Maxim Pharmaceuticals Apoptosis Research Discovery Published in PNAS

Maxim Pharmaceuticals (Nasdaq: MAXM) (SSE: MAXM) reported that its discovery of transferrin receptor's (TfR) role in the rapid activation of apoptosis has been published this month in the Proceedings of the National Academy of Sciences (PNAS).

Using its proprietary screening technology along with chemical genetics, Maxim scientists were able to identify the involvement of transferrin receptor (TfR) as a rapid inducer of apoptosis. Transferrin receptor is a known and validated oncology target, but its ability to rapidly activate apoptosis had not previously been known. It has been determined that a site exists on the TfR which, when occupied, leads to apoptosis possibly by inhibiting TfR internalization. This site is independent of the transferrin binding site. Maxim researchers initially identified gambogic acid as the ligand for binding and activating this pathway. This research was published in the PNAS article entitled "A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid."

Maxim has developed and commenced pre-clinical testing of several viable drug candidates from gambogic acid. MX2167 is the lead anti-cancer candidate from this group of compounds.

Maxim Apoptosis Modulator Discovery Platform

Cancerous cells often exhibit unchecked growth caused by 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 caspase-3 screening technology allows Maxim's 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.

The versatility of the platform also allows for applications beyond cancer, such as inflammatory disease where we have developed an assay to identify immunosuppressive 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.

Maxim Overview

Maxim Pharmaceuticals is a biopharmaceutical company dedicated to developing innovative cancer therapeutics. Maxim has completed one Phase 3 clinical trial of Ceplene(TM) plus Interleukin-2 combination therapy as a remission maintenance therapy for patients with Acute Myeloid Leukemia. The Company is currently seeking a strategic partnership to further develop the compound and to complete commercialization. Maxim is also engaged in the discovery and development of small-molecule apoptosis inducers to treat various cancers. This program has identified four lead candidates that are proceeding to clinical trials independently and through collaborations.

Apoptosis compounds and Ceplene are investigational drugs and have not been approved by the U.S. Food and Drug Administration or any international regulatory agency.