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

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

Research, Antibody Therapy, Lymphoid Leukemias, ALL, Combination therapy, Fundamental Science, Lymphomas, Non-Hodgkin lymphoma, Drug development, Translational Research, Bioinformatics, Chemotherapy, Plasma Cell Disorders, B Cell lymphoma, Drug-drug interactions, CML, Hematopoiesis, Chronic Myeloid Malignancies, Pediatric, Education, Diseases, Immune Disorders, Immune mechanism, Treatment Considerations, Biological therapies, Immunology, Immunotherapy, Aggressive lymphoma, Lymphoid Malignancies, Non-Biological therapies, Metabolism, Computational biology, Young adult , Biological Processes, Myeloid Malignancies, Monoclonal Antibody Therapy, Pharmacology, Technology and Procedures, Molecular biology, Human, Pathogenesis, Omics technologies

Halls G-H (San Diego Convention Center)

4163

Preclinical Proof-of-Concept of an mRNA-Based T Cell Engager Targeting BCMA, FcRH5, and GPRC5D for the Treatment of Multiple Myeloma

Maija Garnaas¹^*, Kristen Cowens¹^*, Zhen Zhang, PhD¹^*, Michael Deci²^*, Maiko Obana, PhD¹^*, John Zielinski²^*, Matthew Sullivan²^*, Russell Karp²^*, Stephanie Christainsen²^*, Brianna Magliozzi²^*, Graham MacLean¹^*, Terrence Washington²^*, Ying Fu²^*, Varun Chavada²^*, Hannah D'Ambrosio²^*, Sunil Singh²^*, John Eldredge¹^*, Kenneth Drombosky, PhD²^*, Pradeep Babu Jagadeesh Reddy²^*, Shilpa Sharma²^*, Harkewal Singh²^*, Neeraj Kaushal, PhD²^*, Binu Philip²^*, Graham Farrington, PhD²^*, Brendan M. Weiss, MD¹, Joshua P Frederick, PhD²^* and Lin Guey²^*

¹Moderna, Inc., Cambridge, MA
²ModernaTX, Inc., Cambridge

4164

Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies

Mark E Robinson, PhD¹^*, Qin Li, PhD¹^*, Chang Zhang, PhD¹^*, Chuanzong Zhan, PhD¹^*, Zhangliang Cheng, BSc¹^*, Kohei Kume, PhD¹^*, Kadriye Nehir Cosgun, PhD¹^*, Shalin Kothari, MD¹^*, Nikol Agadzhanian, MSc¹^*, Daisuke Nakada, PhD² and Markus Müschen, MD¹

¹Center of Molecular and Cellular Oncology, Yale University, New Haven, CT
²Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX

4165

YL0712-3, a Novel ATR/ATM Inhibitor, Demonstrates Anti-Tumor Activity in TP53 Mutant DLBCL through Synthetic Lethality and Degradation of Mutant p53

Li Wang, MD^1,2,3^*, Guo Zhang, PhD²^*, Hui Zhou, MD^1,2,3^* and Ting Niu, MD, PhD^2,3,4

¹Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
²State Key Laboratory of Biotherapy, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
³National Facility for Translational Medicine (Sichuan), West China Hospital, Sichuan University, Chengdu, China
⁴Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

4166

Infiltration of Innate Immune Cells into Tumors By Polatuzumab Vedotin Treatment Contributes to Its Antitumor Effect in Xenograft and Syngeneic Mouse Models

Mayu Tomita¹^*, Natsumi Kawasaki, PhD¹^*, Keigo Yorozu, PhD¹^*, Mitsue Kurasawa¹^*, Bansho Masutani, PhD²^*, Nicolas Sax, MS²^*, Sei Shu, PhD¹^*, Yoriko Yamashita-Kashima, PhD¹^* and Shigeki Yoshiura, PhD¹^*

¹Product Research Dept., Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan
²Biological Technology Dept., Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan

4167

Translational Disruption of NRF2 By Zotatifin Enhances Sensitivity to Ferroptosis and CAR-T Cells in Diffuse Large B-Cell Lymphoma

Paola Manara, MS¹, Venu Venkatarame Gowda Saralamma, PhD²^*, Austin Daniel Newsam, BS¹^*, Marco Vincenzo Russo, PhD³^*, Tyler Andrew Cunningham, PhD⁴^*, Alicia Bilbao Martinez, BS³^*, Nikolai Fattakhov, PhD³^*, Kyle Hoffman, PhD⁵^*, Alexandra Marie Carbone, BS¹^*, Abdessamad Youssfi Alaoui, PhD²^*, Dhanvantri Chahar, PhD²^*, Olivia Barbara Lightfuss, BS¹^*, Francesco Maura, MD⁶, Daniel Bilbao, PhD³ and Jonathan H. Schatz, MD²

¹University of Miami Miller School of Medicine Sheila and David Fuente Graduate Program in Cancer Biology, Miami, FL
²Division of Hematology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL
³Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL
⁴University of Miami Miller School of Medicine Medical Scientist Training Program, Miami, FL
⁵Bioinformatics Solutions Inc, Waterloo, ON, Canada
⁶University of Miami, Coral Gables, FL

4168

CT1113, a Potent, Oral Small Molecule Inhibitor of USP25, Demonstrates Anti-Tumor Activity in Ph-Positive Acute Lymphoblastic Leukaemia

Ting Shi¹^*, Jin Peng²^*, Wei Yuan³^*, Xinghua Zhen²^*, Jieyu Xu, MD⁴^*, Wen Gao⁵, Pumin Zhang²^* and Honghu Zhu^1,6^*

¹Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
²Zhejiang Provincial Key Laboratory of Pancreatic Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
³Hematology, Affiliated Hospital of Jiujiang University, Jiujiang, China
⁴Department of Lymphoma, Zhejiang Cancer Hospital, Hangzhou, China
⁵Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
⁶Chinese Institutes for Medical Research, Beijing, China

4169

Ancestral L-Asparaginases Are Cytotoxic Against ALL Cell Lines with Predicted Reduced Immunogenicity

Kristopher Adrian Knight¹, Harrison C. Brown, PhD²^*, Mathew S. Karpen³^*, H. Trent Spencer, PhD³^*, Christopher B. Doering, PhD⁴^* and Sunil S Raikar, M.D.³

¹Molecular and Systems Pharmacology, Emory University, Atlanta, GA
²Expression Therapeutics, Tucker, GA
³Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University and Children's Healthcare of Atlanta, Atlanta, GA
⁴Aflac Cancer and Blood Disorders Center, Emory University and Children's Healthcare of Atlanta, Atlanta, GA

4170

PAX5 Loss Compromises CD22 Protein Levels and Responses to Inotuzumab Ozogamicin in B-Cell Acute Lymphoblastic Leukemia

Jacinta Davis, PhD¹, JuanCarlos Balandrán, PhD²^*, Katharina Hayer, MS^1,3^*, Sisi Zheng, MD^1,4,5, Zhiwei Ang, PhD¹^*, Evelyn Liu^1,6^*, Bonnie Yates, NP⁷^*, Nirali N. Shah, MD⁸, Iannis Aifantis, PhD² and Andrei Thomas-Tikhonenko, PhD^1,5,9

¹Division of Cancer Pathobiology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA
²Department of Pathology and Laura & Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY
³Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA
⁴UT Southwestern, Dallas, TX
⁵Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA
⁶Department of Biology, University of Pennsylvania, Philadelphia, PA
⁷Pediatric Oncology Branch, National Institutes of Health, Bethesda, MD
⁸Pediatric Oncology Branch, NIH, Bethesda, MD
⁹Department of Pathology & Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA

4171

Revealing the Synergistic Potential of Mosunetuzumab Plus Polatuzumab Vedotin through CD20 Upregulation

Natsumi Kawasaki, PhD^*, Sei Shu, PhD^*, Xiaoxiao Liu, PhD^* and Shigeki Yoshiura, PhD^*

Product Research Dept., Chugai Pharmaceutical Co., Ltd., Yokohama, Kanagawa, Japan

4172

Therapeutic Repurposing of Brincidofovir in Non-Hodgkin Lymphoma – Potential Synergy with Immune Checkpoint Blockade

Jason Yongsheng Chan¹, Elizabeth Chun Yong Lee²^*, Kelila Xin Ye Chai²^*, Boon Yee Lim²^*, Zhimei Li²^*, Jing Yi Lee³^*, Bavani Kannan²^*, Tun Kiat Ko²^*, Jessica Sook-Ting Kok³^*, Kah Suan Lim³^*, Nur Ayuni Muhammad Taib²^*, Dachuan Huang, PhD, BSc, MSc⁴^*, Jing Quan Lim, PhD³^*, Masatoshi Hazama⁵^*, Koji Fukushima⁶^*, Bin Tean Teh³^*, Soon Thye Lim¹^* and Choon Kiat Ong⁷^*

¹Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
²National Cancer Centre Singapore, Singapore, SGP
³National Cancer Centre Singapore, Singapore, Singapore
⁴National Cancer Centre Singapore, SINGAPORE, Singapore
⁵SymBio Pharmaceuticals Limited, Minato-Ku, TKY, Japan
⁶SymBio Pharmaceuticals Limited, Tokyo, Japan
⁷National Cancer Centre Singapore, Singapore, Singapore, SGP

4173

Preclinical Development of a Novel Humanized and Fc-Engineered Antibody-Drug Conjugate for the Therapy of T-Cell Acute Lymphoblastic Leukemia

Steffen Krohn¹^*, Carina Lynn Gehlert, PhD¹^*, Dorothee Winterberg, PhD¹^*, Alexander Jochimsen¹^*, Ammelie Svea Boje¹^*, Natalie Baum, PhD¹^*, Claudia D Baldus, MD^2,3^*, Monika Brüggemann, MD^2,3^*, Gunnar Cario, MD^3,4^*, Martin Schrappe, MD^3,4, Lennart Lenk, PhD^3,4^*, Martin Gramatzki, MD¹, Katja Klausz, PhD^1,3^*, Christian Kellner, PhD⁵^* and Matthias Peipp, PhD^1,3^*

¹Division of Antibody-Based Immunotherapy, Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
²Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
³Clinical Research Unit CATCH ALL (KFO 5010/1) funded by the Deutsche Forschungsgemeinschaft, Kiel, Germany
⁴Department of Pediatrics I, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
⁵Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, LMU University Hospital, LMU Munich, Munich, Germany

4174

Selinexor Induces DLBCL Cell Senescence Mediated By USP1/MDMX/p53 Axis

Yidan Zhang¹^*, Xiyue Xu, PhD²^*, Xianhuo Wang, MD¹^* and Huilai Zhang, MD³

¹Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
²Tianjin Medical University Cancer Institute and Hospital, Tianjin, AL, China
³Tianjin Medical University Cancer Institute and Hospital, Tianjin, Tianjin, China

4175

BR105 Is a Novel Anti-Sirpα Monoclonal Antibody That Demonstrates a Favorable Safety Profile and Potent Anti-Tumor Efficacy in Patients with Relapsed/Refractory Lymphoid Malignancies: Preliminary Results from a Phase I Study

Ningjing Lin, MD¹^*, Tingting Du, MA¹^*, Hui Zhou²^*, Yajun Li, MD²^*, Liang Wang³^*, Xiaomeng Dong, PhD⁴^*, Haochuan Zheng, PharmD⁴^*, Jingtao Lu, PhD⁴^*, Mi Tang, PhD⁴^*, Jihua Wu, PhD⁴^*, Wei Zhu, MD⁴^*, Yuqin Song, MD⁵ and Jun Zhu, PhD⁶

¹Department of Lymphoma, Peking University Cancer Hospital and Institute, Beijing, China
²Hunan Cancer Hospital, Changsha, China
³Beijing Tongren Hospital, Beijing, China
⁴BioRay Pharmaceutical Co., Ltd, Taizhou, China
⁵Key Laboratory of Carcinogenesis and Translational Research, Department of Lymphoma, Peking University Cancer Hospital, Beijing, China
⁶Department of Lymphoma, Peking University Cancer Hospital, Beijing, Beijing, China

4176

Tgrx-678 Penetrates Blood-Brain Barrier and Exhibits Preclinical Anti-Tumor Activity in Murine Ph+ CNS Leukemia and ALL Models

Yingying Zuo, PhD¹^*, Yun Liu, PhD¹^*, Meng Chen¹^*, Yixin Ai²^*, Yanxia Shi, PhD³^*, Jingrong Cao, PhD⁴ and Yihan Wang, PhD⁴^*

¹Department of Preclinical Management, Shenzhen TargetRx, Inc., Shenzhen, China
²Department of Computational Chemistry, Shenzhen TargetRx, Inc., Shenzhen, China
³Department of Biological and Translational Research, Shenzhen TargetRx, Inc., Shenzhen, China
⁴Shenzhen TargetRx, Inc., Shenzhen, China

4177

Dexamethasone Is More Potent Than Prednisone in B-Lymphoblastic Leukemia Despite Dose Adjustment

Jessica A.O. Zimmerman, MD, MS^1,2, Mimi Fang, MS^2,3^*, Dawne Shelton, PhD⁴^* and Miles A. Pufall, PhD^2,3^*

¹Stead Family Department of Pediatrics - Hematology/Oncology, University of Iowa, North Liberty, IA
²Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
³Department of Biochemistry and Molecular Biology, University of Iowa, Iowa City, IA
⁴Illumina, San Diego

4178

The Anti-Myeloma Efficacy of TAS0612, a Triple Inhibitor of RSK, AKT, and S6K, and Itssynergistic Combination with Venetoclax in Multiple Myeloma Irrespective of Cytogeneticabnormalities

Haruya Okamoto, MD¹^*, Shinsuke Mizutani, MD, PhD¹^*, Taku Tsukamoto, MD, PhD¹^*, Yoko Katsuragawa-Taminishi, MD¹^*, Yuka Kawaji-Kanayama¹^*, Kentaro Mizuhara, MD¹^*, Ayako Muramatsu, MD, PhD¹^*, Reiko Isa, MD, PhD¹^*, Takahiro Fujino, MD, PhD¹^*, Yuji Shimura, MD, PhD¹^*, Koji Ichikawa²^* and Junya Kuroda, MD, PhD³

¹Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan
²Taiho Pharmaceutical Co., Ltd., Tsukuba, JPN
³Division of Hematology and Oncology, Department of Medicine,, Kyoto Prefectural University of Medicine, Kyoto, Japan

4179

Metabolic and Cell Cycle Proteins As Novel Targets of Selinexor Activity in Diffuse Large B Cell Lymphoma

Kyla L. Trkulja^1,2, Will Tong²^*, Daisy V. Tran²^*, Li Meng²^*, Evelyn Teh, PhD³^*, Susanne Penny, PhD³^*, Devanand M. Pinto, PhD³^*, Armand Keating, MD², John Kuruvilla, MD, FRCPC^2,4 and Rob C. Laister, PhD²

¹Institute of Medical Science, University of Toronto, Toronto, ON, Canada
²Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
³Human Health Therapeutics, National Research Council, Halifax, NS, Canada
⁴Department of Medicine, University of Toronto, Toronto, ON, Canada

4180

Integrated Quantitative Clinical Pharmacology Analysis Identifies Optimal Englumafusp Alfa Dose Range for Proof-of-Concept Study with Glofitamab in Second-Line Large B-Cell Lymphoma Patients

Candice Jamois, PharmD¹^*, Koorosh Korfi, PhD², Sylvia Herter, PhD³^*, Sabine Wilson, PhD⁴^*, Sreenath Krishnan¹^*, Marie-Helene Wasmer¹^*, Isabel Prieto⁵^*, Heather Hinton⁶^*, Wouter Driessen¹^*, Georgios Kazantzidis¹^*, Denis Sahin, PhD⁷^*, Akiko Tagawa⁸^*, Natalie Dimier, PhD⁹^* and Katharina Lechner¹⁰^*

¹Pharma Research and Early Development, Roche Innovation Center Basel, Roche, Basel, Switzerland
²Pharma Research and Early Development, Innovation Center Zürich, Roche, Zürich, Switzerland
³Pharma Research and Early Development, Roche Innovation Center Zurich, Roche, Schlieren, Switzerland
⁴Pharma Research and Early Development, Roche Innovation Center Welwyn, Roche, Welwyn, United Kingdom
⁵Product Development, Innovation Center Welwyn, Roche, Welwyn, United Kingdom
⁶Product Development, Innovation Center Basel, Roche, Basel, Switzerland
⁷Product Development Oncology and Hematology, Roche Innovation Center Basel, Roche, Basel, Switzerland
⁸Product Development, Roche Innovation Center Basel, Roche, Basel, Switzerland
⁹Pharma Research and Early Development, Innovation Center Welwyn, Roche, Welwyn, United Kingdom
¹⁰Pharma Research and Early Development, Innovation Center Munich, Roche, Munich, Germany

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