Belén Garijo CEO Healthcare Luciano Rossetti Global Head of Research & Development, Biopharma Rehan Verjee Chief Marketing and Strategy Officer, Healthcare June 12, 2017 Biopharma R&D pipeline Update Complete portfolio supporting leadership in a potentially disruptive class DNA damage response (DDR) Genomic instability: a hallmark of late stage cancers 1 • DNA damage response (DDR) keeps genetic information intact • In many cancers DDR pathways are defected, leading to greater dependency on remaining functional DDR pathways • Preferentially inhibiting remaining DDR pathways can result in cancer cell death ("synthetic lethality") 26 1 Sources : O’Connor, Molecular Cell, 2015 | Benjamin et al., Current Drug Targets, 2010, 11, 1336-1340 2 "A multicenter phase I trial of the DNA-dependent protein kinase (DNA-PK) inhibitor M3814 in patients with solid tumors", Mark van Bussel, ASCO (Free ASCO Whitepaper) 2017 Acronyms: ATM: ataxia-telangiectasia mutated |ATR: ataxia telangiectasia and Rad3 | DNA-PK: DNA-dependent protein kinase | Amplifying cytotoxic effects of conventional and novel cancer treatments potentially bears combination potential 1. Inhibitor portfolio targets all three leading pathways of double stranded breaks – enabling unique synergies 2. ASCO (Free ASCO Whitepaper) 2017: leading DNA-PK-I (M3814) found safe and tolerable in a phase I study, with limited single-agent activity (20 % of patients with stable disease for at least 18 weeks) 2 3 Lead Optimization Pre-clinical Phase I Phase II Phase III 28 DNA-PK-i ATR-i ATM-i VX-970 VX-803 VX-984 M-3814 M-3541 Clinical program targets all three DDR pathways, in mono-and combination Acronyms: ATM: ataxia-telangiectasia mutated |ATR : ataxia telangiectasia and Rad3 | DNA-PK: DNA-dependent protein kinase | CT : Chemotherapy | RT: Radiotherapy | Note : timelines are event-driven and may change Phase IB expansion cohorts ongoing in combination with CT (TNBC, NSCLC, SCLC) Phase I dose escalation ongoing for mono-and combination therapy (with CT) Phase I dose escalation ongoing in combination with CT (licensed-in) Two Phase Ib /II proof-of-concept studies in combination with CT and RT ongoing Expected to enter clinic in 2017 DNA damage response (DDR) 3 29 DNA damage response (DDR) Broad combination potential across multiple mechanisms Combination with CT ATR DNA-PK ATM Combination with DDR Combination with ADC Combination with IO Monotherapy Combination with RT At least 50% of all cancer patients receive some type of RADIATION therapy (NCI 2016) At least 70% of all cancer patients receive some type of CHEMOTHERAPY (NCI 2016) Significant share of patients to be treated with CHECKPOINT INHIBITORS 4 3 30 Early stage strengthened – enabling late stage optionality across all TAs 1 Pipeline Immuno-Oncology Immunology Phase I Phase II Phase III Oncology New in pipeline Moved to next phase Maintained position BTK inhibitor RA sprifermin Osteoarthritis Avelumab RCC 1L 1 Tepotinib HCC Avelumab NSCLC 2L 2 Avelumab Gastric 1L MN 1 Avelumab Urothelial 1L MN 1 Avelumab Ovarian plat. res./ref Avelumab Ovarian 1L (Chemo) 1 BTK inhibitor SLE tepotinib NSCLC Avelumab Gastric 3L 3 Avelumab LA SCCHN Atacicept SLE Avelumab NSCLC 1L 1 Biosimilars Adalimumab biosimilar Chr. plaque Psoriasis R Registered (US) Abituzumab SSc-ILD Externalized p70S6K & Akt-i Solid tumors DNA-PK-i Solid tumors BRAF-I (Beigene) Solid tumors BTK inhibitor Hem. malignancies Avelumab Solid tumors Avelumab Hem. malignancies anti-PD-L1/TGF-b trap Solid tumors Avelumab MCC 1L Anti-IL-17 A/F Psoriasis Avelumab 5 Merkel cell (EU) R BTK inhibitor MS DNA-PK-I (VX-984) Solid tumors ATR-i 7 (VX-970) Solid tumors ATR-I (VX-803) Solid tumors Filing Cladribine Tablets RMS (EU) ATX-MS-1467 MS Avelumab + NHS IL 12 Solid tumors Avelumab+41BB/OX40 Solid tumors Avelumab comb.** DLBCL Terminated 2 Atacicept IgA Nephropathy Avelumab (mono/combo) Various ISTs 1 Since R&D Update call on June 20, 2016 | 2 Either terminated (ATX, BRAF-i) or divested (Biosimilars) | Acronyms: SLE = systemic lupus erythematosus, RRMS = relapse remitting multiple sclerosis, NSCLC = non-small cell lung cancer, HCC = hepatocellular carcinoma, STS = soft-tissue carcinoma, MCC = Merkel cell ca rcinoma, RA = rheumatoid arthritis, SCCHN = squamous cell cancer of the head and neck, SSC-ILD: Systemic sclerosis with interstitial lung disease | DLBCL: Diffuse Large B-cell Lymphoma

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