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A new Cancer Target brings new Cancer Hope
Dr. Michael Weickert
Michael J. Weickert, PhD
Interview conducted by:
Lynn Fosse, Senior Editor
Published – November 23, 2020
CEOCFO: Dr. Weickert, what is the vision behind Pacylex Pharmaceuticals?
Dr. Weickert: Pacylex is developing a new first in class therapeutic to hit a new target in cancer. A researcher at the University of Alberta named Dr. Luc Berthiaume discovered a connection between a biological process called myristoylation and certain cancers, particularly blood cancers, like leukemia, lymphoma and myeloma. He also found that a drug that suppresses the process of myristoylation has a disproportionate impact on those leukemia, lymphoma and myeloma cell lines, killing them while sparing normal cells.
Additional research by Pacylex showed that in animal models, where you transplant tumor tissue into mice, you can completely regress or eliminate those tumors by administering an NMT inhibitor, NMT stands for N-
CEOCFO: What is myristoylation?
Dr. Weickert: Myristoylation is a biological process of adding a small fourteen carbon fatty acid to the amino-
The B cell receptor complex has two different myristoylated proteins and when you inhibit myristoylation you completely disrupt the function of this complex; you eliminate the modification of a handful of these important pro-
CEOCFO: Why does the drug work? What is happening in the body?
Dr. Weickert: Because of the importance of this B cell receptor complex in allowing the survival and growth of tumor cells in these hematologic malignancies, they are exquisitely sensitive to the drug. However, there is another factor. One of the two human enzymes involved in myristoylation; they are called NMT1 and NMT2, so it is pretty simple, one of those two enzymes is actually down regulated in these specific cancers, making the cancers even more sensitive than normal cells to an inhibitor of the remaining enzyme. Thus, you are getting and effect equivalent to what you call, “selective lethality”, by administering a drug to which the cancer cells are an order of magnitude or more sensitive than normal cells are.
CEOCFO: What are you working on right now? Where are you in the process?
Dr. Weickert: We are currently preparing to file the regulatory authorization document called a Clinical Trial Authorization to initiate clinical studies at three sites in Canada. The company Pacylex is a Canadian company headquartered in Edmonton, Alberta and our three clinical sites are at the Cross Cancer Institute in Edmonton, Princess Margaret Hospital in Toronto and the BC Cancer Agency in Vancouver. Those three sites are expected to begin clinical trials sometime early in 2021. We are expecting to file for authorization to begin those studies by the end of this year.
CEOCFO: What is special about trial sites you mentioned?
Dr. Weickert: These are three of the most prominent, if not “the” most prominent cancer institutes in Canada. They have an extraordinary number of patients and they have extraordinarily well qualified oncologists through which we can conduct the studies. We have principal investigators at all three sites that are primed to begin enrolling patients as soon as we have the authorization to do so.
In addition, our Chief Medical Officer, John Mackey, is a practicing oncologist and happens to be the Director of Clinical Trials unit at the Cross Cancer Institute in Edmonton. This means that he cannot be the principal investigator for the study, so we actually have a different principal investigator who has been recruited to actually perform and conduct the study at the Cross Cancer Institute. However, these are really marquee institutions within Canada.
CEOCFO: What has been the response from medical people who are aware of what you have developed?
Dr. Weickert: Medical people find it extraordinarily exciting to have a new mechanism and a new first in class therapy. In cancer, most of the therapeutic evolution that has taken place over the last five or six decades has been combination therapy. However, combinations only work when they are working through orthogonal mechanisms; mechanisms that are different at the root of how they affect the cells. Finding a new orthogonal mechanism that could potentially combine with other mechanisms to yield a better outcome for patients is a pretty exiting outcome.
We have physicians, not only in Canada, but also in the United States and in England that are standing by to conduct clinical studies of their own as soon as we have the authorization to do so. We have researchers at the MD Anderson Cancer Center in Houston, Texas and also at the University of Birmingham, who have access to a huge number of potential patients and they are both eager to begin conducting a study in acute myeloid leukemia, which we intend to start probably mid next year.
CEOCFO: You have been personally involved in a number of companies over the years. What attracted you to take on Pacylex? What do you understand about the whole process of development, dealing with the regulatory authorities and all of the pieces that go into it that will help smooth the way?
Dr. Weickert: Those are two really good questions and I am going to separate them completely. The reason why I am exciting about Pacylex is that I have a long-
The second part of your question is what experience do I bring from the development and regulatory side that helps me understand what we have to navigate to get this product developed. I have been working in drug development for over twenty-
I have an intimate knowledge of all the development steps from pre-
CEOCFO: What have you recognized that you might not have known early on how to navigate the system?
Dr. Weickert: There are many things that come around again and again. For example, not necessarily with Pacylex, but with another company I am helping, the priority review vouchers are an important regulatory tool for encouraging the development of compounds that treat diseases that would ordinarily be ignored from most large pharma companies, because the market is too small or it is mostly in the developing world. However, a priority review voucher is a tool that allows a company to get approval in six months or less. Normal approval takes roughly a year. That is the target for the FDA. Now, in a product in a very competitive landscape, where there are multiple companies trying to get their products on the market; going from a twelve month to a six-
Pharma companies are willing to pay up to roughly one hundred million on average right now for a priority review voucher. In some cases, they have gone for over three hundred million. Therefore, a company’s ability to obtain a priority review voucher can yield an early financial return for that company for a product that ordinarily would not get a return that fast. That can become a really useful tool. As I said, this does not apply to Pacylex, but that has come up with another one of my companies recently, where that priority review voucher might be a material asset for that business, because they have a product that is well fitted to potentially obtaining one if they decide to select that indication as one of their initial indications.
There are few things that are completely new, but there is stuff that comes up again and again. However, on the new side of the priority review voucher, just last month that expired for diseases that are impacting children, so there had been a priority review voucher program for certain childhood conditions and that has gone away. Now it is only still in effect for certain tropical and rare diseases. That is a recent change that is quite material for a number of companies and their potential products.
CEOCFO: What, if anything, has changed for Pacylex under the COVID environment?
Dr. Weickert: We do not have face to face meetings anymore. Surprisingly little has changed in terms of our ability to continue to execute towards the clinical trials that I mentioned, except that when India, where we are making our drug substance, was shut down for several months in the early stages of pandemic, the ability to manufacture our drug was also shut down. Therefore, we experienced a several month delay in our ability to obtain the drug necessary to create the capsules that would be used in the clinical studies.
CEOCFO: What is your funding situation today at Pacylex?
Dr. Weickert: Pacylex closed a seed round in February of roughly five million Canadian dollars. We are currently in the midst of a Series A, looking for twelve and one half million (US dollars). We do have some leads and are in negotiations with some companies. We also have some strategic interest, but we do not yet have a deal finished. Therefore, we are still doing our best to highlight the company and we are presenting at a number of conferences, most recently at the BIO Investors Conference last month, and in addition, the recent publication in Nature Communications of the research results on lymphoma, allow us a nice new opportunity to engage with people who have seen those published results.
CEOCFO: Is cancer of interest to investors today?
Dr. Weickert: Oncology has been very hot for a long time. In the last five years, there has probably been more investment in oncology than any other therapeutic area and it remains very attractive to investors. Although, because of the investment and the attractiveness, it is a very crowded space. There are an awful lot of companies working in that same space, but it is still very attractive.
Even the recent pandemic has not dimmed interesting in oncology, but it certainly has highlighted infectious disease as a neglected therapeutic area that perhaps deserves more interest from investors, as well as obviously, the interest it is getting from the governments that are attempting to support it. Yet, oncology is a very, very appealing area and one of the things that drives that is that there have been more transactions in oncology by large pharmaceutical companies than pretty much every other therapeutic area put together. Therefore, if that is what pharma is buying, that is what investors are going to be supporting.
CEOCFO: What was unexpected in your finds so far?
Dr. Weickert: The only thing that I would say that we have obtained since I joined the company almost three years ago, that we did not have plenty of evidence about before, is the toxicology results. Those are essential for going into the clinic. We have elaborated on and embellished the other results we already had, we have not learned necessarily, fundamentally new things. What we learned in the toxicology that surprised me the most was that dogs, one of the two species we used, do not have not have a very close homolog to one of the NMT enzymes in humans. When you are working in animal species you are using them as a surrogate for what you are likely to see in people.
What we learned in the tox study is that dogs, unlike every other species we looked at; mice, rats, pigs, monkeys, humans; those species are all ninety-
CEOCFO: There are so many new ideas to evaluate. Why pay attention to Pacylex Pharmaceuticals?
Dr. Weickert: There are some features about this drug that I have not described that are really important to think about. One is that this drug is oral, so you just take it as a pill once a day. That is really appealing. Patients can be medicating at home; they do not have to come into an infusion center like many cancer patients do. Number two; it is a drug that is very potent. In our in vitro assays it is ten times as potent as Dasatinib and Ibrutinib. These are two multibillion-
Another really critical thing is that because we are working through a new mechanism of action, we have the potential to synergize with other drugs. Oftentimes, when you look at the crowded oncology field you think, “There is so much competition out there!” However, in our case we look at that crowded field and say, “Look at how many potential partners we have.” We could potentially work with almost every drug out there, because we work through a different mechanism of action than they do.
The last really important thing is that this is tumor killing. We are not just inhibiting the growth of the tumor like many drugs do. We are actually triggering apoptosis, a programmed cell death in the tumors. As a result, this drug has the potential to achieve complete durable remissions in patients, even as a mono therapy, and it is exciting to have a potential mechanism that would produce a dramatic improvement in the care and the outcomes for patients.
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“Because we are working through a new mechanism of action, we have the potential to synergize with other drugs. Oftentimes, when you look at the crowded oncology field you think, “There is so much competition out there!” However, in our case we look at that crowded field and say, “Look at how many potential partners we have.” Dr. Michael Weickert