From Bench to Bedside: Biomedical Research Discoveries Offer Hope

October 22, 2019

The University of Texas Health Science Center at Tyler is home to some of the top researchers in the world, sprawling a nearly 150,000-square-foot research facility. The researchers, often referred to as principal investigators (PI), work with the goal of transitioning their bench research to the patient’s bedside with new medications and cures. These Tyler-based researchers successfully compete for National Institutes of Health (NIH) grants and other funding against universities such as Harvard, Yale, Johns Hopkins and Stanford, having earned nearly $300 million to offer hope to patients in need.

This more than a quarter of a billion dollars in research funding over the past fifteen years has bolstered the discovery and development of new drugs and cures. UT Health Science Center at Tyler lays claim to more than ten patents and drugs candidates, hundreds of publications, clinical trials and national research partnerships with collaborators. The university has educated more than three hundred students within their postdoctoral, Master of Science in Biotechnology and undergraduate and high school internship programs.

A recent, major accomplishment of The University of Texas Health Science Center at Tyler’s research team is the commercialization of not one, but two new drug candidates whose blueprints were developed on campus: LTI-01 and LTI-03. LTI-01, currently headed into phase II (efficacy) clinical trial testing after a successful phase I, is an injectable drug that treats scar tissue and reduces fluid buildup around the lungs, which typically occurs with serious cases of pneumonia. Currently, surgery is the default option to clear lung scarring when drainage of the lung cavity is necessary; moreover, current medical therapy is empirically dosed, erratically effective and can cause bleeding. Surgery presents potential life-threatening risks of anesthesia use and other serious complications. To minimize these risks, LTI-01 was conceived as an alternative to surgery, designed to maximize lung scar removal and mitigate frequently occurring damage to the lungs. In preclinical and clinical trial testing thus far, it safely clears scar tissue, allowing drainage around the lung.

The drug’s development has been headed by Senior Vice President for Research and Dean for the School of Medical Biological Sciences, Dr. Steven Idell. Idell joined the faculty of UT Health Science Center at Tyler in 1984, where LTI-01’s work began. Dr. Idell has committed thirty-five years of research and development to enable the new clinical trials. “The LTI-01 project has continuously evolved over time to create what we see today. It’s a derivative of discovery research that will hopefully improve patient outcomes,” said Idell.

To accelerate LTI-01’s development, the decades of work began to pick up speed in 2012 when he sought capital from the UT Horizon Fund, created by The University of Texas System to seed UT-related companies. With an initial investment of $500,000 from the fund, Lung Therapeutics launched in 2013, with Idell serving as the chief scientific officer. Tasked with building the pharmaceutical company, Idell recruited a team of experts and named Dr. Bryan Windsor as CEO. Lung Therapeutics has since secured approximately $52 million in investment funding, which supplements approximately $20 million additional discovery and manufacturing funding from NIH. Notably, the most recent round of funding closed in June, securing an additional $36 million to fund phase II of the clinical trials.

While funding is indicative of LTI-01’s promise, the drug also received orphan drug designation by the U.S. Food and Drug Administration (FDA) and the European Commission, which serves to expedite the evaluation and development of drugs that demonstrate strong potential for the diagnosis and/or treatment of rare diseases or conditions. It is estimated that more than 100,000 U.S. patients annually could benefit from treatment with LTI-01. “This is important work,” says Idell. “The faster we obtain regulatory approval, the more people we can help. There is no FDA-approved drug for this problem. We’re trying to fill that void as quickly as we can.”

Lung Therapeutics is also commercializing LTI-03, slated to partake in phase I clinical trials later this year in Belfast, Ireland. LTI-03 was designed for the treatment of idiopathic pulmonary fibrosis (IPF), a chronic lung disease characterized by progressive lung scarring caused by a loss of healthy lung cells coupled with the growth of fibrotic cells. IPF, with no known cure, usually presents in adults age 65 or older and is generally fatal three to five years following the diagnosis.

The LTI-03 project at UT Health Science Center at Tyler has been spearheaded by Dr. Idell’s colleague, Dr. Sreerama Shetty, cellular and molecular biology professor. Drs. Shetty and Idell envision that LTI-03 will safely and more effectively treat IPF and will test that inference in upcoming clinical trials. “We design the research to improve outcomes for lung diseases that are not well-treated today. LTI-03 represents another effort to help patients with IPF and related lung diseases characterized by scarring,” Idell explained.

Drs. Sreerama Shetty and Steven Idell review data in their lab.​

In 2014, anti-fibrotic drugs, given as pills, were approved to treat the disease but were discovered to only decelerate IPF’s progression. In contrast, LTI-03 is administered through inhalation and has the potential to resolve IPF or block its progression, returning patients to a healthier lung function by uniquely targeting a different cellular signaling pathway than previous pharmaceutical approaches. Preclinical evidence suggests that LTI-03 sustains survival of damaged lung lining cells in addition to slowing and resolving the downstream progress of fibrosis. If successful in clinical trial testing, LTI-03 will offer a paradigm shift for the treatment of lung fibrosis.

IPF affects more than 80,000 people in the U.S. and is the cause of approximately 40,000 deaths annually. However, Dr. Shetty resolutely seeks to improve IPF outcomes. “Preclinical trials have shown very positive results. Building on this work, we hope to help IBF patients with LTI-03,” commented Shetty. “If successful, it’s the real work of my life.”

To further build upon the researchers’ latest work, UT Health Science Center at Tyler was recently awarded $37 million as a recipient of the Clinical and Translational Science Award (CTSA), the largest NIH offering for research and education. The five-year grant aims to enhance and expand existing infrastructure to cultivate collaborative studies in various disciplines, as well as fund expansion, education and training for clinical research.

Researchers from each of the CTSA collaborative institutions meet at UT Health Science Center at Tyler.

This research builds on a strong foundation of internationally recognized research that university investigators have done and continue to do in tuberculosis and non-tuberculous mycobacteria (NTM). A strain of bacteria was even christened Nocardia Wallacei by the NIH and Centers for Disease Control in honor of the PI who unearthed the strain, Dr. Richard Wallace.

Professor of Microbiology Dr. Richard Wallace, who is ranked in the top one percent of physicians in his field by U.S. News and World Report, joined The University of Texas Health Science Center at Tyler in 1982. For nearly 40 years, Dr. Wallace and colleagues have been investigating and treating nontuberculous mycobacteria (NTM) lung disease, a serious infection that leads to debilitating lung damage, caused by common mycobacteria in the environment, specifically near warm water.

NTM has numerous variances of species, but Mycobacterium Avium Complex (MAC) is the most common, accounting for 80% of all U.S. NTM lung disease cases. Although rare, it has become increasingly more common in the United States and other parts of the world, annually affecting 90,000 people in the U.S. While Wallace and his team were globally renowned for their MAC treatment for decades, the disease itself did not have a drug treatment approved by the FDA. However, Dr. Wallace and his colleagues Barbara Brown-Elliott, Dr. David Griffith and Dr. Julie Philley pioneered Amikacin Liposome Inhalation Suspension (ALIS), the first drug approved by the FDA specifically for hard-to-treat MAC in early 2019. Through rigorous trials, ALIS proved to triple the treatment success rate in patients; thereby, ensuring effective treatments worldwide. “This has been my passion for almost forty years,” recounted Dr. Wallace. “When I began, we knew so little about the bacteria, including how to treat them and where they came from. Now, having been a part of this great cadre of colleagues to get us here–that’s been a true fulfillment.”

Dr. Richard Wallace Barbara Brown-Elliott work in their lab.

“This year has been monumental for The University of Texas Health Science Center at Tyler,” said Dr. Kirk A. Calhoun, president of UT Health Science Center at Tyler and chairman of the board for UT Health East Texas. “The research conducted here not only benefits East Texans, but also has a global impact, fulfilling key elements of our mission. These discoveries and advancements are significant and forecast a multitude of great things to come from our university as we continue to grow and advance East Texas.”

To view the original article, pick up a copy of Tyler Today’s August/September 2019 magazine or visit Tyler Today.