1. Chemical Renal Denervation Update and Future Directions
Tim A. Fischell, M.D., FACC, FSCAI
Professor of Medicine
Michigan State University

2. Tim A. Fischell, M.D. Ablative Solutions, Inc. Abbott Vascular
I have the following financial disclosures:
Ablative Solutions, Inc.
Founder, Co-Inventor
Officer and Stockholder  
Abbott Vascular
Member, Medical Advisory Board

3. Important Disclosures About the Peregrine System™ Kit
THE PEREGRINE SYSTEM KIT IS:
An investigational product not currently approved in the United States
Limited to investigational use in clinical trials
Currently being studied as a combination drug/device product to evaluate safety and effectiveness for renal denervation in the TARGET BP I Trial under an investigational new drug (IND) application
This presentation reports clinical data collected with the use of the CE Mark Peregrine System™ Infusion with a neurolytic agent (dehydrated alcohol) for the treatment of patients with systemic hypertension
This presentation is intended solely to aid in scientific discussion and exchange surrounding the development and further evaluation of the product for this use

4. Post-Symplicity HTN-3 Analysis Suggests Design Flaws and “Inadequate Denervation”*
Findings from Report
Renal denervation will work only if sufficient ablation is provided
50% of patients did not receive the minimum of eight total ablations
Adequate treatments (9-10 ablations/artery) with RF requires a vessel length of at least 4-5 cm
The majority of patients don’t have vessels this long
* Cardiology News: Renal denervation Proceeds as U.S. Trial’s Flaws Emerge, June 23, 2014; Kandzari et al, Eur Heart J, 2015

5. Alcohol-Mediated Denervation via Precise Nerve Targeting Device
Perivascular Sites Where Device Infuses Alcohol
Expanded View of Device Infusing Alcohol
Site-specific delivery of alcohol targeted for local nerve inactivation
Micro-volume (0.3 mL−0.6 mL) infused directly to the perivascular region
Extracellular fluid helps spread alcohol circumferentially in the perivascular region
Alcohol activity range self-limited through dilution by extracellular fluid
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union

6. Alcohol-Mediated Neurolysis: Animation
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union

7. Patient Treatment via Peregrine in Post-Market Study
CAUTION: The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union

8. Dose Response/Efficacy Based on Four Independent Surrogate Markers*
% quadrants with injury: score of 3 or 4 (0 to 4 scale)
Norepinephrine: % reduction relative to controls
TH decrease: Maximum reduction = 4
Nerve injury score: 0 to 4 scale
*Fischell, et al.; Cardiovascular Revascularization Medicine, 16, (2015)
Quadrants with significant nerve injury(%)
(%) Norepinephrine Reduction /
Initial dose
Current dose
Alcohol-mediated dose response observed with multiple, independent bio-markers in animal studies

9. Global Clinical Road Map Summary: Stepwise Approaches to Evaluate Technology
Safety/Performance N = 10 pts
Study Closed for Enrollment
CE Mark 5/1/15
First-Human-Use Study (Paraguay) N = 18
Study Complete
RCT double-blinded
2:1 (RDN vs. no RDN)
100 pts
Primary endpoint:
mean 24-hour ABPM at 8 weeks
Post-Market Study Single arm, open label, 0.6 mL alcohol/artery N = up to 120*
Peregrine System™ Kit
(Peregrine catheter + Alcohol)
Peregrine System™ Infusion Catheter
(Peregrine catheter + Neurolytic agent e.g. alcohol)
Global
Europe
Enrollment Underway
IND Allowed to Proceed
* As per Notified Body guidance
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union

10. Clinical Trials: FIM and Pre-CE (N = 28 subjects; 38 procedures; 57 renal arteries)
Peregrine System™ Infusion Catheter successfully navigated to target site in all renal arteries, including complex anatomy (short, tortuous segments, etc.)
Device performance appears to be successful during all 38 procedures with 97.3% device success (1 device failure prior to start of procedure in the FIM)
All vessels (57 in 28 subjects) treated as intended
Minimal to no sedation during the procedures, with short treatment time: average time/renal artery = 9 ± 5 min
Minimal contrast (average 67 ± 25 mL/procedure) and radiation exposure (average 10 ± 12 min/procedure).
FIM:
Systolic Office BP Drop: mean -25 mmHg at 1-M, and mean -22 mmHg at 6-M
Peregrine Study (pre-CE):
Systolic Office BP Drop: mean -29 mmHg and -37 mmHg at 1-M and 3-M (n=10).
24-Hour systolic ABPM drop: mean -12 mmHg and -7 mmHg at 1-M and 3-M, and was maintained at 12-M (-7 mmHg) (n=10)
CAUTION: The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union.
TCT2016 and on file at ASI.

11. Angiographic Follow-Up -> No Stenosis
Angiographic Follow-Up -> No Stenosis* (n = 57 arteries in 28 Subjects)
Baseline
Baseline
Baseline
Baseline
6 Months
6 Months
6 Months
6 Months
CAUTION: The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union.
*As adjudicated by independent core lab

12. The “Peregrine Post-Market” Study (Europe) (Enrollment & Treatment Stage)
A Post-Market Study of Transcatheter Perivascular Renal Denervation for the Treatment of Hypertension using the Ablative Solutions Inc. Peregrine System™ Infusion Catheter
Study Designed to Satisfy Requirement of Notified Body
Horst Sievert, MD
Int. Cardiologist
Peter Blankestijn, MD
Nephrologist
Atul Pathak, MD
Hypertensionist
Felix Mahfoud, MD
Co-Lead Investigators and
Steering Committee Members
CAUTION: The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union

13. The “Target BP I” Study (Global)
A Multicenter, Double-Blind, Sham-Procedure-Controlled Trial of Renal Denervation with Alcohol as delivered by the Peregrine System Infusion Catheter in Hypertensive Subjects
US: IND allowed by FDA to be initiated in the US – EU: Submission on hold
Global Steering Committee
David Kandzari, MD
Int. Cardiologist
Michael Weber, MD
Hypertensionist
Maurice Buchbinder, MD
Melvin Lobo, MD
Mathew Weir, MD
Nephrologist
Atul Pathak, MD
Ronald Schmieder, MD
Felix Mahfoud, MD
Co-Principal Investigators (US)
Co-Principal Investigators (Europe)
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.

14. Summary/Conclusions
Preclinical studies suggest that chemical renal denervation using alcohol, with the Peregrine System Infusion Catheter appears to provide substantial sympathetic denervation, with favorable safety profile.
Early clinical studies (FIM and the Peregrine (pre-CE study)) suggested consistent safety and performance of the Peregrine Catheter.
Anatomical safety at 6-month imaging by Angio and CTA with no apparent evidence of tear, dissection, or new restenosis in any of the 57 renal arteries treated, as confirmed by independent core labs
Early data from these clinical studies suggest a signal of efficacy with drop in blood pressure at various stages of the follow-ups. Larger controlled randomized blinded studies are needed to validate efficacy.
Patient enrollment continues in the Peregrine Post-Market Study in EU with treatment at the “new” volume of 0.6 mL/artery, with efficacy and safety data being collected.
“Target BP I”: FDA allowed initiation of study under its IND in the US and the company expects to start enrollment in 2017.
CAUTION: The Peregrine System kit is currently being studied to evaluate safety and efficacy for renal denervation.
It is an investigational product not approved in the US. Its use is limited to investigational use in clinical trials.
The Peregrine System™ Infusion Catheter is CE Marked, and only for use in the European Union