Transforming Growth Factor (TGFβ) is a ligand that is produced by and can act on many cell types in the body.
It is a plieotropic regulator of cell growth and differentiation, cell motility, production/remodeling of the extracellular matrix, and immune modulation. It is responsible for the homeostatic growth of premalignant cells and thus frequently targeted in the development of cancer. It late stage cancers, inappropriate regulation of this pathway has significant consequences for human disease. Preclinical studies have shown that it stimulates the growth and survival of tumors; is important for tumor metastasis; angiogenesis; and, contributes to a tumors ability to evade the host’s immune system. Patients with cancer where TGFβ is found to be over expressed, have clinically poor prognostic outcomes in comparison to patients where TGFβ expression is lower. It is believed to play a significant role in the development and progression of colon, breast, lung, prostate, and pancreatic cancers as well as, ovarian, bladder, gastric cancers, melanoma and renal cell carcinoma. In addition to its role in oncology, TGFβ is known to play a role in fibrosis.
Through the use of XOMA’s proprietary platform, antibody discovery efforts have identified potent high affinity mono, bi- and pan-reactive antibodies. Lead candidate, XOMA 089 is a fully human, high-affinity, late preclinical monoclonal antibody that neutralizes TGFβ1 and 2 while sparing TGFβ3. Data have shown this compound to be both active against tumor growth in preclinical models of head and neck cancer as well as breast cancer and breast cancer metastasis. Preclinical data also suggest that it may be synergistic with PD1 inhibition and work highlighting these results was recently presented at the 2015 FASEB meeting on the TGFβ Superfamily: Signaling in Development and Disease. XOMA has made significant progress regarding this lead compound on both the understanding of its activity, mechanism of action, as well as preclinical toxicology and manufacturing.
In September 2015, XOMA licensed the global development and commercialization rights to its TGFβ antibody program to Novartis. XOMA received $37.0 million upfront payment and is eligible to receive up to $480.0 million if all development, regulatory, and commercial milestones are met. In addition, XOMA is eligible to receive royalties on product sales that range from the mid-single digits to the low double digits
We also have a product partnered with Novartis in our pipeline: HCD122, a monoclonal antibody to CD40.
|Image courtesy Novartis Oncology