PBT-1033, also known as PBT-2, is a neural protective agent potentially for the treatment of Alzheimer's disease and Huntington's Disease. PBT-1033 is a moderate-affinity 8-hydroxyquinoline transition metal-ligand that acts as a synthetic chaperone, re distributing copper, zinc, and iron from locations where they are abundant to subcellular locations where they might be deficient. Delivery of copper and zinc by PBT-1033 into the cytoplasm deactivates the kinase glycogen synthase kinase 3β and the phosphatase calcineurin, both potential targets for Huntington’s disease. In aged wild-type mice, PBT-1033 improves cognitive ability and markers of neuronal plasticity and function. In Alzheimer’s disease mouse models, PBT-1033 inhibits the accumulation of amyloid β, attenuates neuropathological effects of amyloid β, including amyloid-β-induced hyperphosphorylation of tau, and improves cognition. In a 12-week, phase 2a, randomized, double-blind, placebo-controlled trial in 78 individuals with mild Alzheimer’s dementia, PBT-1033 was safe and well tolerated and significantly reduced concentrations of amyloid β42 in CSF.

DA-6886 is an antagonist of the 5-HT4 receptor, discovered by the Korean Dong-A ST Research Institute. The drug binds with high activity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5 and 7.9 for the human 5-HT4a, 5-HT4b, and 5-HT4d, respectively. DA-886 induced relaxation of the rat esophagus preparation in a 5-HT4 receptor antagonist-sensitive manner. In the normal ICR mice, oral administration of the drug at 0.4 and 2 mg/kg resulted in a marked stimulation of colonic transit. DA-6886 was investigated in phase I clinical trial for the treatment of Irritable Bowel Syndrome.

Lisavanbulin, also known as BAL-101553, a prodrug of the molecule BAL-27862 with potential antitumor activity. BAL-27862 binds to tubulin, prevents tubulin polymerization, destabilizes microtubules, arrests tumor cell proliferation, and induces cell death in cancer cells. Lisavanbulin participated in phase II clinical trials for the treatment of advanced solid tumors. Besides, the drug participates in a 1/2a clinical study in patients with recurrent glioblastoma and in patients with platinum-resistant or refractory ovarian cancer. In this study, will be characterized the safety and tolerability and to obtain efficacy data in these selected cancer types.

Fluorocyclopentenylcytosine (RX-3117) is a novel small molecule nucleoside compound that is incorporated into DNA or RNA of cancer cells and inhibits both DNA and RNA synthesis which induces apoptotic cell death of tumor cells. Fluorocyclopentenylcytosine also mediates the down-regulation of DNA methyltransferase 1 (DNMT1), an enzyme responsible for the methylation of cytosine residues on newly synthesized DNA and also a target for anticancer therapies. Preclinical studies have shown Fluorocyclopentenylcytosine to be effective in both inhibiting the growth of various human cancer xenograft models, including colon, lung, renal and pancreas, as well as overcoming chemotherapeutic drug resistance. Fluorocyclopentenylcytosine has demonstrated a broad spectrum anti-tumor activity against 50 different human cancer cell lines and efficacy in 12 different mouse xenograft models. The efficacy in the mouse xenograft models was superior to that of gemcitabine. In addition, in human cancer cell lines made resistant to the anti-tumor effects of gemcitabine, Fluorocyclopentenylcytosine still retains its full anti-tumor activity. In August 2012, Rexahn reported the completion of an exploratory Phase I clinical trial of Fluorocyclopentenylcytosine in cancer patients conducted in Europe, to investigate the oral bioavailability, safety and tolerability of the compound. In this study, oral administration of Fluorocyclopentenylcytosine demonstrated an oral bioavailability of 34-58% and a plasma half-life (T1/2) of 14 hours. In addition, Fluorocyclopentenylcytosine was safe and well tolerated in all subjects throughout the dose range tested. Fluorocyclopentenylcytosine is in phase I/II clinical trials by Rexahn for the treatment of bladder cancer and pancreatic cancer. This compound was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with pancreatic cancer in September 2014.

KX-02 is a compound demonstrating dual inhibitory activity against Src kinase and tubulin polymerization. It readily crosses the blood-brain-barrier in mice. It is under development for the treatment of solid tumors.

F2BMET (redaporfin or LUZ11), a fluorinated sulfonamide bacteriochlorin, is photosensitizer, with antineoplastic activity upon photodynamic therapy. F2BMET is a third generation bacteriochlorin molecule which has a greater ability to absorb light and convert it into active molecular species (reactive oxygen species), better depth penetration, and improved efficacy. F2BMET has promising Phase I/IIA POC clinical data in advanced head and neck cancer which clearly reinforces the favorable results from non-clinical studies. It has received Orphan Drug Designation (ODD) from EMA in Europe for Biliary tract cancer.

ETC-159 (ETC-1922159) is an inhibitor of membrane-bound O-acyltransferase porcupine. Porcupine palmitoleates Wnt and this modification is essential for binding to chaperone WLS and Frizzled receptors and is therefore required for the activity of all Wnts. ETC-159 exerts antineoplastic properties both in vitro and in vivo due to inhibition of Wnt pathway. ETC-159 development has progressed to phase I clinical trial.