Maxim Announces Initiation of New Apoptosis Screening Campaign and Publication of Manuscript in Journal of Medicinal Chemistry
Maxim Pharmaceuticals, Inc. (NASDAQ:MAXM)(SSE:MAXM) announced today the initiation of a new screening campaign using approximately 60,000 compounds recently acquired for its compound library to identify potential new anticancer agents and novel molecular targets for inducing apoptosis in cancer cells. As with other compounds in Maxim's library, the new compounds are not subject to any financial or legal restrictions aside from the cost of purchase. By synthesis of analogs of the initial hit to improve potency and other pharmacologic properties, Maxim establishes a broad and proprietary intellectual property position on any potential lead compound candidate. The Company has already identified four novel potential cancer drug candidates from prior screening activities. The most advanced of the lead compounds has entered the clinical development through a partnership with Myriad Genetics, and the others are expected to move into the clinic over the next 12 to 18 months, either independently or through additional collaborations.
Maxim further reported today the recent publication of a manuscript in the Journal of Medicinal Chemistry (J. Med. Chem. 2004, 47: pp. 6299-6310), describing Maxim's discovery of a series of 4-aryl-4H-chromenes as potent apoptosis inducers and microtubule inhibitors with vascular targeting activity as shown in preclinical models. The manuscript described the application of Maxim's novel live cell high-throughput caspase-3 screening technology for the identification of 4-aryl-4H-chromenes as potent apoptosis inducers, as well as the application of this platform for structure-activity relationship (SAR) studies and lead optimization, which resulted in the discovery of potent apoptosis inducers and microtubule inhibitors with vascular targeting activity.
These results further validate Maxim's cell-based caspase activation assay as a powerful tool for the discovery of potent apoptosis inducers, and suggest that the 4-aryl-4H-chromenes, exemplified by MX2407 (previously known as MX116407), with strong antitumor activity in pre-clinical in vitro and in vivo studies as reported previously, have the potential to be developed into future anticancer therapeutics.
"Our technology and approach for the discovery of apoptosis modulating compounds and targets continues to prove itself as an exciting means to identify potential new therapeutic candidates and molecular targets for the treatment of cancer," stated Ben Tseng, Ph.D., Vice President, Research of Maxim Pharmaceuticals. "We are progressing to bring multiple cancer drug candidates forward from this pipeline generating process now well established at Maxim."
Maxim Apoptosis Modulator Discovery Platform
Cancer is a group of diseases characterized by uncontrolled cellular growth (e.g., tumor formation). One reason for unchecked growth in cancer cells is the disabling, or absence, of the natural process of programmed cell death called apoptosis. Apoptosis is normally triggered to destroy a cell from within when it outlives its purpose or it is seriously damaged. One of the most promising approaches in the fight against cancer is to selectively induce apoptosis in cancer cells, thereby checking, and perhaps reversing, the improper cell growth.
Maxim researchers can efficiently identify new cancer drug candidates and molecular targets that selectively induce apoptosis in cancer cells through the use of chemical genetics and our proprietary live cell high-throughput caspase-3 screening technology. Chemical genetics is a research approach investigating the effect of small molecule drug candidates on the cellular activity of a protein, enabling researchers to determine the protein's function. Using this approach with its proprietary caspase-3 screening technology, Maxim researchers can focus their investigation on the cellular activity of small molecule drug candidates and their relationship to apoptosis. The focus on apoptosis is achieved by screening for the activity of caspase-3, an enzyme with an essential role in cleaving other important proteins necessary to cause cell death through apoptosis. This combination, of chemical genetics and Maxim's screening technology, allows researchers to discover and rapidly test the effect of small molecules on pathways and molecular targets crucial to apoptosis, and gain insights into their potential as new anticancer agents. Our screening technology is particularly versatile and can be adapted for almost any cell type that can be cultured, and it can measure caspase activation inside multiple cell types (e.g., cancer cells, immune cells, or cell lines from different organ systems or genetically engineered cells). This allows researchers to find potential drug candidates that are selective for specific cancer types, which may help identify candidates that provide increased therapeutic benefit and reduced toxicity. For example, an assay is in development to identify compounds that are selective for the myc oncogene, which is over-expressed in many types of cancers. The versatility of the platform also allows for applications beyond cancer, such as inflammatory disease where we have developed an assay to identify agents that selectively induce apoptosis in activated B and T cells.
Maxim's high-throughput screening capabilities allow researchers to screen approximately 30,000 compounds per day. To date, this program has identified several families of compounds with potentially novel mechanisms that induce apoptosis in cancer cells. Four compounds from within these families have progressed to lead drug candidate status with proven pre-clinical efficacies in tumor models and identified molecular targets. The most advanced candidate from this program is entering a Phase 1 trial through collaboration with Myriad Genetics.
Maxim Overview
Maxim Pharmaceuticals is a biopharmaceutical company dedicated to developing innovative cancer therapeutics. Maxim's lead drug candidate is Ceplene(TM) (histamine dihydrochloride), which has shown a statistically significant improvement in leukemia free survival in a Phase 3 clinical trial as a remission maintenance therapy for patients with acute myeloid leukemia (AML). Maxim is currently seeking a strategic partnership to complete commercialization and further development of Ceplene in AML and other indications. Maxim is also discovering and developing small-molecule apoptosis inducers to treat cancer using its proprietary high-throughput screening technology and its chemical genetics approach. This program has identified four lead oncology candidates that are proceeding to clinical trials independently and through collaborations. The most advanced candidate from this program is entering a Phase 1 trial through collaboration with Myriad Genetics.