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? S.I.S Shulov Innovative Science Ltd. was founded by the late Prof. Aharon Shulov and Mr. Aviv Marx Prof. Aharon Shulov ( ) – 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. Founders 3

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. Scientific Board Who we are? 4

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 Scientific Board (Cont’) Who we are? 5

What do we do? Developing new and innovative products based on snakes’ venom by isolating novel non- toxic 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

 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.) How do we do it? (innovation) 8

Intelectual Property 9 As of February 2013 the European Patent Examiner has approved our claims in a new PCT patent (PCT/IL2012/ – "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.

 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. HSV1 - The Market 10

 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.) HSV1 – The Market (cont’) 11

>Above 40% of genital Herpes is caused by HSV1 and Zep-3 presents a possible prevention as well as cure. HSV1 - The Market (Cont’.) 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 14 Phase I Clinical Study

 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 Development Studies 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. Control - No PeptideZep-3  Zep-3 inhibits in dose dependent manner the replication of HSV1 in Vero cells 19

Inhibition of HSV1 Replication by Zep-3 in Organ Skin Culture Control - None Infected HSV1 - Infected HSV1 – Infected + Scramble (8mg/ml) 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 27 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).

Snakes' serum income 2,000,000 Salaries (685,000) (726,000) Legal, Accounting &General (150,000) Patents & IP (100,000) R&D (1,428,000) (1,500,000)(3,200,000) Total(363,000) (435,000)(2,076,000) Cash Flow- NIS 28

Gant & Capital Requirements 29 * Self funded Task Cost( M$) Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4 Phase I - Safty*0.4 Phase II- HSV1 Cold Sores1.60 Phase II- Genital Herpes2.30 Phase I/Iia - Psoriasis2.90 Mode of Action0.25 Long Term Stability0.15 Degradation Pattern0.25 Mucosal Tissue Permeability & Toxicity0.05 ADME0.80 Anti Viral Specificity0.05 New Formulation0.15 Unpredictable0.89 TOTAL 9.79

Company History 30

Founded in 1985, S.I.S targeted the development of innovative pharmaceutical products based on properties of snake venom History The founding of S.I.S pharmaceutical Ltd. by Prof Aharon Shulov and Mr. Aviv Marx Developing a pain model using HCl for efficacy testing using topical application Viper venom is separated into 5 fractions while the analgesic activity is attributed to the fraction 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 S.I.S reveals the existence of an uniform analgesic fraction in three families of venomous snakes. 31

History S.I.S applies for a second patent after discovering that the analgesic fraction is identified as common, among all venomous snakes The structure of the analgesic peptides was identified chemically 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 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 Conformation of the anti-pain activity in various in-vivo animal models for several clinical indications Continuation of Pre-clinical studies, validation of efficacy in several animal models and accumulating safety toxicology data 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 A new patent was filed claiming the efficacy of the product(s) for various skin disorders including those induced by HSV1 infection Performing safety toxicology studies for the submission of an IND file for Phase I clinical trial to the end of the year Phase I Clinical Study and approval of the claims in the new PCT patent. 32

Contact information Mr. Aviv Marx President and CEO Tel: +972 (8) Mail: Dr. Naftali Primor VP R&D Tel: +972 (50) Mail: Dr. Avigdor Levanon Executive VP, Business Development Tel: + 972(50) Mail: 33

THANK YOU Venoms For Humanity S.I.S Shulov Innovative Science Ltd. April