ENTRX

ENT401 in Otitis Externa Non-Confidential

ENTRX Overview
ENTRX, LLC is a virtual privately-held drug discovery company Founded by a practicing ENT and formulation Pharmacist ENT401 is a classified as a 505(b) 2 product by the FDA ensuring a simpler and shorter development time to market ENTRX, LLC expects to file an IND with the FDA in Q1 2013 ENT401 revenues WW are estimated at ~$300M Primary development path is to license to a Pharma company with expertise in diseases of the ear

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ENT 401
505(b)2 product
Made up of 3 existing API commonly used in otic preparations Unique, novel and patented formulation for instillation into the ear COGs very low

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Otitis Externa (OE) Disease Overview

US incidence of OE is 1.3M-1.9M patients and 2.4M events per year Acute OE (AOE) makes up 91% of all OE patients and events Fungal Otitis Externa is subset of Otitis Externa (OE) but not AOE Nine to ten percent of OE in the US is fungal OE
Presentation
Acute inflammation of ear canal Debris in ear canal Pain, itchiness Chronic ear discomfort

Type of OE Acute

Cause

Current length of treatment

Approx 7 days 1-3 physician visits

Unmet Medical Need

Treatment compliance Reduce treatment time One treatment by physician Potential resistant bacteria Treats fungi Reduce debridement Reduce physician visits and treatment time One treatment by physician

Bacterial High humidity

Fungal

Persistent/recurrent debris in the ear canal Refractory to standard antibiotic otic drops

Fungal Resistant bacteria High humidity

2 weeks to months Multiple physician visits Multiple debridements

Osguthorpe et al, OE:review and clinical update, AFP, 2006, 74 & CDC MMWR 2011, AAO, Head and Neck Surgery, 2006, 135, 787-791 & GP Clinical Review, AOE, 2012, CCBP primary market research, 2012

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OE & fungal OE Pathogens

US incidence of OE = 1.3M to 1.9M patients per year
OE/Pathogen P. aeruginosa S. aureus Gram negative bacteria
(other than P. aeruginosa)

Reported % 20-60% 10-70% 2-3%

(regional differences) (regional differences)

# US patients 400K- 1.2M 200K- 1.4M 40-60K

US incidence of fungal OE = 117K to 190K patients per year

Fungal OE Pathogen Aspergillus Candida Reported % 90% 10% Resistant OE bacteria
AAO, Head and Neck Surgery, Clinical Practice Guidelines; Acute OE, 2006, 134, AAFP, OE: A Clinical Practice Guide, 2001, 63

# US patients 105K-171K 18K-19K

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Acute OE Antibiotic Standard of Care

Acute OE is typically resolved in 7 days however the treatment effect is dependent on patient compliance with self-administered drops multiple time per day
Approved Products Quinolone otics Neomycin otics Polymyxin B Other Aminoglycoside solutions Published Efficacy ~82% 83-94% 81% Authors et.al. Alcon PI 2009 Roland, Schwartz Drehobl

Less used due to ototoxicity

Providers Synergies, Otic Antibiotic review, 2009, Drehobl, 2008, Roland, 2008, Schwartz, 2006

ENTRX

Fungal OE Standard of Care

Diagnosis of fungal OE is typically made after the patient has failed other therapies To date there is no approved antifungal otic treatment Common otic preparations used to treat fungal OE off-label are varied with wide ranging efficacy
Select off-label Products Azoles Nystatin Boric Acid Gentian Violet Published Efficacy 90-100% 50-80% 72-77% ~80% Authors et.al. Nong, Bassiouny, Jadhav Jackman, Besbes Ozcan, del Palacio Spandow, Cohen

By the time the fungal OE is resolved the patient may have received between 2 weeks to several months of treatment
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OE Unmet Needs
OE Type

Unmet Need
Primary Care Physicians treat ineffectively and infection becomes resistant and/or severe Patient compliance is less than 100% Overall cost of treating OE is economically inefficient No approved treatments for fungal OE Patients endure long courses of treatment to resolve the infection Physicians try hit-or-miss approach with off-label drugs Repeat debridement and office visits are costly and time consuming Overall cost of treating fungal OE is economically inefficient
CCBP primary market research, 2012

Acute OE

Fungal OE

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ENT401 Product Attributes

ENT401
One treatment Physician administered Benefits = infection resolved in 2-4 days No need for debridement after treatment Compliance not an issue

Product Profile tested in primary Market Research

ENTs were very positive Would prescribe to over 90% of OE patients

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ENT401 Preliminary Human Data

Product tested in clinical practice on 100 OE patients (physician-initiated)
No AEs, very safe Well-tolerated by patients OE infections resolved in 98% of patients in 2-4 days Non-randomized study conducted in one ENT office

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Regulatory & Clinical Milestones

Q2 2012
ENT401 classified as 505(b)2

Q2 2013
CMC stability studies initiated

Q1 2015 Q1 2014
IND filed

Q1 2013
API Synergy Study completed

File 505(b)2

FDA approval anticipated ~Q4 2015

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ENT401 IP
WW patent filed for
Combination of 3 generic drugs a novel formulation Novel formulation has not been previously contemplated FTO is positive for commercialization protection Patent expiry 2032

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ENT401 CMC
Manufactured under cGMP Scale up process done by US CMO IND filing with stability @ 3 mos & ongoing COGs very low

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ENTRX Partnering Strategy

License after IND to Pharma company with
Existing Otic experience Existing commercial infrastructure

Ideal relationship
Traditional License Acquisition

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