ST400 / Sangamo Therap, Sanofi - LARVOL DELTA

Long - Term Follow Up of Sickle Cell Disease and Beta-thalassemia Subjects Previously Exposed to BIVV003 or ST-400. (clinicaltrials.gov) - P=N/A | N=8 | Active, not recruiting | Sponsor: Sangamo Therapeutics | Enrolling by invitation ➔ Active, not recruiting | N=12 ➔ 8

Enrollment change • Enrollment closed • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

Comparative infectivity, virulence and molecular epidemiology of MDR and XDR Acinetobacter baumannii isolates emerging from war-related injuries in Ukraine. (PubMed, J Infect) - "We report the first results characterizing the pathogenesis and infectivity of the emerging A. baumannii ST19. High MDR and XDR rates alongside clonally related isolates are concerning and highlight the importance of infection prevention and control measures in conflict zones."

Journal • Infectious Disease

High genetic relatedness between multidrug resistant bacteria before and after the 2022 invasion of Ukraine. (PubMed, Genome Med) - "XDR epidemic clones circulating in Ukraine and across Europe since 2022 share a close genetic relationship to historical strains from Ukraine. In some cases, direct links to medical facilities within Ukraine can be inferred. These data suggest that surveillance efforts should focus on tracking nosocomial transmission within Ukrainian hospitals while infection control efforts are being disrupted by the ongoing Russian invasion."

Journal • Infectious Disease

Temporal evolution of bacterial species and their antimicrobial resistance characteristics in wound infections of war-related injuries in Ukraine from 2014 to 2023. (PubMed, J Hosp Infect) - "There is a growing prevalence of multidrug resistant isolates from globally distributed sequence types."

Journal • Infectious Disease • Pneumonia

Long - Term Follow Up of Sickle Cell Disease and Beta-thalassemia Subjects Previously Exposed to BIVV003 or ST-400. (clinicaltrials.gov) - P=N/A | N=12 | Enrolling by invitation | Sponsor: Sangamo Therapeutics | Trial completion date: Aug 2037 ➔ Jul 2038 | Trial primary completion date: Aug 2037 ➔ Jul 2038

Gene therapy • Trial completion date • Trial primary completion date • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Causing Nosocomial Meningitis in the Neurological Intensive Care Unit. (PubMed, Microorganisms) - "The prevalent ST was ST2, belonging to the international clone IC2, and rarer, ST1, ST19, ST45, ST78, ST106, and ST400, with prevalence of KL9 and OCL1...Genes conferring resistance to beta-lactams (bla, bla, bla, bla, bla, bla, and bla-types), aminoglycosides (aac, aad, ant, aph, and arm), tetracyclines (tet), macrolides (msr and mph), phenicols (cml, cat, and flo), sulfonamides (dfr and sul), rifampin (arr), and antiseptics (qac) were identified. Virulence genes of nine groups (Adherence, Biofilm formation, Enzymes, Immune evasion, Iron uptake, Regulation, Serum resistance, Stress adaptation, and Antiphagocytosis) were detected. The study highlights the heterogeneity in genetic clones, antimicrobial resistance, and virulence genes variability among the agents of A. baumannii meningitis, with the prevalence of the dominant international clone IC2."

Journal • CNS Disorders • Critical care • Infectious Disease

ZINC FINGER NUCLEASE-MEDIATED DISRUPTION OF THE BCL11A ERYTHROID ENHANCER IN PLERIXAFOR MOBILIZED CD34+ CELLS RESULTS IN ENRICHED BIALLELEIC EDITING AND ALLELE-ADDITIVE INCREASES IN FETAL HEMOGLOBIN (EHA 2019) - P1/2; "This drug product, ST 400, is in a phase 1/2a clinical trial for transfusion-dependent BT (NCT03432364). Overall, our data revealed that ZFN-mediated disruption of BCL11A ESE resulted in enriched biallelic editing with highly replicable and on-target small indels and increases in HbF. Further characterization of BIVV003 showed that injection of plerixafor mobilized ZFN edited HSPCs into immune-deficient NBSGW mice resulted in robust long-term engraftment (21 weeks) without any impact on the number of HSPCs and their progeny, including erythrocytes.Conclusion These data support the potential efficacy and specificity of plerixafor mobilized ZFN-edited HSPCs as a novel cell therapy for SCD patients."

Updated Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of BCL11A in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia (ASH 2021) - P1/2 | "Leukapheresis was performed following mobilization with G-CSF and plerixafor...The ST-400 product was infused following myeloablative busulfan conditioning... ST-400 is an ex vivo , ZFN-edited autologous HSC product candidate for increased erythroid HbF expression in patients with TDT. All five infused subjects had rapid hematopoietic reconstitution following myeloablative conditioning, on-target indels in PBMCs and elevated HbF levels following HSCGT. After 1 to 2 years, the average HbF levels had declined by 64% from peak to last visit, which necessitated resumption of PRBC transfusions at the same rate as prior to the ST-400 therapy."

Clinical • P1/2 data • Addiction (Opioid and Alcohol) • Beta-Thalassemia • Genetic Disorders • Hematological Disorders • Immunology • CD34 • CSF3

Preliminary Results of a Phase 1/2 Clinical Study of Zinc Finger Nuclease-Mediated Editing of BCL11A in Autologous Hematopoietic Stem Cells for Transfusion-Dependent Beta Thalassemia (ASH 2019) - P1/2; "After routine leukapheresis following mobilization with G-CSF and plerixafor, autologous collections are enriched for CD34+ cells and transfected with mRNA encoding ZFNs with binding sites flanking the GATA-binding region of BCL11A ESE. ST-400 product is infused following myeloablative busulfan conditioning... ST-400 is an ex vivo, ZFN-edited autologous HSC product for increased erythroid HbF expression in TDT. Two infused patients had rapid hematopoietic reconstitution following myeloablative conditioning, and both have elevated HbF levels following HSCGT. These data are preliminary, and additional patients and longer follow-up will be required to understand the safety and efficacy of this therapy."

Clinical • P1/2 data • CD34 • CSF3

Zinc Finger Nuclease-Mediated Disruption of the BCL11A Erythroid Enhancer Results in Enriched Biallelic Editing, Increased Fetal Hemoglobin, and Reduced Sickling in Erythroid Cells Derived from Sickle Cell Disease Patients (ASH 2019) - P1/2; "Previously, we reported successful ZFN-mediated editing of the BCL11A ESE and reactivation of HbF in both dual (granulocyte colony-stimulating factor (G-CSF) and plerixafor) and single plerixafor mobilized HSPCs (Holmes 2017, Moran 2018). Both related drug candidates, ST-400 and BIVV003, are currently in phase 1/2a clinical trials for transfusion-dependent BT (NCT03432364) and SCD (NCT03653247), respectively...Experiments in HSPCs from additional SCD donors are ongoing. Overall, our data have shown that ZFN-mediated disruption of BCL11A ESE results in enriched biallelic editing with on-target small indels, reactivates HbF and reduces sickling, supporting the potential efficacy and specificity of BIVV003 as a novel cell therapy for SCD."

Clinical

Ex Vivo Gene-Edited Cell Therapy for Sickle Cell Disease: Disruption of the BCL11A Erythroid Enhancer with Zinc Finger Nucleases Increases Fetal Hemoglobin in Plerixafor Mobilized Human CD34+ Cells (ASH 2018) - P1/2; "This drug product, ST-400, passed extensive safety testing and is currently in a phase 1/2a clinical trial for transfusion-dependent beta-thalassemia (ClinicalTrials.gov number NCT03432364). Overall, these data demonstrate potential efficacy of ZFN-edited HSPCs (BIVV003) as a novel cell therapy for SCD patients. Holmes et al., 2017 (ASH abstract) Fitzhugh et al., 2009 Lagresle-Peyrou et al., 2018 Hsieh and Tisdale, 2018 Yannaki et al., 2012"

Preclinical • Biosimilar • Gene Therapies • Hematological Disorders

A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT) (clinicaltrials.gov) - P1/2 | N=5 | Completed | Sponsor: Sangamo Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Transplantation

Antibiotic susceptibility and genotypic characterization of Neisseria gonorrhoeae isolates in the Comunidad Valenciana (Spain): GONOvig project. (PubMed, Enferm Infecc Microbiol Clin (Engl Ed)) - "Low resistance to ceftriaxone, a worrying resistance to azithromycin and a wide variety of circulating sequence types have been detected, some of which show correlation with certain resistance profiles."

Journal • Infectious Disease

Long - Term Follow Up of Sickle Cell Disease and Beta-thalassemia Subjects Previously Exposed to BIVV003 or ST-400. (clinicaltrials.gov) - P=N/A | N=12 | Enrolling by invitation | Sponsor: Sangamo Therapeutics | Recruiting ➔ Enrolling by invitation

Enrollment status • Gene therapy • Preclinical • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT) (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: Sangamo Therapeutics | Trial primary completion date: Jan 2021 ➔ Nov 2022

Trial primary completion date • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Transplantation

An Observational Long-term Safety and Efficacy Follow-up Study After Ex-vivo Gene Therapy With BIVV003 in Severe Sickle Cell Disease (SCD) and ST-400 in Transfusion-dependent Beta-thalassemia (TDT) With Autologous Hematopoietic Stem Cell Transplant (clinicaltrials.gov) - P=N/A | N=13 | Recruiting | Sponsor: Bioverativ, a Sanofi company | Trial completion date: Mar 2043 ➔ Aug 2037 | Trial primary completion date: Mar 2043 ➔ Aug 2037

Preclinical • Trial completion date • Trial primary completion date • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

An Observational Long-term Safety and Efficacy Follow-up Study After Ex-vivo Gene Therapy With BIVV003 in Severe Sickle Cell Disease (SCD) and ST-400 in Transfusion-dependent Beta-thalassemia (TDT) With Autologous Hematopoietic Stem Cell Transplant (clinicaltrials.gov) - P=N/A; N=13; Recruiting; Sponsor: Bioverativ, a Sanofi company; Not yet recruiting ➔ Recruiting

Enrollment open • Preclinical • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT) (clinicaltrials.gov) - P1/2; N=6; Active, not recruiting; Sponsor: Sangamo Therapeutics; Trial completion date: Mar 2023 ➔ Nov 2022; Trial primary completion date: Nov 2022 ➔ Jan 2021

Clinical • Trial completion date • Trial primary completion date • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Transplantation

β-Thalassemia: evolving treatment options beyond transfusion and iron chelation. (PubMed, Hematology Am Soc Hematol Educ Program) - "Luspatercept, a transforming growth factor-β inhibitor, has demonstrated efficacy in reducing ineffective erythropoiesis, improving anemia, and possibly reducing iron loading...Several medications in development aim to induce hemoglobin F (HbF): sirolimus, benserazide, and IMR-687 (a phosphodiesterase 9 inhibitor). Another group of agents seeks to ameliorate ineffective erythropoiesis and improve anemia by targeting abnormal iron metabolism in thalassemia: apotransferrin, VIT-2763 (a ferroportin inhibitor), PTG-300 (a hepcidin mimetic), and an erythroferrone antibody in early development. Mitapivat, a pyruvate kinase activator, represents a unique mechanism to mitigate ineffective erythropoiesis...One such product, betibeglogene autotemcel (beti-cel), has reached phase 3 trials with promising results. In addition, 2 gene editing techniques (CRISPR-Cas9 and zinc-finger nucleases) are under investigation as a means to silence BCL11A to induce HbF with agents designated..."

Journal • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Hematological Disorders • Transplantation

An Observational Long-term Safety and Efficacy Follow-up Study After Ex-vivo Gene Therapy With BIVV003 in Severe Sickle Cell Disease (SCD) and ST-400 in Transfusion-dependent Beta-thalassemia (TDT) With Autologous Hematopoietic Stem Cell Transplant (clinicaltrials.gov) - P=N/A; N=13; Not yet recruiting; Sponsor: Bioverativ, a Sanofi company

New trial • Preclinical • Beta-Thalassemia • Bone Marrow Transplantation • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • Transplantation

[VIRTUAL] Campylobacter Genotypes Present At Austrian Broiler Farm Level Indicate Global Character (WMF 2021) - "The following C. jejuni and C. coli genotypes were detectable in caecal samples at several sampling times: ST-267, ST-354, ST-400, ST-2066, ST-446 and ST-828...Antimicrobial resistance genes were detected in the isolates to ciprofloxacin, ampicillin and tetracycline...Since a co-selection of antibiotics and biocides is reported for particularly environmentally adapted genotypes, the isolates should be tested subsequently to gain insight into the potential adaptability of individual genotypes. The study will give an insight into the genetic diversity of thermophilic Campylobacter species in different Austria districts in order to help the poultry industry to track down the pathways of contamination, so that control measures can be implemented."

Clinical • Complement-mediated Rare Disorders

A Study to Assess the Safety, Tolerability, and Efficacy of ST-400 for Treatment of Transfusion-Dependent Beta-thalassemia (TDT) (clinicaltrials.gov) - P1/2; N=6; Active, not recruiting; Sponsor: Sangamo Therapeutics; Trial primary completion date: Mar 2021 ➔ Nov 2022

Clinical • Trial primary completion date • Beta-Thalassemia • Bone Marrow Transplantation • Genetic Disorders • Transplantation

Effect of Photobiomodulation on Critical Swimming Velocity: A Randomized, Crossover, Double-Blind, and Placebo-Controlled Study. (PubMed, Int J Sports Physiol Perform) - "A PBM application prior to front crawl swimming test did not significantly modify the CV, ST, physiological factors of metabolic fatigue, perceptual, and front crawl stroke efficiency parameters in competition swimmers covering distances of 100, 200, and 400 m."

Clinical • Journal • Cardiovascular • Fatigue

ST-400: Primary completion of P1/2 trial (NCT03432364) for beta-thalassemia in March 2021 (Sanofi) - Q4 & FY2020 Results: Completion of P1/2 trial for beta-thalassemia in March 2023

Trial completion date • Trial primary completion date • Beta-Thalassemia

ST400: Follow-up data from P1/2 trial (NCT03432364) for beta-thalassemia in 2021 (39th Annual J.P. Morgan Healthcare Conference (Virtual Meeting), Sangamo Biosciences)

P1/2 data • Beta-Thalassemia