PLX-R18 AS A MEDICAL COUNTERMEASURE AGAINST RADIATION · events or circumstances after the date hereof or to reflectthe occurrence of unanticipated events. For a more detailed description

PLX-R18 AS A MEDICAL COUNTERMEASURE AGAINST RADIATION

Study in collaboration with the Armed Forces Radiation Research Institute (AFRRI), Uniformed Services University of the Health Sciences

Sanchita P. Ghosh, PhD and Vidya P. Kumar, PhD

This presentation contains express or implied forward-looking statements within the Private Securities Litigation Reform Act of 1995 and other U.S. Federalsecurities laws. For example, we are using forward-looking statements when we discuss the expected timing of obtaining regulatory approval for our variouspatient trials and clinical data readout, proposed trials that may occur in the future, the timing and implementation of our collaborations with various partnersand the execution of definitive agreements relating to such collaborations and the potential benefits and impact our products could have on improving patienthealth care. These forward-looking statements and their implications are based on the current expectations of our management only, and are subject to anumber of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. The followingfactors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and marketrequirements; we may encounter delays or obstacles in launching and/or successfully completing our clinical trials; our products may not be approved byregulatory agencies, our technology may not be validated as we progress further and our methods may not be accepted by the scientific community; we may beunable to retain or attract key employees whose knowledge is essential to the development of our products; unforeseen scientific difficulties may develop withour process; our products may wind up being more expensive than we anticipate; results in the laboratory may not translate to equally good results in real clinicalsettings; results of preclinical studies may not correlate with the results of human clinical trials; our patents may not be sufficient; our products may harmrecipients; changes in legislation; inability to timely develop and introduce new technologies, products and applications; loss of market share and pressure onpricing resulting from competition, which could cause our actual results or performance to differ materially from those contemplated in such forward-lookingstatements. Except as otherwise required by law, we undertake no obligation to publicly release any revisions to these forward-looking statements to reflectevents or circumstances after the date hereof or to reflect the occurrence of unanticipated events. For a more detailed description of the risks and uncertaintiesaffecting us, reference is made to our reports filed from time to time with the Securities and Exchange Commission

2

Forward looking Statement

• Cell therapy company focused on Regenerative Medicine

• Off-the-shelf placenta-derived cell product candidates

• Two ongoing Multinational Phase III studies

• Cell manufacturing technology producing high quality

cell products at a commercial scale

• Strong IP portfolio (over 120 granted patents)

• Full time employees: 160

Background

Pluristem Therapeutics

3

Background

PLURISTEM in one slide

4

Placenta

Technology

Allogeneic off-the-shelf

Simple IM administration

Adaptive slow release secretion of cytokines

Long term regenerative effect

MSC-like properties

Adherent and spindle shaped Surface marker profile

Limited in vitro differentiation capability

Differences from

classical MSCs

No prolonged engraftment

Immunocompetent (Balb/c)

24hrs 4 days 6 days 16 daysPost IM injection (bioluminescence)

24hrs 4 days 6 days Post IM injection (bioluminescence)

Immunocompromised (NOD/Scid)

Level of PLX-R18 in muscle injection site after IM administration over time.

BackgroundPLX Cells Characterization

PLX- R18Oxidative

Stress

Neuronal damage

Inflammation

SOD1, SOD2, PRX2, TRX1

MMPs (1, 2, 10), TIMPs (1 and 2)

M2 macrophages

Immunomodulation

GDF15, SDF1, MIF, Galectin,

IL-11, IDO, TGFβ, PD-L1

T cellsIL10

ECM Remodeling

GDNF, BDNF, bFGFHGF, HB-EGF

NPC

IL-6, IL-8, SCFG-CSF, MCP-1,

Gro-β

Neurogenesis

Bone marrow failure

Platelets

Neutrophils

Monocytes

Reconstitution of blood cells

IschemiaAngiogenesis

VEGF, Angiogenin,

HGF

Myeloid precursures proliferation and

differentiation

BackgroundPLX-R18 MoA

Cytokine secretions were measured using multiplex Luminexassays and enzyme-linked immunosorbent assays (ELISAs)

Study Design

BackgroundPLX-R18 mitigates H-ARS when given up to 72 hrs. following exposure to Radiation

CH3 & C57BL/6

2 3

Study Termination

IM PLX-R18 2 million cells

Days 1+5, 2+5, 3+5

BackgroundPLX-R18 mitigates H-ARS when given up to 72 hrs. following exposure to Radiation

Control (naïve)

Vehicle

PLX-R18 (day 1&5)

PLX-R18 (day 2&5)

PLX-R18 (day 3&5)

Survival

WBCs RBCs Platelets

Weight

PLX-R18 AS A MEDICAL COUNTERMEASURE AGAINST RADIATION

• AFRRI• Sanchita P. Ghosh, PhD• Vidya P. Kumar, PhD

Pluristem LTD• Racheli Ofir, PhD• Michal Sheleg, PhD

STUDY 1- PROOF OF CONCEPT

Study Design

C57BL/6 male mice 8.0 TBI

2 3

Study Termination

IM PLX-R18 2 million cells at Days -1, +3

Assess survival efficacy of prophylactic PLX-R18 administration to in a mouse H-ARS model

C57BL/6 male mice subjected to TBI of 8.0 Gy.

Objective

Log-rank test p < 0.0003

GT3PLX-R18

Plasma-LyteSaline

ResultsPLX-R18 mitigates H-ARS when given 24 hrs. prior exposure to Radiation

GT3

PLX-R18

Plasma-LyteSaline

0 1 0 2 0 3 00

2 5

5 0

7 5

1 0 0

T im e p o s t- ir ra d ia t io n (d a y s )

Pe

rce

nt

su

rviv

al

74%

13%

S a l in e

G T 3

P la s m a -L y te

P L X -R 1 84%

100%

Log-rank test p < 0.0001

R V d 3 0

R D d 3 0

R D d 4 50 .0 1

0 .1

1

W B C

WB

C (

x1

03 cel

ls/µ

l)

N R5

R V d 3 0

R D d 3 0

R D d 4 51

1 0

1 0 0

1 0 0 0

P L T

PL

T (

x103 c

ells

/µl)

N R

R V d 3 0

R D d 3 0

R D d 4 50 .0 1

0 .1

1

N E U

NE

U (

x103 c

ells

/µl)

N R5

ResultsPLX-R18 mitigates H-ARS when given 24 hrs. prior exposure to Radiation

N a iv e V e h P L X -R 1 8 P L X -R 1 80

2 0

4 0

6 0

1 0 0

2 0 0

B o n e M a rro w :C F U

CF

U B F U -E

G M

G E M M

T O T A L

D a y 3 0 D a y 4 5

2 6 0

No significant difference was observed in H&E stained jejunal sections between Plasma-Lyte treated group and PLX-R18 treated group.

STUDY 2- OPTIMIZATION OF DOSING SCHEDULE

Optimize the time of administration (IM) of PLX-R18Objective

C57BL/6 male mice subjected to TBI of 8.0 Gy.

Study Design

Study Design

2 3

Study Termination

IM PLX-R18 2 million cells

-24h, -12h, +4h and at +3 days

4h-12h


ResultsPLX-R18 mitigates H-ARS when given 12 & 24 hrs. prior exposure to Radiation

CBC

P lasm

a lyte

, 0 G

y

P L X -R1 8 , 0

Gy

P lasm

a lyte

, 8 G

y

P L X -R1 8 , 8

Gy

0

5 0

1 0 0

1 5 0

2 0 0

2 5 0

Co

lon

y F

orm

ing

Un

its

B F U -E C F U -G M C F U -G E M M T O T A L

d a y 3 0

D a y s p o s t ir ra d ia t io n

Femoral BM by CFU Assay


Sternal Bone Marrow Megakaryocytes Day 30


p<0.05

STUDY 3- TIME COURSE OF CBC AND BM

Time course study following (IM) of PLX-R18

Study Design

2 3

Study Termination

IM PLX-R18 2 million cells at Days -1, +3

Collection time-points +2 h, and + 1, 3, 9, 14, 21 and 30 days post-TBI

1 9 14 212h


Objective

ResultsPLX-R18 mitigates H-ARS when given 24 hrs. prior exposure to Radiation- CBC

0 1 3 9 1 4 2 1 3 00 .0 1

0 .1

1

1 0

W B C

D a y s p o s t irra d ia tio n

WB

C (

x1

03

ce

lls

/µl)

20

*

0 1 3 9 1 4 2 1 3 00 .0 1

0 .1

1

1 0

N E U


NE

U (

x1

03

ce

lls

/µl)

20

*

*

0 1 3 9 1 4 2 1 3 00 .0 1

0 .1

1

1 0

L Y M

D a y s p o s t irra d ia tio nL

YM

(x

103

ce

lls

/µl)

20

*

*

0 1 3 9 1 4 2 1 3 01 0

1 0 0

1 0 0 0

P L T


PL

T (

x1

03

ce

lls

/µl)

5 000

*

*

0 1 3 9 1 4 2 1 3 00

2 5

5 0

7 5

1 0 0

% H C T


% H

em

ato

cri

t

*

P la s m a L y te (0 G y )

P L X -R 1 8 (0 G y )


P L X -R 1 8 (8 G y )

P las m

a lyte

, 0 G

y

P L X -R1 8 , 0

Gy

P las m

a lyte

, 8 G

y

P L X -R1 8 , 8

Gy

P las m

a lyte

, 0 G

y

P L X -R1 8 , 0

Gy

P las m

a lyte

, 8 G

y

P L X -R1 8 , 8

Gy

P las m

a lyte

, 0 G

y

P L X -R1 8 , 0

Gy

P las m

a lyte

, 8 G

y

P L X -R1 8 , 8

Gy

0

1 0 0

2 0 0

3 0 0

Col

ony

Form

ing

Uni

ts

B F U -E C F U -G M C F U -G E M M T O T A L

d a y 0 d a y 1 4 d a y 2 1

D a y s p o s t ir ra d ia t io n

* * *

Femoral BM CFU Assay

ResultsPLX-R18 mitigates H-ARS when given 24 hrs. prior exposure to Radiation- BM CFU

M e g a k a ry o c y te s

D a y s p o s t- ir ra d ia t io n

# of

meg

akar

yocy

tes

1 2 3 1 4 3 00

2 0

4 0

6 0

5


P L X -R 1 8 (0 G y )


P L X -R 1 8 (8 G y )

N o n -IR

* * *

ResultsPLX-R18 mitigates H-ARS when given 24 hrs. prior exposure to Radiation- BM Megakaryocytes

ConclusionsPLX-R18 mitigates H-ARS when given 24 hrs. prior exposure to Radiation

Improved parameters• Survival• BM cellularity and functionality• Peripheral Blood Counts

Upcoming studies:

1. GI recovery study (12Gy TBI)

2. DRF with 6 doses of radiation

Documents

PLX-R18 AS A MEDICAL COUNTERMEASURE AGAINST RADIATION · events or circumstances after the date hereof or to reflectthe occurrence of unanticipated events. For a more detailed description