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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.
The world we know is changing. I'm Moira Gunn, and welcome to Biotech Nation. Doctor Robert Eng from Voor Biopharma will talk about Voor's unique approach to a particular kind of cancer, acute myeloid leukemia, perhaps better known to you as AML. And now, doctor Robert Eng. Well, Robert, welcome to Bio Tech Nation.
Dr. Robert Ang:Thank you very much, Moira. It's a privilege to be here.
Dr. Moira Gunn:Now today we're gonna talk about a particular kind of cancer, acute myeloid leukemia, AML for short. What is it? Who gets it? And how prevalent is it?
Dr. Robert Ang:Yeah. So AML acute myeloid leukemia is a, blood cancer, therefore, leukemia, and it affects, something called the myeloid compartment. Now the myeloid compartment is actually the bone marrow. Yeah. In in our bone marrow, we produce cells that we need in our circulation.
Dr. Robert Ang:And so acute myeloid leukemia is where you get disease of this bone marrow that causes, the bone marrow to be taken over by these blast cells, these cancerous cells. Now AML happens across all ages. It tends to be more common as you get older. So a lot of patients are in their fifties, sixties, or even older. And, it's actually very common.
Dr. Robert Ang:It's actually the most common acute leukemia in adults.
Dr. Moira Gunn:What is it like when you have it? What is that experience?
Dr. Robert Ang:Yeah. You know, a lot of patients when they get AML, they don't know they have cancer. In fact, a lot of the symptoms are pretty nonspecific. So for example, they could feel weak. Maybe they get easy bruising.
Dr. Robert Ang:They get out of breath. And what it's due to is, in fact, that this cancer is slowly taking over the bone marrow. And, in fact, it's squeezing out the healthy cells, such that regular cells that you need for survival, like immune cells or or platelets that clot your blood or even simple red blood cells that carry oxygen, are squeezed out and and your body tends to start dysfunctioning. And so that's really how you can tell. And then your doctor would take your blood.
Dr. Robert Ang:They would also take a sample of your bone marrow, and they would discover these AML blast cells, sitting in there.
Dr. Moira Gunn:Now if nothing is done, how long can this go on?
Dr. Robert Ang:Yeah. Unfortunately, a lot of AML is very aggressive. And when simply these healthy cells are squeezed out of the bone marrow, that is not compatible with survival. These cells end up taking up all the space and all the nutrients that are needed to produce normal healthy blood cells that, you know, you'll need to carry oxygen around your body or to, have important immune functions. And, unfortunately, you really only have months of survival in some cases.
Dr. Robert Ang:And so the prognosis is actually pretty dismal without therapy.
Dr. Moira Gunn:Well, doctor Ang, today how is it treated? I mean, what is what we call the standard of care for someone with AML?
Dr. Robert Ang:Yeah. So, in fact, the standard of care for AML was established back in the sixties seventies. And chemotherapy is a dirty word in a lot of circumstances. However, in AML, chemotherapy is generally very beneficial. And there's a chemotherapy regimen called 7 plus 3 chemo based on the number of days that you receive it.
Dr. Robert Ang:And 7 plus 3 chemo is actually very effective at knocking down this cancer in roughly 70 to 80% of patients. There's a couple of caveats to that. Firstly, some patients may have other complications or the disease may be severe enough that chemo doesn't work. But probably the more important complication is that even though the chemo is initially effective at knocking down their cancer, if you were to stop the chemo, the cancer would aggressively return. And what happens is that these cancer cells end up hiding out in little niches in the bone marrow.
Dr. Robert Ang:And so chemotherapy, as well as radiation, which is sometimes used, just can't touch it. And, the moment you stop therapy, the cancer returns. And so another thing that's done that was actually revolutionized, back in the seventies was this bone marrow replacement, that you could actually take healthy marrow from an individual that is matched to your own blood and replace your diseased cancerous marrow with this healthy marrow. What you need to do there is you need to actually clear out the bone marrow of your diseased cells, and they can use high strength chemotherapy or or radiation to do that. And then you can replace the bone marrow with these healthy cells from a healthy donor.
Dr. Robert Ang:That could be a relative, like a sibling or a child, or or it could be a stranger that happens to be matched to you. And that's really a revolution that that someone else's cells can reside in you for forever, basically, and replace your diseased cells. And so that was quite a revolution, and and that is called an allogeneic stem cell transplant.
Dr. Moira Gunn:How effective is that?
Dr. Robert Ang:Allogeneic stem cell transplants are effective in some people. And in fact, it's curative because you're using this high strength chemo to clear out the cancer and replace, you know, these healthy cells. And so roughly about half the time, it is, very effective and and even curative. Unfortunately, in the other half of patients, that is not the case. And you end up getting recurrence of this cancer despite all the trouble of going through this, stem cell transplant.
Dr. Moira Gunn:Well, now the important question. What is CD 33?
Dr. Robert Ang:CD 33 is actually a molecule that sits on the cell surface of cancer cells and, in fact, in 95% of AML patients, their AML cells express this protein called CD 33. Think of it like a little flag, and we're looking for all the cells with a red flag on the surface. And this red flag is CD 33. And so if you were to kill anything that has this red flag, it would kill all the cancer cells. There's a problem with that though.
Dr. Robert Ang:There's a lot of healthy cells in your body that also have the same red flag, the CD 33 molecule. And in fact, if you end up doing that and killing all cells that express CD 33, you also kill healthy bone marrow cells. You can become very sick or you can even die from killing all of these cells with that same flag. And so CD 33 is known to be a very good marker of cancer cells, of AML cells, but unfortunately, it's it's inherently flawed because of its expression on healthy cells.
Dr. Moira Gunn:Okay. So what do you do?
Dr. Robert Ang:So, you know, people really struggled with this. A lot of people have tried different ways of targeting that molecule, but it doesn't solve the issue at all. And so what we're doing at Vohr is really a fundamental shift. What we're doing is we are taking the bone marrow cells that would be given to the patient. But ahead of that time, we're processing it, and we're genetically modifying these cells to remove this CD 33 molecule, to essentially remove this red flag.
Dr. Robert Ang:And so now the patient is receiving a new bone marrow that doesn't have the red flag at all. And anything left in the patient that is waving this red flag should be cancer cells. So what we're actually doing is making the CD 33 target much more cancer specific, and so you can then give treatments after the stem cell transplant, and hopefully, the patient will be much more healthy because they wouldn't get this toxicity from, these treatments. And these treatments can really solely pursue cancer because anything expressing that that this target will be cancer cells.
Dr. Moira Gunn:Can you tell before the transplant whether or not that they've got any CD 30 3 left or cancer producing cells left in their body after getting the big chemo or radiation, whatever it was to clean out. Can you tell what, that somebody has that left?
Dr. Robert Ang:Yeah. In fact, you can. So routinely after a stem cell transplant, you take samples of the bone marrow and you can tell from expression of this CD 33 marker or other markers if there's any residual cancer left. This is actually a test, called MRD, minimal residual disease, And you can actually either see cancer cells directly or you can look for these molecular flags to detect if the cancer is still present. And so in our circumstance, hopefully, those marrow samples would contain a lot of healthy cells that no longer show this red flag and hopefully no evidence of that cancer left.
Dr. Moira Gunn:Well, if we're producing if healthy people are producing CD 33 in other parts of their body, don't we need it for something?
Dr. Robert Ang:Yeah. That's a that's a really good question, Moira, because, you know, maybe God put it there for a reason. Now our experimentation shows that actually it seems to be biologically dispensable, meaning that if you remove expression of the CD 33, you can retain solid function of these stem cells, you can produce all the blood cells that you need for survival, and these blood cells seem to function completely normally. Now, in addition to all these experiments, we also looked at human genetics And there's some big genetic databases showing that there are individuals walking among us who have never ever expressed CD 33 in their entire lives. They just happen to have mutations that prevent its expression And that's really interesting.
Dr. Robert Ang:So it shows whatever CD 33 is there for, it seems that you can do without it.
Dr. Moira Gunn:Now you can test in humans. You've gotten the go ahead from the FDA. You're in the very first phase, phase 1. What's your plan for this phase one trial?
Dr. Robert Ang:Yeah. So what we're offering patients are 2 things. Firstly, we're offering patients this next generation bone marrow transplant, where we are genetically modifying these cells to remove this red flag, the CD 33. And so patients are undergoing a transplant procedure that they would have undergone anyway, except they're receiving our cells instead of a regular stem cell transplant. The second thing we're offering patients in the same study is patients are being treated 60 days after their transplant with a drug called Mylertag.
Dr. Robert Ang:This drug, Mylotarg, is designed to attack anything with this red flag, anything showing CD 33. And, normally, you'd never give Mylotarg. In fact, you'd never give any type of anticancer agent after the transplant because the transplant is still fragile, and it could die or be be severely damaged as a result of these drugs. In this case, we believe this new transplant will be robust because of this genetic modification we're providing. And so the benefit that we're hoping to, provide patients is that this next generation transplant will allow this kind of therapy soon after their transplant and prevent or extremely delay any type of relapse of their cancer.
Dr. Robert Ang:And I should say, Mylotarg is actually already a marketed agent. It's, It's marketed by Pfizer and it's used for AML right now. And it's very well understood. In fact, you know, tens of thousands of patients have received this. And, we think, however, this new use of Mylotog in the post transplant period could be extremely beneficial to patients.
Dr. Moira Gunn:Well, here's the important part. You're enrolling now and you're actually going to be enrolling in other studies for AML. Can you tell people how they can find out about it, what it would take to participate, etcetera?
Dr. Robert Ang:Yes. So, our study is is open for enrollment in multiple centers all throughout the United States. This is open for patients with AML. And what we're doing here is actually selecting the highest risk patients who are very likely to relapse after their cancer. And so the easiest way to find out about this is go to our website.
Dr. Robert Ang:So our company is called Vor Bio. So go to v for Victor, v o r, biobio.com. So vorbiobio.com, and there's a special page on that website just for patients that they can learn more about the study and if they might be eligible. And they can also see all the different clinical trial sites throughout the US and which one might be closest to them.
Dr. Moira Gunn:Well, doctor Ng, thank you so much for joining us. I hope you come back and and see us again.
Dr. Robert Ang:Well, thank you, Mara. I hope to come back with great results from patients who, can receive our next generation therapies, and we can hopefully change the lives of some people out there.
Dr. Moira Gunn:Doctor Robert Eng is the president and CEO of Voor Biopharma. That's Voor, v o r, on the web at Vorbiopharma.com. Listen to more biotech podcasts at biotechnology.com or on your favorite podcast provider. Biotech Nation is a regular feature of the weekly public radio program, Tech Nation. Listen to the full show via podcast or on your local public radio station.
Dr. Moira Gunn:For Bio Tech Nation, I'm Moira Gunn.