NCI Develops Therapeutics for the Treatment of Cancer, Psoriasis, and More

NCI Membrane

Cancer is caused by the improper regulation of cascading signals, or pathways, within the cell.

One of the most prevalent means of fighting cancer involves the development of drugs and biologics that target and bind the specific proteins that disrupt the proper regulation of the pathways.

The Hedgehog pathway is normally involved in embryonic development, and it is also improperly activated in many different tumor types. Smoothened (SMO) is a protein that plays an integral role in the regulation of this pathway.

To reduce the growth of tumors, the National Cancer Institute (NCI) has developed novel drugs that disrupt the Hedgehog pathway by inhibiting the activity of the SMO protein.

These inhibitors belong to the class of drugs known as peptidomimetics (PMDs), which are synthetic drugs created by altering naturally occurring proteins.

To help the PMDs enter the tumor cells and deliver the drug directly into the cells, separate technologies needed to be developed. NCI is working on developing self assembling nanoparticles that can incorporate PMDs. The resulting PMD nanoparticle delivery vehicle can permeate tumors and deliver the PMDs directly to cancer cells. This technology platform overcomes many of the specificity and stability issues associated with these types of drugs. The PMD technology, in conjunction with the nanoparticle delivery system, allows researchers great flexibility in developing a variety of cancer treatment options that can be used on “undruggable” proteins that are considered too difficult to be therapeutically targeted by existing therapeutics.

Transfer of this technology involved a Cooperative Research and Development Agreement (CRADA) between NCI and Calidris Therapeutics, a start up company, and a license to the NCI technology. The CRADA is designed to accelerate pre-clinical development of the PMD technology. This CRADA/licensing approach allows for continued development of the technology under the CRADA, while the license will allow Calidris to secure background rights in the technology and help to attract potential investors.

In addition to the technology transfer agreements in place with Calidris, the National Institutes of Health (NIH) has exclusively licensed the Hedgehog technology to Lee’s Pharmaceuticals for the development of psoriasis therapeutics. Lee’s Pharmaceuticals is an established Asian company that focuses on several indications, including dermatology, gynecology, and cardiovascular and infectious diseases. The license allows Lee’s to expand its dermatology portfolio to include psoriasis treatments and to leverage its resources to bring products to market in Asia, a region where the NIH has not traditionally capitalized. By separating the field of use and geographical territories, the NIH is ensuring that its technologies are having a maximal impact promoting public health and stimulating economic development worldwide.

The potential benefit of this technology transfer effort extends beyond the development of a single therapeutic. The parties are attempting to establish the framework for creation of a new therapeutic field and a new generation of drugs that are highly specific, potent, and applicable to a multitude of diverse diseases. The inventors refer to these new therapeutics as “synthetic biologicals” because they possess the high specificity and reduced side-effects associated with many protein therapeutics.