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Translational Oncology: How to Better Transform Targets Into Relevant Drugs for Patients

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Translational Oncology: How to Better Transform Targets Into Relevant Drugs for Patients Translational Oncology: How to Better Transform Targets into Relevant Drugs for Patients March 4 – 5, 2014 Conrad New York Translational Oncology: How to Better Transform Targets into Relevant Drugs for Patients Moderators: • Jeffrey M. Bockman, PhD, VP, Defined Health • Mike Rice, MS, MBA, Senior Consultant, Defined Health Panelists: • Joseph Beechem, PhD, SVP, Research and Development, NanoString Technologies • Pamela Carroll, PhD, VP, Oncology, Innovation Center in Boston, Janssen Research & Development • Rajesh Chopra, MD, PhD, Corporate VP, Translational and Early Drug Development, Celgene Corporation • Victoria Richon, PhD, VP and Head of Cancer Research, Discovery and Early Development, Sanofi • Spiro G. Rombotis, President & CEO, Cyclacel Pharmaceuticals, Inc. Cancer Progress Conference by Defined Health 2 Conrad NY, March 4 – 5, 2014 Key Topics Have We Reduced This to Practice, Is There a State of the Art? • Role of academia and industry – Business models – Industry, government initiatives • Focus on disease biology • Moving beyond kinases, targeting final common pathways • Model systems predictive of clinical activity • Biomarkers, biomarkers, biomarkers • Phase I efficacy, Chabner’s Phase I approval trials – “Experiment in the clinic” Cancer Progress Conference by Defined Health 3 Conrad NY, March 4 – 5, 2014 Sapacitabine oral capsules • Single strand DNA breaks (CH2)14CH3 • G2/M accumulation HN O N • Disrupts HR-repair (Plunkett et al) HO N O • Ph 3 frontline AML, Ph 2 in MDS after O NC frontline failure, Ph 1 solid tumors HO H Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 4 Concomitant gBRCA deficiency & CDK inhibition may be particularly lethal to cancer cells * * Source: Shapiro et al, AACR Proceedings, 2013, LB-202. Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 5 Sapacitabine RECIST Evaluable gBRCA Carriers * * Source: Shapiro et al, AACR Proceedings, 2013, LB-202. Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 6 2013 AACR Sapacitabine Phase 1 Best Responses * Best Total Cancer Prior Treatment Response cycles gBRCA mutation carriers (n=16) (* PARP inhibitor naïve gBRCA mutation carriers) Breast* PR adriamycin, cyclophosphamide, paclitaxel, cisplatin >29 Ovary* SD paclitaxel, carboplatin, gemcitabine 21 Ovary* PR paclitaxel, carboplatin, gemcitabine, topotecan, iniparib >16 Breast* PR adriamycin, Cytoxan, paclitaxel, carboplatin >14 tamoxifen, raloxifen, anastrozole, adriamycin, Cytoxan, Breast* SD 7 paclitaxel, carboplatin, navelbine Pancreas* PR gemcitabine, 5-FU, oxaliplatin 7 Others (n=22) Uterine leiomyosarcoma SD gemcitabine, flavopiridol 9 Sigmoid colon SD 5-FU, folfox, irinotecan, cetuximab, bevacizumab 7 Non-small cell lung paclitaxel, carboplatin, pemetrexed, navelbine, SD 6 (poorly differentiated) erlotinib, cetuximab Nasopharyngeal docetaxel, paclitaxel, cisplatin, carboplatin, 5-FU, SD 6 (squamous) pemetrexed, cetuximab, SCH727965 doxorubicin, ifosfamide, dacarbazine, vinorelbine, LE sarcoma SD 4 trabectedin, ALB-109564, Ro4929097, PF-04554878 Pancreas SD folfox, gemcitabine, erlotinib, Abraxane, 5-FU 4 * By investigator assessment. Source: Shapiro et al, AACR Proceedings, 2013, LB-202. Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 7 Sapacitabine oral capsules • Single strand DNA breaks (CH2)14CH3 • G2/M accumulation HN O N • Disrupts HR-repair (Plunkett et al) HO N O • Ph 3 frontline AML, Ph 2 in MDS after O NC frontline failure, Ph 1 solid tumors HO H Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 8 Concomitant gBRCA deficiency & CDK inhibition may be particularly lethal to cancer cells * * Source: Shapiro et al, AACR Proceedings, 2013, LB-202. Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 9 Sapacitabine RECIST Evaluable gBRCA Carriers * * Source: Shapiro et al, AACR Proceedings, 2013, LB-202. Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 10 2013 AACR Sapacitabine Phase 1 Best Responses * Best Total Cancer Prior Treatment Response cycles gBRCA mutation carriers (n=16) (* PARP inhibitor naïve gBRCA mutation carriers) Breast* PR adriamycin, cyclophosphamide, paclitaxel, cisplatin >29 Ovary* SD paclitaxel, carboplatin, gemcitabine 21 Ovary* PR paclitaxel, carboplatin, gemcitabine, topotecan, iniparib >16 Breast* PR adriamycin, Cytoxan, paclitaxel, carboplatin >14 tamoxifen, raloxifen, anastrozole, adriamycin, Cytoxan, Breast* SD 7 paclitaxel, carboplatin, navelbine Pancreas* PR gemcitabine, 5-FU, oxaliplatin 7 Others (n=22) Uterine leiomyosarcoma SD gemcitabine, flavopiridol 9 Sigmoid colon SD 5-FU, folfox, irinotecan, cetuximab, bevacizumab 7 Non-small cell lung paclitaxel, carboplatin, pemetrexed, navelbine, SD 6 (poorly differentiated) erlotinib, cetuximab Nasopharyngeal docetaxel, paclitaxel, cisplatin, carboplatin, 5-FU, SD 6 (squamous) pemetrexed, cetuximab, SCH727965 doxorubicin, ifosfamide, dacarbazine, vinorelbine, LE sarcoma SD 4 trabectedin, ALB-109564, Ro4929097, PF-04554878 Pancreas SD folfox, gemcitabine, erlotinib, Abraxane, 5-FU 4 * By investigator assessment. Source: Shapiro et al, AACR Proceedings, 2013, LB-202. Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 11 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 12 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 13 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 14 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 15 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 16 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 17 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 18 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 19 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 20 Cancer Progress Conference by Defined Health Conrad NY, March 4 – 5, 2014 21 .
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