66th ASH Annual Meeting: 802. Chemical Biology and Experimental Therapeutics: Poster II

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

Research, Artificial intelligence (AI), Lymphoid Leukemias, Acute Myeloid Malignancies, ALL, Combination therapy, AML, Fundamental Science, Lymphomas, CLL, Non-Hodgkin lymphoma, Drug development, APL, MPN, Translational Research, Assays, B Cell lymphoma, Hematopoiesis, Chronic Myeloid Malignancies, Diseases, Treatment Considerations, Biological therapies, Immunotherapy, Lymphoid Malignancies, Non-Biological therapies, Biological Processes, Myeloid Malignancies, Pharmacology, Technology and Procedures, Molecular biology, Profiling, Imaging, Molecular testing

Halls G-H (San Diego Convention Center)

3584

Cancer Pathway Connectivity Resolved By Drug Perturbation and RNA Sequencing

Thi Huong Lan Do^1,2^*, Caroline Lohoff, MSc^3,4^*, Ferris Jung⁵^*, Sandra Kummer¹^*, Vladimir Benes⁵^*, Wolfgang Huber⁴^*, Junyan Lu^4,6^* and Thorsten Zenz^1,2,7

¹Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland
²University of Zurich (UZH), Zurich, Switzerland
³Medical Faculty Heidelberg, Heidelberg University Hospital, Heidelberg, Germany
⁴Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
⁵Genomic Core Facility, European Molecular Biology Laboratory, Heidelberg, Germany
⁶Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
⁷INTeRCepT Consortium, The LOOP Zurich Medical Research Center, Zurich, Switzerland

3585

AUTX703, a Novel and Potent KAT2A and KAT2B Protein Degrader, Induces Differentiation and Offers Survival Advantage in a Primary Human AML Xenograft Model

Hélène Duparc, PhD¹^*, James Neef, BS²^*, Janany Kandiah, MS¹^*, Maulasri Bhatta, PhD²^*, Agathe Chédeville, PhD¹^*, Joe DeBartolo, PhD²^*, Sara Sinicropi-Yao, PhD²^*, Betty Chan, PhD²^*, Alex Constan, PhD²^*, Christophe Marzac, MD¹^*, Jean-Baptiste Micol, MD^1,3, Laura Antipov, PhD²^*, Stephane De Botton¹^*, Katharine E Yen, PhD², David S Millan, PhD²^*, Iléana Antony-Debré, PhD, PharmD¹^* and Kimberly S Straley, BS²

¹Institut Gustave Roussy, Villejuif, France
²Auron Therapeutics, Newton, MA
³Institut Gustave Roussy, Villejuif, FRA

3586

Discovery of BTC-86, a Novel Second-Generation Menin-MLL Inhibitor to Overcome the Acquired Resistance in MEN1 for R/R Acute Leukemia

Suxing Liu¹^*, Weimin Hu, PhD²^*, Dexiao Yang, MS³^*, Liang Han, MS³^*, Minghui Tong, PhD³^*, Yuna Yan, PhD²^*, Shek Ling Chan, PhD²^*, Zhiguo Xi, PhD³^*, Xuan Shi, MS³^* and Qiyue Hu, MS²^*

¹Beyang Therapeutics Co. Ltd., Edison, NJ
²Beyang Therapeutics Co. Ltd., Shanghai, China
³3D BioOptima, Suzhou, China

3587

Genome-Wide CRISPR/Cas9 Knockout Screen Reveals Novel LP-168 (Rocbrutinib) Combinations Targeting BCL-2 Protein Members for Chronic Lymphocytic Leukemia

Britten K. Gordon, BS¹, Ethan C. Whipp, MSc²^*, Lianbo Yu, PhD¹^*, Samon Benrashid, BS¹^*, Andrew D. Mitchell, MS¹^*, Alexander He, BS¹^*, Jazmin Urrutia, BS¹^*, Shrilekha Misra, PhD¹^*, Alexander R. Marr, BS¹, Tzung-Huei Lai, DVM, PhD¹^*, Naina Karnati¹^*, Shanmugapriya Thangavadivel, PhD³^*, Kerry A. Rogers, MD⁴, Seema A. Bhat, MD⁵^*, Nicole R. Grieselhuber, MD, PhD⁶, Yi Chen, PhD⁷^*, Fenlai Tan, MD, PhD⁸, Stephen P. Anthony, DO⁹, Yu Chen, MD, PhD⁷, Deepa Sampath, PhD¹⁰, Rosa Lapalombella, PhD¹ and Jennifer A. Woyach, MD¹¹

¹The Ohio State University, Columbus, OH
²Comprehensive Cancer Center - Wexner Medical Center, The Ohio State University, Columbus, OH
³Division of Hematology, The Ohio State University, Dublin, OH
⁴Division of Hematology, The Ohio State University, Columbus, OH
⁵Division of Hematolopgy, The Ohio State University, Columbus, OH
⁶Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH
⁷Newave Pharmaceutical Inc., Pleasanton, CA
⁸Guangzhou Lupeng Pharmaceutical Co. Ltd, Guangzhou, China
⁹Newave Pharmaceutical Inc., Colbert, WA
¹⁰Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
¹¹Division of Hematology, Ohio State University Comprehensive Cancer Center, Columbus, OH

3588

KT-253, a Highly Potent and Selective MDM2 Protein Degrader, Eliminates Malignant Myelofibrosis Stem/Progenitor Cells

Min Lu¹, Lijuan Xia²^*, Yogesh Chutake³^*, Joyoti Dey, PhD, MPH³^* and Ronald Hoffman, MD⁴

¹The Tisch Cancer Institute, Division of Hematology & Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
²Tisch Cancer Institute, Department of Medicine, Division of Hematology/Oncology, Myeloproliferative Neoplasm-Research Consortium, Icahn School of Medicine at Mount Sinai, New York, NY
³Kymera Therapeutics, Watertown, MA
⁴Division of Hematology & Oncology, Icahn School of Medicine at Mount Sinai, New York, NY

3589

PIM447, a Pan-PIM Kinase Inhibitor, in Combination with Venetoclax Exerts a Potent Anti-Tumor Activity in the Bone Marrow Niche

Fernanda Marconi Roversi, PhD^1,2^*, Maura Lima Pereira Bueno²^*, Samara de Sousa Mariano³^*, Fernanda Soares Niemann, MSc²^*, Adriana da Silva Santos Duarte, PhD²^*, Audrey Bastos²^*, Nádia Ghinelli Amôr, PhD²^*, Irene Santos, MSc²^*, Jose Andres Yunes⁴^*, Sandra Pinho, PhD⁵ and Sara Teresinha Olalla Saad, MD PhD²

¹Department of Surgery, Emory University (currently), Atlanta, GA
²Hematology and Transfusion Medicine Center, State University of Campinas – UNICAMP, Campinas, Brazil
³Centro Infantil Boldrini, Campinas, Brazil
⁴Boldrini Research Center, Campinas, Sao Paulo, Brazil
⁵Department of Pharmacology & Regenerative Medicine, University of Illinois at Chicago, Chicago, IL

3590

Targeting Cytidine Triphosphate Synthase 1 Promotes Anti-AML Immunity

Meng Liu¹^*, Lei Zhang, PhD, MD²^*, Haojie Dong, PhD²^*, Xin He, MD²^*, Yang Li, MD^2,3^*, Umesh Yadav²^*, Guido Marcucci^4,5 and Ling Li, PhD²

¹Department of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope National Medical Center, Monrovia, CA
²Department of Hematological Malignancies Translational Science, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
³Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
⁴Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA
⁵Department of Hematologic Malignancies Translational Science, Duarte, CA

3591

ASTX295 a Novel Potent MDM2 Antagonist Induces More Than One Mechanism of Programmed Cell Death (PCD) in Lymphoid Malignancies

Nishat Iqbal, BSc, MSc¹^*, Sandrine Jayne, PhD¹^*, Harriet S. Walter, MD, PhD, MRCP¹^*, Andrea Biondo, MD, PhD²^*, Martin Sims, PhD²^*, Maria Ahn, PhD³^* and Martin J.S. Dyer, MA, DPhil, FRCP, FRCPath¹^*

¹The Ernest and Helen Scott Haematological Research Institute, University of Leicester, Leicester, United Kingdom
²Astex Pharmaceuticals, Cambridge, United Kingdom
³Astex Pharmaceuticals, Cambridge, GBR

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^*signifies non-member of ASH