STAT Inhibitors, Potential Market Opportunity & Clinical Pipeline Insights, 2019

STAT proteins, known as Signal Transducer and Activator of Transcription is a family of cytoplasmic transcription factors having 7 members like STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6. These factors are activated by tyrosine kinase that could be either receptor associated as Janus Kinase (JAKs) or intrinsic tyrosine kinases such as PDGFR, FLT3, and EGFR. Non-receptor protein tyrosine kinase (PTKs) including Brk, Bcr-Abl, c-Src can also play a significant role in their activation. Phosphorylation at specific sites by tyrosine kinase is playing a major role in homo, and heterodimerization of STAT proteins is thereby imparting a role in DNA binding and transcriptional activation. Improper regulation of the STAT proteins will give negative feedback increasing its activity further leading to tumor genesis. On the other hand, the over-expression of different STAT protein is related to Rheumatoid Arthritis, Asthma, Viral and Bacterial Infections. STAT inhibitors play a vital role in the treatment of various diseases. STAT3 and STAT5 inhibitors mainly target the oncology-based indications including pancreatic cancer, colorectal cancer, melanoma, breast cancer, gastrointestinal cancer, and hematological malignancies. These inhibitors work by targeting the SH2 Domain, DNA-Binding Domain, N-terminal Domain of STAT proteins.

Market Overview

Currently, the pipeline activity of STAT inhibitors is very robust with 20+ active pipeline products. Now, there is only one therapeutic candidate Napabucasin (BBI-608) in the late clinical stage (phase III) under-development by Boston biomedical for the indications mainly related to oncology. The drug stands a bright chance to get approved and launched into the market in the near future. Some of the drugs in phase III trials of drug development include LCZ696 (sacubitril/valsartan), Ramipril by Novartis, MK-1439A by Merck Sharp & Dohme Corp., Olokizumab q4w by Quintiles, Inc., Vincristine, Daunorubicin, and Prednisone by Bristol-Myers Squibb. OPB-111077 by Otsuka pharmaceutical is in mid-stage phase II trial of drug development useful for treating solid tumors. Reata Pharmaceuticals announced positive phase 2 data for Bardoxolone Methyl in IgA Nephropathy and Type 1 Diabetic Chronic Kidney Disease. Phase I study of OPB-31121, an Oral STAT3 Inhibitor, by Otsuka is used in Patients with Advanced Solid Tumors. Majority of the pipeline drugs belongs to the pre-clinical phase signifying STAT Inhibitor development as the emerging potential area of therapeutic research. BioVision proudly offered an array of STAT inhibitors that will either directly act on STAT proteins or other proteins playing a significant role in the STAT-signaling pathway.

Furthermore, a few natural products are presently undergoing clinical trials or approved for clinical applications, which also modulate STAT signaling among others. The effect of curcumin on pancreatic cancer is being evaluated in a Phase II trial. The effectiveness of 3,3′-diindolylmethane in the treatment of breast cancer is being studied in Phase II/III study. Further, an observational clinical study is under study to assess the activation status of STAT1, STAT3, STAT5A, STAT5B and STAT6 in leukocytes isolated from patients with rheumatoid arthritis treated with tocilizumab, a humanized IL-6R-specific monoclonal antibody.

The rising prevalence of autoimmune diseases and cancer are significant drivers of the STAT inhibitors market. Moreover, increased application of STAT inhibitors in inflammatory diseases and the increase in investment from pharmaceutical companies is some other drivers of the STAT inhibitors market. However, stringent government regulations, the high cost of treatment, and lack of funds for conducting research are going to hamper the STAT market during the forecast period.

Key Developments

• In Mar 2019, Bio-Path Holding’s announces their intention to submit IND for BP 1002 to US FDA for Chronic lymphocytic leukemia and Acute Myeloid Leukemia in 2019.


• In Jan 2019, Reata Pharmaceuticals plans to initiate enrolment in the phase III FALCON trial for Renal failure in mid-2019.

Segmentation

This Pipeline research report segments the STAT inhibitors pipeline on the basis of therapies employed (combination therapy, and monotherapy + combination therapy), therapeutic modality (small molecules, and unknown), RoA (oral and unknown), drugs under development (discovery, pre-clinical, phase I, phase I/II, phase II, and phase III), and recruitment status (recruiting, active not recruiting, enrolling by invitation, and undisclosed).

Some of the major market players in the research and development of STAT inhibitor drugs include Boston Biomedical, Reata Pharmaceuticals, Otsuka, GLG Pharma, Ionis Pharmaceuticals, StemMed, Moleculin Biotech, Glactone Pharma, Singh Biotechnology, Janpix Bio, and others.