Inviting pharma to the dance

The words you don’t want to hear from a pharmaceutical company after presenting a new potential drug that obliterates cancer in mice: “It’s too early.” 

That’s code for: you haven’t convinced us this could actually work and is safe for humans.

NewCures at Northwestern University is a novel accelerator poised to prevent that brush-off. It will identify the most promising new potential therapies in development at the University for cancer, depression, pain, Parkinson’s disease and other diseases. Then it will fund outside research to answer the key questions a pharmaceutical company typically requires before it agrees to invest in later-stage development, such as clinical trials.

Northwestern is on the crest of an early wave of universities accelerating the development of their therapies as pharmaceutical companies shift from completely developing in-house drugs to licensing proven technology from academia and startups.

“There’s a new ecosystem of small biotechs spun from academic research collaborating with larger industry partners,” said Karl Scheidt, NewCures executive director. “We’re capitalizing on that. We can’t wait for them to come to us. We need to invite them to the dance, and we need to understand what they’re looking for.”

Scheidt is a professor of chemistry at Northwestern’s Weinberg College of Arts and Sciences and a professor of pharmacology at the Feinberg School of Medicine.

An external advisory board of pharmaceutical executives, venture capitalists and scientific leaders help choose the therapies for NewCures and how to invest in these new technologies.

“Having pharma thought leaders as key partners in this program allows us to build the technology together as opposed to the University trying to advance the technology on its own and assume what industry people might want,” Scheidt said.

“You want to make sure you are setting out on the right foot,” said Dr. Scott Brun, vice president of scientific affairs and head of AbbVie Ventures, who is a member of the NewCures external advisory board. “You need to understand what other therapies are available and in development, and how a discovery can be turned into a treatment that will help patients better than what is already out there. It’s not enough to be new and shiny.”

A vital question: Will the drug make a meaningful difference or a remarkable impact in patients’ lives if it is successful? 

An early partnership is key to getting a project on the right track. “A university has scientists who understand the biology and technology,” Brun said. “We have industry experts who understand the steps you need to take to get something into the clinic. That makes an excellent combination of expertise to get these programs on the right track at the very inception." 

The seed for NewCures was an earlier pilot program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University called Compounds for Cures. It supports early therapeutic discoveries in oncology and was developed by Scheidt and Dr. Leon Platanias, director of Lurie Cancer Center. The discoveries at Lurie and throughout the University provided the momentum to form the new, broader accelerator. 

“Supporting research early in the pipeline is critical to bringing it to clinical trials,” Platanias said.

“NewCures is the missing step that helps set the stage for a potential drug to be commercialized and make it into the clinic,” said Caroline Ko, NewCures project leader. “We are helping scientists go from bench to bedside with unparalleled support.” 

NewCures is housed in Northwestern’s Innovations and New Ventures Office, led by executive director Alicia Loffler, and supported by funding from the Office for Research. NewCures will leverage this initial investment to partner with units within Northwestern to move new potential treatments towards clinical commercialization. 

Other biomedical development programs available to the Northwestern faculty include Chicago Biomedical Consortium (CBC) and NIH Center for Accelerated Innovations at Cleveland Clinic (NCAI-CC).

A case study: Hurdling tall barriers in cancer drugs

Cancer really likes a protein called MYC. If you remove the gene that produces MYC, tumors wither and leukemia remits. But it’s been tough to design a molecule to inhibit MYC. The protein is all smooth, slick surfaces with no handy grooves for a molecule to latch on. Scientists had given up on it.

Enter Dr. Sarki Abdulkadir, a professor of urology at Feinberg, who, with Gary Schiltz and Rama Mishra of the Center for Molecular Innovation and Drug Discovery at Northwestern, used molecular modeling to test 16 million compounds to see if their geometric structure could bind to the protein. 

He discovered several, synthesized the most promising ones and began testing them in animals. They caused regression in prostate cancer and in leukemia in animal models. In human cancer cell lines, the compounds inhibited more than a dozen types of cancer including colon, lung and pancreatic cancer. 

What are the odds of taking one of these compounds to the next level, so it will be considered as a candidate drug for clinical trials?

“The odds are very low,” Abdulkadir said. “This is a big barrier.”

Abdulkadir also is the John T. Grayhack, MD, Professor of Urological Research and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.   

He needs funding – which is hard to come by -- to conduct extensive testing in larger animals to de-risk his drug. National Institutes of Health grants cover only basic science and early animal studies. Plus, most academic labs aren’t equipped for the sheer scale of the next research stage.

One of Abdulkadir’s compounds is a promising candidate for NewCures. If it’s chosen, an outside lab will conduct a raft of experiments on the drug so it’s ready for consideration as an investigational drug by the U.S. Food and Drug Administration and a candidate for acquisition. 

“If you give a compound to a living organism, where does it go … to the liver, the kidney?” Abdulkadir asked. “How is it excreted from the body? Does it stay in the fat for a long time? What’s the safety profile? Is it easy to dissolve in a solution so you can inject it? We need to understand all that. You can’t jump from mice to humans. These things take time and a lot of resources.”

Another leukemia therapy candidate is from Platanias and colleagues, who have shown the pathway of the enzyme Mnk is critically important in the spread of acute myeloid leukemia (AML). They also have shown that Mnk inhibitors cause remission of leukemia in vitro and in vivo in preclinical models.

Platanias believes targeting Mnk kinases may provide a novel approach for treating AML and brain cancers, such as glioblastoma multiforme. Using a molecular modeling-based high throughput screen, a new series of compounds that act as Mnk inhibitors were identified. The series of compounds are currently being developed into a novel potent compound to inhibit Mnk.