Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNVXAW)

• DTT Name: Lymphocyte activation gene 3 protein (LAG3)
• Synonyms: Protein FDC; LAG-3; FDC; CD223
• Gene Name: LAG3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Immunoglobulin
• UniProt ID: LAG3_HUMAN
• TTD ID: T94718
• Sequence:
  MWEAQFLGLLFLQPLWVAPVKPLQPGAEVPVVWAQEGAPAQLPCSPTIPLQDLSLLRRAG
  VTWQHQPDSGPPAAAPGHPLAPGPHPAAPSSWGPRPRRYTVLSVGPGGLRSGRLPLQPRV
  QLDERGRQRGDFSLWLRPARRADAGEYRAAVHLRDRALSCRLRLRLGQASMTASPPGSLR
  ASDWVILNCSFSRPDRPASVHWFRNRGQGRVPVRESPHHHLAESFLFLPQVSPMDSGPWG
  CILTYRDGFNVSIMYNLTVLGLEPPTPLTVYAGAGSRVGLPCRLPAGVGTRSFLTAKWTP
  PGGGPDLLVTGDNGDFTLRLEDVSQAQAGTYTCHIHLQEQQLNATVTLAIITVTPKSFGS
  PGSLGKLLCEVTPVSGQERFVWSSLDTPSQRSFSGPWLEAQEAQLLSQPWQCQLYQGERL
  LGAAVYFTELSSPGAQRSGRAPGALPAGHLLLFLILGVLSLLLLVTGAFGFHLWRRQWRP
  RRFSALEQGIHPPQAQSKIEELEQEPEPEPEPEPEPEPEPEPEQL
• Function: Delivers inhibitory signals upon binding to ligands, such as FGL1. FGL1 constitutes a major ligand of LAG3 and is responsible for LAG3 T-cell inhibitory function. Following TCR engagement, LAG3 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation. May inhibit antigen-specific T-cell activation in synergy with PDCD1/PD-1, possibly by acting as a coreceptor for PDCD1/PD-1. Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells. Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function. Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation. Binds MHC class II (MHC-II); the precise role of MHC-II-binding is however unclear. Lymphocyte activation gene 3 protein: Inhibitory receptor on antigen activated T-cells.
• Reactome Pathway: MHC class II antigen presentation (R-HSA-2132295)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Relatlimab	DM28AZV	Melanoma	2C30	Approved	[2]

15 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anti-LAG3	DMJO402	Gastric adenocarcinoma	2B72	Phase 2	[1]
BMS-986016	DMDCHM7	Hematologic tumour	2B33.Y	Phase 1/2	[3]
Favezelimab	DMYAIE2	Non-hodgkin lymphoma	2B33.5	Phase 1/2	[4]
IMP-321	DM18ZLW	Allergy	4A80-4A85	Phase 1/2	[5]
A289	DMO4DSH	Aggressive cancer	2A00-2F9Z	Phase 1	[6]
ADPT01	DMS6DPF	Breast cancer	2C60-2C65	Phase 1	[7]
FS118	DM0QH9K	Advanced cancer	2A00-2F9Z	Phase 1	[8]
GSK2831781	DMC47M9	Autoimmune disease	4A40-4A45	Phase 1	[9]
GSK4074386	DMI3FU6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
IMP-701	DMXSMF9	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
INCAGN2385	DMDSZNC	Melanoma	2C30	Phase 1	[12]
MK-4280	DMCA1NX	Neoplasm	2A00-2F9Z	Phase 1	[13]
RG6139	DMJFM3O	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
Sym022	DMCK2YR	Lymphoma	2A80-2A86	Phase 1	[15]
XmAb22841	DMQB3HD	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Concatameric LAG3Ig	DMRPV0A	Discovery agent	N.A.	Investigative	[11]
IMP-731	DM1TQXO	Autoimmune diabetes	5A10	Investigative	[11]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 761234
• [3] Nivolumab in NSCLC: latest evidence and clinical potential. Ther Adv Med Oncol. 2015 March; 7(2): 85-96.
• [4] A first-in-human study of the anti-LAG-3 antibody favezelimab plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer. ESMO Open. 2022 Dec;7(6):100639.
• [5] A soluble form of lymphocyte activation gene-3 (IMP321) induces activation of a large range of human effector cytotoxic cells. J Immunol. 2007 Sep 15;179(6):4202-11.
• [6] Clinical pipeline report, company report or official report of Klus Pharma
• [7] Clinical pipeline report, company report or official report of Novartis.
• [8] Development of Inhibitors of the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signaling Pathway.J Med Chem. 2019 Feb 28;62(4):1715-1730.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Clinical pipeline report, company report or official report of GlaxoSmithKline.
• [11] IMP321 (sLAG-3), an immunopotentiator for T cell responses against a HBsAg antigen in healthy adults: a single blind randomised controlled phase I study. J Immune Based Ther Vaccines. 2007 Mar 29;5:5.
• [12] Clinical pipeline report, company report or official report of Agenus.
• [13] Establishment of engineered cell-based assays mediating LAG3 and PD1 immune suppression enables potency measurement of blocking antibodies and assessment of signal transduction. J Immunol Methods. 2018 May;456:7-14.
• [14] Clinical pipeline report, company report or official report of Genentech.
• [15] Clinical pipeline report, company report or official report of Symphogen.
• [16] Clinical pipeline report, company report or official report of Xencor.