OC-459 is a highly potent and selective CRTH2 antagonist which is active on both the recombinant and native human receptor. The Atopix lead compound OC-459 is effective in improving lung function and symptoms in patients with atopic eosinophilic asthma. This group represents 40-50% of all asthmatics and the magnitude of improvement in the responder population is equivalent to high dose inhaled corticosteroids. OC-459 has also been shown to reduce both nasal and eye symptoms in allergic subjects exposed to grass pollen. Of particular interest is the ability of OC-459 to reduce the rate of respiratory infections, an effect related to reduction in Th2 immunity which has a damaging effect on host defence. OC-459 has also demonstrated an excellent safety profile in around 800 subjects exposed drug and no safety issues have been highlighted in long term toxicology. OC-459 is in Phase 2 clinical trial in patients with moderate to severe atopic dermatitis.

TAK-875 (Fasiglifam) is the potent, selective and orally bioavailable GPR40 agonist. The drug was in Phase III clinical trials for the treatment of type 2 diabetes mellitus. Termination phase III development of TAK-875 for the potential treatment of type-2 diabetes mellitus was announced in 2013 due to concerns about liver safety.

Rapastinel (formerly known as GLYX-13) is an investigational intravenous formulation of a novel NMDA receptor partial agonist, which is being evaluated for adjunctive treatment of Major depressive disorder, and has shown a rapid onset of antidepressant efficacy 1 day after a single dose in a Phase 2 clinical trial of patients with Major depressive disorder who had an inadequate response to one or more antidepressants. No psychotomimetic or hallucinogenic side effects were observed with rapastinel. Few adverse events were reported by 5% or more of subjects and these were rated as mild or moderate. These included headache, somnolence, dizziness, dysgeusia, and fatigue. On January 29, 2016, Allergan (who acquired Naurex in July 2015) announced that rapastinel had received Breakthrough Therapy designation from the U.S. FDA for adjunctive treatment of major depressive disorder.

Pterostilbene is a naturally derived compound found primarily in blueberries and Pterocarpus marsupium heartwood. The multiple benefits of pterostilbene in the treatment and prevention of human disease have been attributed to its antioxidant, anti-inflammatory, and anti-carcinogenic properties leading to improved function of normal cells and inhibition of malignant cells. The antioxidant activity of pterostilbene has been implicated in anti-carcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. Pterostilbene increases LDL and reduces blood pressure in adults. Low doses of pterostilbene seem to hold some benefit for cognition.

Rigosertib sodium (ON 01910.Na) is a small molecule inhibitor of critical pathways important in the growth and survival of cancer cells, being developed by Onconova Therapeutics ("Onconova") for the treatment of hematologic malignancies and solid tumors. Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Extensive Phase I and Phase II studies with rigosertib have been conducted at leading institutions in the U.S. and abroad in more than 450 patients with solid tumors and hematological cancers, including MDS and AML. MDS and AML are blood disorders widely recognized as difficult to manage, with limited therapeutic options available for patients, especially those with drug-resistant disease. The multi-site Phase III ONTIME trial in MDS patients is under a Special Protocol Assessment (SPA) from the U.S. FDA and is being supported by an award from the Therapeutics Acceleration Program (TAP) of the Leukemia and Lymphoma Society (LLS). FDA has granted Orphan Drug Designation for the use of rigosertib in MDS. The clinical program in solid tumors is also advancing with initiation of the Phase II/III combination ONTRAC trial (ON 01910.Na TRial in Patients with Advanced Pancreatic Cancer) and Phase II single agent trial in ovarian cancer. In Japan, SymBio is developing rigosertib for the treatment of refractory/relapsed HR-MDS (IV form) and first-line LR-MDS (oral form).

AZD-4547 is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. FGFR inhibitor AZD4547 binds to and inhibits FGFR, which may result in the inhibition of FGFR-related signal transduction pathways, and, so, the inhibition of tumor cell proliferation and tumor cell death. FGFR, up-regulated in many tumor cell types, is a receptor tyrosine kinase essential to tumor cellular proliferation, differentiation and survival. AZD-4547 is a selective FGFR inhibitor targeting FGFR1/2/3 with IC50 of 0.2 nM/2.5 nM/1.8 nM in cell-free assays, weaker activity against FGFR4, VEGFR2 (KDR), and little activity observed against IGFR, CDK2, and p38. Compared to FGFR1-3, AZD-4547 displays weaker activity against FGFR4 with IC50 of 165 nM. AZD-4547 only inhibits recombinant VEGFR2 (KDR) kinase activity with IC50 of 24 nM, in the in vitro selectivity test against a diverse panel of representative human kinases. AZD-4547 is under clinical investigation for the treatment of FGFR-dependent tumors. It is in phase II clinical studies for the treatment of breast cancer; gastric cancer; lung cancer; oesophageal cancer and in phase II/III clinical studies for the treatment of non-small cell lung cancer.

Tirasemtiv is a fast skeletal troponin activator and is a candidate amyotrophic lateral sclerosis (AML) therapeutic. It is a small molecule that enhances the signals between motor neurons and neuromuscular junctions. Tirasemtiv increases muscle strength by amplifying the response of muscle when neuromuscular input is diminished secondary to a neuromuscular disease. Tirasemtiv selectively binds to the fast skeletal troponin complex, thus slowing down the rate of calcium release from troponin C and sensitizing muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards as does the force-frequency relationship of a nerve-muscle pair.

Galeterone (TOK-001, formerly called VN/124-1) is a potent anti-androgen with three modes of action. The compound acts as a specific androgen receptor antagonist, inhibits CYP17 lyase while conserving CYP17 hydroxylase function, and decreases overall androgen receptor levels in prostate cancer cells. Galeterone is a first in class, multi-targeted small-molecule drug that disrupts the growth and survival of prostate cancer cells. Tokai Pharmaceuticals is developing galeterone as an oral treatment for castration-resistant prostate cancer. Phase III clinical development of galeterone is underway in the US, Canada, Australia, Western Europe, Spain and the United Kingdom.

Encenicline (EVP-6124; MT-4666) acts as a potent partial and selective agonist at alpha-7 nicotinic acetylcholine receptor. Encenicline significantly improved memory function in animal models. FORUM Pharmaceuticals (formerly EnVivo Pharmaceuticals) is developing encenicline for the treatment of cognition disorders such as schizophrenia and for Alzheimer's disease.

Peficitinib (formerly known as ASP015K) is a pyrrolo[2,3-b]pyridine derivative orally administered once-daily JAK inhibitor in development for the treatment of Rheumatoid Arthritis. In preclinical studied Peficitinib inhibited JAK1 and JAK3 with IC50 of 3.9 and 0.7 nM, respectively. Peficitinib also inhibited IL-2-dependent T cell proliferation in vitro and STAT5 phosphorylation in vitro and ex vivo. Furthermore, Peficitinib dose-dependently suppressed bone destruction and paw swelling in an adjuvant-induced arthritis model in rats via prophylactic or therapeutic oral dosing regimens.In clinical trials, Peficitinib treatment prescribed at 50, 100 and 150 mg amounts each showed statistically significantly higher ACR20 response rates compared to the placebo and response rates increased up to the 150 mg dosage. Adverse events included neutropenia, headache, and abdominal pain. The treatment-emergent adverse events occurring more frequently in the Peficitinib group compared with the placebo group included diarrhea, nasopharyngitis, and increased serum creatine phosphokinase activity. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in the peficitinib 25 and 100 mg cohorts). The authors concluded that treatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed an acceptable safety profile.