Panoptes is developing PP-001, a best-in-class DHODH inhibitor, for local ophthalmic treatments. PP-001 has shown proof of concept in preclinical studies for posterior uveitis, dry eye disease, and viral conjunctivitis by inhibiting T-cells, IL-17, IFN-γ, and VEGF. Animal studies demonstrate PP-001's ability to reduce uveitis severity and prevent recurrences with intravitreal injection, as well as inhibit choroidal neovascularization. Panoptes is preparing to initiate a Phase 1b study in 2015 for intravitreal PP-001 and seeking commercialization partners.

1.
Panoptes
Franz Obermayr
CEO

2.
Development Pipeline
2
• Panoptes is developing PP-001 for local treatment in ophthalmology
Research Pre-clinical Phase 1 Phase 2
Intravitreal
and oral
Posterior
Uveitis
topical
Anterior/
Uveitis
topical
Dry Eye
(Sjögren)
topical
Viral
Conjunctivitis
Inflammatory
diseases

3.
Unique mode of action by PP-001, a best in class inhibitor of
DHODH
• Best in class DHODH inhibitor more than 100 fold more potent than Arava
and Aubagio (RA and MS)
• Inhibits proliferative T cells
• Is a potent anti adenoviral agent
• Is a selective nanomolar inhibitor of IL-17, IFN-g and VEGF
3

4.
Proof of Concept in Experimental Autoimmune Uveitis (EAU)
– once daily p.o.
4
EAU/R14 in Lewis rats
Clinical
uvei4s
score
days
post
immuniza4on
sclera
sclera
vitreous
vitreous
re-na
re-na
Placebo
PP-­‐001
EAU
unpublished
results
Prof.
Wildner
0
500
1000
1500
2000
2500
3µM
10µM
30µM
PBS
PP-­‐001
IFN-­‐gamma
pg/ml
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
3µM
10µM
30µM
PBS
PP-­‐001
IL-­‐17
pg/ml
INF-­‐gamma
IL-­‐17

5.
Therapeutic use of PP-001 in uveitis - single intravitreal
injection
5
Clinical
uvei4s
score
placebo PP-001
Days
post
immuniza-on
• PP-001 reduced the number of relapses by >50%
• Parallels real clinical need in patients to prevent
relapses
treatment
treatment
Right
and
leT
eye
placebo PP-001
Prevention of recurrence in relapsing-remitting EAU/R14

6.
Developed an Uveitis animal model for choroidal
neovascularization
• Choroidal neovascularization (CNV) is one of the most severe causes of
visual impairment in patients with posterior uveitis and is one of major sight
threatening mechanism.
• Rats were immunized with specific
antigens to induce experimental
autoimmune uveitis
• After initial uveitis flare rats develop to a
high frequency CNV as a sequel
6
GL
ganglion
cell
layer
INL
inner
nuclear
layer
ONL
outer
nuclear
layer
CH
choroid

7.
PP-001 inhibits choroid neovascularization
7
EAU Rat model was treated with PP-001 at beginning
(day9) or at the peak (day 15) of clinical symptoms of
uveitis
A: Vehicle control 20x B: PP-001 day 9 20x
Inhibition of CNV in rat eyes

8.
PP-001 inhibits CNV via VEGF
8
PP-001 inhibits VEGF
Peripheral lymphnodes of EAU rats induced
by the PDSAg peptide were harvested at day
14 and were assayed for activity on cytokines.
VEGF is the hallmark effector molecule
for neovascularization and
angiogenesis and the major target for
therapy in wet AMD

9.
PP-001 mode of action in CNV
9
Schema-c
model
for
promo-on
of
CNV
taken
from
Hasegawa
et
al,
Jimmunol;
Jan
13,
2013.
PP-­‐001
PP-­‐001

10.
Science Summary PP-001
• POC in EAU rat model for uveitis
• is superior to cyclosporineA in Uveitis
• inhibits choroidal neovascularization via VEGF/IL-17
• administered locally (intravitreal injections) as maintenance therapy for uveitis
• Excellent tolerability
• POC in scopolamine mouse dry eye model
• First time proof that topical formulation of PP-001 is efficacious
• Significant reduction of corneal defects, the crucial endpoint in dry eye disease
• Excellent tolerability
• POC in adenoviral conjunctivitis rabbit model
• Clear dose response with topical formulation comparable with cidofovir
• Excellent local tolerability (draize scale analysis)
10

11.
Summary Panoptes
11
• Recently closed financing round
• Phase 1b study in 2015 with intravitreal PP-001
• We are looking for experienced development and
commercialization partners in the field