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Clinical and Pre-Clinical Pharmacokinetics and Pharmacodynamics of Bentracimab

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Abstract

Antiplatelet agents are among the most frequently used medications in cardiovascular medicine. Although in patients with atherosclerotic disease manifestations, in particular those treated by percutaneous coronary intervention, antiplatelet agents are beneficial for the prevention of ischemic events, they inevitably increase the risk of bleeding. Furthermore, 5–15% of patients treated by percutaneous coronary intervention may need a surgical procedure within 2 years, creating challenges to safe and effective antiplatelet drug management. Importantly, major spontaneous or procedural-related bleedings are associated with increased hospital admission, length, costs, and poor prognosis. Although the effects of other antithrombotic therapies, such as direct oral anticoagulants, can be reversed by approved specific agents, there are no approved reversal agents for any antiplatelet drugs. The fact that many antiplatelet agents, such as aspirin and thienopyridines (i.e., clopidogrel and prasugrel), bind irreversibly to their targets represents a challenge for the development of a drug-specific reversal agent. In contrast, ticagrelor is a non-thienopyridine with a plasma half-life of 7−9 h that reversely binds the P2Y12 receptor producing potent signaling blockage. In 2015, bentracimab (also known as PB2452 or MEDI2452), a neutralizing monoclonal antibody fragment that binds free plasma ticagrelor and its major active metabolite, was identified. This systematic overview provides a comprehensive summary of the drug development program of bentracimab, focusing on its pharmacodynamic, pharmacokinetic, and safety profiles.

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Fig. 1
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Fig. 3

Reproduced with permission from Bhatt DL, Pollack CV, Weitz JI, Jennings LK, Xu S, Arnold SE, et al. Antibody-Based Ticagrelor Reversal Agent in Healthy Volunteers. N Engl J Med. 2019 May 9;380(19):1825–33

Fig. 4

Reproduced with permission from Bhatt DL, Pollack CV, Weitz JI, Jennings LK, Xu S, Arnold SE, et al. Antibody-based ticagrelor reversal agent in healthy volunteers. N Engl J Med. 2019 May 9;380(19):1825–33

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References

  1. Angiolillo DJ, Galli M, Collet JP, Kastrati A, O’Donoghue ML. Antiplatelet therapy after percutaneous coronary intervention. EuroIntervention. 2022;17(17):e1371–96.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Capodanno D, Bhatt DL, Gibson CM, James S, Kimura T, Mehran R, et al. Bleeding avoidance strategies in percutaneous coronary intervention. Nat Rev Cardiol. 2022;19(2):117–32.

    Article  PubMed  Google Scholar 

  3. Capodanno D, Angiolillo DJ. Management of antiplatelet therapy in patients with coronary artery disease requiring cardiac and noncardiac surgery. Circulation. 2013;128(25):2785–98.

    Article  PubMed  Google Scholar 

  4. Salter B, Crowther M. A historical perspective on the reversal of anticoagulants. Semin Thromb Hemost. 2022;48(8):955–70.

    Article  PubMed  Google Scholar 

  5. Capodanno D, Milluzzo RP, Angiolillo DJ. Intravenous antiplatelet therapies (glycoprotein IIb/IIIa receptor inhibitors and cangrelor) in percutaneous coronary intervention: from pharmacology to indications for clinical use. Ther Adv Cardiovasc Dis. 2019;13:1753944719893274.

  6. Franchi F, Ortega-Paz L, Rollini F, Galli M, Been L, Ghanem G, et al. Cangrelor in patients with coronary artery disease pretreated with ticagrelor: the Switching Antiplatelet (SWAP)-5 Study. JACC Cardiovasc Interv. 2023;16(1):36–46.

    Article  PubMed  Google Scholar 

  7. Franchi F, Rollini F, Muniz-Lozano A, Cho JR, Angiolillo DJ. Cangrelor: a review on pharmacology and clinical trial development. Expert Rev Cardiovasc Ther. 2013;11(10):1279–91.

    Article  CAS  PubMed  Google Scholar 

  8. Vaduganathan M, Harrington RA, Stone GW, Deliargyris EN, Steg PG, Gibson CM, et al. Evaluation of ischemic and bleeding risks associated with 2 parenteral antiplatelet strategies comparing cangrelor with glycoprotein IIb/IIIa inhibitors: an exploratory analysis from the CHAMPION trials. JAMA Cardiol. 2017;2(2):127–35.

    Article  PubMed  Google Scholar 

  9. Vaduganathan M, Harrington RA, Stone GW, Deliargyris EN, Steg PG, Gibson CM, et al. Cangrelor with and without glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol. 2017;69(2):176–85.

    Article  CAS  PubMed  Google Scholar 

  10. Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303–13.

    Article  CAS  PubMed  Google Scholar 

  11. Franchi F, Rollini F, Rivas A, Wali M, Briceno M, Agarwal M, et al. Platelet inhibition with cangrelor and crushed ticagrelor in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation. 2019;139(14):1661–70.

    Article  CAS  PubMed  Google Scholar 

  12. Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med. 2007;357(24):2482–94.

    Article  CAS  PubMed  Google Scholar 

  13. US FDA. Prasugrel FDA label. 2009. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022307s002lbl.pdf. Accessed 28 Dec 2022.

  14. Teng R, Carlson GF, Nylander S, Andersson TL. Effects of autologous platelet transfusion on platelet inhibition in ticagrelor-treated and clopidogrel-treated subjects. J Thromb Haemost. 2016;14(12):2342–52.

    Article  CAS  PubMed  Google Scholar 

  15. Sharma S, Bhambi B. Use of platelet transfusion to facilitate surgery in patients on clopidogrel and aspirin therapy after drug-eluting stent percutaneous coronary intervention. Catheter Cardiovasc Interv. 2012;79(3):498 (author reply 9–500).

    Article  PubMed  Google Scholar 

  16. Ariotti S, Ortega-Paz L, van Leeuwen M, Brugaletta S, Leonardi S, Akkerhuis KM, et al. Effects of ticagrelor, prasugrel, or clopidogrel on endothelial function and other vascular biomarkers: a randomized crossover study. JACC Cardiovasc Interv. 2018;11(16):1576–86.

    Article  PubMed  Google Scholar 

  17. Ariotti S, van Leeuwen M, Brugaletta S, Leonardi S, Akkerhuis KM, Rimoldi SF, et al. Effects of ticagrelor, prasugrel, or clopidogrel at steady state on endothelial function. J Am Coll Cardiol. 2018;71(11):1289–91.

    Article  PubMed  Google Scholar 

  18. Teng R, Oliver S, Hayes MA, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010;38(9):1514–21.

    Article  CAS  PubMed  Google Scholar 

  19. Zhou D, Andersson TB, Grimm SW. In vitro evaluation of potential drug-drug interactions with ticagrelor: cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metab Dispos. 2011;39(4):703–10.

    Article  CAS  PubMed  Google Scholar 

  20. Calderone D, Capodanno D, Angiolillo DJ. An updated drug profile of ticagrelor with considerations on the treatment of patients with coronary artery disease and diabetes mellitus. Expert Rev Cardiovasc Ther. 2020;18(8):449–64.

    Article  CAS  PubMed  Google Scholar 

  21. Cattaneo M, Schulz R, Nylander S. Adenosine-mediated effects of ticagrelor: evidence and potential clinical relevance. J Am Coll Cardiol. 2014;63(23):2503–9.

    Article  CAS  PubMed  Google Scholar 

  22. Zafar MU, Santos-Gallego C, Vorchheimer DA, Viles-Gonzalez JF, Elmariah S, Giannarelli C, et al. Platelet function normalization after a prasugrel loading-dose: time-dependent effect of platelet supplementation. J Thromb Haemost. 2013;11(1):100–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schoener L, Jellinghaus S, Richter B, Pfluecke C, Ende G, Christoph M, et al. Reversal of the platelet inhibitory effect of the P2Y(12) inhibitors clopidogrel, prasugrel, and ticagrelor in vitro: a new approach to an old issue. Clin Res Cardiol. 2017;106(11):868–74.

    Article  CAS  PubMed  Google Scholar 

  24. Angheloiu GO, Gugiu GB, Ruse C, Pandey R, Dasari RR, Whatling C. Ticagrelor removal from human blood. JACC Basic Transl Sci. 2017;2(2):135–45.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Buchanan A, Newton P, Pehrsson S, Inghardt T, Antonsson T, Svensson P, et al. Structural and functional characterization of a specific antidote for ticagrelor. Blood. 2015;125(22):3484–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sandinge AS, Janefeldt A, Pehrsson S, Nylander S. Quantification of unbound concentration of ticagrelor in plasma as a proof of mechanism biomarker of the reversal agent, MEDI2452. PLoS ONE. 2018;13(7): e0201202.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Almquist J, Penney M, Pehrsson S, Sandinge AS, Janefeldt A, Maqbool S, et al. Unraveling the pharmacokinetic interaction of ticagrelor and MEDI2452 (ticagrelor antidote) by mathematical modeling. CPT Pharmacometrics Syst Pharmacol. 2016;5(6):313–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Barrett JS, Fossler MJ, Cadieu KD, Gastonguay MR. Pharmacometrics: a multidisciplinary field to facilitate critical thinking in drug development and translational research settings. J Clin Pharmacol. 2008;48(5):632–49.

    Article  PubMed  Google Scholar 

  29. Behr TM, Goldenberg DM, Becker W. Reducing the renal uptake of radiolabeled antibody fragments and peptides for diagnosis and therapy: present status, future prospects and limitations. Eur J Nucl Med. 1998;25(2):201–12.

    Article  CAS  PubMed  Google Scholar 

  30. Pehrsson S, Johansson KJ, Janefeldt A, Sandinge AS, Maqbool S, Goodman J, et al. Hemostatic effects of the ticagrelor antidote MEDI2452 in pigs treated with ticagrelor on a background of aspirin. J Thromb Haemost. 2017;15(6):1213–22.

    Article  CAS  PubMed  Google Scholar 

  31. Bhatt DL, Pollack CV, Weitz JI, Jennings LK, Xu S, Arnold SE, et al. Antibody-based ticagrelor reversal agent in healthy volunteers. N Engl J Med. 2019;380(19):1825–33.

    Article  CAS  PubMed  Google Scholar 

  32. Kathman SJ, Wheeler JJ, Bhatt DL, Arnold SE, Lee JS. Population pharmacokinetic-pharmacodynamic modeling of PB2452, a monoclonal antibody fragment being developed as a ticagrelor reversal agent, in healthy volunteers. CPT Pharmacometr Syst Pharmacol. 2022;11(1):68–81.

    Article  CAS  Google Scholar 

  33. U.S. NLM. Study to evaluate the safety, tolerability, PK and PD of PB2452 in healthy younger, older and elderly subjects. 2020. https://clinicaltrials.gov/ct2/show/NCT03928353. Accessed 16 Dec 2022.

  34. PhaseBio-Pharmaceuticals. PhaseBio announces completion of phase 2a clinical trial of PB2452 for the reversal of the antiplatelet activity of ticagrelor of PB2452 for the reversal of the antiplatelet activity of ticagrelor. 2019. https://investors.phasebio.com/news-releases/news-release-details/phasebio-announces-completion-phase-2a-clinical-trial-pb2452/. Accessed 13 Dec 2022.

  35. PhaseBio-Pharmaceuticals. PhaseBio announces positive preliminary results from phase 2a clinical trial of PB2452 for the reversal of the antiplatelet activity of ticagrelor in older and elderly subjects. 2019. https://investors.phasebio.com/news-releases/news-release-details/phasebio-announces-positive-preliminary-results-phase-2a/. Accessed 13 Dec 2022.

  36. PhaseBio-Pharmaceuticals. Corporate overview. 2021. https://investors.phasebio.com/static-files/0be2e15a-8c3d-4698-877d-11c9a3be7a76. Accessed 14 Dec 2022.

  37. PhaseBio-Pharmaceuticals. PhaseBio announces positive results from phase 2b trial for bentracimab. 2022. https://investors.phasebio.com/news-releases/news-release-details/phasebio-announces-positive-results-phase-2b-trial-bentracimab. Accessed 14 Dec 2022.

  38. U.S. NLM. Phase 2B study to evaluate the efficacy of bentracimab (PB2452) in reversal of ticagrelor in subjects aged 50-80 years old. 2022. https://clinicaltrials.gov/ct2/show/NCT04122170. Accessed 14 Dec 2022.

  39. Bhatt DL. Bentracimab immediately and significantly reverses the antiplatelet effects of ticagrelor in older people. ACC Annual Scientific Session, 2–4of April 2022, Washington DC; 2022.

  40. Curry B, Brown R, Bhatt D, Arnold S, Lee J, Jennings L. Bentracimab demonstrates reversal of antiplatelet effects of ticagrelor: impact of hematocrit and generic versions of ticagrelor in vitro. Eur Heart J. 2022;43(Suppl_2).

  41. Bhatt DL, Pollack CV, Mazer CD, Angiolillo DJ, Steg PG, James SK, et al. Bentracimab for ticagrelor reversal in patients undergoing urgent surgery. NEJM Evid. 2022;1(3):EVIDoa2100047.

  42. Investigators G. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329(10):673–82.

  43. Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, et al. Full study report of andexanet alfa for bleeding associated with Factor Xa inhibitors. N Engl J Med. 2019;380(14):1326–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bhatt DL. Effect of bentracimab on platelet inhibition and hemostasis in patients on ticagrelor with major bleeding or requiring urgent procedures. American Heart Association Scientific Sessions, 13–15th of November; 2021; Boston (MA).

  45. Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, et al. Idarucizumab for dabigatran reversal: full cohort analysis. N Engl J Med. 2017;377(5):431–41.

    Article  CAS  PubMed  Google Scholar 

  46. Makhdoum A, Dhingra NK, Kirubaharan A, Eikelboom R, Luc J, Dagher O, et al. Ticagrelor use and practice patterns among Canadian cardiac surgeons. J Card Surg. 2021;36(8):2793–801.

    Article  PubMed  Google Scholar 

  47. U.S. NLM. Study to evaluate the safety, tolerability, PK, and PD of PB2452 with and without ticagrelor pretreatment in Chinese healthy volunteers. 2022. https://clinicaltrials.gov/ct2/show/NCT05162131. Accessed 15 Dec 2022.

  48. AstraZeneca. AstraZeneca announces initiation of development programme for BRILINTA® reversal agent. 2014. https://www.astrazeneca.com/media-centre/press-releases/2014/astrazeneca-brilinta-development-programme-cardiovascular-13112014.html#. Accessed 15 Dec 2022.

  49. PhaseBio-Pharmaceuticals. PhaseBio enters worldwide license agreement with MedImmune for a reversal agent for ticagrelor. 2017. https://investors.phasebio.com/news-releases/news-release-details/phasebio-enters-worldwide-license-agreement-medimmune-reversal/. Accessed 15 Dec 2022.

  50. PhaseBio-Pharmaceuticals. PhaseBio Pharmaceuticals achieves enrollment milestones supporting interim analysis of REVERSE-IT global phase 3 trial, enabling preparation of a BLA submission for bentracimab for reversal of antiplatelet effects of ticagrelor. 2021. https://investors.phasebio.com/news-releases/news-release-details/phasebio-pharmaceuticals-achieves-enrollment-milestones. Accessed 15 Dec 2022.

  51. PhaseBio-Pharmaceuticals. PhaseBio announces successful pre-BLA meeting with U.S. FDA for bentracimab. 2022. https://investors.phasebio.com/news-releases/news-release-details/phasebio-announces-successful-pre-bla-meeting-us-fda-bentracimab. Accessed 15 Dec 2022.

  52. PhaseBio-Pharmaceuticals. PhaseBio reports first quarter 2020 financial results and recent business highlights. 2022. https://investors.phasebio.com/news-releases/news-release-details/phasebio-reports-first-quarter-2020-financial-results-and-recent/. Accessed 15 Dec 2022.

  53. PhaseBio-Pharmaceuticals. PhaseBio Pharmaceuticals and SFJ Pharmaceuticals® announce approval of IND application in China for bentracimab. 2021. https://investors.phasebio.com/news-releases/news-release-details/phasebio-pharmaceuticals-and-sfj-pharmaceuticalsr-announce. Accessed 16 Dec 2022.

  54. PhaseBio-Pharmaceuticals. PhaseBio announces dosing of first patient in European Union as part of REVERSE-IT global phase 3 trial of bentracimab for reversal of antiplatelet effects of ticagrelor. 2021. https://investors.phasebio.com/news-releases/news-release-details/phasebio-announces-dosing-first-patient-european-union-part. Accessed 16 Dec 2022.

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Authors and Affiliations

  1. Division of Cardiology, University of Florida College of Medicine, ACC Building 5th Floor, 655 West 8th Street, Jacksonville, FL, 32209, USA

    Luis Ortega-Paz, Salvatore Giordano, Francesco Franchi, Fabiana Rollini & Dominick J. Angiolillo

  2. Division of Cardiology, Department of Medical and Surgical Sciences, “Magna Graecia” University, Catanzaro, Italy

    Salvatore Giordano

  3. Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MI, USA

    Charles V. Pollack Jr.

  4. Mount Sinai Heart, Icahn School of Medicine at Mount Sinai Health System, New York, NY, USA

    Deepak L. Bhatt

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  1. Luis Ortega-Paz
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Correspondence to Dominick J. Angiolillo.

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Francesco Franchi declares that he has received payment as an individual for consulting fees or honoraria from AstraZeneca, Bayer, and Sanofi; and institutional payments for grants from PLx Pharma and The Scott R. MacKenzie Foundation. Charles V. Pollack Jr discloses the following relationships pertinent to this work: consulting fees or honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, PhaseBio, Provepharm, Milestone, and eXIthera; and research support from AstraZeneca, Provepharm, eXIthera, Janssen Pharma, CSL/Behring, DaiichiSankyo, and Portola. Deepak L. Bhatt discloses the following relationships: Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; Board of Directors: Angiowave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Consultant: Broadview Ventures; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither Francesco Franchi nor Brigham and Women’s Hospital receives any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; trustee: American College of Cardiology; unfunded research: FlowCo and Takeda. Dominick J. Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, Novartis, PhaseBio, PLx Pharma, Pfizer, Sanofi, and Vectura; he also declares that his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, and the Scott R. MacKenzie Foundation. Luis Ortega-Paz, Salvatore Giordano, and Fabiana Rollini have no conflicts of interest that are directly relevant to the content of this article.

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LO-P, SG, and DJA: conceptualization, methodology, project administration, visualization, writing, reviewing and editing. FF FR, CVP, DLB: reviewing and editing.

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Ortega-Paz, L., Giordano, S., Franchi, F. et al. Clinical and Pre-Clinical Pharmacokinetics and Pharmacodynamics of Bentracimab. Clin Pharmacokinet 62, 673–692 (2023). https://doi.org/10.1007/s40262-023-01245-3

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