Three biopharmaceutical startups led by Drexel University researchers are one step closer to bringing new, potentially life-saving drugs to the market.
The companies — Context Therapeutics, Kerberos Biopharma and PolyCore Therapeutics — each were supported with funding from the Coulter-Drexel Translational Research Partnership Program, which provides both grants and guidance for academics to commercialize inventions.
Now the startups have the opportunity to vie for the attention of venture capitalists and technology transfer professionals during the Coulter Investment Forum on May 16 and 17, in Ann Arbor, Mich.
“There is a general understanding in the scientific community that the collaboration between academia and the private sector has to be more than what it has been in the past,” said Olimpia Meucci, MD, PhD, chair of the College of Medicine’s Department of Pharmacology and Physiology and head of pre-clinical research at Kerberos. “Drexel is really at the forefront and exceptional in this regard, with its strong support of entrepreneurial pursuits.”
At Drexel, the program, which is endowed by the Wallace H. Coulter Foundation, has awarded $7.6 million to 50 projects since its inception 11 years ago. Formatted like the popular reality television show “Shark Tank,” faculty members submit applications to an oversight committee at the university and advance to other rounds, where they are grilled with questions ranging from regulatory requirements to reimbursement strategies.
“Coulter challenged us to find ways to address the problems of entering a market that might be quite resistant to the problem we are trying to solve,” said Alessandro Fatatis, MD, PhD, a professor in the College of Medicine, and chief scientific officer at Kerberos.
But in the end, it will be patients who reap the greatest benefits from the Coulter program, say Meucci and Fatatis, who are developing drugs to treat metastatic breast cancer. Funding secured from the Investment Forum could pave the way for the startups to apply to the Food and Drug Administration for an Investigational New Drug (IND) designation, and then to begin clinical studies.
Though understandably cautious, the scientists are largely optimistic about bringing their research from the bench to the bedside within the next five years.
Here is more about the startups representing Drexel at the Coulter Investment Forum.
Prostate cancer is the most common non-skin cancer among American men, according to the Centers for Disease Control and Prevention. Though many patients beat the disease, once the cancer has spread to distant organs — a process known as metastasis — the five-year survival rate is less than 30 percent. In 2016, more than 26,000 American men died from prostate cancer, the vast majority of whom developed resistance to standard drug treatment.
At all stages of the disease, prostate cancer cells are dependent on a protein called the androgen receptor (AR), the primary driver of tumor growth and disease progression. Since testosterone is the fuel that enables the androgen receptor to drive prostate cancer, current therapies involve suppressing the androgen receptor with targeted drugs that directly bind to and block the protein.
Currently, there are three main drugs used to treat advanced prostate cancer in men, but they ultimately provide limited benefits to patients. While the current medications are effective for a limited time, eventually the androgen receptors in prostate tumors reactivate and develop drug resistance.
“Prostate cancer is a highly adaptive and constantly evolving disease. Ironically, treatment resistance is driven, in part, by the AR-targeted drugs that are designed specifically to suppress the disease,” said Felix Kim, PhD, assistant professor in the College of Medicine and co-founder of Context Therapeutics.
Realizing a need to address this problem of drug resistance, Kim became interested in a unique protein called Sigma1 (also known as the sigma-1 receptor), which was identified over four decades ago as a potential target for treating pain. Kim and his research team found that Sigma1 is enriched and abnormally expressed in prostate tumors, making it a novel target for treating prostate cancer.
Kim likens the Sigma1 system to the cellular version of ride-share companies like Uber or Lyft, whose drivers sit idle until a rider sends an alert. Similarly, Sigma1 is found in every cell, but it remains inactive until promoted. Cellular stress, a hallmark of cancer, activates Sigma1 to pick up cancer-promoting client proteins and transfer them to sites of action. The androgen receptor is one such client protein of Sigma1.
As described in a recent paper published in Cancer Research, Kim and his colleagues have developed a new series of drugs that target Sigma1 to block the activity of the androgen receptor and essentially eliminate it from prostate cancer cells. By targeting Sigma1, rather than the androgen receptor directly, the researchers were able to knock out the receptor’s support system. Importantly, Kim said, this approach was effective in suppressing prostate cancer cells that had become resistant to all other drugs.
This discovery paves the way for Context Therapeutics — Kim’s startup that launched in 2015 — to develop a drug candidate that targets Sigma1 and stops the progression of tumors in men with lethal prostate cancers that are resistant to current treatments.
Meucci and Fatatis are also looking for new methods to treat the metastatic spread of cancer. Women diagnosed with breast cancer rarely die from their primary tumor. Instead, when the tumors metastasize — often to the bone, brain, liver or lungs — treatment options dwindle.
“There is a strong hesitation from the pharmaceutical industry to tackle metastasis,” Fatatis said. “For the longest time, doctors have tried to treat metastasis with the same approaches they used for the primary tumor, which is not necessarily the best way to go.”
Alessandro Fatatis, MD, PhD
In 2004, Fatatis and his research team identified the chemokine receptor CX3CR1 as a crucial player in regulating and steering the growth of breast cancer cells to skeleton and soft-tissue organs. Building on that evidence, the researchers were able to synthesize small-molecule compounds to target CX3CR1, which have disrupted tumor growth in pre-clinical animal models.
Following the launch of their biotechnology company, Kerberos Biopharma, the research team has now identified a clinical candidate that is able to contain the number of metastatic lesions.
It was previously believed that cancer cells only seeded to other areas of the body before the primary tumor is removed — lying dormant for months or years before they resurface. In addition to this scenario, it is now established that metastases can seed new lesions or reseed existing metastases even in the absence of the primary tumor.
“This new evidence changes the game plan,” Fatatis said. “One can now prevent initial metastases from spreading, thus providing more time for effective therapies by avoiding ‘chasing the disease.’ ”
Moreover, when testing the drug candidate in mice, the researchers found that it not only blocked new tumors from forming, but it also stopped the initial tumors from growing.
The drug already seems much safer than typical chemotherapy, since it does not directly kill cancer cells, but stops them from seeding. The researchers are hoping to test it in human patients by 2019.
The standard treatment for Parkinson’s disease — a progressive neurodegenerative disorder — is a 40-year-old strategy that replenishes dopamine in the brain. These medications, such as L-DOPA (Sinemet), are associated with a long-term side effect of dyskinesia, or involuntary muscle movements that can be painful and debilitating.
Now, thanks to research from Sandhya Kortagere, PhD, an associate professor in the College of Medicine’s Department of Microbiology and Immunology, a new drug with few side effects is in the pipeline.
The drug compound developed by Kortagere is called PCT-3010, and it modulates both dopamine and norepinephrine in the brain to treat both motor and cognitive function in Parkinson’s patients.
The compound is highly selective to the little-understood dopamine D3 receptor subtype, which behaves differently from its D2 counterparts.
Kortagere designed and developed PCT-3010 and she has shown that the compound has more selective signaling properties than current drugs available on the market.
“We believe the compound signals only through the desired pathway, thereby producing efficacy and not side effects,” Kortagere said. “Other compounds, including L-DOPA and Pramipexole, although they produce beneficial effects, also signal through a pathway that is thought to cause side effects like dyskinesia.”
A 2016 paper published in Neuropharmacology showed that their novel dopamine D3 receptor agonist not only improved the motor deficits in rodents with Parkinson’s symptoms, but also blocked the dyskinesia produced by L-DOPA when treated in combination with the drug. Kortagere launched PolyCore in 2014 to commercialize PCT-3010, which is being touted as an oral, once-a-day treatment that can be used alone or in conjunction with L-DOPA.
“I think we have very good results, and if everything progresses as planned we anticipate that this drug could be in the market five years from now,” Kortagere said.