Almac Group, an integrated drug development services company based in Craigavon, Northern Ireland, has formed a partnership with Queen’s University Belfast aimed at breaking through two bottlenecks in discovery: target validation and identifying novel hits against those targets. They will concentrate their efforts in oncology.

The program is being co-funded by Almac Group, Queens University Belfast and Invest Northern Ireland, a regional economic development agency that is part of the Department of Enterprise, Trade and Investment.

Target validation work will be carried out at Queen’s, and Almac Group will manage the project as well as own the intellectual property. The agreement between the two organizations allows Almac to commercialize output from the program, while Queen’s will receive payments when certain milestones are reached based on the commercialization of drugs as they come through the pipeline.

Through this agreement, Almac Group has access to the 350 scientists working at Queen’s University Belfast’s Centre for Cancer Research and Cell Biology (CCRCB). “It allows us to tap into a significant resource to validate multiple targets at the same time. That, to us, was a real issue because that really is a bottleneck in terms of the drug discovery pipeline,” said Paul Harkin, president, managing director and co-founder of Almac Diagnostics and professor of molecular oncology at Queen’s University Belfast.

Almac and Queen’s already have close ties. In addition to Harkin’s role at both organizations, the other co-founder of Almac Diagnostics is the dean of Medicine at Queen’s. Almac Diagnostics itself was a spinoff from the university. “Our relationship with the university goes back many years. There’s a natural fit, and there’s a lot of very good relationships that exist already,” Harkin said.

Drug Discovery Capability

Though Almac Group is best known as a service organization, the company developed its own drug discovery capability within the past few years and established Almac Discovery in 2008. Almac has a portfolio of lower-risk, late-stage products and has some in-licensed compounds, but the focus of the partnership is the early stage of the pipeline.

Harkin stated that Almac’s approach to target discovery is differentiated from others’ because it is driven from human tumor analysis.

“A lot of target discovery is based on in vitro saline model systems or in vivo models of various diseases. Because of the technology we have at Almac, we’re able to analyze primary tumors, and we have very large data sets of thousands of tumor samples with linked clinical information. We’re able to identify targets that are biologically important in the disease type that we’re studying, so, rather than try to identify an in vitro system and then validate it in tumors later on, we’re doing all of our discovery from the actual tumor material itself. Because of the high throughput approach that we take to this, we’re able to identify large numbers of what look like on the surface to be very biologically meaningful and interesting targets,” Harkin said.

Almac Diagnostics will carry out the high-throughput target discovery component of the program. The division’s ability to identify promising biological cancer targets from human material derives from its disease-specific array (DSA) technology.  “[DSA technology offers] the most complete transcriptal information content available. They’re the highest density arrays containing the most information relevant to a given disease. The second thing is they’ve specifically been developed and optimized to work with formalin-fixed, paraffin-embedded (FFPE) tumor material,” Harkin said.

DSA Technology Allows Different Strategy

FFPE is the way biopsy material is stored globally. One of the problems with this method of storage is that the DNA and RNA in it degrade over time, which necessitates access to more biological specimens for discovery and validation work than if they were flash-frozen in liquid nitrogen—a time-consuming and complicated process. One of the challenges to building a drug discovery pipeline is creating libraries of compounds that can be used in a high-throughput screening approach. Big Pharma can have libraries of up to 1 million compounds, according to Harkin, so the challenge for Almac is to distinguish its library of compounds from libraries that have already been created. The technology that allows the company to have a different target identification strategy is a major differentiating factor.

“The technology that Almac has developed allows us to extract very robust information from FFPE-based tumor material,” Harkin said. “Hospitals and clinical trial cooperative groups [COGs] will have hundreds of thousands of tumor samples, but they’re all stored in this manner. These tumor samples have typically not been amenable to genomic technologies, so there’s a huge untapped resource of information contained within those samples. The reason they’re so important is because a lot of these samples have been collected as part of large randomized clinical trials, so not only will you have tumor samples stored but you’ll also have outcome on the patients—which patients were cured, relapsed, all of that linked information to the cohorts of tumors. To be able to mine that information from those data sets is extremely valuable.”

The success of the program will be measured by the number of targets that are validated and the number of compounds identified that specifically inhibit the growth of those targets that then move down the drug discovery pipeline through to initial commercialization. Almac’s intention is to take the compounds to phase I and then look for commercialization partners to out-license to at that stage. In addition, Almac Diagnostics will determine a biomarker strategy linked to each of the targets that come through the drug discovery pipeline.

The program got under way in the second half of last year, and the first targets are already being sent from Almac to Queen’s, with prostate cancer being the initial focus.

New U.S. Headquarters

Almac Group is investing $120 million in its new U.S. headquarters, which it plans to open in Souderton, Pa., in late summer. The new headquarters will create space for two Almac divisions on-site—Almac Sciences and Almac Pharma Services—that have not had a physical presence in the U.S. It will also allow existing divisions—Almac Clinical Technologies and Almac Clinical Services—to expand. Almac Diagnostic already works with some major cooperative oncology groups in the U.S. and about 40 cancer centers.

“What we’re obviously keen to do is use this, in part, to highlight some of the more traditional services that we offer across all of our divisions. It serves as a forum to announce Almac’s move into developing its own drug development capacity and also serves to highlight integrated services that we offer to our partners already and hopefully to bring in new partners,” Harkin said.