Research
Pharmagenesis’ mission is to create value-added products based on the bioactive Natural Products found in Traditional Chinese Medicines (TCM). The following diagram describes the process used by Pharmagenesis in its discovery program as well as the types of pharmaceutical products that are generated:
Natural products have been a source of drugs and drug leads for
decades. According to scientists at the US National Cancer Institute, 61% of the
877 small-molecule new chemical entities (NCEs) introduced as drugs worldwide
during 1981–2002 are related to natural products.[1]
The natural product related NCEs include natural products (6%), natural
product derivatives (27%), synthetic compounds with natural-product-derived
pharmacophores (5%), and synthetic compounds designed on the basis of knowledge
gained from a natural product (that is, a natural product mimic; 23%).
If specific therapeutic areas are examined, the percentages are
higher. For example, 74% of
anticancer compounds are natural products or have been derived from, or inspired
by, a natural product.
Traditional Chinese Medicines (TCM)
The Company believes
that by focusing its research on TCM's which have been used effectively and
safely for millenna, there is a significant likelihood of finding new safe and
effective therapeutic products. The number of products already derived from that source
supports this view.
The TCM tradition is
a rich one that spans over 4,000 years of use. Herbal medicine has historically
been an integral part of Chinese culture and medical practice.
Descriptions of herbal therapy occur in the earliest texts that discuss
medical practice in China. Manuscripts
from tombs excavated in Hunan dating to 168 BC describe therapeutic combinations
of different herbs.[2]
This tradition continues today and China is making a drive to modernize
its traditional medicines. The
Pharmagenesis, Inc. strategy fits perfectly with the Chinese policy.
Currently in China,
there are 360,000 doctors specializing in TCM, over 2,000 specialized hospitals,
28 colleges of TCM, as well as 57 research institutes devoted to TCM.[3]
Also, virtually all hospitals that specialize in Western medicine have
departments of TCM.
Cell systems
Pharmagenesis has selected the cell systems responsible for immune
responses and generation of blood cells as its initial research focus.
Clinical situations
where suppression or stimulation of these systems is important are areas of high
medical need and, as such, represent significant economic opportunity.
This is especially true since in many cases the problems are chronic in
nature and require long-term therapy. Importantly,
TCM's are frequently used to treat disease conditions by modulation (stimulation
or suppression) of the immune system or the blood forming cells in order to
restore "balance".
Using reliable in
vitro and in vivo models, Pharmagenesis, Inc. is able to quickly validate those
TCM’s which are of highest value in treating these disorders, and to identify
those bioactive substances in the selected TCM’s which have the greatest
potential for development into new therapeutic products.
The identification
of product candidates from TCM's involves the isolation of highly-purified
active fractions and verification of their bioactivity in vivo, and subsequently,
in clinical studies.
Phytopharmaceuticals today
Natural sources such
as microorganisms or plants have long been an important source of drug products.
All antibiotics are derived from microorganisms found in nature and have
had an impact that has been enormously beneficial from both a medical and
economic perspective. Insects and
plants have also yielded important therapeutic substances.
Pilocarpine, an
important ophthalmic product for treating glaucoma, originates from a plant, as
does the anticholinergic, atropine.
The antimalarial
drug quinine is plant derived, as is theophylline, the asthma drug.
The once standard cardiovascular medicines digoxin and reserpine
originated from plants, as did the important anticancer drugs vincristine and
vinblastine.
Among many others,
the most prominent recent example is the drug Taxol, which was initially
isolated from the bark of a Yew tree growing in the Pacific Northwest.
It is a life-saving drug that is effective in treating certain resistant
cancers, notably ovarian cancer.
With thousands of plants in the Chinese Pharmacopoeia, Pharmagenesis, Inc.
believes that there is an enormous reservoir of bioactive molecules with a
history of human use that can be developed, either as new chemical entities or
as mixtures, into new products worldwide and/or as new drugs under Chinese
State Drug Administration Regulations.
Patent strategy and
Technology
Pharmagenesis
currently isolates low molecular weight (LMW) compounds from TCM’s and, when
possible, makes structural modifications to improve desirable drug properties and/or reduce
undesirable drug properties.
An example developed by Syntex, is a drug prepared from a naturally-derived, already-known compound: mycophenolic acid.
Syntex derivatized it to a patentable compound, Mycophenolate Mofetil, which
has now been approved by the FDA, as CellCept, for use in organ transplantation.
Another tactic is to isolate high molecular weight (HMW)
compounds from TCM's. This approach
has been overlooked, but promises to provide new drug candidates, especially when
tied to bioassay-guided isolation.
Our aggressive patent strategy has allowed Pharmagenesis, Inc. to develop an extensive patent estate.
[1] Newman, D.J., Cragg, G.M., and Snader, K.M., [J. Nat. Prod., 66, 1022 (2003)]
[2] P. Unshuld, Medicine in China: A History of Ideas, University of California, Berkeley (1985).
[3] MDIS Publication Ltd., The Chinese Medical Market (December 1995).