GlaxoSmithKline plc. –
Oncology Drug Pipeline Insights – June 2021

Molecule	Target	Phase	Indication	NCT Number	Mol Type
Dostarlimab / GSK4057190 / TSR-042	PD1	III	Advanced Endometrial Cancer	NCT03981796	Monoclonal Antibody
		III	Ovarian Cancer	NCT04679064
		II	Urothelial Bladder Cancer	NCT04779151
		II	Gastric Adenocarcinoma	NCT04493060
			Metastatic Pancreatic Cancer
		II	Non-Small Cell Lung Cancer	NCT04581824
		II	Melanoma Stage IV	NCT04139902
GSK3359609	ICOS	III	Relapsed/Metastatic Head and Neck Cancer	NCT04128696	Monoclonal Antibody
			Squamous Cell Carcinoma
		II	R/M Non-small Cell Lung Cancer	NCT03739710
Letetresgene autoleucel / GSK 3377794	NY-ESO-1	II	Advanced Non Small Cell Lung Cancer	NCT03709706	Engineered TCR Therapy
		II	Advanced Synovial Sarcoma	NCT03967223
Cobolimab / GSK4069889 / TSR-022	TIM-3	II	Advanced Liver Cancer	NCT03680508	Monoclonal Antibody
		II	Late Stage Melanoma	NCT04139902
GSK3326595 / EPZ015938	PRMT5	II	Early Stage Breast Cancer	NCT04676516	Small Molecule
		I	Myelodysplastic Syndrome	NCT03614728
			Acute Myeloid Leukaemia
		I	Solid Tumors	NCT02783300
			Non-Hodgkin's Lymphoma
GSK3368715 / EPZ019997	PRMT	I	Solid Tumors	NCT03666988	Small Molecule
			Diffuse Large B-cell Lymphoma
GSK3537142 / IMCnyeso	NY-ESO, CD3	I	Advanced Solid Tumors	NCT03515551	Fusion Protein
GSK3745417	STING	I/II	Advanced Solid Tumors	NCT03843359	Small Molecule
GSK4074386 / TSR-033	LAG-3	I	Advanced Solid Tumors	NCT03250832	Monoclonal Antibody
GSK6097608	CD96	I	Advanced Solid Tumors	NCT04446351	Monoclonal Antibody
GSK3901961 + GSK3845097	NY-ESO-1, LAGE-1a	I	Solid Tumors	NCT04526509	Engineered TCR Therapy
			Advanced Synovial Sarcoma
			Advanced Non Small Cell Lung Cancer

GlaxoSmithKline Active Oncology Pipeline Drug Description

• Dostarlimab/ TSR-042 is a humanized PD-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2.
• Dostarlimab was discovered by AnaptysBio and licensed to TESARO, Inc.,
  GSK3359609 is an inducible T cell co-stimulatory (ICOS) agonist antibody designed to selectively enhance T cell function
• Letetresgene autoleucel (lete-cel, GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor engineered T cells.
• GSK4069889 / TSR-022 is a monoclonal antibody against TIM-3 (also called HAVCR2), an immune checkpoint receptor.
• GSK3326595 (EPZ015938) is a potent, selective, reversible inhibitor of protein arginine methyltransferase 5 (PRMT5).
• GSK3368715 (EPZ019997) is a first-in-class, orally active, potent and selective, SAM-Noncompetive inhibitor of Type I Protein Arginine Methyltransferases (PRMTs).
• GSK3537142 / IMCnyeso is a new biological therapy designed for the treatment of non-small cell lung cancer (NSCLC), bladder cancer, melanoma and synovial sarcoma, positive for NY-ESO-1 and/or LAGE-1A.
• GSK is developing GSK3537142 in collaboration with Immunocore Ltd.
• GSK3745417 is an oral highly selective STING agonist, that modulates the innate immune cGAS‒STING‒TBK1 signaling pathway.
• GSK4074386 / TSR-033 is a humanized Anti-lymphocyte activation gene-3 (LAG-3) antibody, generated from a mouse hybridoma.
• GSK6097608 is a monoclonal antibody that inhibits CD96, that binds to and inhibits CD96 expressed primarily on T-cells and natural killer (NK) cells, thereby preventing its downstream signaling pathways.
• GSK3901961 and GSK3845097 are next generation engineered TCR T-cells, co-expressing the CD8α cell surface receptor, targeting NY-ESO-1, and co-expressing the dnTGF-βRII cell surface receptor, targeting NY-ESO-1, respectively to potentially improve function. This is a master protocol evaluating first time in human T-cell therapies. It will initially consist of two independent sub studies, investigating GSK3901961 and GSK3845097 in HLA*A02+ participants with NYESO1+ previously treated advanced (metastatic or unresectable) synovial sarcoma (SS) and/or previously treated metastatic non-small cell lung cancer (NSCLC).