nulabeglogene autogedtemcel (GPH101) / Graphite Bio - LARVOL DELTA

One Year Follow-up on the First Patient Treated with Nula-Cel: An Autologous CRISPR/Cas9 Gene Corrected CD34+ Cell Product to Treat Sickle Cell Disease (ASH 2023) - "Two aphereses of plerixafor-mobilized CD34+ cells were performed followed by fresh CD34+ cell purification...In August, 2022 the thawed drug product was infused after the patient received AUC-adjusted busulfan myeloablative conditioning chemotherapy...Because of the lack of platelet recovery and continued platelet and RBC transfusion requirements, the patient was started on eltrombopag on day +106 (marrow cellularity of 5%)...Improvements in cell manufacturing are being implemented to shorten the duration of transfusion needs and increase the level of gene correction of engrafted cells. Plans to treat the next patients with an improved nula-cel product are in place."

Clinical • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • CD34 • HBB

Continued Clinical Scale Process Development to Enable Safe and Effective Homology Directed Repair Gene Edited Hematopoietic Stem and Progenitor Cells for Sickle Cell Disease (ASGCT 2025) - P1/2 | "Nulabeglogene autogedtemcel (nula-cel) is a phase I/II investigational drug product (NCT04819841), consisting of ex-vivo gene corrected, plerixafor-mobilized CD34+ HSPCs to cure Sickle Cell Disease (SCD)...While P1 has done clinically well and met pre-defined safety and efficacy endpoints, including <10% HgbS at T24 months, the engraftment of red blood cells and platelets was delayed, requiring transfusions up to D+263 and eltrombopag to temporarily boost HSC growth...In conclusion, we demonstrated the clinical readiness of an improved V2.0 nula-cel product, with continuing FDA clearance for phase I/II clinical trial implementation. Disease Focus of Abstract:Hemoglobinopathies"

Clinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • ANXA5 • CD34 • HBB • PTPRC • TP53BP1

CEDAR: Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease (clinicaltrials.gov) - P1/2 | N=6 | Terminated | Sponsor: Graphite Bio, Inc. | N=15 ➔ 6 | Trial completion date: May 2026 ➔ Apr 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2026 ➔ Apr 2023; Study Stopped at Sponsor Discretion

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Cedar Trial in Progress: A First in Human, Phase 1/2 Study of the Correction of a Single Nucleotide Mutation in Autologous HSCs (GPH101) to Convert HbS to HbA for Treating Severe SCD (ASH 2021) - P1/2 | "After eligibility confirmation including screening for pre-treatment cytogenetic abnormalities, participants will undergo plerixafor mobilization and apheresis, followed by CD34+ cell enrichment and cryopreservation, undertaken locally at each trial site before shipment to a centralized manufacturer for GPH101 production. After GPH101 release, participants will undergo eligibility reconfirmation prior to busulfan conditioning and DP infusion...In addition, cerebral hemodynamics and oxygen delivery will be assessed by magnetic resonance techniques. Key exploratory endpoints include evaluation of patient-reported outcomes, erythrocyte function, on-target and off-target editing rates, and change from baseline in select SCD characteristics."

P1/2 data • Anemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Immunology • Sickle Cell Disease • Transplant Rejection • Transplantation • CD34

CEDAR: Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease (clinicaltrials.gov) - P1/2 | N=15 | Active, not recruiting | Sponsor: Graphite Bio, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Single-Cell RNA Sequencing of Sickle Cell Reticulocytes to Identify Beta-Globin Genotypes and Associated Gene Expression Differences (ASH 2022) - "GPH101 (nulabeglogene autogedtemcel) is an investigational gene-edited autologous hematopoietic stem cell–based therapy in clinical development for SCD that is designed to directly correct the underlying mutation, thereby decreasing HbS production and restoring HbA expression... Our data demonstrate the utility of scRNAseq for evaluating differential HBB editing outcomes in erythroid progenitors from patients treated with nulabeglogene autogedtemcel to support clinical development. Further evaluation of the clinical utility of the scRNAseq pipeline is planned."

Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • Glycophorin A • HBB • PTPRC • TFRC

CEDAR Trial in Progress: A First in Human, Phase 1/2 Study of the Correction of a Single Nucleotide Mutation in Autologous HSCs (GPH101) to Convert HbS to HbA for Treating Severe Sickle Cell Disease (ASGCT 2022) - P1/2 | "After eligibility confirmation including screening for pre-treatment cytogenetic abnormalities, participants will undergo plerixafor mobilization and apheresis, followed by CD34+ cell enrichment and cryopreservation, undertaken locally at each trial site before shipment to a centralized manufacturer for GPH101 production. After GPH101 release, participants will undergo eligibility reconfirmation prior to busulfan conditioning and DP infusion...Secondary endpoints will explore efficacy and pharmacodynamics, including levels of globin expression as compared to baseline, gene correction rates, clinical manifestations of SCD (including VOC and ACS), and changes in packed red blood cell transfusion needs. Key exploratory endpoints include evaluation of patient-reported outcomes, erythrocyte function, characterization of gene correction rates, and change from baseline in select SCD characteristics and organ function."

P1/2 data • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation • CD34

CEDAR: Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease (clinicaltrials.gov) - P1/2; N=15; Recruiting; Sponsor: Graphite Bio, Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HP

CEDAR: Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease (clinicaltrials.gov) - P1/2; N=15; Not yet recruiting; Sponsor: Graphite Bio, Inc.; Trial completion date: Dec 2025 ➔ May 2026; Initiation date: Mar 2021 ➔ Aug 2021; Trial primary completion date: Dec 2025 ➔ May 2026

Trial completion date • Trial initiation date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HP

CEDAR: Gene Correction in Autologous CD34+ Hematopoietic Stem Cells (HbS to HbA) to Treat Severe Sickle Cell Disease (clinicaltrials.gov) - P1/2; N=15; Not yet recruiting; Sponsor: Graphite Bio, Inc.

New P1/2 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • HP

Clinical Trial Cleared for GPH101, First Potentially Curative SCD Therapy (Sickle Cell Anemia News) - "The investigational gene editing therapy GPH101 will be the first potentially curative treatment for sickle cell disease (SCD) to be tested in a Phase 1/2 clinical trial. The U.S. Food and Drug Administration (FDA) has cleared GPH101 for clinical testing....The new, open-label trial, called CEDAR, is designed to evaluate the safety and pharmacological properties of GPH101, as well as its preliminary efficacy in adults and adolescents with severe SCD. Patient recruitment and enrollment is expected to start soon."

New P1/2 trial • Sickle Cell Disease