1. AVENOVA
(formerly i-Lid™
Cleanser)
A NEW DIMENSION IN LID AND LASH HYGIENE
NovaBay Pharmaceuticals, Inc.
(New York Stock Exchange: NBY)
For more information contact:
Ron Najafi, Ph.D.
CEO & Founder
And consult: www.Avenova.com
2. The San Francisco Bay Area
Home to NovaBay Pharmaceuticals
(A view from our facilities)
3. NovaBay Pharmaceuticals
Employees: 28, founded in 2000 by Ron Najafi, Ph.D. (chemist)
NovaBay Dedicated Sales Force: 37, all across the US
Location: Emeryville, CA
Capital Structure: Public Company, listed on NYSE: NBY
Focus: Non-Antibiotic Antimicrobials
Marketed products (Neutrox platform)
– AVENOVA: (formerly i-Lid™ Cleanser ) . Lid & Lash Hygiene, Blepharitis,
MGD and Dry Eye.
– NeutroPhase: Diabetic Ulcer, Venous and Pressure Ulcers, including NF
– CelleRx: Burn associated with Post Laser Resurfacing
Pre-Market Products (Aganocide platform)
– Bladder Irrigation Solution for patients with Spinal Cord Injury and recurrent
blockage and encrustation
– Skin Infection (Impetigo and Acne)
Global Partnerships: PBE (in the US), IHT (USA), Galderma (France), Virbac
(France), Pioneer Pharma (China and Southeast Asia), Shin Poong (Korea), Biopharm
(North African and Middle East), Alpha Pharma (Ukraine) and Sarmedic (Israel)
12. Blepharitis / Meibomian Gland Dysfunction/
Associated Dry Eye / Pre-Operative Lid
Hygiene
Chronic lid & lash hygiene
- 24 million blepharitis patients
- 6.5 million MGD dry eye patients
- 3 million cataract patients
- 1.5 million refractive surgery patients
Total Potential Market: $700 million
13. Antibiotics (topical or systemic)
Steroid (topical or systemic)
Warm Eye Compress to help with
Meibomian Glands
Gland Expression
Food supplements such as Omega 3 fatty
Acid
No FDA approved Therapy
Standard of Care includes
21. Avenova (formerly i-Lid™
Cleanser)
for Conditions of the Lids and Lashes
Proprietary Technology
– Neutrox : NovaBay Proprietary (>99% Pure) 0.01% Pure (99%)
hypochlorous solution in saline is by prescription only.
– No hypochlorite impurity, which is often present in OTC
solutions.
– No resistance is expected based on novel mechanism of
action
Significant Market / Poorly Served
– Eyelid hygiene therapy, part of the treatment for blepharitis
– Currently marketed products have little to no benefit
– 4% of 18 – 22 year olds
– 71% of 65+ year olds
– U.S. Market Estimate of $500+ mil
24. Organism (ATCC number) Time to Kill %Reduction
Aspergilus brasiliensis 16404 60 seconds >99.99%
Bacteroides fragilis 25285 60 seconds >99.999%
Candida albicans 10231 60 seconds >99.99%
Clostridium perfingens 13124 60 seconds >99.99%
Enterobacter aerogenes 51697 60 seconds >99.999%
Enterococcus faecium (VRE) 51559 60 seconds >99.99%
Haemophilus influenzae 49144 60 seconds >99.999%
Klebsiella pneumoniae 10031 60 seconds >99.999%
Proteus mirabilis 14153 60 seconds >99.999%
Pseudomonas aeruginosa 27853 60 seconds >99.9999%
Serratia marcescens 14756 60 seconds >99.999%
Corynebacterium amycolatum 49368 60 seconds >99.99%
Staphylococcus aureus (MRSA) 33591 60 seconds >99.999%
Staphylococcus aureus 29213 60 seconds >99.999%
Staphylococcus epidermidis 12228 60 seconds >99.999%
Staphylococcus haemolyticus 29970 60 seconds >99.99%
Staphylococcus hominis 27844 60 seconds >99.99%
Staphylococcus saprophyticus 35552 60 seconds >99.99%
Streptococcus pyogenes 49399 60 seconds >99.99%
Propionibacterium acnes 29399 60 seconds >99.999%
Vibrio vulnificus 27562 60 seconds >99.999%
Neutrox®
NovaBay’s Proprietary Pure (>99%), 0.01% hypochlorous Acid in saline.
Skin pathogens are highlighted. The CLSI guideline for evaluating the bactericidal activity of an antimicrobial agent was adapted for this study. A 500 ul aliquot of each test organism was
added to separate tubes containing 5 mL AVENOVA (final inoculum 107 CFU/mL). After 1 min, a 30 ul aliquot was removed from each tube and diluted 1:10 in Dey/Engley (D/E) neutralizing
broth, followed by three additional ten-fold dilutions in D/E. This procedure was repeated at 4 minutes and 10 minutes post-inoculation. Each dilution was plated onto the appropriate agar
media in duplicate for quantitation. Plates were then incubated under the appropriate conditions for each organism, and CFU were counted. Details of the procedures can be found in Report
#: FD-1403R.00
Excellent in-
solution
activity
against a
broad range
of pathogens
Fast acting
onset of
activity
Effective
against
pathogens
commonly
found on the
lids & lashes
25. 27
Avenova™ demonstrated excellent activity in solution
compared with the market leading lid and lash cleanser*
Organism S. aureus MRSA S. epidermidis S. haemolyticus P. acnes
NovaBay
Avenova®
< 1 minute < 1 minute < 1 minute < 1 minute < 1 minute
OcuSoft® Lid
Scrub Foam
> 30 minute > 30 minute > 30 minute > 30 minute > 30 minute
NovaBay’s in-house methodology for determining therapeutic index was utilized.
fibroblast cells were used to assess safety. Each agent was serially diluted to arrive at a “cell safe” concentration. At that concentration,
antimicrobial time kill was measured vs. various microorganism (shown above). More on this methodology at:
The In Vitro Antimicrobial Activity of Wound and Skin Cleansers at Nontoxic Concentrations
Suriani Abdul Rani, MS; Russell Hoon; Ramin (Ron) Najafi, PhD; Behzad Khosrovi, PhD; Lu Wang, PhD; and Dmitri Debabov, PhD
ADVANCES IN SKIN & WOUND CARE, FEBRUARY 2014, VOL. 27 NO. 2, page 66-69
26. Avenova has higher Therapeutic
Index than Betadine
• Fast acting
onset of
microbial
activity
• Extremely
low toxicity
levels
• 1,000 times
less toxicity
than
Betadine®
28
Tested AVENOVA® Betadine® Surgical
Scrub (Povidone-
iodine, 7.5%)
Nontoxic
Dilution
1:10 1:10,000
Time to 4 log10
kill
<1 minute >24 hours
Tested Against S. aureus ATCC 33591
*Antimicrobial Activity Comparison of Pure Hypo-chlorous Acid (0.01) with other Wound and Skin Cleansers at Non-Toxic Concentrations,
Russell Hoon, Suriani Abdul Rani, Ramin Najafi, Lu Wang, Dmitri Debabov; SAWC Spring 2013 and WHD 2013
The In Vitro Antimicrobial Activity of Wound and Skin Cleansers at Nontoxic Concentrations
Suriani Abdul Rani, MS; Russell Hoon; Ramin (Ron) Najafi, PhD; Behzad Khosrovi, PhD; Lu Wang, PhD; and Dmitri Debabov, PhD
ADVANCES IN SKIN & WOUND CARE, FEBRUARY 2014, VOL. 27 NO. 2, page 66-69
27. Bacteria / Biofilm Complicates Blepharitis
29
• Hypothesis is that
bacterial biofilm
plays a significant
role in delaying
wound healing
(Mertz – Wounds – May
2003)
A scanning electron micrograph of a porcine wound surface
with Staphylococcus aureus biofilm (6000X)
29. 31
NovaBay Avenova® has Potent Anti-biofilm
Activity Compared to Saline
• In vitro Biofilm of P. fluorescens breaks up upon
introduction of Avenova®
SALINE (control) NovaBay AVENOVA®
For literature references pointing to anti-biofilm activity of Avenova
Click here
30. Hypochlorous Acid
Hypochlorous acid
(HOCL) released from
neutrophil cells
Part of body’s immune
response
Kills microorganisms
Neutralizes toxins
released from pathogens
and inflammatory
mediators
– helps suppress the body’s
inflammatory response
32
neutrophil
cell
HOCL
33. Representation of human cell response to
bacteria-produced toxins
35
Biological reactivity of hypochlorous acid: Implications for microbicidal mechanisms of leukocyte myeloperoxidase
J. MICHAEL ALBRICH, CAROL A. MCCARTHY, AND JAMES K. HURST*
Proc. National Acad. Sci. Vol. 78, No. 1, pp. 210-214, January 1981
34. Representation of the Mechanism of Action of
Hypochlorous .01% in In-Vitro Models
Kills
bacteria
Blocks
bacteria
produced
toxins
Blocks
human
cell
produced
pro-
inflammat
ory
mediators
Different effects of hypochlorous acid on human neutrophil metalloproteinases: activation of collagenase and inactivation of collagenase and
gelatinase. Michaelis J1, Vissers MC, Winterbourn CC., Arthritis Rheum. 1994 Mar;37(3):424-7
Inhibition of collagenase activity by N-chlorotaurine, a product of activated neutrophils. Davies JM1, Horwitz DA, Davies KJ. Department of Medicine,
Albany Medical College, New York 12208.
35. Dx of DES and Blepharitis:c/o irritation, pain; used Maxitrol drops and
ointment for 2 wks + warm compress and eye scrub with Baby Shampoo. Was
shown how to clean his lids and lashes in the office with Saline.
Still returned 2 wks later with similar symptoms. Maxitrol was d/c’d and
Avenova given. After 2 wks RTC with improved symptoms and improved
clinically on Exam.
After Use of Baby Shampoo After use of Avenova
36. Typical Blepharitis Case
Vision:
– OD 20/30
– OS 20/20-
TAP: OD 21 OS 23
Exam:
– Blepharitis
– Debris on lashes
– Conjunctival
hyperemia
37. • From end of 2008 until end of 2012
• Patient was seen 25 times
• Between visits he would call and get Rx for Ab.
• Received courses of:
• Bacitracin, neomycin, polymyxin, tobradex,
maxitrol, zylet, oral doxy, used Ocusoft.
• Patient developed skin ulcer from Ocusoft use
• 10% of patients who use these over the counter
eye lid scrubs will develop contact dermatitis
• Eczema type reaction due to their detergent
based components
Patient Case History: Chronic Blepharitis
47. After 3 wks of use of Avenova™
fewer Demodex & better looking Lids and Lashes
48.
49.
50. Patients with acute or early stage meibomian gland
disease have a frothy tear film, or bubbles, which is
evident of soapy like substance here at the lid margin.
52. Staph aureus is a consistent Lipase producer
Breaking down natural lipids (triglycerides)
produced by Meibomian Glands
Bacteria Lipase activity is responsible for the
breakdown of lipid to fatty acids
– [Invest. Ophthalmol. Vis. Sci.April 1986 vol. 27 no. 4 486-491]
Assuming Lipase causes saponification of lipid
and conversion to fatty acid and soap. Can
Avenova breakdown Lipase and prevent
saponification (soap making)
53. In Laboratory Testing, Avenova™(formerly i-Lid
Cleanser) inactivates Rapidly Bacterial Lipase
Comparison of Bacterial Lipase Activity in the Presence of Eye Lid Cleansers
A. Epstein, L. Pang, K. Najafi-Tagol, R. Najafi, D. W. Stroman, D. Debabov.
Accepted for presentation at ARVO 2015
54. • Serial dilutions of AVENOVA™ were incubated for
1 h with S. aureus alpha-hemolysin toxin (1
ug/mL) and S. pyogenes streptokinase (175 u/mL)
• 0.1 ug/mL AVENOVA™ (1,000 dilution)
completely inactivated S. aureus alpha-hemolysin
toxin
• 0.001 ug/mL AVENOVA™ (100,000 dilution)
completely inactivated S. pyogenes streptokinase
Activity of AVENOVA™ against
Bacterial Toxins
55. Mechanism of Action
for Anti-Toxin and anti-Lipase Activity
S
S
R
R’
+ HOCl S
S
R
R’
O O
O O
S
S
R
R’
Cl
Cl
H2O
HOCl
Cl
Very Fast
Reaction
Kinetics of the reactions of hypochlorous acid and amino acid chloramines with thiols, methionine, and ascorbate. Free Radic. Biol. Med.
2001;30(5):572-9.
Herbert Spiegel, Advances in Clinical Chemistry, Vol 35, 2001, Academic Press
Oxidized
And unfolded Protein.
Highly water soluble and
non-immunogenic
Waldemar Gottardi, Dmitri Debabov and Markus Nagl, N-Chloramines, a Promising Class of Well-Tolerated Topical Anti-Infectives, Antimicrob.
Agents Chemother. 2013, 57(3):1107.
Staphylococcus aureus alpha toxin
56. Chronic use of antibiotic will
result in antibiotic resistant
strains… we must be vigilant !
59. To Open an account contact:
NovaBay by calling:
1-800-890-0329
Retail to patients: $30-40
If used according to instructions:
1st bottle will last 2 weeks
(2X per day application)
2nd bottle will last 1 month
(1X per day application)
