Lumateperone (ITI-722/ITI-007) is a dual 5HT2A receptor antagonist/dopamine phosphoprotein modulator (DPPM) for the treatment of schizophrenia. It is an orally available compound which combines potent 5HT2A receptor antagonism with cell-type-specific modulation of phosphoprotein pathways downstream of dopamine receptors. Lumateperone was developed by Intra-Cellular Therapies, Inc., and is being evaluated for the treatment of schizophrenia and bipolar depression. In 3 efficacy studies in patients with acute schizophrenia, lumateperone was well-tolerated with a favorable safety profile, and in 2 studies of 3 demonstrated significantly superior efficacy over placebo.

Pitolisant (INN) or tiprolisant (USAN) is a histamine receptor inverse agonist/antagonist selective for the H3 subtype. It has stimulant and nootropic effects in animal studies and may have several medical applications, having been researched for the treatment of narcolepsy, for which it has been granted orphan drug status in the EU and US. It is currently in clinical trials for schizophrenia and Parkinson’s disease. Pitolisant hydrochloride was approved by European Medicine Agency (EMA) on Mar 31, 2016. It was developed and marketed as Wakix® by Bioprojet in EU. Wakix® is available as the tablet for oral use, containing 4.5 mg and 18 mg of Pitolisant hydrochloride. The initial dose of 9 mg (two 4.5 mg, tablets) per day, and it should be used at the lowest effective dose, depending on individual patient response and tolerance, according to an up-titration scheme, without exceeding the dose of 36 mg/day. Pitolisant was the first clinically used H3 receptor inverse agonist.

Selinexor (KPT-330) is a first in class XPO1 antagonist being evaluated in multiple later stage clinical trials in patients with relapsed and/or refractory hematological and solid tumor malignancies.

Tenapanor is an inhibitor of the sodium-proton (Na(+)/H(+)) exchanger NHE3 and reduces sodium absorption in the GI tract, thus increasing intestinal fluid. Ardelyx has completed Phase 3 development of tenapanor for the treatment of irritable bowel syndrome with constipation (IBS-C) and submitted a new drug application to the U.S. Food and Drug Administration for the treatment of patients with IBS-C. In addition, tenapanor successfully completed phase III clinical trial for the treatment of hyperphosphatemia in people with end-stage renal disease who are on dialysis and RDX013, a potassium secretagogue program for the potential treatment of high potassium, or hyperkalemia, a problem among certain patients with kidney and/or heart disease.

LEFAMULIN is a pleuromutilin antibiotic under development for the treatment of community-acquired bacterial pneumonia, as well as acute bacterial skin and skin structure infections. It inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosome, resulting in the cessation of bacterial growth.

Ubrogepant, a small molecule drug, is being developed by Merck & Co for the treatment of migraine. The calcitonin gene-related peptide receptor (CGRP) antagonist is administered orally as a film coated tablet. Ubrogepant is a competitive antagonist with high affinity, potency, and selectivity for the human CGRP receptor. In the four clinical studies (ACHIEVE I, ACHIEVE II, UBR-MD-04 and 3110-105-002) ubrogepant demonstrated efficacy, safety and tolerability in the acute treatment of migraine among a broad patient population, including those who had an insufficient response to a triptan or those patients in whom triptans were contraindicated, as well as in patients who had moderate to severe CV risk profile.

Upadacitinib (ABT-494) is a Janus kinase 1 (JAK1) inhibitor currently being developed by AbbVie for the treatment of rheumatoid arthritis (RA), Crohn’s disease, ulcerative colitis, atopic dermatitis, and psoriatic arthritis. It is also being investigated as a potential treatment for people with active ankylosing spondylitis (AS). Currently, upadacitinib is being evaluatedin six global phase III studies in RA and twophase III studies in psoriatic arthritis (PsA), inaddition to phase II studies in Crohn’s disease and atopicdermatitis and a combined phase II/III study inulcerative colitis. Upadacitinib is a potent and selective Janus kinase (JAK) 1 inhibitor with an IC50 of 43 nM.

LASMIDITAN is a serotonin (5-HT) receptor agonist without vasoconstrictor activity, which selectively binds to the 5-HT(1F) receptor subtype. It is under development for the treatment of migraine.

Fedratinib (SAR-302503, TG-101348) is a selective small-molecule inhibitor of Janus kinase-2. Fedratinib demonstrated therapeutic efficacy in a murine model of myeloproliferative disease. Sanofi was developing Fedratinib for the treatment of myeloproliferative diseases and solid tumors. The clinical development of fedratinib was terminated after reports of Wernicke's encephalopathy in myelofibrosis patients.

Pexidartinib (PLX3397) is a small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Pexidartinib binds to and inhibits phosphorylation of stem cell factor receptor (KIT), colony-stimulating factor-1 receptor (CSF1R) and FMS-like tyrosine kinase 3 (FLT3), which may result in the inhibition of tumor cell proliferation and down-modulation of macrophages, osteoclasts and mast cells involved in the osteolytic metastatic disease. FDA has granted Breakthrough Therapy Designation to pexidartinib (PLX3397) for the treatment of tenosynovial giant cell tumor (TGCT) where surgical removal of the tumor would be associated with potentially worsening functional limitation or severe morbidity. In addition to Breakthrough Therapy Designation, pexidartinib (PLX3397) has been granted Orphan Drug Designation by FDA for the treatment of pigmented villonodular synovitis (PVNS) and giant cell tumor of the tendon sheath (GCT-TS). It also has received Orphan Designation from the European Commission for the treatment of TGCT.