With the number of blockbuster drugs approaching patent expiration and pharma companies struggling to maintain pipeline and portfolios with in-house programs, companies are increasingly turning to licensing, aquisitions and partnerships. Early-stage licensing deals tend to carry more risk for pharma companies in-licensing. To offset this risk, additional data may be required from the pharma partner to confirm any internal research performed by the biotech/out-licensing company.

Mini-case study. MD Biosciences helps a medium-sized biotech company to develop Rheumatoid Arthritis drug for out-licensing in under two years.

A medium-sized biotech company approached us with a compound that showed some efficacy in rheumatoid arthritis (RA) with a business goal of out-licensing the potential drug within two years. In order to push this compound through in approximately 18 months, a strategic and precisely timed development program needed to be established. MD Biosciences was able to present the sponsor with a program that entailed 25 preclinical studies over the course of 18 months. This was made possible by modifying models such as the rapid 10-day Collagen Antibody-induced arthritis (CAIA) model using ArthritoMab™ antibody cocktail. Each study was customized specifically to address the appropriate questions, building from one study to the next.

The outcome was a successful preclinical program in which 25 carefully designed studies were executed with rapid turn-around times and quality, consistent results. This is critical to allow data comparison over the course of the development period. After 18 months, the compound was developed to an appropriate stage and the company succeeded in out-licensing in a multi-billion dollar deal, indicating this development program as central to the success.

C57Bl/6 is a common background for generating genetically modified strains for use in in vivo models of arthritis. While these strains are commonly used, they are also known for requiring larger amounts of induction reagents, present with lower incidence rates and often times a milder disease course. In the classical CIA model, investigators are often required to nearly double the group size to accommodate the incidence rates, which can be as low as 50%.

In the alternative collagen-antibody induced arthritis (CAIA) model, investigators often need to boost the levels of antibody substantially. MD Bioproducts arthritogenic cocktail of four antibodies has been optimized for use in C57Bl/6 strains allowing investigators to induce arthritis in C57Bl/6 with nearly 100% incidence using as low as 2 mg/mouse. Histological data also shows pannus formation, hyperplasia, bone erosion and cellular infiltration in the joints of C57Bl/6 strains with just 2 mg/mouse ArthritoMab™ Antibody Cocktail in just 12 days

Advantages of the CAIA model using ArthritoMab™

• High Incidence rates
• Synchronized Disease
• Susceptible in a variety of strains
• Flexible protocol design
• Rapid 12 day model

The collagen antibody induced arthritis model (CAIA, also called anti-collagen induced arthritis) uses of cocktail of 4 collagen type II (CII) antibodies to induce arthritis. The antibodies bind to well-defined epitopes associated with arthritis. In this way, the CAIA model and the K/BxN model are very similar, relying on passive transfer of antibodies to induce arthritis. The severity, mechanisms of action and length of disease are similar giving similar disease scores and histology.

There are however, significant differences, which make running the CAIA model an advantage over the K/BxN:

• Epitope location: GP6i is ubiquitously expressed while CII has a restricted distribution and is concentrated in the joints ensuring antibody is directed to the site of interest.
• K/BxN sera is an undefined polyclonal mixture that can vary batch to batch. The CAIA model uses the ArthritoMab™ Antibody cocktail which is a defined and standardized mixture so there is no batch variation.
• With CAIA, arthritis is induced by clinically relevant anti-collagen antibodies.
• There is no need to maintain expensive colonies.
• Easy and constant availability of induction material.
• No waiting for animals to develop arthritis before harvesting sera.
• No concerns about colonies going down through sickness or breeding issues.