Advancing Cancer Treatment
The Therapeutics Discovery division at MD Anderson was created to eliminate the bottlenecks that hamper traditional drug development.
Our team of more than 100 dedicated cancer researchers, doctors, drug developers and scientific experts develops small molecule drugs, biologics and cellular therapies, inspired by the needs of MD Anderson cancer patients and guided by the expertise of the center’s clinicians. To create life-saving transformational medicines quickly, safely and effectively, Therapeutics Discovery works with unparalleled proximity to patients and an unmatched wealth of clinical experience.
Therapeutics Discovery doesn’t bring the “bench to bedside” – it starts with the bench at the bedside – with each patient and their cancer.
The platforms of Therapeutics Discovery are supported by MD Anderson’s Moon Shots Program®.
We have leveraged our unique approach to discover and advance novel small-molecule, biologic and cell-based therapies to answer unmet needs that will improve the lives of our patients.Learn more about our therapeutics pipeline
In the News
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The glutaminase (GLS1) inhibitor IACS-6274, discovered and developed by The University of Texas MD Anderson Cancer Center’s Therapeutics Discovery division, appears to be well-tolerated with successful target inhibition and early signs of anti-tumor activity in a biomarker-driven Phase I trial. Interim results of the study will be presented at the 2021 American Society for Clinical Oncology (ASCO) Annual Meeting on June 4.
On the trial, 17 of 20 evaluable patients achieved a best response of stable disease, with a disease control rate of 60% at 12 weeks. Six patients with biomarker-defined advanced cancers had meaningful durable disease stabilization for greater than six months, with evidence of tumor shrinkage.
Comprehensive pharmacokinetics (PK) and pharmacodynamics (PD) analyses on serial tumor and/or blood samples from trial participants established a robust PK/PD relationship across dose levels. Using a clinical assay developed in-house to measure metabolic activity in patients’ blood mononuclear cells, the team also observed strong inhibition of glutamine metabolism at the recommended Phase II dose level, suggesting IACS-6274 robustly functions as intended to block GLS1 activity.
This represents the first major clinical data reported by MD Anderson’s Therapeutics Discovery division, a unique group of clinicians, researchers and drug development experts working collaboratively to advance impactful new therapies. By working seamlessly with MD Anderson physicians, the team gains unique clinical insights that aid in the development of impactful medicines.
“Within Therapeutics Discovery, we have focused our efforts to develop new therapies that meet the needs of our patients,” said principal investigator Timothy A. Yap, M.B.B.S., Ph.D., associate professor of Investigational Cancer Therapeutics and medical director of the Institute for Applied Cancer Science (IACS). “Our comprehensive efforts to understand and advance IACS-6274 identified select groups of underserved patients as those most likely to benefit from treatment, and we are encouraged by the early results thus far in the study.”
Developing a therapy for underserved patient groups
The development of IACS-6274, previously known as IPN60090, was led by a team of scientists and drug development experts in the IACS and Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platforms, both engines within Therapeutics Discovery.
IACS-6274 was selected for development based on its potency, selectivity and PK profile to provide sustained GLS1 inhibition in patients. The research team then conducted patient-driven translational studies to identify unique populations of patients likely to respond.
Based on these studies, priority indications for the trial include non-small cell lung cancers (NSCLC) with KEAP1/NFEL2L2 mutations, ovarian cancers with low expression of asparagine synthetase (ASNS) and tumors with immune checkpoint inhibitor resistance. Additional insights have revealed that cancers with STK11 and NF1 mutations may respond to GLS1 inhibitors, so the trial also has enrolled those patients.
Evaluating IACS-6274 in a Phase I clinical trial
The first-in-human dose-escalation study was conducted by MD Anderson’s Phase I Clinical Trials Program in the Department of Investigational Cancer Therapeutics. The study was designed to evaluate the safety and tolerability of IACS-6274, to identify the maximum tolerated dose and to establish a recommended Phase II dose. Secondary objectives included PK, PD, anti-tumor activity and correlation of biomarkers with clinical outcomes.
The study has enrolled 22 patients with a median age of 63.5, all of whom had received at least two prior therapies. Sixteen patients (73%) are female and six (27%) are male. The trial included patients with different tumor and molecular subtypes, including many of the identified priority patient populations.
The six patients with durable stable disease included those with advanced ASNS-low ovarian cancer, melanoma resistant to anti-PD-1 therapies, NF1-mutant leiomyosarcoma and STK11-mutant NSCLC.
The most common side effects were mild transient visual disturbances. Less common grade 3 toxicities at higher dose levels included reversible nausea, vomiting and fatigue. One patient experienced dose-limiting acute renal failure and posterior reversible encephalopathy syndrome (PRES) at the highest dose level, which fully resolved.
“IACS-6274 appears to be safe and well-tolerated at our recommended Phase II dose, with early signs of anti-tumor activity in patients with certain molecular features,” Yap said. “As the study progresses and we continue to learn from those participating, we will work to explore rational combination therapies that are predicted to maximize the benefits for distinct groups of patients based on key biomarkers of response.”
A full list of collaborating authors and their disclosures can be found with the abstract.
The University of Texas MD Anderson Cancer Center and Refuge Biotechnologies, Inc. today announced a strategic collaboration to advance new cell therapies for potential treatment of solid tumors. The agreement pairs Refuge’s innovative technologies with the experience and industrial capabilities of MD Anderson’s Biologics Development platform, within the Therapeutics Discovery division.
Under the agreement, MD Anderson will possess exclusive rights to apply Refuge’s proprietary platform for next-generation cell engineering to its tumor infiltrating lymphocyte (TIL) programs. MD Anderson also will co-develop Refuge’s RB-340, a HER-2 targeted CAR T cell therapy with context dependent inducible down-regulation of PD-1, including Investigational New Drug (IND) filing, Good Manufacturing Practice (GMP) production and Phase I/II clinical trials.
“MD Anderson has extensive expertise in developing and manufacturing innovative cell therapies, including groundbreaking work with TILs,” said Bing Wang, Ph.D., chief executive officer and co-founder of Refuge Biotechnologies. “We look forward to working closely with MD Anderson researchers to apply our technology to this promising field of research, while also advancing development of our lead intelligent cell therapy program.”
Using Refuge’s platform for programming cells to selectively react to tumor cells through direct modulation of gene expression utilizing CRISPR interference and activation, RB-340 is designed to conditionally and smartly down-regulate expression of PD-1 on approaching tumor cells, reducing T cell exhaustion and increasing T cell persistence and proliferation, thus creating better efficacy against solid tumors. Treatment with RB-340 in preclinical models has shown a clear survival benefit compared to conventional CAR T cell therapy. IND filing is anticipated in the first half of 2022, with clinical development of RB-340 focused in solid tumors.
Through its Biologics Development platform, MD Anderson is advancing research into therapeutic applications for TILs – naturally occurring lymphocytes that can recognize cancer cells and penetrate a tumor. MD Anderson and Refuge will explore the use of Refuge’s platform to engineer TILs for enhanced anti-tumor activity.
“It is my belief that TILs are poised for a significant impact in the field of cancer therapy, and engineering improved TILs is a vital part of advancing this modality,” said Jason Bock, Ph.D., vice president of Therapeutics Discovery and head of Biologics Development at MD Anderson. “We have been encouraged by the data coming from Refuge’s applications of its next generation, context dependent and inducible cell engineering platform, and we look forward to incorporating its potential into our TIL programs.”
MD Anderson’s Biologics Development platform is built around an experienced team focused on pioneering impactful biologic therapeutics, including antibodies and cell therapies. With a state-of-the-art GMP cell therapy manufacturing facility, the platform unites MD Anderson research with industrial therapeutic development.
Our Unique Model
We are a drug development engine built within MD Anderson, taking an approach unlike anywhere else. Our experienced teams work collaboratively across industry-scale research platforms to advance new therapies, and we collaborate with leading biopharmaceutical companies to bring new medicines to patients in need.Learn more about our approach