Ensuring Translational Scientific Understanding Underpins Your Biomarker-Dx Strategy. Thomas Krahn Bayer Pharma AG

Transcription

1 Ensuring Translational Scientific Understanding Underpins Your Biomarker-Dx Strategy Thomas Krahn Bayer Pharma AG

2 Forward-Looking Statements / Disclosures This presentation may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer s public reports which are available on the Bayer website at The company assumes no liability whatsoever to update these forwardlooking statements or to conform them to future events or developments. Page 2

3 Introduction We are committed to develop a biomarker strategy for every compound going into clinical studies and to fully leverage the opportunities of personalized medicine for the benefit of our patients. Personalized Medicine will be a major driver of innovation and the next evolutionary step towards a more effective and efficient use of therapeutic interventions. Today with only few successful examples industry is still at an early stage. Bayer Pharma aims to become a leader in providing personalized treatment solutions by Page 3

4 Personalized Medicine. means something different to patients, physicians, regulators, payers Patients From trial & error to personalized medicine - It is about getting the right dose, of the right drug, to the right patient at the right time based on a refined diagnosis of the underlying disease. Research & Development Patients can respond differently to the same medication. On average, cancer drugs are ineffective in 75% of the treated population. Regulators Regulatory bodies will demand greater proof of positive patient outcomes to justify approval, reimbursement and price. Market Access Focused on providing these improved services to each individual patient, personalized medicine is an integral part of Medco s mission. Medco Health Solutions Page 4

5 One Aspect of Personalized Medicine is the Development of Companion Diagnostic Tests PHARMA DIAGNOSTIC Source: vfa Page 5

6 Definition of Companion Diagnostic A companion diagnostic device can be in vitro diagnostic device or an imaging tool that provides information that is essential for the safe and effective use of a corresponding therapeutic product. The use of an IVD companion diagnostic device with a particular therapeutic product is stipulated in the instructions for use in the labeling of both the diagnostic device and the corresponding therapeutic product, as well as in the labeling of any generic equivalents and biosimilar equivalents of the therapeutic product. List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools) Page 6 lprocedures/invitrodiagnostics/ucm htm

7 Early Cooperation with a Diagnostics Partner is Essential for Success Target Discovery Drug Discovery & Lead Optimization Biomarker discovery & development Preclinical Testing Ph I Project specific predictive biomarker discovery Ph II IVD partner selection & definition of commercial model Ph III Impact of Dx / clinical validation Regulatory Planning Reimbursement & Commercialization Need to have a technically validated test available for Phase III, including definition of the relevant cut-off point where applicable. Ideally the development of the diagnostic is ahead of the therapeutic. Development of a Companion Diagnostic takes time, START EARLY! Page 7

8 Collaboratively Implementing the Biomarker Strategy Responsible Functions Global Biomarker Research Identify and validate biomarker candidates Establish potential prototype assays Conduct indication profiling Technology evaluation GPF D1 D2 CSM D3 D4 POC D8 Biomarker Strategists Develop & implement global biomarker strategies Member of GPT Implement, evaluate and report biomarkers in clinical studies (I-IV) Lead CDx development through strategic partnerships BM Research Biomarker Strategists Supported by TAT Translational Assay Technologies Development/validation of preanalytic protocols Internal and external technical assay validation Evaluation of new (translational) technologies Support of external CDx development projects Research Biobank and sample sourcing Page 8

9 Development of CDx Target Product Profile (TPP) Global project team is the owner of the CDx TPP Approval required for any CDx TPP at D4 Always in conjunction with Drug TPP Definition of most relevant attributes (value drivers) at D3 Diagnostic TPP validation through emerging data Project-specific refinement/ supplement as necessary (approval required!) Increasing level of granularity and precision Page 9

10 What is the Role and Objective of a CDx TPP? Identify Key Metrics required for a viable CDx launch strategy (from the beginning) Appropriate Rigor to all aspects of the diagnostic to prepare for commercial adoption & support the drug program Pressure tests the competitive advantage to the overall program Benchmark which diagnostic platform to use for best Dx adoption and viability in the market (globally) Provide a Road Map Identifying key team members and drivers of the TPP Page 10

11 Collaboratively Implementing the Biomarker Strategy Early Commercial Diligence 1. Co-Develop CDx TPP, Business Case and CDx Commercial Plan 1. Choose a platform that optimizes global test adoption (e.g., some platforms are preferred, less expensive, easier to interpret) 2. Guard against misaligned CDx partner incentives derailing access (e.g., test intellectual property issues and pricing could prevent widespread test use) 3. Anticipate development complexity (e.g. installed base, bridging) 2. Covering Commercial Questions to ask around CDx from D2 - D7 1. Evaluate test platform availability/feasibility by country 2. Anticipate market access/reimbursement for the CDx, including where centralized testing can present a barrier 3. Partnership Management from Commercial point of View 1. Serve as the Functional Global Commercial Leader on Joint Steering Committees 2. Drive commercial discussions, raise potential issues, identify/propose potential solutions, coordinate with internal cross-regional commercial colleagues and global/local Dx partners Page 11

12 CDx Target Product Profile Establishing CDx TPPs to secure implementation of biomarker requirements at each decision point. Page 12

13 CDx Target Product Profile Commercial TPP R&D/Clinical TPP Project Approach Comprehensive CDx TPP Framework Clinical Value and Utility Clinical Specimen Requirements % sensitivity % specificity % prevalence e.g. of biomarker mutation Blood-based e.g. relevant clinical matrix xx hours shelf life ILLUSTRATIVE Stand-alone vs. Multiplex Stand-alone test Delivery or Distribution Testing Invasiveness Geographical Footprint TAT Decentralized, local lab testing / processing model Low (e.g., blood / plasma-based technology) Worldwide <72 hours Project specific comprehensive CDx profile will be generated Page 13 Cost per Test/Procedure Label Requirements $150 per test, $100 service fee Any FDA-approved test IP Requirements Global, non-exclusive

14 Companion diagnostics (CDx) Technology and Regulatory Guidance Regulatory Environment Little to no regulatory guidance Evolution of Drug / CDx Combinations Increasing FDA requirements for drug / CDx approvals Further refinement of guidelines and pathways expected Key Drug Approvals? CDx Technology - Immunohisto-chemistry (IHC) - Fluorescent in situ hybridization (FISH) - IHC - FISH - Polymerase chain reaction (PCR) - Multiplex PCR - Multiplex IHC - Next generation sequencing - Algorithmic proteomics - Circulating tumor cell isolation - Exosome analysis Historically, pairing of drugs with well-established CDx platforms has been the key to success however, novel platforms will play a central role in the future. Page 14

15 Exploration of Emerging Technologies: e.g. Circulating Free Tumor DNA ctdna Assay Issues: Sensitivity: ctdna is most of the times present at extremely low levels Assay standardization: procedures and technologies need to be standardized, incl. the pre-analytical sample handling Quantification: accurate quantification is needed Validation: most assay platforms are not validated for clinical use Page 15 Diaz and Bardelli (2014) Liquid biopsies: genotyping circulating tumor DNA. Am. Soc. Clin. Oncol. 32, 579.

16 Innovative Medicine Initiative: Biofluid Based Biomarker Assays IMI s CANCER-ID: Defining Standards for the Use of Blood-Based Biomarkers at the European Scale Thomas Schlange (EFPIA Project Coordinator/Bayer Pharma AG) Cancer-ID is a project funded by the Innovative Medicines Initiative Joint Undertaking (IMI JU). Page 16

17 The IMI CANCER-ID Consortium 37 Page 17

18 Interaction with Regulatory Authorities Regulatory agencies will be invited to join SAB, FDA/CDER supportive: Page 18

19 A CANcer Development monitor FP7-CanDo Platform Structure Maximum information from cells can be extracted through a combination of advanced CTC enrichment technology with an integrated detection method Page 19 This work is carried out within the FP7-ICT CanDo project, funded by the European Commission.

20 Predicted Class Differentiation WBCs / Pancreatic Tumor Cells PCA-SVM based classification models can effectively differentiate between WBCs and pancreatic tumor cell lines HPAF-II Panc1 WBC Original Class WBC Panc1 HPAF-II WBC Panc HPAF-II C. Krafft, I. W. Schie, T. Meyer, M. Schmitt and J. Popp; Developments in spontaneous and coherent Raman scattering microscopic imaging for biomedical applications, Chem. Soc. Rev., 2016 Page 20

21 Biomarker Testing Rates (%) Market Test Penetration does not follow the same logic as Drug Adoption st Approval in respective biomarker pool 47% 22% 95% 93% 90% 90% 93,2% 90% Biomarker Test Rates, % 27% in Asian population (Japan) 74.9% 65.4% 56% 61.1% 35.8% 32.7% CRC, KRAS WT Gastric Ca, HER2+ NSCLC, EGFR mut NSCLC, EML-4 ALK+ Melanoma, BRAF mut 87% 63.8% % 50% US EU Japan Page 21 # of Drugs in respective biomarker pool XX% Biomarker Prevalence Source: 1. Mattson Jack Treatment Architecture Report Gastric Ca, US: Jun 2013, v1.1, EU: May 2013, JP: Jan 2014; 2. Mattson Jack Treatment Architecture Report NSCLC, US: Jun 2013, v1.1, EU: Oct 2013, JP: Dec 2013, v Mattson Jack Treatment Architecture Report Melanoma, US: Jun 2013, EU: May Mattson Jack Treatment Architecture Report CRC, US: Dec 2012, v1.1, EU: Nov 2012, v1.1, JP: Feb 2013

22 Summary Bayer is committed to develop a biomarker strategy for every compound going into clinical studies and to fully leverage the opportunities of Personalized Medicine for the benefit of our patients. Companion diagnostics will be used as tool for patient selection. Activities start early in research phase with project specific programs for the identification of predictive biomarkers. Established and emerging technologies are constantly explored and included in early and late stage clinical trials. Strategic partnerships for Companion Diagnostics have been established. Page 22

23 Thank you!