From GENES to INNOVATIVE ONCOLOGY

Luck!!!Luck!!! ~38 mln country with high level of genetic homogeneity ~38 mln country with high level of genetic homogeneity PolandPoland

BRCA1 FOUNDER MUTATIONS IN POLAND GÓRSKI B. ET AL. GÓRSKI B. ET AL. PATENT NO P PATENT NO P MULTIPLEX PCR - 50 MULTIPLEX PCR - 50 GÓRSKI B. ET AL. GÓRSKI B. ET AL. PATENT NO P PATENT NO P MULTIPLEX PCR - 50 MULTIPLEX PCR - 50

BRCA1 – REGISTRY – SZCZECIN – POLAND >4739 CARRIERS THE LARGEST REGISTRY IN THE WORLD Szczecin May 11, 2009

Poland – limited number of founder / recurrent mutations in other cancer susceptibility genes NBS1, NBS1, NOD2, NOD2, CHEK2, CHEK2, MSH2, MSH2, MLH1, MLH1, APC. APC. NBS1, NBS1, NOD2, NOD2, CHEK2, CHEK2, MSH2, MSH2, MLH1, MLH1, APC. APC.

PENETRANCE AND PROPORTION OF CANCERS 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 0%20%40%60%80%100% PENETRANCE PROPORTION

Genetic contribution to all cancers: Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology Genetic contribution to all cancers: Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology Lubiński J. et al. Breast Can Res Treat 15 April 2008 Patent US61/069, Lubiński J. et al. Breast Can Res Treat 15 April 2008 Patent US61/069,

ConclusionConclusion At present, the major significance of the current findings is the proof of principle that there is no cancer without a genetic component. At present, the major significance of the current findings is the proof of principle that there is no cancer without a genetic component. DNA analysis will be the initial starting point for prevention, surveillance and treatment schemes for all adults. DNA analysis will be the initial starting point for prevention, surveillance and treatment schemes for all adults. At present, the major significance of the current findings is the proof of principle that there is no cancer without a genetic component. At present, the major significance of the current findings is the proof of principle that there is no cancer without a genetic component. DNA analysis will be the initial starting point for prevention, surveillance and treatment schemes for all adults. DNA analysis will be the initial starting point for prevention, surveillance and treatment schemes for all adults.

BRCA1 PROPHYLACTICS Sodium selenite – clinical trial Sodium selenite – clinical trial 1343 BRCA1 carriers 2.9 yrs supplementation Decoding –

New cases of cancer in the study Lubiński J. et al. The Lancet Oncology 2009 (under review)

Hazard ratios associated with selenium supplementation for various cancers Lubiński J. et al. The Lancet Oncology 2009 (under review)

Cumulative risk of cancer (all types) among selenium women randomised to selenium or placebo Lubiński J. et al. The Lancet Oncology 2009 (under review)

Proportion of BRCA1 mutation carriers affected by breast/ovarian cancers depending on selenium concentration in peripheral blood Lubiński J. et al. Patent application 2009 (pending)

Se concentration in the blood is the strong marker of cancer risk for BRCA1 carriers Se concentration in the blood is the strong marker of cancer risk for BRCA1 carriers PLACEBOPLACEBO <50 169/ / /18 μg/l p = ; OR = 6.4; CI – 2.1 – 19.4 Lubiński J. et al. Patent application 2009 (pending)

Genotypes associated with sensitivity to Se? 6 candidate genes (13 variants) involved in Se metabolism

Gene X

BRCA1 carriers should consider the options of: BRCA1 carriers should consider the options of: a)Supplementation with Sel-BRCA1 ® if they have X1 genotype b)Lowering of Se level (diet, pharmaceuticals) if they are X2 and Se level is above 50 μg/l BRCA1 carriers should consider the options of: BRCA1 carriers should consider the options of: a)Supplementation with Sel-BRCA1 ® if they have X1 genotype b)Lowering of Se level (diet, pharmaceuticals) if they are X2 and Se level is above 50 μg/l CONCLUSIONCONCLUSION

PROSTATE CANCER RISK DNA testing 1 prostate cancer among relatives + 1 prostate cancer among relatives + CHEK 2, NBS 1 or BRCA 1 (C61G, 4153 delA) CHEK 2, NBS 1 or BRCA 1 (C61G, 4153 delA) ~10× increased risk ~10× increased risk PSA, saturation biopsies PSA, saturation biopsies 1 prostate cancer among relatives + 1 prostate cancer among relatives + CHEK 2, NBS 1 or BRCA 1 (C61G, 4153 delA) CHEK 2, NBS 1 or BRCA 1 (C61G, 4153 delA) ~10× increased risk ~10× increased risk PSA, saturation biopsies PSA, saturation biopsies

Breast cancers with BRCA1 Treatment – Neo-Adjuvant therapy Byrski T et al.: Br Ca Res Treat 2007

BRCA1 breast cancer cell lines BRCA1 breast cancer cell lines -resistance to taxans -sensitivity to cis-platinum BRCA1 breast cancer cell lines BRCA1 breast cancer cell lines -resistance to taxans -sensitivity to cis-platinum TREATMENTTREATMENT

Response to treatment

Numbers of patients treated with, and responding to different chemotherapy regimens Byrski T. et al. J Clin Oncol 2009 (accepted)

Prophylactic adnexectomy Prophylactic adnexectomy Tamoxifen Tamoxifen Chemotherapy Chemotherapy Prophylactic adnexectomy Prophylactic adnexectomy Tamoxifen Tamoxifen Chemotherapy Chemotherapy DIFFERENCES IN TREATMENT OF BRCA1 BREAST CANCERS

FURTHER INVESTIGATIONS Monotherapy with cis-platinum of BRCA-1 dependant: Monotherapy with cis-platinum of BRCA-1 dependant: 1. Disseminated breast cancers 2. Cancers of other sites Monotherapy with cis-platinum of BRCA-1 dependant: Monotherapy with cis-platinum of BRCA-1 dependant: 1. Disseminated breast cancers 2. Cancers of other sites

CHEMOTHERAPYCHEMOTHERAPY Known drugs but selected for sub-groups of patients !!! Known drugs but selected for sub-groups of patients !!! New drugs created against constitutional changes !!! New drugs created against constitutional changes !!! Known drugs but selected for sub-groups of patients !!! Known drugs but selected for sub-groups of patients !!! New drugs created against constitutional changes !!! New drugs created against constitutional changes !!!

ADVANTAGESADVANTAGES Cancer bio-bank probably the largest in the world with biological samples and clinical data from > cancer patients, relatives and controls. Cancer bio-bank probably the largest in the world with biological samples and clinical data from > cancer patients, relatives and controls. Exclusive access basing on agreement with its owner – IHCC, PMU, Szczecin Poland Exclusive access basing on agreement with its owner – IHCC, PMU, Szczecin Poland Cancer bio-bank probably the largest in the world with biological samples and clinical data from > cancer patients, relatives and controls. Cancer bio-bank probably the largest in the world with biological samples and clinical data from > cancer patients, relatives and controls. Exclusive access basing on agreement with its owner – IHCC, PMU, Szczecin Poland Exclusive access basing on agreement with its owner – IHCC, PMU, Szczecin Poland

ADVANTAGESADVANTAGES Very unique system for scientific progress at IHCC on elaboration of new: diagnostic genetic tests, supplements for cancer prevention, treatment protocols, drugs Very unique system for scientific progress at IHCC on elaboration of new: diagnostic genetic tests, supplements for cancer prevention, treatment protocols, drugs Homogenous Polish population – very low cost of genetic studies Homogenous Polish population – very low cost of genetic studies Infrastructure of IHCC Infrastructure of IHCC Very unique system for scientific progress at IHCC on elaboration of new: diagnostic genetic tests, supplements for cancer prevention, treatment protocols, drugs Very unique system for scientific progress at IHCC on elaboration of new: diagnostic genetic tests, supplements for cancer prevention, treatment protocols, drugs Homogenous Polish population – very low cost of genetic studies Homogenous Polish population – very low cost of genetic studies Infrastructure of IHCC Infrastructure of IHCC

LATESTS ACHIEVEMENTS 5 signed agreements on clinical trials 5 signed agreements on clinical trials 5 approved international patents 5 approved international patents realisation of research project financed by Polish Ministry of Science (60%) – from October 2008 realisation of research project financed by Polish Ministry of Science (60%) – from October 2008 large investments in R&D structure – European projects large investments in R&D structure – European projects selling of counselling/DNA tests via Internet selling of counselling/DNA tests via Internet 5 signed agreements on clinical trials 5 signed agreements on clinical trials 5 approved international patents 5 approved international patents realisation of research project financed by Polish Ministry of Science (60%) – from October 2008 realisation of research project financed by Polish Ministry of Science (60%) – from October 2008 large investments in R&D structure – European projects large investments in R&D structure – European projects selling of counselling/DNA tests via Internet selling of counselling/DNA tests via Internet

READ GENE Stock exchange Warszawa – New Connect: Stock exchange Warszawa – New Connect: PLN PLN ,35 PLN ,35 PLN Stock exchange Warszawa – New Connect: Stock exchange Warszawa – New Connect: PLN PLN ,35 PLN ,35 PLN 61% 61%

PLANS FOR 2009 Income: ~ PLN Income: ~ PLN Profit: ~ PLN Profit: ~ PLN Income: ~ PLN Income: ~ PLN Profit: ~ PLN Profit: ~ PLN

PLANS FOR 2009 Major investment: Construction of R&D Read-Gene centre with laboratories (diagnostics, research) outpatient and chemotherapy clinics Construction of R&D Read-Gene centre with laboratories (diagnostics, research) outpatient and chemotherapy clinics PLN PLN 60% - structural funds – Innovative Economy Operational Programme 60% - structural funds – Innovative Economy Operational Programme Major investment: Construction of R&D Read-Gene centre with laboratories (diagnostics, research) outpatient and chemotherapy clinics Construction of R&D Read-Gene centre with laboratories (diagnostics, research) outpatient and chemotherapy clinics PLN PLN 60% - structural funds – Innovative Economy Operational Programme 60% - structural funds – Innovative Economy Operational Programme

Main task: global leadership in cancer chemoprevention READ GENE SA

MAJOR GOALS 5-10 y: PROFIT Clinical trials DNA testing Network of outpatient clinics Chemoprevention main goal TOTAL: > EUR per/year

Welcome for collaboration…

Welcome for collaboration Welcome for collaboration Welcome for collaboration Welcome for collaboration READ-GENEREAD-GENE Read-Gene SA, 2008

Jaki wpływ ma patent na polską innowacyjną gospodarkę? A jaki ma wpływ innowacyjność w Państwa przedsiębiorstwie ? Fundamentalny jest to najlepsza forma uwiarygodnienia innowacyjności produktu Fundamentalny jest to najlepsza forma uwiarygodnienia innowacyjności produktu

Jaki wpływ ma patent na Państwa działalność – rola i znaczenie ochrony własności intelektualnej w Państwa działalności ? Fundamentalny testy DNA, farmaceutyki muszą być zabezpieczone patentami Fundamentalny testy DNA, farmaceutyki muszą być zabezpieczone patentami

Ocena skuteczności, efektywności i zasadności prowadzonej polityki innowacyjnej w odniesieniu do patentów Programy: Min. Nauki, PARP Programy: Min. Nauki, PARP Bardzo duże ograniczenia Bardzo duże ograniczenia Np. aplikacje 2x w roku Np. aplikacje 2x w roku Brak pokrycia kosztów postępowania już rozpoczętego Brak pokrycia kosztów postępowania już rozpoczętego Zbyt duży udział własny Zbyt duży udział własny Brak systemu Brak systemu Programy: Min. Nauki, PARP Programy: Min. Nauki, PARP Bardzo duże ograniczenia Bardzo duże ograniczenia Np. aplikacje 2x w roku Np. aplikacje 2x w roku Brak pokrycia kosztów postępowania już rozpoczętego Brak pokrycia kosztów postępowania już rozpoczętego Zbyt duży udział własny Zbyt duży udział własny Brak systemu Brak systemu

Ocena skuteczności, efektywności i zasadności prowadzonej polityki innowacyjnej w odniesieniu do patentów Brak systemu Brak systemu Innowacje w fazie patentowania i początkowych prac przed szeroką komercjalizacją muszą być realizowane przez badaczy (nie przedsiębiorców) i dlatego wymagają wsparcia państwa Innowacje w fazie patentowania i początkowych prac przed szeroką komercjalizacją muszą być realizowane przez badaczy (nie przedsiębiorców) i dlatego wymagają wsparcia państwa Brak systemu Brak systemu Innowacje w fazie patentowania i początkowych prac przed szeroką komercjalizacją muszą być realizowane przez badaczy (nie przedsiębiorców) i dlatego wymagają wsparcia państwa Innowacje w fazie patentowania i początkowych prac przed szeroką komercjalizacją muszą być realizowane przez badaczy (nie przedsiębiorców) i dlatego wymagają wsparcia państwa

Jakie korzyści niesie za sobą patent? Straty, czy korzyści ? Jakie korzyści niesie za sobą patent? Straty, czy korzyści ? tylko korzyści tylko korzyści odkryć, których ujawnienie może przynieść straty nie patentujemy odkryć, których ujawnienie może przynieść straty nie patentujemy tylko korzyści tylko korzyści odkryć, których ujawnienie może przynieść straty nie patentujemy odkryć, których ujawnienie może przynieść straty nie patentujemy