Xtem Pharmaceuticals, Inc. was recently founded to develop novel therapeutics for Chronic Myelogenous Leukemia. Although current treatment protocols can manage this disease, in most cases this requires continuous treatment. If treatment is terminated, the disease returns due to a refractory population of stem-like cells known as leukemia initiating cells. Our technology, which was developed in the laboratory of founder, Steven Reed, Ph.D., at Scripps Research Institute, La Jolla, is designed to sensitize this resistant population of leukemia initiating cells in order to effect a complete cure that is stable in the absence of treatment. To date, we have identified small druglike molecules that look promising in cell-based assays in vitro. We are now seeking early stage investment to carry out proof of concept experiments in animal models. Ultimately, we hope to develop lead compounds that can be tested in human clinical trials.
developing novel therapeutics for
chronic myelogenous leukemia
Chronic Myelogenous Leukemia
Chronic myelogenous leukemia (CML) was the first malignancy associated with a specific chromosomal anomaly termed the Philadelphia Chromosome. The anomaly was shown to cause the fusion of two genes to produce the BCR-ABL oncogene, which drives the disease. Bcr-Abl induces CML by driving aberrant differentiation of hematopoietic stem cells. This occurs specifically because Bcr-Abl expression causes elevated expression of another oncoprotein, c-Myc.
CML patients in the early stages of the disease, known as chronic phase are usually responsive to drugs known as tyrosine kinase inhibitors (TKIs) that target Bcr-Abl, in that the 5-year progression-free survival rate is 68%. However, long-term remission is achieved less than half the time, with a large percentage of patients experiencing relapse upon cessation of TKI treatment. This has been interpreted as indicating that a population of leukemia initiating cells (LICs) is refractory to TKI treatment. LICs are thought to possess properties similar to hematopoietic stem cells such as self-renewal and quiescence, rendering them resistant to most therapies. Therefore, CML LICs serve as a reservoir of BCR-ABL possessing but TKI-resistant cells that prevent cure. Patients must remain on TKI drugs indefinitely, which has a number of deleterious implications. Xtem Pharmaceuticals is developing technology aimed at both killing CML LICs and sensitizing them to other treatments, such as TKI drugs. Our goal is to help CML patients achieve permanent remission without continuous therapy.
Dr. Steven Reed, Ph.D.
Dr. Steven Reed joined the faculty of the Scripps Research Institute in 1986. He is currently professor of Molecular Medicine. Dr. Reed received a B.S. in Molecular Biophysics and Biochemistry from Yale University and a Ph.D. in Biochemistry from Stanford University. He then carried out postdoctoral work in Genetics with Leland Hartwell at the University of Washington. He was on the faculty of UCSB prior to joining the Scripps Research Institute. Dr. Reed’s major research focus has been in the areas of control of cell proliferation and cancer. This work ultimately led to the identification of a potential therapeutic target for treating chronic myelogenous leukemia and the drug discovery program that represents the core technology being developed by Xtem Pharmaceuticals. Dr. Reed is currently the Chief Scientific Officer of Xtem Pharmaceuticals.
Dr. Susanna Ekholm-Reed, Ph.D.
Dr. Ekholm-Reed received a B.A. in Biochemistry from the University of Lund and a PhD in Cancer Biology from the Karolinska Institute in Stockholm, Sweden, in 2004. Her thesis focused on the role of cyclin E and SCF Fbw7 , the E3 ligase that targets cyclin E for degradation, in the context of cell cycle progression and cancer. This work, which was continued during post-doctoral studies in Steven Reed’s laboratory at the Scripps Research Institute, was central to the identification of a therapeutic target for treatment of chronic myelogenous leukemia, which is the basis for Xtem’s technology. Subsequently she has been a key person involved in developing and testing therapeutic molecules in our drug discovery program.
Dr. Linda Sherman, Ph.D.
Professor Linda Sherman received her A.B. from Barnard College in Physics, Ph.D. from M.I.T. in Biology, and did postdoctoral research in immunology at Albert Einstein Medical College and Harvard Medical School. Over the years her research interests have focused on the basis for recognition of self and non-self antigens by T lymphocytes as exemplified by allorecognition, immune tolerance, cancer immunotherapy and autoimmunity. She has served on advisory review panels for the National Science Foundation, The American Cancer Society, The Juvenile Diabetes Foundation, and The National Institutes of Health. She is currently Professor of Microbiology and Immunology at Scripps Research, formerly the Scripps Research Institute.
Dr. Bruce E. Torbett, MSPH, Ph.D.
Dr. Torbett is an Associate Professor in the Department of Immunology and Microbiology, at Scripps Research, La Jolla, CA. He received his B.S. at Colorado State University, Fort Collins, CO, MSPH at UCLA, Los Angeles, CA, and PhD, (focus: Immunology), at UCLA. He is the Co-Director of the International HIVE Center and San Diego CFAR, and Director of the CFAR Proteomics Center. Bruce studies genetic modification of human blood cells to correct diseases and investigates HIV-drug resistance. He was a co-founder of VaxDesign, INC, and Chair of the Scientific Advisory Board. VaxDesign was started to provide an in vitro immune system for rapid evaluation of vaccines and adjuvants and biologic drug immunogenicity. VaxDesign was acquired by Sanofi Pasteur in 2010.
Dr. Anton Cheltsov, Ph.D.
Anton Cheltsov holds an M.S. in Chemistry from Moscow State University in Russia and a Ph.D. in Medical Sciences from the University of South Florida, College of Medicine. He is the founder of Q-MOL LLC and the developer of Q-MOL’s high fidelity protein-ligand docking technology. Dr. Cheltsov has an extensive background in computational biology and in silico drug discovery that he developed during postdoctoral training at The Scripps Research Institute. Shortly after, he continued these studies at the Prebys Chemical Genomics Center at the Sanford-Burnham-Prebys Discovery Institute. There he was a member of the cheminformatics and high content analysis group within high throughput screening team. Dr. Cheltsov is currently engaged in several drug discovery collaboration projects with premier academic research institutions such as The Scripps Research Institute (where he is an Adjunct Professor), The Sanford-Burnham-Prebys Discovery Institute and Duke University. Dr. Cheltsov carried out the in silico screens of chemical compounds that provided the core of Xtem’s technology.