bevantolol (SOM3355) / SOM Biotech - LARVOL DELTA

Positive orphan drug opinion supports SOM3355’s potential as first-line treatment in Europe (PharmaTimes)

Orphan drug • Huntington's Disease

Identification and characterization of binding thermodynamics and kinetics of inhibitors targeting FGFR1 via molecular modelling and ligand Gaussian accelerated molecular dynamics simulations. (PubMed, Phys Chem Chem Phys) - "The binding constant was estimated to be 7.4 ± 0.27 nM, which was similar to the type II tyrosine kinase inhibitor ponatinib. Overall, this study highlights the dynamics of FGFR1-ligand interaction while proposing bevantolol and its analogue molecule ANLG-2 as promising drug candidates for FGFR1 therapeutic intervention."

Journal • Oncology • FGFR1

Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2 | N=140 | Completed | Sponsor: SOM Innovation Biotech SA | Active, not recruiting ➔ Completed

Trial completion • Huntington's Disease • Movement Disorders

Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2 | N=129 | Active, not recruiting | Sponsor: SOM Innovation Biotech SA | Recruiting ➔ Active, not recruiting

Enrollment closed • Huntington's Disease • Movement Disorders

Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2 | N=129 | Recruiting | Sponsor: SOM Innovation Biotech SA | Trial primary completion date: Mar 2024 ➔ Jun 2024

Trial primary completion date • Huntington's Disease • Movement Disorders

Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2 | N=129 | Recruiting | Sponsor: SOM Innovation Biotech SA

Trial completion date • Trial primary completion date • Huntington's Disease • Movement Disorders

Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2 | N=129 | Recruiting | Sponsor: SOM Innovation Biotech SA | Phase classification: P2b ➔ P2

Phase classification • Huntington's Disease • Movement Disorders

Risk of venous thromboembolism (VTE) in first-degree relatives of patients with VTE compared with general population VTE risk (ISTH 2023) - "Among the 2617 FDR of 507 IC with VTE, 123 had VTE (annual incidence 1.2/1000 person-years); among the 367,911 inhabitants of Brest district, 576 had VTE (annual incidence 1.6/1000 person-years). VTE risk in FDR was higher when IC had unprovoked VTE (SIR 131 [95%CI 109-153]) or had VTE < 47 years (SIR 328 [95%CI 269-385]) or when VTE occurred in ≥2 FDR (SIR 556 [95%CI 484-628]) (Table 1). FDRs with highest risk were when IC had unprovoked VTE and ≥2 FDR had VTE (SIR 636 [95%CI 552-720]) or when IC had VTE < 47 years and ≥2 FDR had VTE (SIR 993 [95%CI 775-1212])."

Clinical • Cardiovascular • Hematological Disorders • Venous Thromboembolism

Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2b | N=129 | Recruiting | Sponsor: SOM Innovation Biotech SA | Trial primary completion date: Apr 2023 ➔ Aug 2023

Trial primary completion date • Huntington's Disease • Movement Disorders

β-arrestin2 recruitment by β-adrenergic receptor agonists and antagonists (PubMed, Sheng Li Xue Bao) - "We used TANGO (transcriptional activation following arrestin translocation) assay to detect the β-arrestin2 recruitment by β-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and β-arrestin2-TEV fusion gene...The results showed that β-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted β-arrestin2 recruitment at β1-AR and β2-AR. β1-AR selective agonists dobutamine and denopamine both promoted β-arrestin2 recruitment at β1-AR...β-AR non-selective antagonists alprenolol and pindolol promoted β-arrestin2 recruitment at β1-AR. β1-AR selective antagonists celiprolol and bevantolol showed β-arrestin2 recruitment at β1-AR. β2-AR selective antagonists butoxamine showed β-arrestin2 recruitment at β1-AR. These results provide some clues for the potential action of β-AR drugs, and lay a foundation for the screening of β-arrestin-biased β-AR ligands."

Journal • Cardiovascular • ARRB1

A proof-of-concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease. (PubMed, Br J Clin Pharmacol) - P2a | "Within the limits of this study, the results suggest that SOM3355 reduces chorea in patients with Huntington's disease and is well-tolerated. Larger studies are necessary to confirm its therapeutic utility as an antichoreic drug. EudraCT number: 2018-000203-16 and ClinicalTrials.gov Identifier: NCT03575676."

Journal • Huntington's Disease • Movement Disorders

Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2b | N=129 | Recruiting | Sponsor: SOM Innovation Biotech SA | Not yet recruiting ➔ Recruiting

Enrollment open • Huntington's Disease • Movement Disorders

Efficacy and Safety on SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2b | N=129 | Not yet recruiting | Sponsor: SOM Innovation Biotech SA

New P2b trial • Huntington's Disease • Movement Disorders

Proof-of-Concept Study Testing SOM3355 in the Treatment of Chorea Symptoms in Huntington’s Disease (HSG 2021) - "SOM3355 reduces chorea in HD and has a good safety profile. SOM Biotech discovered that SOM3355 (bevantolol) has VMAT2 inhibitor activity and could be repositioned in the treatment of chorea in HD. A proof-of-concept study was conducted to confirm that SOM3355 effectively reduces Huntington’s chorea and has a good safety profile."

Huntington's Disease • Hypertension • Movement Disorders

Variation of tuberculosis prevalence across diagnostic approaches and geographical areas of Indonesia. (PubMed, PLoS One) - "The variation of TB prevalence across geographical regions could be confounded by the diagnostic approaches."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

SOM Biotech granted Orphan Drug Designation by the FDA for SOM3355 (GlobeNewswire) - “M Biotech…announces that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for SOM3355, currently in clinical development for the treatment of chorea movements in Huntington´s Disease (HD). The FDA Office of Orphan Products Development grants orphan status to support the development of drugs for the safe and effective treatment of rare disorders. Receiving ODD may qualify SOM Biotech for a seven year period of US marketing exclusivity upon approval of SOM3355.”

Orphan drug • CNS Disorders • Huntington's Disease

[VIRTUAL] Proof-of-concept study testing bevantolol (SOM3355) as treatment of chorea in Huntington's disease (MDS Congress 2021) - "This study confirms that bevantolol reduces chorea in patients with HD and has a good safety profile."

CNS Disorders

Tandem H/D Exchange-SET Reductive Deuteration Strategy for the Synthesis of α,β-Deuterated Amines Using DO. (PubMed, J Org Chem) - "The H/D exchange of the -CHCN group was achieved by DO/EtN, which were also the required reagents in the tandem SmI-mediated SET reductive deuteration of the α-deuterated nitrile. The potential application of this method was further showcased by the synthesis of bevantolol-d."

Journal

Prognostic value of estimated plasma volume in patients with chronic systolic heart failure. (PubMed, J Investig Med) - "ePVS determined using hemoglobin and hematocrit was independently associated with clinical outcomes for patients with stable CHF. Our study thus further strengthens the evidence that ePVS has important prognostic value in patients with stable CHF.Trial registration number ChiCTR-ONC-14004463."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

[VIRTUAL] ALTERNATE DONOR HSCT FOR 109 CHILDREN WITH ACQUIRED SEVERE APLASTIC ANEMIA: A SINGLE CENTER RETROSPECTIVE ANALYSIS (EBMT 2020) - " Fludarabine (180mg/m2-200mg/m2) +Cyclophosphamide (120mg/kg) +Anti-thymocyte globulin ( thymoglobulin 10mg/kg) +TBI 3GY were the conditioning regimen and peripheral blood stem cell was as the main stem cell source for all the HSCT children. These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It's reasonable to consider AD HSCT as first line therapy for SAA children without MSD. Better strategies are required to prevent PTLD and aGVHD."

Retrospective data • Anemia • Aplastic Anemia • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

[VIRTUAL] ALTERNATE DONOR HSCT FOR 109 CHILDREN WITH ACQUIRED SEVERE APLASTIC ANEMIA: A SINGLE CENTER RETROSPECTIVE ANALYSIS (EBMT 2020) - " Fludarabine (180mg/m2-200mg/m2) +Cyclophosphamide (120mg/kg) +Anti-thymocyte globulin ( thymoglobulin 10mg/kg) +TBI 3GY were the conditioning regimen and peripheral blood stem cell was as the main stem cell source for all the HSCT children. These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It's reasonable to consider AD HSCT as first line therapy for SAA children without MSD. Better strategies are required to prevent PTLD and aGVHD."

Retrospective data • Anemia • Aplastic Anemia • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

[VIRTUAL] ALTERNATE DONOR HSCT FOR 109 CHILDREN WITH ACQUIRED SEVERE APLASTIC ANEMIA: A SINGLE CENTER RETROSPECTIVE ANALYSIS (EBMT 2020) - " Fludarabine (180mg/m2-200mg/m2) +Cyclophosphamide (120mg/kg) +Anti-thymocyte globulin ( thymoglobulin 10mg/kg) +TBI 3GY were the conditioning regimen and peripheral blood stem cell was as the main stem cell source for all the HSCT children. These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It's reasonable to consider AD HSCT as first line therapy for SAA children without MSD. Better strategies are required to prevent PTLD and aGVHD."

Retrospective data • Anemia • Aplastic Anemia • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

[VIRTUAL] ALTERNATE DONOR HSCT FOR 109 CHILDREN WITH ACQUIRED SEVERE APLASTIC ANEMIA: A SINGLE CENTER RETROSPECTIVE ANALYSIS (EBMT 2020) - " Fludarabine (180mg/m2-200mg/m2) +Cyclophosphamide (120mg/kg) +Anti-thymocyte globulin ( thymoglobulin 10mg/kg) +TBI 3GY were the conditioning regimen and peripheral blood stem cell was as the main stem cell source for all the HSCT children. These excellent outcomes suggest that unmanipulated AD PBSC is a good HSCT source for children with SAA. It's reasonable to consider AD HSCT as first line therapy for SAA children without MSD. Better strategies are required to prevent PTLD and aGVHD."

Retrospective data • Anemia • Aplastic Anemia • Graft versus Host Disease • Hematological Disorders • Immunology • Transplantation

U-shaped association between plasma sphingosine-1-phosphate levels and mortality in patients with chronic systolic heart failure: a prospective cohort study. (PubMed, Lipids Health Dis) - "Plasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Efficacy and Safety of SOM3355 in Huntington's Disease Chorea (clinicaltrials.gov) - P2a; N=30; Not yet recruiting; Sponsor: SOM Biotech SL

New P2a trial • Biosimilar • Genetic Disorders • Huntington's Disease