Locus Pharmaceuticals, Inc. is a world leader in computational drug design. Since beginning operations in 2000, Locus has developed and evolved unique and potentially transformational capabilities for the in silico design and optimization of small molecule drugs. These proprietary computational approaches are combined with in-house expertise in chemistry, biology and crystallography to create a fully integrated drug discovery platform. Locus believes that its capabilities offer the potential to substantially lower the cost of drug discovery and greatly increase the speed of advancing novel therapies to clinical trials and, ultimately, to the market.

Locus had its beginnings at the Sarnoff research laboratories in Princeton, NJ. In 2001, the company moved its headquarters to Blue Bell, in the Philadelphia suburbs, where it built chemistry laboratories and a 2.3 tera-flop Linux-based supercomputer cluster, one of the largest civilian supercomputers in the United States. Locus in privately held and has approximately 40 employees.

“For Locus, the Philadelphia area provides a rich infrastructure of world-class academic collaborators, major pharmaceutical partners and a technically sophisticated workforce for our unique needs in the fields of computational and medicinal chemistry, molecular biology and drug development,” said Dr. H. Joseph Reiser, chairman and CEO.

Locus is developing oral drug therapies to address major unmet medical needs, principally in cancer and inflammation. Locus expects to file its first Investigational New Drug (IND) Application in 2005, for an oral cancer compound that targets resistant tumors.  Over the next eighteen months two additional INDs are planned, one in inflammation and a second in cancer. Locus has earlier stage pipeline programs in kinase-related disease areas, macular degeneration and AIDS/HIV. All of the Company's development programs emanate from its computational technology and are wholly owned by the company.

Based on this portfolio, Locus has evolved a strong and comprehensive intellectual property foundation.

Development Programs

Anti-Mitotic Program (Oncology). This is the Company’s most advanced program. Its lead compound, LP-261, is active against resistant cell lines and potentially blocks tumor growth both through anti-mitotic and anti-angiogenic mechanisms of action. LP-261 has novel pharmacology via a clinically validated target and induces regression in preclinical animal models by oral administration. Locus expects to file an IND by the end of 2005.

Onco-Kinase Program (Oncology). Because of the ability of cancer cells to develop resistance to single-target agents, Locus has created multi-kinase inhibitors that block several key growth (e.g. angiogenic) stimulation pathways simultaneously. This approach has also shown strong tumor regression when orally-dosed in preclinical animal models and may provide an effective combination therapy. Locus expects to begin IND-directed activities in 2005 and file an IND in 2006.

p38 Program (Inflammation). Using its computational capabilities, Locus has created exquisitely selective, highly potent and orally-active p38 inhibitors that are unique in targeting only an allosteric binding site rather than the ubiquitous ATP site that other drug developers target. Allosteric sites may offer an improved safety profile as well as provide a dual mode of action. The area of inflammation represents a vast market opportunity with high clinical need. Locus expects to begin IND-directed activities in 2005 and file an IND in 2006.

Locus’ Technology

Locus addresses the two key technical challenges in computational drug design. Locus has (1) the only practical means to rapidly and accurately predict drug potency, and (2) the ability to model protein motion. Locus believes it has a three to five year lead over others in its field.

Locus starts with a protein crystal structure and its in silico library of 40,000 molecular fragments derived from compounds in the world drug index. Then, using one of the world’s largest Linux-based supercomputer clusters, Locus computationally maps relevant ligand binding sites on protein targets, computes ligand-protein interactions and simultaneously optimizes for ADMET properties. Locus creates and evaluates custom-built, project specific ‘virtual libraries’ of candidate ligands ranging from 750 million to over 1 billion potential compounds, exceeding the size of physical screening libraries by orders of magnitude.

Using its suite of computational tools, Locus can model physically realistic long-range timescales of protein motion and then uniquely combine accuracy and speed to evaluate ligand-protein binding potency. Locus’ protein motion simulations of up to 150 nsec are 10 times longer than other approaches, allowing for the identification of structures not available by crystallography and providing insights into protein function. Locus can compute binding potencies in almost real time and, in a typical design effort, 75% of the compounds physically synthesized have the predicted potency. In comparison, other computational methods with similar speed would be successful with, at best, 10% of the compounds actually synthesized, while approaches with similar accuracy are 10,000 times slower. Locus typically needs to synthesize only hundreds of compounds from its virtual libraries to generate highly potent, orally-active lead molecules.

Greater chemical diversity, design flexibility and biological relevance allow Locus to design compounds with optimal ligand-protein interactions. Moreover, compound diversity can “open up” novel patent space, which can allow for the expansion of a drug franchise into future generations or provide the ability to design around an existing composition of matter patent. This broadly applicable and proprietary technology platform is Locus’ pipeline engine for future growth.

During 2005, Locus has transitioned into a high value IND directed company. Using its cutting edge computational technology, Locus is forging a new paradigm in drug discovery and development to accelerate the process of bringing novel therapies to patients.