1. Strategy for drug discovery targeting protein-protein interaction (PPI)

Summary
Interprotein’s business focus is the development of small molecule that interfere with PPI. Recent epoch making progress in biotech and pharmaceutical industries has come from the use of monoclonal antibodies for the treatment of significant diseases including cancer and rheumatoid arthritis. Monoclonal antibodies are the only proven pharmaceutical method of inhibiting PPI strongly associated with diseases eg TNF-TNF receptor inhibition by Infliximab and Adalimumab for Rheumatoid Arthritis, both of which are now $bn drugs.

Blocking PPI by antibodies is now a clinically proven and significantly effective method to treat and prevent progressions of many diseases ? several hundred monoclonal antibodies are currently in clinical trials or on the market.

Although Monoclonal Antibodies are effective, they are relatively expensive to manufacture, and must be given by injection.  From a commercial perspective, orally available small molecule inhibit the same PPI, would have improved cost of goods and patient acceptance advantages.
Our approach is to design small molecule with our novel method to achieve the same clinical outcomes as established antibody products.  We have developed a method to identify small molecule to inhibit PPI with high specificity and potency.  We have successfully created new chemical entities interfering with PPI both in-vitro and in-vivo proof of concept models. We are committed to deliver highly innovative therapeutics with affordable drug prices and versatility.

Selection of targets with Proof of Concept
We believe that successful drug development depends on the wise selection of the targets for which patients need alternative drugs to current biological approaches.  In view of these considerations, we have first chosen the PPI between IL-6, IgE and VEGF with their specific receptors. 　These targets have been clinically validated as important drug targets by antibody therapeutics such as Tocilzumab, Omalizumab and Bevacizumab, respectively, but an orally available small molecule alternative would offer significant competitive advantages.  Interprotein believes that this approach should give us much higher success rates in developing and commercializing our projects than industry averages.

Our belief is “Consider the advantages of small molecule compounds!”.
Antibody drugs and a few other biopharmaceuticals have proven the clinical rationale for targeting PPI. It is truly epoch making approach which has provided better QOL for patients with diseases which therapeutics never treated well before.  Despite this benefit, there are major concerns on significant increase of medical costs and inconvenient usage of drugs due to limitation of administration route of biopharmaceuticals. High medical costs hamper application of those drugs to broader range of diseases and patient’s access to drugs particularly in the developing coutries. In addition, monoclonal antibodies can only be used to inhibit extracellular PPI eg secreted proteins or cell surface receptors.  Interprotein can create drugs that will also inhibit disease-associated PPI inside cells eg signal transduction molecules.
Our mission for PPI projects is to provide therapeutic benefits to all the patients in the world through developing small molecule inhibitors.

International Collaboration
We are actively seeking collaboration partners for our drug discovery projects.  We are talking to companies including several global pharmaceutical companies for future collaboration opportunities.

3. Cold sensitive enhancer for protein production (CIRP)

Professor Jun Fujita, Kyoto University discovered cold inducible enhancer elements, enhancer of cold-inducible RNA-binding protein (CIRP), that works in brain and testis. This is the first cold sensitive enhancer discovered in mammalian cells. Professor Fujita developed the enhancer element to be applied for industrial purpose. The CIRP enhancer improves production yield of recombinant proteins and consequently we can reduce cost of goods which are major issues for biological product manufacturers. Together with other projects, we believe that we can provide the world with drugs and technologies at a reduced cost through this new technology.

4. Tubulin polymerization inhibitor (IPC-003)

We found out a potent and effective tubulin polymerization inhibitor, IPC-003, in the process of strategic screening for anti-cancer drugs.  IPC-003 showed inhibitory effects on growth of not only solid tumor but also acute leukemia (including therapeutic administration schedule) in vivo.  Since it exhibited an excellent balance of efficacy and toxicity, we believe that IPC-003 would be a good lead compound for best-in-class tubulin polymerization inhibitor.

5. Platform technology of Interprotein; INTENDD

One of the drug discovery functions of Interprotein is “in silico molecular design” and its approach is unique integration of molecular design technologies based on successful experiments.  We named this innovative drug design concept “INTENDD”.  Outlines of INTENDD are as follows:

2. Strategy for drug discovery targeting zinc chelators for allergy treatment

Prof. Toshio Hirano, Osaka University and Deputy Director of Riken Research Center for Allergy and Immunology, first found that zinc ions are required for initiation of allergic response. Upon allergic stimulation, granules in mast cells and eosiophils migrate along the cyoskelton to the plasma membrane, and finally fuse to plasma membrane and release chemical mediators. Zinc ions are required for translocation of granules. We are developing therapeutics to suppress allergic response by depriving zinc ion from a diseased site. We believe that this should be effective for the treatment of diseases such as atopic dermatitis and allergic rhinitis.