Target/Description	Examples of Candidates In Development
OX40: OX40, also known as CD134, is a member of the TNFR superfamily of receptors that is not constitutively expressed on resting naïve T cells. OX40 is a secondary co-stimulatory molecule, expressed 24 to 72 hours after activation. Its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell.	Glenmark Pharmaceuticals Ltd.'s GBR 830 (Phase II atopic dermatitis, Phase I celiac disease); Kyowa Hakko Kirin Co. Ltd.'s KHK4083 (Phase II ulcerative colitis, Phase I atopic dermatitis); Roche's RG788 (Phase II bladder cancer); Bristol's BMS986178 (Phase I/II solid tumors); GlaxoSmithKline PLC'sGSK3117498 (Phase I/II solid tumors)
Programmed death-1 receptor and ligand 1 (PD-1/L1): PD-1, a member of the CD28/CTLA-4/ICOS co-stimulatory receptor family, delivers negative signals that have profound effects on T-cell and B-cell immunity. PD-L1 and PD-L2 are the ligands for PD-1 receptor that are expressed by many tumors to protect against T-cell-mediated immune responses. Class is approved for multiple cancer indications and current development is mostly focused in oncology.	Bristol's BMS936559 (Phase I/II sepsis and septic shock); Celgene Corp./AnaptysBio Inc.'s CC-90006 (Phase I psoriasis); Ono Pharmaceutical Co. Ltd. and Celgene – Opdivo (Phase I hepatitis C virus, sepsis/septic shock); Alnylam Pharmaceuticals Inc.'s ALN-PDL (preclinical liver failure, cirrhosis); Tasly Pharmaceutical Co. Ltd./Genexine Inc.'s GXP2 (preclinical psoriasis, inflammatory bowel disease); Fate Therapeutics Inc.'s ToleraCyte (preclinical type 1 diabetes)
Cluster of differentiation 40 (CD40): CD40 is a member of the TNF receptor superfamily. This receptor has been found to be essential in mediating a broad variety of immune and inflammatory responses including T-cell-dependent immunoglobulin class switching, memory B-cell development and germinal center formation. The interaction of this receptor and its ligand (CD40L) is necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer’s disease pathogenesis. Development is ongoing in a mix of autoimmune and oncology indications.	Apexigen Inc./Boehringer Ingelheim GMBH's APX005M (Phase II esophageal cancer and Phase I/II melanoma); Astellas Pharma Inc.'s ASKP1240 (Phase II transplant rejection); Abbvie/BI's 655064 (Phase II lupus); Novartis AG's CFZ533 (Phase II for Graves' ophthalmopathy/orbitopathy, myasthenia gravis, Sjogren's syndrome); Johnson & Johnson/Alligator Bioscience AB's ADC-1013 in solid tumors
Cluster of Differentiation 28 (CD28)/ICOS and B7RP-1 Pathway: The inducible co-stimulator (ICOS) is structurally and functionally homologous to CD28. The B7-Related Protein-1 (B7RP-1) is structurally and functionally homologous to B7.1 and B7.2 (B7.1/2), and is the ligand for ICOS. ICOS/B7RP-1 is emerging as a co-stimulatory pathway for a variety of effector and memory T-cell responses. Manipulation of the pathway results in alterations of immune responses that may be applicable in therapeutic indications as diverse as cancer, infectious and autoimmune diseases, and transplantation.	Atox Bio Inc.'s reltecimod (Phase III skin and skin structure infections); Bristol's BMS931699 (Phase II Sjogren's syndrome, lupus); AstraZeneca/Amgen Inc.'s MEDI5872 (Phase II Sjogren's, Phase I lupus); GSK's GSK3359609 (Phase I/II solid tumors); Jounce Therapeutics Inc./Celgene's JTX-2011 (Phase I/II solid tumors); Jounce/OSE Immunotherapeutics SA's FR104 (Phase I autoimmune disorders); AstraZeneca's MEDI0700 (Phase I lupus)
Interleukin-2 receptor (IL-2R): The IL-2 receptor is a heterotrimeric protein expressed on the surface of certain immune cells, such as lymphocytes, that binds and responds to a cytokine called interleukin 2. Three protein chains (alpha, beta and gamma) are non-covalently associated to form the IL-2R. IL-2R drugs are approved for cancer and transplant rejection, and development includes a mix of cancer and autoimmune indications.	Avadel Pharmaceuticals PL's IL2-XL (Phase II renal cell carcinoma); Nektar's NKTR-214 (Phase I/II in range of cancers including bladder cancer and melanoma); Amgen's AMG592 (Phase I/II in inflammatory disorders); Eli Lilly & Co./Nektar's NKTR-358 (Phase I lupus); Roche's RG7461 (Phase I solid tumors); Celgene's DEL-106 (preclinical in autoimmune disorders)
Macrophage colony-stimulating factor 1 (M-CSF1, CSF1R): Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation and function of two related white cell populations of the blood, the granulocytes and the monocytes/macrophages. CSF-1 induces cells of the monocyte/macrophage lineage. It plays a role in immunological defenses, bone metabolism, lipoproteins clearance, fertility and pregnancy.	Daiichi Sankyo Co. Ltd.'s pexidartinib (Phase III for pigmented villanodular synovitis (PVNS) and Phase II for solid tumors); Bristol/Five Prime Therapeutics Inc.'s cabiralizumab (Phase I or I/II in PVNS, solid tumors, rheumatoid arthritis); Daiichi's AC708 (preclinical for inflammatory disorders and cancer)
Stimulator of interferon genes (STING): The STING receptor is involved in the induction of an innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines.	Aduro Biotech Inc.'s Adu-S100 (Phase I in cancer); Nimbus Therapeutics/Celgene STING autoimmune program (preclinical autoimmune disorders and cancer)
SOURCE: Biomedtracker; Pharmaprojects \| Pharma Intelligence, 2018

A Virtuous Cycle: What The Immuno-Oncology Revolution Means For Other Disease Areas

More from Innovation

More from In Vivo