1. ContiPressSense A/S DTU April 9. 2013 Lars Lading LL@sense-as.dk

2. Topics ContiPress: The problem and our solution Sense history How to succeed? Some general comments about venture capital andIPR IPR: The procedure What can you do yourself and what not? About claims, descriptions, figures Publications and patents Venture Capital: Do you really need it? Consequences Summary2 3. The Challenge3 4. Hypertension 25% of world populationssuffers from hypertension 33% of these are beingtreated 1 out of 8 deaths areattributted to hypertension4 5. Blood Pressure: Continuous measurementsare needed A strong need for continuous, non interfering blood pressuremeasurements: Ambulatory Blood Pressure Measurements (ABPM) No current commercial product satisfies this need First product focus is non-interfering 24 hours ABPMSBPSleepDip 1100%SBPWakeUnhealthy Pressure Healthy WakenSleep 24 hours5 6. No interference! 6 7. Recommendations: HypertensionNICE guideline 34: Hypertension, August 20111.2.3 If the clinic blood pressure is 140/90 mmHgor higher, offer ambulatory blood pressuremonitoring (ABPM) to confirm the diagnosis ofhypertension. [new 2011]1.2.4 If a person is unable to tolerate ABPM, homeblood pressure monitoring (HBPM) is asuitable alternative to confirm the diagnosisof hypertension. [new 2011]- In line with extensive investigations on the value of continuous BP measurements 7 8. Cost-effectiveness of Ambulatory BPKate Lovibond et al, Cost-effectiveness of options for thediagnosis of high blood pressure in primary care: a modelingstudy. www.thelancet.com published online August 24, 2011DOI:10.1016/S0140-6736(11)61184-7Ambulatory monitoring was the most cost-effectivestrategy for the diagnosis of hypertension for menand women of all ages 8 9. Solution forBlood Pressure 10 10. Continuous non-interferingblood pressure Disposablepatch/sensor band Miniaturizedelectronics forexcitation, collection,processing, andstorage of data Docking station fordata transfer andcharging Dedicated software11 11. Key Features Distension Stiffness No counter pressure No wire or hose connections to external devices Disposable patch: no cross-contamination The method is model based! Why is this not common practice? Because arterial distension is (has been) difficult tomeasure and Arterial stiffness has been almost impossible to measureat a single location 12 12. ContiPress consists of four partsPatch2134 Control panelDocking station (Charging/Transfer) 13. Usage2 413 514 14. Graphical User Interface 15 15 15. Blood Pressure: How? Arterial distension (artery expansion with heart beat) from dynamic tissue response Arterial stiffness from Pulse Wave velocity The nonlinear stress-strain relation facilitates the mean arterial pressure from the pulse pressure and distensionCompare with a spring: If the increase in length (distension)as a result of an unknown force (pressure) is measured thenthe force can be calculated if the spring constant (stiffness)is known 16 16. The Circulatory System:Pump, vessels, capillaries, organs From: McDonalds Blood Flow in Arteries 17 17. The circulatory systemMost important: Transport (flow + content) according to needs: awake, work/rest, sleep Can the pump deliver according to needs? Can the vascular (arterial) system support flow and pressure?What affects the functioning of the cardiovascular system? Psychological (white coat syndrome) Physiological Genetics, intake (salt), diseases + + +What is measured? Pressure when flow is blocked (systolic) At a single point in time, in doctors office: a psychological and a very strong physiological impact on the subject (e.g. inflating a cuff during sleep defeats the purpose)No current system complies with the need of continuousand non-interfering blood pressure measurements. 18 18. From ZYGOTE BODY19 19. AnatomyMR images20 20. Arterial stiffness Highly nonlinear (Pressure) Central and periphalstiffnesses aredifferent(Diameter)21 21. Pulse Wave Velocity A good indicator of the state of the cardiovascularsystem in particular of arteries High velocity large stiffnessfragile arteries Typically measured over largestretches, e.g. heart to wrist Velocity depends on:o Stiffnesso Diametero Blood densityo Wall thickness22 22. Pulse reflections are important At bifurcations At localized depositions23 23. Field Lines and tissue properties A simplified cross-section of an organ and the distribution of field linesBioimpedance: See e.g. S. Grimnes and . G. Martinsen,Bioimpedance and Bioelectricity Basics, AP Oxford 2008 24 24. Electrical ImpedanceA macroscopic quantity 25 25. Permittivity and refractive index The permittivity relates to a materials ability totransmit (or "permit") an electric field. Complex permittivity i Refractive index n r r26 26. Electrical properties of tissue and blood Conductivities and permittivities are generallydifferent for different types of tissues. They vary greatly with excitation frequency. Anisotropic.1.81.61.41.2Conductivity, muscle [S/m] 1Conductivity, blood [S/m]0.8 Conductivity, skin dry0.6 Conductivity, skin wet0.4 Conductivity, fat0.2 0 1.00E+03 1.00E+04 1.00E+05 1.00E+06 1.00E+07 1.00E+08 1.00E+09 27 27. Permittivity 28 28. Impedance of a cross-section Finite element calculations Equivalent circuits29 29. Sensor Band30 30. Pulse Pressure and Waveforms30 year old healthy 20young male100BMI = 24 kg/m2 10SBP = 126 mmHg 20 BP = 45 mmHg 112 113114 115 116 117Sec62 year old female4020BMI = 23 kg/m2 20 0SBP = 182 mmHg 40 60 BP = 85 mmHg5678 9 10Sec52 year old male2010BMI = 46 kg /m2 10 0SBP = 186 mmHg 20 BP = 62 mmHg 30 2345 6 7SecFrom a clinical study at Copenhagen Univ. Hospital:Tine Willum Hansen et al. 201131 31. Sense History32 32. Sense History Established in 2000: A device for monitoring amountand quality of milk to prematurely born babies duringbreast feeding. Technology principles developed, butpotential investors did not beleive in market. 2005: Similar technology for vascular transportmonitoring: A new technology and a new application:Too much up-hill 2006-7: Non-interfering blood pressure 2008-9: A scheme identified and some verypreliminary measurements (Innovation funding) 2009: Vkstfonden decides to invest jointly with SeedCapital 2010: Personnel hired (now 10 persons) 2010-now: Product development, key itereations, QAand regulatory, clinical trials33 33. Sense IPRPatent appl. Status Priority ImportanceAction Freedom tofrom to Sense operateWO Pending2006 PreventiveRejected; A successful appeal is Large2007/000164considered very likelyA2WO2007 Granted in 2007 Small Maintain in Europe Large, can beDK00553Europe affected byRFID patentsPCT/DK2009/Pending2009 PreventiveMaintained at least until aLarge000241 Protectionpreliminary evaluation of 5 has been given Not2010 Substituted Withdrawn before publication inLarge publicizedby 5 before order not to become prior art to being 5 publicized 5 Submitted2011 ProtectionSubmitted as a methodVery large Feb. 2011 Prevention 6 In2012ProtectionImpedance sensing methods -Large preparation Preventionadditional 34 34. How tosucceed? 35 35. How to succeed? There is no safe recipe! But a few things may help: A need Existing Potential A unique solution (not a me too product) Market access Financing IPR Avoid dead ends Keep it small but not too small! And luck! 36 36. Device Challenges Market needs and trends Basic method Algorithms Electronics Patches Design (aesthetic) and usability 37 37. 38 38. Organizational Challenges Interdisciplinary Physics Electrical and mechanical Medical needs, clinical methods, anatomy, and physiology Engineering competences Electronics IT Materials/mechanics Market Management Financing Accounting Regulatory Partnerships 39 39. IPR Time consuming Expensive Often frustrating But mandatory esp. for attracting venture capital Make it short! Claims and figures are most important Description should support claims but alsocontain material that prevents other applicationsthreatening the freedom to operate.40 40. Financing The valley of death Venture capital Preferable to avoid May strengthen milestones and plans You loose control There may be no other way Strategic partners May pay for development conditioned by Full right to product Right to marketing Right of first refusal Self financing Slow growth Higher risk Potentially much higher return Crowd Funding 41 41. External ResourcesMedical Rigshospitalet (the major university hospital in Denmark) Odense Univ. Hospital Frederiksberg HospitalMarket LundbeckTechnology DELTA, Electronics, Sound, and Optics Danish Technological Institute Technical Univ. of Denmark Univ. of Southern Denmark Ambu A/SIPR and Legal Hegner and Partners Law Firm Bech-BruunA strong international network 42 42. Summary Starting a company implies a lot of work, can bevery frustratingbut few other activities are more challengingand rewarding Market needs Idea: a relevant solution, novel, design andusability People: The right competences Money: Difficult with impossible without! 43 43. Hales methodfor BPmeasurements44