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.

1,1-DIETHYL-4-PHENYLHOMOPIPERAZINIUM (ASM-024), a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short-acting beta-2 agonists in dog and human bronchi. ASM-024 is able to activate the α7 nAChR channel opening in the presence of the positive allosteric modulator (PNU-120596), indicating that ASM-024 behaves as a ‘silent agonist’ that places the receptor in a desensitized state. Compounds with similar properties have been shown to induce signal transduction pathways independently of ion channel activation. ASM-024 has demonstrated an antagonist effect on ACH-evoked activation at the M1, M2 and M3 muscarinic receptors expressed in Xenopus oocytes. A comprehensive nonclinical safety program was conducted with ASM-024 including pharmacokinetic and metabolism studies, safety pharmacology studies, toxicology and genotoxicity studies. In all, seven clinical studies were completed to evaluate the safety, tolerability and clinical activity of ASM-024. Three Phase I and four Phase II clinical trials were conducted on healthy subjects and patients with mild allergic asthma, stable moderate asthma and subjects with COPD. Altogether, ASM-024 has been safely administered to more than 200 subjects via the oral and inhalation delivery, i.e. nebulized solution and dry powder inhalation. However, the outcome of two phase II pilot studies in patients failed to demonstrate sufficient efficacy of ASM-024 in asthma and COPD. Thus, further work on ASM-024 on pulmonary diseases was stopped. In light of the findings that ASM‐024 blocks both nicotinic and muscarinic receptor activation, it is believed that ASM-024 will be a potent inhibitor of cell growth. These properties may have the potential to reduce the development or progression of tumors expressing these receptors. Based on a greater knowledge of the unique pharmacological mechanisms of action of ASM-024 developed at Asmacure, Odan is exploring the potential therapeutic role of ASM-024 in the treatment of selected oncology diseases. These studies include the in vitro anti-proliferative properties against a panel of various cancer cell lines and the in vivo anti-tumor activity in selected mouse models. Overall, the most significant inhibitory effect on in vitro cell proliferation was observed on the following cell lines: human lung adenocarcinoma, breast cancer, brain neuroblastoma, prostate adenocarcinoma and malignant melanoma. Preliminary data from a mouse model of lung carcinoma (Lewis Lung Cancer) using a slow infusion delivery method that ASM-024 treatment reduces the size and number of tumor nodules in the lung. In addition the potential therapeutic synergism between ASM-024 with commonly used chemotherapeutic agents will be investigated. Cisplatin and the taxanes (e.g. paclitaxel or Taxol) are commonly used chemotherapeutic agents, but their use is limited by their toxicity rates and innate or acquired resistance to these drugs. The concomitant effect of ASM-024 and cisplatin or Taxol on the proliferation of tumor cells will be assessed in vitro and potentially in in vivo mouse models. In the long term, Odan will consider to pursue the development of ASM-024 in a solution formulation administered intravenously (IV) in conjunction with the commonly-used cancer chemotherapeutic agents, for the growth inhibition and possibly regression of tumors in cancer patients.

CG-200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed by CrystalGenomics, Inc for treatment of various hematological and solid cancers. Combinations of CG-200745 with SN38 (the active form of irinotecan), or oxaliplatin were more effective than the agents alone when used to inhibit the growth of HCT116 cells. The protein expressions of acetyl-H3, p21, caspase-3, -8, and -9, PARP, and XIAP were affected in a time- and dose-dependent manner in HCT116 cells treated with the CG-200745 alone or combined CG-200745 and SN-38. In HCT116 xenografts, the HDACI CG-200745 in combination with irinotecan dramatically inhibited tumor growth without showing additive toxicity.

GlaxoSmithKline was developing GSK-364735 as a human immunodeficiency virus (HIV) integrase inhibitor. The inhibition of viral DNA integration takes place by interacting at the two-metal binding site within the catalytic center of HIV integrase. GSK-364735 was successfully studied at Phase II in HIV-infected patients; however, adverse liver effects of GSK364735 were recently observed in a long-term preclinical safety study in the monkey and preclude further development of the compound.

A-689 (AZD-7295) was the lead compound from Arrow Therapeutics' second series of hepatitis C virus (HCV) NS5a inhibitors. AZD-7295 is a selective inhibitor of HCV NS5A within vitroantiviral activity of 7nM and 1.24mM against HCV genotype1b and 1a replicons respectively, with significant liver concentrationin preclinical studies. AZD-7295 was well tolerated at repeated doses ofup to 700 mg daily. AZD-7295 shows potent antiviral activity ingenotype 1b patients. Genotype 1a and genotype 3 patients showedno antiviral effects.

ACT-281959 (molecular weight 850.9 g/mol), the di-ester prodrug of ACT-246475 (molecular weight 618.6 g/mol), was developed to improve absorption after oral dosing and is rapidly converted by esterases in vivo to ACT-246475 in two-steps via the formation of ACT-409100 (molecular weight 734.7 g/mol), the mono-ester prodrug. ACT-281959 is a novel potent and selective P2Y12 receptor antagonist with a wider therapeutic window. ACT-281959 showed antithrombotic efficacy after oral administration in the rat ferric chloride model. ACT-281959 entered clinical studies in healthy volunteers. ACT-281959 had been in phase I clinical trials by Actelion for the treatment of thrombosis. But there is no development reported for this study recently.