David Platt, PhD, CEO of Pro-Pharmaceuticals, a carbohydrate drug-developing company, reviewed the companyï¿½s recent clinical trial success with a colorectal cancer treatment, Davanat.
David Platt, PhD, CEO of Pro-Pharmaceuticals, a carbohydrate drug-developing company, reviewed the company’s recent clinical trial success with a colorectal cancer treatment, Davanat.
What makes Pro-Pharmaceuticals’ unique?
Pro-Pharmaceuticals is engaged in the discovery, development, and commercialization of first-in-class, targeted therapeutic carbohydrate compounds for advanced treatment of cancer, liver, microbial, and inflammatory diseases. Our initial focus is the development of a new generation of anti-cancer treatments using carbohydrate compounds to increase survival and improve the quality of life for cancer patients. Davanat, our lead pipeline candidate, is a proprietary chemical entity that is currently in Phase II trials for first-line treatment of colorectal and biliary cancers.
As a result of their structural complexity, carbohydrates have not received as much scientific attention as nucleic acids and proteins and are not as well understood. Carbohydrate molecules, which are essential to the transmission and recognition of cellular information, have been shown to play an important role in major diseases, including cancer, cardiovascular disease, Alzheimer’s disease, inflammatory disease, and viral infections. We believe this offers a largely untapped area for treatment of disease, including chemotherapeutics, infection treatment, vaccines, and antibiotics. Our company is one of the pioneers focused on development of carbohydrate-based drugs. We are keeping patients alive longer and improving their quality of life. That is the power of carbohydrate chemistry.
What is so promising about carbohydrate chemistry, and why has it been an underrepresented field of research?
Carbohydrate drugs are great candidates as cancer drugs because they are extremely stable, and they have great biological activity. This type of chemistry can affect the biological system. By combining two drugs like Davanat and 5-FU, we show better data than the existing standard of care. We show great promise in this type of chemistry to affect biological structures.
Carbohydrate chemistry is a complex, organic chemistry, and historically, it was called a neglected science because of that complexity. Carbohydrates are very difficult to manufacture or to mold into a chemical structure. It requires a person to be an expert in organic chemistry as a chemist and then to understand the biological systems and the complexity of the synthesis. There are not many people in the field. They are underrepresented in terms of students, making the field underdeveloped.
What clinical success has Pro-Pharmaceuticals had with Davanat?
The lab results and pre-clinical animal results were outstanding, which has allowed us to test in humans. In Phase-I & Phase-II clinical trials, we showed that the combination of Davanat & 5-FU increased the median survival of end-stage patients. These patients had fewer serious adverse events from the chemotherapy, and this is in a patient population that had failed all standard chemotherapies and which had, on average, about three months to live. Based on those results, we went to the FDA and are now conducting two front-line trials for colorectal and biliary cancers. We dramatically lowered the toxic side effects of 5-FU and expect to file an NDA this year based on a claim of functionality. We showed in pre-clinical studies that when 5-FU is used in combination with Davanat, more of the 5-FU accumulates in the tumor, and it stays there longer than when 5-FU is used alone. That’s the claim.
What will Davanat mean to cancer patients, oncologists, and researchers?
It’s a major breakthrough in terms of reducing toxicity. The holy grail of drug development is how to get the drug into the right place. That targeted therapy is one of the aspects of Davanat. We are seeing benefits for patients—significant reductions of toxicity. By reducing side effects, we are improving patients’ quality of life. For insurance companies, this translates into reduced costs, as patients do not need to stay longer in hospitals and do not need expensive drugs to treat toxic side effects.
As I mentioned earlier, we are prolonging life. Davanat works and enhances the anti-tumor activity of existing chemotherapy drugs. Davanat can enhance chemotherapy drugs activity and reduce toxicity.
What is the next step for Davanat?
We hope to find a sponsor to do a Phase III study to conduct superiority testing in a control group for survival. That may require only several hundred patients. We plan to show that patients that failed all other therapies can live longer. We’ll have a major claim of superiority, better than any other drug on the market.
What is more important than prolonging life and improving quality of life by reducing toxicity? We attach the polysaccharide, the carbohydrate, to an existing chemistry. So you can attach the chemical structure of carbohydrates to an existing drug, any drug, permanently. That is in the future. You give the chemical structure recognition capacity the same way an antibody can recognize a receptor.
With that, it will revolutionize the way drugs are designed. You can do a precision delivery and recognition on the chemical structure. That is the concept behind the drug design. It opens the door to better antibiotics and, actually, more accurate drugs embedded in the chemicals.
What else does Pro-Pharmaceuticals have in the pipeline?
We have two major technologies, again based on carbohydrate chemistries. The first one, which we announced today, is an extremely powerful technology. It will stabilize hemoglobin with polysaccharides by killing tumor cells by delivering oxygen. Oxygen will treat hypoxia, a state in which the tumor loses oxygen. That is the source of resistance for tumors to radiation and chemotherapy. That is why chemotherapy will not work well if there are extreme or partial hypoxic conditions in the tumor cells. We have the potential to treat that with stabilized hemoglobin that can deliver oxygen to those tumor cells. Together with chemotherapy and Davanat as a targeting mechanism, we can now more efficiently kill all of those hypoxic cells that are left in the tumor mass.
The other technology we’re working on parallel to that is a drug that, again is a carbohydrate chemistry that we collaborated on with Mt. Sinai and the head of the Liver Disease Unit, Dr. Scott Freidman. That drug showed in animal testing on rats that we can put liver fibrosis in remission. It’s a major experiment we’ve done. We will submit it to the FDA for clinical trials next year.