Smart Drug Delivery: Modern Techniques Used to Develop Drugs

Kansas City area biotech companies are making significant strides in developing advanced drugs that work better and keep patients healthier.

Approximately 200,000 Americans are diagnosed with locally advanced cancer of various kinds. Five-year death rates range from 30% to 60%. While there is currently no drug treatment delivered directly into these types of cancers, Hylapharm, a drug delivery company founded in 2010 by a team of KU faculty, has developed a patented drug delivery system that makes chemotherapy treatment for locally advanced cancer safer and more effective.

Dr. Laird Forrest, Hylapharm’s founder, chief executive officer and pharmaceutical chemist by trade, developed the Hylaplat technology. Dr. Forrest and Dr. Dan Aires both University of Kansas professors, lead the Hylapharm team with support from former KU graduate student Dr. Shuang Cai.

The drugs can be administered as a simple shot. The proprietary method is the first to target these cancers by delivering over 100 times more drug directly to the tumor and the local lymph nodes where these cancers spread. The treatment increases uptake by the cancer cells and local lymph nodes. Hylaplat uses nanoparticles of hyaluronic acid, a natural compound in the body that cancers stick to, as its delivery method for anti-cancer drugs such as cisplatin. Cisplatin, effective for a broad range of cancers, doxorubicin and docetaxol have all been tested and come back with encouraging results. This technology has also been applied to anti-infective agents and for immune suppression.

“There are advantages to this drug delivery compared to intravenous infusion,” Dr. Cai says. “Hyaluronic acid is FDA-approved. It’s safe and biodegradable. Also, with an IV, the drug goes everywhere into organs and the blood. Our drug is targeted to a specific area of the body’s tissue. So, it spares healthy organs from toxicity.”

The drug is primarily injected into the breast, head and neck. Drug exposure is limited in the kidneys, nerves and auditory organs. Side effects are also reduced throughout the body. Toxicity from the anti-cancer drug is reduced due to a lower overall dosage and lower peak blood level with any given dose.

“We are very excited about this new line of cancer treatment. The method is new but the drug components are well-understood,” says Dr. Aires, director of the division of dermatology at KU. “The safety profile is better than chemotherapy. Direct injection results in less destructive treatment and also improved survival rates.”

“This type of treatment can have an impact,” Dr. Aires says. “An estimated 100 Americans die daily from locally advanced cancers. That’s our measure. We want the drug treatment to help save people.”

The Kansas Bioscience Authority awarded $200,000 for FDA Investigational New Drug (IND), enabling animal trials, in January 2013. In other words, the animal studies will be conducted to validate that the technology is safe. Efficacy has been demonstrated in multiple mouse models in numerous peer-reviewed scientific publications in top journals.

Further, the drug has safely and successfully treated a pet dog with a large cancer in his mouth. Intra-tumoral HylaPlat used in dogs delivers over 100 times more of the drug to both tumors and draining nodes (where cancer cells tend to spread first), allowing for lower overall dosing. The technique has shown success in xenograft models of locally advanced/regionally metastatic melanoma, head and neck cancer and breast cancer, as well as lymphoma.

The next phase will allow Hylapharm to begin preparations for an IND as a step toward clinical studies for treating cancer in human patients.

Compared to conventional chemotherapy treatment through an IV, which may require the patient to receive multiple treatments five times daily over three weeks, Hylaplat can be administered once per week.
Dr. Cai says, “It depends on the patient’s condition, but the reduced time and dosage can lead to better patient compliance and possibly lower overall cost.”

HylaPharm plans to develop human trials both in the U.S. and internationally. The drug is manufactured in a university incubator space in Lawrence, Kan.

The company has received preliminary interest from Merck and other major drug companies. The impact of this new drug delivery method, if successfully approved and adopted, can help improve or save the lives of hundreds of thousands of Americans diagnosed each year with deadly locally advanced cancers.

In terms of bringing Hylaplat to market quickly, Hylapharm’s advantage is that an abbreviated Federal Drug Administration application is possible since the product is a novel complex of approved drugs. It represents a huge potential for a multi-billion dollar, undeveloped, local-regional chemotherapy market.