Programa Cooperación Farma-Biotech Jornada II: Oncología

Transcription

1 : A highly selective and efficient virus specifically designed to treat refractory tumors Barcelona, 13 de abril de 2011

2 Content 1. About VCN Biosciences 2. Our product: a) Innovative mechanisms of action b) IPR protection c) Differential features facing the market d) Current status of development: Preclinical Manufacturing Clinical Program 3. Our expectatives cooperation

3 WHAT s VCN BIOSCIENCES VCN Biosciences was created in 2009 as an spin-off from Virotherapy group at l ICO / IDIBELL with the aim of developing new agents for the treatment of cancer using the oncolytic adenovirus technologic platform. VCN Biosciences VCN s mission implies the valuation of new candidate viruses from its early identification and preclinical studies to the validation of its antitumoral efficacy in human patients during initial clinical trials (Phase I and II)

4 VCN Biosciences TEAM Current shareholders distribution: 100% private capital ENTERPRENEUR TEAM Strategic Consultancy BIOEMPREN SL (Mr. Jaume Amat) Scientific Advisory Board Dr. Jose Costa (Yale Univ., USA) Dr. Nick Lemoine (QMCR, UK) Dr. Ramon Salazar (ICO, Spain) Dr. Gabriel Capellà President Dr. Ramon Alemany Chief Scientific Officer Dr. Manel Cascalló Chief Executive Officer

5 VCN Biosciences TEAM Differential Scientific Value: - Internationally recognized scientifics in cancer virotherapy, molecular oncology, pancreatic cancer and pre-clinical models - inventors of more than 5 patents in adenovirus field - consultants in different biotech companies in the field and relevant regulatory committees (EMEA) - previous expertise in moving an oncolytic adenovirus to the clinic (ICOVIR-5 for melanoma treatment in a forthcoming Phase I clinical trial & Solid Enterpreneur Expertise: - Bioemprenedor XXI 2010 Award winner - SME (Micro, small or medium-sized Enterprise) qualification by EMA - Strong business formation (IESE) and strategic assessment by Bioemprèn (Jaume Amat),

6 VCN BIOSCIENCES PIPELINE Pipeline: - T1 technology ( WO 2008 / A2 ) - sub-licensed to ORCA Therapeutics (Holland) - participant in EUREKA AMBAssADOR project (Σ!4582) licensed-out of VCN - Hyaluronidase technology (WO 2010 / A1 ) Clinical candidate for the treatment of refractory tumors (i.e. pancreatic tumors)

7 VCN BUSINESS STRATEGIC MODEL ALLIANCES VCN Biosciences Technological platform (oncolytic viruses) for head&neck tumors for pancreatic cancer Phase I Phase II Contract research (i.e. Virotherapy group at ICO/IDIBELL) for additional tumors VCN-02 for XX cancer

8 VCN STRATEGIC ALLIANCES Technological platform (oncolytic viruses) for pancreatic cancer Phase I Phase II Contract research (i.e. Virotherapy group at ICO/IDIBELL) for additional tumors VCN-02 for XX cancer Innovative & powerful technology Commercial agreement with GenIBET (Portugal) as CMO for clinical batches of (EUREKA project ONCOVIR, Σ!4947) Strategic alliance for future product development (clinical / scientific) Biomedical & biotechnology Cluster of health care facilities

9 TECHNOLOGY Programa Cooperación Farma-Biotech Oncolytic adenoviruses = viruses which replication is restricted to tumor cells Normal cell: abortive replication Productive replication selective killing of tumor cells Oncolytic virus HYALURONIDASE Technology (expression of a matrix-degrading enzyme from virus genome) tumor cell Clinical candidate for the treatment of pancreatic tumors generation of thousand copies of itself (self-amplification effect) dissemination within tumor stroma

10 TECHNOLOGY Programa Cooperación Farma-Biotech : oncolytic adenovirus expressing HIALURONIDASE Adwt LITR E1a Fiber MLP L1 L2 L3 L4 L5 RITR (wild-type virus): ICOVIR-17: LITR E2F boxes E1a- 24 FiberRGD MLP L1 L2 L3 L4 L5 SA K pa RITR hialuronidase : LITR E2F boxes E1a- 24 FiberRGDK MLP L1 L2 L3 L4 L5 SA K pa RITR hialuronidase selectivity of replication in tumor cells biodistribution selectivity (tumor targeting) tumor potency (spread)

11 IPR PROTECTION on TECHNOLOGY Initial Submission to Spanish Office (Priority date): May 6 th, 2009 (IDIBELL (ICO) PCT / ES2010 / PCT protocol (May 2010) WO 2010 / A1 FREEDOM TO OPERATE FOR HAS BEEN STABLISHED AT EXPECTED PRODUCT APPROVAL (2019/2020) VCN proprietary technology (September 2010)

12 and ITS MARKET Pancreatic cancer - diagnosed at late stages - fast and systemic clinical course - resistant to chemotherapy - highly desmoplasic diagnostic 120,000 patients / year in main pharma makets 15-20% 80-85% eligible for surgery 15% 85% non-resectable tumor overall survival (OS): w/o treatment: 20 months with treatment: 22 months Chemotherapy 18,000 patients / year 33% 50% locally advanced disease overall survival (OS): w/o treatment : 3-4 months with treatment : 6-10 months Palliative Chemotherapy 102,000 patients / year metastatic disease overall survival (OS): w/o treatment : 2-3 months with treatment : 3-6 months - it represents the 4th most common cause of cancer-related death in developed countries although ranks only at 13th position by incidence (1.3 in 10,000 person in EU) - incidence = death cases associated to the disease (by year) - treatment costs are estimated in 11,000-15,000 / patient & year (1,320-1,800 M ) - up to 80% of treatments become palliative

13 and ITS MARKET Pancreatic cancer - diagnosed at late stages - fast and sytemic clinical course - resistant to chemotherapy - highly desmoplasic Differential characteristics of Classical chemotherapy Pancreatic tumor low selectivity: systemic side effects Selective killing of tumor cells effective dose diminishes with time generation of thousand copies of itself: selfamplification of the effect low penetrance due to high interstitial pressure dissemination within tumor stroma

14 TECHNOLOGY tumor cells ICOVIR-15: oncolytic virus without hyaluronidase ICOVIR-17: ICOVIR-15 SKMel28 expressing hyaluronidase NP18 : ICOVIR-17 with capsid modification ICOVIR-15, ICOVIR-17 or Single endovenous injection at virus/mice 100X Evaluation of intratumoral HA content by staining with biotinylated HABP ICOVIR-15 ICOVIR-17 CONFIDENCIAL ICOVIR-15 ICOVIR-17

15 TECHNOLOGY Programa Cooperación Farma-Biotech % tumor growth vs day 0 % tumor growth vs day 0 Days post-injection Days post-injection % tumor growth vs day 0 % tumor growth vs day 0 Days post-injection Days post-injection

16 COMPETENCE ANALYSIS Experimental treatments for pancreatic cancer Preclinical Phase I Phase II Phase III Approval increase side effects without improving survival alternative resistance mechanisms have been described in the clinics based in immune response stimulation (never observed in pancreas) - Abraxane - EndoTAG-1 - Triapine - TARCEVA - Cetuximab - Avastin - NEXAVAR - AMG OncoVex - Reolysin NEW CHEMOTHERAPEUTIC DRUGS TARGETED AGENTS (antibodies or specific inhibitors) OTHER ONCOLYTIC VIRUSES

17 DEVELOPMENT SCHEDULE ( ) PRE-CLINICAL + REGULATORY ASSESSMENT Regulatory Road-map Preclinical studies (VALTEC project) IMPD V.1 Preclinical Regulatory IMPD V.2 Approval Clinical Phase (2 assays) Production process definition Engineering Run release Clinical Batch release Stability testing of Clinical batch 2014 Regulatory CMC MANUFACTURING

18 PoC (Proof of concept) STUDIES In vitro cytotoxicity in tumoral cell lines IC 50 value (TU/cell) (in parenthesis fold-increase vs. )

19 TOXICOLOGICAL PROFILE of Toxicological profile after single systemic administration in Immunocompetent mice Balb-C i.v. (tail vein) vp virus Variation body weight Biochemistry (transaminases) Hematology MICE day 0 day 7 day 12 day 28 Tested viruses: - Adwt - ICOVIR-17 - % vs. Day 0 15,00 10,00 5,00 0, ,00-10,00-15,00 * * * * * Body weight variation * * * * * * * * * Ul/l 7000, , , , , , ,00 0,00 Day Concentració de transaminases ICOVIR17 Transaminases en sèrum 3000,00 # # # 2000,00 PBS * Adwt-RGD ICOVIR ,00 ICOVIR17-RGDK 0,00 AST AST (day dia 7) 7 AST (day dia 12) ALT (day dia 7) 7 ALT (day dia 12) Transaminases PBS Adwt *, p<0,05 with respect topbs #, p<0,05 with respect to AdwtRGD UI/l 7000, , , ,00 Cèl lules/ml AST (day 28) ALT (day 28) , , ,00 100,00 10,00 1,00 Lymphocytes Platelets White serie Monocytes Eosinophils Day 7 p.i * * * * * * *, p<0,05 with respect topbs PBS Adwt ICOVIR *, p<0,05 with respect topbs Days p.i. *, Neutrophils Lymphocytes Monocytes * Eosinophils Day 12 p.i. Neutrophils

20 TOXICOLOGICAL PROFILE of Toxicological profile after single systemic administration in Immunocompetent hamster SYRIAN Gold HAMSTER i.v. (cephalic vein) vp virus Variation body weight Biochemistry (transaminases) Hematology day 0 day 28 Tested viruses: - 30,0 25,0 20,0 15,0 10,0 5,0 0, ,0 Day p.i. Body weight variation *, p<0,05 with respect topbs UI/l PBS Transaminases PBS UI/l Platelets Day 3 p.i. Day 7 p.i. Day 28 p.i *, p<0,05 with respect topbs 50 cellsx10 6 /ml Day 3 p.i. Day 7 p.i. Day 28 p.i. cellsx10 6 /m PBS 50 PBS cellsx10 6 /m Day 3 Day 7 Day 28 AST 1 30 Day 3 Day 7 Day 28 ALT Cells/ml 20 Cells/ml Cells/ml Transaminases White serie 10 0 Lymphocytes Monocytes Eosinophils Neutrophils 10 0 Lymphocytes Monocytes Eosinophils Neutrophils 10 0 Lymphocytes Monocytes Eosinophils Neutrophils

21 as a PRODUCT Programa Cooperación Farma-Biotech as a pharmaceutical product - pharmaceutical form: sterile solution for injection - clinical batch production (under cgmp quality) Commercial agreement with GenIBET (Portugal) as CMO for the clinical batch of (EUREKA project ONCOVIR, Σ!4947)

22 PRODUCTION PROCESS for clinical batch

23 PRODUCTION PROCESS for clinical batch Quality controls & characterization: manufacturing

24 CLINICAL DEVELOPMENT of Preclinical + Regulatory Clinical Phase I intratumoral Clinical Phase I intravenous Clinical Phase II i.v Pancreas Clinical Phase II i.v. Other tumor target Phase III program Conditional Approval

25 CLINICAL DEVELOPMENT of PHASE I for Preliminary planning for phase I trials Intratumoural administration Patients with advanced solid tumours (refractory to Cx) amenable for direct injection and clinical measurement (HN, pancreas, melanoma, RCC, lung, CCR, breast ) Expanded cohort at the highest dose level enriched with head and neck and pancreas. Single dose+ follow-up of 4 months. Strategic aim: to obtain evidence of biological activity Intravenous administration Patients with advanced solid tumours (melanoma, RCC, lung, CCR, breast ). Expanded cohort at the highest dose enriched with pancreatic cancer patients. Single dose + follow-up of 4 months. Strategic aim: starting study for clinical program

26 ORPHAN DRUG DESIGNATION for in PANCREATIC CANCER INCENTIVES Market exclusivity Fee reduction or exemption Protocol Assistance by EMA EU-funded research

27 CONTACT INFORMATION Manel Cascalló, PhD. CEO Bioincubadora 1- BioPol H BioPol H L Hospitalet de Llobregat (Barcelona) -SPAIN Phone: Phone (2): mcascallo@vcnbiosciences.com