Drug-discovery company Znomics said last week that it has inked an alliance with the University of Utah’s Huntsman Cancer Institute to develop pre-clinical compounds for treating T-cell leukemia, autoimmune diseases, inflammation, and complications related to organ transplantation.
Under the terms of the collaboration, Znomics will provide an unspecified amount of funding for research in the laboratory of Nikolaus Trede, an investigator and pediatric oncologist at HCI, and an expert in the zebrafish immune system.
Trede and his team, in collaboration with Znomics researchers, will develop proprietary T-cell disease assays in the zebrafish based on endogenous T-cell markers. These assays will then be used to screen the university’s compound library to identify leads for further clinical testing.
Znomics said that it has an exclusive option to license any promising small molecules or lead compounds and all related intellectual property discovered during the collaboration. All financial terms were pre-negotiated, Znomics said, although specific terms were not disclosed.
As part of the agreement, Trede has also joined Znomics’ scientific advisory board.
According to Trede, the collaboration took root when he and David Ranson, Znomics’ director of genetics and functional genomics, were postdocs together in the laboratory of zebrafish expert Len Zon at Children’s Hospital Boston.
“[David] contacted me and asked if we were doing any drug screening, because they were looking for possible drug screens that were interesting to them,” Trede told BTW this week.
Among other projects, Trede and colleagues had been working on identifying potential anti-leukemic compounds in a zebrafish model.
“The idea was that, as T-cells develop in the thymus in a young zebrafish larvae on day six or eight or so, they are very young … and in a way comparable to the stage when leukemia cells are arrested,” Trede said.
“We could actually kill those cells with dexamethasone, but that also has lots of side effects. And I am a pediatric oncologist, and I see all these side effects on the kids …so we wanted to find some drugs that were fraught with fewer side effects,” he added.
Trede’s lab then developed a method to screen compounds in a genetically engineered zebrafish leukemia model. “The nice thing about the fish is that you can immediately assess the effect on the entire vertebrate on days six to eight when they already have a liver, heart, et cetera,” Trede said. “So we just add this compound and see if we can kill the cells. That, of course, is a very rough measure of a possible effect of these drugs on zebrafish T-cells. But then we put them through a more detailed testing looking at the effect on the cell cycle.”
The researchers in Trede’s lab then test active compounds on human T-cell leukemia lines, and unrelated cell lines such as kidney and B-cells. So far they have identified at least one promising compound that kills the jurkat T-cell line, but not other normal cell lines, and have determined the compound’s pharmacokinetics. “The next step then is to test whether they can kill human leukemia cells in an immune-compromised mouse,” Trede said.
Trede’s lab performed these screens, however, with a compound library licensed from ChemBridge, a San Diego-based contract research organization.
“I told Znomics what we were doing, and I think they were more interested in the proprietary compounds we have here than the compounds I came up with in our screen using the ChemBridge library,” Trede said.
“That personal relationship helped jump start this; otherwise they might not have heard of it, because this is all unpublished work we have so far with our compounds.”
“I think they liked the [screening] concept, and then the availability of a proprietary library” at the University of Utah, Trede added. “That personal relationship helped jumpstart this; otherwise they might not have heard of it, because this is all unpublished work we have so far with our compounds.”
Eric Gosnick, a licensing manager at the University of Utah Technology Commercialization Office, told BTW this week that the office normally works from the side of licensing pre-existing IP to a company. However, “Trede had already been doing that screening at the university, and that kind of raised his level of publicity,” Gosnick said. “When we were out trying to get interest in his compounds, Znomics realized the system he was using was more interesting to them … and now wants to use its system to test their compounds.”
Although specific financial details have not been disclosed, for the University of Utah the Znomics agreement is a modest one that could eventually pay big dividends, Gosnick added.
“What distinguishes this from many of the life sciences deals is that when we have something actually being sold and marketed – like a pharmaceutical – they can be big money makers right off the bat,” he told BTW. “In this case they’re covering [Trede’s] operation costs. We hope that something big will come out of it, and there are options for the future licensing of any IP that does come out of it.”
According to the Association of University Technology Managers’ Annual Licensing Activity Survey, the University of Utah closed 61 licensing and option agreements and collected about $16.3 million in licensing income in its fiscal year 2006, which ended on June 30 of that year.
However, the university garnered particular attention for its prowess at spinning out companies: It reported the formation of 17 companies in FY 2006 based on research conducted on its campus, second only to the Massachusetts Institute of Technology, which boasted 23 but with three times as much annual research funding.
For Znomics — itself a 2001 spinout of the Oregon Health and Science University — Trede’s zebrafish method is another feather in its cap in the area of genetically engineered zebrafish disease models for drug screening.
Based in Portland, Ore., Znomics has developed a proprietary ZeneMark library of more than 11,000 strains of zebrafish, which it created through a gene-modification technology known as retroviral insertional mutagenesis.
The library, which is stored in the form of sperm aliquots, represents roughly half of all known zebrafish genes, and the company plans to add enough additional strains to represent 80 percent to 90 percent of the zebrafish genome, according to a report last year by Cell-Based Assay News, a BTW sister publication.
Znomics has also created two subsets of the ZeneMark library: the Living library and the Human Disease library. The Living library is a collection of zebrafish strains maintained as living lines that contain defined retroviral insertional mutations, while the Human Disease library is maintained as living lines or frozen sperm and contains retroviral insertions in genes homologous to known human disease genes.
After announcing in November that it had secured $4.9 million as part of a reverse merger with publicly traded shell company Pacific Syndicated Resources, Znomics said in April that it had launched a drug-discovery program for screening potential drug candidates using a genetically engineered zebrafish obesity model that it licensed from OHSU.
Znomics has also said that after identifying preclinical candidate compounds, it hopes to partner with a larger pharmaceutical or biotech firm to bring the candidates through clinical trials.
Znomics officials could not be reached for comment prior to the publication of this article. In a statement, Roger Cone, president and CSO of the company, said that “Trede’s screens combined with our ZeneMark library of knockout mutants can give us a significant competitive advantage, not only in identifying active small molecules, but rapidly validating them and identifying the molecular targets and pathways responsible for the therapeutic effects.”
Trede told BTW that Znomics seems to have a strong interest in academic collaborations. As for his lab’s collaboration with Znomics, “let’s see how it goes for a year,” Trede said. “But they really want to collaborate with academics, and they know the downsides and upsides to that.”