REPROGRAMMING CANCER CELL DEATH
REPROGRAMMING CANCER CELL DEATH
Dialectic Therapeutics’ mission is to create innovative new technologies to cure cancer. Our goal is to relieve the suffering of patients with cancer, to give them hope, and prolong their productive lives through targeted therapies with limited toxicities and complications.
Dialectic Therapeutics (DT) is a pre-clinical biotechnology company dedicated to the development of unique, impactful anti-cancer drugs that effectively treat patients with few to no other options. DT was founded by three respected cancer scientists and two successful biotech investors and operators. DT is located in Dallas, Texas and has research partners and facilities at UT Health at San Antonio and the University of Florida Health Cancer Center.
DT’S LEAD CANDIDATE, DT2216, is a novel Antiapoptotic Protein Targeted Degradation (APTaD™) compound that selectively induces cancer cells to degrade B-cell lymphoma extra large, or BCL-XL, stimulating the cells to commit suicide, or become more susceptible to chemotherapy. DT2216 is currently in the IND-enabling phase as a single agent and combination therapy in liquid and solid cancer tumors and expects to enter the clinic in 2021.
Pre-clinical studies show that DT2216 is highly effective in various liquid and solid tumors as a single agent and in combination with chemotherapy. Further, these studies show cancer cells are less likely to develop resistance to DT2216 than to other chemotherapy drugs. DT2216 accomplishes this with very little toxicity, particularly to platelets.
As with BCL-XL, there are many other significant proteins associated with cancer that cannot be targeted with current therapies. APTaD™ is a novel approach that can be applied to the broader BCL family and other protein targets. DT’s efforts are focused on developing drug candidates to address this high unmet need. If successful, we will be able to provide cancer patients who have little hope with increased disease-free survival.
The DT team is focused on creating innovative new technologies to address late-stage difficult cancer diagnoses. We are comprised of protein degradation experts and leadership with a strong track record of clinical development and commercial success.
David Genecov, MD – President & CEO, Co-Founder, Board Member
Dr. Genecov is a successful health care entrepreneur and trained as a cranio-facial surgeon. He most recently co-founded and served on the Board of AveXis with Mr. Harkey, which was acquired by Novartis for $8.7bn in 2018. AveXis created the first successful therapy for spinal muscular atrophy, now FDA-approved. Along with Mr. Harkey, he co-founded and serves on the board of Cessation Therapeutics as well as the board of directors of CerSci Pharmaceuticals. Dr. Genecov received a M.D. from the Long School of Medicine at the University of Texas Health Science Center at San Antonio.
John Harkey Jr., JD, MBA – Chairman of the Board & Co-Founder
Mr. Harkey is the Founder of JDH Investment Management, LLC, which is focused on leading innovative and impactful opportunities in the biotechnology industry. Notably, he was the Co-Founder and Executive Chairman of AveXis, which was acquired by Novartis for $8.7bn in 2018. He currently serves as Co-Founder, Board Member and Co-CEO of Cessation Therapeutics, Board Member of CerSci Therapeutics and Board Member of Emisphere Technologies. Mr. Harkey received a B.B.A. in Business Honors and a J.D. from the University of Texas at Austin, and an M.B.A. from Stanford University School of Business.
Larry Tremaine, PhD – Chief Scientific Officer
Dr. Tremaine has 34 years of experience in the pharmaceutical industry, mainly at Pfizer. There he led a variety of laboratory groups with the Drug Metabolism and preclinical PK (DMPK) discipline, providing experimental data for all small molecule programs. He contributed to the development of successfully approved drugs, including Zoloft, Geodon, Chantix, Eliquis, and Xeljanz. Dr. Tremaine received a Ph.D. in Pharmacology from the University of Minnesota Medical School.
James Strauss, MD – Chief Medical Officer
Dr. Strauss specializes in clinical trial development, trial recruitment and clinical oncology and currently serves as a principle investigator for clinical trials at the Mary Crowley Cancer Center in Dallas. Dr. Strauss received a B.A. from Harvard University, an M.D. from New York University School of Medicine and trained at Baylor University Medical Center in Dallas.
Guangrong Zheng, PhD – Director of Medicinal Chemistry & Scientific Co-Founder
Dr. Zheng is an Associate Professor in the Department of Medicinal Chemistry at the University of Florida College of Pharmacy. He received his B.S. in Medicinal Chemistry from Fudan University and his Ph.D. in Synthetic Organic Chemistry from Shanghai Institute of Materia Medica. He then completed his postdoctoral training in drug design and discovery at the University of Kentucky College of Pharmacy. Dr. Zheng’s expertise is in the design, synthesis and structure-activity relationship study of both synthetically derived and natural product-based compounds.
Eric Rasmussen – Chief Financial Officer
Mr. Rasmussen has 25 years of experience in business accounting, mergers and acquisitions, legal administration and corporaterecord keeping. He was a member of original founding team of AveXis and has been an integral part of portfolio investments in over 50 public and private companies. Mr. Rasmussen received a B.A. in Business Administration and Management from Dallas Baptist University.
Joshua Sills – VP of Operations
Mr. Sills has 15 years of experience in technical operations, project management, and leading teams on location and remotely while working in over seventy countries. Mr. Sills received a B.S. in Management Information Systems from Florida State University.
Robert Hromas, MD – Board Member & Scientific Co-Founder
Dr. Hromas is currently the Dean of the Long School of Medicine at the University of Texas Health Science Center at San Antonio. Previously he was Chair of Medicine at the University of Florida, Deputy Director of Indiana University Cancer Center, and Deputy Director and Chief of Hematology-Oncology at the University of New Mexico Cancer Center. Dr. Hromas has been continuously funded by the NIH in cancer research for almost three decades. He currently serves as Chairman of the SAB of Abfero Pharmaceuticals.
Daohong Zhou, MD – Board Member & Scientific Co-Founder
Dr. Zhou is a Professor of Pharmacodynamics at the College of Pharmacy at the University of Florida. He serves as the Associate Director for Translation and Drug Development and the Harry E. Innes Professorship of Cancer Research at the UF Health Cancer Center. Dr. Zhou has published more than 110 peer reviewed scientific articles and book chapters and co-invented more than 8 patents pending in the last five years. His research has been continuously funded for almost two decades by the National Cancer Institute and the National Institute of Allergy and Infectious Disease. He also co-founded Unity Biotechnology (NASDAQ: UBX) to develop senolytic drugs for aging and age-related diseases.
David Hitt, JD, MTax – Board Member
Mr. Hitt practiced transactional intellectual property law for 30 years, including over two decades at Hitt Gaines, gaining extensive experience in patent procurement and counseling in a wide array of physical, electrical, mechanical, mathematical, and computer technologies. He now dedicates his time to protection strategy and teaming with other entrepreneurs to launch and lead early-stage companies. Mr. Hitt received a B.S. in Physics and a B.S. in Business and Public Administration from the University of Texas at Dallas, J.D. from Southern Methodist University, and M.S. in Taxation from Baylor University.
Dialectic Therapeutics Receives $3 Million Seed Award for Product Development Research from the Cancer Prevention & Research Institute of Texas
A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity
Khan, S. et al.
B-cell lymphoma extra large (BCL-XL) is a well-validated cancer target. However, the on-target and dose-limiting thrombocytopenia limits the use of BCL-XL inhibitors, such as ABT263, as safe and effective anticancer agents. To reduce the toxicity of ABT263, we converted it into DT2216, a BCL-XL proteolysis-targeting chimera (PROTAC), that targets BCL-XL to the Von Hippel-Lindau (VHL) E3 ligase for degradation. We found that DT2216 was more potent against various BCL-XL-dependent leukemia and cancer cells but considerably less toxic to platelets than ABT263 in vitro because VHL is poorly expressed in platelets. In vivo, DT2216 effectively inhibits the growth of several xenograft tumors as a single agent or in combination with other chemotherapeutic agents, without causing appreciable thrombocytopenia. These findings demonstrate the potential to use PROTAC technology to reduce on-target drug toxicities and rescue the therapeutic potential of previously undruggable targets. Furthermore, DT2216 may be developed as a safe first-in-class anticancer agent targeting BCL-XL.