1. Mapping Sympathetic Nerve Distribution for
Renal Ablation and Catheters for the Same
Jie Wang, MD, PhD
Executive Vice-President, Clinical Research and Translational Medicine
Jiangsu Province Hospital
Nanjing, China
Disclosure: the study is financially supported by SyMap Medical, Ltd

2. J Wang is a co-founder of SyMap Medical Ltd
Disclosure
J Wang is a co-founder of SyMap Medical Ltd

3. Renal Denervation (RDN)
Key Area of Strategic Interest for large device companies (MDT, BSX, JNJ, STJ, COV)
Billion dollar companies need billion dollar markets
Hypertension: Largest Unmet Clinical Need in CV
25% in US, 46% in EU, 52% in Japan and 160M Chinese
Cost of hypertension to the healthcare system was $76B in 2011
~1/3 of people are unaffected by drugs used to treat hypertension

4. Three Different Diseases, One Common Pathway
Hypertension, Congestive Heart Failure, and Chronic Renal Failure all have multiple origins
Physiologic changes, caused by the kidney, accelerate progression of these conditions due to:
Abnormal hormone secretions (renin, aldosterone, norepi)
Renal and pulmonary vasoconstriction
Salt and water retention
The Common Pathway:
Renal Sympathetic Nerve Hyperactivity

5. Renal Sympathetic Nerve Plays a Key Role In Hypertension, Heart Failure, Renal Failure
Renal Efferent
Renal Afferent
↑ Renin，Angiotensin
Vasoconstriction
Hypertrophy
Arrhythmia
Heart Failure
Hypertension ↑

6. Targeting Renal Sympathetic Nerve to Treat Hypertension: Renal Denervation
Catheter inserted from groin to renal artery
RF energy heats artery wall, destroying nerve
4-6 discrete two-minute ablations per artery
Each ablation is separated longitudinally and rotationally to obtain total coverage
Both renal arteries treated in same case
Average procedure time 38mm
In the United States: Caution: Investigational Device. Limited by U.S. law to investigational use. 6 6

7. Change in Blood Pressure (mmHg)
Effect on Blood Pressure after One Procedure
Blood Pressure
decreased
27 mmHg
at One Year
Change in Blood Pressure (mmHg)
Repeated measures ANOVA: P<0.001 for SBP & DBP
P< vs. baseline for each SBP & DBP
Confidential

8. Opportunity RDN market opportunity: $700M by 2016, $2.3B by 2020*
M&A Comp: Ardian Acquisition (Jan 2011):
$800M upfront cash payment & $500M potential milestone payments at pre-revenue stage
Competitors are differentiating from MDT by altering the energy source and shapes of ablation catheters
No approach is optimized
*JP Morgan, Renal Denervation: The Next Big Thing in CV Devices, Oct, 2011

9. Unresolved Issues in RDN
Need to increase efficacy and safety of RDN procedure:
“real world” response rates are 50-60%
Limit potential side effects from “too much” denervation
Resolve complexity of the renal sympathetic nerve distribution
Significant variability in length and diameter of the renal artery
Length: LRA, cm; RRA, cm
Diameter: LRA, mm; RRA, mm
Question: Can the renal sympathetic nerve be mapped using clinically relevant parameters to monitor?
Significant variability in length and diameter of the renal artery
Length: LRA, cm; RRA, cm
Diameter: LRA, mm; RRA, mm
Can the renal sympathetic nerve be mapped using clinically relevant parameters to monitor?

10. Our Solution
Using clinically relevant approaches to identify renal innervation for renal denervation therapy
Develop a differentiated RDN system with mapping and denervation functions
Use mapping capabilities to increase the response rate and safety for RDN therapy and establish new gold standard for the therapy

11. SyMap: Proof-of-Concept Study
Acute animal experiment: anesthetized pigs
Catheter applied electrical stimulation to at least 4 sites within left and right renal arteries
Blood pressure and heart rate measurements during electrical stimulation, recording max/min

12. Changes in Blood Pressure and Heart Rate in Response to
Right Renal Artery Stimulations
Confidential

13. Changes in Blood Pressure and Heart Rate in Response to
Left Renal Artery Stimulations
Confidential

14. It is feasible to map the renal sympathetic nerve
Proof of Concept Study Summary
Electronic stimulation in renal artery caused changes in blood pressure and heart rate.
The changes in blood pressure and heart rate due to intra-renal artery stimulations are site-specific.
These “stimulation sites” caused the maximum increases in blood pressure and heart rate may correlate with sympathetic innervation of renal arteries.
Mapping these “stimulation sites” may provide optimal locations for renal denervation therapy.
Conclusion:
It is feasible to map the renal sympathetic nerve

15. Intellectual Property
First to File

16. Summary Renal nerve mapping to optimize RDN therapy:
Solid physiology basis
Clinical relevant approaches and measurements
Differentiated SyMap from Ardian/Medtronic and other competitors
Significant potential for RDN market opportunity

17. Thank You

18. Average Procedure Time: 38 Min
Maximize coverage
Avoid circumferential energy in a single segment

19. Surgical Data Confirms Therapeutic Effects of Renal Nerve Blocking in 1,266 Cases
Surgical Renal Denervation in patients with severe Hypertension
Patients were followed 5-14 years
Blood Pressure and Heart Failure significantly improved
Method was abandoned due to invasiveness and high surgical complication rate