The development stakes are high for drug companies. Recently, Targacept announced it will slash almost half of its workforce due to a recent failure of a compound in Phase III trials. The compound, TC-5214, which was being developed in partnership with AstraZeneca, repeatedly failed to prove that it was better than a placebo in treating depression. The Winston-Salem, N.C.-based Targacept has no U.S. Food and Drug Administration (FDA)-approved drugs to its credit yet, but is working with AstraZeneca on a compound targeted to Alzheimer’s disease. But for the near-term, that promise doesn’t help the 65 people who’ll be packing their desks at Targacept.  

 

According to the experts, the new plan of attack must be to maximize technology. And numerous businesses—not merely pharma companies and research organizations—are looking to do just that.   On the other hand, as a step forward, the pharma industry is focused on exploring the full potential of a broad spectrum of compounds and pro-drugs at earlier stages—that is, those in preclinical development—with the aim to provide additional opportunities and diminish risk.  

 

As mentioned last month, Translational Life Sciences is working on a crowdsourcing model to develop the blood pressure medicine lisinopril for multiple sclerosis. The model, which was introduced in beta form on Jan. 31, seeks to enlist collaborators to design Phase II trials of this indication. Founder Dr. Tomas Sablinski, a transplant surgeon by training, calls the idea for his company “a Linux of drug development, in a sense.”  

 

Biovista, also mentioned last month, is well known in drug development and the repositioning space.  

 

Another interesting opportunity to use existing information in a new way is taking shape at a company known as Cellworks. Founded by experts in software and semiconductors, the company seeks to develop models to mine vast repositories of known information about drugs, protein interactions and genetics to predict what will work in humans.  

 

Cellworks is a private, venture-backed biopharmaceutical therapeutic design and development company based on platform predicting clinical outcomes. The model will offer the pharmaceutical community innovative best-in-class therapies that are substantially de-risked, yet have a dramatically increased probability of success.  

 

Founders Pradeep Fernandes and Taher Abbasi base their work on the notion that it takes an average of 12 years and $1.2 billion for a drug to travel from the research lab to the patient. These astronomical and rising costs are, they say, in part due to the high failure rate inherent in drug discovery—less than 10 percent of drugs that begin preclinical testing ever make it to human testing, they say. From there, the funnel to the patient narrows even further with only one in five drugs that enters human testing achieving  approval for treatment.  

 

“Our model takes molecularly targeted therapies and measures their impact on specific diseases,” says Fernandes. “We can also theoretically mix and combine doses in computer models.”  

 

For new medicines to continue to reach patients, today’s drug developers must find new avenues that increase the likelihood a drug will make it from discovery to approval, and in a perfect world, predict clinical outcomes upfront.  

 

The company has a pipeline of preclinical programs targeting autoimmune disorders and epithelial-based tumors. Its lead compound, CWG952, is ready for clinical development for the treatment of rheumatoid arthritis. It also seeks to enter the oncology space in the near future.  

 

Cellworks was founded in 2005 with a novel approach of designing therapies based on technology emulating human physiology and predicting clinical outcomes. In 2009, Cellworks closed a $7.5 million Series A financing. The company has facilities in both California and India.  

 

The company’s founders say their strategy was to begin slowly, growing collaborations and broadening and deepening their experience in demonstrating that their algorithms could accurately crunch massive amount of data to spit out likely compounds for success in treatments. Since then, they say they’ve pursued roughly 40 collaborations with partners both large and small, running a range of academic medical centers and researchers across the country, but will seek a few commercial partnerships on the horizon.  

 

The speed at which their model works is noteworthy, given the notion that traditional drug development can take more than a decade. Some data sets can be processed in less than an hour, rather than months. In the arthritis work the company has done, the founders say that more than a million in-vivo equivalency studies were crunched to produce results in days. They were able to evaluate three drugs not used before in that indication, combined them in sub-therapeutic levels and found success in animal tests. All three drugs were previously FDA-approved.

 

“We have the building blocks,” says Abbasi. “We can now expand these compounds into other areas, with fewer side effects.”  

 

Sanford-Burnham Medical Research Institute at Lake Nona in Orlando is also working on the library concept.   Using a comprehensive listing of clinically approved drugs that was made available through recent efforts by the National Institutes of Health as a starting point, the organization is creating the Sanford-Burnham Drug Repurposing Collection, which can be leveraged against the group’s strengths in stem-cell biology, phenotypic cell-based screening and high-throughput chemical biology.  

 

The library will be made available to local nonprofit research institutions such as the Salk Institute, the Scripps Research Institute, the University of California at San Diego and its affiliated children’s hospital, Rady, as a resource to further advance translational medicine for rare diseases.  

 

Dr. Layton Smith, the director of drug discovery at Sanford-Burnham, points out that this private, independent research group is 100-percent focused on basic sciences, not on education or patient care. Smith estimates that the group will have, by summer's end, a library of about 2,000 to 3,000 small molecules and stem cells ready for researchers to use to prove the efficacy of their compounds and move on to FDA approval. Many will have not only FDA approval, but also the nod of European and Japanese authorities.  

 

If a molecule is patented, the group looks for vendors to work with, or synthesizes a version of the molecule themselves to complete the inventory. As with Cellworks, the group promises to compress the time needed to run screens from molecules in the library.

 

Smith also points out that the setup of the center for pure research for this purpose gives it a “boutique” capability, cutting time and drawing together the technology and talent to make this approach to drug discovery happen.   “We hope people get excited about this approach,” he says.

    Cellworks    Sanford-Burnham Research    National Institutes of Health    Salk Institute Scripps Research Institute University of California at San Diego Rady Children’s Hospital