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Millennium Pharma to Characterize Cell Lines for Horizon Discovery

Horizon Discovery announced this week that Millennium Pharmaceuticals will broadly characterize seven of Horizon’s X-MAN Mutant and Normal human-isogenic cell lines against drug targets provided by Millennium.
Under the terms of the agreement, Millennium will pay Horizon an undisclosed six-figure fee and share key data sets during the eight-month evaluation period, set to begin next month, a Horizon official told CBA News.
Horizon CEO Christopher Torrance declined to elaborate on the financial details of the collaboration. However, he said that Millennium will do a number of tests during that eight-month period, and the figure they agreed to pay is not milestone-based.
Horizon has developed a panel of in vitro models, called “double knock-in” isogenic cell lines, that have secondary and tertiary mutations associated with cancer. The lines are genetically defined cell lines with a specific cancer-relevant mutation that drives malignancy, but each mutated cell is paired with a matched normal cell. 
The X-MAN name marks a re-branding of Horizon’s original isogenic cell lines, which originally did not have a brand name (see CBA News, 4/18/08).
“We have decided to call our matched isogenic cell line pairs X-MAN cell lines now, because we think it nicely captures what they are — one is a genetically defined mutant diseased version and the other is perfectly matched, but normal,” said Torrance.
He added that Horizon was finding that too many people had different interpretations of the term “isogenic,” and the name X-MAN “allows you to explain it in a way that people can easily understand.”
Torrance went on to say that whether Millennium continues to use the cell lines past this agreement will depend on the tests that they are doing. “I cannot really further discuss the tests that they will be doing, but it really involves just broadly characterizing the cell lines,” Torrance said.
Millennium did not respond to a request for comment in time for deadline.
Cancer Rx Gets Personal
As a pharmaceutical company, Millennium is looking at targeted cancer medicine and “realized the advantage of having in vitro models so that they can potentially predict patient responses and resistance to targeted agents,” said Torrance.

“Once Millennium is happy with the cell lines, they can break out all different parts of the agreement, in terms of a particular cell line or using a particular cell line or lines for a particular application.”

This ability to predict response and resistance requires understanding a patient’s genetics — “not just the primary cancer gene that one is trying to target, but also all the other cancer genes that may influence a patient’s sensitivity to the drug,” he said. However, to date no good in vitro models have been developed for these ends.
“I think Millennium is well-positioned to understand what [the availability of these cell lines] can do for people in this field. They have decided to take a route where they can actually evaluate a broad panel of these cell lines,” Torrance said.
Millennium believes that it is a good idea to test many possible combinations of genes broadly in such an in vitro model as part of what Torrance referred to as a “broad access” evaluation, with an option to “dig deeper on these models in various applications if itworks out well for them.” 
The agreement, which marks the first time that Horizon has collaborated with Millennium, is designed to be continued. Although it is an initial evaluation, if the data looks good Millennium has the option to use it in more applications for finding new drugs.
Branching Out
Horizon is “branching out” the X-MAN panel, Torrance said. Because cancer is widely believed to be caused by several genetic mutations in sequence, “if patients have a single genetic event, they could be sensitive [to a particular drug], but if there is a second event that uses another pathway that interacts with the pathway that you trying to target, it could result in resistance,” said Torrance.
“We are seeing that quite a lot in patients now, and we are gaining an understanding of what kind of second or third genes can impart resistance,” he added.
“The actual single knock-in genes we have are common cancer genes: k-ras, b-raf, PI3 kinase, and EGFR. The double knock-ins are basically permutations of those,” said Torrance. The three that Horizon currently has available are EGFR/b-raf, PI3 kinase/k-ras, and EGFR/PI3 kinase.
The company is currently in the process of creating additional double knock-in isogenic cell lines, he added.
There will likely be a second phase of this project, Torrance said, “but it will not necessarily be a defined phase 2, because [the terms of the current] agreement allow Millennium to sort of splinter off any number of aspects from it.”
For example, Millennium could take an extended license for one of the seven cell lines that it is testing at any point in the agreement, and that would be defined as a new agreement.
There is also room for Millennium to, for example, do drug screening on the X-MAN cell lines, “so if they wanted to start doing big drug screens on a particular cell line, that is a facility provided for as part of the current agreement, and it would become an agreement in its own right,” Torrance said.
“Once Millennium is happy with the cell lines, they can break out all different parts of the agreement, in terms of a particular cell line or using a particular cell line or lines for a particular application,” he said.

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