64th ASH Annual Meeting and Exposition: 802. Chemical Biology and Experimental Therapeutics I

Symposia: Chemical Biology and Experimental Therapeutics Oral and Poster Abstracts
Oral

Research, Fundamental Science, Bleeding and Clotting, Acute Myeloid Malignancies, AML, Biological therapies, Translational Research, hemophilia, Bispecific Antibody Therapy, Non-Biological therapies, Plasma Cell Disorders, Combination therapy, Chemotherapy, Coagulant Drugs, drug development, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies, metabolism, Myeloid Malignancies, Pharmacology, Biological Processes, Technology and Procedures, molecular biology, omics technologies

353-355 (Ernest N. Morial Convention Center)

Moderators:

Yana Pikman, MD, Dana Farber Cancer Institute and Philipp B. Staber, MD, PhD, Medical University of Vienna

Disclosures:

No relevant conflicts of interest to declare.

Chemical biology involves the development of novel drugs to modulate key targets of a disease. Recent technology has allowed the development of different therapeutics (including cellular and immune therapies, molecular glues and degraders/PROTACs) and rapid integration of combination therapies to accelerate the transaltion of new therapies to the clinic. This oral session will highlight 6 new discoveries into the drivers of benign and malignant hematology and how to modulate them with new therapeutics.

2:00 PM

271

A Novel Bi-Specific T-Cell Engager Targeting ILT3 Is Potently Effective in Multiple Myeloma

Francesco Di Meo, PhD¹^*, Anjushree Iyer²^*, Keith Akama, PhD²^*, Christina Yu¹^*, Rujin Cheng, PhD²^*, Annamaria Cesarano¹^*, Silvia Marino, PhD¹, Arafat Aljoufi, MD¹, Rajesh Soni³^*, Julie M Roda, PhD²^*, James Sissons, PhD²^*, Ly P Vu, PhD⁴, Monica L. Guzman, PhD⁵, Kun Huang, PhD¹^*, David G. Roodman, MD, PhD¹ and Fabiana Perna, MD, PhD¹

¹Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
²NGM Biopharmaceuticals, South San Francisco, CA
³Proteomics and Macromolecular Crystallography Shared Resource, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY
⁴Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada
⁵Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medicine/New York Presbyterian Hospital, New York, NY

2:15 PM

272

Orthogonal Proteogenomic Approaches Identify the Druggable PA2G4-MYC Axis in 3q26 AML

Matteo Marchesini, PhD^1,2^*, Andrea Gherli¹^*, Elisa Simoncini¹^*, Anna Montanaro¹^*, Natthakan Thongon³, Luca Pagliaro¹^*, Federica Vento⁴^*, Lucas Moron Dalla Tor¹^*, Chiara Liverani²^*, Raffaella Zamponi¹^*, Elena Follini⁵^*, Benedetta Cambò, MD⁶^*, Bruno Lorusso¹^*, Roberta La Starza⁷^*, Antonio Cuneo⁸^*, Cristina Mecucci, MD, PhD⁷, Simona Colla, PhD³^*, Federico Quaini¹^* and Giovanni Roti, M.D., Ph.D.^1,6

¹Department of Medicine and Surgery, University of Parma, Parma, Italy
²IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" IRST, Meldola (FC), Italy
³Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX
⁴Department of Medical Sciences, University of Ferrara, Ferrara, Italy
⁵Hematology and Bone Marrow Transplantation Unit, Ospedale “Guglielmo da Saliceto”, Piacenza, Italy
⁶Hematology and BMT Unit, Azienda Ospedaliera-Universitaria di Parma, Parma, Italy
⁷Department of Medicine, Hematology and Clinical Immunology, University of Perugia, Perugia, Italy
⁸St. Anna University Hospital, Ferrara, Italy

2:30 PM

273

Dual IKZF2 and CK1α Degrader Targets Acute Myeloid Leukemia Cells

Sun Mi Park¹^*, David Miyamoto²^*, Grace Han³^*, Mandy Chan, BS³^*, Nicole Curnutt²^*, Nathan Tran²^*, Anthony Velleca⁴^*, Jun Hyun Kim¹^*, Alexandra Schurer, BS¹^*, Kathryn Chang⁵^*, Christina M Woo²^* and Michael G Kharas, PhD⁶

¹Memorial Sloan Kettering Cancer Center, New York, NY
²Harvard University, Boston
³Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York City, NY
⁴Memorial Sloan Kettering Cancer Center, New York
⁵Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York city, NY
⁶Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY

2:45 PM

274

A FVIII-Mimetic Bispecific Antibody with an Embedded Self-Regulation Mechanism Reduces the Risk of Prothrombotic Events for the Treatment of Haemophilia a

Vincent Muczynski, PhD^1,2^*, Angel Smith¹^*, Thibaud Sefiane³^*, Olivier D. Christophe, PhD³^*, Peter J. Lenting, PhD³^*, David Granger, PhD¹^*, Kerry Chester, PhD^1,2^* and Amit C. Nathwani, MD, PhD^1,2,4

¹NovalGen Ltd, London, United Kingdom
²University College London - Cancer Institute, London, United Kingdom
³Inserm U1176, Le Kremlin-Bicetre, France
⁴Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free NHS Foundation Trust, London, United Kingdom

3:00 PM

275

Targeting SAMHD1 Promotes Anti-Tumor Immunity in Acute Myeloid Leukemia

Lei Zhang, MD¹^*, Haojie Dong, PhD²^*, Xin He, MD¹^*, Yichun Lin³^*, Weidong Hu, PhD⁴^*, Amandeep Salhotra, MD⁵, Saro H. Armenian, DO, MPH⁶, Guido Marcucci, MD^5,7, Yun Luo, PhD⁸^* and Ling Li, PhD⁹

¹Department of Hematologic Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope National Medical Center, Monrovia, CA
²Department of Hematologic Malignancies Translational Science, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
³College of Pharmacy, Western University of Health Sciences, Pomona, CA
⁴Department of Immunology & Theranostics, City of Hope National Medical Center, DUARTE, CA
⁵Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
⁶Department of Pediatrics, City of Hope National Medical Center, Duarte
⁷Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
⁸Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA
⁹Department of Hematological Malignancies Translational Science, Department of Pediatrics, Gehr Family Center for Leukemia Research, Hematologic Malignancies and Stem Cell Transplantation Institute, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA

3:15 PM

276

Genome-Wide CRISPR/Cas9 Knockout Screen Reveals Novel Gilteritinib Combinations Targeting Oxidative Phosphorylation and De-Novo Purine Biosynthesis Pathways for FLT3-ITD⁺ Acute Myeloid Leukemia

Steven Sher^1,2^*, Pu Zhang, PhD³^*, Lindsey Brinton, PhD⁴, Mehdi Gharghabi, PharmD⁴^*, Katie Williams, MS⁴^*, Matthew Cannon, PhD⁵, Janek S. Walker, PhD⁴, Daniel Canfield⁶^*, Larry Beaver, BS⁴^*, Casey B. Cempre, B.S.⁴^*, Hannah Phillips, BS⁴^*, Xuyong Chen, PhD⁷^*, Pearlly S. Yan, PhD⁸^*, Amy M. Lehman, M.A.S⁹^*, Peggy Scherle, PhD¹⁰, Min Wang¹¹^*, Kris Vaddi, PhD¹⁰, Robert A. Baiocchi, MD, PhD¹², Ruoning Wang, PhD¹³^*, Deepa Sampath, PhD¹⁴, Lapo Alinari, MD, PhD¹², James S. Blachly, MD⁴ and Rosa Lapalombella, PhD¹²

¹Division of Hematology, Department of Internal Medicine, THE OHIO STATE UNIVERSITY, COLUMBUS, OH
²Medical Scientist Training Program, The Ohio State University, Columbus, OH
³Beth Israel Deaconess Medical Center, Boston, MA
⁴Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH
⁵The Ohio State University Wexner Medical Center - Experimental Hematology Lab, Columbus, OH
⁶Ohio State University, Columbus, OH
⁷The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, OH
⁸Genomic Shared Resource, The Ohio State University, Columbus, OH
⁹Center for Biostatistics, The Ohio State University, Columbus, OH
¹⁰Research and Development, Prelude Therapeutics, Wilmington, DE
¹¹Prelude Therapeutics, Wilmington, DE
¹²Department of Internal Medicine, Division of Hematology, College of Medicine, The Ohio State University, Columbus, OH
¹³Nationwide Children's Hospital, Columbus, OH
¹⁴Department of Hematopoietic Biology & Malignancy, The University of Texas, MD Anderson Cancer Center, Houston, TX

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^*signifies non-member of ASH

802.O1.6 802. Chemical Biology and Experimental Therapeutics I