Immuno-Oncology Axel Hoos, MD, PhD Senior Vice President, Oncology R&D

Slides:



Advertisements
Similar presentations
Moskowitz CH et al. Proc ASH 2014;Abstract 290.
Advertisements

Antoni Ribas, M.D., Ph.D. Professor of Medicine Professor of Surgery
Immune therapy in NSCLC Presentation – 劉惠文 Supervisor – 劉俊煌教授.
Brown JR et al. Proc ASH 2013;Abstract 523.
1 Marine Technology Summit November 16, Discovering and Developing New Medicines from Marine Microbes Nereus Pharmaceuticals Ken Lloyd, Ph.D. Chief.
Evading Immune Responses and Tumor Immunology
1 HIV Curative Strategies: Key Research Priorities Deeks S, et al., (2013) Nat Rev Immunol. 12(8):
Novel Agents for Indolent Lymphoma and Mantle Cell Lymphoma Stephen Ansell, MD, PhD Mayo Clinic.
October 23, 2014 John C. Lin, M.D. Ph.D. Vice President, Experimental Medicine Rational Combination of Immunotherapies in Preclinical Cancer Models.
Lesokhin AM et al. Proc ASH 2014;Abstract 291.
Immunotherapy for Multiple Myeloma
118/2/2015 Cancer & the Immune System Hugh B. Fackrell.
The Promise of Immunotherapy for Cancer Treatment
Cancer Vaccines Medicines that belong to a class of substances known as biological response modifiers. Biological response modifiers stimulate or restore.
Novel strategies for prevention and treatment of HIV infection Prasit Faipenkhong Pairoaj Vonghathaipaisarn Rodjana Chunhabundit Zhang Jianjun.
New Developments in Cancer Treatment Dulcinea Quintana, MD.
ODAC SCHERING-PLOUGH RESEARCH INSTITUTE 1 Temozolomide Oncology Drug Advisory Committee March 13, 2003 Craig L. Tendler, M.D. Vice President, Oncology.
Immunotherapy Sara Engh & Tenzin Yiga. Role of the Immune system ➔ Defends against pathogens such as bacteria, fungi, and viruses that enter the body.
Viardot A et al. Proc ASH 2014;Abstract 4460.
Immunotherapy (Cancer therapy with T-Cells)
A Phase 2 Study of Elotuzumab in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma Lonial.
Progress in Cancer Therapy Following Developments in Biopharma
Clinician-led Workshop MEDM5121M Immunity and Disease Alan Melcher
Cancer immunotherapy: an update
Meredith Baker, MD PI: Bo Lu, MD – Radiation Oncology May 29th, 2014
Dr Mahendra Deonarain, Chief Science Officer Antibody Fragment Drug Conjugates (FDCs) Breakthrough ADC therapy BioTrinity April.
1 Trends in drug development programs in the era of Personalized Medicine Gunnar Saeter, M.D., Ph.D. Head, Institute for Cancer Research Oslo University.
YOUR CANCER TREATMENT: WHAT TO EXPECT FROM THE LATEST ADVANCEMENTS MIRIAM J. ATKINS, M.D.
MM-005: A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib,
이근욱 분당서울대학교병원/서울의대 혈액종양내과 부교수
The Role of Immunotherapy for the Treatment of Hematologic Malignancies Patrick Stiff MD Coleman Professor of Oncology Loyola University Medical Center.
Phase II Study: Pembrolizumab + Pomalidomide/Dexamethasone for Patients With R/R MM New Findings in Hematology: Independent Conference Coverage* of ASH.
Theme Colours HSV Oncolytic Immunotherapy BioTrinity 2016 Lynne Braidwood.
Brian Boulmay, MD LSUHSC- New Orleans Section of Hematology & Oncology
Wolfram C. M. Dempke SaWo Oncology Ltd May 13, 2017
Evolving Therapies for Elderly Patients with Blood Cancers
CCO Independent Conference Highlights
Statistical Considerations for Safety Assessment in Cancer Immunotherapy Trials Andrew Lloyd Biometrics Manager PSI Conference May 2017.
Metastatic Head Neck Cancer and Immunotherapy
An APC activator (IMP321 or LAG-3Ig) combined with anti-PD-1 blockade
Pembrolizumab Drugbank ID :DB09037 Half life : 28 days.
Society of Clinical Trials Conference
Immune Oncology Drugs: A Wolf in Sheep’s Clothing?
Nivolumab in Patients (Pts) with Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Clinical Outcomes from Extended Follow-up of a Phase 1 Study.
Figure 5. Treatment of the checkpoint inhibitor related toxicity
Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth
Elotuzumab, Lenalidomide, and Low-Dose Dexamethasone in Relapsed/Refractory Myeloma Slideset on: Lonial S, Vij R, Harousseau JL, et al. Elotuzumab in combination.
Future Strategies for Myeloma
COMPLICATIONS OF IMMUNOTHERAPY IN THE HOSPITALIZED PATIENT Vivek Batra MD, Emma Weaver MD Division of Medical Oncology, Thomas Jefferson University, Philadelphia.
Intervista a Lucio Crinò
Tumor Immunity: Exploring the Role of a Checkpoint
Treatment Algorithms in Melanoma: Past, Present, and Future
Immunotherapy for lymphoma: The time is now
Learning Goals. Harnessing the Immune System: Mechanism of Action of Immunotherapies in B-Cell Malignancies.
Nat. Rev. Clin. Oncol. doi: /nrclinonc
Discussion Outline Cells of the Immune System.
Figure 1 Four nodes to target when inducing anti-tumour immunity
Nat. Rev. Urol. doi: /nrurol
Nat. Rev. Urol. doi: /nrurol
Immunotherapy.
Multiple Myeloma Overview all transplants, autologous and allogeneic (period ) N=28.887
Potential mechanisms of therapeutic synergy between epigenetic modulation and PD-1 pathway blockade. Potential mechanisms of therapeutic synergy between.
Figure 2 Approaches to improve CAR-T-cell therapy
Figure 2 Site of action of checkpoint inhibitors and agonists being
Targeting T Cell Co-receptors for Cancer Therapy
Figure 1 Mechanisms of action of immunotherapy modalities
Clinical response to anti-ERBB3 mAb therapy in a patient with an advanced NRG1-rearranged non–small cell lung cancer. Clinical response to anti-ERBB3 mAb.
Efficacy of nivolumab in Japanese patients with advanced non-squamous non-small cell lung cancer (A) Kaplan-Meier curve for PFS, (B) Kaplan-Meier curve.
Human cancer immunotherapy strategies targeting B7-H3 A, blockade of B7-H3 with blocking mAbs neutralizes inhibitory signaling in its unidentified receptor(s)
Presentation transcript:

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

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

3 Generations of therapies Multiple therapies under development Anti-PD-L1 YERVOY ipilimumab (CTLA-4) KEYTRUDA pembrolizumab (PD-1) 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 PROVENGE sipuleucel-T (Cell Therapy) BLINCYTO blinatumomab (BITE) CAR-Ts OPDIVO nivolumab (PD-1) Key Approved IMLYGIC T-Vec (Oncolytic Virus) Under development

Substantial survival improvements Main trends SOC replacements Elimination of chemotherapy from SOC regimens Immune profiling Patient selection to predict response New technologies Expansion of the toolbox CURE 2016 Substantial survival improvements Across wide populations Complex combinations Maximise efficacy Improved endpoints Accelerated development

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

3rd Generation opportunities GSK’s multi-modality pipeline Adaptive Immunity Innate Immunity T-Cell Immunity B-Cell Immunity Cytokines Cellular Therapies - NK Cells* Cancer Vaccines T-cell Checkpoint Modulators Checkpoint Modulators “Connector” Bi-specific Abs - Dual-specific Abs Small Molecules Oncolytic Viruses Adjuvants GSK Pipeline * in planning

3rd Generation leadership Innovation across novel targets, modalities and combinations (5 in the clinic) Modality Program Mechanism Pre-clinical Phase 1 Phase 2 GSK3174998 OX40 agonist Solid Tumours, Heme Malignancies GSK3359609 ICOS agonist mAbs GSK2857916 BCMA -ADC Multiple Myeloma Brontictuzumab * Notch1 Solid Tumours, Heme Malignancies Tarextumumab * Notch2/3 SCLC GSK Immune checkpoints NY-ESO-1* TCR-T Sarcoma, Multiple Myeloma, NSCLC, Ovarian, Melanoma Cell Therapy GSK/Adaptimmune TCR-T GSK CAR-T Synthetic / Small Molecules GSK1795091 TLR-4 agonist GSK Novel mechanisms Bi- Specific Molecules GSK/ImmunoCore ImmTacs GSK mAb-dAbs GSK/AdiMab Dual-specific Abs * Collaboration with third party

Change in target lesion from baseline (%) NY-ESO T-Cell Therapy Sarcoma Phase I/II: Individual patient complete response (CR) TCR T-cell therapy 50% ORR seen in sarcoma Ongoing studies in ovarian and other solid tumours and haematological malignancies Planned studies in combination with checkpoint modulators Collaboration with Adaptimmune Baseline Day 2: Inflammation Day 100: CR Sarcoma Phase I/II: Best Response in treated patients (N=12)* 60 40 Best response Stable disease Confirmed complete or partial response 17 20 15 Change in target lesion from baseline (%) -20 -15 -16 -26 -40 Status: Phase I/II Indications: NY-ESO-1 positive Cancers: Sarcoma, Myeloma, NSCLC, Melanoma, Ovarian Cancer Filing strategy to be agreed with Adaptimmune -60 -50 -55 -58 -64 -80 -70 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 -100 -100 -120 261* 230 206* 207 200 204 202 209 205 208 201 Subject number Note: GSK3377794 subject to exercise of option by GSK GSK, data on file.

Survival in animal model (CT26) Survival in animal model (CT26) GSK3174998 OX40 agonist mAb Survival in animal model (CT26) OX-40 + PD-1 control aPD-1 aOX40 aOX40 /aPD-1 Percent survival Time (days) 20 30 40 50 60 80 100 70 90 GSK3174998 is one of four humanised OX-40s in clinic Dual mechanism: enhancing effector T-cell and suppressing T-regs Phase I Study started in eight cancers Combination with Merck PD1 in 2016 Combination with GSK TLR4 in 2017 Collaboration with MD Anderson aOX40 TLR4a TLR4a / aOX40 control Survival in animal model (CT26) OX-40 + TLR-4 Percent survival Study day 50 100 150 Status: Phase I Indications: Solid tumours, Heme Malignancies Planned Filing: 2020 GSK, data on file.

GSK3359609 first-in-class ICOS agonist antibody Universal mechanism across multiple cancers Patient selection biomarker Enhances T-cells associated with survival Use after CTLA-4 and PD-1 in unresponsive or refractory patients Possible anchor for use in combinations Collaboration with INSERM ICOS in ipilimumab-treated patients GSK3359609 Ipilimumab Responders Ipilimumab Non-Responders Baseline W7 W12 W24 20 40 60 80 CD4 ICOS T cells % of total CD4 T cells ICOS Ab (ug/ml) T cell Activation in-vitro CD69+ CD4 T cells 24hr after stimulation 20 40 60 80 100 0.01 0.1 1 10 Cell count/L 12 24 36 48 20 40 60 100 CD4 ICOS T cells OS (%) 80 Time (months) CD4 ICOS >4 CD4 ICOS ≤4 T cell Proliferation in-vitro % of total CD4 T cells ICOS Ab (ug/ml) Ki67+ CD4 T cells 48hr after stimulation 0.01 0.1 1 10 100 5 15 20 25 Status: Phase I start Q1 2016 Indications: Solid tumours, Heme Malignancies Planned Filing: 2020 DiGiacomo, Clin Immunol Immunother 2013

GSK2857916 BCMA-ADC B Cell Maturation Antigen 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 Bone Marrow Dissemination Model (SCID Mice) Status: Phase I Indications: Multiple Myeloma Planned Filing: Data dependent (post 2020) Tai et al, Blood (2014), 123(20):3128-38

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 3rd generation targets, modalities & combinations Build world-class discovery and development team Fully-integrated programs from early discovery through licensure Partnerships Best science Access to combinations Goals Transformational effects for patients Maximise survival Pipeline sustainability Long-term leadership position in Oncology