Dr. Rafi Hofstein, CEO, Hadasit

Berlin Meets Israel

Biotechnology in Israel and Biomed 2007

Israel`s Academic Institutions and their Technology Transfer Companies (TTC)

Institutions TTC Hebrew U. (Jerusalem) Yissum

Tel-Aviv U. (TA) Ramot

Technoion (Haifa) Mosad Technion

Weizmann Inst. (Rehovot) Yeda

Ben-Gurion U. (Beer-Sheba) B.G.Negev

Hadassah University Hospital (Jerusalem) Hadasit

Israel`s Investments at the Academic Stage

2001NIS 480B

2004NIS 520B

2006NIS 570B

Israel`s GDP

R&D Expenditure (GDP Basis)

Israel4.6 %

Europe3.5 %

Japan3.0 %

R&D Expenditure (2005)

Total R&D NIS 27.4B

Government Portion

NIS 4.9B

Government Portion (Nis 4.9B)

VATAT 44%

OCS – MOITAL 38%

OCS – Health 0.7%*

*0.7% reflects $8M while NIH is $30B

Israel`s Investments at the Academic Stage – Cont.

National Patent Estate

Medical Device Patents per million Capita

Source: www.uspto.gov, Analysis: ILSI ©

Number of BioPharma Patents per million Capita

Source: www.uspto.gov, Analysis: ILSI ©

Life Science Patents % of Total Patents Registered

Source: www.uspto.gov, Analysis: ILSI ©

Average

17.9%

28.3%

Significant Outcome

Product Licensor Licensee Copaxone Yeda Teva

Rasageline Technion Teva

Exelone Yissum Novartis

Rebif Yeda Serono

Doxil Yissum/Hadasit J&J (alza)

StemEx Hadasit Gamidacell

HADASIT LTD.• Technology Transfer Company of Hadassah

Medical Hospitals located in Jerusalem, Israel.

• Promote and Commercialize IP (270 patent families) & R&D activity (1000 MDs and PhDs).

• Develope Therapeutics, Diagnostics & Devices

• Conduct Clinical trials and offers Pre-clinical services

Hadasit’s Mission

Promote and commercialize the applied R&D and innovative discoveries of HMO, for the purpose of maximizing return on R&D and increasing the revenue base of the institute.

Thereby, the institute can further its investments in technology, medical infrastructure, research activities, and education.

Main BottleneckFinancial Gap Problem

ChasmChasm

Main BottleneckFinancial Gap Problem

$ $50-500K50-500KInternalInternalSourcesSources

$ > $ >5M5MVenture fundsVenture funds

--CompaniesCompanies- -

ChasmChasm

I. Patent Protection

II. Licensing to Multinational companies

III. Collecting royalties

The Classical Commercialization Models

New/Additional Commercialization Models

Initiating Start-Up companies

Hadasit Clusters

Hadasit

ProTab

Verto

Tolaren

PP-14Cellcure

DMMT

Condrosite

HaptoAPEI

Trombotech

GVT

Theravir

CancerCure

KAHR

TK SignalRe

gen

era

tive

Other

Ca

nce

r

Inflammatory

Investment in start-up companies

Hadasit

Angels

Others

Start-up companies

Bioline Rx

Incubators

HBL

VCs

Glioblastoma

• Most malignant of cancers• Affects about 17,000 patients• 55 weeks median survival from time of Dx• 30 weeks median survival after recurrence with

best approved therapeutic agent, temozolomide• Effectiveness measured in weeks added to survival• Only 15% of patients achieve 6-month progression free

survival• Complete radiological tumor responses about 1/200• Often selected as 1st application of new biologic therapies• New therapeutic approaches urgently needed

TheraVir’s Vision

NewcastleVirus

GlioblastomaBrain Cancer

•“Good” viruses can be developed that will home in on and kill cancers that are beyond the range of current medicine and

•Treatments will emerge that are effective, free of side-effects and maintain the patient’s quality of life

The Product – NDV HUJ• New strain of the avian Newcastle

Disease Virus discovered by Prof. Zichria Zakay-Rones

• Advantages: Not a human pathogen, not engineered, not harmful to poultry (no environmental impact)

• Acts by causing cancer cells to kill themselves (apoptosis) and by activating the immune response

• Administered by intravenous injection

• Relatively economical to manufacture

Schematic of a paramyxovirus from University of Warwick

Remarkable Response in Glioblastoma Patient

• Complete responses are extremely rare with best Rx

• No serious side-effects • Phase I/II Study of

Intravenous NDV HUJ published in leading journal

Complete tumor response: baseline (a), first follow-up (b), second follow-up (c), 20. 25 and 30 weeks (d, e, f).

Summary• NDV HUJ is a new

candidate for a the biologic treatment of cancer

• Very encouraging early results for safety and efficacy in brain cancer

• Probable activity in broad range of cancers

• Completing negotiations with a major partner for continued development and marketing

• Phase II studies planned for US  

fighting cancer with therapeutic viruses

Hadasit

HBL

Ortec

Incure TolarexThrombo Protab KahrVerto TKSCellcure

7.7% 66% 94% 100% 100% 75% 39% 45% 27%

Hadasit 67% Public 33%

Vision – Cure neurodegenerative diseases using human embryonic stem cell based cell replacement therapies

1st Product – Committed dopaminergic neural progenitor cells for Parkinson’s disease

Status – Pre-clinical testing in animal models

Team – leading scientific group in the fieldheaded by Benjamin Reubinoff

IP – key patents in the field in-licensed fromES Cell International

Investment - $3 M in addition to $3M from Hadasit Bio-Holding to reach clinical trials

Jointly owned with ES Cell Int. from Singapore. Part of “Genesis” Consortium.

Hapto Biotech – Ortec International

During April 2006, Hapto Merged with ORTN (NASDAQ) Key Platform Technologies:

Haptides™ (~20 amino acids) synthetic peptides Synthetic peptides, Non-toxic up to high concentrationsEnabling technology: 1. Coat biological materials to produce “smart dressings”. Wound healing product2. Augment penetration of drugs and gene delivery into cell. Proof of concept

Fibrin Micro Beads (FMB) (50-300 m) Fabricated fibrin beads to attach and grow cells in suspension, able to bind different cell types, well tolerated in vivo, biodegradableEnabling technology. Proof of concept1. Non cellular tissue regeneration matrix – tissue filling2. Cellular – Grow cells in suspension; select stem cells for expansion & implantation

Major IP Estate in place, Fully Operative Team R&D collaboration agreements with TEVA & Major US Pharma Co.

The product: GMP produced Haptized-collagen sponge

TK Signal - Profile• Development and commercialization of targeted

EGFR radiopharmaceuticals for application in cancer diagnostics and cancer therapy using PET imaging.

• Radiopharmaceutical market estimated at $ 2 B at 2005 and growing at 10% per year.

• Key personnel - 2 world renowned cancer and imaging researchers from Hadassah and Hebrew U. (A. Levitzki, E. Mishani)

• Multi disciplinary team (chemists, radio- chemists, nuclear-engineers, biologists)

• Strong IP position (2 approved, 1 pending)• Feasibility demonstrated in vitro and in vivo• Wide collaboration metwork• Completed UK funding of $ 1.6 M

ThromboTech Ltd.ThromboTech Ltd.Novel Thrombolytic

Agents• Thrombotech has discovered the use of a specific hexa-

peptide having a sequence that is used for the docking of tPA to PAI-1.

• Thrombotech has demonstrated that utilizing this peptide in conjunction with tPA increases the safety profile of these thrombolytic therapeutics and offers key advantages: Expanded treatment window, PAI-1 resistance & Fibrin specificity.

• Market: All thrombolytic agents existing today cause severe side effects as they damage blood vessels, increasing internal hemorrhage. Presently, only 3% of the patients receive tPA after stroke due to the adverse side-effects. The annual targeted USA market for a thrombolytic product is over 3 million patients per year.

• IP: Wide claims covering the use of urokinase derived peptide for dissolving of blood clots.

• The peptide production is manufactured in GMP conditions, Tox. And pre-clinical testing to be completed during 2006.Initial clinical indications to be tested: Myocardial Infarction.

Vision – Treat autoimmune diseases by highly selective removal of the damaging antibodies from circulation

1st Product – Revolutionary treatment of Lupus (SLE) using the Lupusorb plasmapheresis immunoabsorption column

Status – Clinical studies to start within 4 months

Team –Scientific group led by leading authority in the field, Prof. Yaakov Naparstek

IP – Therapeutic and diagnostic patents issued

Business Model – Alliance with major US supplier of plasmapheresis equipment

Investment - $1 M to extend clinical studies

Systemic Lupus Erythematosus (SLE)US Prevalence 500K, Cost of SeverePatients $20K/yr, No specific drugMarket $500M

Vision –Autoimmune diseases will be treated with a new type of drug that activates anti-inflammatory agents to supplement or replace current blockbusters

1st Product – anti-peptide 6 monoclonal antibody for RA arthritis and diabetes

Status – Animal studies completed; awaiting production of humanized monoclonal antibody

Team –Scientific group led by leading authority in the field: Prof. Y. Naparstek

IP – Strong core patent on HSP65 peptides, antibodies and use in inflammatory diseases

Business Model – Out-licensing to pharma /biotechs after demonstration of efficacy

Investment - $5 M to produce humanized mAB

Rheumatoid Arthritis, affects 2.1M Americans, $5B/yr spent on antiarhritic drugs, Blockbuster inbibitors of anti-inflammatory agents, Enbrel, Remicade, Humira, reduce scores 50% in 50% of patients.

ProtabProtab Developing new therapies for Developing new therapies for

autoimmunityautoimmunity

Incure is developing a patent protected diagnostic kit based on PAR1-released peptide, for the detection and treatment of tumor metastatic spread in blood samples

PAR1 (Protease Activated Receptor 1- an oncogene) plays a central role in the malignant tumor invasion process

Initial indications to be explored: Breast, Ovary, Colon, Prostate

Metastatic cancers are particularly difficult to treat - Therapeutic intervention could be:

Too aggressive – deleterious side-effectsInsufficiently aggressive – no cure

Early detection of potential tumor invasion is critical for determining the appropriate treatment strategies and improving recovery prospects

Development status: In vitro assay using polyclonal antibodies – established, Optimization assay for peptide detection in patients – in progress, Collection of breast cancer patients blood samples (various stages) – in progress

InCure

KAHR Medical Ltd.KAHR Medical Ltd.PP14 Based Immuno-Therapeutic

Proteins• Essential functional features of PP14 : directly inhibits T cells, targets an early stage of T cell activation via a unique mechanism, binds to T cell surfaces in a carbohydrate-dependent fashion.• In- Vivo Results: Ectopically expressed PP14 inhibits the activation and proliferation of Human peripheral blood mononuclear cells (PBMC) in SCID mice.• KAHR is now positioned to move forward with preclinical studies on the use of PP14 to treat Psoriasis, Multiple Sclerosis, Rheumatoid arthritis, Organ Transplant Rejection and Graft-versus-Host Disease.• During pregnancy auto-immune diseases undergo remarkable remissions - KAHR has discovered this is probably due, at least in part, to the production of a unique immuno-regulatory protein - PP14• The value of biological drugs indicated for autoimmune diseases was roughly $6.8 billion in 2003 and is predicted to triple by 2008.• IP: KAHR’s IP covers the use of PP14 and its therapeutic derivatives for treatment of auto-immune diseases.

•

A Treatment Device For Recipients of Transplanted Organs and for Other Auto-

Immune Diseases Self material does not normally trigger an immune response due to a conditioning of the immune system. This conditioning is called tolerance. An important mechanism of creating tolerance is the sampling of apoptotic cells that die daily in the body. The anti-inflammatory properties of self apoptotic cells can be used in a variety of clinical conditions including in GVHD. The use of autologous apoptotic cells ensures a high safety profile. The repeated “pulses” of treatment maintain peripheral tolerance. Potential Indications: GVHD, Auto-immune Disorders, Inflammatory Conditions Milestones expected: Q1 2007: Completion of human in-vitro studies. Completion of validation of the final mode of delivery of autologous cells, Q3 2007: Phase I clinical trial Acute GVHD.

Tradition

• Biomed 2006 already indicated to us that a tradition has been established and that members of the international life science community cannot afford to not attend

Tradition

• Indeed we were proud to host official delegations from: Belgium, Canada, France, Germany, India, Ireland, Italy, Singapore, South Korea, Switzerland, The Netherlands, UK, USA

• along to visitors from: Australia, Austria, Brazil, Czech Republic, China, Denmark, Egypt, Greece, New Zealand, Nigeria, Senegal, Sierra Leone, Spain, Sweden, Taiwan, Turkey and Ukraine.

One-on-One Meetings

• During the three days of the event, we could sense the highly positive energy in the air and the best indication is that many one-on-one sessions took place between Israeli delegates and those from the international venture capital and production/sales industries.

BioTech

• The 2006 program already took into consideration the assimilation of biotech and medical device (Biomed – being our brand name) and in each of the sessions (cardiology, orthopedics, nerve-stimulation) the combination of the two disciplines has been emphasized.

BioTech

• Biomed 2007 will be a natural extension of the same approach of converging medical device, diagnostics and biotechnology.

• Just as a catalyst of attraction.

Highlights

• Stem Cell ResearchTogether with the Weizmann Institute of Science we will revisit the whole area of stem cell research including review of the basics, analysis of the IP / patent policy, trends in the industrialization process and convergence with medical device approaches

Highlights

• Biomarkers-a tool in personalized medicineA topic that was placed on the international agenda several years ago and needs to be addressed once more within the realms of Biomed 2007. Keynote speakers from industry and academic arena, will share with us their views on how to adopt modern technologies into a better design of therapeutics and their adjustment into patient special requirement (personalized medicine).

Highlights

• Medical DeviceThe program of this year will address the topic of monitoring and treatment of chronic diseases, mainly in areas of Cardiology, metabolic disorders and Nero stimulation.

Highlights

• BioBusiness: From a scientific discovery to a profitable industry-opportunities and hurdles.A series of panel discussions will address the crossroad and meeting site between tech-transfer, regulation, investment at various stages and marketing strategies.