The vision of Life Science Leader is to help facilitate connections and foster collaborations in pharma and med device development to get more life-saving and life-improving therapies to market in an efficient manner. Connect, Collaborate, Contribute
Issue link: https://lifescienceleadermag.epubxp.com/i/320415
insights LIFESCIENCELEADER.COM JUNE 2014 60 DRUG DEVELOPMENT 10,000 compounds. Doing so would be too costly to build the tissues at a rea- sonable price. A better scenario would be if there were 100 or fewer compounds to test, and the company was seeking the perfect molecule to move forward with — without liver toxicity issues. "The model allows a company to put its faith in a molecule that represents the desired potency and efficacy to move into a clini- cal trial," says Murphy. "While the cur- rent drug discovery process typically takes between three and six years, this would help pharmaceutical companies reject an ineffective or dangerous drug in a matter of months." BUILDING THE DATA The benefits of rapid drug discov- ery and early identification of toxic- ity issues have caught the attention of pharmaceutical companies. For instance, Organovo signed a collabora- tive research agreement with Roche last year. While Murphy cannot describe the scope of the work, it is presumably to test Roche's compounds. Unrelated to Roche, Organovo has released quite a bit of data on its 3D liver model. Organovo's 3D liver tissues exhib- it dose-dependent responses to acet- aminophen, a known liver toxicant. And Murphy explains that the liver tissues successfully produced albumin, fibrino- gen, and transferrin. The bioprinted liver tissues also possess the ability to synthe- size cholesterol. While Murphy admits that no test can be 100 percent accurate, he says 3D bio- printing represents a huge leap forward from animal testing and Petri dishes. For example, he says the small tissue being created is indeed representative of the larger tissue. "We are starting from a place where it's so bad that slight improvements are incredibly good, and we're creating what we think is a dra- matic improvement," he says. "We may fall short of being perfect, but we are so much closer to perfect than the available methods that the benefit is huge." Murphy says the promising data is not only a story to be shared with phar- ma, but also with federal regulators. "Remember that regulators are scien- tists, and they want to see good data. That is what they will use to determine a drug's approval. The bottom line is if we provide the scientific value that we think we can, which is a better model than some of the existing animal models, the FDA should be extremely comfortable letting people move forward." Organovo has already been speaking with the FDA. Murphy says the agency is aware of how the company's science works and how it can potentially be ben- eficial. "If we show that 3D bioprinting is a predictive tool, the FDA will accept the test and could theoretically ask that pharma use the technology," he says. FIGURING OUT WHY GREEN-LIGHTED DRUGS GO BAD But until that point is reached, more work needs to be done. Going forward, Murphy says Organovo will test drugs that failed in the clinic but were initially green-lighted based on the results of animal models and 2D cell-culture testing. "We want to discern what things light up that we could have seen to help pharmaceutical devel- opment become more predictive." Organovo will also commence the com- mercial launch of its 3D liver and start generating revenue through a contract research service model before the end of the year whereby a pharma client would provide its compounds and Organovo will perform a set of tests for the client. While the cost for such a service will depend on the tissue, Organovo will work with each customer on an individual basis and build tissue specifically to a client's need. Murphy does say, though, that the cost for tissue for liver fibrosis would be different than tissue for liver toxicity testing. While Organovo anticipates that pre- clinical toxicology testing services could command prices in the high tens of thou- sands per compound for standard liver screening alone, Murphy points out that the cost of drugs that fail is estimated at about 40 percent of all drug spending. "So if the drug spending is more than $50 billion per year, there is an opportu- nity to save more than $20 billion. Even if using 3D bioprinting testing only causes modest improvement, there is signifi- cant potential benefit." And Murphy says that, under the right circumstances and with the right part- ner, Organovo could license the bioprint- ing technology to a life sciences com- pany to perform its own testing. Organovo also plans to release addi- tional data in 2014 on its 3D kidney tis- sues and breast cancer tissues, which are now in development. Organovo is about six years away from entering clinical studies to make tissues for surgical implant. "Everyone quickly thinks about large organs; bioprint an organ and implant it into the body. But, instead, we are focused a little smaller. Think of a 3D bioprinted liver patch to help repair a damaged liver. We could take cells from the patient to create the patch, which would almost assure no immune response." The applications and the implications are plentiful. Organovo will continue to work with liver and kidney tissue, but other 3D bioprinting research will include oncology, lung tissue, muscle tis- sue, and blood vessels. Murphy says: "Three-dimensional bio- printers are a powerful tool, and while they might not solve every issue in drug development, they can be leveraged to make headway in areas where tradi- tional animal models and 2D cell-cul- ture methods aren't allowing pharma to make good progress." L By C. Dubin 3D BIOPRINTING COULD SPEED UP DRUG DEVELOPMENT K E I T H M U R P H Y CEO and President, Organovo Holdings Three-dimensional bioprinted tissues can help pharmaceutical companies speed up the drug discovery process. 0 6 1 4 _ D r u g _ D e v . i n d d 2 0614_Drug_Dev.indd 2 5 / 2 1 / 2 0 1 4 1 1 : 5 7 : 4 8 A M 5/21/2014 11:57:48 AM