2. Ultrasonic drug dispersion
• A New Drug Delivery Method
• For serious conditions
– examples for serious infections of skin and soft
tissue
• Achieves:
a) Local delivery of drug or biologic molecules at
therapeutic concentrations to skin, tissue or organs;
b) minimal systemic drug exposure
• Product: Durable device + consumables + drug
2
3. Simple procedure for serious conditions
1. Patient is given brief anesthesia or conscious sedation
2. The antibiotic or other drug is injected through a blunt infusion needle
under the skin, using a peristaltic pump
3. The device disperses the antibiotic into the tissue using high frequency,
high power ultrasound
– The total process that takes no more than 10 minutes
Device Consumables Drug
3
4. UDD can put >250x more drug in
tissue than IV administrationmg/Lorµg/gcefazolin
6.9
199.2
1328
4.8
0
200
400
600
800
1,000
1,200
1,400
1,600
1,800
2,000
TPS Serum IV Serum TPS Tissue IV Tissue
277x Higher tissue
concentration
UDD IV UDD IV
Human Phase 1 clinical PK
study on 9 patients (UDD
n=7, IV n=2)
29x Lower
systemic exposure
Serum levels Tissue Levels
(mg/L) (µg/g)
each patient
received 1g
cefazolin in
100mL saline
4
5. Example Case Study
• Patient: 75-year old female diabetic with open wound of the lower leg
• Organisms cultured: Staphylococcus aureus (MRSA)
• History: 6 weeks IV antibiotics, 36 days hospitalization, multiple debridements
• Treatment: Debridement +UDD 1g cefazolin in 100mL + rotation flap closure and
split thickness skin graph (STSG)
• Outcome: Grafts take 100%, infection completely healed; no recurrence at 3
month visit
Clinical evidence of efficacy: treating drug
resistant skin and soft tissue infections
*Silberg and Nicolau, 2015 SAWC Poster CR-030
Before UDD cefazolin 3 mo after UDD cefazolin14 days after UDD
cefazolin + STSG
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6. 78% of MRSA patients completely respond
to only 1 UDD Cefazolin treatment
*Silberg and Nicolau, 2015 SAWC Poster CR-030
• 78% of MRSA patients completely respond with only 1 UDD Cefazolin
treatment (18/23)
• No more than 3 treatments required for any patient
• 76% of patients refractory to other treatments including IV antibiotics
responded to a single UDD Cefazolin treatment (13/17)
18 1x
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7. Works on other serious infections
Ex. Necrotizing Fasciitis Patient: diabetic female
with Necrotizing fasciitis cellulitis infection of the
left leg with extensive skin necrosis.
Ex. Diabetic Foot Ulcer Patient: scheduled
for amputation
Before UDD
cefazolin
After UDD
cefazolin +
STSG
*Silberg, 2015 SAWC Poster CS-098
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STSG = Split Thickness Skin Graft
8. Connecting the dots = a new
treatment paradigm
1.NO MRSA isolates resistant to >1,000mg/L Cefazolin
2.Ultrasonic Drug Delivery (UDD) introduced cefazolin
to tissue at levels >1,000mg/L
3.UDD Cefazolin eliminated treatment-resistant MRSA
infections in ONE treatment in 3/4ths of patients
1. Nicolau, DP and Silberg BN. ICAAC 2015. Poster # C-1071.
2. Silberg BN. Supplement to Plastic and Reconstructive Surgery, 2013 Vol. 132( 4S-1):p51-52.
3. Silberg BN and Nicolau, DP. SAWC 2015. Poster # CR-030.
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9. Dose sparing: reducing drug exposure
• Vancomycin
– Narrow therapeutic window: risk of nephrotoxicity
– IV requires carefully timed infusion
– Usual Adult Dose for Skin or Soft Tissue Infection (SSTI)
• 15 mg/kg IV every 12 hours (>2g/day for 70kg person)
• Duration: 10 to 14 days, depending on the nature and severity of
the infection
• UDD Vancomycin for serious SSTI
– 6 patients treated off label
• 50µg to 1mg total dose (in 5-100mL) (>1,000 times LESS than IV)
• Only 1 (n=4) or 2 (n=2) treatments required to eradicate infection
(including 1 MRSA case) not 1.5-2 weeks on IV therapy
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10. UDD drug delivery advantages
Higher target tissue/
organ concentration
= greater efficacy
IV/Oral
Standard of care
Ultrasonic Drug
Dispersion (UDD)
Target tissue
Lower systemic
(body) exposure
= fewer side effects
Delivery independent of:
1. Circulatory system
2. Lymph system
3. Diffusion
= effective in
compromised patients
①
②
③
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11. Sonescence Team combines surgery, ultrasound,
anti-infective and drug delivery experts
Michael J. Weickert, PhD; CEO
Former CEO and co-founder SEA
Medical Systems, CBO Corium, CBO
Stratagent, Nektar, Inhale, Ligand,
Somatogen, Auspex, NIH
Seth J. Putterman, Ph.D.; CTO
Professor of Physics Department of
Physics & Astronomy, UCLA, President
&CEO of Julian Schwinger Foundation
for Physics Research, Chair Science
Advisory Board Tribogenics Inc.
former Board Member Parametric
Sound (NASDAQ:PAMT).
Michele Brulé, MBA; COO and Co-
Founder, Director Operations, Santa
Rosa Antibiotic Effectiveness Project
Barry N. Silberg, M.D., F.A.C.S; CMO
and Founder
Plastic and Reconstructive Surgeon,
inventor TPS system and Ultrasonic
Drug Dispersion
David P. Nicolau, PharmD, FCCP,
FIDSA, Advisor
Director of the Center for Anti-
Infective Research and Development
and Coordinator for Research in the
Department of Medicine, Division of
Infectious Disease and Pharmacy at
Hartford Hospital, CT
11
12. Sonescence is seeking UDD partners
• Antibiotic suppliers/partners for serious skin
and soft tissue infections
• Development partners for proprietary
products in other serious conditions where
– targeted therapy has inherent advantages or
– dose sparing therapy is beneficial
• Investors
12
13. In the 1980s Barry Marshall and J. Robin Warren demonstrated that Heliobacter
pylori caused gastric ulcers. That led to a simple and effective therapy.
Dr. Barry Silberg discovered how to put enough drug directly into infected tissue to
kill resistant organisms. This innovation is simple and its impact on wound healing
and drug delivery could be just as profound as Marshall and Warren’s was for ulcers.
Contact:
Michael J. Weickert, Ph.D.
650-218-1840
mweickert@sonescence.com
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