Multimeric Biotherapeutics, Inc.

MegaLigand image

Technology
TNF SuperFamily (TNFSFs): The TNFSFs are a pharmaceutical treasure chest of 19 proteins that are structurally related to Tumor Necrosis Factor (TNF). Despite its name, TNF is important in inflammation and is a key molecule involved in rheumatoid arthritis. Blockers of TNF include some of the world's best selling drugs such as Humira®, Enbrel®, Simponi®, and Cimzia®. Blockers of other TNFSFs are also marketed, including Benlysta® to block BAFF and Prolia® to block RANKL. Collectively, these TNF blocking drugs have over $25 billion annual sales. However, while these TNFSF blockers have been enormously successful, there has been no way to apply the TNFSF ligands in a positive fashion and no TNFSF ligand has yet been approved for therapeutic use. This is the problem that Multimeric's technology can solve.

Many-trimer TNFSFs are required: Dr. Richard Kornbluth and subsequently Dr. Jürg Tschopp recognized that a single trimer of a TNFSF ligand is often unable to stimulate its receptor. Instead, maximal stimulation occurs when a many-trimer form of TNFSF ligands is used to cluster their receptors on the surface of responding cells. The production of many-trimer forms of all 19 TNFSF ligands is Multimeric's core technology.
Single vs Multimeric TNFSF ligand
   
MegaLigands™ are Multimeric's preferred method for producing many-trimer TNFSF ligands. These are 2-trimer molecules produced by using the body of Acrp30 (a serum protein) as a scaffold and linking it to TNFSF ligand trimers. One protein in this series, MegaFasL™ or APO010, has been tested in a Phase I clinical trial for cancer. Multimeric's lead molecule is based on CD40 ligand (CD40L), which is the most powerful immune-stimulating molecule made by the body. Studies by Multimeric and by independent academic scientists have proven that MegaCD40L™ is a strong "adjuvant" for vaccines and an effective immunotherapy agent to treat cancer.  

2-trimer MegaLigand

   
UltraLigands™ are 4-trimer molecules produced by using the body of surfactant protein D (SP-D) as a scaffold and linking it to TNFSF ligand trimers. UltraCD40L™ is a powerful immune stimulant. Using the same technology, 9 other UltraLigands™ have been produced, which demonstrates the versatility of this technology.
4-trimer SP-D-TNFSF ligand