Q3 2020 Sales Performance
GSK'609 ICOS receptor agonist
Differentiated MOA with encouraging clinical data at ESMO 2019
gsk
Target
Agent
Status
• ICOS, a member of the CD28 family of co-stimulatory receptors, has a
•
pivotal role in the proliferation, differentiation, survival, and function of T cells
Highly upregulated upon T-cell receptor stimulation1 and is expressed on
tumour infiltrating lymphocytes in many tumours²
Consistent with CTLA-4 and PD-1 blockade, ICOS agonism is anticipated to
modulate T-cell dynamics resulting in prolonged control of tumour growth
kinetics and survival in patients
• Humanised IgG4 antibody selected for its potent binding, agonist activity
through the human ICOS receptor and low/no T-cell depleting effects via
antibody-dependent cellular toxicity
• Anti-tumour activity observed with an ICOS agonist is further enhanced in
combination with CTLA-4 and PD-1 blockade in non-clinical models 3,4 ICOS
agonist treatment led to upregulation of PD-1/PDL-1 expression in these
models³
•
RNA-sequencing data shows strong correlation of ICOS and PD-L1 in solid
tumours, further supporting clinical evaluation of this combination4
Clinical activity observed with both monotherapy and PD-1 combination;
HNSCC data presented at ESMO September 2019
⚫ INDUCE-3 and 4 gated Ph2/3 studies in HNSCC started end 2019 and mid
2020
T-cell
T-cell priming/
periphery
CD80/CD86
Local antigen
re-challenge
Memory
effector T-cell
Activation
ICOS
TCR
Survival
Proliferation
CD28
MHC CTLA4
TCR
MHC CD40L
CD80/CD86
CXCR5
Granzyme B
ICOS-L
IFNy/other
cytokines
APC
Maturation
APC, antigen-presenting cell; CXCR5, C-X-C motif chemokine receptor 5;
ICOS-L, ICOS ligand; IFN-y, interferon gamma; MHC, major histocompatibility
complex
1.Hutloff A, et al. Nature 1999;397:263–6. 2. Mayes P, et al. Nat Rev Drug Disc 2018;17:509-27. 3. Brett S, et al. ESMO 2018 poster presentation: Abstract 1840P.4. Yadavilli S, et al. AACR 2017 poster
presentation: Abstract 1637/15
RRMM = Relapsed/ Refractory malignant melanoma; RR HNSCC = Relapsed/ Refractory Head and Neck Squamous Cell Carcinoma; NSCLC = non small cell lung cancer
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