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.
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.
(oral mucosal
and systemmic approaches)
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.
(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.
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.
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