BioTech Nation ... with Dr. Moira Gunn

This week on BioTech Nation, Dr. Amit Kumar, President and CEO of Anixa Biosciences, talks about their work on a breast cancer vaccine which targets a protein thought only to be expressed during breastfeeding. Building on research by the Cleveland Clinic, Dr. Kumar describes ongoing human clinical trials and their potential for women with BRCA mutations.

What is BioTech Nation ... with Dr. Moira Gunn?

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.

Dr. Moira Gunn:

Neon Tech nation, new science which has led to new efforts to prevent triple negative breast cancer, and following that, ovarian cancer. I speak with doctor Amit Kumar, president and CEO of Anixa Biosciences. Then Sarah Friar, a Bloomberg News journalist who covers such familiar social media companies as Facebook, Snapchat, and Twitter. Her book, No Filter, The Inside Story of Instagram, received the 2020 Financial Times and McKinsey Business Book of the Year award. And this 2021 interview carries new relevance as the bounds and potential owners of social media companies are meeting head on.

Dr. Moira Gunn:

And now, doctor Amit Kumar. Well, doctor Kumar, welcome to Bio Tech Nation.

Dr. Amit Kumar:

Thank you for having me.

Dr. Moira Gunn:

Just hearing the term breast cancer, it's terrifying. It's terrifying for anyone just even to think about it. And there are many different types of breast cancer, some far more aggressive than others.

Dr. Amit Kumar:

That's right. The breast cancers are typically characterized by specific proteins that are expressed on the breast cancer cells. And so many breast cancers are either expressed proteins that are receptors for certain hormones like estrogen. Another type is progesterone. Other types of breast cancers are characterized by expression of a protein called HER2neu, which is a growth factor.

Dr. Amit Kumar:

But the most aggressive type of breast cancer is called triple negative breast cancer because it has none of those 3 proteins that I mentioned. And as a result, those cells grow without influence from those outside factors, and so they're very aggressive. We, as a society, don't have, very good therapies for that type of breast cancer. And in fact, the largest percentage of women who die of breast cancer are, those who have triple negative breast cancer.

Dr. Moira Gunn:

Now you said to me in an earlier conversation, you have one cell that has a mutation that makes it cancerous and that multiplies and multiplies. It has to get to a trillion cells before it's a lump and you can fill it?

Dr. Amit Kumar:

Well, yeah. I the you know, typically, cancer begins with one aberrant cell, that becomes a cancer cell, essentially, and then that becomes 2 cells, reproduces and becomes 4, 8, 16, and so forth, and eventually getting to a large number of cells. I just use a trillion as a big round number. That's not exactly what, what it becomes, but, but it becomes a large number of cells. And, eventually, you start feeling it as a lump when you do a self exam, and you see it on your mammogram.

Dr. Moira Gunn:

So there have to be a lot of cells, a lot of cancer cells to become, a cancer tumor.

Dr. Amit Kumar:

That's correct. If you have 8 cells or 16 cells or 32 cells in the earliest stages of, neogenesis, you don't see that on a either you can't feel that when you do your self exam, and you won't see that on a mammogram. Once it's, you know, billions to trillions of cells, that's when you see it as a lump.

Dr. Moira Gunn:

And that's true of any of the breast cancers?

Dr. Amit Kumar:

That's correct. That's true of any of the breast cancers that in fact, that's true of any type of cancer as well, any type of solid tumor.

Dr. Moira Gunn:

The Cleveland Clinic has had such a tremendous reputation for breakthrough research over the years and I know that they have been working on triple negative breast cancer and you are now working with them. Now tell us the story of their work over the last decade.

Dr. Amit Kumar:

Well, yeah. There's a visionary immunologist there named Vincent Tuohy who had this idea of preventing breast cancer, or I should I should say preventing cancer in general from, even arising, which is a little different than what the typical approach for addressing cancer has been in the past. And, over the last decade, he and his research team has been working on this approach, and, a lot of animal studies have been done demonstrating that, it works. And so in 2019, Anixa you know, I met the Cleveland Clinic, and Anixa decided to partner with Cleveland Clinic to take that technology into, you know, clinical setting, the human testing setting, and then eventually commercialize that technology. And so we've been part we partnered with the Cleveland Clinic to do that, which includes doing the clinical studies, you know, which are the human studies demonstrating the efficacy and safety of this vaccine and then eventually commercializing it so that, women can benefit.

Dr. Moira Gunn:

Now I have to say that all products start with basic research. What was the idea? What did they look at? What were they going for in this basic scientific research?

Dr. Amit Kumar:

Well, they made a discovery. And as you, indicated, typically, a lot of, you know, products come with a discovery, sometimes discoveries that are sort of surprising. And they found that there was a protein called alpha lactalbumin that is expressed in the breast of mammals, but only when those mammals are lactating because this protein is necessary to help produce mother's milk. So when a woman gives birth, the protein is expressed only in the breast to help produce milk to feed the infant. Once the mother stops breastfeeding, that protein disappears because it's not necessary, and, we say it's it's a retired protein.

Dr. Amit Kumar:

However, the discovery that Cleveland Clinic made was that when a woman gets breast cancer, and specifically triple negative breast cancer, those cells, those cancer cells are frequently producing that protein again. So Vincent Tuohy had a had a hypothesis. He said, if we could train the immune system to destroy cells making that protein, then when cancer cells arise, the immune system will destroy those cells, and the cancer cells will never have a chance to become a tumor. Because as I noted earlier, tumors start as a single cell, then they become 2 cells and 4 cells and 8 cells and eventually becoming a big mass of cells up to 1,000,000,000 to 1,000,000,000 to 1,000,000,000,000 of cells. When they're at that large stage, it's very difficult to to deal with.

Dr. Amit Kumar:

However, the immune system could potentially destroy those cells when they're at the 2, 4, 8, 16 cell stage. And, hence, those cells will never have the chance to gain critical mass and become a tumor.

Dr. Moira Gunn:

Well, let's take the part where we've already had all our babies. We're not gonna be doing any more breastfeeding that we know of and we're saying, okay, great. Now we either have it or we're afraid we're going to get it. We have some indication there. So we're going to want to equip the immune system to destroy any cell that makes that protein with the presumption that, that would be a triple negative potentially cancer cell.

Dr. Moira Gunn:

Is that right?

Dr. Amit Kumar:

That's correct. That's exactly right.

Dr. Moira Gunn:

But how do you do that?

Dr. Amit Kumar:

Typically, you vaccinate the patient. A vaccine is a group of chemicals that teach the immune system to attack something. You know, we're all very familiar with the recently approved or authorized COVID vaccine, and the the purpose there to enable the immune system or equip the immune system to attack the virus if you're exposed to the virus. In this case, what we're doing is we're equipping the immune system to attack alpha lactalbumin producing cells, And we do that by creating a vaccine that includes alpha lactalbumin and something called an adjuvant, which is what, helps spur the immune system to recognize alpha lactalbumin. And then there's a whole bunch of other things that are incorporated that, are not you know, we don't necessarily need to go into those details right now.

Dr. Moira Gunn:

So here's here's what we're looking for and the rest is to coax the immune system. Hey. Look for this. Look for this. This is what this is what you're after.

Dr. Amit Kumar:

That's correct. That's correct. And this is the alpha lactalbumin.

Dr. Moira Gunn:

Now all of these human trials start with animal trials. Yes. I know we're we're trying to get off of animal trials to other things, and that's great. A lot of work being done there. But usually, at this point, we have preclinical trials.

Dr. Moira Gunn:

It's the animal trials before we go to humans. What has been done in the animal trials? How did they turn out?

Dr. Amit Kumar:

There are a number of animal studies that we've done. The most compelling one was a study where, mice that were designed to get breast cancer were used. Now these are mice that if you just let them grow after they're born, then you let them grow, They'll all develop breast cancer. This is a special type of mouse that has been designed specifically to study breast cancer therapies. We did something a little different with these mice.

Dr. Amit Kumar:

We took half these mice and vaccinated these mice with the breast cancer vaccine, and then the other half got a placebo. And then we watched them as they grew. It turns out that 100% of the mice that were given the vaccine, were remained cancer free, whereas almost all of the mice that were given the placebo developed breast cancer and died. So what that told us is that we were able to, in a mammal species, you know, obviously, mice are not mice are not humans, but, but they are mammals, and we demonstrated that this vaccine could eliminate breast cancer in, in that species. Now we are engaged in human trials to demonstrate the same effect in human beings, and we're in the phase 1, portion of the human trials.

Dr. Amit Kumar:

So just beginning.

Dr. Moira Gunn:

Now this phase 1 of the phase 1, 2, 3 clinical trial trifecta, I call it, it's like you gotta get through all of them. Phase 1 is where we test for safety and we escalate dosages over time to see at what point will we create other side effects that we don't see now. As I understand it, you've got 2 different phase one studies going on. Explain that.

Dr. Amit Kumar:

Yeah. This is a very unique situation, that ordinarily doesn't occur for most types of studies. But we have a phase 1 a and a phase 1 b. In the phase 1 a, we are, as you noted, testing for safety in escalating dosage, and we're also looking for indicators of efficacy. So what that means is we are going to be vaccinating women who already have been diagnosed with triple negative breast cancer, and they're going through standard of care, which is, you know, typically surgery and chemotherapy.

Dr. Amit Kumar:

And we're gonna vaccinate these women and look for t cells and antibodies in their blood. Specifically, we're looking for t cells and antibodies that are created by the vaccine to target alpha lactalbumin. And secondly, you know and, of course, we're also gonna be looking for all the indicators of safety. We're looking for function of, you know, of all of their organs, temperature, etcetera, etcetera to just make sure that we're not creating any kind of, adverse side effect. And then we're gonna do a phase one b.

Dr. Amit Kumar:

Now this is a very unique type of trial that ordinarily is not possible in most studies, but it turns out that many women that have mutations in their BRCA genes are often choosing to have prophylactic mastectomies. So what that means is they're having their breasts surgically removed even though they're perfectly healthy at the time because they have a very high probability of getting breast cancer.

Dr. Moira Gunn:

This would be Angelina Jolie would be the example of this.

Dr. Amit Kumar:

That's right. Angelina Jolie had that done some time ago. And the purpose is to, eliminate the possibility of cancer because it's most likely that they will get cancer, and it's most likely that they'll get the triple negative, very aggressive form of the cancer. So many of these women are having their breasts removed, and so we're we're taking the opportunity to vaccinate them before they have their surgeries. And then not only are we gonna be looking for t cells and antibodies in their blood and safety, but we get a massive amount of tissue after their surgery, and we can look at the tissue at a microscopic level to evaluate whether the t cells are surveilling the tissue because there may be, you know, micro, micro tumors in that tissue.

Dr. Moira Gunn:

Now a couple of questions here. Are the women in these phase one studies receiving a permanent vaccine?

Dr. Amit Kumar:

Well, we, you know, when you think about permanency, we we like to think that it's going to be permanent, but we won't know. We will be following 1 and done or like like many vaccines are, or it's going to be something that requires periodic, boosting. Boosters. We we don't we don't think

Dr. Moira Gunn:

We know that. Boosters.

Dr. Amit Kumar:

Yeah. We don't we don't think it'll require boosters because the target, which is alpha lactalbumin, is not a virus that's mutating, for example. It's a it's a set protein, and it's the same, you know, throughout your lifetime.

Dr. Moira Gunn:

But let's say you're one of these women who know very early on, say in their early 20s, that they have BRCA 1 and or BRCA 2 mutations and they say, this I really need this but I want to have children. Can you take the vaccine and have children?

Dr. Amit Kumar:

Well, you know, we look at the animal studies to tell us what would happen, And you're right. There will be many women that know that they have mutations, that have a history of, breast cancer, and they may want to take this vaccine before they've had their children. In those cases, a woman can still get pregnant, still give birth, but the breasts of those women will not produce milk because the immune system is destroying those cells that are making alpha lactalbumin, which are helping to produce the milk. And and there may be some inflammation in the breast that may produce some discomfort, but this is not life threatening.

Dr. Moira Gunn:

Have you ever had a baby, doctor Kumar? It's it's kind of uncomfortable.

Dr. Amit Kumar:

I I I understand.

Dr. Moira Gunn:

Now when you're finished with phase 1, you're gonna presumably go on to phase 2 and phase 3. What will those clinical trials look like?

Dr. Amit Kumar:

The, the design of phase 2 and phase 3 will be dependent on the data from phase 1. So I can't give you all the details, but in general, a phase 2 trial utilizes a larger number of patients to look again for safety. And typically, you use the dose, the maximum tolerated dose that is, appropriate in that study. The MTD, maximum tolerated dose, is something you determined in phase 1, and now you're gonna test all of the women in phase 2 with that dose. And then the critical trial is the phase 3 trial, and that's where you take a large number of patients who would get the vaccine and then a large number that get a placebo.

Dr. Amit Kumar:

And it's double blinded. So the patient and the physician don't know if they got the vaccine or if they got the placebo. And then you watch these women, and you watch over a period of time to see how many incidents of cancer occur. And when they occur, you put them into the placebo bucket or you put them into the vaccine bucket, and the ratio indicates how efficacious the vaccine is relative to nothing. So so it's, you know, similar to what what was done with the COVID vaccine.

Dr. Amit Kumar:

A large number of patients were given the vaccine, and a large number were given the placebo, and you watched how many COVID infections occurred in the vaccine arm versus the placebo arm. And that told you what the, race you know, what the efficacy was. And so that's what we're gonna do with that type of trial, and it may take a few years to complete that, section of the of the trial, but we hope that we see the results similar to what we saw in the in the animal studies.

Dr. Moira Gunn:

Now you said in phase 2, it's a smaller study. In phase 3, it's a larger study. What kind of numbers are we looking at? How many how many subjects are in each?

Dr. Amit Kumar:

It'll depend on what the data looks like in phase 1 and phase 2, frankly. But in general, it'll be, on the order of thousands of of women who will be participating in the trial. I mean, you know, a couple of 1,000.

Dr. Moira Gunn:

Now in phase 3, with these several thousands of women, how do you qualify the women?

Dr. Amit Kumar:

Well, in this particular trial, we're interested in women that have mutations in their BRCA genes because these women are highly susceptible to getting breast cancer. And, typically, when they do get breast cancer, it's triple negative. And so this is what we call you'd call an enriched population. And then we will be testing it will be giving half of them the vaccine and the other half a placebo, and we'll just be watching them over time to see how many women in each, arm gets cancer.

Dr. Moira Gunn:

Now can you detect that cancer early?

Dr. Amit Kumar:

Well, there are a number of companies that are trying to develop technologies to try and identify cancer as early as possible. However, the FDA is you know, those are not FDA approved products at the current time. So the FDA is going to require in our clinical trial that we diagnose the cancer using the standard techniques, which is typically mammography.

Dr. Moira Gunn:

So it has to be well along to be acceptable to the FDA.

Dr. Amit Kumar:

That's correct.

Dr. Moira Gunn:

And if you had that mutation and you have thousands of women, how many would you expect to develop cancer without the vaccine?

Dr. Amit Kumar:

Just a handful. In fact, it it depend you know, the the trial will last long enough to get statistically significant ratio between one bucket and the other bucket. So if we find that, you know, an equal number of women are getting cancer in the vaccine group versus the, placebo group, then the trial is gonna last a long time. If, however, if we see a large number of women in the placebo group get cancer, but no or few women in the vaccine group get cancer, then then it'll be a shorter trial. And, you know, you might be able to, complete the trial with only 20 or 30 women having, having contracted cancer in the placebo group if if the vaccine group is 0 or just a handful.

Dr. Moira Gunn:

Doctor Emmett Kumar is the president and CEO of Anixa Biosciences. I keep going back to the original idea of the discovery that, this well known protein was on the surface of of breast cells while you were lactating and then it retired. You didn't need it anymore. But when you got to this one stage and you had it on the the cancer cells of triple negative breast cancer. It came out of retirement.

Dr. Moira Gunn:

This was an enormous discovery. Does this relate at all to ovarian cancer?

Dr. Amit Kumar:

Well, it turns out that there is a similar protein on the ovaries that retires over time. In this case, the protein retires by the time a woman reaches menopause. However, when epithelial ovarian cancer arises, which is, you know, the most common form of ovarian cancer, those cells are producing that protein again. So similar to the breast cancer case, we are working with the Cleveland Clinic on developing an ovarian cancer vaccine that targets that protein. Now that program is a little earlier, you know, little earlier stage, and so we're probably about a year and a half away from getting into clinical trials there.

Dr. Moira Gunn:

Doctor Kumar, we have one incidence here in breast cancer, triple negative breast cancer. We have another in ovarian. Could this have general applicability?

Dr. Amit Kumar:

Yeah. We think, in the breast cancer situation, we think, that, it's possible that this vaccine could eliminate many other types of breast cancer. We're focused on triple negative because it's the most aggressive type of breast cancer, and we've studied it very well. But, any breast cancer that's producing alpha lactalbumin should be could be targeted by this this, vaccine. And potentially, we could eliminate a large number of, all types of breast cancer.

Dr. Amit Kumar:

And And then on top of that, more generally, as we discover new proteins, new retired proteins and other types of cancer, In principle, we could develop vaccines against all of those other types of cancer.

Dr. Moira Gunn:

And who does not have cancer somewhere in their family?

Dr. Amit Kumar:

Absolutely. Cancer is one of those diseases that every one of us has either personally dealt with or, knows someone who's, you know, who's had it. And, it affects, it affects the, the person, who has the disease as well as everyone in that person's orbit. In fact, a few years ago, my mother, contracted breast cancer and, now my 2 daughters, for example, are at high risk. And, I would love to be able to, at some point, vaccinate both of them and not have to worry about breast cancer for them.

Dr. Moira Gunn:

Well, doctor Kumar, thank you so much for coming in. I hope you'll come back and see us again.

Dr. Amit Kumar:

Thank you very much, Moira.

Dr. Moira Gunn:

Doctor Amit Kumar is the president and CEO of Anixa Biosciences. More information is available at anixa, a n I x a, anixa.com. I'm Moira Gunn. You're listening to Tech Nation.