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
Stay up to date on our new collaborations and recent progress.
The University of Texas MD Anderson Cancer Center and Blueprint Medicines Corporation today announced a three-year strategic research collaboration focused on accelerating development of BLU-222, an investigational precision therapy designed to target cyclin-dependent kinase 2 (CDK2).
The collaboration brings together MD Anderson translational research scientists, the drug development capabilities of MD Anderson’s Therapeutics Discovery division and Blueprint Medicines’ precision therapy pipeline and expertise. The teams seek to characterize the range of cancer types susceptible to treatment with a selective CDK2 inhibitor, advance BLU-222 mono- and combination-therapy strategies with the potential to maximize patient benefit, and identify novel biomarkers that may better predict treatment response and optimize patient selection.
“This collaboration highlights our commitment to rapidly advance innovative science and builds on our prior efforts – also supported by MD Anderson investigators – that led to two FDA-approved and breakthrough therapy-designated precision therapies for patients with cancer,” said Fouad Namouni, M.D., President of Research and Development at Blueprint Medicines. “By leveraging the power of MD Anderson’s expertise in translational research, we aim to reveal the broad potential of BLU-222 and optimize our clinical development strategy to bring treatment innovation to as many patients as possible.”
Under the preclinical collaboration agreement, Blueprint Medicines expects to collaborate primarily with MD Anderson’s Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platform, which leads cutting-edge translational biology research to rapidly position new therapies for clinical trials. TRACTION is a core component of MD Anderson’s Therapeutics Discovery division, an integrated team of clinicians, researchers and drug development experts working to advance impactful therapies that address patient needs.
MD Anderson and Blueprint Medicines will jointly design translational studies, and Blueprint Medicines will provide funding, research compounds and additional support. As part of the agreement, MD Anderson is eligible to receive certain payments based on the future development of BLU-222.
“As a critical regulator of the cell cycle, CDK2 is an exciting therapeutic target in oncology with broad potential across multiple patient populations and treatment settings,” said Timothy Heffernan, Ph.D., executive director of TRACTION and head of oncology research in MD Anderson’s Therapeutics Discovery division. “Through our collaboration with Blueprint Medicines, we aim to improve the scientific understanding of the role of CDK2 inhibition in cancer treatment and advance a new therapeutic option for patients with difficult-to-treat tumors, which further demonstrates our commitment to work at the forefront of cancer research.”
Cyclin-dependent kinases and their cyclin partners regulate the cell cycle, which is the process of cell growth and division. In certain cancers, aberrant cyclin E (CCNE) hyperactivates CDK2, resulting in cell cycle dysregulation and tumor proliferation. Aberrant CCNE has been observed as a primary driver of disease in subsets of patients across a wide range of tumor types and has been shown to promote resistance to CDK4/6 inhibitors and other therapies. BLU-222 is a potential best-in-class CDK2 inhibitor that has shown robust anti-tumor activity in preclinical models of CCNE-aberrant ovarian, breast and gastric cancer. Blueprint Medicines plans to initiate a first-in-human Phase 1 clinical trial of BLU-222 in patients with CCNE-aberrant cancers in the first half of 2022.
MD Anderson’s relationship with Blueprint Medicines creates a financial conflict of interest, and therefore MD Anderson is implementing an Institutional Conflict of Interest Management and Monitoring Plan for this research.
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.
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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