66th ASH Annual Meeting: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster II

Symposia: Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms Oral and Poster Abstracts
Poster

Research, Antibody Therapy, Autoimmune disorders, Lymphoid Leukemias, ALL, Hodgkin lymphoma, Combination therapy, Fundamental Science, Apoptosis, Adult, Bispecific Antibody Therapy, Lymphomas, CLL, Non-Hodgkin lymphoma, Drug development, Translational Research, CHIP, Assays, Plasma Cell Disorders, B Cell lymphoma, Clinical Research, Health outcomes research, Diversity, Equity, and Inclusion (DEI), T Cell lymphoma, Diseases, Immune Disorders, Treatment Considerations, Biological therapies, Immunology, Immunotherapy, Aggressive lymphoma, Real-world evidence, Lymphoid Malignancies, Metabolism, Biological Processes, Pharmacology, Technology and Procedures, Molecular biology, Study Population, Animal model

Halls G-H (San Diego Convention Center)

2779

PRPS2 Facilitates the Tumorigenesis of Diffuse Large B-Cell Lymphoma By Promoting Fatty Acid β-Oxidation

Liemei Lv¹^*, Ran Kong¹^*, Yu Zhang²^*, Cong Wang³^*, Guangcai Zhong²^*, Yujie Jiang, MD⁴^*, Kang Lu⁵^*, Tiange Lu²^* and Xiangxiang Zhou, MD²

¹Department of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, China
²Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
³Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, AL, China
⁴Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
⁵Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China

2780

Preclinical Proof-of-Concept of a Novel mRNA-Based Therapeutic Combination of an FcRH5 Targeted NK Cell Engager and an IL-15 Superagonist for the Treatment of Multiple Myeloma

Ailin Bai, PhD^*, Maija Garnaas^*, Zhen Zhang, PhD^*, Rebecca L Riding, PhD^*, Ankita Mishra, MS^*, Kristen Cowens^*, Haley BrinJones^*, Khushbu Bhatt, PhD^*, John Zielinski^*, Matthew Sullivan^*, Anu Yammanuru, PhD^*, Graham MacLean^*, Sam Farlow^*, Russell Karp^*, John Eldredge^*, Maiko Obana, PhD^*, Darren Potz^*, Neeraj Kaushal, PhD^*, Christopher Rowbottom, PhD^*, Kenneth Drombosky, PhD^*, Linh Van, PhD^*, Graham Farrington, PhD^*, Brendan M. Weiss, MD, Joshua P Frederick, PhD^* and Sushma Gurumurthy, PhD^*

Moderna, Inc., Cambridge, MA

2781

The Cyclin-G Associated Kinase (GAK) Is a Critical Targetable Dependency for Successful Mitosis By Diffuse Large B-Cell Lymphomas Linked to Retinoblastoma Loss of Function

Olivia Barbara Lightfuss, BS¹^*, Preet Kumar, BS¹^*, Austin Daniel Newsam, BS¹^*, Lingxiao Li, PhD¹^*, Pierre A. Younes²^*, Toral Shastri, DO³^*, Abdessamad Youssfi Alaoui, PhD⁴^*, Diego E. Hernandez Parets²^*, Paola Manara, MS¹, Daniel Bilbao, PhD⁵, Stephan Schürer, PhD⁶^*, Vance P. Lemmon, PhD⁷^*, Francesco Maura, MD⁸, Yangbo Feng, PhD⁶^*, Hassan A. Ali, PhD, MSM⁹^* and Jonathan H. Schatz, MD¹⁰

¹Sylvester Comprehensive Cancer Center, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
²University of Miami, Miami, FL
³Sylvester Comprehensive Cancer Center, Department of Medicine, University of Miami, Miami, FL
⁴Myeloma Institute, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
⁵Cancer Modeling Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
⁶Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL
⁷Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL
⁸University of Miami, Coral Gables, FL
⁹Department of Neurological Surgery, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
¹⁰Sylvester Comprehensive Cancer Center, Department of Medicine, Division of Hematology, University of Miami Miller School of Medicine, Miami, FL

2782

ATR Inhibition and Replication Stress Converge on a BCL6-Mediated Reversal of the Dark Zone Signature in DLBCL

Allison Chan, PhD¹^*, Akshaya Anbuselvan¹^*, Patrick Jaynes¹^*, Nayana Prabhu²^*, Yuan Ju³^*, Jane Jia Hui Lee³^*, Tze King Tan¹^*, Jasmine Goh¹^*, Marco Foiani^1,4,5^*, Takaomi Sanda, MD, PhD⁶, Wai Leong Tam^1,3,7,8^*, Mark J O'Connor⁹^*, Edward K Chow¹⁰^* and Anand Devaprasath D. Jeyasekharan, MBBS, MRCP, PhD^1,11,12,13^*

¹Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
²A*STAR Institute of Molecular and Cell Biology, Singapore, Singapore
³Laboratory of Translational Cancer Biology, Genome Institute of Singapore, Singapore, Singapore
⁴IFOM, The FIRC Institute of Molecular Oncology, Milan, Italy
⁵University of Milan, Department of Oncology and Hematology-Oncology, Milan, Italy
⁶Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
⁷Department of Biochemistry, National University of Singapore, Singapore, Singapore
⁸School of Biological Science, Nanyang Technological University, Singapore, Singapore
⁹Oncology R&D, AstraZeneca, Cambridge, United Kingdom
¹⁰KYAN Therapeutics, Singapore, Singapore
¹¹NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
¹²Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore
¹³Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

2783

Development of ZE66-0205, a Novel MALT1 Degrader for Treatment of B-Cell Malignancies

Sara Elgamal, PhD¹, Casie Furby¹^*, Marissa Long¹^*, Kaytlynn Fyock¹^*, Thomas M. Sesterhenn¹^*, Megan E. Johnstone, PhD¹, Jianmin Pan, PhD²^*, Shesh N. Rai, PhD²^*, Alexander Khvat, PhD³^*, Ruben Karapetian, PhD³^*, Alexey Ryakhovskiy, PhD³^*, Elena Bulanova, PhD³^*, Vladislav Parchinsky, PhD³^*, Nikolay Savchuk, PhD⁴^*, Iain Dukes, DPhil⁴^*, Amy Burd, PhD⁴^*, Erin K. Hertlein, PhD¹ and John C. Byrd, MD¹

¹Department of Internal Medicine, University of Cincinnati, Cincinnati, OH
²Division of Biostatistics and Bioinformatics, Department of Environmental and Public Health Sciences, University of Cincinnati, Cincinnati, OH
³ChemDiv Inc, San Diego, CA
⁴Eilean Therapeutics, Philadelphia, PA

2784

Sky-1214, a Small Molecule Splicing Modulator Targeting FANCL and Fanci, Provides a New Mechanism of Action Targeting Multiple Myeloma and Non-Hodgkin’s Lymphoma

Simone Rauch, Ph.D.¹^*, Stefan Reber, Ph.D.¹^*, Montserrat Perez-Salvia, Ph.D.¹^*, Marco Pregnolato, Ph.D.¹^*, Botao Liu, Ph.D.²^*, Loren Berry, Ph.D.²^*, Olesia Buiakova, Ph.D.²^*, Hasane Ratni, Ph.D.¹^*, Brian Gudenas, Ph.D.¹^*, Carlo Cusulin, Ph.D.¹^*, Lauren Shanahan, Ph.D.¹^*, Douglas V Faller, M.D., Ph.D.², Veronica Costa, Ph.D.¹^*, Sergey Paushkin, M.D., Ph.D.²^* and Steven Taylor, PhD³^*

¹Skyhawk Therapeutics, Basel, Switzerland
²Skyhawk Therapeutics, Waltham, MA
³Skyhawk Pharmaceuticals, Waltham, MA

2785

LY4152199, a First-in-Class BAFF-RxCD3 Bispecific Antibody for the Treatment of B Cell Malignancies

Wei Yang¹^*, Colleen Burns¹^*, Kevin Lindquist²^*, Julie Dobkin¹^*, Hee Rae Shin¹^*, Cindy Nguyen¹^*, Xiaodong Huang¹^*, Whitney Helms³^*, Nicholas Arce²^*, Yvonne Mak²^*, Audrey Au¹^*, Abraham Abouzeid⁴^*, Marta Witek⁴^*, Ching Ching Leow¹^*, Xueqian Gong⁴^*, Mohan Srinivasan²^*, Joshua I. Park²^*, Kyla Driscoll¹^*, Andrew Hass⁴^*, Rikke Holmgaard¹^*, Omar Duramad²^* and Kristin Bedard²^*

¹Loxo@Lilly, New York, NY
²Loxo@Lilly, South San Francisco, CA
³Loxo@Lilly, Silver Spring, MD
⁴Eli Lilly and Company, Indianapolis, IN

2786

Protein Degrader WH25244 Eliminates Venetoclax Resistance Factors: Mutant or Hyperphosphorylated BCL2, and BCL-XL

Daisy Y. Diaz Rohena, BS¹, Andrew D. Mitchell, MS²^*, Jing Wang, PhD³^*, Stephanie Chamberlain³^*, Chaomei Liu¹^*, John R. Sanchez II, BSc¹, Charmelle D. Williams, MSc, BSc¹, Trisha K. Wathan, BS¹^*, Bailey Slawin, BS¹^*, Kevin Bowman, BS¹^*, Yaxia Yuan⁴^*, Peiyi Zhang⁵^*, Wanyi Hu⁵^*, Guangrong Zheng, PhD⁵^*, William G. Wierda⁶, Nitin Jain, MD⁶, Matthew S. Davids, MD, MMSc⁷, Daohong Zhou, MD^4,8^*, Jennifer A. Woyach, MD² and Deepa Sampath, PhD⁹

¹Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX
²Division of Hematology, Ohio State University Comprehensive Cancer Center, Columbus, OH
³Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
⁴Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX
⁵Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL
⁶Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
⁷Department of Medical Oncology, Dana-Farber Cancer Institute, Inc., Boston, MA
⁸Center for Innovative Drug Discovery, University of Texas Health Science Center at San Antonio, San Antonio, TX
⁹Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX

2787

Targeting Nucleotides Dependency Via SIRT3 Inhibition to Overcome Metabolic Plasticity and Flexibility of Dlbcls

Meng Li, PhD¹^*, Noel Park, PhD²^*, Coraline Mlynarczyk, PhD³, Christopher Chin, PhD⁴^*, Shawn Davidson, PhD⁵^* and Ari M Melnick, MD⁶

¹Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY
²Department of Molecular Biology, Princeton University, Princeton
³Department of Medicine, Division of Hematology & Medical Oncology, Weill Cornell Medicine, New York
⁴Department of Medicine, Weill Cornell Medicine, New York, NY
⁵Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ
⁶Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York, NY

2788

Targeted Therapy with CX4945 Biomimetic Nanodrug Delivery System for High-Risk B-Cell Acute Lymphoblastic Leukemia

Yan Wang¹^*, Fei Wang²^*, Haoan Wu²^*, Qi Han¹^*, Yu Zhang²^*, Chunhua Song, M.D., Ph.D.³ and Zheng Ge, M.D., Ph.D.¹

¹Department of Hematology, Zhongda Hospital, School of Medicine, Southeast University, Institute of Hematology Southeast University, Nanjing, China
²State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Southeast University, Nanjing, China
³The Division of Hematology, The Ohio State University Wexner Medical Center, the James Cancer Hospital, Columbus, OH

2789

A Novel Approach Combining Type II JAK Inhibitor Chz-868 with Nutrient Restriction to Augment Cell Death in Philadelphia like Acute Lymphoblastic Leukemia

Muneera Alhaddad, MBChB^1,2^*, Roberta Buono, PhD¹^*, Van Thu Huynh², Sarah K Tasian, MD³ and David A Fruman, PhD¹

¹Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA
²Division of Oncology, Children's Hospital of Orange County, Orange, CA
³Division of Oncology & Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA

2790

EVOLVE205, a Highly Potent 2:1 CD20-Targeted CD2 Co-Stimulatory T Cell Engager Engineered for the Treatment of B Cell Malignancies and B Cell Autoimmune Diseases

Xingyue An¹^*, Mohosin Sarkar²^*, Guixian Jin²^*, Tiffany Liang²^*, Tracy Lichter²^*, Danielle Klaskin²^*, Afsana Sabrin²^*, Evelyn Teran²^*, Abliz Abdukadir²^*, Hayden Karp²^*, Julio Rodriguez²^*, Hemachander Capiralla²^*, Zengzu Lai²^*, Martin Preyer²^*, Louis Matis²^*, Stella Martomo²^*, Agnes Meade²^*, Jay S. Fine²^* and Jeremy S. Myers²^*

¹EvolveImmune Therapeutics, Inc., BRANFORD, CT
²EvolveImmune Therapeutics, Inc., Branford, CT

2791

Venetoclax Alone or in Combination Shows Promising Activity in Preclinical Models and Clinical Cases of Relapsed/Refractory North American Adult T-Cell Leukemia Lymphoma

Ankit Tanwar, PhD¹, Emma Cordover²^*, Shikhar Sharma³^*, Zixuan Tong⁴^*, Kith Pradhan, PhD⁵^*, Latoya S Townsend, DNP⁴^*, Ioannis Mantzaris, MD⁶, Mendel Goldfinger⁷^*, Nishi Shah, MBBS, MPH⁸, Aditi Shastri, MD⁸, Noah Kornblum, MD⁸, Dennis L Cooper, MD⁷, Ridhi Gupta, MD⁹^*, Simon Zhen¹⁰^*, Nechama Dreyfus, MD¹¹^*, Julie Nguyen⁴, Lauren Shapiro, MD⁸, Eric J. Feldman, MD⁸^*, Ira Braunschweig, MD⁹^*, Beth McLellan, MD⁴^*, Alyssa de Castro, PharmD¹²^*, Xingxing Zang¹³^*, Ali Bazarbachi, MD, PhD¹⁴, Murali Janakiram, MBBS¹⁵, Erik Guillen, MSc¹^*, Gregoire Lauvau, PhD⁴^*, Eric Liu¹⁶^*, Kira Gritsman, MD, PhD⁸, B. Hilda Ye⁴^*, Amit Verma, MD¹⁷, Marina Konopleva, MD¹⁸ and R. Alejandro Sica, MD⁷

¹Albert Einstein College of Medicine, Bronx, NY
²Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
³Department of Oncology, Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY
⁴Albert Einstein Collge of Medicine, Bronx, NY
⁵Department of Oncology, Blood Cancer Institute, Albert Einstein College of Medicine, Bronx, NY
⁶Montefiore Einstein Comprehensive Cancer Center, Bronx, NY
⁷Hematology/Oncology, Montefiore Medical Center/ Albert Einstein College of Medicine, Bronx, NY
⁸Montefiore Einstein Comprehensive Cancer Center, Blood Cancer Institute, Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
⁹Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
¹⁰Columbia Medical Center, New York
¹¹Montefiore Medical Center, Albert Einstein Collge of Medicine, New York, NY
¹²Montefiore Medical Center, Albert Einstein Collge of Medicine, New York
¹³Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY
¹⁴American University of Beirut Dept. of Medicine, Beirut, Lebanon
¹⁵Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope, Duarte, CA
¹⁶Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY
¹⁷Blood Cancer Institute, Department of Oncology, Albert Einstein College of Medicine, Bronx, NY
¹⁸Montefiore Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, NY

2792

Synergistic Antitumor Effect of a Novel First-in-Class Small Molecule OPB-111077 That Inhibits Mitochondrial Oxidative Phosphorylation in Combination with Alkylating Agent

Emiri Omori Takaki^* and Naoto Ohi, PhD^*

Osaka Research Center for Drug Discovery, Otsuka Pharmaceutical Co., Ltd., Osaka, Japan

2793

APR-246 Overcomes Resistance to Asparaginase in Lymphoid Malignancies By Targeting Metabolic Cell Vulnerabilities

Amira Marouf, MD, PhD¹, Raphaël Liévin, MD²^*, Mathilde Bonnet des Claustres³^*, Matthias Titeux, PhD³^*, Mathieu Simonin⁴^*, Manon Vavasseur⁵^*, Amandine Mainreck⁶^*, Mehdi Latiri⁷^*, Aurore Touzart, MD, PhD⁸^*, Marie Bouillié⁹^*, Olivier Pellé¹⁰^*, Nicolas Gaidot¹¹^*, Mathieu Rocquet¹²^*, Didier Bouscary, MD, PhD¹³^*, Arnaud Jaccard, MD, PhD¹⁴^*, Vahid Asnafi, MD, PhD⁸^*, Olivier Hermine, MD, PhD^15,16^*, Guillaume P Andrieu, PhD^17,18^* and Lucile Couronné, MD, PhD¹⁹^*

¹INSERM U1163 Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Institut IMAGINE, Université Paris Cité, PARIS, France
²INSERM U1163 Laboratory of molecular mechanisms of hematological disorders and therapeutic implications, Institut IMAGINE, Université Paris Cité, Paris, France
³INSERM UMR 1163, Laboratory of Genetic Skin Diseases, Imagine Institute, Paris, France
⁴INSERM UMR_S 1151, Laboratory of Onco-Hematology, Necker Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, Paris, France
⁵INSERM U1163 Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Institut IMAGINE, Paris, France
⁶LEAT platform – Animal Facility, Imagine Institute-SFR Necker, Paris Cite University, France., Imagine Institute-SFR Necker, Paris, France
⁷INSERM UMR_S 1151, Necker Enfants Malades Institute (INEM), Laboratory of Onco-Hematology, Assistance Publique-Hopitaux De Paris (AP-HP), Paris, France
⁸Laboratory of Onco-Hematology, Necker Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France
⁹INSERM 1163, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Institut IMAGINE, Paris, France
¹⁰Plateforme de Cytométrie en Flux, Structure Fédérative de Recherche Necker, INSERM US24-CNRS UMS3633, Paris, France
¹¹INSERM UMR_S 1151, Necker Enfants Malades Institute (INEM), Laboratory of Onco-Hematology, Assistance Publique-Hopitaux De Paris (AP-HP), Université Paris Cité, paris, France
¹²Department on Hematology, Necker Enfants Malades, Paris, France
¹³Hematology, Cochin Hospital, Greater Paris University Hospitals (AP-HP), Paris, France
¹⁴Hématologie Clinique, CHU de Limoges, Limoges, France
¹⁵INSERM U1163 Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Institut IMAGINE, Université Paris Cité, Paris, France
¹⁶Hopital Necker, Paris, France
¹⁷Laboratory of Onco-Hematology, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
¹⁸INSERM UMR_S 1151, Laboratory of Onco-Hematology, Institut Necker Enfants Malades (INEM), Assistance Publique-Hopitaux De Paris (AP-HP), Université Paris Cité, Paris, France
¹⁹INSERM 1163, Laboratory of cellular and molecular mechanisms of hematological disorders and therapeutic implications, Institut IMAGINE, Université Paris Cité, Paris, France

2794

Exposure-Response Analysis and Quantitative Systems Pharmacology Modeling for Optimal RP2D Selection of AZD0486 in Follicular Lymphoma Patients

Xu (Sue) Zhu¹^*, Damilola Olabode¹^*, Massimo Lai²^*, Cesar Pichardo-Almarza²^*, Kevin Smart²^*, Denise Brennan¹^*, David Sermer³^* and Robin Lesley, PhD⁴^*

¹AstraZeneca, Waltham, MA
²AstraZeneca, Cambridge, United Kingdom
³AstraZeneca, New York, NY
⁴AstraZeneca, South San Francisco, CA

2795

Activity of Orally Available CBP/p300 Degraders in Pre-Clinical Models of Multiple Myeloma

Praveen Kumar Tiwari, PhD^1,2^*, Drew A Harrison¹^*, Samuel Ojeda¹^*, Ajinkya S Kawale, PhD^1,2^*, Sai Reddy Doda, PhD^1,2^*, Raghu Vannam, PhD^1,2^*, Barbara Karakyriakou¹^*, Ann-Sophie Koglin¹^*, Sarah Rizvi¹^* and Christopher J Ott, PhD^2,3

¹Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA
²Harvard Medical School, Boston, MA
³Krantz Family Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA

2796

Generation of FcRH5xCD28 Bispecific Antibodies Synergizing with T-Cell Engagers for Enhanced Multiple Myeloma Treatment

Sara Majocchi^*, Valéry Moine^*, Giovanni Magistrelli^*, Franck Gueneau^*, Nicolas Fischer, PhD^*, Limin Shang, PhD^*, Krzysztof Masternak, PhD^* and Walter Giovanni Ferlin, PhD^*

Light Chain Bioscience - Novimmune SA, Plan-Les-Ouates - Geneva, Switzerland

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^*signifies non-member of ASH