Welcome To - S I S Presentation 2014

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S.I.S
Venoms For Humanity
S.I.S Shulov Innovative Science Ltd.
A biopharmaceutical company focused on
the discovery and development of novel
human therapeutics.
April 2013
Presentation’s Agenda
• Who we are?
– Scientific Board
•
•
•
•
•
•
•
•
•
What do we do?
Our products
How do we do it?
IP
The Market
Company’s snap shot
Milestones and Finance
Company’s History
Contact info
Who we are?
Founders
S.I.S Shulov Innovative Science Ltd. was
founded by the late Prof. Aharon Shulov
and Mr. Aviv Marx
• Prof. Aharon Shulov (1907-1997)
– Dept. of Zoology at the Hebrew University of Jerusalem, Founder and
General Manager of The Jerusalem Biblical Zoo for over 40 years.
– Proposed a research program to identify the analgesic components of snake
venom
• Mr. Aviv Marx - President and CEO
– Entrepreneur and family friend provides funding.
3
Who we are?
Scientific Board
• Dr. Naftali Primor – VP of R&D
– Dr. Primor is a world renowned expert in the toxicology and chemistry of
snake venoms.
– He has featured in the National Geographic Film entitled "Snakes in The Holy
Land", and is constantly sought for his expertise and skills in the handling and
toxicology of venomous reptiles and scorpions.
• Dr. Avigdor Levanon – VP of Business Development
– Formerly VP, Research at BioTechnology General (Israel) Ltd.(BTG), Chairman
of the Board at Target-In Ltd. and Director at the Israel Oceanographic and
Limnological Research Ltd. with over 31 years in the biotech industry.
• Prof. Israel Steiner (M.D.) – Board Member
– Head of Dep. of Neurology, Beilinson Hospital Petach-Tikva, Israel. Head of
Neurology Sciences Unit, Hadassah University Hospital, Jerusalem and a world
expert in molecular basis of HSV1 latency and HSV1 infectivity.
4
Who we are?
Scientific Board (Cont’)
• Prof. Elka Touito - Board Member
– Dep. of Pharmacy, the Hebrew University Hadassah Medical School, Jerusalem. Head
of Innovative Dermal, Trasdermal and Transmucosal Delivery Group and a world
expert in enhancement of dermal drug delivery for systemic action.
• Prof. Amos Panet - Board Member
– Dep. of Biochemistry and the Chanock Center for Virology – IMRIC, the Hebrew
University Hadassah Medical School, Jerusalem.
– Prof. Emeritus of Cancer Research, Virus replication and viral diseases, a world expert
in HSV1 molecular biology.
• Prof. Yechiel Shai - Board Member
– Dep. of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
– World expert in protein-membrane interaction and protein-protein recognition within
the cell membrane
5
What do we do?
Developing new and innovative
products based on snakes’
venom by isolating novel nontoxic short peptides.
6
Our products
• Treatment for skin psoriasis
– Psoriasis is a chronic skin disease that is the most prevalent autoimmune
disease in the U.S., with as many as 7.5 million Americans affected (2.45% of
the population). It occurs when the immune system mistakes the skin cells as
a pathogen, and sends out faulty signals that speed up the growth cycle of
skin cells.
• Treatment for Genital and simplex Herpes
– Herpes is the most common form of infection. Herpes viruses cycle between
periods of active disease presenting as blisters containing infectious virus
particles that last 4–21 days, followed by a remission period. Unfortunately, a
cure for herpes has not yet been developed. Once infected, the virus remains
in the body for life
– Globally, about 4.0 billion people are estimated to be infected with Herpes
Viruses.
7
How do we do it? (innovation)
 Novel non-toxic short peptide has been isolated from snake
venom based on its highly potent in-vivo analgesic activity upon
topical application.
 Based on the above novel molecule a whole family of related
compounds has been identified in various snake venoms.
 One of the naturally occurring peptides (coded Zep-4) and its
chemically modified version coded Zep-3, were chemically
synthesized in gram quantities.
 These peptides were formulated as a cream and assessed
for their analgesic and anti-viral activities and for the
treating of psoriasis symptoms upon topical application on
the skin. (Based on histological observations and specific
psoriasis bio- Markers.)
8
Intelectual Property
As of February 2013 the European Patent
Examiner has approved our claims in
a new PCT patent
(PCT/IL2012/050105 – "method for treating disorders
of the skin")
including the therapeutic use of the peptides as
treatment for viral induced clinical
symptoms, such as HSV1 Cold Sores, HSV2
Genital Herpes and psoriasis.
9
HSV1 - The Market
 The total skin disorders market is estimated to be $28
Billion annually (for 2011), about 1/3 of which is due to viral
infections, most of these being the Herpes virus (HSV1,
HSV2 and Herpes Zoster)
 By the age of 40, nearly 90% of adults, have been exposed
to HSV1, 15% of those exposed to HSV1 may develop
symptoms (blisters, cold sores) every year.
 In the Western World (U.S., Europe and Japan) the potential
market is over 100 Million patients, these patients develop
clinical symptoms every year. A large percentage of them
have several episodes annually.
10
HSV1 – The Market (cont’)
 Globally, about 4.0 billion people are estimated to be infected
with Herpes Virus
 The incidence rate of cold sores, caused by the HSV1 virus, is the
second largest worldwide, trailing only behind common cold
 About 79% of the U.S. population is infected with HSV1, with
about 25-35% of the adults enduring recurrent spate of cold
Sores
 in recent years HSV1 has become the most common cause of
newly diagnosed genital herpes infections
”The need for innovative therapies for the treatment of herpes
simplex infection, and the search for novel antiviral drugs continues.
This presents a huge potential for the growth of herpes simplex
therapeutics market in future”.
(Global Industry Analysts, Inc.)
11
HSV1 - The Market (Cont’.)
>
Above 40% of genital Herpes is caused by HSV1 and Zep-3
presents a possible prevention as well as cure.
12
Psoriasis - Market
Psoriasis is a chronic skin disease that is the most
prevalent autoimmune disease in the U.S., with as many
as 7.5 million Americans affected (2.45% of the
population).
Psoriasis Market Info™ captures all the relevant data on
this disease. The overall market value is $1.8+ billion in
2010 in the U.S alone and $3.4 billion world-wide. This
market is expected to grow significantly in the future,
largely due to the chronic nature of the disease, the high
unmet and continued need for topical therapies which will
make this market approachable for any new therapy that
is both effective and safe.
13
Company’s snap shot
• Development Studies
• Current status of SIS's products
• Inhibition of HSV1 replication and spreading
in tissue culture
• Safety and Toxicology
• Trans Dermal Permeability
• Phase I Clinical Study
14
Development Studies
 Analytical and bio-analytical assays to trace the products in buffers and
in body fluids have been developed.
 The % of trans-dermal permeability has been determined in a Franz cell
model (permeability via pig’s ear skin is less than 0.1%)
 Intra vaginal permeability in rabbits as a model for mucosal
endothelial cells rich in blood vessels.
A 90 days sub-chronic toxicity study in rates
 Anti viral activity was established In- vitro and In- vivo.
 Determination of product stability Intra vaginal permeability in rabbits
as a model for mucosal endothelial cells rich in blood vessels was
performed.
 A 90 days sub-chronic toxicity study in rats is being performed
15
Current status of SIS's products
S.I.S has conducted a large variety of pre-clinical studies in accordance with
the requirements of the health regulatory authorities and in order to support
the development processes of Zep-3 and Zep-4 cream as a product and to
establish its safety and efficacy.
 S.I.S has completed all essential toxicology and safety studies required for
the submission of a file for Phase I Clinical Study.
Safety Parameters: The drug permeation studies reviled that during the 24 hrs
experiment, Zep-3 and Zep-4 have a very low absorption profile across the
skin (less than 1%) while significant amount of drug is accumulated in the skin.
Identical results were obtained upon intra vaginal application (3 times per day
for 7 days) in rabbits as a model to blood vessel rich tissue .
Phase I Clinical Study: A Helsinki approved Phase I Clinical Study was
performed at the Dep. Of Dermatology at Shiba hospital (Israel). All the 22
(100%) healthy volunteers enrolled into the study were subjected to Zep-3
cream treatment administrated topically 4 times daily during 5 consecutive
treatment days at either 0.1% or 1.0% in dose escalating area size 1cm; 10cm
and 20cm.
Zep-3 was found in this clinical study to be well tolerated, safe to use and
didn't present any undue risks to the study participants.
16
Inhibition of HSV1 replication and
spreading in tissue culture

The anti HSV1 activity of Zep-3 is determined by
measuring plaque forming unit, using tissue culture vero
cells in vitro.

The results depicted below are representative of one out
of six repeated experiments using two different batches of
Zep - 3

Infected HSV1 treated with Zep-3 (4mg/ml or 8mg/ml)

Infected HSV1 treated with “Scrambled” peptide (4mg/ml
or 8mg/ml).

“Scrambled” refers to the identical amino acids such as
Zep-3 but in altered sequence

The anti-viral effect was induced without causing Cell
Toxicity in the Control Vero Cells
17
Inhibition of HSV1 Replication by Zep-3
Zep – 3 (4mg/ml)
Zep – 3 (8mg/ml)
Scramble (4mg/ml)
Scramble (8mg/ml)
18
Zep-3 inhibits virus replication and spreading in tissue
culture.
 Zep-3 inhibits in dose dependent manner the replication of HSV1
in Vero cells
Control - No Peptide
Zep-3
19
Inhibition of HSV1 Replication by Zep-3 in Organ Skin
Culture
Control - None Infected
HSV1 – Infected + Scramble (8mg/ml)
HSV1 - Infected
HSV1 – Infected + ZEP-3 (8mg/ml)
20
Zep-4 for Treating Psoriasis
 Anecdotal data indicates that Zep-4 upon
topical application is efficient for treating
psoriasis in patients.
 Zep-4 reduce the expression of
psoriasis specific biomarkers in human
skin organ culture stimulated by EGF
and LPS.
21
Safety and Toxicology
of Zep-3 and Zep-4
Safety studies were carried out in rats in which the
following end points were recorded:
•body weight
•Vitality
•blood picture
•Internal organs histopathology
No adverse side effects were observed at twice a week
administration (topical or I.V.) of high dosages for 200
days
22
Trans Dermal Permeability of Zep-3
and Zep-4
Dermal Permeability was tested using the
ear-skin pig model.
Zep-3 and Zep-4 show permeability profile
below 1% after 24 hrs.
 Significant amount of drug accumulated in
the skin.
 Identical results were obtained upon intra
vaginal application (3 times per day for 7 days)
in rabbits as a model to endothelial membrane
rich in blood vessels.
23
Summary of Zep-3
 Zep -3 upon topical application inhibits/prevents
within less than 5 minutes the itching and pain
induced by Herpes Simplex Virus Type I (HSV1)
and eliminates swelling and blister formation in
less than 36 hours
 Zep-3 inhibits in a dose dependent manner the
replication and spreading of HSV1 and HSV2 in
Vero cells infected by the viruses.
 In a Phase I Clinical Study (22 healthy
volunteers), Zep-3 cream was found to be well
tolerated, safe to use and didn't present any
undue risks to the study participants.
24
Summary of Zep-3
 Zep – 3 inhibits in a dose dependent manner the
replication of HSV1 in Vero cell line infected by
the virus
 Zep-3, demonstrates analgesic properties in
acute and chronic pain animal models
24
Milestones and Finance
26
Cash Flow
Income
 The Company has annual income of NIS 1.8M from
selling snakes’ serum to the Israeli Ministry of Health
Hard Expenses
 The Company has annual hard expenses as follows:
 Salaries – NIS 726K
 Legal, Accounting and general – NIS 150K
 Patents – NIS 100K
 Total annual hard expenses – NIS 3.1 M (245K monthly)
 The Company has additional soft expenses that are
varied according with the R&D requirements (next
slide).
27
Cash Flow- NIS
2011
2012
2013
Snakes' serum income
2,000,000
2,000,000
2,000,000
Salaries
Legal, Accounting
&General
(685,000)
(685,000)
(726,000)
(150,000)
(150,000)
(150,000)
Patents & IP
(100,000)
(100,000)
(100,000)
R&D
Total
(1,428,000) (1,500,000) (3,200,000)
(363,000)
(435,000) (2,076,000)
28
Gant & Capital Requirements
2013
Cost(
M$)
Task
Phase I - Safty*
Phase II- HSV1 Cold Sores
Phase II- Genital Herpes
Phase I/Iia - Psoriasis
Mode of Action
Long Term Stability
Degradation Pattern
Mucosal Tissue Permeability & Toxicity
ADME
Anti Viral Specificity
New Formulation
Unpredictable
TOTAL
Q2
Q3
2014
Q4
Q1
Q2
2015
Q3
Q4 Q1
Q2
Q3
0.4
1.60
2.30
2.90
0.25
0.15
0.25
0.05
0.80
0.05
0.15
0.89
9.79
* Self funded
29
Q4
Company History
30
History
Founded in 1985,
S.I.S targeted the development
of innovative pharmaceutical
products based on properties
of snake venom
1985
-
The founding of S.I.S pharmaceutical
Ltd. by Prof Aharon Shulov and Mr.
Aviv Marx.
1989
-
Developing a pain model using HCl
for efficacy testing using topical
application.
1990
-
Viper venom is separated into 5
fractions while the analgesic activity
is attributed to the fraction.
1992
-
The viper venom in the above non
toxic
fraction
was
further
fractionated on a size exclusion
chromatography column
S.I.S applies for first patent based on
viper venom following the discovery
of the analgesic fraction.
1993
-
1996
-
S.I.S reveals the existence of an
uniform analgesic fraction in three
families of venomous snakes. 31
History
1998 -
S.I.S applies for a second patent after
discovering that the analgesic fraction
is identified as common, among all
venomous snakes.
2000 -
The structure of the analgesic
peptides was identified chemically.
2001 -
The peptides and a chemically
modified version of one of them, Zep,
were chemically synthesized and
assessed for their analgesic activity
relative to the natural snake venom
derived molecules.
2002 -
Third Patent is filed. Composition
comprising an analgesic peptide (Zep)
and its therapeutic use.
Zep is successfully formulated as
cream and tested to confirm its
efficacy.
2003 -
Conformation of the anti-pain activity in
various in-vivo animal models for several
clinical indications.
2007 - Continuation of Pre-clinical studies, validation
2011
of efficacy in several animal models and
accumulating safety toxicology data.
2011 -
S.I.S focuses on the development of one of its
products for the treatment of Herpes Simplex
Virus (HSV1) induced symptoms, such as Cold
Sores, preventing itching, lesion and scab
formation.
2011 -
A new patent was filed claiming the efficacy of
the product(s) for various skin disorders
including those induced by HSV1 infection.
2012 -
Performing safety toxicology studies for the
submission of an IND file for Phase I clinical
trial to the end of the year.
2013 -
Phase I Clinical Study and approval of the
claims in the new PCT patent.
32
Contact information
Mr. Aviv Marx
Dr. Naftali Primor
Dr. Avigdor Levanon
President and CEO
VP R&D
Executive VP,
Business Development
Tel: +972 (8) 931-4114
Mail: [email protected]
Tel: +972 (50) 536-3748
Mail: [email protected]
Tel: + 972(50)724-4287
Mail: [email protected]
33
THANK
YOU
April
2013
S.I.S Shulov Innovative
S c i e n c e
L t d .
Venoms For Humanity
34
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