1. How we make implants disappear after operations Andreas Karau June 21, 2016, Essen, Germany

2. June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Therapeutic needs: Product lifetime corresponds to required function Physiological properties Patient-specific solutions Avoiding further surgery Medical devices – increasing therapeutic needs of aging population We are working on new material systems that will meet these therapeutic requirements Page 2

3. Today: reparative medicine Treatment of symptoms Permanent medical devices Paradigm shift from reparative to regenerative medicine June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Vision: regenerative medicine Replace, produce, or regenerate cells, tissues, and organs Restore normal bodily functions Page 3

4. Regenerative medicine needs biodegradable materials, which take over the biological or mechanical function of the tissue for a time, and are finally replaced by human tissue We’re working to improve Mechanical properties Biocompatibility Customizability Step 1: Improved materials and solutions June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgeryPage 4

5. The bioimplant spectrum June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Biocompatible implants Biologized implants Biological implants Biocompatible/biodegradable materials Implants that release actives Surface functionalized implants In vivo cell coatingsBiohybrid systems Embedding engineered implants into tissues Tissue engineering Bioartifical organsCell therapy Engineered componentsCellular components Evonik today Page 5

6. Biodegradable medical polymers such as RESOMER ® / RESOMER ® Select are based on polylactic acid They degrade completely within the body into non-toxic components (CO 2, H 2 O) Mechanical properties are adjustable Degradation can be adjusted from weeks to several months Our starting point: biodegradable polymers June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery We are extending the range of applications in the direction of bioimplants Page 6

7. Osteoporosis alone results in roughly 8.9 million broken bones each year Commonly affects vertebrae or extremities Example: broken bones Need Problem June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Bone fixation usually accomplished with metal screws and plates These either have to remain in the body or be removed in a second operation Biodegradable materials are not yet strong enough or biocompatible enough for use in large, weight-bearing bones Healthy bonesOsteoporosis Page 7 Source: fotolia / peterjunaidy

8. Biodegradable materials with mechanical and biological properties more like those of bones: Strength similar to that of natural bones Support of bone formation Improved biocompatibility Goals Approach Combination of biodegradable polymers and inorganic fillers Ready-to-use granulate for producing screws, plates, etc. by a co-extrusion process Our approach to the problem of bone implants: biocomposites June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgeryPage 8

9. Applications for patient-specific implants June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Relatively large segments of bone sometimes need to be replaced, because of accident or disease Current options: Bone transplants or metal implants Frequently affects vertebrae, skull bones, or extremities Need Problem Future: use of 3D printing for producing patient-specific implants from biocompatible plastics The available materials are not suitable for clinical use Page 9 Source: fotolia / belekekin

10. Our approach: printable filaments and microparticles June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Materials used must meet regulatory requirements Materials must be processable using current 3D printing methods Goals Approach Production of suitable filaments and microparticles based on RESOMER ® or PEEK Page 10

11. Application: coronary heart disease June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Over two million stents are used throughout the world each year for the treatment of coronary heart disease—most of these are made of metal Need Problem Five percent of patients experience a thrombosis or restenosis within 5 years of receiving a metal stent Treating the patient again with another stent is not an option because the old metal stent is still in place Roughly 4 percent of biodegradable stents rupture when inserted Page 11

12. Evolution of stent technology June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery A coating based on RESOMER ® that releases an active agent aimed at reducing the risk of restenosis Stent made of RESOMER® that breaks down after 6 to 12 months Biodegradable stent Risk of complications: Available materials are very brittle and can lead to the development of thrombosis Risk of complications: Renewed vascular occlusion Metal stent that releases an active agent Normal metal stent Need: Materials for improved biodegradable stents Page 12

13. Approach Our approach: RESOMER ® with enhanced flow properties June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Improved material flow properties without sacrificing mechanical stability System solution using different biodegradable polymers and specific additives Goals PLLARESOMER ® ExtrusionReinforcement Enhance ductilityEnhance strength Ductility Strength Page 13

14. June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgery Production of patient-specific implants with biological tissues, made by culturing living cells on suitable polymer systems We are working on Polymer system biocompatibility Suitable 3D structures Suitable growth media Also in focus: biological implants Our goal: to become a leading solution provider for innovative medical device manufacturers Cells Polymer matrix Growth Media Page 14

15. Global polymer and applications expertise Darmstadt, Germany Manufacturing of RESOMER ® polymers Application lab Regulatory support team Birmingham, AL, USA Manufacturing of RESOMER ® Select polymers Regulatory support team Medical Devices Project House Shanghai, China Application lab Logistics center Regulatory support team Piscataway, NJ, USA Logistics center Medical Devices Project House Short-term strategic research unit Over 20 employees Close collaboration with polymer specialists from the business lines June 21, 2016 | R&D Press Briefing | How we make implants disappear after surgeryPage 15