TNF-Alpha antagonists

Chronic constipation is a common condition of both elderly humans and companion animals including dogs, cats and horses. However, the underlying physiology of this disorder is not well understood, and effective treatment options are limited.

Currently, chronic constipation is difficult to manage in humans and animals although a combination of diet and nutraceuticals, home remedies, over the counter preparations and pharmaceutical drugs have some impact on this condition.

We have previously shown that short-term treatment with an anti-TNF drug can reverse age-related constipation in a mouse model. This project sought to explore whether the development of these drugs as treatments for chronic constipation in older humans and companion pets was a viable option.

Through BBSRC funded research, we have identified that elevated TNF-alpha (anti-TNF) is associated with symptoms of chronic constipation in an aged mouse model. A marketed anti-TNF drug, etanercept could reduce these symptoms in the model, but has some drawbacks including administration by sub-cutaneous injection, and a potential suppressive effect on the immune system. We would therefore like to understand whether i) stakeholders feel this route of administration is acceptable or whether reformulation would be necessary; ii) whether the potential of the drug to suppress the immune system is perceived as a major drawback for the treatment of chronic constipation.

We believe that there would be a market demand for more effective management of age-related chronic constipation. However, we first need to assess the market appetite and needs of a range of stakeholders to understand the most effective approach. This includes patients and pet owners, GPs and vets, care homes and hospitals, as well as the animal health, pharmaceutical and consumer health companies.

The proposed Pathfinder work will prepare the ground for a full Follow on Fund project by conducting essential market analysis and IP research that will provide an understanding of the unmet market needs. Outcomes of the project and the knowledge gained will inform and refine the objectives of our plans to exploit the technology, including the best route to market and the evidence needed in the next phase of development. This will allow the Follow on Fund project to deliver a compelling proof of concept for our research ideas with a clear route to application.

Our objectives are:

1.To perform a comprehensive assessment of the potential market for the proposed therapeutic approach. This will include a competitor analysis, analysis of existing competition and barriers to adoption, and analysis of the relevant unique selling points of the technology. We will also understand the key players involved with management of this condition, and examine stakeholder perceptions of different treatment regimes and drug administration methods.

2.To establish new contacts with potential collaborators/licensees across the biopharmaceutical, consumer health and animal health sectors to understand their needs and how the University may be able to address these. This would help to inform both the market pull for the medicine and the alternative routes to market.

3.To understand the overall intellectual property landscape for anti-TNF drugs and treatments for constipation, to allow us to develop a suitable IP strategy to support the appropriate exploitation route, identify potential freedom to operate constraints, and particularly to identify commercial companies with an active interest in this area.
4.To identify a commercialisation route map for the medicine. This will include an analysis of the potential licensees, and comparison with alternatives that might encourage the widest uptake and impact. The most likely exploitation route is thought to be through licensing to an established partner. Potential alternative exploitation routes could include collaborative research, or perhaps formation of a spin-out company.

These objectives will be achieved through a combination of secondary market research in the potential market sectors and primary market research with patients, pet owners, healthcare professionals and other stakeholders, and to gather market requirements through direct contact with potential partners.

While the expense and current route of delivery of anti-TNF drugs was seen as a major problem for the treatment of chronic constipation in older humans there was a possibility that this treatment could be used for age companion pets, particularly cats that are susceptible to age-related constipation.