May 19 2008
LIUS Molecular Design is pleased to announce that it has successfully created two antipsychotic drug candidates with third party confirmation of predicted biological activities via in vitro testing.
The two drug candidates are the first to have been designed, synthesized and tested based upon knowledge obtained from spectral analysis of known antipsychotics. LMD's patented Spectral Modeling technology employs a methodology of computer modeling and mathematical techniques based on spectral analysis to predict the biological properties of molecules on crucial parameters relevant to drug action in humans, such as receptor affinities.
LMD, in collaboration with Dr. Herbert Y. Meltzer, an internationally-recognized expert in schizophrenia, has been using proprietary in silico Spectral Modeling techniques to create a bank of antipsychotic drug candidates designed to have similar or better effectiveness than available antipsychotic drugs, but without certain antipsychotic-associated harmful side effects. These side effects include weight gain and agranulocytosis (an acute blood disorder characterized by a reduction in white blood cells which is a serious side effect of antipsychotics as well as other drug classes).
The goal of the spectral analysis was to produce molecules which are more potent serotonin 2A than dopamine D2 receptor antagonists (the profile of the most widely used antipsychotics: quetiapine, risperidone, olanzapine and ziprasidone). Two of LMD's antipsychotic drug candidates were synthesized and tested for these affinities and they were not only shown to have the expected ratio of activities, but they were almost exactly the absolute affinities predicted by spectral analysis. These agents are now being tested in vivo to confirm their antipsychotic activity, but as this profile has great predictive validity for antipsychotic action, it is expected that the results in tests such as blockade of amphetamine-induced locomotor activity or conditioned avoidance response will be positive.
The complete bank of antipsychotic drug candidates, including the two confirmed antipsychotic candidates, is available to be out-licensed to pharmaceutical companies for further development.
Dr. Bill W. Massey, President of LMD, said: "Spectral Modeling is a highly accurate, lead generation and characterization technology. We have created a bank of antipsychotic compounds, which is the first of many targets we are pursuing where the unmet medical need is great. While we have already synthesized and have in vitro confirmation of two compounds as having the desired receptor affinities, we have a number of other antipsychotic candidates that should also have the desired profile according to our predictive models."
"Each of the compounds we generate for out-license, or existing compounds we modify as a service, is designed to exhibit the desired attributes. It is also important to note that only human data was used in this program which should improve accuracy in predicting the clinical profile of these drug candidates by eliminating interspecies differences. The ability to predict toxicities not usually found until much further in clinical development can save drug companies hundreds of millions of dollars on compounds that would never receive FDA approval or gain market acceptance."
"To put this achievement in perspective, Spectral Modeling has thus far shown a success rate of 100%, whereas the current industry practices success rate ranges from 0.01 % to 0.001 %. The entire program was also completed in only six months as compared with the typical five to seven year period of current industry practices. This accomplishment substantiates the Spectral Modeling technology as having significant commercial value in the drug development arena."
"Since Spectral Modeling is not based on chemical structure, LMD has been able to create new antipsychotic drug candidates that are structurally unrelated to existing antipsychotics, but have receptor binding profiles indicative of atypical antipsychotic activity. During this program, a number of significant achievements were also made including the first predictive models for agranulocytosis and antipsychotic-associated weight gain. These models also expand the range of phenomena that can be used by Spectral Modeling beyond experimental data to include human epidemiological and clinical data."
In addition to receptor-binding affinities, Spectral Modeling can be used to predict chemical reactivity, carcinogenicity, biological activity, toxicity, metabolism, absorption, and chemical and physical properties.
Dr. Herbert Meltzer, award-winning Professor of Psychiatry and of Pharmacology at the Vanderbilt University School of Medicine, commented: "The pharmaceutical industry continues to make a huge effort to develop novel drugs, many of which are based upon already known receptor profiles but the pipeline is far from full. Being able to design multiple novel putative antipsychotic compounds with a number of desired attributes within a matter of mere months is indicative of the power of Spectral Modeling. If future clinical testing shows that the compounds which results from Spectral Modeling methodology lack side effects such as adverse metabolic side effects and agranulocytosis, it is reasonable to conclude that LIMTUS Molecular Design's success in this class of agents can do the same for other unmet needs in many fields of medicine where there are effective agents whose structures can be subjected to Spectral Modeling."
LMD is a wholly owned subsidiary of LIUS LLC, a leading global technology innovations company. Currently, LMD has a number of predictive models that are accurate across drug classes. Additional models can be developed for other activities upon request or in collaboration. LMD has a unique business model based on designing new series of drug candidates for unmet medical needs every 3 to 4 months that can then be out licensed to pharmaceutical companies for development. In addition, LMD offers consulting and evaluation services to the pharmaceutical industry.
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