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Maxim Seeks Partners for HT Cell-Based Screening Tech to Fund Own Discovery


In an attempt to raise funds as it waits for its own lead compounds to advance into the clinic, Maxim Pharmaceuticals seeks to provide drug-screening services based on its high-throughput live-cell caspase-3 screening technology, executives from the San Diego-based company told Cell-Based Assay News last week.

The company said it believes it can also offer drug makers target identification, validation, and pathway analysis based on the screening technology.

In addition, Maxim last week said in a statement that it will be using the caspase-3 assay technology as part of a new internal screening campaign of approximately 60,000 recently acquired small molecules. The company said it hopes this move will help it identify anticancer agents and molecular targets for inducing apoptosis in cancer cells.

Although the company continues to pursue this internal drug-development initiative, it now also plans to use its cell-based screening technology to perform screening services for other drug makers.

Maxim has "engage[d] an investment banking firm to assist in identifying and evaluating strategic opportunities that best leverage and build on Maxim's assets, including its research and core drug-development teams, as well as its apoptosis modulator discovery platform and pipeline that uses high-throughput technology to screen for molecules that specifically modulate the apoptosis pathway," the company said in a February statement.

The company is also beginning to hit the conference, trade show, and symposium circuits to promote its screening capabilities. In May, Maxim's senior director of research, Ben Tseng, will be presenting at a special partnering forum at the World Pharmaceutical Congress, to be held in Philadelphia. According to the abstract, Tseng will describe the caspase-3 screening technology and the newest set of candidate compounds it helped uncover.

Last week, Maxim chairman and CEO Larry Stambaugh provided Cell-Based Assay News with more detail on the company's partnering strategy.

"I think it's appropriate, because this is a tool that we think is proprietary and unique," he said. "The tool we have is for discovery of anti-cancer drugs. We've purchased libraries to screen ourselves, and … as a result of this proprietary tool, we have found novel targets and pathways never before know, and some potential cancer drugs.

"But we have, as well, screened libraries for other people," he added. "And we are open to making this tool available to more people, because we've got such a unique position here."

According to Stambaugh, the company has landed one such deal thus far, with Rockville, Md.-based Celera Genomics, for whom Maxim screened approximately 700,000 compounds. That deal was announced in 2000, and Celera is currently evaluating the results, Stambugh said. According to the terms of the deal, Maxim has the option to jointly develop with Celera any compounds that are taken into clinical trials, sharing equally the development costs and commercial revenues.

In addition to the Celera partnership, Stambaugh said, Maxim has "done other minor screenings," but that the Celera deal remained the best example of Maxim's capabilities to date.

Calls to Celera seeking were not immediately returned.

Unique Reagent

Maxim's decision to begin playing in drug-screening services comes after the company has made modest strides in its own drug-discovery research, even as these efforts have recently experienced a regulatory set-back.

In its statement announcing its plan to use the caspase-3 assay technology as part of its project to screen 60,000 small molecules, Maxim publicized its recent discovery of a series of small molecules known as 4-aryl-4H-chromenes, calling them potent apoptosis inducers and microtubule inhibitors. The company said that this research, which was published in the Dec. 2 issue of the Journal of Medicinal Chemistry, validates its cell-based caspase activation assay as a viable tool to discover apoptosis inducers.

Maxim also noted that the chromenes described in the paper have previously shown strong anti-tumor activity in pre-clinical in vitro and in vivo studies, and have the potential to be further developed into anticancer drugs.

The candidate compounds add to Maxim's stable of potential anticancer compounds that the company hopes into advance to the clinic either through partnerships or on its own. However, in January, Maxim received news from the US Food and Drug Administration that its most advanced therapeutic candidate, Celpene — a treatment for acute myeloid leukemia — would need to undergo additional Phase III trials before the company could submit an NDA.

There are many caspase-3 assay kits offered commercially, and the concept of screening for apoptosis-inducing compounds by monitoring caspase-3 activity is not new.

However, what Maxim feels puts it in a unique position is its possession of IP surrounding a profluorescent substrate that it acquired in 2000 after buying biotech firm Cytovia.

Overall, Maxim now has more than 20 patents covering various screening methods using the reagent (in addition to the many patents it has surrounding pharmaceutical formulations and other drug-discovery methods). The core substrate from Cytovia is covered by US Patent Nos. 6,248,904; 6,335,429; 6,342,611; and 6,759,207 — each of which roughly share the same title, "Fluorogenic or fluorescent reporter molecules and their applications for whole-cell fluorescence screening assays for caspases and other enzymes and the use thereof."

"The proprietary substrate is highly amenable to high-throughput screening," Tseng told Cell-Based Assay News last week. "It's a pro-fluorescent substrate; that is, in the absence of cleavage, there is no fluorescence, but after it gets cleaved by the caspase-3, it becomes fluorescent.

"In addition, we've joined that together with our chemical genetics approach," Tseng added. "We have a very good chemistry group that analogs around these various hits that we find, and the ones that are interesting, we then identify the molecular target for those compounds. We do that by using a compound and making analogs around it that will allow us to identify and purify out the molecular target," he said.

Hence, Maxim will not only provide screening for apoptosis inducers, but also believes it can offer target ID and validation and pathway analysis services.

Thus far, Maxim has identified two unique molecular targets to activate apoptosis, one of which is a transferrin receptor, said Tseng. He would not disclose the second one.

The transferrin receptor is "a cell-surface receptor that transfers iron into cells," he said. "What's unique about this is that we activated apoptosis very rapidly — within 15 minutes or so — which is one of the fastest times that have been seen. Also, it activates both the intrinsic and extrinsic pathways of apoptosis."

— BB

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