Aiming to prove its proteomics technology in a new area of drug development, Activx Biosciences of La Jolla, Calif., announced a collaboration with Tokyo-based biotechnology company Sosei last week. The companies did not disclose financial terms of the agreement, which has an initial duration of one year.
Rather than using its so-called activity-based chemo-proteomic technology to help develop drugs de novo, like it does in other collaborations, Activx is going to apply it to teach old dogs some new tricks: company scientists will study a collection of about 200 drug candidates and drugs that Sosei has licensed from a double-digit number of undisclosed Japanese pharmaceutical companies to find new disease indications for them. These molecules have either failed in clinical trials for reasons other than toxicity — mainly lack of efficacy — or are marketed as drugs in Japan but not in Western countries, for example because they occupy niche markets and have not attracted any commercial interest outside of Japan.
Sosei declined to specify the percentage of compounds in its collection that have failed in clinical trials vs. those on the market.
“It’s a nice opportunity for Activx to apply its technology to see if we can find some potential targets that these compounds might be useful for, and that might lead to potential indications for them,” said John Kozarich, Activx’s president and CEO.
Activx launched in 2000 and has raised $26 million in venture capital financing.
The company’s core technology, parts of which are licensed from the Scripps Research Institute, rests on fluorescent chemical affinity probes that bind to the active sites of a specific class of proteins. Its technology also allows to separate and identify proteins that a probe has bound to. This binding pattern changes when a drug that competes with a probe is present. While Activx initially focused on developing probes for enzymes, it has now also incorporated receptors.
In total, the company has developed probes for about 20 different protein classes, with a focus on a few large families that include kinases and hydrolases. Probes for phosphatases and receptors are still at an early development stage, according to Kozarich.
Since last summer, Activx has been collaborating with Kyorin Pharmaceuticals, also based in Tokyo, to find drug candidates for type 2 diabetes. Kyorin has invested almost $8 million in total in Activx, including equity and research support. Activx also has a partnership with Genomics Collaborative to identify and validate protein and gene targets that are associated with colon cancer.
In the project with Sosei, Activx will look for proteins that Sosei’s compounds interact with in various human cell lines and tissue samples. These proteins might give clues to why a drug failed to show efficacy in clinical trials, or point to new indications.
Kozarich’s confidence in the promise of this approach comes from studies that Activx performed in house, for example on Xenical, a drug marketed by Roche for obesity. This study, he said, revealed a novel indication for the drug, which acted on a target it was not designed for. Activx has filed a patent on that indication, which is not covered by any of the Roche patents, he added.
However, there are some caveats that make this approach more challenging than using the technology earlier in the lead development process. “This kind of retrospective analysis is always a little more difficult because in some cases, you don’t know what the target of the drug is,” said Kozarich. For example, if the drug does not bind to any of the protein classes that Activx’s probes cover, its study will yield no results. But Kozarich believes that there is strength in the numbers. “I am not expecting to find something for every compound,” he said. “Even if we are successful only a small percentage of the time, that could still be a significant number of interesting compounds.”
Also, since the safety of the compounds has already been established in prior clinical trials, “we could probably enter into a clinical trial soon after we could identify a new indication,” said Yoshiyuki Yamakawa, vice president and director of corporate planning and public relations at Sosei, in an e-mail.
Activx is not the only company Sosei has partnered with to test its panel of compounds; however it is the first proteomics company. According to Yamakawa, Sosei has similar collaborations with 12 other firms, among them UK-based Pharmagene, Belgium-based Euroscreen, Boston-based CombinatoRx, and San Diego-based Axiom Biotechnologies. Each offers a proprietary platform, among them cell-based assays and high throughput screening.
“We are trying to cover complementary technologies to reprofile shelved drugs,” said Yamakawa. “Accordingly, a proteomic approach is important for us. Activx has established a unique proteomics approach using their proprietary chemical probes. However, we would not limit ourselves to only one proteomic partner, if others have different approaches.”
For Activx, the collaboration provides an opportunity to apply its technology in untested waters. “We have always viewed as one of the strengths of our technology that you can use it in many different places in the drug discovery and development process,” said Kozarich. “This is a very interesting opportunity to highlight the technology in a very novel and different way.”