Article Excerpt:
TWST: What is Adherex Technologies?Dr. Peters: Adherex is a biopharmaceutical company with a broad portfolio of anti-cancer products, focused on two main areas. The first is the development of inhibitors of cell adhesion and signaling molecules, known as cadherins, to kill cancer cells. The second is the development of a product called eniluracil, which we are developing to enhance the effectiveness of 5-FU (one of the most commonly used anti-cancer drugs in the world). Beyond those two value drivers, the company has a broad platform of compounds in earlier development that offer unique opportunities to solve clinical problems and the potential to provide sustainable business opportunities for the company. The company initially was founded as a spinoff from McGill University; it evolved into a public corporation based in Ottawa and traded on the Toronto Stock Exchange, and currently is traded both on the Toronto Stock Exchange as well as the American Stock Exchange. The company is now located in the Research Triangle Park in North Carolina.
TWST: Give us an idea of the current targets for your company as far as
products, research and development, and where they fit in as far as markets and
opportunity?
Dr. Tyler has found, however, in repeated experiments that when ADH-1 is given
with the infused melphalan, all of the treated animals achieved complete
remissions of their tumors. Further, they did not return over the several month
course of the study. We have posted on our Website some examples of the results
with this combination. Dr. Tyler and his team were very impressed by these data
and are interested in pursuing clinical studies with ADH-1 in combination with
melphalan.
This data has provided very strong motivation for pursuing clinical studies in
combination, and we have refocused some of our internal resources to make this
happen as quickly as possible. Interestingly, we have seen similar results in
the treatment of ovarian cancer in animal models and are similarly working
toward moving these into the clinic as well.
Not only have we seen intriguing data combining ADH-1 with chemotherapy agents,
we also have reason to believe that the combination of our drug with biologic
agents such as Tarceva or Avastin may offer substantial additional
opportunities.
For example, in our recent Phase I clinical trial, we reported on a patient with
an N-cadherin positive esophageal cancer who achieved a formal RECIST criteria
partial response, defined as a reduction of at least 50% in tumor size, in the
multiple metastatic lesions in her lungs.
When that patient finally progressed after nine months of treatment with ADH-1,
the disease did not progress in the pulmonary metastases, which had shown a
response, but rather at the original tumor site in the esophagus. When that
recurrence was biopsied and studied for its cadherin expression, the recurrent
tumor was found to be N-cadherin negative and E-cadherin positive, where it had
been N-cadherin positive and E-cadherin negative at the start of ADH-1
treatment. This suggests that ADH-1 killed off the N-cadherin positive
population and that an E-cadherin subpopulation of the tumor grew out.
While we had always expected that ADH-1 would be specific for N-cadherin
positive tumors, what makes the tumor's change in cadherin expression
particularly intriguing is the recent finding by investigators at the University
of Colorado, and subsequently confirmed by others, that the FDA-approved drug
Tarceva, or erlotinib as it is known, is only active against E-cadherin positive
tumor cells. Tumor cells that are E-cadherin negative and N-cadherin positive
are resistant to Tarceva.
This is the exact opposite and reciprocal phenotype of the setting in which our
drug appears to be working. It implies that not only are these molecular
features of the tumor very important in deciding the sensitivity of the tumor to
particular drugs, it also suggests that ADH-1 is active at a particularly
important switch point in cancer progression, one that defines resistance to one
of the newest and most important therapies in cancer, Tarceva. Thus the
combination of Tarceva and ADH-1 might be a very attractive combination.
ADH-1's target, N-cadherin, is increasingly being seen as a very important
target in cancer therapy. It is a molecule that appears when certain tumor
suppression genes are turned off and serves as a survival factor for the cancer
cells. It is intimately involved in invasion and the metastatic process. And
importantly from a business perspective, to our knowledge, ADH-1 is the only
drug in clinical development that targets this important molecule. So there is a
great deal of scientific and clinical interest in combining our drug with drugs
like Tarceva or the other EGFR inhibitors. I personally think this could be a
very powerful approach.
As I mentioned earlier, ADH-1 is also able to affect the tumor vasculature very
specifically, and this presents another area of interest for combining our drug
with other biologics. Because ADH-1 causes vascular disruption in mature tumor
vessels, there is considerable interest in combining ADH-1 with an anti-
angiogenic compound such as Avastin, which targets newly forming micro-
vasculature. In this case, one agent, ADH-1, would target mature tumor vessels
and the other, Avastin or a similar compound, would prevent new vessel growth.
The complementary nature of these activities could be substantial.
To get ADH-1 to market, we will need to conduct pivotal registration trials. We
have two Phase II single agent trials ongoing and are getting ready to explore
ADH-1 in combination with chemotherapy in the clinic. These trials should
provide guidance for the tumor types, the proper design, and the target markets
for our drug.
So, in summary, there are several tumors that could be susceptible to ADH-1,
each expressing the N-cadherin target. ADH-1 has been well tolerated, even in
high doses for extended periods, and has shown anti-tumor activity in the
clinical setting as a single agent and synergy when combined with chemotherapy
in the preclinical setting. Ultimately the data will define the value of the
drug in the clinic, but thus far not only have there been no showstoppers in
developing this drug, the potential for the drug continues to grow as we move
forward in its development.
Tickers included in this excerpt: AHX:TSX
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