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Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
One extremely important step in the development of a new drug is that point which is called first in human. It's the very first time that a promising new treatment is actually given to a human. And this happens in what we call a phase one clinical trial. Its first priority is safety. The drug must be safe for humans to take.
Dr. Moira Gunn:And there's a second priority, and it has everything to do with finding a workable dose. While there are several ways to do it, a typical one is to start with a very small dose and then a slightly larger one and so on until you reach the dose you believe will have a therapeutic effect. At each dose level, you check the side effects. Are they increasing? Are they tolerable?
Dr. Moira Gunn:And sometimes, as in very infrequently, something unexpected happens. Sometimes in phase 1, you begin to get an indication that the drug is actually working. And that's exactly what happened for Pacylex Pharmaceuticals. Doctor Michael Weickert is its CEO. Doctor Weickert, welcome to Bio Tech Nation.
Dr. Michael Weickert:Thank you. Delighted to be here.
Dr. Moira Gunn:I'm starting this in a somewhat different place than I normally would an interview relating to emerging treatments in cancer. But the first thing that struck me was that paselex is committed to not long infusions at hospitals and cancer centers, but rather a treatment that is a once a day pill. That doesn't happen so often in, cancer treatments. So let's start with this once a day pill. What it does is called Zelenirstat, that's with a z, Zelenirstat.
Dr. Moira Gunn:If you don't mind me just attempting to pronounce it. But if we could, we we can call it our drug, your drug, from here on in. But what does this once a day pill do?
Dr. Michael Weickert:So what Zelenirstat does is it actually inhibits a biological process that has never been addressed before in cancer or any other disease. So this biological process makes proteins sticky and they need to stick to cell membranes or other proteins in order to be active. And that stickiness is what our drug, Zelenirstat inhibits. And that stickiness is important because cancer cells have hijacked a bunch of processes in the cell. And they hijack those processes because they're involved in control of normal cell growth.
Dr. Michael Weickert:What is cancer? It's uncontrolled cell growth. So cancer has to hijack these processes to stop the control of growth and allow the cancer cells to grow uncontrollably. But there are many different processes that use this biology to stick those proteins, you know, to where they need to be. And we interrupt that process.
Dr. Michael Weickert:So the cancer cells that have hijacked this biology, those cancer cells are extremely vulnerable to any drug that inhibits this process. And so those cancer cells are going to be killed by our drug at concentrations of drug that don't affect normal cells. And that's the beauty of this approach, is that you can give patients a once a day oral dose of our drug. It will selectively kill the cancer cells, but it doesn't affect the normal cells.
Dr. Moira Gunn:Now what exactly is it doing with respect to cancer?
Dr. Michael Weickert:Yeah to to get into a little bit more detail, the processes that are hijacked by cancer cells involve signaling to the cancer cells to grow and not grow. It involves growing new blood vessels into the tumor to feed the tumor. It involves producing energy for the cell and especially for new cells as they grow. And so those processes are the processes that cancer cells have hijacked that are sensitive to inhibiting this biology. And that's what we're actually doing.
Dr. Michael Weickert:We're destroying all three of those things at the same time with a single drug that you can take once a day.
Dr. Moira Gunn:Now let's go to your experience with this drug in humans. You are well past phase 1, but I think that your phase one experience is very telling. Let's go there. What cancer patients participated in phase 1? What was their experience?
Dr. Moira Gunn:And while you were only looking at safety, what else did you learn?
Dr. Michael Weickert:Yeah. Our phase 1 was very illuminating. So in our phase 1 study we basically took what we call all commerce. Anybody with, cancer that has failed their prior therapies was eligible to participate And the most abundant patients are solid tumor cancer patients, patients with lung cancer, breast cancer, colon cancer, ovarian cancer, those kinds of cancers. So we had many different cancer types participate in the study and we actually, saw we were looking for safety.
Dr. Michael Weickert:We wanted to see is this safe to administer to patients. What we didn't expect to see when you do a study like this is you don't expect to see patients benefit because we're taking all comers. We're not trying to target the patients that are expected to respond to the drug like a lot of studies do. We're just saying anybody who has a cancer that has basically exhausted all their treatment options, you can come on the study. Despite doing that, when we got to the dose we've now taken into phase 2, most of the patients were staying on the study.
Dr. Michael Weickert:And they can only stay on the study if they have benefit, meaning the disease is now stable or improving. And so 57% of our phase 1 patients that got to the dose we've taken into phase 2 stayed on the study drug for 6 months or longer because they had stable disease or better, which was a very big surprise because these patients were from all different types of cancers. So that's what's really distinctive about this. Most cancer therapies being developed today are targeting something very specific. This was a broad patient population with a lot of different prior treatments, an average of 4 prior therapies that they failed.
Dr. Michael Weickert:And many of those patients were seeing benefit.
Dr. Moira Gunn:Now 57%, that means either tumor stoppage, there's no more tumor growth, or tumor reduction?
Dr. Michael Weickert:That's exactly what it means.
Dr. Moira Gunn:And some of those original participants have continued with the drug?
Dr. Michael Weickert:Yeah. We have a colorectal patient that's had drug for more than 450 days. And of course, again, you would only stay on drug if you're seeing a benefit, if you're seeing stable disease or better. And that patient had about a 50% reduction in tumor volume and about a 50% reduction in the tumor biomarker, that's, in the blood that tells you what type of cancer you have. So, that was very exciting and that's led us to actually start a phase 2 program looking at colorectal cancer patients to see if we can reproduce this in more patients.
Dr. Michael Weickert:And that study has just gotten underway, but we do have the first patient on that study now has stable disease. They've gone through their 1st checkup and, they have stable disease. So that's looking very exciting too. We also have started a phase 2 in lymphoma, and the second patient in the lymphoma study has what we call a partial response. They have a certain threshold of tumor reduction that they've already achieved.
Dr. Michael Weickert:So that's also looking very promising. But again, it's very, very, very early stage for those phase 2 studies.
Dr. Moira Gunn:Now you do have a phase 2 that is ready to go and you're partnering with the well known MD Anderson Cancer Center and you've received partial funding from the Department of Defense. Now I know you're looking to finish up that funding and to get underway, and this treatment is leukemia. So let me ask you this, why is the Department of Defense interested in funding a treatment for leukemia?
Dr. Michael Weickert:Well, it's it is very interesting and, we were just as surprised as you were that they were available for as a agency that would grant funds for studies. But they are very concerned about the health of their war fighters and their veterans, and this is all part of their programs for health care, for the people in the Department of Defense. Many of them are exposed to things in the course of their service that could potentially cause leukemia, but of course veterans live a long life after their retirement from the military and a lot of them get leukemia just like the regular population does. So the Department of Defense has been very generous in supporting the phase 1 program that we're doing and, we are just looking for matching funds because you can't start a clinical study without enough money to finish. And right now the Department of Defense grant covers about half of what we need and we're just looking to support the other half in order to get that launched.
Dr. Moira Gunn:Now leukemia is present in many professions.
Dr. Michael Weickert:Oh, yeah. Definitely. I mean, it's a very common cancer and acute myeloid leukemia, which is the leukemia that we're targeting first, is a form of leukemia that's particularly challenging. Its 5 year survival rate is only about 30%. So that is, you know, very poor.
Dr. Michael Weickert:And so even despite all the therapies that are currently available, patients, you know, do poorly over the long term. Now one of the other exciting things about our drug is that we've looked in vitro, meaning in the lab, at a combination of Zelanirstat, our drug, and venetoclax, another drug that's already approved for acute mitralukemia. And it turns out that if you combine those two drugs, they are extremely synergistic against leukemia cells. They actually kill leukemia cells at much higher rates than either drug does alone. So the physicians at MD Anderson are very, very eager to get this clinical study underway because as soon as we've established that our drug is safe to dose leukemia patients, then we can start combining it with this drug, which is also an oral once a day pill.
Dr. Michael Weickert:So the idea of having a combination of 2 oral therapies that patients can take instead of the highly invasive procedures that are currently used for treatment is extremely attractive.
Dr. Moira Gunn:Now I understand the FDA has just changed the status on this drug with respect to acute myeloid leukemia.
Dr. Michael Weickert:Well, they they have granted us a couple different important designations. Orphan drug designation, which allows for additional exclusivity, when your product is approved in the market, and then fast track designation, which means that we would be reviewed much more quickly by the US FDA than a normal drug. So fast track means that we would be reviewed in 6 months rather than the normal 12 months.
Dr. Moira Gunn:Well, fast track you better get fast track to funding here, buddy.
Dr. Michael Weickert:Yeah. No kidding.
Dr. Moira Gunn:Fast track doesn't do
Dr. Michael Weickert:you any good if you have to delay. But at any rate That's right. That's what you said.
Dr. Moira Gunn:Now this is the 3rd study we've just been talking about where you're looking for more funding in addition to the Department of Defense funding, and that's focusing on leukemia. Your other two phase two studies, one is for lymphoma, the other for colorectal cancer. What is it like for these phase 2 participants? Who qualifies? How is it different from phase 1?
Dr. Moira Gunn:And are they different from each other?
Dr. Michael Weickert:Well, thanks. The difference, between phase 1 and phase 2 is very minor for the patients. The same kinds of patients are enrolled, so the same kind of lymphoma and colorectal cancer patients are enrolled. In the phase 1 study we took all comers, all different types of cancer, so we're limiting it to specific types of cancer that we've seen potential benefit in. And in fact, in the phase 2 lymphoma study, we've already observed a patient, as I mentioned, who's gotten a partial response in the colorectal study.
Dr. Michael Weickert:Our first patient in that has also seen stable disease at their first checkup. So those are the 2 promising types of patients. They will receive, the effective dose. The dose that we established in phase 1 that looked promising, that's what all patients receive now. They don't get any other doses.
Dr. Michael Weickert:Difference is that they will potentially have that dose split over twice a day rather than once a day to see if splitting the dose into twice a day pieces makes it more effective and maybe, you know, less side effects. So that is the only difference. But the big benefit is everybody gets the dose. There's no placebo in these studies, and we're planning to add some ovarian cancer patients, to the study as well. So we saw benefit in a couple of ovarian cancer patients in the phase one study.
Dr. Michael Weickert:They had 6 months or longer benefit of stable disease or better. So we're also planning to add some ovarian cancer patients soon. We just got a grant to add some of those patients into the study.
Dr. Moira Gunn:So we talked about how in phase one, if you your participants were doing well, that they would continue on the drug. One person over a year has been on this drug to this day. Yeah. What about people in phase 2? If they continue to do well, will they continue to receive drug?
Dr. Michael Weickert:Yes. As long as patients are benefiting from the drug, they will continue to receive the drug. You know, we look at it as sort of a moral and ethical imperative. If you have benefited patients by providing them with a drug, it's not really appropriate to withdraw that access if they're benefiting.
Dr. Moira Gunn:Now all of these studies are, on humans who have exhausted all treatments. At what point could a drug like this, a once a day pill or even just a twice a day pill, be tried as a first treatment someone gets? How does that work?
Dr. Michael Weickert:So for all new cancer drugs they're almost always used in patients that are last line like like this, like patients who have exhausted everything else. Because it's really not appropriate to give a cancer patient a drug that hasn't been proven yet when you have other drugs that might work. But once we have established that our drug is effective in these patients, then we can start studying the patients at earlier stages. Because when you have a once a day pill, you don't want to wait till the end and take that as the last thing. That should be the thing you try first before you do a cell based therapy or a bone marrow transplant or some of these extremely expensive and invasive procedures that these cancer patients undergo.
Dr. Michael Weickert:So eventually we would like to move up to second and first line therapy, but we have to prove the drug works first. And that's going to be in these last line patients. The other thing that I'll bring up that's really exciting in leukemia in particular, and probably will apply to other cancers as well in the future, we've done some testing in the lab combining our drug with another drug in leukemia. And that combination of drugs is much more potent than either drug is alone. And the data has been shared with the physicians at MD Anderson and they're very eager to start trying that combination in leukemia patients because the other drug is also a once a day pill.
Dr. Michael Weickert:So the idea of having a combination of 2 oral medications you can take in patients and have a very, very strong leukemia response is extremely attractive.
Dr. Moira Gunn:Well, doctor Weichart, thank you so much. I I we wish you luck, and, we hope you come back. See us again.
Dr. Michael Weickert:Well, it's been a delight. I really appreciate you taking the time.
Dr. Moira Gunn:Doctor Michael Weickert is the CEO of Pacylex Pharmaceuticals, a Canadian biotech firm focusing on the treatment of a broad range of cancers and taking advantage of the ease of use patients experience taking a simple oral capsule once or twice a day. Information about the cancers they are studying and the status of their clinical trials is available at pacylex.com. That's pacylex.com.