An official at drug maker EpiCept this week said that the company’s internally developed cell-based assay has helped drive progress in its lead candidate pipeline.
John Drewe, director of lead discovery at the Tarrytown, NY-based company, said the platform, Anti-cancer Screening Apoptosis Platform, or ASAP, can efficiently identify new drug candidates and molecular targets that selectively induce apoptosis in tumor cells.
EpiCept’s ASAP technology platform represents a fast and efficient way to identify molecular targets and lead candidates for cancer drugs.
Drewe, who spoke with Cell-Based Assay News after presenting his company’s finding at GTCbio’s Apoptosis in Drug Discovery Conference in San Diego this week, said that the platform accomplishes this by using chemical genetics and EpiCept’s proprietary live-cell high-throughput caspase-3 screening technology.
So far, the company has used ASAP to identify four lead compounds: Azixa, that is currently in phase 2 clinical trials for metastatic brain cancer and licensed to Myriad Genetics; EPC2407, that is in phase 1 trials for solid tumors; EP2167, a rapid inducer of apoptosis specifically targeting the transferrin receptor that is currently in preclinical development; and EP128504, an inducer of apoptosis that targets the novel cytoplasmic protein TIP47, which affects the IGF growth signaling pathways, and has been shown in preclinical testing to be selective for breast and colorectal cancer cells.
During his presentation, Drewe also presented data from a study that used ASAP to target apoptosis in oncogene-dependent cell lines, specifically Myc-dependent Burkitt’s lymphoma cell lines. Drewe said that deregulating Myc is closely associated with the development of several cancers.
He said the company is “particularly interested in following up” on this research, but “it is too early to specify a lead drug entity at this time.”
However, he noted that ASAP identified compounds that selectively cause apoptosis in tumors with deregulated Myc expression. “The latest work we’ve done is take two cells — one that is Myc-dependent and one that is not Myc-dependent — and identify compounds that differentiate between the two.
“We use those hits to follow up with the same techniques that came to fruition with EPC2407,” Drewe said. “From there we can come up with new chemical entities against Myc-dependent tumors.”
Screening Cells, ASAP
ASAP, which was designed as a cell-based screening platform for cancer drug discovery, is “particularly useful for positioning the molecular entity under investigation in the market and determining what biomarkers would be applicable,” said Drewe.
Ben Tseng, EpiCept’s chief scientific officer, added that the company feels “it is faster to identify a chemical molecule that has in vivo biological activity, and then subsequently identify the molecular target, rather than finding small molecules for selected protein targets.
It is faster to identify a chemical molecule that has in vivo biological activity, and then subsequently identify the molecular target, rather than finding small molecules for selected protein targets.
“In the past, target identification was technically challenging,” said Tseng. “It was also difficult to do in a timely manner. But combining techniques such as higher resolution mass spectrometry with current knowledge of the human genome and cell-based screening is a much more rapid approach.
“Our program differs from a forward genetics approach that begins with validation of a target by genetic means, then continues with discovery of a chemical entity that modulates this target in vitro, and is followed by verification of in vivo biological activity,” Tseng said.
Tseng added that chemical genetics “allows us to identify new and different molecular targets that activate apoptosis. We might not find these targets using classic molecular genetic techniques.”
One of the challenges with ASAP technology is to continue developing different strategies for using this platform, according to Tseng. “We’ve applied it to Myc so far,” he said, “and we are currently applying it to other oncogene pathways as well.”