ONL Therapeutics is developing a first-in-class drug called Met12 to prevent photoreceptor cell death in retinal diseases. Met12 works by inhibiting the FAS receptor pathway to block apoptosis. Preclinical studies show Met12 protects photoreceptors after retinal detachment. ONL Therapeutics plans to pursue an orphan drug indication for retinal detachment and expand to other large retinal markets. The company has strong intellectual property, management experience, and plans to advance Met12 through clinical trials with capital efficient development.

1. onltherapeutics.com
onltherapeutics.com
Visionary science.
onltherapeutics.com
Visionary science.
OIS @ AAO 2014
John Freshley | President & CEO

2. onltherapeutics.com
ONL Therapeutics Highlights
+ First-in-class therapeutics to prevent photoreceptor cell death
+ Relevant in many retinal diseases addressing existing > $7B
worldwide market
+ Orphan Drug status in retinal detachment
+ Rapid and capital efficient development path
+ Strong intellectual property position
+ Experienced management and expert advisory teams

3. onltherapeutics.com
Photoreceptor CellApoptosis Substantial Unmet Need in
Retinal Disease
+ Despite current therapies photoreceptor cell death
remains the root cause of vision loss and leading
cause of blindness
(AREDS / CATT / Seven-Up)
+ Implicated in a wide range of ocular diseases and
conditions
+ When the photoreceptor – RPE interface is disrupted,
the photoreceptors die by apoptosis
+ This death is mediated by the FAS pathway which is
the most upstream activator of programmed cell death
1,2
Fas
Apoptosis Necroptosi
sFrom Vavvas 20131Zacks 2007 2Vavvas 2013

4. onltherapeutics.com
RetinalApoptosis Inhibition: Market Size
Others
Wet AMD
Retinal
Detachment
• Orphan designation
• Simplified & capital efficient development
• Rapid POC and market entry
• $300M - $500M global market

5. onltherapeutics.com
RetinalApoptosis Inhibition: Market Size
Others
Wet AMD
Retinal
Detachment
• Orphan designation
• Simplified & capital efficient development
• Rapid POC and market entry
• $300M - $500M global market
• 200,000 new cases annually
• Integrates well with current therapies
• $2-4B global market

6. onltherapeutics.com
RetinalApoptosis Inhibition: Market Size
Others
Wet AMD
Retinal
Detachment
• Orphan designation
• Simplified & capital efficient development
• Rapid POC and market entry
• $300M - $500M global market
• 200,000 new cases annually
• Integrates well with current therapies
• $2-4B global market
• Dry AMD
• Diabetic retinopathy
• Hereditary retinal degenerations
• $5-10B global market

7. onltherapeutics.com
Retinal Detachment: ASerious Disease with Unmet Needs
+ Surgery is only treatment option for
patients
– Effective at reattaching retina
– 90%+ “Success”
+ Anatomic success, but functional failure
– Photoreceptor cell death occurs
between detachment and surgery
– Macula-off detachments:
• Mean best corrected vision is
~20/501
• 1/3 of patients have vision worse
than 20/602
1Based on extensive literature review
2Mitry et al., BJO 2012

8. onltherapeutics.com
FAS-MediatedApoptosisActivated by Retinal Detachment
PR Cell
Surface
FAS-
Receptor
Pro-Caspase 8 Cleaved-Caspase 8
FAS-Ligand
Apoptosis
Cascade
PHOTORECEPTOR
CELL DEATH
§ Receptor activated when retina
is separated from RPE
§ Attractive therapeutic target
§ Focal point of cascade
Pro-Caspase 8 Cleaved-Caspase 8
§ Receptor activated when retina is
separated from RPE
§ Attractive therapeutic target
§ Focal point of cascade

9. onltherapeutics.com
§ Met12 is a small peptide inhibitor
of FAS receptor
§ Competitively binds to FAS
§ Prevents activation of apoptosis
cascade
§ Prevents photoreceptor cell death
FAS-MediatedApoptosis Blocked by Met12
PR Cell
Surface
FAS-
Receptor
Pro-Caspase 8 Cleaved-Caspase 8
FAS-Ligand
PHOTORECEPTOR
CELL DEATH
Pro-Caspase 8 Cleaved-Caspase 8
Met12

10. onltherapeutics.com
Pre-Clinical Efficacy of Met12: Blocking FAS Protects Photoreceptors
Two months after detachment,
up to 80% more cells treated
with Met12 survive
2-Month
Detachment1
2-Month
Detachment
w/ Met122
Attached
Retina1
1Zacks et al. IOVS, 2003
2Besirli et al., IOVS, 2009

11. onltherapeutics.com
Pre-Clinical Efficacy of Met12: Blocking FAS Protects Photoreceptors
Two months after detachment,
up to 80% more cells treated
with Met12 survive
0
0.05
0.1
0.15
0.2
0.25
0.3
Attached Retinal
Detachment
Met12
p=0.001
normalizedretinalthickness

12. onltherapeutics.com
Retinal Detachment: Market Opportunity
+ ~50,000 detachments / year in US
– ~20,000 macula off rhegmatogenous detachments
+ Orphan indication / single treatment with lasting benefit
– High price point
– $300M global market for macula-off detachments alone
+ Fits perfectly with current clinical practice
– Single injection at time of diagnosis, standard surgical plan to
follow
– Intravitreal delivery well established in retinal practice

13. onltherapeutics.com
Intellectual Property
§ Multiple patents filed, issued and licensed from University of
Michigan and Mass Eye and Ear
– 8,343,931
– 7,811,832
§ Orphan Drug Designation received from FDA in March 2013
– Provides 7 years exclusivity post-approval in retinal detachment
§ Additional IP filed in 2014

14. onltherapeutics.com
Management Team
Co-Founder &
CSO
Sr. VP. Operations
David Zacks, MD, PhD
– Physician/Scientist, U of Michigan, Kellogg Eye Center
– Thought-leader in the field of photoreceptor neuroprotection
Linda Johnson
– Former Executive Director, Global Development, Pfizer
– Two decades of experience leading teams from discovery to NDA
President & CEO
John Freshley
– Serial life sciences entrepreneur and business leader
– Recently Chief Business Officer of Compendia Bioscience
CMO
David Kleinman, MD, MBA, FACS
– Thought leader in ophthalmic drug development
– Experienced, venture backed clinical leader with MacuSight
Clinical
Joan Miller, MD, Chief & Chair, Dept. Of Ophthalmology, Mass Eye and
Ear
Pravin U. Dugel, MD, Managing Partner, Retinal Consultants of Arizona
Regulatory Judy Gordon, DVM, Founder, ClinReg Consulting Services, Inc.
Pharmacology Jeff Jamison, PhD, Founder & CEO, Ophthy-DS & Co-Founder of ONL
Toxicology Bill Brock, PhD, Founder, Brock Scientific Consulting
CMC Anna Schwendeman,PhD, Founder, Schwendeman Consulting
Advisors &
Lead Consultants

15. onltherapeutics.com
ONL Development Plan
ONL-101 (Met12) Development
IND Enabling Studies
Phase I Retinal Detachment
Phase II POC Retinal Detachment
Pre-Clinical POC New Indication
Corporate Development 2014 2015 2016 2017
Seed Funding ($3M)
Series A ($8-10M)
Series B and/or Partnership or Exit
= Past Milestones
= Future Milestones

16. onltherapeutics.com
ONL Therapeutics Highlights
+ First-in-class therapeutics to prevent photoreceptor cell death
+ Relevant in many retinal diseases addressing existing > $7B
worldwide market
+ Orphan Drug status in retinal detachment
+ Rapid and capital efficient development path
+ Strong intellectual property position
+ Experienced management and expert advisory teams

17. onltherapeutics.com
onltherapeutics.com
Visionary science.
onltherapeutics.com
Thank you
John Freshley
t: 734.926.5530
e: jfreshley@onltherapeutics.com