Table 1.
Therapeutic approaches targeting the IFN/pDC pathway
ApproachTargetDrug (name)CompanyIndicationStatus
pDC depletion/inhibition ILT7 VIB7734 Viela Bio Myositis Active 
BDCA2 BIIB-059 Biogen SLE, cutaneous LE Active 
CD123 and CD3 XmAb-14045 Xencor AML Active 
CD123 IMGN632 Immunogen AML, BPDCN, MDS, B-cell acute lymphocytic leukemia, and other CD123-positive malignancies Active 
CD123 Talacotuzumab Johnson & Johnson MDS, LE, systemic cancer, AML Active 
CD123 and CD3 Flotetuzumab MacroGenics AML and MDS Active 
CD123 Elzonris (tagraxofusp) Stemline Therapeutics, Inc. BPDCN, AML, CMML, chronic MF, multiple myeloma in combination with pomalidomide Approved by the FDA in 2018, for the treatment of BPDCN 
IFN pathway IFNAR1 MEDI546, anifrolumab AstraZeneca/MedImmune SLE Active 
IFN-α MEDI545, sifalimumab AstraZeneca/MedImmune SLE, dermatomyositis, and polymyositis Inactive 
IFN-α IFNa Kinoid Neovacs SLE, dermatomyositis, type I diabetes, HIV/AIDS Active 
IFN-α and IFN-ω JNJ-0839, JNJ-55920839 Johnson & Johnson SLE Active 
IFN-β PF-06823859 Pfizer Inc. Dermatomyositis, SLE Active 
IFN-I antagonist RSLV-601 Resolve Preclinical autoimmune Active 
Tyk2 BMS-986165 Bristol Myers Squibb Co. SLE, psoriasis, Crohn's disease Active 
Tyk2 NDI-031232, NDI-031301, NDI-031407 Nimbus Therapeutics LLC Preclinical Possibly inactive; new allosteric inhibitors in development 
Tyk2/JAK-1 PF-06700841 Pfizer Inc. Ulcerative colitis, plaque psoriasis, and alopecia areata Active 
Tyk2/JAK-1 SAR-20347 Sareum Holdings plc/SRI International IBD, MS, SLE, psoriasis, RA Active 
JAK-3/JAK-1 Tofacitinib Pfizer Inc. RA, psoriatic arthritis, ulcerative colitis, ankylosis spondylitis, juvenile arthritis, dry eye syndrome Active 
JAK kinase Baricitinib Eli Lilly RA, atopic eczema, SLE, GVHD, psoriatic arthritis, alopecia areata Active 
Nucleic acid sensors STING antagonist TBD Nimbus Therapeutics LLC/Cellgen SLE, interferonopathies Active 
TLR7/9 antagonist IMO-3100 Idera Psoriasis Active 
TLR7/8/9 antagonist IMO-8400 Idera Cancer: Waldenström’s; DLBCLMyD88(L265P); psoriasis Active 
TLR7/9 antagonist DV1179 Dynavax SLE Inactive 
Immune complex digestion RNA/immune complexes RSLV-132 Resolve SLE, Sjogren's syndrome Active 
ApproachTargetDrug (name)CompanyIndicationStatus
pDC depletion/inhibition ILT7 VIB7734 Viela Bio Myositis Active 
BDCA2 BIIB-059 Biogen SLE, cutaneous LE Active 
CD123 and CD3 XmAb-14045 Xencor AML Active 
CD123 IMGN632 Immunogen AML, BPDCN, MDS, B-cell acute lymphocytic leukemia, and other CD123-positive malignancies Active 
CD123 Talacotuzumab Johnson & Johnson MDS, LE, systemic cancer, AML Active 
CD123 and CD3 Flotetuzumab MacroGenics AML and MDS Active 
CD123 Elzonris (tagraxofusp) Stemline Therapeutics, Inc. BPDCN, AML, CMML, chronic MF, multiple myeloma in combination with pomalidomide Approved by the FDA in 2018, for the treatment of BPDCN 
IFN pathway IFNAR1 MEDI546, anifrolumab AstraZeneca/MedImmune SLE Active 
IFN-α MEDI545, sifalimumab AstraZeneca/MedImmune SLE, dermatomyositis, and polymyositis Inactive 
IFN-α IFNa Kinoid Neovacs SLE, dermatomyositis, type I diabetes, HIV/AIDS Active 
IFN-α and IFN-ω JNJ-0839, JNJ-55920839 Johnson & Johnson SLE Active 
IFN-β PF-06823859 Pfizer Inc. Dermatomyositis, SLE Active 
IFN-I antagonist RSLV-601 Resolve Preclinical autoimmune Active 
Tyk2 BMS-986165 Bristol Myers Squibb Co. SLE, psoriasis, Crohn's disease Active 
Tyk2 NDI-031232, NDI-031301, NDI-031407 Nimbus Therapeutics LLC Preclinical Possibly inactive; new allosteric inhibitors in development 
Tyk2/JAK-1 PF-06700841 Pfizer Inc. Ulcerative colitis, plaque psoriasis, and alopecia areata Active 
Tyk2/JAK-1 SAR-20347 Sareum Holdings plc/SRI International IBD, MS, SLE, psoriasis, RA Active 
JAK-3/JAK-1 Tofacitinib Pfizer Inc. RA, psoriatic arthritis, ulcerative colitis, ankylosis spondylitis, juvenile arthritis, dry eye syndrome Active 
JAK kinase Baricitinib Eli Lilly RA, atopic eczema, SLE, GVHD, psoriatic arthritis, alopecia areata Active 
Nucleic acid sensors STING antagonist TBD Nimbus Therapeutics LLC/Cellgen SLE, interferonopathies Active 
TLR7/9 antagonist IMO-3100 Idera Psoriasis Active 
TLR7/8/9 antagonist IMO-8400 Idera Cancer: Waldenström’s; DLBCLMyD88(L265P); psoriasis Active 
TLR7/9 antagonist DV1179 Dynavax SLE Inactive 
Immune complex digestion RNA/immune complexes RSLV-132 Resolve SLE, Sjogren's syndrome Active 

AML, acute myeloid leukemia; BPDCN, blastic pDC neoplasm; CMML, chronic myelomonocytic leukemia; FDA, US Food and Drug Administration; GVHD, graft-versus-host disease; IBD, inflammatory bowel disease; LE, lupus erythematosus; MDS, myelodysplastic syndrome; MF, myelofibrosis; MS, multiple sclerosis; RA, rheumatoid arthritis; TBD, to be determined.

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