Biolux Research - Evaluation Program 082014
Transcription
Biolux Research - Evaluation Program 082014
OrthoPulse TM Light Accelerated Orthodontics Evaluation Program Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft QUICK START 1 How to Use OrthoPulse™ 2 Registering as an Evaluator 3 Familiarizing yourself with the Evaluation and Documents 4 The OrthoPulse™ App ! 5 Starting Patients with OrthoPulse™ ! OrthoPulse™ 6 Sharing Clinical Data with Biolux 7 Clinical Recommendations Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 2 5 STARTING PATIENTS WITH ORTHOPULSE™ 1 Add new patient to the app The patient will receive an email instructing them on how to download and use the app ! 3 ! Ensure OrthoPulse™ is fully charged We recommend to charge OrthoPulse™ for a minimum of 3 hours before assigning to a patient and before using. ! 2 Fill in all required patient information ! ! OrthoPulse™ ! ! 4 ! Demo how to use OrthoPulse™, walk through the Quick Start & User Guide, and introduce status light definitions to your patient ! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft ! ! 3 5 STARTING PATIENTS WITH ORTHOPULSE™ 5 Have the patient complete one full treatment 5 minutes upper and 5 minutes lower, while in the chair. ! 7 Pulsing purple indicates OrthoPulse™ is syncing ! ! Click Settings and select Pair Device. ! ! ! ! 6 Place the device on the charging case to initiate Bluetooth ! OrthoPulse™ 8 ! Check to see that the treatment was logged Swipe the screen on the app to the left to show the Treatment Log. ! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 4 5 STARTING PATIENTS WITH ORTHOPULSE™ Let patient know that they should have received the OrthoPulse™ Welcome email. 9 11 We recommend you to help the patient download and sync the device at your practice. Remind the patient to consult Quick Start & User Guide when they get home. ! ! ! ! ! 10 ! patient does not have If the access to an iOS7 device, instruct them to bring their OrthoPulse™ to every appointment so that it may be synced. 12 Devices have a limited memory and can store data for up to approximately 60 days. Syncing is crucial for archiving complete treatment history and tracking compliance. ! OrthoPulse™ ! ! ! ! ! Remind the patient to contact support@bioluxresearch.com if they have any questions or concerns about OrthoPulse™ or the app. We also welcome their suggestions. Their comments are considered, immediately, and extremely helpful. ! ! ! ! ! ! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 5 6 SHARING CLINICAL DATA WITH ORTHOPULSE™ 1 Login to your OrthoPulse™ Profile page ! orthopulse.com/profile Once a patients is added to the app, they will automatically be added to the OrthoPulse™ Profile page, providing you with the ability to upload photos and x-rays so these may be shared with Biolux Research. ! ! ! 2 Add initial, intermediate and ! records final photos and as each patient! progresses through treatment. ! Successful uploads will be indicated by a checkmark. ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 6 7 CLINICAL RECOMMENDATION OrthoPulse™ treatment accelerates the biology of orthodontic tooth movement. For optimum reduction of treatment time, light and continuous forces should be maintained throughout orthodontic treatment. • This may require clinical protocol and appointment scheduling modifications. ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 7 ORTHOPULSE™ LIGHT ACCELERATED ORTHODONTICS OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 8 KNOWN PHOTOBIOMODULATION MECHANISMS 1 Mitochondrial chromophores (inc. Cytochrome C Oxidase) ! absorb photons, proton pumping and ATP production ! 2 3 Increased energy available to the cell -> increased / normalized metabolism ! Reactive Oxygen Species ! (ROS) production and ! mitochondrial signalling Stimulates/suppresses transcription factors, DNA/RNA synthesis -> plethora of tissue/cellular activity Inducible Nitric Oxide (NO) production through ! absorption of !photons by Nitric Oxide Synthase ! ! ! Increased micro and regional blood flow and osteoclastic activity ! ! Download the OrthoPulse™ Clinical and Scientific Dossier orthopulse.com/dossier.pdf OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 9 PHOTOBIOMODULATION AND ENHANCEMENT OF ORTHODONTICS IN ANIMAL MODELS (54+ ARTICLES) ! ! ! ! • Kawasaki and Shimizu, 2000 concluded that the low energy laser irradiation can accelerate tooth movement accompanied with alveolar bone remodelling in the rat model. ! • The same effects were observed when the LLL therapy was applied to the rabbit model. Zhu et al, 2001 ! • Fujita et al, 2008 demonstrated that laser irradiation stimulates the velocity of tooth movement via induction of RANK and RANKL in rats. ! • Increased expression of fibronectin and Type I collagen in LLL tooth movement in rats. Kim et al, 2008 ! • LLLT accelerates the velocity of tooth movement via stimulation of the alveolar bone remodelling in rats. Yoshida et al, 2009 ! • OrthoPulse™ LLLT facilitates the velocity of tooth movement and MMP-9, cathepsin K, and integrin subunits of alpha(v)beta3 expression in rats. Yamaguchi at al, 2010 Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 10 POSITIVE EFFECTS OF PHOTOBIOMODULATION ON HUMAN ORTHODONTIC TOOTH MOVEMENT ! ! ! ! • Increased velocity (by 2.0 fold) of canine movement (N=15) and decreased pain in lased group (809nm). 0,3,7,14 day exposure monthly. Youssef et al. (2008). ! • Significantly higher acceleration (by 1.3 fold) of the retraction of treated (780nm) canines (N=11). 0,3,7,14 exposure monthly. Cruz et al. (2004). ! • Laser irradiated canines moved significantly faster (by 1.9 fold) than that of the nonirradiated group (p<0.05). Sousa et al. (2011). ! • OrthoPulse™ An average increase (by 30%) in the rate of tooth movement found for the low-intensity laser therapy group (p<0.05). Mehta & Patil (2012). Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 11 PUBLISHED in vivo EVIDENCE ✓ 46% acceleration of tooth movement in 620nm treated animals ✓ 80% less root resorption in 620nm treated animals Ekizer et al. Effect of LED-mediated-photobiomodulation therapy on orthodontic tooth movement and root resorption in rats. Laser Med Sci., 2012 Aug 29. ! ✓ Significantly more mature bone in expanded suture of LED treated rats Ekizer A et al. Light-emitting diode photobiomodulation: effect on bone formation in orthopedically expanded suture in rats-early bone changes. Lasers Med Sci., 2012 Nov 9. ! ✓ Significantly lower failure rate of immediately loaded TADs with 620nm Uysal T et al. Resonance frequency analysis of orthodontic miniscrews subjected to light-emitting diode photobiomodulation therapy. European Journal Orthodontics 2012 Feb; 34(1):44-51. ! OrthoPulse™ ! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 12 ORTHOPULSE™ in vivo EVIDENCE SUBMITTED FOR PUBLICATION - UNDER REVIEW ! ! ! ! Photobiomodulation-induced tooth movement using extra-oral transcutaneous phototherapy utilizing Red LED (625nm) radiation versus nIR-Laser (855nm) radiation on the rat periodontium and on orthodontic tooth movement ! ! Susanne Chiari1,2, Susan S. Baloul1,3, Emilie Goguet-Surmenian1, Thomas E. Van Dyke1, Alpdogan Kantarci1 ! 1 Boston University Goldman School of Dental ! Medicine, Department of Periodontology and Oral Biology, Boston MA USA ! 2 ! 3 36 healthy CRL-CD male rats: • 5 groups of 6 rats (experimental) • 1 group of 6 rats (baseline) OrthoPulse™ University of Vienna, Department of Orthodontics, Vienna, Austria Boston University Goldman School of Dental Medicine, Department of Orthodontics, Boston MA USA ✓ Light treated animals showed 2.8 - 3.7 fold increase in tooth movement compared to control Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 13 ORTHOPULSE™ (EXTRA-ORAL PROTOTYPE) PUBLISHED CLINICAL EVIDENCE ✓ 2.3x faster alignment rate versus control Kau et al. Photobiomodulation accelerates orthodontic alignment in the early phase of treatment. Progress in Orthodontics 14:30. 2013 ! ✓ No negative effect on root resorption Nimeri et al. The effect of photobiomodulation on root resorption during orthodontic treatment. Clin Cosmet Investig Dent. 6:1-8. ! ✓ ~35% reduction in overall treatment time ! OrthoPulse™ Multi-centre trials IP (N=30) (in progress) ! ! ! ! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 14 CURRENT CLINICAL STUDIES AND TRIALS IN PROGRESS Investigator / Institution! TS1.5 Tim Shaughnessy Suwanee, GA, USA! Completed (n=11 of 11)! Pilot: Non-extraction. Alignment and total Tx time, (CTB and SLB) Adolescent & Adult. Submitted for publication. Under review.! TS2 Tim Shaughnessy Suwanee, GA Univ Alabama and Forsyth Institute, USA! IP (n=26 of 30)! RCT Pivotal: Non-extraction. Alignment and total Tx time, Root integrity & Pain evaluation. Sham Controls. (CTB) Adolescent.! EUC2 Said Samara & Don Ferguson Completed European University College Dubai, (n=60 of 60)! UAE! RCT: Extraction. Velocity of space closure in en-masse retraction. (Passive SLB) Adolescent & Adult. Manuscript in preparation.! MC Peerapong Santiwong Mahidol Univ., Bangkok, Thailand ! IP (n=42 of 45)! RCT: Non-Extraction. Alignment and total Tx time, Bone Quality and Root integrity eval CBCT (Passive SLB) Adult and Adolescent.! TS3 Tim Shaughnessy Suwanee, GA, USA IP (n=25 of 30)! Case series. Total Tx time. Adolescents and Adults. (Mixed brackets and mechanics)! KHU1 Young Guk Park & Min Ki Noh, IP (n=40 of 45)! Kyung Hee U., South Korea OrthoPulse™ Clinical Trials Focus of Study! Status / Enrolled RCT: Effect of OrthoPulse™ on the rate of retraction en-masse 6 anterior teeth! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 15 CURRENT CLINICAL STUDIES AND TRIALS IN PROGRESS Investigator / Institution! OrthoPulse™ Clinical Trials Focus of Study! Status / Enrolled! BX8 Marc Lemchen, NYC, NY Tito Norris, San Antonio, TX Tim Shaughnessy, Suwanee, GA ! IP (n= 55 of 100)! Case Series: Beta OrthoPulse™ evaluation and assess clinical effectiveness. ! TD1/TD2 Todd Dickerson, Phoenix, AZ! ! Completed (n=12 of 12)! Pilot Study: Efficacy of OrthoPulse™ and Invisalign® treatments. ! Cross-over design.! ! TD3 Todd Dickerson, Phoenix, AZ! ! IP (n= 4 of 10)! RCT: Effect of OrthoPulse™ on aligner change rate during Invisalign® treatment. Cross-over design.! TD4 Todd Dickerson, Phoenix, AZ! IP (n= 2 of 28)! RCT: Effect of OrthoPulse™ on total Invisalign® treatment time.! UAB2 ! Chung How Kau, University of Alabama at Birmingham, AL! IP (n= 0 of 40! RCT: Effect of OrthoPulse™ on treatment timeline with clear aligners.! EUC3 Don Ferguson et al. European University College Dubai, UAE! IP (n=0 of 40)! RCT Pivotal: Non-extraction. Alignment and total Tx time, Root integrity & Pain evaluation. Sham Controls. (CTB) Adolescent.! ! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 16 INTRA-ORAL PHOTOBIOMODULATION INDUCED ORTHODONTIC TOOTH ALIGNMENT: PILOT FEASIBILITY STUDY SUBMITTED FOR PUBLICATION (UNDER REVIEW) ! ! ! ! Measure Alignment Rates Days to Alignment Group Arch N Mean SD Min Max Difference P-Value 10 0.20 0.19 0.83 Control 0.44 Intraoral 18 1.27 0.53 0.24 2.06 Control 10 104 55 42 204 Intraoral 18 48 39 17 164 Control 10 5.77 1.57 3.70 8.80 Starting LII Intraoral 18 7.27 2.99 3.72 14.58 186.3% 53.6% 26.0% 0.0002 Intra-oral photobiomodulation induced orthodontic tooth alignment: pilot feasibility study ! 0.0049 Tim ! Shaughnessy et al.1 1 ! USA Private practice, Suwannee, GA, N.S ✓ OrthoPulse™ treated arches exhibit significantly faster alignment rates (186% faster), and reduces days to alignment by over 50% when compared to conventional methods. OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 17 PILOT: OPTIMIZING INVISALIGN® AND ORTHOPULSE TREATMENT PI: TODD DICKERSON, PHOENIX, AZ ! ! INTERIM RESULTS ! ! N=12 Design: Crossover Study Method: Determine optimal aligner switching intervals based on patients’ subjective daily analysis of pain, aligner fit and pressure and air gap presence. ! Every day, patients assess: A) pain levels: rated 1-3 B) aligner fit/pressure on teeth: rated 1-3 C) air gaps present: rated 1-3 ! Patients progress into the subsequent aligner when: A) pain = 1 B) aligner fit = 1 C) no air gaps ! ! ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft ! 18 PILOT: OPTIMIZING INVISALIGN® AND ORTHOPULSE TREATMENT PI: TODD DICKERSON, PHOENIX, AZ ! ! ! • INTERIM RESULTS ! Patients received intervention period of 10- and 20-minute OrthoPulse™ treatment a day while progressing through a number of aligners. ! • The average number of days in aligners for each OrthoPulse™ intervention is determined . ! • % reduction of the average number of days in aligners is compared to conventional Invisalign aligner change frequency ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 19 INTERIM RESULTS PILOT: OPTIMIZING INVISALIGN® AND ORTHOPULSE TREATMENT PI: TODD DICKERSON, PHOENIX, AZ ! ! ! ! Days in Each Aligner for TD1-004 (OrthoPulse Intervention) Aligner2525@@Day Day88 88 Aligner (OrthoPulse iO X1 Intervention) 10min/day 15 Aligner Day3232 Aligner 88 @@Day (OrthoPulse iO X2 Intervention) 20min/day 10 No Pain 7 7 6 5 Days in Aligner Worst Imaginable Pain 6 5 5 4 4 3 4 4 3 0 4 4 4 4 4 3 2 2 1 1 5 3 2 1 1 22 2 2 1 1 4 3 3 2 1 2 2 2 2 3 3 2 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Aligner # OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 20 INTERIM RESULTS PILOT: OPTIMIZING INVISALIGN® AND ORTHOPULSE TREATMENT PI: TODD DICKERSON, PHOENIX, AZ ! ! ! ! 9" 68" 99" p-value 66%" 0.000" 69%" 0.000" 80.0 from standard 66%*% 69%*% ✓ OrthoPulse™ reduced aligner switching durations 66-69% compared to Invisalign® standard (p=0.000). OrthoPulse™ 0.0 20.0 OrthoPulse™,20min/day, 8" # of Percentage Reductions (%) aligners 60.0 OrthoPulse™,10min/day, Patient N 40.0 Intervention Type 100.0 Percent Reduction from Conventional Invisalign Prescription Prescribed Standard! ! ! Means iOx1 10min/day! ! ! ! iOx2 20min/day +/- 1 Standard Deviation * = p(z) < 0.05 two-tailed t-tests used to assess H0: Percentage Reduction = 1 Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 21 OVERALL TREATMENT TIMES COMPLETED ORTHOPULSE™ PATIENTS ! ! ! ! Patient ID Age Sex Est Tx Time Actual Tx Time % Reduction Mechanics TS1.5-001 13 M 24 mo 10 mo, 11 days 57% Fixed TS1.5-004 13 F 20 mo 13 mo, 12 days 33% Fixed TS1.5-010 13 F 20 mo 10 mo, 11 days 48% Fixed TS3-002 51 M 18 mo 11 mo, 15 days 39% Fixed TS3-006 30.9 F 30 mo 13 mo, 24 days 54% Fixed TS3-007 13.9 M 24 mo 13 mo, 1 day 45% Fixed TS2-004 13.8 F 21 mo 12 mo, 24 days 61% Fixed BX8ML-001 44 F 15 mo 5 mo, 23 days 62% Invisalign BX8ML-019 49.2 F 15 mo 4 mo, 24 days 68% Invisalign BX8RN-001 15 M 18 mo 5 mo, 21 days 63% Fixed BX8RN-002 39.4 M 20 mo 6 mo, 27 days 66% Fixed BX8RN-005 16.2 F 12 mo 7 mo, 9 days 39% Fixed BX8TD-011 24.1 F 18 mo 3 mo, 18 days 65% Invisalign 19.6 mo 9.3 mo 54% ✓ OrthoPulse™ treated patients show average 54% reduction in overall treatment time compared to estimated conventional treatment times. OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 22 ORTHOPULSE™ CLINICAL ADVANTAGES 1 2 3 Photobiomodulation increases energy production (ATP) in stressed cells and tissue. No change in Doctor’s preferences or clinical techniques ! ! ! ! Photobiomodulation accelerates bone and soft tissue remodelling process. There may be optimization through the use of modified mechanics and protocols ! ! ! ! Non-specific: ALL cells and tissues benefit Non-invasive, drug-free and extremely low risk profile (Class II device) ! ! 4 5 6 7 ! Works with any orthodontic system - technique independent ! Scientifically proven effect and mechanisms understood ! 8 ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 23 ORTHOPULSE™ OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 24 ORTHOPULSE™ ✓ Microprocessor controlled • • Continuous monitoring of internal device state (temps, errors etc.) Logs all activity for upload and sync to App and Cloud ! ✓Made in Canada by global leader of medical and electronic device manufacturer • • • ! OrthoPulse™ Ultrasonically welded parts Highest durability and biocompatible implantable medical grade silicone mouthpiece Flexible and conforms to all dental arches ! ! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 25 PATIENT BENEFITS ✓Easy, comfortable daily 10min intra-oral treatment ! ✓Comfortable soft medical grade silicone appliance ! ✓Lockable charging case with induction charging for convenience and easy travel. ! ✓iOS app for patient tracking of Tx, incentives for compliance ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 26 ORTHODONTIST BENEFITS ✓No fitting or adjustments required ! ✓Ready to use “out of the box”, no device set-up or assembly ! ✓Easily delegable to auxiliaries ! ✓Fast pairing of device with iOS app ! ✓Auto-compliance monitoring ! ✓Practice differentiator ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 27 ORTHOPULSE™ APP 1 Distinct doctor app with OrthoPulse™ patients’ compliance at a glance. 2 Tracking of the overall patient’s treatment consistency and percentage compliance. ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 3 Detailed treatment log to track individual selftreatment sessions 28 ORTHOPULSE™ APP OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 29 LIGHT ACCELERATED ORTHODONTICS™ CLINICAL GUIDELINES ! ! ! ! OrthoPulse™ treatment accelerates the biology of orthodontic tooth movement. For optimum reduction of treatment time • Maintaining light, continuous forces throughout orthodontic treatment may require clinical protocol and appointment scheduling modifications. ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 30 INVISALIGN® CLINICAL GUIDELINES ! ! ! ! • OrthoPulse™ treatment accelerates the rate of orthodontic tooth movement so aligners will become passive sooner, and tooth movement will stop. ! • Therefore requires patients advancing earlier to the next aligner. ! • Compliance is crucial • • ! ! Invisalign® wear 22+ hours/day Daily OrthoPulse™ treatment - no missed treatments ! Rx: 7-day aligners Rx: 14-day aligners ! • ! Recommend patients switch aligners every 3 or 4 days • Recommend patients switch aligners every 6 or 7 days ✓ Suggested guidelines are a subject to clinician’s discretion based on the individual patient treatment plan, biology and confirmation of Invisalign® tracking. OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 31 FIXED APPLIANCES CLINICAL GUIDELINES ! ! ! ! ✓ Teeth move quicker, alignment occurs sooner, therefore to maintaining light continuous forces throughout orthodontic treatment requires changing arch wires more quickly and shorter intervals during the levelling and alignment phase. Space closure Intervals between orthodontic visits ! ! • During rapid alignment phase, recommend more frequent visits every 2-3 weeks in order to advance to next larger wire size. • ! • Once alignment is achieved you can go to your customary treatment visits. ! Sliding mechanics optimal. Closing loops to be avoided as accelerated tooth movement will decrease focus rapidly and become passive unless you activate more frequently. ! ! ! ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 32 CLINICAL INVESTIGATOR TIPS AND TECHNIQUES ✓ Set expectations for patients early. ! ✓ Be sure patients fully understand that the compliance is crucial. If they “fall off the wagon” and do not use OrthoPulse™ and their appliances they may be dismissed from the evaluation. ! ✓ Take photos of aligners in the mouth if they start not to track. ! ✓ Mention that the treatment is safe and has been used in orthopaedics and wound healing. ! ✓ Patient selection - choose highly motivated patients. ! ✓ Take photos more frequently of patient’s progress. ! ✓ If your patients experience OrthoPulse™ device issues as bugs can occur on occasion with any new technology, please contact Biolux as we would like to avoid interruption in treatment progress. support@orthopulse.com OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 33 ORTHOPULSE™ SSG1 EVALUATION TIMELINE Doctor Registration Doctor license copy and a CV are required for ethics approval by IRB Services Inc. to register for SSG1 evaluation. Patient Enrolment 3 patients to be enrolled within 30 days of receiving the devices. ! 3 Patients to be added to the OrthoPulse™ app Welcome Email to register and download the app August Webinar Post webinar, all participants will receive a welcome email to register for an OrthoPulse™ doctor profile. OrthoPulse™ Analytics Data collection and analysis ! ! Doctor & Patient Surveys to be completed est. 2015 Q1 September ! 3 OrthoPulse™ Devices at no charge Records for each case to be submitted Devices at no charge Initial, interim, final records Upon completion of the registration, Biolux will send the doctor 3 devices. ! Using your doctor profile web page submit your patient records. ! Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft FDA Approval Sales in the U.S. ! ! 34 MARKET SURVEYS - AJO DO URIBE F, PADALA S, ALLAREDDY V, NANDA R. AM J ORTHOD DENTOFACIAL ORTHOP. 2014 APR;145(4 SUPPL):S65-73 ! ! ! ! Patients’, parents’, and orthodontists’ perceptions of the need for and costs of additional procedures to reduce treatment time. • Electronic surveyed 683 AAO members 70% orthodontists interested in adopting procedures to reduce treatment time ! • 50% reduction in treatment time, the majority were willing to pay 50% more in treatment fees ! ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 35 MARKET SURVEYS - IPSOS - ASI ONLINE QUANTITATIVE SURVEY - MAY 2014 ! ! ! ! 3 groups • • all 3 groups were very interested in OrthoPulse™ 10 minutes per day self-treatment at home. most respondents are interested because of the convenience of OrthoPulse™ being quick and simple ! ! $1,000$2,000 • respondents were willing to pay based on 50% or 67% reduction in time • > 50% would prefer to pay a monthly payment for the OrthoPulse™ premium • 86% considering ortho treatment expect to use clear aligners Survey sampling • • • • N=252 Group 1: Considering orthodontic treatment Group 2: Currently in orthodontic treatment Group 3: Completed orthodontic treatment in last 5 years or less ! OrthoPulse™ 18-34 • undergoing treatment are more willing to pay $2,000 premium for the time reduction years old Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 36 ORTHOPULSE™ NET PRICE / PATIENT PREMIUM • Post FDA Approval commercial product ! • OrthoPulse™ online ordering: www.orthopulse.com ! • OrthoPulse™ $979 net price includes: 1) OrthoPulse™ App – Patient Motivation / Compliance Tracking System 2) FedEx Just-in-Time delivery • Two day FedEx • Shipping included ! • OrthoPulse™ Patient Premium up to $500.00 ! • Orthodontic fee for fixed or clear aligners + $1495 = _____ ! ! ! ! ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 37 QUESTIONS & ANSWERS OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 38 THANK YOU! Contact: John Nabors VP of Global Sales and Marketing ! j.nabors@bioluxresearch.com orthopulse.com ! Support support@orthopulse.com ! ! OrthoPulse™ Copyright Biolux Research Holdings Ltd @ 2014 All Rights Reserved - Confidential & Draft 39