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20 May 2015 The Immuno-Oncology Company BATTLING CANCER WITH BISPECIFIC ANTIBODIES NON-CONFIDENTIAL COMPANY SNAPSHOT Bispecific Antibody Leader Blue-chip Investors Raised $ 60 M in VC funding Lead therapeutic: start of clinical trials in Feb 2015. Pipeline: 5 Immuno-Oncology therapeutics in clinical trials by Q2/18 Bispecific antibody-based, technology platform – partnership with ONO pharmaceutical HQ Utrecht, The Netherlands - 38 employees 20 May 2015 NON-CONFIDENTIAL Adapted from Bispecifics Antibody Therapeutics Market (2014 Roots Analysis) CURRENT PIPELINE – Q2 2015 Drug Targets disease MCLA128 HER2 x HER3 Solid tumors MCLA117 CD3 x CLEC12A AML MCLA122 EGFR x HER3 Solid tumors MCLA134 PD1 x TIM-3 Solid tumors MCLAxxx iMOD x iMOD. Solid tumors MCLAyyy Cancer stem cell targets Solid tumors Not disclosed AID AID = autoimmune disease 20 May 2015 NON-CONFIDENTIAL Discovery IND enabling Phase I/II for outlicensing Partnered ONO PHARMACEUTICAL PIPELINE Q1 2015 → Q2 2018 mezz proceeds Drug Targets disease MCLA-128 HER2 x HER3 Solid tumors MCLA-117 CD3 x CLEC12A AML 2015 IPO proceeds 2016 2017 2018 Single agent Combination Single agent Combination MCLA-122 EGFR x HER3 Solid tumors MCLA-134 PD1/PD-L1 x YYY Solid tumors MCLA-xxx iMOD x iMOD Solid tumors MCLA-yyy cancer stem cell target combinations Solid tumors Discovery Tox batch Mfg 20 May 2015 for outlicensing Clinical batch Mfg & non clinical safety studies Phase I/II NON-CONFIDENTIAL optional STRATEGY – WHY BISPECIFIC ANTIBODIES Novel mode of action Large target combination space Improved specificity/ targeting Functional screening Attractive pharmacoeconomics Developability 20 May 2015 NON-CONFIDENTIAL MISSION & OVERALL STRATEGY Develop differentiating therapeutics to cure cancer patients Bispecific antibodies (Biclonics®) that kill tumor cells and recruit the immune system for prolonged survival revive T cells to kill kill the tumor (stem) cell CD28 CTLA-4 OX40 Tumor cell PD-1 TIM-3 GITR CD137 T cell LAG-3 CD27 20 May 2015 NON-CONFIDENTIAL T cell Tumor cell BTLA HVEM ADCC-enhanced activate/recruite T cells to kill VISTA ? ? Fc-silenced DISCOVERY AND DEVELOPMENT OF BICLONICS® Human antibodies phage display MeMo® transgenic mouse Common light chain (cLC) Biclonics®: full length IgG human bispecific antibodies Fc region engineering CH3: > 99% pure Biclonics® CH2: Fc-silencing Low fucosylation: enhanced ADCC CHO cLC Stability like IgG cLC Fcsilencing ADCCenhanced normal pK in mice/cyno behaviour like IgG in antibody stress tests 20 May 2015 Manufacturability stability: > 60 passages yield: > 1 g/L scalability: 2000 L formulation: standard Dependable IgG format with true platform characteristics NON-CONFIDENTIAL ® PRODUCT STRATEGY - ONCOLOGY Receptor tyrosine kinases 20 May 2015 Cancer stem cells Target combinations of growth factor receptors for ADCC-enhanced tumor cell killing Kill the cells that cause relapse and are resistent to most therapies Activate T cells irrespecive of specificity to selectively kill tumor cells Modulate immune checkpoint molecules to unleash tumorspecific T cells NON-CONFIDENTIAL T cell retargeting Immunemodulation BICLONICS® DISCOVERY PROCESS - OVERVIEW Steps in Biclonics® discovery: • generation of high quality panels of common light chain human monoclonal antibodies • functional screening of > 1000 Biclonics® for lead panel identification • final lead selection after multiple in vitro assays and in vivo animal models Generation of large panels of human antibodies 1. Target pair for immunization and phage selections 9-12 months 2. Production of ~1000 different Biclonics® for functional screens 3. Functional screening in cell-based assays Lead Biclonics® selection 1 June 2015 6/1/2015 CONFIDENTIAL 9 DISCOVERY STRATEGY – FUNCTIONAL SCREENING Functional screening of thousands of different Biclonics® supports the identification of differentiating therapeutics Cell growth Functional screen of 750 Biclonics® for inhibition/ stimulation of cancer cell growth (EGFR x HER3) 20 inhibition % normalized cell growth stimulation 0 -20 -40 BxPC3 ligand independent assay Best in class anti-cancer drug BxPC3 EGF + HRG dependent assay -60 Biclonics® with superior inhibition of cell growth 20 May 2015 NON-CONFIDENTIAL without heregulin heregulin 20 May 2015 MCLA-128 (HER2 x HER3) KEY PRECLINICAL DATA NON-CONFIDENTIAL MCLA-128 FOR TARGETED THERAPY IN SOLID TUMORS MCLA-128: HER2 x HER3 Biclonics® for HER2+ solid tumors High unmet medical need designed to overcome inherent and acquired resistance to HER2-targeted therapies Attractive clinical development phase I/II design is focused on biomarker defined patient populations and yields early safety and efficacy data Unique mode of action dual action: blocks HER2/HER3-driven growth and escape; enhanced ADCC for immune effector cell engagement First-in-Human Study: Tumor cell 20 May 2015 NK cell NON-CONFIDENTIAL first patient dosed on February 03, 2015 MCLA-128: UNIQUE MODE OF ACTION In contrast to trastuzumab + pertuzumab and HER3 monoclonal antibodies, MCLA-128 completely inhibits heregulin-driven cancer cell growth. N87 HER2-amplified cell line stimulated with heregulin SKBR-3 cell line stimulated with heregulin 4 3 2 0 20 May 2015 NON-CONFIDENTIAL Akt thr308 1 Akt ser473 LJM 716 heregulin T+P MCLA-128 Erk1/2 AMG-888 MM 121 Fold change in phosphorylation % heregulin driven growth MCLA-128: UNIQUE MODE OF ACTION In contrast to trastuzumab + pertuzumab, MCLA-128 inhibits the growth of cell lines resistant to HER-2 targeted therapies • JIMT-1 is an aggressive breast cancer line resistant to lapatinib, trastuzumab + pertuzumab and T-DM1). MCLA-128: > 80% reduction in tumor size MCLA-128: > 50% survival after 60 days 100 vehicle Vehicle MCLA-128 MCLA-128 TTrastuzumab +P + Pertuzumab 100 Percent survival Tumor volume (mm3) 1000 50 vehicle MCLA-128 T+P 0 0 20 40 60 Days mice dosed 4qw @ 2.5 mg/kg 20 May 2015 NON-CONFIDENTIAL 0 20 40 60 Days 20 May 2015 MCLA-117 (CD3 x CLEC12A) KEY FACTS – DATA - DIFFERENTIATION NON-CONFIDENTIAL BICLONIC® ENGAGERS FOR IMMUNOTHERAPY MCLA-117: CD3 x CLEC12A Biclonics® for AML High unmet medical need little change in standard treatment in 40 years; no cure available; increasing patient population Rapid iv administration and superior to antibody fragments; eligible for Orphan IgG-like dosing schedules; Drug Designation ( EU/US); high chance of breakattractive clinical development through designation (FDA); Unique mode of action T cell retargeting T cells via novel AML target with restricted tissue expression; kills tumor (stem) cells AML blast CD3 First-in-Human Study: Q1, 2016 Tumor (stem) cell 20 May 2015 NON-CONFIDENTIAL CLEC12A – RESTRICTED TISSUE EXPRESSION a myeloid differentiation antigen only expressed on certain blood cells present on 95% of newly diagnosed and relapsed AML selective expression on AML tumor stem cells • not present on normal hematopoetic stem cells • not present on red blood cell and platelet precursor cells CLEC12A expression on AML stem cells % CLEC12A CD34+CD38- cells 100 % 7 5 5 0 2 5 0 AML BM 20 May 2015 NON-CONFIDENTIAL Normal BM rB M MCLA-117 EFFICIENTLY MEDIATES AML TUMOR CELL KILLING Recruits and activates T cells to lyse CLEC12A -expressing autologous AML tumor cells. MCLA-117 induces antigen-specific T cell activation and proliferation TotalTTcells cells Total CD4 T cells CD8 TCD8 CD4 T cells cells T cells Ctrl IgG Ctrl IgG T cell CD3 CD3 IgG IgG AML blast CD3xTT TT x CD3 ctrl Biclonics® Ctrl Biclonics® counts MCLA-117 MCLA-117 ® Biclonics Biclonics® CFSE 20 May 2015 NON-CONFIDENTIAL CSFE MCLA-117 EFFICACY IN PRIMARY AML MATERIALS (I) Specific and efficient lysis of a patient’s AML tumor cells by low numbers of T cells present in primary samples T cell population expands as a result of MCLA-117 Day 10 ctrl Biclonics® Day 0 Day 10 MCLA-117 81% 93% 1% 16% CD34 CD34 5% CD3 CD3 T cell expansion CLEC12A Isotype Tumor cell killing CLEC12A expression on AML blasts 20 May 2015 NON-CONFIDENTIAL 96% 20 May 2015 Biclonics® for immunomodulation Overall survival UNCOVERING THE RIGHT TARGET COMBINATIONS FOR DIFFERENTIATING THERAPEUTICS control standard of care immunotherapy Immunotherapy combinations ‘Lifting the curve’ Time NON-CONFIDENTIAL Improving survival of cancer patients Breakthrough of the Year 2013 BICLONICS® IN CANCER IMMUNOTHERAPY What target combination will trump? • increase frequency and/or duration of responses in patients • manageable toxicity (autoimmunity) Merus - three different approaches based on Biclonics®: • block two checkpoint inhibitory pathways • block a checkpoint inhibitory pathway and provide a costimulatory signal • target an overexpressed signalling receptor & an immunomodulatory pathway OX40 PD-1 CD28 TIM-3 GITR CTLA-4 T cell CD137 LAG-3 CD27 BTLA HVEM agonistic 20 May 2015 PD-1 x OX-40 VISTA ? NON-CONFIDENTIAL ? blocking PD-1 x TIM-3 BISPECIFIC - MONOVALENCY dual targeting of 2 antigens on the same cell leads to improved target selectivity over normal tissues • that express only one target or express low levels of targets (same cell) • over-expression of a tumor target may direct bispecific to the tumor environment favorable toxicity profile compared to a combination of antibodies ?? combination A B overexpression tumor + + normal + - Tumor cell 20 May 2015 Normal cell NON-CONFIDENTIAL A B tumor +++ + normal + + Tumor cell Normal cell targeting A B tumor +++ + normal + + Tumor cell T cell A UNIQUE MODULAR DISCOVERY STRATEGY Antibody panels are combined in the Biclonics® format for functional screening • antibody panels for 6 IMOD targets generated and 4 more planned for 2015 • screen in functional assays for differentiating activities of Biclonics ongoing with current focus on PD-1 and PD-L1 centric approaches (one arm = PD-1 or PD-L1) Functional screens PD-1 centric Reporter cell line PD-L1 centric Exhausted T cells (HIV, Miha) TIM-3 AAA EGFR ZZ BBB CCC ZZ ZZ TILS Lead 20 May 2015 NON-CONFIDENTIAL iMOD targets RTK targets HIGHLIGHTS Unique technology suite • human bispecific antibodies based on the proven IgG format • high throughput functional screening for the identification of bispecific antibodies with unique functional properties • manufactured using industry standard processes • predictable in vivo behavior associated with IgG format A pipeline of differentiating therapeutics in oncology • modes of action that can not be achieved with conventional therapeutic antibodies • recruitment of the immune system for unprecedented tumor cell killing An extremely attractive investment opportunity 20 May 2015 NON-CONFIDENTIAL T cell AML blast Tumor cell 20 May 2015 Thank you for your attention TON LOGTENBERG CEO NON-CONFIDENTIAL