Lessons Learned A year Into A Pandemic

he Food and Drug Administration approved a record-breaking 59 new drugs and biologics in 2018 – nearly double its average of 33 new drugs per year. The U.S. drug-discovery process is a multi-billion dollar industry that despite advancing technology and fast tracks, is a rigorous, regulated process.

Partially funded by the Texas Emerging Technology Fund and The University of Texas System Star Awards, the Texas Therapeutics Institute (TTI), part of the McGovern Medical School, was founded in 2010 to bridge the gap between the world of biomedical research and the pharmaceutical industry and encourage drug discovery.

During the last nine years, TTI has established a network of collaborators from institutions across Texas and the nation with more than 30 active drug discovery projects targeting cancer, metabolic diseases, neurodegenerative diseases, spinal cord injury, fibrosis, acute drug induced liver injury, and viral infections. Five TTI Texas Therapeutics Institute – Drug Discovery Engine of McGovern Medical School inventions have been licensed to biotech companies for drug development. These licensing deals resulted in significant upfront payments, potential milestone payments, and royalties.

While TTI focuses on drug discovery and development, the institute’s investigators have garnered more than $30 million from the pharmaceutical and the biotechnology industry, such as Merck and J&J, the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and the Department of Defense, and have made significant scientific discoveries in the areas of antibody drug resistant mechanisms in cancer, antibody response to viral infection and vaccination in animal models and humans, cancer biology, fungal natural products, linker and conjugation chemistry for antibody-drug conjugates. Some of TTI’s research was reported in more than 100 publications in highly reputable scientific journals including “Nature,” “PNAS,” “Cell Reports,” “Neuron”, “Nature Communications,” “Clinical Cancer Research,” and “ACS Chemical Biology.”

“Our ultimate goal is to benefit patients’ health with the creation of new drug therapies that can be brought to market by partnering with the pharmaceutical and biotechnology industries,” says Zhiqiang An, PhD, director of TTI and holder of the Robert A. Welch Distinguished University Chair in Chemistry.

Dr. An knows the pharma world – he worked for 15 years in the pharmaceutical industry before being recruited to McGovern Medical School to lead TTI. In addition to Dr. An, three other senior TTI investigators also were recruited from the pharma industry. Qingyun (Jim) Liu, PhD, who holds the Janice D. Gordon Distinguished Professorship in Bowel Cancer Research, previously headed up the drug discovery effort at Lexicon Pharmaceuticals. Gerald F. Bills, PhD, holder of the Kay and Ben Fortson Distinguished Chair in Neurodegenerative Disease Research, is an industry veteran in natural products drug discovery. Ningyan Zhang, PhD, joined TTI after 15 years at Merck Research Labs with experience in cancer antibody drug discovery and development.

The institute’s areas of expertise include antibody drug discovery.

“Antibodies are a part of our
natural immune system, and
they fight infectious diseases and
cancer. The rapid rise of
antibody-based therapies is
largely due to their desirable
safety profile, target specificity,
and efficacy.”

Dr. Zhiqiang An
Texas Therapeutics Institute Director

Antibodies can be engineered to bind to disease targets, including receptors on cell surfaces and circulating proteins. In addition, they can be designed to carry toxins and radioisotopes to kill cancer cells. In fact, antibody-drug conjugates (ADCs) are emerging as a highly desirable drug modality for cancer therapy. Kyoji Tsuchikama, PhD, who is a Scripps-trained synthetic chemist joined TTI three years ago to develop the necessary linker and conjugation chemistry for the ADC construction.

Not limited to the treatment of disease, antibodies also are used to diagnose medical conditions by detecting disease biomarkers in cells, tissues, and in body fluids.

“Antibodies are extremely sensitive and specific to the disease biomarkers,” Dr. An says.

TTI has developed an antibody that targets acute myeloid leukemia (AML). The most common acute leukemia (blood and bone marrow cancer) in adults, it is characterized by the proliferation of abnormal myeloblasts (a type of white blood cell) in the bone marrow. Despite advances in treatment, only about 27 percent of acute myeloid leukemia patients survive 5 years after diagnosis.

“This is the first step to bringing an effective therapy to AML patients,” Dr. An says.

In an effort to expedite the drug-delivery process, in 2017, TTI licensed its cancer immunotherapies and other biotherapeutics to Immune-Onc Therapeutics, a startup in Palo Alto, Calif.

“This is an important step in translating our therapeutic antibody from discovery to development,” Dr. An says.

A new $6 million grant from the U.S. Department of Defense in collaboration with UT Health San Antonio will help Dr. An develop an innovative antibody-based drug to stem the spread of breast cancer to bone.

The goal of the researchers is to develop a less toxic treatment and reduce deaths tied to the spread of breast cancer to the bone. At the end of the study, the researchers hope to have a drug that can advance to clinical trials.

In addition to the basic and translational research programs, TTI is building two major drug discovery platforms: the Therapeutic Monoclonal Antibody Lead Optimization and Development Platform and the Natural Products and Small Molecular Drug Discovery Platform. The drug discovery platforms not only support TTI projects but also collaborative projects with scientists from across the nation and world.

“We are confident that TTI will continue to grow and play a critical role in advancing the biotech industry in Houston and the state of Texas,” Dr. An notes