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4994 Safety and Efficacy of RM-001 (Autologous HBG1/2 Promoter-modified CD34+ Hematopoietic Stem and Progenitor Cells) in Patients with Transfusion-Dependent β-ThalassemiaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 801. Gene Therapies: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Research, clinical trials, Thalassemia, Clinical Research, Hemoglobinopathies, Gene Therapy, Diseases, Therapies, Technology and Procedures, gene editing
Monday, December 11, 2023, 6:00 PM-8:00 PM

Rongrong Liu1*, Li Wang2*, Hui Xu, PhD3, Xiaolin Yin4*, Junbin Liang3*, Wenqiang Xie1*, Gaohui Yang1*, Yaoyun Li5*, Yali Zhou5*, Lei Shi3*, Bin Xiao5*, Lingling Shi1*, Zeyan Shi1*, Xuemei Zhou1*, Xiangmin Xu6*, Jianpei Fang7*, Yongrong Lai1*, Junjiu Huang8* and Xinhua Zhang, MD2*

1Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
2923rd Hospital of the People's Liberation Army, Nanning, Guangxi, China
3Reforgene Medicine, Guangzhou, China
4Department of Hematology, 923rd Hospital of the People's Liberation Army, Nanning, China
5Department of Pediatrics, 923rd Hospital of the People's Liberation Army, Nanning, China
6Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
7Sun Yat-Sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
8School of Life Sciences, Sun Yat-sen University, Guangzhou, China


Reactivating fetal globin (HbF) is a promising treatment for β-hemoglobinopathies. Natural mutations in the promoter region of γ-globin genes (HBG1/2) that disrupt the binding of the transcriptional repressors BCL11A could lead to a lifelong persistence of fetal γ-globin expression. Using gene editing to mimic these mutations should reactivate γ-globin in patients with transfusion-dependent β-thalassemia (TDT) and ameliorate the symptoms of patients. RM-001 is a novel cell therapy that uses non-viral, ex vivo CRISPR-Cas9 gene editing in autologous hematopoietic stem and progenitor cells (HSPCs) at the promoter of the γ-globin genes (HBG1/2) to disrupt the binding site of BCL11A.


ChiCTR2100053406 and ChiCTR2100052858 are ongoing multi-center, first-in-human studies of RM-001 for TDT. Here, we present available safety and efficacy results from 7 patients that have been dosed with RM-001.


Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2ys were eligible. Peripheral CD34+ HSPCs were collected by apheresis after mobilization with G-CSF and plerixafor. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-3. Patients were monitored for stem cell engraftment/hematopoietic recovery, adverse events (AEs), Hb production, HbF and F-cell expression, and pRBC transfusion requirements. Bone marrow cells were obtained at 3, 6, 12 and 24 months after RM-001 infusion to measure the on-target allelic editing frequency using next-generation sequencing.


Data presented here for 7 TDT patients have been treated with RM-001. As of July 31, 2023, patients were followed up from 1 to 20 months and 5 of them have been followed up more than 15 months. Six patients have β00 genotype (CD17/CD41-42, n=1; CD41-42/CD41-42, n=5) and the other has β0+ genotype (CD41-42/IVS-II-654). In addition to β-thalassemia (CD41-42/CD41-42), two patients also carry a Southeast Asian deletion of α-globin genes (--SEA/αα). Patients had received a mean of 55.8 units/y pRBC transfusions (range: 39-79.6 units/y).

All patients received a single dose of RM-001 cells, and achieved both neutrophil and platelet engraftments 2 to 3 weeks after RM-001 infusion (neutrophil: day 11-19, platelet: day 10-22). All patients ceased pRBC transfusions within 1 month after RM-001 infusion and remained transfusion-free through the reported period (Figure). For the 6 patients that have been followed up more than 6 months, HbF reached 9g/dL at 4 month post-RM-001 infusion and continuously maintained over this level through the reported period. From 6 month post-RM-001 infusion, hemoglobin in all patients consists of HbF (97.6%-99.8%) and HbA2 only, including the fifth patient who has a β0/β+ genotype (99.5% HbF). Five participants have remained transfusion independent more than 15 months and the mean HbF in the first 4 patients was 11g/dL(10.9-11.3 g/dL) at 18 month post-RM-001 infusion.

The safety profile was generally consistent with busulfan myeloablation and autologous hematopoietic stem cell transplantation. No RM-001 related SAE report.


This updated data reported here from 7 patients with TDT infused with RM-001 demonstrated clinically meaningful increases in total hemoglobin (Hb) and HbF levels. All patients stopped receiving pRBC transfusions within 1 month after RM-001 infusion and remained transfusion-free through the time of this analysis. The safety profile of RM-001 is generally consistent with myeloablative conditioning and autologous hematopoietic stem cell transplantation. These results strongly support continued investigation of RM-001 as a potential cure for patients with TDT.

Data will be updated for the presentation.

Submitted on behalf of the RM-001 Investigators.

Disclosures: No relevant conflicts of interest to declare.

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