The project will evaluate the feasibility of inhaled delivery of a cocrystal-enabled known drug to treat idiopathic pulmonary fibrosis (IPF) in-vivo. The 1st therapies for IPF - a growing disease (5000 UK patients diagnosed/year*) with high mortality (50% die in 2-3 years of diagnosis*) were approved in 2014 (Pirfenidone & Nintedanib). These new therapies do not prevent disease progression and as oral treatments have highly undesirable side-effects. The project aims to show that by delivering a more effective drug directly to the lung, the efficacy of treatment can be increased without side effects. There are 4 innovative aspects: 1. Inhalation for IPF is a novel concept & enables drug delivery direct to the site of need, increasing efficacy and minimising undesirable drug exposure. >80% of patients have the lung function to use a dry powder inhaler (DPI)**. 2. The active ingredient will be Tranilast – a Japanese oral asthma drug with a strong safety profile. Tranilast is also well validated as an anti-fibrotic agent and therefore has new potential for use in IPF. 3. Cocrystal technology can improve key physical properties for drug molecules. Tranilast is highly insoluble and cocrystal technology will improve lung solubility & biodistribution, maximising performance. This cocrystal application would be a 1st for inhalation. 4. Bleomycin is an accepted IPF disease model but has limitations. The Lung Slice Culture (LSC) model addresses its problems & reduces the number of animals used, but is less validated. The 2 models have not been compared using the same drug. This novel combined approach will further validate both the result and the LSC model for future studies. 5. The processes & devices used for DPI delivery in-vivo are limited and less validated than other methods. The study will develop reliable processes to investigate the delivery concept that matches the envisaged end product (DPI). *NHS data **Prof. G. Jenkins

Nuformix and Vectura will explore pre-competitive applications for the use of cocrystal technology within inhalation formulation and product development for the treatment of respiratory disease. It is hoped the output will provide indications for future product development opportunities and TSB funding will accelerate that process.

The CODE-PM project represents a new approach to drug development. The aim of CODE-PM is to generate high-value Intellectual Property (IP) in the emerging field of pharmaceutical cocrystals for subsequent out-licensing to the pharmaceutical industry. A cocrystal is a crystalline entity in which more than one molecular substance is incorporated into the repeating unit cell (see Annex 1: Scientific Appendix). A pharmaceutical cocrystal therefore is comprised of a drug compound and one or more other compounds, referred to as coformers. CODE-PM is an extension of the development activities of Nuformix Ltd - a virtual drug development company based at The Wilton Centre, formed in October 2008. CODE-PM will help address an immediate market opportunity arising from the convergence of advances in the sciences of crystal engineering, continuous processing and nanoparticulates, combined with a buoyant pharmaceutical in-licensing market. i) Why is there a need? Drug cocrystals often have very different physical properties from their pure form and these important changes offer great commercial and societal potential. Varying the coformer provides a new opportunity to optimise or improve a drug's performance in any number of aspects, including: • Bioavailability and product efficacy • Cost of manufacture • Ease of formulation and manufacture • Chemical stability • Product shelf life and ease of storage • Patient benefits such as a reduction in side effects and removal of food effects It is estimated that as many as 70% of the world's top 500 drugs perform sub-optimally in any number of the above key performance areas. Delivering such improvements to existing drug products will substantially benefit both patients and drug manufacturers alike. Ultimately the products developed in the CODE-PM project will deliver cheaper medicines and more effective treatment of disease whilst enabling the pharmaceutical industry to sustain important new product development activities.