Profound Medical Corp · TSX:PRN
Profound Medical — Technical Presentation (May 2015)
29 slides from Profound Medical's technical presentation, May 2015
Slide 1: Heidelberg First Clinical Experience with Profound Medical Inc.'s MRI-Guided TULSA-PRO
Heidelberg First Clinical Experience with Profound Medical Inc.’s MRI-Guided TULSA-PRO Ionel Valentin Popeneciu1, Timur Kuru1, Gencay Hatiboglu1, Matthias Röthke2, Maya Müller-Wolf2, Joseph Chin3, Michele Billia3, James Relle4, Jason Hafron4, Mathieu Burtnyk5, Heinz-Peter Schlemmer2, Markus Hohenfel
Slide 2: MRI-Guided TULSA-PRO
MRI-GUIDED TULSA-PRO Novel minimal-invasive treatment of localised prostate cancer Main objectives: Improve ultrasound prostate ablation (e.g. HIFU) by • Better treatment control • MRI Thermometry = Dose • Dose control = Focal • Better safety profile (fewer side effects) Ultimately: better cancer co
Slide 3: TULSA-PRO Device
TULSA-PRO DEVICE Transurethral Device Prostate Ultrasound Transducers Bladder Urethra Heating Pattern Thermal Ablation Boundary Rectal Cooling Device DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 4: TULSA-PRO Difference: Anatomy
TULSA-PRO DIFFERENCE: ANATOMY Transurethral Focal Source Heating Directional Heating Prostate Increased Rectal Rectum Contact Transrectal Source DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 5: TULSA-PRO Difference: Treatment
TULSA-PRO DIFFERENCE: TREATMENT Discrete Heating (Outside-In) Urethral Cooling Prostate Rectum Continuous Heating (Inside-Out) DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 6: TULSA-PRO Difference: Imaging
TULSA-PRO DIFFERENCE: IMAGING DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 7: MRI-Guidance
MRI-GUIDANCE 1 MRI Thermometry Acquisition 3 Adjust Power, Frequency, Rotation Rate Device Planning 1 cm 2 Temperature Feedback Control Treatment CE-MRI Positioning Verification 40 min Precise Treatment Planning Visualization of NPV DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 8: Phase I Study Design
PHASE I STUDY DESIGN Study Design • Prospective, multi-center, single-arm Inclusion Criteria • Age ≥ 65 years • Low-/intermediate-risk prostate cancer – Biopsy confirmed organ-confined prostate cancer: cT1c or T2a, N0, M0 – PSA ≤ 10 ng/ml – Gleason score 3+3 (Germany/USA), ≤ 3+4 (Canada) • No prior
Slide 9: Patient Recruitment
PATIENT RECRUITMENT Recruitment: Entire Study • 30 patients enrolled: March 2013 – March 2014 • Clinical trial sites in 3 jurisdictions, all under same protocol – Urology / DKFZ (Heidelberg, Germany): 14 patients – Western University (London ON, Canada): 12 patients – William Beaumont Hospital (Roya
Slide 10: Patient Preparation
PATIENT PREPARATION • General Anesthesia • GI anti-spasmodic drug – Eliminate peristaltic motion of the colon which can cause artifacts on MRI thermometry • Supra-Pubic Catheter (SPC) – Drains bladder prior and during treatment – Eliminate filling of bladder after treatment planning and during treat
Slide 11: TULSA-PRO Devices
TULSA-PRO DEVICES Urethral Device 10 independent ultrasound transducer elements; 4 & 13 MHz; 0 to 4 W acoustic / element Rigid catheter; Size 22 French; Sterile, single-use, disposable Rectal Cooling Device Passive cooling; Non-sterile, single-use, disposable DKFZ Heidelberg, Universitätsklinik Heid
Slide 12: MRI-Guided Device Positioning
MRI-GUIDED DEVICE POSITIONING Transurethral Device Rectal Transurethral Cooling Device Device Rectal Cooling Device DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 13: Phase I Treatment Planning
PHASE I TREATMENT PLANNING • Conservative whole-gland treatment planning • 3 mm safety margins at capsule and apex • 10% residual viable tissue expected at periphery DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 14: MRI-Guided Treatment
MRI-GUIDED TREATMENT DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 15: Treatment Assessment
TREATMENT ASSESSMENT Maximum Temperature > 43°C on T2w planning MRI: 90 Apex Base 80 Maximum Temperature (˚C) Acute cell kill 1cm 70 Maximum Temperature 52-55°C on acute post-treatment CE-MRI: Apex Base 60 Late cell kill 50 Sub-lethal 1cm 43 • Pre-clinical trials: “acute cell kill” zone = contrast e
Slide 16: Treatment Duration vs. Prostate Volume
TREATMENT DURATION vs. PROSTATE VOLUME 70 60 50 Treatment time (min) 40 30 20 10 0 0 10 20 30 40 50 60 70 80 90 100 Prostate volume (ml) Profound® Medical, DKFZ Heidelberg, Urologische Universitätsklinik Heidelberg
Slide 17: Temperature Control
TEMPERATURE CONTROL AVERAGE 95% CI RANGE PARAMETER (n=30) (n=30) (n=30) Prostate Volume (cc) 47 cc 41 – 54 21 – 95 Treatment Time (min) 36 min 32 – 40 24 – 61 Targeting Accuracy (mm) 0.1 mm -0.1 – 0.2 -0.6 – 1.1 Linear Targeting Precision (mm) 1.3 mm 1.2 – 1.5 0.7 – 2.4 Volume Over-Targeted Volume (
Slide 18: Safety Overview
SAFETY OVERVIEW • No intraoperative complications • No rectal injury or fistula • No severe urinary incontinence • No Grade 4 or higher adverse events • Total of one attributable Grade 3 adverse event (epididymitis resolved with IV antibiotics) • Majority are acute Grade 1 and 2 events related to GU
Slide 19: Adverse Events
ADVERSE EVENTS* • Hematuria Grade 1 (13 patients) and G2 (2 patients), resolved • Infections: – Urinary Tract Infection: G2 (10 patients), resolved with no action (1) or oral antibiotics (9) – Epididymitis: G3 (1 patient), resolved with IV-antibiotics • Urinary retention: – G1 (3 patients) resolved
Slide 20: Urinary Symptoms
URINARY SYMPTOMS IPSS Box: 25% / Median / 75% Whiskers: Min / Max within 1.5 IQR 35 Squares: Average Severe Symptoms Circles: Outliers 30 25 IPSS Score 20 Moderate 15 10 5 Mild 0 Pre-Treatment 1 month 3 months 6 months 12 months n = 30 n = 28 n = 29 n = 29 n = 29 DKFZ Heidelberg, Universitätsklinik
Slide 21: Uroflowmetry
UROFLOWMETRY Peak Urine Flow Box: 25% / Median / 75% Whiskers: Min / Max within 1.5 IQR 60 Squares: Average Circles: Outliers 50 Peak Urine Flow (mL/sec) 40 30 20 10 0 Pre-Treatment 1 month 3 months 6 months 12 months n = 30 n = 28 n = 26 n = 29 n = 29 DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 22: Erectile Function
ERECTILE FUNCTION IIEF-15 Erectile Function Domain 30 Moderate Mild to Mild No ED Box: 25% / Median / 75% 25 Whiskers: Min / Max within 1.5 IQR IIEF-15 EF Domain Score Squares: Average Circles: Outliers Moderate 20 15 10 Severe 5 0 Pre-Treatment 1 month 3 months 6 months 12 months n = 29 n = 28 n =
Slide 23: Bowel Habits
BOWEL HABITS UCLA-PCI-SF Bowel Habits Domain 100 UCLA-PCI-SF BH Domain Score 80 60 40 Box: 25% / Median / 75% Whiskers: Min / Max within 1.5 IQR 20 Squares: Average Circles: Outliers 0 Pre-Treatment 1 month 3 months 6 months 12 months n = 30 n = 28 n = 29 n = 30 n = 29 DKFZ Heidelberg, Universitätsk
Slide 24: Ablation Efficacy
ABLATION EFFICACY PSA Box: 25% / Median / 75% Whiskers: Min / Max within 1.5 IQR 10 Squares: Average Circles: Outliers 9 8 7 PSA (ng/ml) 6 5 4 3 2 1 0 Pre-Treatment 1 month 3 months 6 months 12 months n = 30 n = 30 n = 28 n = 30 n = 30 DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 25: Biopsy Results at 12 Months
BIOPSY RESULTS AT 12 MONTHS • Phase I treatment parameters were conservative Phase I Treatment Parameters – First-in-human study as primary treatment for prostate cancer – Lethal thermal dose -0.7 ± 1.2 mm inside prostate – 10% viable prostate expected at prostate periphery • MRI & TRUS biopsy show
Slide 26: Clinical Histology
CLINICAL HISTOLOGY Acute H&E Histology • Dr. Laurence Klotz, Dr. Masoom Haider & Dr. Rajiv Chopra at Sunnybrook Research Institute (Toronto ON, Canada) • Second Phase 0 “Treat & Resect” study • Targeted MRI-visible cancer for ablation, with pivotal trial treatment parameters • Demonstrated complete
Slide 27: What's Next?
WHAT’S NEXT ? • Pivotal clinical trial being initiated in larger prostate cancer population • Reduced safety margin for complete whole-gland ablation Phase I Parameters Pivotal Trial Parameters DKFZ Heidelberg, Universitätsklinik Heidelberg
Slide 28: Conclusions
CONCLUSIONS First Experience with TULSA-PRO • Clinically Feasible • Low toxicity & Good safety profile • Ambulatory procedure • Suitable to focal treatment (scalable) – No MRI/TRUS fusion errors What’s next? • Phase I follow-up to 5 years • Pivotal trial to commence in 2016 • Endpoints: ablation eff
Slide 29: Acknowledgements
ACKNOWLEDGEMENTS Profound Medical Inc., VA, Canada Mathieu Burtnyk Matthew Asselin Goldy Singh Dept. of Radiology, German Cancer Research Center (DKFZ), Heidelberg Heinz-Peter Schlemmer Matthias Röthke Maja Müller-Wolf Dept. of Anesthesiology, University Heidelberg Johann Motsch Simon Dubler Dept. o