HematologyCardiovascular & coagulationRare disease PKPDTMDD

Befovacimab PK and TFPI target binding

Reference paper ↗

A QSS-TMDD model representing intravenous or subcutaneous befovacimab disposition, TFPI turnover, free antibody, and antibody–TFPI complex dynamics.

Therapeutic
Befovacimab, BAY 1093884 / befovacimab
Modality
Monoclonal antibody
Target
TFPI, tissue factor pathway inhibitor
Disease
Translational hemophilia prophylaxis
Model type
PKPD, TMDD

Complete model workspace

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Parameters
12
States
8
Equations
8
Derived outputs
25

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cynomolgus IV 5 mg/kg QSS-TMDD

How do route and dose change befovacimab exposure, free antibody, TFPI, and bound complex? Explore this biological starting configuration through Total central befovacimab, Free central befovacimab, Total TFPI, Befovacimab–TFPI complex, Cumulative exposure.

Starting result

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Starting configuration

Time: 0–720 hour; step 1

InputDefaultAvailable range
Systemic clearance2.87e-4 L/h/kg1.43e-4–4.31e-4 L/h/kg
Central distribution volume0.0491 L/kg0.02455–0.07365 L/kg
Quasi-steady-state binding constant232 nM116–348 nM
Target internalization rate55.4 1/h27.7–83.1 1/h
Target synthesis rate2.6 nM/h1.3–3.9 nM/h

Expected readouts

Total central befovacimab · Free central befovacimab · Total target concentration (nM) · Befovacimab TFPI complex · Exposure (AUC) (mg*h/L)

Adjustable model parameters

This public explorer exposes 5 curated parameters. Sign in to edit all 12 declared model parameters.

More key parameters (1)

How the model represents the biology

A QSS-TMDD model representing intravenous or subcutaneous befovacimab disposition, TFPI turnover, free antibody, and antibody–TFPI complex dynamics.

How do IV or subcutaneous befovacimab entry, TFPI turnover, and QSS binding interact?A scenario initializes intravenous central befovacimab or fast and delayed subcutaneous depots. Absorbed antibody enters central total-drug disposition and exchanges as free antibody with a peripheral pool. TFPI is synthesized and turned over, while an algebraic QSS allocation determines antibody-TFPI complex and its internalization.BIOLOGY OVERVIEWHow do IV or subcutaneous befovacimab entry, TFPI turnover, and QSS bindinginteract?Route initializationIV central or SC depot statesFast + delayed SCdepotsRoute-specific absorptionBefovacimabdispositionCentral total/free andperipheral freeTFPI synthesisBaseline production andturnoverTotal TFPIDynamic target poolQSS antibody–TFPIcomplexAlgebraic binding allocationDrug + target removalLinear CL, turnover,internalizationPRIMARY READOUTSCentral total antibodyCentral total antibodyCentral free antibodyCentral free antibodyTotal TFPITotal TFPIAntibody–TFPI complexAntibody–TFPI complexCumulative exposureCumulative exposure

Solid arrows show modeled movement or change; two-headed arrows show reversible exchange; dashed arrows show modulation without material transfer.

Model scope: Kinetic association/dissociation states, coagulation-cascade dynamics, thrombin generation, bleeding outcomes, and modeled dose events are not represented; public routes initialize states and binding is algebraic QSS.

Modeled relationships (9)
  • Route initialization → Fast + delayed SC depots: SC initialization (flow)
  • Route initialization → Befovacimab disposition: IV initialization (flow)
  • Fast + delayed SC depots → Befovacimab disposition: absorption (flow)
  • TFPI synthesis → Total TFPI: target synthesis (production)
  • Befovacimab disposition → QSS antibody–TFPI complex: QSS allocation (modulation)
  • Total TFPI → QSS antibody–TFPI complex: QSS allocation (modulation)
  • Befovacimab disposition → Drug + target removal: free-drug CL (loss)
  • Total TFPI → Drug + target removal: target turnover (loss)
  • QSS antibody–TFPI complex → Drug + target removal: internalization (loss)

Modeled relationships: Route initialization to Fast + delayed SC depots: SC initialization (flow); Route initialization to Befovacimab disposition: IV initialization (flow); Fast + delayed SC depots to Befovacimab disposition: absorption (flow); TFPI synthesis to Total TFPI: target synthesis (production); Befovacimab disposition to QSS antibody–TFPI complex: QSS allocation (modulation); Total TFPI to QSS antibody–TFPI complex: QSS allocation (modulation); Befovacimab disposition to Drug + target removal: free-drug CL (loss); Total TFPI to Drug + target removal: target turnover (loss); QSS antibody–TFPI complex to Drug + target removal: internalization (loss).

Primary readouts: Central total antibody; Central free antibody; Total TFPI; Antibody–TFPI complex; Cumulative exposure.

Found a scientific issue? Email helpdesk@unibiointelligence.com with model ID gu_2017_bay1093884_tfpi_qss_tmdd.

Research use only — not for patient-specific prediction or dosing advice.

Ubi Biologics