For the past few decades, Dr. Iwao Ojima has been working in his Stony Brook University Department of Chemistry Laboratory and through the Institute of Chemical Biology & Drug Discovery (ICB&DD) to develop next-generation anti-cancer agents. One of these agents – a second-generation taxane conjugate in a nanoemulsion formulation (called NE-DHA-SBT-1214) – has shown great promise against solid tumors – particularly against colorectal cancer. The taxane compounds were licensed to a Stony Brook University spinout, clomiphene ovarian cancer risk TargaGenix, Inc., in 2016, to advance their development toward clinical use. Since then, TargaGenix has further developed the compounds, addressing formulation, toxicity and in vivo efficacy, and has now attracted significant investment into NE-DHA-SBT-1214.
TargaGenix plans to work with its partners to develop the new taxane as a stand-alone drug, as well as look to use it in combination with other treatment modalities, including immune-oncology agents. The company and its collaborators expect to advance the drug development into clinical testing in humans in the near future.
TVM Capital Life Science (TVM) is committing up to $24 million for a development program in order to help advance NE-DHA-SBT-124 to market as an alternative medicine to treat colorectal cancer and other solid tumors.
Taxanes are a class of oncology drugs widely used to treat solid tumors. They are represented by paclitaxel, docetaxel and cabazitaxel. The drug class inhibits tumor growth by blocking cancer cell mitosis. However, multidrug resistance (MDR) and cancer stem cells (CSCs), along with various adverse effects, often hamper the effective use of these drugs. Dr. Ojima and his team developed a highly potent second-generation taxane conjugated to DHA (widely known omega-3 fish oil supplement) in nanoemulsion formulation. The agent (NE-DHA-SBT-1214) exhibited not only excellent activity against MDR solid tumor xenograft models, but also against CSC-initiated tumor xenografts models.
"A primary indication for NE-DHA-SBT-1214 is colorectal cancer, which is a very challenging cancer to deal with due to strong multidrug resistance," says Dr. Ojima, Distinguished Professor and Director of the ICB&DD. "But it also shows promise with pancreatic cancer and prostate cancer in preclinical testing. For example, we examined NE-DHA-SBT-1214 in combination with PLD-1 antibodies for pancreatic cancer. The combination therapy exhibited superior results over the current best standard treatment against this deadly disease."
Cancer Research eBook
The new taxane conjugate is formulated using a nanotechnology called nanoemulsion, originally developed by Dr. Mansoor Amiji at Northeastern University. This nano-formulation together with DHA-conjugation allows for tumor-selective drug delivery by means of an "Enhanced Permeability and Retention (EPR)" effect characteristic to nano-size particles, as well as a controlled release of highly potent second-generation taxane. This has been shown in preclinical testing to make the taxane efficacious against MDR and CSCs within the tumor.
"The novel taxane originally developed by Dr. Ojima and his team shows great promise in pre-clinical studies of colorectal and pancreatic cancer, two of the deadliest cancers in humans. I am delighted that after decades of research, the drug will be entering clinical trials in patients. This example illustrates the importance of research in Stony Brook's basic science departments for developing new potential treatments for cancer," says Peter Igarashi, MD, Dean of the Renaissance School of Medicine at Stony Brook University.
"Taxanes have been a cornerstone of cancer treatment for decades, but they can come with significant side effects, and treated cancers frequently recur," says James E. Egan, CEO of TargaGenix. "We are excited to have TVM's strong support and to now have the resources to further the development of this potentially game-changing molecule," adds Egan, who received his PhD at Stony Brook University in Molecular Pharmacology.
Stony Brook University's Intellectual Property Partners (IPP) worked with TargaGenix to secure TVM's investment.
"My office worked closely with James and TVM through this investment, and we are elated to see it close," says Sean Boykevisch, PhD, Director of IPP. "The funding will accelerate this new potential therapeutic into the clinic, where we hope it will provide meaningful clinical responses and potentially become a new standard of care."
Stony Brook University
Posted in: Drug Discovery & Pharmaceuticals | Medical Condition News
Tags: Alternative Medicine, Antibodies, Cancer, Cancer Treatment, Cell, Clinical Testing, Colorectal, Colorectal Cancer, Conjugation, Docetaxel, Drug Delivery, Drug Discovery, Drugs, Efficacy, Fish, Fish Oil, in vivo, Laboratory, Life science, Medicine, Mitosis, Molecule, Nanotechnology, Oncology, Paclitaxel, Pancreatic Cancer, Pharmacology, Preclinical, Preclinical Testing, Prostate, Prostate Cancer, Research, Stem Cells, Therapeutics, Tumor, Xenograft
Source: Read Full Article