Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Stavudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. Stavudine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. Stavudine is used for the treatment of human immunovirus (HIV) infections. Stavudine is sold under the brand name Zerit among others.

CMX157 is a lipid (1-0-hexadecyloxypropyl) conjugate of the acyclic nucleotide analog tenofovir (TFV) with activity against both wild-type and antiretroviral drug-resistant HIV strains, including multidrug nucleoside/nucleotide analog-resistant viruses. CMX157 was designed to mimic lysophosphatidylcholine to take advantage of natural lipid uptake pathways and to achieve high intracellular concentrations of the active antiviral, with the aim of increasing the effectiveness of TFV against wild-type and mutant HIV. CMX157 demonstrated potential to effectively suppress replication of multiNRTI-resistant (MNR) HIV that cannot be treated with any currently available NRTIs, including TDF. It is in phase II clinical trial for HIV infections in USA and phase Ib portion of the phase I/II trial for Hepatitis B in Thailand (PO).

CMX157 is a lipid (1-0-hexadecyloxypropyl) conjugate of the acyclic nucleotide analog tenofovir (TFV) with activity against both wild-type and antiretroviral drug-resistant HIV strains, including multidrug nucleoside/nucleotide analog-resistant viruses. CMX157 was designed to mimic lysophosphatidylcholine to take advantage of natural lipid uptake pathways and to achieve high intracellular concentrations of the active antiviral, with the aim of increasing the effectiveness of TFV against wild-type and mutant HIV. CMX157 demonstrated potential to effectively suppress replication of multiNRTI-resistant (MNR) HIV that cannot be treated with any currently available NRTIs, including TDF. It is in phase II clinical trial for HIV infections in USA and phase Ib portion of the phase I/II trial for Hepatitis B in Thailand (PO).

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.