aβ in astrocytes and rescues neurons from Aβ-induced cell death. J Neuroinflammation, 15 (1): 98. [PMID:29592816]
17. Tsui JSM, Au DM, Uhm H, Wong WW, Lo RMN, Jiang Y, Ip FCF, Mok KY, Wong HY, Kwok TCY et al.. (2025) The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes. Alzheimers Dement, 21 (9): e70586. [PMID:40960087]
18. Tucker S, Möller C, Tegerstedt K, Lord A, Laudon H, Sjödahl J, Söderberg L, Spens E, Sahlin C, Waara ER et al.. (2015) The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis, 43 (2): 575-88. [PMID:25096615]
19. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S et al.. (2022) Lecanemab in Early Alzheimer’s Disease. New England Journal of Medicine, Online ahead of print. DOI: 10.1056/NEJMoa2212948
20. Yang H, Kim D, Yang Y, Bagyinszky E, An SSA. (2025) TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting. Int J Mol Sci, 26 (15). [PMID:40806186]
21. Yeh FL, Wang Y, Tom I, Gonzalez LC, Sheng M. (2016) TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron, 91 (2): 328-40. [PMID:27477018]
22. Yuan S, El Gaamouch F, Cho S, Kuncewicz K, Nada H, Gabr MT. (2025) Discovery of a Small Molecule TREM2 Agonist with Improved In Vitro Pharmacokinetic Profile and Validated Target Engagement. ACS Med Chem Lett, 16 (8): 1634-1640. [PMID:40832531]
23. Zhao Y, Wu X, Li X, Jiang LL, Gui X, Liu Y, Sun Y, Zhu B, Piña-Crespo JC, Zhang M et al.. (2018) TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function. Neuron, 97 (5): 1023-1031.e7. [PMID:29518356]

References

1. Cho S, Gaamouch FE, Upadhyay S, Nada H, Kuncewicz K, Gabr MT. (2025)
As48, a First-in-Class Dual-Function TREM2 Modulator: Receptor Activation and Shedding Inhibition.
bioRxiv,. [PMID:40909719]

2. Cho S, Kaur B, Lam K, Gaamouch FE, Kuncewicz K, Doering NP, Wolber G, Gabr MT. (2025)
Structure-Based Virtual Screening Identifies TREM2-Targeted Small Molecules that Enhance Microglial Phagocytosis.
bioRxiv,. [PMID:40909477]

3. Cho S, Szalai TV, El Gaamouch F, Bajusz D, Keserű GM, Gabr M. (2025)
AI-Assisted Discovery and Optimization of Small Molecule TREM2 Agonists with Functional Microglial Activity.
bioRxiv,. [PMID:41000669]

4. Curtis D, Joseph S, Alzheimer’s Disease Neuroimaging Initiative. (2025)
Analysis of whole genome sequence data shows association of Alzheimer's disease with rare coding variants in ABCA7, PSEN1, SORL1 and TREM2.
J Neurogenet, 39 (4): 95-104. [PMID:40990081]

5. Gellerfors P, Lannfelt L, Sehlin D, Pettersson FE, Englund H. (2011)
Protofibril selective antibodies and the use thereof.
Patent number: US8025878B2. Assignee: Bioarctic Neuroscience AB. Priority date: 23/03/2006. Publication date: 27/09/2011.

6. Hoy SM. (2023)
Lecanemab: First Approval.
Drugs, 83 (4): 359-365. [PMID:36856953]

7. Ji KY, Kim SM, Yee SM, Kim MJ, Ban YJ, Kim EM, Lee EH, Choi HR, Yun H, Lee CW et al.. (2021)
Cyclophilin A is an endogenous ligand for the triggering receptor expressed on myeloid cells-2 (TREM2).
FASEB J, 35 (4): e21479. [PMID:33710680]

8. Logovinsky V, Satlin A, Lai R, Swanson C, Kaplow J, Osswald G, Basun H, Lannfelt L. (2016)
Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody.
Alzheimers Res Ther, 8 (1): 14. [PMID:27048170]

9. Long H, Simmons A, Mayorga A, Burgess B, Nguyen T, Budda B, Rychkova A, Rhinn H, Tassi I, Ward M et al.. (2024)
Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.
Alzheimers Res Ther, 16 (1): 235. [PMID:39444037]

10. Mummery CJ, Mayorga AJ, Simmons A, Chow TW, Burgess B, Nguyen T, Gao J, Budda B, Park LQ, Gupta R et al.. (2026)
The TREM2 agonistic antibody AL002 in early Alzheimer's disease: a phase 2 randomized trial.
Nat Med, 32 (5): 1708-1716. [PMID:41787076]

11. Roberts M, Sevastou I, Imaizumi Y, Mistry K, Talma S, Dey M, Gartlon J, Ochiai H, Zhou Z, Akasofu S et al.. (2020)
Pre-clinical characterisation of E2814, a high-affinity antibody targeting the microtubule-binding repeat domain of tau for passive immunotherapy in Alzheimer's disease.
Acta Neuropathol Commun, 8 (1): 13. [PMID:32019610]

12. Saeb D, Lietzke EE, Fuchs DI, Aldrich EC, Bruce KD, Sprenger KG. (2025)
The flexible stalk domain of sTREM2 modulates its interactions with brain-based phospholipids.
Elife, 13. [PMID:40928206]

13. Schlepckow K, Morenas-Rodríguez E, Hong S, Haass C. (2023)
Stimulation of TREM2 with agonistic antibodies-an emerging therapeutic option for Alzheimer's disease.
Lancet Neurol, 22 (11): 1048-1060. [PMID:37863592]

14. Sharma C, Mazumder A. (2025)
From Bench to Bedside: Cutting-Edge and Emerging Therapies for Alzheimer's Disease.
Cent Nerv Syst Agents Med Chem, [Epub ahead of print]. [PMID:40993929]

15. Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, Bradley H, Rabe M, Koyama A et al.. (2022)
Correction to: A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody.
Alzheimers Res Ther, 14 (1): 70. [PMID:35598024]

16. Söllvander S, Nikitidou E, Gallasch L, Zyśk M, Söderberg L, Sehlin D, Lannfelt L, Erlandsson A. (2018)
The Aβ protofibril selective antibody mAb158 prevents accumulation of Aβ in astrocytes and rescues neurons from Aβ-induced cell death.
J Neuroinflammation, 15 (1): 98. [PMID:29592816]

17. Tsui JSM, Au DM, Uhm H, Wong WW, Lo RMN, Jiang Y, Ip FCF, Mok KY, Wong HY, Kwok TCY et al.. (2025)
The TREM2 H157Y variant is associated with more severe neurodegeneration in Alzheimer's disease and altered immune-related processes.
Alzheimers Dement, 21 (9): e70586. [PMID:40960087]

18. Tucker S, Möller C, Tegerstedt K, Lord A, Laudon H, Sjödahl J, Söderberg L, Spens E, Sahlin C, Waara ER et al.. (2015)
The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice.
J Alzheimers Dis, 43 (2): 575-88. [PMID:25096615]

19. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S et al.. (2022)
Lecanemab in Early Alzheimer’s Disease.
New England Journal of Medicine, Online ahead of print. DOI: 10.1056/NEJMoa2212948

20. Yang H, Kim D, Yang Y, Bagyinszky E, An SSA. (2025)
TREM2 in Neurodegenerative Disorders: Mutation Spectrum, Pathophysiology, and Therapeutic Targeting.
Int J Mol Sci, 26 (15). [PMID:40806186]

21. Yeh FL, Wang Y, Tom I, Gonzalez LC, Sheng M. (2016)
TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia.
Neuron, 91 (2): 328-40. [PMID:27477018]

22. Yuan S, El Gaamouch F, Cho S, Kuncewicz K, Nada H, Gabr MT. (2025)
Discovery of a Small Molecule TREM2 Agonist with Improved In Vitro Pharmacokinetic Profile and Validated Target Engagement.
ACS Med Chem Lett, 16 (8): 1634-1640. [PMID:40832531]

23. Zhao Y, Wu X, Li X, Jiang LL, Gui X, Liu Y, Sun Y, Zhu B, Piña-Crespo JC, Zhang M et al.. (2018)
TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function.
Neuron, 97 (5): 1023-1031.e7. [PMID:29518356]