|
Company’s
Products and Services
return to top
The first products to be developed will be
reagents for diagnosing cancer in tissue specimens, as performed
in a cytopathology lab. The second generation of products will
be TCPP complexed with radioactive copper, in separate
formulations for imaging and treating human lung cancer.
Biomoda’s immediate product objectives for the U.S. market
include sputum sample cytopathology reagent kits using TCPP, a
lung cancer in vivo diagnostic product, and a lung cancer
therapeutic product.
There are presently no tests that are
recognized as effective for early detection of lung cancer, and
the present chemotherapeutic and radiotherapeutic treatment for
lung cancer do not use porphyrin derivatives. For early
diagnosis of lung cancer, the company’s success will depend on
developing a new market in response to the company’s products.
For diagnosing cervical cancer in vitro and for the use of
radioactive porphyrin for diagnosing and treating lung cancer in
vivo, the company’s success will depend both on capturing
customers in existing markets and on developing new markets in
response to the company’s products.
To date the company has not manufactured,
distributed, or marketed any products. The company believes that
contract manufacturing facilities will enable it to produce
commercial quantities of its products at least through 2003.
There can be no assurance, however, that manufacturing or
quality control problems will not arise as the company increases
production of its products, or as additional contract
manufacturing facilities are required in the future.
Product
Advantages
return to top
The use of porphyrins, specifically TCPP, for
diagnosis and subsequent treatment of cancer may have a number
of very real advantages over competing technologies that are
currently being used or that are in development. Some of the
advantages depend on porphyrin biology, while some are strictly
economic. Chemically, TCPP has a metal binder that makes it
beneficial for various therapeutic uses.
One biological advantage is the proven
specificity of TCPP for malignant tissue as well as for sites of
inflammation. Although porphyrins have been known for decades to
have an affinity for cancer cells, the specificity of TCPP is
unique, and patented. Biomoda is aware of no other companies
using porphyrins to diagnose cancer. The company is not aware of
any other company that is focusing on lung cancer treatment with
targeted radioactivity or cellular toxins.
Another biological advantage of TCPP is its
small size (less than 860 molecular weight). Since it is so
small and so closely related to naturally occurring porphyrins
(such as heme in hemoglobin), it is extremely unlikely to be
immunogenic. This is distinct contrast to monoclonal or even
“single chain” antibodies, with molecular weights from 45,000 to
over 150,000. It is generally accepted that foreign proteins
greater than 10,000 molecular weight are likely to be
immunogenic, and therefore likely to cause significant side
effects if administered repeatedly or in high doses. TCPP’s
small size also may facilitate diffusion out of blood vessels to
bind specifically to cancer cells, and should be a distinct
advantage for aerosol administration.
Since TCPP is not a protein and is of low
molecular weight, it should be easier to formulate as a
radiopharmaceutical than its protein competitors. Since each
molecule is smaller, an equivalent number of molecules
represents proportionately less mass than antibodies. In
addition, TCPP is expected to last longer in the bloodstream
than larger molecules, affording more opportunity for cancer
cells to be exposed to the radiopharmaceutical.
The porphyrin nucleus can be manufactured
inexpensively by bacterial fermentation, analogous to the
fermentation used to produce antibiotics, and TCPP can be
synthesized less expensively in a strictly chemical process. By
contrast, proteins are 10-100 fold more expensive to produce (on
a weight basis), and because of the difference in molecular
weight the mass of protein required per dose is likely to be at
least 30-fold higher. Porphyrin chemistry is fairly well
understood, and the porphyrin nucleus is amenable to
modification. It is possible that Biomoda will develop
porphyrins with affinities for different cell types, or else use
TCPP to carry other “killer ligands” or imaging agents to tumor
cells.
Although the biology of porphyrin uptake is
not completely understood, many tumor cells express a high
affinity (10nM) receptor for heme. This may be part of the
specificity that TCPP exhibits for cancer cells. There are very
few antigen-antibody or receptor-ligand interactions that are of
equally high affinity. There are a variety of syndromes
associated with disorders of porphyrin metabolism. These
syndromes may give clues to other diseases that may be amenable
to diagnosis or treatment with TCPP or other modified porphyrins.
Porphyrins as a class are relatively stable
biologically, particularly when compared to peptides or even
many antibodies.
For treatment of lung cancer by derivatives of
TCPP, there is a powerful rationale for expecting efficacy: if
the cancer cells take up the TCPP in a sputum sample, they
should take up Cu-TCPP in vivo. This makes effective TCPP
radiotherapy much more likely than for externally beamed
radiation or the case of treatment by a different modality than
used for diagnosis. Finally, if a surgical approach is taken,
Cu-TCPP administered prior to surgery could help a surgeon with
a hand-held radiation detector identify and excise all of the
tumor mass. Use of Cu-TCPP might also be indicated
diagnostically, to provide a radiographic view of whether the
tumor is diffuse, or isolated and solid. The information
provided might well determine the approach to therapy. At
present, no other modality can be used both for diagnosis and
treatment.
Basis for Product
Development
return to top
Product development will be accomplished based
on four mechanisms: licensing-in of patented technology,
applications development contracts with licensor laboratories,
contract laboratories with existing expertise, and automated
staining equipment manufacturers; development of technology and
products in house; and clinical development managed by Biomoda
in collaboration with NIH and FDA.
Significant progress has been made by Biomoda
to license-in patents and to forge cooperative research
agreements with licensor laboratories. Biomoda has exclusively
licensed the TCPP patents from the University of California for
lung cancer diagnosis and treatment.
Biomoda will be working in-house to develop
expertise in cytopathology and the biochemistry of porphyrin
uptake, including certifying cell lines for use as standards
(positive and negative controls) for use of TCPP and staining
protocols in cytopathology. Synthesis of porphyrin variants will
probably be contracted out to various companies.
Biomoda will pursue collaborative development
agreements with instrumentation companies to standardize
reagents and protocols consistent with their apparatus (flow
cytometers, robot stages, fluorescence detectors, and image
analyzers).
After either the sputum cytology or the pap
smear protocols have been validated, Biomoda may establish a
licensed cytopathology laboratory to perform these analyses at
least on a regional basis, and to serve as a
demonstration/training facility to expand use of the proprietary
tests.
Present Product
Status
return to top
One licensed U.S.
patent covering detection of cancers of the lung issued on
November 10, 1992. A second licensed U.S. patent,
covering treatment of cancers of the lung, issued on February
21, 1995. A third U.S. patent, owned by Biomoda, is
pending. International patents have been issued in the United
States, Australia, Brazil, Japan, Korea, Russia and, issued in
May 2002, Canada. The costs of preparation, filing and
prosecution as well as the maintenance of all resulting patents
are the responsibility of the company and are covered under the
License agreement.
On a low volume basis, the protocols for
sputum sample screening and pap smear screening have been
developed for developmental laboratory application. Formats need
to be developed that are sufficiently robust for use in large
volume operations and for clinical trials.
Essentially no coherent work has been done on
certifying standard cell lines as positive and negative
controls. Cell lines may be developed on a joint venture basis
with various companies.
A small amount of animal work has been done on
inflammatory focus imaging, and essentially no work has been
done on lung cancer imaging or treatment using Cu-TCPP. These
in-vivo products are in an early pre-clinical stage of
development.
|
