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Found in Translation: Building an Early Development Strategy for Complex Biologics

On-Demand Webinar

The discovery of immune targets CTLA-4 and PD-1 in the 1990s opened the door to the dramatic curative advances in cancer treatment seen over the last decade.  Central to this success are biologic-based treatment modalities, such as the monoclonal antibody-based drugs nivolumab and pembrolizumab and the unique bi-specific T-cell engager (BiTE) antibody fragment platform-based drug blinatumomab.  The success of biologics in oncology along with advances in other therapeutic areas such as autoimmune and rare disease has enhanced interest in the development of biologic-based platforms.  The immuno-oncology market alone is predicted to generate over $30 billion by 2024 with the largest proportion derived from checkpoint inhibitors.  The number of companies developing complex biologic therapeutics has increased exponentially with limited precedent to guide successful development in this novel emerging market.

What is a complex biologic? Here, complex biologics include therapeutic modalities such as monoclonal antibodies against immunomodulatory targets, engineered proteins and antibody fragments, bi-specific platforms, T-cell directed therapies, chimeric antigen receptor T-cell (CAR-T) therapies, antibody-drug conjugates, vaccines, gene therapies, and more.

Nonclinical to clinical translation of complex biologic therapeutics requires integrating the totality of available data for successful projection of target dose range and effective design of Phase 1/2 studies. Intentional pharmacology-driven early development of complex biologics can mitigate downstream risks, reduce costs, simplify critical decision points, streamline regulatory reviews, and substantially shorten the time to pivotal studies.

This webinar will describe some important strategic considerations for successful development of these challenging therapeutics in early development including appropriate data collection and timings, analyses requiring cross-functional data integration, and key pharmacology-related critical questions.  Some of these considerations include:

–          Development and evolution of the target product profile (TPP)

–          Risk assessment and mitigation planning

–          Translational exposure-response (E-R) and exposure-safety (E-S) analyses

–          Defining PK-PD relationships and application of quantitative modeling & simulation (M&S)

–          First-in-human (FIH) starting dose calculation methodology

–          Phase 1 and 2 integrative dose selection strategy

–          Clinical pharmacology data collection and analysis plans

The complex biologic development road map proposed here is intended to guide cross-functional data generation and analysis from nonclinical to early clinical development with the ultimate goal of improving confidence and probability of success at critical decision points.

About Our Speakers

Dr. Moss joined Certara in November 2017 as Director, Integrated Drug Development, focusing on Translational and Clinical Pharmacology, bringing with him over 10 years’ experience in translational modeling and simulation (M&S). Dr. Moss has developed a number of novel therapeutic modalities and drug delivery systems in the pharmaceutical industry during his tenures at Alpine Immune Sciences, AbbVie, Seattle Genetics, Amgen, and Sonus Pharmaceuticals. Dr. Moss has extensive experience in project representation and team leadership for both preclinical and clinical phases of development. His expertise includes:

– Preclinical PK and TK analysis, reporting, and regulatory integration

– PKPD strategy, study design, and modeling and simulation

– First In Human dose selection and rationale

– Integration of PK, TOX, and PD for translation to human clinical trials

– DMPK strategy for ADME and DDI characterization

– Translation of biomarker and PKPD into early phase clinical studies

He received his PhD in Pharmaceutics from the University of Washington where his research focused on pharmacokinetics, transporters and drug-drug interactions (DDIs). Throughout his career in pharma, Dr. Moss has used his expertise in quantitative pharmacology to support the progression of lead candidates from discovery and early clinical development through to regulatory IND and BLA submission.

His recent research has focused on novel Antibody Drug Conjugates, Immuno-oncology, CAR T-cell, and auto-immune therapeutic areas. For the past 5 years he has shared his expertise with budding clinical pharmacologists as an Affiliate Instructor in the School of Pharmacy, Department of Pharmaceutics, at the University of Washington.

As an Associate Director of Clinical Pharmacology in the Integrated Drug Development group at Certara Strategic Consulting, Dr. Mayer provides expertise in nonclinical/translational and early to mid-stage clinical development of oncology biologics including traditional monoclonal antibodies as well as novel platforms/approaches such as engineered antibodies, bi-specifics, gene therapies, cell therapies, and combination therapies.

Dr. Mayer’s experience in this area includes:

•       NME to IND strategy including nonclinical pharmacokinetic (PK)/pharmacodynamic (PD) and TK study design and analysis

•       Pre-IND NME risk assessment including justification of first-in-human dose, regimen, escalation strategy, maximum dose, flat dosing

•       Sampling schemes, bioanalytical considerations, and analysis plans for PK, PD, receptor occupancy, and target engagement

•       Phase 1 in-stream evaluation of PK relationships with safety, efficacy, and PD

•       Phase 2 dose justification

•       Risk assessment and strategy for biologic drug material and process changes

•       Multi-drug combination study dose selection and trial design

Dr. Mayer earned her Bachelor of Science Degree from Boston College (Chestnut Hill, MA, USA) and PharmD with Honors from the University of North Carolina – Chapel Hill (Chapel Hill, NC, USA). She completed a postdoctoral fellowship in Clinical PK/PD at the University of North Carolina – Chapel Hill and GlaxoSmithKline. Prior to Certara, she worked as a Clinical Pharmacology Lead at Janssen Biotherapeutics (Johnson & Johnson).  Dr. Mayer is also a practicing pharmacist and an active lecturer in clinical pharmacology globally.

The discovery of immune targets CTLA-4 and PD-1 in the 1990s opened the door to the dramatic curative advances in cancer treatment seen over the last decade. Central to this success are biologic-based treatment modalities, such as the monoclonal antibody-based drugs nivolumab and pembrolizumab and the unique bi-specific T-cell engager (BiTE) antibody fragment platform-based drug blinatumomab. The success of biologics in oncology along with advances in other therapeutic areas such as autoimmune and rare disease has enhanced interest in the development of biologic-based platforms. The immuno-oncology market alone is predicted to generate over $30 billion by 2024 with the largest proportion derived from checkpoint inhibitors. The number of companies developing complex biologic therapeutics has increased exponentially with limited precedent to guide successful development in this novel emerging market.

What is a complex biologic? Here, complex biologics include therapeutic modalities such as monoclonal antibodies against immunomodulatory targets, engineered proteins and antibody fragments, bi-specific platforms, T-cell directed therapies, chimeric antigen receptor T-cell (CAR-T) therapies, antibody-drug conjugates, vaccines, gene therapies, and more.

Nonclinical to clinical translation of complex biologic therapeutics requires integrating the totality of available data for successful projection of target dose range and effective design of Phase 1/2 studies. Intentional pharmacology-driven early development of complex biologics can mitigate downstream risks, reduce costs, simplify critical decision points, streamline regulatory reviews, and substantially shorten the time to pivotal studies.

This webinar described some important strategic considerations for successful development of these challenging therapeutics including appropriate data collection and timings, analyses requiring cross-functional data integration, and key pharmacology-related critical questions.

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