Table 1. S1P modulators under development or in clinical testing.
RRMS: Relapsing Remitting Multiple Sclerosis, PPMS: Primary Progressive Multiple Sclerosis, SPMS: Secondary Progressive Multiple Sclerosis, RMS: Relapsing Multiple Sclerosis, UC: Ulcerative Colitis, CIPD: Chronic Inflammatory Demyelinating Polyradiculoneuropathy, ALS: Amyotrophic Lateral Sclerosis, SLE: Systemic Lupus Erythematosus, SCLE: Subacute Cuteaneous Lupus Erythematosus RA: Rheumatoid Arthritis, AMD: Age-related Macular Degeneration.
| MOLECULE NAME | DRUG NAME | TARGETED PROTEIN | SPONSOR | PROPOSED OR APPROVED USE | CURRENT TRIAL PHASE | CT ID |
|---|---|---|---|---|---|---|
| Fingolimod (Gilenya) | S1PR1, 3, 4, 5 | Novartis | RRMS | Marketed | ||
| Transplant | III | NCT00099801 | ||||
| CIPD | III | NCT01625182 | ||||
| PPMS | III | NCT00731692 (INFORMS) | ||||
| ALS | II | NCT01786174 | ||||
| Asthma | II | NCT00785083 | ||||
| BAF312 | Siponimod (Mayzent) | S1PR1, 5 | Novartis | SPMS | FDA approved | NCT01665144 (EXPAND) |
| RRMS | II | NCT01185821 | ||||
| Active dermatomyositis | II | NCT02029274 | ||||
| Hemorrhagic stroke, ICH | II | NCT03338998 | ||||
| Hepatic impairment | I | NCT01565902 | ||||
| KRP-203 | S1PR1, 5 | Novartis | UC | II | NCT01375179 | |
| SCLE | II | NCT01294774 | ||||
| Hematological malignancies | I | NCT01830010 | ||||
| ACT-128800 | Ponesimod | S1PR1, 3, 5 | Actelion | MS | III | NCT03232073 (OPTIMUM-LT) |
| Psoriasis | II | NCT01208090 | ||||
| ACT-334441 | Cerenimod | S1PR1, 5 | Actelion | SLE | II | NCT02472795 |
| APD334 | Etrasimod | S1PR1 | Arena Pharmaceuticals | UC | III | NCT03945188 |
| RPC1063 | Ozanimod | S1PR1, 5 | Receptos (Celgene) | Crohn | III | NCT03440372 |
| NCT03440385 | ||||||
| UC | III | NCT02435992 | ||||
| NCT02531126 | ||||||
| RMS | III | NCT02576717 | ||||
| ONO-4641 | Ceralifimod | S1PR1, 5 | Ono | RRMS | II | NCT01081782 (DreaMS) |
| MT-1303 | Amiselimod | S1PR1, 4, 5 | Mitsubishi Tanabe | RRMS | II | NCT01742052 |
| Crohn | II | NCT02389790 | ||||
| Psoriasis | II | NCT01987843 | ||||
| SLE | I | NCT02307643 | ||||
| AKP11 | S1PR1 | Akaal Pharma | Atopic dermatitis | II | ACTRN12617000763347 | |
| RA | II | ACTRN12617001223325 | ||||
| GSK-2018682 | S1PR1 | GlaxoSmithKline | RRMS | I | NCT01431937 (P1A114347) | |
| BMS-986104 | S1PR1 | Bristol-Myers Squibb | RA | I | NCT02211469 | |
| CS-0777 | S1PR1 | Daiichi Sankyo, Inc | MS | I | NCT00616733 | |
| LT1009 (Sonepcizumab) | ASOPNEP | S1P antibody | Lpath Inc / Pfizer | Renal cell carcinoma | II | NCT01762033 |
| iSONEP | AMD | II | NCT01414153 (Nexus) | |||
| ABC294640 | Opaganib (Yeliva®) | SphK2 | RedHill Biopharma Limited | Cholangiocarcinoma | II | NCT03377179 |
| Hepatocellular carcinoma | II | NCT02939807 | ||||
| Solid Tumor | I | NCT01488513 (ABC-101) | ||||
| DHS (L-threo-Dihydrosphingosine) | Safingol | SphK1 | MSKKC/NCI | Locally advanced or metastatic solid tumors | 1 | NCT00084812 |
| LX3305 | SPGL1 | Lexicon Pharmaceuticals | RA | II | NCT00903383 |