Success Story

April 17, 2019  |  Jola Glotzer

UIC’s TTC-352 and G1T48

Two agents developed by CBC affiliates Debra Tonetti and Greg Thatcher, UIC, tested in clinical trials as potential anti-breast cancer therapeutics

Today we feature two UIC scientists, Debra Tonetti and Greg Thatcher, who are long time CBC affiliates. Over the course of less than a year, this collaborative team managed to have two agents approved to enter clinical trials: in March 2018, an agent known as TTC-352, and in November 2018, a second agent — G1T48. Both compounds developed by Tonetti and Thatcher are being tested as potential treatments for metastatic estrogen receptor positive, or ER+, breast cancer. Tonetti and Thatcher have many ties to the CBC: they both actively participated in several CBC educational events, including the CBC Annual Symposia, CBC Tech Day and CBC Science Day. Each scientist is also a multiple CBC awardee: Tonetti received a CBC Catalyst Award (2009) and a CBC HTS Award (2015), the latter together with Thatcher, who was also granted a second CBC HTS Award the same year. Finally, both, Tonetti and Thatcher have served on CBC Catalyst Review and CBC Accelerator Review Boards, respectively. The CBC is grateful for their service and wishes them continuous success on the path to therapeutics!

Second UIC breast cancer drug enters clinical trial

this is UIC  |  by Jacqueline Carey  |  November 13, 2018

Debra Tonetti & Greg Thatcher, UIC

Debra Tonetti and Greg Thatcher, UIC

The University of Illinois at Chicago now has two breast cancer drugs in federally approved clinical trials.

Both drugs are potential treatments for metastatic estrogen receptor positive, or ER+, breast cancer and both were approved for human trials this year.

UIC’s Gregory Thatcher and Debra Tonetti collaborated to develop the drugs, which have been licensed to biopharmaceutical companies.

“Very few research centers can claim to have advanced a drug, not to mention two investigational new drugs, into a clinical trial within the span of a single year,” said Thatcher, the Hans W. Vahlteich Chair of Medicinal Chemistry at the UIC College of Pharmacy.

The most recent of these two drugs to enter a Phase 1/2a clinical trial is named G1T48. It is taken orally and it is categorized as a selective estrogen receptor degrader, or SERD. It works by destroying the estrogen receptor, which is a key part of how ER+ breast cancers grow.

About 70 percent of breast cancer patients have ER+ tumors, said Tonetti, professor of pharmacology in the UIC College of Pharmacy. And while other hormone therapy drugs are used to treat women with this type of cancer, up to 50 percent of these patients have cancers that either do not respond to the treatment or acquire resistance within five years of therapy, she said. When the tumors become resistant, new drugs are needed to keep patients in remission.

Currently, there is no oral SERD on the market. In preclinical trials, G1T48 was demonstrated to be more powerful than the only SERD currently available to patients, called fulvestrant, which is delivered by injection.

“If the trials are successful, we feel G1T48 may be the first in its class and the best in its class,” said Thatcher, who is also director of the UICentre for Drug Discovery and co-director of the UI Cancer Center’s Translation and Oncology Program.

Thatcher said that G1 Therapeutics, the company that licenses the drug from UIC, had been interested in licensing a SERD drug, but had not found one that they thought would succeed. However, after reproducing the pre-clinical data for the UIC-developed drug, they decided to invest. “They believed it was the one,” Thatcher said.

The other drug in clinical trials is called TTC-352, and it is categorized as a selective human estrogen receptor partial agonist, or ShERPA. This drug, like G1T48, works on the estrogen receptor, but in a different way. Having different ways of targeting the estrogen receptor is important in a disease where the receptor can adapt and drive resistance.

TTC-352 is licensed to TTC Oncology. UIC’s Office of Technology Management is overseeing the patents for both drugs, along with a number of other drugs in various stages of development, three of which are for cancer.

“I think the success of these two drugs shows that there is space for academic drug discovery centers to either compete with or complement corporate biopharmaceutical research centers,” said Thatcher. “Academic scientists and centers have a core of knowledge, built up over many years of research, that is unique.”

If the trials for these two ER+ breast cancer drugs are successful, UIC could have its fourth and fifth drugs in the market.

Adapted (with modifications) from the this is UIC, by Jacqueline Carey, published on November 13, 2018.

Featured CBC Community member(s):

Debra Tonetti, UIC

Gregory Thatcher, UIC

Articles published in the past about the featured CBC community members:

March 23, 2018
▸ TTC-352, a new breast cancer agent developed by Debra Tonetti and Greg Thatcher, UIC, may become a therapeutic for patients with estrogen receptor-positive breast cancer that expresses specific biomarkers

November 5, 2017
▸ Three UIC researchers and CBC awardees featured in the UIC College of Pharmacy Annual Report 2017