TMi has developed an animal model and lead compound that aims to de-risk and accelerate drug development for dry age-related macular degeneration (AMD). The animal model mimics dry AMD and has quantifiable regions of tissue loss analogous to geographic atrophy in humans. TMi's lead compound, TMi-018, is a first-in-class transcriptional regulator of M1 macrophages that has shown efficacy in reducing the onset and expansion of lesions in the animal model. TMi-018 has also demonstrated a clinically safe profile and potential for sustained release delivery required for treating dry AMD.

1. TMi de-risks & accelerates drug development for
“dry” Age Related Macular Degeneration

2. TMi de-risks & accelerates drug development for dry AMD
Shelley Boyd, MD, FRCSC
Clinician-Scientist, Ophthalmologist, specializing in diseases of the Retina
formerly Global Head, Ocular Angiogenesis Research Program, Novartis, Switzerland
Founder & Chief Scientific Officer, TMi

3. Age Related Macular Degeneration
Dry AMD
85%
Geographic atrophy (GA)
= loss of the photoreceptors & retinal
pigment epithelium (RPE)
the leading cause of
blindness in developed
world
Multi-billion $ market
No approved therapies

4. The Challenge
1) complex disease of innate immunity
2) no animal models develop dry AMD
3) clinical trial design is complex
4) sustained release will be required
Mariam Karmal, AAO EyeNet, 2011

5. Fundus Autoflourescence
(FAF)
Quantification of GA is central to clinical trial design
Size of GA is an entrance
criterion

6. Rate of expansion of GA
is a clinical trial endpoint
Quantification of GA is central to clinical trial design
Fundus Autoflourescence
(FAF)

7. TMi’s approach:
cellular arm of innate immune system
focus on macrophage biology

8. TMi’s science
macrophage polarization
M1
- pro-inflammatory
- highly phagocytic
- “house-keeping”
M2

9. TMi’s science
Macrophage polarization
M1
- pro-inflammatory
- highly phagocytic
- “house-keeping”
M2

10. TMi’s science
M1
therapeutic goal is to reduce pro-inflammatory M1 activity
TMi HYPOTHESIS:

11. TMi de-risks drug development

12. A. animal model uniquely mimics disease
quantifiable regions of tissue loss analogous to GA
rodenthuman

13. …and has GA-like patch expansion
thus aligns with clinical trial endpoints

14. Macrophages RPE
macrophages are associated with RPE loss

15. Macrophages RPE
… with excess M1 activity
M1 macrophage mRNA
mRNAfoldchange
Time (days/weeks/months)BL

16. Macrophages RPE
… with shift in M1/M2 polarization
M1 macrophage mRNA
mRNAfoldchange
Time (days/weeks/months)BL

17. 2. Lead compound TMi-018
1st in class transcriptional regulator
proximal
Basal conditions
mRNA
distal proximal
Inflammatory conditions
mRNA

18. B. Lead compound TMi-018
1st in class transcriptional regulator reduces M1-related gene expression
X
proximal
Basal conditions
mRNA
distal proximal
Inflammatory conditions
mRNA

19. Pre-clinical testing:

20. TMi-018 protects against tissue loss:

21. TMi-018 preserves retinal function

22. TMi-018 preserves the RPE

23. TMi-018 reduces M1 mRNA
reduces M1 targets

24. TMi-018 reduces downstream inflammation
reduces M1 targets reduces inflammasome

25. shifts M1/M2 balance
TMi-018 shifts the M1/M2 balance
reduces M1 targets reduces inflammasome

26. TMi-018 reduces patch expansion
+ saline + TMi-018

27. TMi-018 – known to be clinically safe
• demonstrated to be safe in Phase II clinical trial
• for non-ophthalmic autoimmune disease
• 400+ patients
• known MoA & confirmed druggable target
• demonstrated scalability for GMP production

28. TMi-018 - LMW compound suitable for sustained release
time
dose

29. • successfully prosecuted US Patent Office
• on accelerated Patent Prosecution Highway internationally
Cooley LLP, Morgan Lewis LLP
TMi-018 - patent protected

30. TMi de-risks drug development
B. Lead compound – TMi-018
• 1st in-class regulator of M1 macrophages
• is dose-dependently efficacious reducing onset & expansion of GA
• is systemically safe
• is scalable
• is patent-protected
A. Animal model uniquely mimics disease
• aligns with acceptable clinical trial endpoints
• and supports role of macrophages

31. • Transition to early phase clinical trial
• ocular toxicity
• IND approval from US FDA
TMi is poised to accelerate:

32. TMi has raised seed funds
• closed seed round of investment, effective October 31st, 2015
• in discussions for next rounds

33. President & CSO: Shelley Boyd, formerly Head Ocular Angiogenesis Research Program, Novartis
Chief Business Officer: Wayne Schnarr, formerly VP Oncolytics Biotech, Equicom
Strategic Advisory Committee:
Mike Grey, Pappas Ventures; formerly CEO Lumena, SGX, VP Corporate Development, Glaxo
Scientific & Medical Advisory Committee:
David Boyer, KOL, Retina Associates
Julia Levy, formerly CEO &CSO, QLT
Barrett Katz, Director, Clinical Trials, Albert Einstein, NY; formerly CMO Fovea, CEO Danube
TMi’s team

34. De-risks & accelerates drug development for
“dry” Age Related Macular Degeneration