TG Therapeutics

TG Therapeutics is a publicly owned biopharmaceutical company headquartered in New York City, New York that was founded in 1993 by Michael Sean Weiss and Laurence H. Shaw. It focuses on the acquisition, development, and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. The company's product pipeline has two therapies in clinical development, TG-1101 and TG-1202.

TG-1101, also known as Ublituximab, is a monoclonal antibody that targets a specific epitope on the B-lymphocyte CD20 antigen. It has been bioengineered to deliver enhanced clinical activity and potency. The product is aimed at treating B-cell proliferative disorders including, Non-Hodgkin's Lymphoma (NHL) and Cronic Lymphocytic Leukemia (CLL). It has also shown effectiveness against autoimmune diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE), as well as the neurological disorder, Multiple Sclerosis (MS). Ublituximab is in Phase 3 clinical development for patients with hematologic malignancies and patients with multiple sclerosis.

TG-1202, also known as Umbrasilib, is an orally available PI3K delta inhibitor. It targets delta isoforms, which is believed to be important in the proliferation and survival of B-cell lymphocytes. Umbrasilib is in Phase 3 clinical development in combination with Ublituximab for patients with hematological malignancies.

TG-1801 is the first treatment that targets both CD19 and CD47. CD19 is a B cell-specific marker widely expressed in B cell malignant tumors, while CD47 is expressed in both healthy and tumor cells, transmitting the "don't eat me" signal. In order to escape macrophage-mediated phagocytosis, CD47 is widely expressed in normal cells, including red blood cells and platelets. Co-targeting CD47 and CD19,TG-1801 has the potential to overcome the limitations of existing CD47 targeting therapy and avoid the side effects of indiscriminate blocking of CD47 on healthy cells.

TG has two therapies into III clinical development: (1) ublituximab, a new type of glycosylated anti-CD20 monoclonal antibody, Targeting specific epitopes of CD20 antigen on mature B lymphocytes; (2) umbralisib, an oral, daily, new generation of PI3K δ inhibitors, can uniquely inhibit CK1- ε, which may enable it to overcome some tolerance problems associated with the first generation of PI3K δ inhibitors.

The combination of ublituximab, umbralisib and U2 is in the clinical stage of III in the treatment of hematological malignant tumors, in addition, the treatment of multiple sclerosis with ublituximab has also been in the clinical stage of III. Just recently, the company pushed its anti-PD-1 monoclonal antibody TG-1501, a covalently bound BTK inhibitor TG-1701, into Phase I clinical practice.

TG Therapeutics has several other products in its pipeline, which are at various stages of preclinical studies:

A key signaling kinase that becomes inappropriately activated in tumors that carry certain oncogenic mutations of MYD88, which can be found in most patients with Waldensrom's Macroglobulinemia, a rare B-cell cancer, as well as in some specific cases of Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia. IRAK4 is also key in regulating immune and inflammatory processes, suggesting that it may be useful in treating autoimmune related disorders.

Anti-PD-L1 antibodies target programmed cell death ligand 1 (PD-L1). They are designed to block signals permitting effector T-cells to attack cancer. Anti-GITR antibodies target glucocorticoid-induced tumor necrosis factor receptor related protein (GITR). It has shown to amplify the antitumor immune responses in animal models. Pre-clinical research on therapies using a combination of these two antibodies have yielded positive results. The Anti-PD-L1 monoclonal antibody has been brought into Phase 1 of clinical development.

TG-1601 is a small molecule that binds to the epigenetic BET family of bromodomain-containing proteins and inhibits their binding to chromatin. It can increase the sensitivity of tumors to chemotherapy or specific standard of care by resetting the genome in tumor cells. TG-1601 is in pre-clinical development and is being tested in various IND-enabling studies.

TG-1701 is an orally available BTK inhibitor. Targeting BTk with small molecule inhibitors has demonstrated effectiveness as a treatment option for B-cell lymphomas and autoimmune diseases. The product is in Phase 1 clinical trials in China.

TG-1801 is the first treatment that targets both CD19 and CD47. CD19 is a B cell-specific marker widely expressed in B cell malignant tumors, while CD47 is expressed in both healthy and tumor cells, transmitting the "don't eat me" signal. In order to escape macrophage-mediated phagocytosis, CD47 is widely expressed in normal cells, including red blood cells and platelets. Co-targeting CD47 and CD19, TG-1801 has the potential to overcome the limitations of existing CD47 targeting therapy and avoid the side effects of indiscriminate blocking of CD47 on healthy cells.

TG has two therapies into III clinical development: (1) ublituximab, a new type of glycosylated anti-CD20 monoclonal antibody, Targeting specific epitopes of CD20 antigen on mature B lymphocytes; (2) umbralisib, an oral, daily, new generation of PI3K δ inhibitors, can uniquely inhibit CK1- ε, which may enable it to overcome some tolerance problems associated with the first generation of PI3K δ inhibitors.

The combination of ublituximab, umbralisib and U2 is in the clinical stage of III in the treatment of hematological malignant tumors, in addition, the treatment of multiple sclerosis with ublituximab has also been in the clinical stage of III. Just recently, the company pushed its anti-PD-1 monoclonal antibody TG-1501, a covalently bound BTK inhibitor TG-1701, into Phase I clinical practice.

On February 29, 2012 TG Therapeutics announced raising $25 million in Post-IPO capital.