S.I.S

1. 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

2. 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

3. Who we are? 3 Founders S.I.S Shulov Innovative Science Ltd. was founded by the late Prof. AharonShulov and Mr. Aviv Marx • Prof. AharonShulov (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.

4. Who we are? 4 Scientific Board • Dr. NaftaliPrimor – 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. AvigdorLevanon – 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.

5. Who we are? Scientific Board (Cont’) 5 • Prof. ElkaTouito - 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

6. What do we do? 6 Developing new and innovative products based on snakes’ venom by isolating novel non-toxic short peptides.

7. Our products 7 • 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.

8. How do we do it? (innovation) 8 • 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.)

9. 9 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. Intelectual Property

10. 10 • 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

11. 11 • 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’)

12. 12 > Above 40% of genital Herpes is caused by HSV1 and Zep-3 presents a possible prevention as well as cure. HSV1 - The Market (Cont’.)

13. 13 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. Psoriasis - Market

14. Company’s snap shot 14 • 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

15. 15 • 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 isbeing performed Development Studies

16. 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 Current status of SIS's products

17. 17 • 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 Inhibition of HSV1 replication and spreading in tissue culture

18. Zep – 3 (4mg/ml) Scramble (4mg/ml) Zep – 3 (8mg/ml) Scramble (8mg/ml) 18 Inhibition of HSV1 Replication by Zep-3

19. 19 • Zep-3 inhibits in dose dependent manner the replication of HSV1 in Vero cells Zep-3 inhibits virus replication and spreading in tissue culture. Control - No Peptide Zep-3

20. Control - None Infected HSV1 - Infected 20 Inhibition of HSV1 Replication by Zep-3 in Organ Skin Culture HSV1 – Infected + ZEP-3 (8mg/ml) HSV1 – Infected + Scramble (8mg/ml)

21. 21 • 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. Zep-4 for Treating Psoriasis

22. 22 • Safety studies were carried out in rats in which the following end points were recorded: • body weight • Vitality • blood picture • Internal organs histopathology Safety and Toxicology of Zep-3 and Zep-4 • No adverse side effects were observed at twice a week administration (topical or I.V.) of high dosages for 200 days

23. 23 • 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. Trans Dermal Permeability of Zep-3 and Zep-4

24. 24 • 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. Summary of Zep-3

25. 24 • 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 Summary of Zep-3

26. Milestones and Finance 26

27. 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). Cash Flow

28. Cash Flow- NIS 28

29. 29 Gant & Capital Requirements * Self funded

30. Company History 30

31. 31 Founded in 1985, S.I.S targeted the development of innovative pharmaceutical products based on properties of snake venom History

32. 32 History

33. 33 Contact information Mr. Aviv Marx President and CEO Dr. NaftaliPrimor VP R&D Dr. AvigdorLevanon Executive VP, Business Development Tel: +972 (8) 931-4114 Mail: aviv@sis-shulov.com Tel: +972 (50) 536-3748 Mail: naftali@sis-shulov.com Tel: + 972(50)724-4287 Mail: alevano@bezeqint.net

34. 34 THANK YOU April 2013 Venoms For Humanity S.I.S Shulov Innovative Science Ltd.