PF-07059013 / Pfizer - LARVOL DELTA

Digitalizing the TIM-1 Model using Computational Approaches-Part One: TIM-1 Data Explorer. (PubMed, Mol Pharm) - "The TIM-1 Data Explorer was validated in two case studies. In the first case study with paracetamol, we have shown the ability of the simulator to adequately describe mass transfer events within the TIM-1 system, and in the second study with a weakly basic in-house compound, PF-07059013, the TIM-1 Data Explorer was successfully used to describe dissolution and precipitation processes."

Journal • Gastrointestinal Disorder • KIM1

Digitalizing the TIM-1 Model Using Computational Approaches─Part Two: Digital TIM-1 Model in GastroPlus. (PubMed, Mol Pharm) - "In a second set of experiments, a case example with PF-07059013 was performed, where luminal concentrations and bioaccessible fractions were predicted for 200 and 1000 mg doses under fasted and achlorhydric conditions...Toward future applications, the digital TIM-1 model will be thoroughly applied to explore a link between in vitro and in vivo outcomes based on more case examples with model compounds with the access of TIM-1 and plasma data. Ideally, this digital TIM-1 can be directly used in GastroPlus to explore an in vitro-in vivo correlation (IVIVC) between the fraction dissolved (digital TIM-1 settings) and the fraction absorbed (human PBPK settings)."

Journal • Gastrointestinal Disorder • KIM1

Using Mitra sampling to support first-in-human pharmacokinetic evaluations for PF-07059013. (PubMed, Bioanalysis) - P1 | "Correlation coefficient between blood concentrations obtained from liquid-incurred blood samples and dried-incurred blood samples is 0.95. Clinical Trial Registration: NCT04323124 (ClinicalTrials.gov)."

Journal • P1 data • PK/PD data • Review

A Pharmacometrics Model to Characterize a New Type of Target-Mediated Drug Disposition (TMDD) - Nonlinear Pharmacokinetics of Small-Molecule PF-07059013 Mediated By Its High-capacity Pharmacological Target Hemoglobin With Positive Cooperative Binding. (PubMed, AAPS J) - "Our final model provided valuable insight on target binding-related parameters, such as the Hill coefficient γ (estimated to be 1.6), binding constant K (estimated to be 1450 µM), and the amount of total hemoglobin R (estimated to be 2.13 µmol). As the dose selection of a compound with positive cooperative binding is tricky and challenging due to the nonproportional and steep response, our model may be valuable in facilitating the rational dose regimen selection for future preclinical animal and clinical trials for PF-07059013 and other compounds whose nonlinear pharmacokinetics are caused by similar mechanisms."

Journal • PK/PD data • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Study of Single and Multiple Ascending Doses of PF-07059013 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=61 | Terminated | Sponsor: Pfizer | Active, not recruiting ➔ Terminated; Study was terminated as it did not demonstrate sufficient pharmacological effect. Termination was not related to safety reasons.

Trial termination

Identification and route optimization of PF-07059013 for the treatment of sickle cell diesease (ACS-Sp 2022) - "Polymerized HbS leads to acute illness including vasooclusion, hemolytic anemia, and stroke. This talk will cover the identification of a non-covalent modulator, PF-07059013, and the evolution of the routes to deliver compound for safety studies."

Anemia • Cardiovascular • Genetic Disorders • Hematological Disorders

Study of Single and Multiple Ascending Doses of PF-07059013 in Healthy Adult Participants (clinicaltrials.gov) - P1; N=70; Active, not recruiting; Sponsor: Pfizer; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Study of Single and Multiple Ascending Doses of PF-07059013 in Healthy Adult Participants (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Pfizer; Trial primary completion date: Aug 2021 ➔ Dec 2021

Clinical • Trial primary completion date

PF-07059013: A Non-Covalent Hemoglobin Modulator Favorably Impacts Disease State in a Mouse Model of Sickle Cell Disease. (PubMed, Am J Hematol) - No abstract available

Journal • Preclinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Study of Single and Multiple Ascending Doses of PF-07059013 in Healthy Adult Participants (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: Pfizer; Trial completion date: Apr 2021 ➔ Oct 2021

Clinical • Trial completion date

PF-07059013: A Noncovalent Modulator of Hemoglobin for Treatment of Sickle Cell Disease. (PubMed, J Med Chem) - "In a 2-week multiple dose study using Townes SCD mice, 23 showed a 37.8% (±9.0%) reduction in sickling compared to vehicle treated mice. 23 (PF-07059013) has advanced to phase 1 clinical trials."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hematological Disorders • Sickle Cell Disease