TMi de-risks & accelerates drug development for

“dry” Age Related Macular Degeneration

TMi de-risks & accelerates drug development for dry AMD

Shelley Boyd, MD, FRCSCClinician-Scientist, Ophthalmologist, specializing in diseases of the Retinaformerly Global Head, Ocular Angiogenesis Research Program, Novartis, SwitzerlandFounder & Chief Scientific Officer, TMi

Age Related Macular Degeneration

Dry AMD85%

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

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

Fundus Autoflourescence(FAF)

Quantification of GA is central to clinical trial design

Size of GA is an entrance criterion

Rate of expansion of GA is a clinical trial endpoint

Quantification of GA is central to clinical trial design

Fundus Autoflourescence(FAF)

TMi’s approach:

cellular arm of innate immune system

focus on macrophage biology

TMi’s science

macrophage polarization

M1- pro-inflammatory- highly phagocytic

- “house-keeping”M2

TMi’s science

Macrophage polarization

M1- pro-inflammatory- highly phagocytic

- “house-keeping”M2

TMi’s science

M1

therapeutic goal is to reduce pro-inflammatory M1 activity

TMi HYPOTHESIS:

TMi de-risks drug development

A. animal model uniquely mimics disease

quantifiable regions of tissue loss analogous to GA

rodenthuman

…and has GA-like patch expansion

thus aligns with clinical trial endpoints

Macrophages RPE

macrophages are associated with RPE loss

Macrophages RPE

… with excess M1 activity

M1 macrophage mRNA

mR

NA

fo

ld c

han

ge

Time (days/weeks/months)BL

Macrophages RPE

… with shift in M1/M2 polarization

M1 macrophage mRNA

mR

NA

fo

ld c

han

ge

Time (days/weeks/months)BL

2. Lead compound TMi-018

1st in class transcriptional regulator

proximal

Basal conditions

mRNA

distal proximal

Inflammatory conditions

mRNA

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

Pre-clinical testing:

TMi-018 protects against tissue loss:

TMi-018 preserves retinal function

TMi-018 preserves the RPE

TMi-018 reduces M1 mRNA

reduces M1 targets

TMi-018 reduces downstream inflammation

reduces M1 targets reduces inflammasome

shifts M1/M2 balance

TMi-018 shifts the M1/M2 balance

reduces M1 targets reduces inflammasome

TMi-018 reduces patch expansion

+ saline + TMi-018

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

TMi-018 - LMW compound suitable for sustained release

time

dose

• successfully prosecuted US Patent Office

• on accelerated Patent Prosecution Highway internationally

Cooley LLP, Morgan Lewis LLP

TMi-018 - patent protected

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

• Transition to early phase clinical trial

• ocular toxicity

• IND approval from US FDA

TMi is poised to accelerate:

TMi has raised seed funds

• closed seed round of investment, effective October 31st, 2015

• in discussions for next rounds

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

De-risks & accelerates drug development for

“dry” Age Related Macular Degeneration