Siponimod (BAF312) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. The S1P receptor is commonly found on the surface of specific cells residing in the central nervous system (CNS), that are responsible for causing CNS damage that drives loss of function in secondary progressive multiple sclerosis (SPMS). Siponimod (BAF312) enters the brain and by binding to these specific receptors, may prevent the activation of these harmful cells, helping to reduce the loss of physical and cognitive function associated with SPMS.

Cenobamate (also known as YKP3089) is a small molecule sodium channel blocker in development for the treatment of partial-onset seizures in adult patients. In mice and rats, Cenobamate displayed an anticonvulsant activity in the maximal electroshock test and prevented seizures induced by chemical convulsants such as pentylenetetrazol and picrotoxin. In addition, Cenobamate was reported to be effective in two models of focal seizure, the hippocampal kindled rat and the mouse 6 Hz psychomotor seizure models. Two completed adequate and well-controlled clinical studies demonstrated a significant reduction in focal seizures with Cenobamate in patients with epilepsy, and a long-term open-label phase 3 safety clinical trial is currently ongoing. Cenobamate is considered a new generation antiepileptic therapy and clinical trials have shown that it may be more effective and safer than existing drugs. If licensed, Cenobamate will offer a new adjunctive treatment option for patients with partial focal epilepsy.

Binimetinib (MEK162) is an oral small-molecule with potential antineoplastic activity. It is a selective mitogen-activated protein kinase 1 and 2 (MEK1/2) inhibitor, a key protein kinase in the RAS/RAF/MEK/ERK pathway, which regulates several key cellular activities including proliferation, differentiation, migration, survival and angiogenesis. Inappropriate activation of this pathway has been shown to occur in many cancers, in particular through mutations in BRAF, KRAS and NRAS. MEK162 at 6 mg/kg, BID combined with BEZ235 (dual PI3K/mTOR inhibitor) resulted in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells. There are three ongoing Phase 3 trials with binimetinib in advanced cancer patients: NEMO (NRAS-mutant melanoma), COLUMBUS (encorafenib in combination with binimetinib in BRAF-mutant melanoma) and BEACON CRC (encorafenib, binimetinib and cetuximab in BRAF-mutant colorectal cancer).

Revefenacin (trade name Yupelri is a long-acting muscarinic antagonist developed by Mylan Ireland ltd for the treatment of chronic obstructive pulmonary disease (COPD). It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo models, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours.

Lutetium Lu 177 dotatate binds to somatostatin receptors with highest affinity for subtype 2 receptors (SSRT2). Upon binding to somatostatin receptor expressing cells, including malignant somatostatin receptor-positive tumors, the compound is internalized. The beta emission from Lu 177 induces cellular damage by formation of free radicals in somatostatin receptor-positive cells and in neighboring cells. LUTATHERA® (lutetium Lu 177 dotatate) is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults.

Eravacycline, known as Xerava by Tetraphase Pharmaceuticals, is a fully synthetic fluorocycline antibiotic of the tetracycline class with activity against clinically significant gram-negative, gram-positive aerobic, and facultative bacteria. This includes most of those bacteria resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug-resistant strains, and carbapenem-resistant Enterobacteriaceae, and the majority of anaerobic pathogens. It was first approved by the FDA on August 27, 2018. Eravacycline disrupts bacterial protein synthesis by binding to the 30S ribosomal subunit thus preventing the incorporation of amino acid residues into elongating peptide chains.

Stiripentol is an anticonvulsant drug used in the treatment of epilepsy. It recently proved to increase the GABAergic transmission in vitro in an experimental model of immature rat. Clinical studies were based on the fact that STP also acts as an inhibitor of CYP3A4, CYP1A2, and CYP2C19 in vivo in epileptic patients. Side effects are largely due to the increase in plasma concentrations of other anticonvulsants and can be reduced by lowering the dose of those drugs. Nausea and vomiting are particularly noted when used in combination with sodium valproate. It appears to increase the potency of phenobarbital, primidone, phenytoin, carbamazepine, clobazam and diazepam.

Amifampridine (Firdapse), currently approved in the European Union, is the first and only approved drug for the symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS) in adults, a rare autoimmune disease with the primary symptoms of muscle weakness. In LEMS, the body’s own immune system attacks connections between nerves and muscles and disrupts the ability of nerve cells to send signals to muscle cells. Amifampridine blocks voltage-dependent potassium channels, thereby prolonging pre-synaptic cell membrane depolarization. Prolonging the action potential enhances the transport of calcium into the nerve ending. The resulting increase in intracellular calcium concentrations facilitates exocytosis of acetylcholine containing vesicles, which in turn enhances neuromuscular transmission. Amifampridine phosphate has been granted Orphan Drug Designation and Breakthrough Therapy designation by the FDA for the treatment of Lambert-Eaton Myasthenic Syndrome (LEMS).

Tecovirimat (ST-246) is a low-molecular-weight compound (molecular weight = 376), that is potent (concentration that inhibited virus replication by 50% = 0.010 microM), selective (concentration of compound that inhibited cell viability by 50% = >40 microM), and active against multiple orthopoxviruses, including vaccinia, monkeypox, camelpox, cowpox, ectromelia (mousepox), and variola viruses. The antiviral activity is specific for orthopoxviruses and the compound does not inhibit the replication of other RNA- and DNA-containing viruses or inhibit cell proliferation at concentrations of compound that are antiviral. ST-246 targets vaccinia virus p37, a viral protein required for envelopment and secretion of extracellular forms of virus. The compound is orally bioavailable and protects multiple animal species from lethal orthopoxvirus challenge. rug substance and drug product processes have been developed and commercial scale batches have been produced using Good Manufacturing Processes (GMP). Human phase I clinical trials have shown that ST-246 is safe and well tolerated in healthy human volunteers. Based on the results of the clinical evaluation, once a day dosing should provide plasma drug exposure in the range predicted to be antiviral based on data from efficacy studies in animal models of orthopoxvirus disease.

Enasidenib, aslo known as AG-221 and CC-90007, is a potent and selective IDH2 inhibitor with potential anticancer activity (IDH2 = Isocitrate dehydrogenase 2). The mutations of IDH2 present in certain cancer cells result in a new ability of the enzyme to catalyze the NAPH-dependent reduction of α-ketoglutarate to R(-)-2-hydroxyglutarate (2HG). The production of 2HG is believed to contribute to the formation and progression of cancer. The inhibition of mutant IDH2 and its neoactivity is therefore a potential therapeutic treatment for cancer. Enasidenib is an orally available, selective, potent inhibitor of the mutated IDH2 protein, making it a highly targeted investigational medicine for the potential treatment of patients with cancers that harbor an IDH2 mutation. Enasidenib has received orphan drug and fast track designations from the U.S. FDA. Enasidenib mesylate is in phase II clinical trials for Solid tumours and phase III clinical trials for the treatment of acute myeloid leukaemia.