1. Entrepreneurial Track, “Developing Your Product” Target Product Profiles Medical & Development Considerations and Challenges Barbara Wirostko, M.D., Jade Therapeutics, Inc 2013 BioUtah Life Science Symposium November 6, 2013

2. Disclosures
Co Founder and Chief Scientific Officer of Jade Therapeutics, Inc
Based at Echelon, University of Utah Research Park, Salt lake City
Adjunct Clinical Associate Professor; Moran Eye Center, University of Utah, Salt Lake City, Utah
Consult for various drug delivery companies focused in ophthalmology
The success factors for successful drug discovery may be reflected by the past and present scenario for anti-glaucoma prostanoids. The first in class, latanoprost became a successful drug despite a high incidence of iridial & periocular hyperpigmentation, ocular surface hyperemia, lash lengthening and even occasional and rechallenge episodes of inflammation (CME). But they were very well tolerated systemically, much so than beta blockers and were exceedingly efficacious as a once a day drop. Although they were approved Pharmacia/ Pfizer had to collect 5 year safety data to support the ocular safety and determine the “long” term outcome of the iridial hyperemia. More recently prostanoid EP2 receptor agonists have taken center stage. These do not appear to have advanced beyond clinical efficacy studies to date. Reports of corneal “thickening” appear to be an impediment as well as evidence of photophobia and elements of inflammation. This is, arguably, surprising as virtually all topical drugs used clinically to treat glaucoma have now been claimed to alter corneal thickness. This evidence does not appear to represent a prima facia reason for disapproval, when placed in the general context of corneal thickness. However much like the iridial hyperpigmentation, the long term effects are unclear. Only now are there reports of “orbital sulcus deepening” after years of treatment. A more likely reason for arrested or delayed development may be ocular hypotensive efficacy. The ratio or marriage of the risk and benefit is key. Clinical studies to date reveal no dramatic superiority to other prostanoids but the safety could be less than ideal and or less than PGAs. This may raise concerns regarding advantageous product labeling and persuading ophthalmologists to prescribe an EP2 agonist. EP2 agonists also cause ocular surface hyperemia and are clearly inferior to recently marketed 0.01% bimatoprost in this regard. EP2 agonists have long been reported to be neuroprotective but clinical confirmation would require extensive clinical investigation. In looking at the next IOP lowering agent, the hurdle will be high not only for ocular and systemic safety but also for efficacy. Safety has always been but is even more so paramount to the approval process.

3. Objectives
Medical need in Ophthalmology
What is a Target Product Profile (TPP)?
What is the purpose of the TPP?
How did we use it?

4. Ophthalmology – $ 23 Billion
Chronic diseases + aging population = attractive area to be in
Aging population
chronic ocular pathologies: glaucoma, diabetic retinopathy, and macular degeneration,
many require chronic therapy
Daily self application is difficult
The ability to develop new drugs and deliver them through novel technology is attractive
Recognized unmet medical need

5. A lot of different deliveries in development

6. Topical eye drops
Confidential

7. This can’t always be easy….
Confidential

8. Identify the Unmet Need
Where is the unmet need?
What is the unmet need?
Confirm it….
Nail it then Scale it. The Entrepreneur’s Guide to Creating and Managing Breakthrough Innovation
Nathan Furr & Paul Ahlstrom
“Entrepreneurs don’t necessarily invent – they innovate”
Go out into the field
Don’t propose the solution
BUT ask the questions
Is there a need?
Could we solve it ?
What would the solutions look like?
Would this solution work?

9. Help you to fulfill that unmet need of the customer!!
The Target Product Profile (TPP) is the cornerstone of pharmaceutical product development.
Represents the envisioned product
Think about what will the eventual label be
Help guide development to get to this label
Living document
Help you to fulfill that unmet need of the customer!!
Develop the TPP
TPP can help you fullfill the unmet medical need

10. Patient population Endpoints Safety and efficacy Phase 3 comparator
Traditional TPPs have served as an R & D tool used to guide the clinical program
Patient population
Endpoints
Safety and efficacy
Phase 3 comparator
Also serves as a business tool for determining asset value and capital commitment.

11. Target Product profile for XXX
compound
compound
Active Ingredient
Indication
Target population
Mechanism of Action
Dosage
Route of Administration
Safety
Efficacy
Competitive Advantage over Other Therapies

12. Jade’s unmet need: Sustained Delivery of Antibiotics for Bacterial Keratitis
A corneal-blinding condition (scarring/perforation)
Most common cause in US is contact lens wear
Standard of care is topical antibiotics dosed as often as hourly
No marketed/ approved drug product in U.S.
Likely orphan drug indication
U.S. Army interest
NSF Phase I SBIR funded grant

13. Is there an unmet need? Confirmed with end users & customers
No current eye drop for this indication
Off label use and or compounding of approved antibiotics
Difficult to administer topical drops every hour x 2-3 days
Rapidly blinding condition
Ocular emergency
Compliance and Adherence are NOT GOOD
Poor compliance with topical drops
Confirmed with end users & customers

14. Initial Target Product Profile(s)
4-7 day drug-eluting strip/film
Use of approved ocular antibiotics to treat bacterial keratitis
(also known as corneal ulcers)
Applied in-office by M.D.
Local topical placement
Inferior Cul de sac
under bandage contact lens
Improved efficacy and safety over
“Off label” compounded drops (SOC)

15. Key Messages Focus on an attractive area Address a critical unmet need
Ophthalmology
Orphan diseases
Address a critical unmet need
Increased compliance/drug exposure Improved outcomes
Mitigate risk
Focus on local administration of already-approved drugs (505(b)2)
Proprietary polymer-based platform for novel delivery (strong IP)

16. “It is Fun to do the impossible” Walt Disney
Thank You!
“It is Fun to do the impossible” Walt Disney
Confidential