Immuno-Oncology. Axel Hoos, MD, PhD Senior Vice President, Oncology R&D. February 24, 2016

Transcription

1 Immuno-Oncology Axel Hoos, MD, PhD Senior Vice President, Oncology R&D February 24, 216

2 GSK Pipeline Oncology R&D strategy Focusing on 3 areas fundamental to oncology Cancer Epigenetics Long-Term Survival & Cures Reprogram Cancer Cells Immuno-Oncology Stimulate Anti-Tumour Immunity First in Class Medicines & Combination Therapy Cancer Stem Cells & Targeted Therapies 2

3 3 Generations of therapies Generation 1 Generation 2 YERVOY ipilimumab (CTLA-4) KEYTRUDA pembrolizumab (PD-1) Anti-PD-L1 Generation 3 Multiple therapies under development PROVENGE sipuleucel-t (Cell Therapy) Key Approved Under development BLINCYTO blinatumomab (BITE) OPDIVO nivolumab (PD-1) IMLYGIC T-Vec (Oncolytic Virus) CAR-Ts 3

4 Main trends SOC replacements Elimination of chemotherapy from SOC regimens Immune profiling Patient selection to predict response New technologies Expansion of the toolbox 216 CURE Substantial survival improvements Across wide populations Complex combinations Maximise efficacy Improved endpoints Accelerated development 4

5 3 rd Generation opportunities Spectrum of immuno-oncology modalities T-Cell Immunity Adaptive Immunity B-Cell Immunity Innate Immunity Cytokines Cellular Therapies - NK Cells Cancer Vaccines T-cell Checkpoint Modulators Checkpoint Modulators Connector Bi-specific Abs - Approved therapies Dual-specific Abs Small Molecules Oncolytic Viruses Adjuvants 5

6 3 rd Generation opportunities GSK s multi-modality pipeline T-Cell Immunity Adaptive Immunity B-Cell Immunity Innate Immunity Cytokines Cellular Therapies - NK Cells* Cancer Vaccines T-cell Checkpoint Modulators Checkpoint Modulators Connector Bi-specific Abs - GSK Pipeline * in planning Dual-specific Abs Small Molecules Oncolytic Viruses Adjuvants 6

7 3 rd Generation leadership Innovation across novel targets, modalities and combinations (5 in the clinic) Modality Program Mechanism Pre-clinical Phase 1 Phase 2 GSK OX4 agonist Solid Tumours, Heme Malignancies GSK ICOS agonist mabs GSK Brontictuzumab * BCMA -ADC Notch1 Multiple Myeloma Solid Tumours, Heme Malignancies Tarextumumab * Notch2/3 SCLC GSK Immune checkpoints Cell Therapy NY-ESO-1* GSK/Adaptimmune TCR-T TCR-T Sarcoma, Multiple Myeloma, NSCLC, Ovarian, Melanoma GSK CAR-T Synthetic / Small Molecules GSK GSK TLR-4 agonist Novel mechanisms Bi- Specific Molecules GSK/ImmunoCore GSK GSK/AdiMab ImmTacs mab-dabs Dual-specific Abs * Collaboration with third party

8 Change in target lesion from baseline (%) NY-ESO T-Cell Therapy TCR T-cell therapy 5% ORR seen in sarcoma Sarcoma Phase I/II: Individual patient complete response (CR) Baseline Day 2: Inflammation Day 1: CR Ongoing studies in ovarian and other solid tumours and haematological malignancies Planned studies in combination with checkpoint modulators Collaboration with Adaptimmune Status: Phase I/II Indications: NY-ESO-1 positive Cancers: Sarcoma, Myeloma, NSCLC, Melanoma, Ovarian Cancer Filing strategy to be agreed with Adaptimmune Note: GSK subject to exercise of option by GSK Sarcoma Phase I/II: Best Response in treated patients (N=12)* 17 Best response Stable disease -26 Excludes 3 subjects who did not receive a T-Cell Infusion. One subject with disease progression is excluded because lesion could not be measured *Subjects did not receive the target cell dose Subject number Confirmed complete or partial response 261* 23 26* GSK, data on file. 8

9 Percent survival Percent survival GSK OX4 agonist mab GSK is one of four humanised OX-4s in clinic Dual mechanism: enhancing effector T-cell and suppressing T-regs Phase I Study started in eight cancers Combination with Merck PD1 in 216 Combination with GSK TLR4 in 217 Collaboration with MD Anderson control Survival in animal model (CT26) OX-4 + PD-1 apd Time (days) aox4 aox4 /apd-1 Survival in animal model (CT26) OX-4 + TLR TLR4a / aox4 TLR4a Status: Phase I Indications: Solid tumours, Heme Malignancies Planned Filing: 22 control 5 Study day aox GSK, data on file. 9

10 OS (%) % of total CD4 T cells Cell count/ L % of total CD4 T cells GSK first-in-class ICOS agonist antibody Universal mechanism across multiple cancers Patient selection biomarker Enhances T-cells associated with survival ICOS in ipilimumab-treated patients CD4 ICOS T cells GSK T cell Activation in-vitro CD69+ CD4 T cells 24hr after stimulation Use after CTLA-4 and PD-1 in unresponsive or refractory patients Possible anchor for use in combinations Collaboration with INSERM Status: Phase I start Q1 216 Indications: Solid tumours, Heme Malignancies Planned Filing: Baseline W7 W12 W24 Ipilimumab Responders Ipilimumab Non-Responders CD4 ICOS T cells CD4 ICOS 4 CD4 ICOS > Time (months) DiGiacomo, Clin Immunol Immunother ICOS Ab (ug/ml) T cell Proliferation in-vitro Ki67+ CD4 T cells 48hr after stimulation ICOS Ab (ug/ml) 1

11 GSK BCMA-ADC B Cell Maturation Antigen Bone Marrow Dissemination Model (SCID Mice) Antibody Drug Conjugate (ADC) with MMAF (auristatin derivative) High-expression target in multiple myeloma ADCC enhanced Immunogenic cell death inducer Strong pre-clinical activity High potential for combinations Status: Phase I Indications: Multiple Myeloma Planned Filing: Data dependent (post 22) Tai et al, Blood (214), 123(2):

12 Immuno-Oncology at GSK Mission: Maximise patient survival Achieve a long-term leadership position in Oncology Scientific Focus Optimise T-cell Immunity Rationale: has delivered transformational medicines Synergies and transformational effects through combinations Tactics Diversified pipeline Across key modalities Innovation 3 rd generation targets, modalities & combinations Build world-class discovery and development team Fully-integrated programs from early discovery through licensure Goals Transformational effects for patients Maximise survival Pipeline sustainability Long-term leadership position in Oncology Partnerships Best science Access to combinations 12