PHILADELPHIA Hurel, a Beverly Hills, Calif.-based corporation attempting to commercialize a compartmentalized, microfluidics-based cell culture system for cell-based drug-discovery applications, has struck a research collaboration with pharma giant Johnson & Johnson, founder and CEO Robert Freedman said in a presentation at the World Pharmaceutical Congress held here last week.
The partnership will be Hurel's first with big pharma, and one that the company hopes will serve as the platform's first major industry validation for its platform. Freedman said that Hurel is also currently pursuing additional early partnerships to speed the product toward commercialization.
If the product is successfully commercialized, it could complement, or possibly even supplant, the types of high-content cell-based screening techniques that have recently popularized drug discovery, due to what Freedman believes will be a higher amount of relevancy to actual in vivo animal and human models.
Presenting during the conference's "Cell-Based Assays for HTS" track, Freedman said that Hurel short for "human relevance" was about a year to a year-and-a-half away from its first industrial-scale product. The tool, as yet unnamed, is a coverslip-sized biochip with individual compartments fluidically interconnected and designed to contain various cell, tissue, and organ cultures, against which small molecules might be tested for efficacy, toxicity, or even bioavailability.
The idea, Freedman said in his presentation, is that the device should offer pharmaceutical and other biology researchers "greater physiological relevance and realism" than static cell-based assays, and help drug makers adhere to their 'kill early, kill often' strategy.
"We're initially targeting the pre-candidate stage, with the further thought that as people become experienced with the technology, they'll tend to want to migrate its use earlier upstream in the discovery process," Freedman told CBA News following his presentation.
Even if Hurel can only sell its technology to drug makers for use in the pre-candidate stage, Freedman thinks that it can significantly increase productivity in pharmaceutical research.
"I estimate that the productivity impact of introducing this technology as a late-stage, cell-based screen for metabolism, hepatotoxicity, general toxicity, and bioavailability … to reduce the number of compounds that are promoted into pre-clinical animal studies, may be 20 percent," Freedman said.
Freedman added that "if you use the 20-percent assumption, you're talking about a productivity improvement benefit for any of the large pharmas that you'd have to measure on the order of $100 million to $150 million per pharma per year."
The technology, protected by US Patent No. 5,612,188, "Automated, multicompartmental cell culture system," was actually developed in the late 1980s at Cornell University by Michael Shuler, the school's director of biomedical engineering, and Gregory Baxter, who was working in Shuler's lab at the time. Baxter went on to co-found Hurel several years ago with Freedman, and is currently the company's chief scientific officer. Shuler, meanwhile, retains his Cornell professorship and currently serves on Hurel's scientific advisory board.
Freedman said that Hurel is now the worldwide, exclusive licensee of the technology, and has since filed for additional patents related to the technology, including US Patent Application No. 20030082795, "Devices and methods for pharmacokinetic-based cell cultures system."
The multiple cell culture technology has been relatively mature for some time, according to Freedman, but lacked a killer application. However, when Freedman and Baxter founded Hurel, they quickly realized that it showed a great deal of promise for drug discovery applications.
In terms of the current application areas that Hurel envisions, Freedman said that a major area is predictive toxicology.
"We envision a series of product embodiments that deal with different pairs of multi-organ toxicity," he said. "So we would expect to have a first embodiment that is for hepatotoxicity alone, followed by chips that are optimized for combinations such as liver-kidney, liver-heart, et cetera."
In fact, Hurel has to this point conducted proof-of-principle studies using immortalized human cell lines, particularly HepG2-C3A liver cells, as well as rat primary hepatocytes.
Envisioning future R&D collaborations with pharmaceutical partners, Freedman said that the work would be performed "substantially on rat primary hepatocytes, with the thought being that if we can demonstrate good metabolic competency results on those cells, the extrapolation to human primaries is not that tough to take," Freedman said. "However, we will do work on human primaries as well."
Other product applications will be for metabolic studies, particularly time-based metabolic studies; absorption and bioavailability of orally ingested compounds; and compound library screening, Freedman said.
Regarding the latter, "we feel this is an area where we can re-screen promising areas of the massive portfolios of chemical entities that the pharmas have got, using our active liver compartment, so that a compound can be screened for potential efficacy in the presence of its active metabolites," he said.
"That's a new capability that's uniquely available because of our multi-tissue or multi-organ functionality," he added. "Combined with the fact that we think our technology is going to demonstrate greater concordance with in vivo results particularly if you're testing with primary cells we may find favorable efficacy on compounds that have previously been rejected."
At the conference, Freedman presented data from the studies, which looked at the effect of chemotherapeutic pro-drugs Tegafur and Sulindac, as well as acetaminophen, on colon cancer cells and hepatocytes, respectively.
Hurel already has a prototype, which is based on glass chips of about 22 mm2, and has the microfluidics component controlled by a standard peristaltic pump. As the product develops, the glass chips will eventually be replaced by plastic, which Freedman said will allow compatibility with a variety of standard plate readers or microscopy platforms for assay readouts. Freedman also said that the platform is intended to be largely agnostic when it comes to what types of assay reagents would be used.
Not Seeking VC Cash
In addition to being the co-founder and CEO of Hurel, Freedman is managing principal of Athena Capital Partners, a Los Angeles-based enterprise sponsorship firm that is an angel investor in Hurel. Despite Athena's early participation, Freedman said the company is not actively seeking additional VC cash in the near term primarily because the product still needs conceptual and experimental validation.
"The thought had not been to seek conventional venture capital investment for this, because … if we had we gone to financial investors, they would have sent us back to the pharmas anyway and said 'Before we will invest in you, go get confirmation from your ultimate customers that this is something that they're really interested in,'" Freedman said.
With a Johnson & Johnson collaboration lined up, Hurel will now focus on garnering additional pharma partners for validation. Freedman declined to comment on additional potential partners.
Calls to Johnson & Johnson were not returned in time for this publication.
As for possible collaborations with readout instrumentation, microscopy, or reagent providers, Freedman said the company is "absolutely interested" in such endeavors but at a later time.
"They're not on the top of our list right now, because we think we can deliver a lot of value even without instrumentation-directed collaborations at the beginning, and we need to focus our limited resources on setting up this initial program and getting our partnership arrangements in place, he said, referring to the Johnson & Johnson collaboration. "So they won't happen in the first six to 12 months, necessarily, but if you look out to the 24- to 36-month horizon, then you would start to see multiple relationships there."
Ben Butkus ([email protected])