|Overview Proxima Concepts Limited is an international biopharmaceutical R&D company which has made 4 significant advances since the year 2000 to fulfil the unmet need for technologies to help the products of the biotechnology industry achieve their full potential in the area of healthcare and therapeutics.
Three oral peptides in clinical development and two oral peptides in pre-clinical
WITHOUT NEW CHEMICAL ENTITIES
Proxima’s lead projects focus on new delivery systems for enhancing the uptake of peptides, proteins and other macromolecules when administered via the oral route in a tablet or capsule. Proxima has developed its own proprietary technology which can increase the absorption of peptides across the intestine by at least an order of magnitude. Patent applications have been filed, and proof of concept of the system has been demonstrated in small & large animals and humans, showing detectable levels of peptide in the blood stream, and a significant biological response. In contrast to all other known systems for oral peptide delivery currently being commercialised, Proxima’s delivery vehicle is simple and cheap to manufacture, and consists entirely of registered pharmacopeal excipients, for which no new regulatory obstacles are anticipated. Product scale-up (to GMP manufacture has been completed for one oral peptide), trial and launch can therefore be conducted very rapidly, particularly in emerging markets, and as a consequence, human Phase IIa clinical trials have been completed for insulin and salmon calcitonin aswell as a phase I trial for parathyroid hormone. In addition, phase I is in the planning stage for two further molecules of high potential market value. This delivery vehicle is potentially capable of incorporating a range of peptides for proof of concept feasibility studies to show oral absorption.
Vaccine delivery vehicles (oral mucosal and systemmic approaches)
WITHOUT NEW CHEMICAL ENTITIES
Proxima has extensive knowledge in-house in the construction of lipidic vehicles for use as oral vaccine delivery systems, targetting the Peyers patches to generate mucosal immunity in the intestine and further afield. A range of different vehicles are available for testing, including innovative variations on liposomes, emulsions and micelles, for which proprietary manufacturing technology has been generated. Proxima is conducting fully-funded feasibility studies with a major pharmaceutical company working in the vaccine field, and a collaboration with an innovative UK biotechnology company to work on DNA vaccines is underway. Proxima is also working with a non-commercial body to develop oral vaccines for respiratory diseases.
A New Method of Identifying and Targeting Cell Function Modulating Therapeutics(an alternative to high throughput screening with targeting)
Having established a role for itself in the area of delivery of biologicals, Proxima plans to grow through the exploitation of a new technology termed “Mozaic”. This proprietary technique, utilising unique characteristics of fluid membrane mosaics, takes the power of combinatorial chemistry several stages further to create a system which can construct receptors capable of binding to cell-surface ligands. In particular, the initial assay screen is conducted in vivo, or with whole cells, and the probes presenting the different structures are prototype delivery vehicles. The technology therefore provides a potentially rapid method for solving drug delivery problems in a few simple steps without reliance on a long list of assumptions inherent in conventional combinatorial search methods. In addition to identification of receptors for targeting, the technique has already created a potentially new class of therapeutic agents capable of eliciting a range of TNF responses after binding to cells. These molecules are now in preclinical testing to downregulate TNF production for arthritis treatments.
A new method of constructing Building Blocks to make fluid micelle structures Druggable
1. Lexcicon is an approach developed by Proxima to engineer secondary and tertiary structure into short oligopeptides which would normally form random disordered chains. Fixing peptides in rigid conformations in this way is important in achieving strong binding interactions with ligands and receptors. 2. The Lexcicon construct is large enough to accommodate several distinct binding sites, and these can be identical, or completely different from each other. 3. These binding sites can be incorporated into a single therapeutic unit either by bringing them all into one Lexcicon peptide construct, or by allowing different constructs to associate together. Thus, in the final therapeutic agent, one epitope could encourage its transport across gut cells to make it orally active, a second epitope can target a specific cell type in the blood stream, while a third can down-regulate its activity after internalisation.