Sergio Iadevaia Email & Phone Number

Radnor, Pennsylvania, Us

Cambridge, Ma, Us

Provided strategic pharmacometrics input and subject-matter expertise for the design of clinical studies across the Relay portfolioPlanned and executed exposure/efficacy and exposure/safety analyses to optimize RLY-4008 dose regimens and support dose selection for filing of breakthrough therapy designation to the FDAInitiated the development of a preliminary population PK/tumor growth model to predict the longitudinal changes in tumor growth at various RLY-4008 dose levelsDeveloped a preliminary population PK model used to support dose escalation of RLY-2608 in an ongoing ph1 studyConstructed a PK/PD model linking exposure of RLY-2608 to inhibition of a clinically-validated, predictive biomarker. This model was used to define the dose level and exposure threshold necessary to expect clinical responseManaged external collaborations and modeling vendors

Boston, Ma, Us

Developed analysis plans, provided strategic modeling input and delivered high-quality hands-on analyses to guide the design of ph2 and ph3 studies in acute pain (bunionectomy and abdominoplasty)Effectively communicated modeling results to cross-functional teams and all levels of management, represented Modeling and Simulation function in highly-matrixed teams and coordinated integration of efforts from multiple modelersContributed to develop a ph1 population PK model used to guide dose selection for subsequent ph2 studies in models of acute pain Wrote a report and a cover letter that were submitted to the FDA to summarize the results of the population PK model and support submission of the ph2 bunionectomy protocol, respectivelyDeveloped a ph2 population PK model that integrated data from three ph1 and two ph2 studies, including relevant covariatesConducted ER analyses linking exposure of pain agents to sum of pain intensity difference (SPID) to guide dose selection for ph3 studies in bunionectomy and abdominoplastyDeveloped a population PK/PD model of Ibuprofen to deconvolute the effect of rescue medicines from effect of Vertex’s pain therapeutics tested in ph3 clinicals studiesBuilt population PK/PD models of pain agents to simulate the head-to-head comparison vs placebo arm and guide dose selection for planned ph3 studies in acute pain settingsConducted exploratory E-R analyses to quantify the exposure needed to attained meaningful pain relief pain relief within a given time to establish target product profiles of various pain therapeuticsConducted model-based meta-analyses for acute pain to position Vertex’s compounds in the landscape of opioids and non-opioids pain agents with respect to efficacy, safety, tolerability and other relevant endpointsMentored and managed direct reports, peers and summer interns

Tokyo, Jp

Managed the development of QSP platforms for celiac disease and for Crohn's diseaseConstructed a QSP modeling platform that links key neuronal circuitry and neurotransmitters involved in emesis pathophysiology with the effects of neural and humoral inputs in relevant compartments and the mechanisms of action of selected therapies. The platform was used to support dose selection and guide the design of proof of concept clinical studies in patients suffering from post-operative nausea and vomitingBuilt a human QSP model for tau spreading in Alzheimer’s disease. The model was calibrated to qualitatively describe tau kinetics from preclinical mouse studies and quantitatively match tau PET data in patients. The model was used to assess the effect of mAb and ASO in reducing NFT accumulation and quantify the impact of timing of drug administration relative to seeding on NFT accumulation as a function of disease progressionConstructed a longitudinal disease evolution model to predict emerging response of chronic myeloid leukemia patients to Ponatininb. This model was coupled to an existing machine learning algorithm predicting safety events to adaptively fine-tune dosing regimens and optimally reduce disease burden while avoiding adverse eventsLiaised between the departments of Quantitative Solutions, Clinical Pharmacology and Imaging to facilitate the integration of imaging data into QSP and advanced PK/PD modelsMentored and managed direct reports, modeling vendors, external collaborations, peers and summer interns

Tokyo, Jp

Assembled a QSP model that connects systemic dosing of DAAO inhibitors to D-serine increase in the cerebellum to activation of NMDAR signaling to modulation of clinical outcomes, such as SANS and PANSS negative. The model guided dose selection for a phase 2 study in subjects with stable schizophreniaDeveloped a population PK model to establish TAK-653 dose-exposure relationship using clinical data from healthy subjects. The model was used to compute safety margins and probability to exceed NOAEL caps, thus providing a quantitative tool to safely escalate TAK-653 doses across SRD/MRD cohortsFormulated a population PK model that was used to fully redesign the TAK-041-1001 clinically-paused study. The modeling results provided a dose escalation strategy that was included in a justification document submitted to the FDA that enabled to safely restart the paused studyDeveloped a population PK/PD model to predict how TAK-041 plasma exposure would modulate blunting of amphetamine-induced dopamine release in the brain of healthy subjects. The model was used to select optimal dosing regimens for proof-of-concept and PET imaging clinical studies.Developed a semi-mechanistic, population PK/PD/efficacy model to couple the kinetics of tumor blast cells with hematologic improvement to modulation of clinical endpoints (overall response rate, composite complete remission and event-free survival) in patients with high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia and low-blast acute myeloid leukemia. The model was extensively used to compute the probability of technical success of ongoing and planned Phase 3 studiesMentored peers and internsProvided a full Matlab training to the department of Quantitative Clinical Pharmacology

Cambridge, Massachusetts, Us

Led computational efforts to forecast clinical analytics, including timelines, budget and drug supply necessary to complete clinical trialsDesigned biomarker-based clinical trials in collaboration with clinical teams and statisticians. Conducted extensive scenario analyses to optimize trial design. Participated in identifying biomarker cut-points to prospectively select patientsProvided clinical programs with per-quarter budget estimates to support strategic planningForecasted the amount of drug needed across all organizational programs to facilitate the decision of not acquiring additional building capabilities for manufacturing purposes Provided manufacturing and supply chain teams with timelines for drug processing and resupplyEstimated the number of trial managers necessary to support ongoing and planned clinical trials to guide hire/no hire decisions for additional managersConstructed and developed computational tools to dynamically monitor and reforecast timelines of ongoing trials. This tool was routinely used to assess performance of clinical sites and design mitigation strategies for delayed trialsPerformed statistical analysis to identify biomarkers in translational and clinical settingsUsed non-linear, mixed-effect models of tumor growth to compare the activity of various therapeutic agents and identify responders and non-responders in translational in vivo studies

Cambridge, Massachusetts, Us

Performed statistical analysis to identify biomarkers in translational and clinical settingsConducted population PK studies to support the decision to change MM-141 regimen from weight-based to fixed dosing in the ongoing CARRIE Phase 2 trialLed modeling efforts that supported the decision of administering MM-141 in combination with everolimus to patients with solid tumors in a Phase 1 trialUsed non-linear, mixed-effect models of tumor growth to compare the activity of various therapeutic agents and identify responders and non-responders in translational in vivo studiesPerformed noncompartmental and PK/PD analysis to guide the selection of MM-141 dose and schedule in miceFormulated mechanistic models aimed at comparing the activity of monoclonal and multispecific antibodies to advance lead molecules into pre-clinical development

Cambridge, Massachusetts, Us

Formulated and developed mechanistic models to rationalize the mechanism of actions of therapeutics and identify optimal therapeutic combinations targeting large-scale signaling networks Used noncompartmental and PK/PD analysis to optimize drug dosing and scheduling in translational in vivo experiments. Participated in writing PK documentation to support IND applicationApplied statistical modeling to identity and validate biomarkersDeveloped mechanistic models to understand the role of cross-linking efficiency in the activity of monoclonal and multispecific therapeutic antibodiesDeveloped computational approaches to extract and visualize key information from available databases, such as TCGA and CCLE

Cambridge, Massachusetts, Us

Formulated and developed mechanistic models to rationalize the mechanism of actions of therapeutics and identify optimal therapeutic combinations targeting large-scale signaling networks Used noncompartmental and PK/PD analysis to optimize drug dosing and scheduling in translational in vivo experiments.Applied statistical modeling to identity and validate biomarkersDeveloped mechanistic models to understand the role of cross-linking efficiency in the activity of monoclonal and multispecific therapeutic antibodies

Houston, Tx, Us

Engineered mechanistic models to identify optimal therapeutic combinations targeting large-scale signaling networksValidated predicted drug combinations in human cancer cell lines using immunoblotting, reverse phase protein arrays, and cell viability assaysFormulated stochastic models to predict the dynamics of signaling networks in individual cancer cellsUsed FACS analysis and fluorescence microscopy to experimentally validate modeling resultsPredicted controllability and robustness of network motifs in the design and mutational evolution of synthetic circuits

Houston, Tx, Us

Independently taught the course on Dynamics and Process Control (CHBE 470) to senior engineersManaged and organized the process control laboratory. Designed review sessions; graded midterm and final exams

Doctor Of Philosophy (Ph.D.), Chemical And Biomolecular Engineering

Laurea, Chemical Engineering