On Target's technology is based on the work done by Dr. Philip S. Low; the Ralph C. Corley distinguished professor of chemistry at Purdue University. A major focus in his lab has been the discovery and development of small molecules that target specific pathological cells. Early on, he discovered that receptors for folic acid are measurably over-expressed on activated macrophages (promote inflammation) and many types of human cancer cells. Using folate as a "Trojan Horse", Dr. Low and his lab have been able to introduce therapeutics, radio imaging agents and optical imaging agents to these diseased cells. Over 15 years ago Dr. Low co-founded Endocyte, Inc. a company founded to commercialize the therapeutic and diagnostic applications for folate and other more recently discovered targeting agents. In the winter of 2011 Endocyte went public. On Target, incorporated at the end of 2010, is focused on applying Dr. Low's targeting technology to optical imaging. Dr. Low is a board member, significant shareholder and Chief Science Officer.
Dr. Low's partner in On Target is Tom Hurvis, Chairman of Old World Industries, LLC, a worldwide chemical manufacturer of ethylene glycol and ethylene oxide. Peak Automotive distributes products worldwide, which includes motor oil, antifreeze, windshield washer fluid and windshield wiper blades, all of which is a major part of Old World Industries, LLC. On Target's CEO is Martin Low who has had products successfully developed under his leadership in healthcare and renewable energy. The products have won awards from and been recognized by Business Week, The New York Times, The Smithsonian Institute, The Thomas Edison Foundation, and National Geographic. Sean F. Bradley is MS – Director of CMC. Sean brings 20 years of pharma manufacturing experience with specialization in synthesis development, scale-up manufacturing, and validation. He joins On Target as a veteran of both manufacturing and business from Regis Technologies.
More on Dr. Low: http://www.chem.purdue.edu/people/faculty/faculty.asp?itemID=44
Philip S. Low
Ralph C. Corley Distinguished Professor–Biochemistry
Office: WTHR 331B
For Professor Low's individual Home Page click here.
Our laboratory is working in two areas that stem from a basic interest in membrane structure and function. First, we are investigating the function and molecular organization of the human red blood cell membrane (see cartoon below).
Included in this research are projects aimed at characterizing: i) the interactions between the membrane and its underlying cytoskeleton (see sketch), ii) the signal transduction pathways that control cell shape and flexibility, iii) the crystallographic structure of important membrane proteins, and iv) the changes in membrane architecture that trigger unwanted red cell adhesion.
A second research thrust focuses on the use of targeting ligands to deliver covalently attached therapeutic and imaging agents specifically to pathologic tissues for medical purposes. Because the receptor for the ligand, folic acid, is measurably over expressed by activated macrophages (but no other hematopoietic cells) and many types of human cancers, we are attaching folic acid to drugs in order to facilitate their binding and uptake by both activated macrophages and cancer cells. Molecules targeted to tumors with folate to date include: i) radio imaging agents, ii) chemotherapeutic drugs, iii) gene therapy constructs, iv) liposomes with encapsulated drugs, v) protein toxins, vi) immunotherapeutic agents, vii) radio therapeutic complexes, viii) MRI contrast agents, ix) nanoparticles, x) optical imaging agents, xi) oligonucleotides, and xii) various therapeutic proteins. In general, the folate conjugates have proven to be highly potent and nontoxic to normal tissues. Two folate targeted drugs are currently in human clinical trials for various types of cancer.
As mentioned above, folate-drug conjugates are also targeted with high specificity to activated macrophages. Because activated (but not resting) macrophages either cause or worsen a variety of serious human diseases, including rheumatoid arthritis, atherosclerosis, ulcerative colitis, Crohn's disease, psoriasis, osteomyelitis, multiple sclerosis, graft versus host disease, glomerulonephritis, systemic lupus erythematosis, and osteoporosis, we have undertaken to develop targeted therapies that selectively eliminate or inactivate the responsible activated macrophages. Preclinical data from our lab that have resulted in soon-to-be initiated clinical trials in rheumatoid arthritis have demonstrated that the strategy is highly effective and is accompanied by little or no toxicity.
B.S., 1971, Brigham Young University; Ph.D., 1975, University of California, San Diego. Recognitions
- Outstanding Commercialization Award for Purdue University Faculty, 2006
- National Institutes of Health MERIT Award, 1999
- Elected Fellow of the American Association for the Advancement of Science, 1998
- Sigma Xi Research Award, 1997
- Herbert Newby McCoy Award(Purdue University's award for the best research on campus), 1993
- Indiana Lions Club Cancer Research Award, 1991
- International Union Against Cancer Fellow, 1987
- Research Associate, University of Massachusetts, 1975-76
- Kodippili G. C.;Spector, J.;Sullivan, C.;Kuypers, F. A.;Labotka, R.;Gallagher, P. G.;Ritchie, K.;Low, P. S., Imaging of the diffusion of single band 3 molecules on normal and mutant erythrocytes . Blood 2009, 113, 6237-6245.
- Kularatne S. A.;Wang, K.;Santhapuram, H. K. R.;Low, P. S., Prostate-Specific Membrane Antigen Targeted Imaging and Therapy of Prostate Cancer Using a PSMA Inhibitor as a Homing Ligand . Molecular Pharmaceutics 2009, 6, 780-789.
- Kularatne S. A.;Zhou, Z. G.;Yang, J.;Post, C. B.;Low, P. S., Design, Synthesis, and Preclinical Evaluation of Prostate-Specific Membrane Antigen Targeted Tc-99m-Radioimaging Agents . Molecular Pharmaceutics 2009, 6, 790-800.