For the Love of Health

Knocking Out Cancer Through New CRISPR Therapy with Eric Kmiec and Kelly Banas

• ChristianaCare • Season 3 • Episode 14

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Lung cancer remains one of the deadliest cancers worldwide. Patients often face a fast-moving disease and few treatment choices.

But what if you could treat lung cancer with something as simple as an inhaler? It's an option that may be closer than you think thanks to groundbreaking research from ChristianaCare's Gene Editing Institute.

At the heart of the technique is at-home CRISPR gene editing, designed to switch off tumor resistance at its source. Drs. Eric Kmiec and Kelly Banas of the Gene Editing Institute unpack the decade-long journey from a big idea to a viable therapy. We dig into the hardest parts of genetic medicine - delivery, stability, and safety - and why inhalation could be the breakthrough. Looking ahead, the team frames this as a platform that could expand to head and neck cancers and beyond, while easing the clinical toll on patients through lower doses and at-home care.

Whether your interest lies in lung cancer treatment specifically or the future of cancer therapeutics more generally, this episode provides a ray of hope for cancer patients everywhere. Listen now to find out how ChristianaCare and the Gene Editing Institute are paving the way for cancer breakthroughs.

Eric B. Kmiec, Ph.D., is the Executive Director and Chief Scientific Officer of the Gene Editing Institute (GEI) at the Helen F. Graham Cancer Center & Research Institute at ChristianaCare. His research centers on understanding the process of gene repair and gene editing with a focus on CRISPR-directed genome engineering in human cells. He is widely recognized for his pioneering work in the fields of molecular medicine and gene editing having discovered many of the molecular activities that regulate the efficiency of human gene editing.

Kelly Banas, Ph.D., is the Associate Director of Research of the Gene Editing Institute. She leads a team of researchers working to identify new clinically relevant genomic targets as well as working to understand the specificity and safety of CRISPR/Cas systems as a therapeutic modality. Her previous research has led to an innovative foundational approach to the treatment of solid tumors using CRISPR-directed gene editing, which is currently being developed for Investigational New Drug status.

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Setting The Mission And Stakes

SPEAKER_00

Our science is is proving true to making a potential breakthrough for these patients.

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You're listening to For the Love of Health, a podcast about delivering care and creating health, brought to you by Christiana Care. Hello, everyone, I'm Jason Takarski.

SPEAKER_03

And I'm Megan McGerman. Welcome to For the Love of Health, brought to you by Christiana Care.

Why Inhaled CRISPR For Lung Cancer

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Lung cancer remains one of the deadliest cancers worldwide. Patients often face a fast-moving disease and few treatment choices.

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Corixer Therapeutics, Christiana Care's first commercial biotherapeutic spin-out, is working on a way to breathe new life into lung cancer treatment.

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To talk more about this groundbreaking research, we're joined by Eric Kamesh, Executive Director and Chief Scientific Officer of Christiana Care's Gene Editing Institute and the Gene Editing Institute's Associate Director of Research, Kelly Bannis.

SPEAKER_03

Eric and Kelly, thank you for joining us today.

SPEAKER_00

Thank you for having us.

SPEAKER_03

When people think about cancer treatment, it's usually chemotherapy, immunotherapy. You guys are looking at an inhaled genetic therapy. Talk to us about how that works.

SPEAKER_01

The program of getting to the inhalation uh delivery mechanism for lung cancer has come about from the uh about 10 years of research. And this started with Kelly's uh initial discovery of using CRISPR on a specific gene that controls tumor cell survival and how the tumor cell resists anti-cancer treatment like chemotherapy, immunotherapy, and radiation. And um that work went on for a long period of time. It was using the uh genetic tool CRISPR to disable the genes that cause the tumor cell to survive and to enhance that resistance to standard care. But we had trouble figuring out how we're gonna get it there, right? And this is always the conundrum about genetic medicine. Uh the molecules are big, they're very effective, but in general, if you take a CRISPR molecule in some formulation, it's much like uh our our COVID vaccine. Much of it, if you injected it intravenously, it would go to the liver. And so that's not helping us in lung cancer. So uh Kelly continued with her team um kind of understanding the basic mechanism of how it all worked.

Delivery Hurdles And The Inhaler Pivot

SPEAKER_01

We thought about direct injection of lung tumors. This is possible. Johnson ⁇ Johnson has a huge program if we like to use a robot to do injection into uh tumor cells and lung. But along came the development of this inhalation therapy, and this had actually started in Europe and it's been ongoing for some time, and the idea was to formulate in like an asthma inhaler the opportunity to deliver larger molecules. So the concept is that rather than inject the tumors, the people would simply inhale CRISPR to disable the gene that causes the cells to be resistant to chemotherapy or immunotherapy. And what appealed to us initially was that you could do this at home. So uh large patient costs is based type primarily on patient coming into chemotherapy suites, radiation, taking heavy doses of both of those and immunotherapy or preconditioning for immunotherapy. And at the end of the day, uh the patient debilitates, he gets sicker and sicker, and so the more you try to do over period time, you're not dealing with a healthy patient. If a patient could take this at home uh routinely, keep it in the refrigerator, just like an asthma inhaler, treat themselves for lung cancer, we think that would be a big win. And so it's first in humans, first in class, and uh there's a tremendous amount of excitement uh about it uh in Europe. So we'll uh keep our fingers crossed. I think we will have our first solid animal data by uh May or early June, which they will conduct. So they'll do all the animal work over there. And if that looks positive, then by the end of this year, we will certainly have a plan or a synopsis for a clinical trial. Take some time to work that through, but we're we're pretty excited. So the inhalation idea came out of necessity for how the best way to deliver the drugs that Kelly had developed for lung cancer and uh Merksen and InHatarga, the two companies in Brussels and London, respectively, that um have a uh had the opportunity to develop that. So the the mechanism and the way the inhalation is carried out has already been developed. We're just piggybacking on their really good uh good approach.

SPEAKER_00

And I think what's amazing is we started this project uh really thinking about what this could look like in the future. And at the time, I think we started this project saying, wouldn't it be cool if we could do this as an inhalable treatment? And here we are already working on this and seeing that come to fruition has been amazing as a scientist on the ground, really leading those efforts.

SPEAKER_02

That is just striking to me, knowing the kinds of things we're used to for dealing with cancer treatment, that in inhalation is what we're looking at to make this one work here.

Timelines, Safety, And FDA Path

SPEAKER_02

How long does it take to develop a new cancer treatment in general?

SPEAKER_00

Great question. It really depends on patient population, on your target of choice. Um, all of those variables really play into how quickly you can get something into patients. Um, I think for us, it has taken us about 10 years, but we started with a concept. So we had this idea, we had a paper that we looked at, and we said, you know what, let's push forward and let's make this happen. So over those 10 years, we've been working diligently to really understand what this looks like from a patient safety perspective, what this looks like from a molecule perspective. So really understanding how our CRISPR molecule works, making sure that we can translate this into a manufacturing and scale up. So our part has taken quite a bit, but that's because we're ensuring that what we're delivering and what we hope to deliver it to patients really fits into that safety profile that is needed for drug development. So I think on the gene editing side of drug development, it can take a little bit of time because there's so many variables and so much collaboration that really takes into making this a complete drug. I think a little bit more on the just general cancer drug side. I know our partners have really scaled this up, so it's quite effective. Uh, but I think for us, we're a first-in-human type of drug. So we're really paving the path for this for oncology-based purposes. So we're not sure how that timeline looks, uh, but we've made sure that we've really hit the mark on patient safety along every step of the road.

SPEAKER_01

So we've been through the first round of FDA approval and it was successfully. And that was uh actually a couple years ago. And uh as Kelly mentioned, we stepped back and really wanted to understand how CRISPR works at the DNA level. Um a lot of the concerns around CRISPR are frankly unfounded. People think that it goes and runs up and down your chromosome and breaks DNA randomly and causes cancer and stuff. That that just isn't true. There is an approved drug, Caschevi, which made it in the clinic, I think, in three or four years, but that's because there was twenty years of work behind it that got it to that point. And as Kelly mentioned, you know, our objective is to be s is to make sure the drug is safe. But this year we will enter into one or two rounds of FDA approval and the clinical trial we believe will happen probably at the end of twenty seven. And as uh as Kelly and I have been talking about endlessly, um the United States uh sort of the the environment in the United States for approval of novel therapies is still good. I think this is a a misconception, but the time it takes to accrue patients into the trial is still quite challenging for novel drugs. So a number of companies, a number of groups are beginning to run their initial clinical trials overseas, and that allows people to make sure that it is safe in humans or call first in humans and safety is the first thing. And we're considering that too. So the most important thing for us is to do as much as we can at the mechanistic level to ensure safety, but then you won't know until you put it into patients, so the sooner we can get it into patients and see that reaction, that'll that that will be the telling tale. You know, there are a number of our colleagues in different companies are headed to China to do it, frankly. It's uh the it it's not any faster than the approval process, it's just that people will join clinical trials there much quicker. Lung cancer is endemic in Asia, it is much worse, head and neck cancer is terrible. So there are plenty of patients there, and the access to this kind of uh innovative therapies is uh is much greater there. So that that's where it heads.

Global Trials And Patient Accrual

SPEAKER_03

Let's back up a little. What milestones did you expect to hit 10 years ago when you first started having this conversation? Did you say by 2026 we will be looking at FDA approval?

SPEAKER_00

Great question. I think uh that was definitely in the back of our minds. Uh we were hopeful we we wanted to see that really take shape. But I think we were very driven on making sure that the science made sense. So along the way, we've really done our due diligence to make sure that the science really speaks for itself. So we didn't want to move forward with something that didn't seem robust or didn't have reproducibility. Uh so really those milestones have been our scientific accomplishments. Uh, while we we hope to be in patience, I think even just meeting those scientific milestones adds to the field and really supports others, uh, our own, you know, neighbors in the space, driving this forward as a potential therapeutic. So anything that we can contribute has been a milestone, at least in my book. Uh, we've learned a lot over the course of those 10 years. We've learned what it takes to really scale something up from the bench, which is where it started at the Helen F. Graham Cancer Center, to bedside, which is where we're actively talking about this going within the next several, several short years. Uh, so it's been really exciting to see those milestones from the scientific level. They've supported our concept from our initial studies that we've done.

SPEAKER_01

I think that's true. We are embedded as uh true molecular biologists, and uh we have had the opportunity uh to create a novel approach to oncology. Anything

Milestones, Reproducibility, And Buy‑In

SPEAKER_01

novel is scary to oncologists. Uh they tend to like to you know do standard things, but we always remind people that most of the therapies in solid tumors eventually fail. And so there's plenty of room for innovation there. We have found some terrific innovative oncologists here at Helen F. Graham and uh Cancer Center and Research Institute, as well as uh across the country, and most recently at McGill University in Montreal, where the top scientist in the NRF2 field, it's just the drug the gene we target, has just recently joined um the Spinout Company Scientific Advisory Board. His name is Gerald Batiste, and I think the thing that attracts him and the things that attract the major players are Kelly's basic science work and their mechanism of of action of how this thing works. So uh it's not necessarily a um, you know, a very exciting, it's not necessarily uh breathtaking science breakthroughs that you'll read in the New York Times, but it's the underlying science that makes it tangible and sustainable. Um a lot of the publicity that comes out of some of the more the larger institutions are surface level publications, and uh ultimately it's really understanding the depth of the science, and that's what we were dedicated to, particularly Kelly. So we're very confident now that this drug will work because we understand how it works at the DNA level.

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You've been working on this for 10 years. And as you've mentioned before, there were some roadblocks along the way, some some hiccups in the process here. What keeps that team focused as you hit some of those roadblocks? And it's just such a long amount of time. What keeps the team focused on this and working towards that goal?

SPEAKER_00

Yeah, I think first off, it's really the the fact that this has uh potential to

What Keeps The Team Going

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impact a patient's life. I think that really is what drives us. You'll get that same answer from every single scientist at the Gene Editing Institute. Uh, they're all embedded in making a difference for a patient. I think we all see the best of biotech and we see all these breakthroughs, but I think it's very easy to forget that there's a patient on the other side of this breakthrough. And I think that really makes it impactful. And for us, we're a smaller team and we're right there embedded within Christiana care, and we see these patients, we talk to these oncologists. So it's very tangible, and I think that's what really keeps us level-headed. Um, and I think, second of all, we're a team of scientists. We love the science. So we're over here questioning each other all day long, making sure that we continue to learn, continue to expand our knowledge. So it's really just the pure love of the research, the pure love of the science. And I think meshed together with seeing an impact on patient lives is really where our team feels that they're making that real life impact, not something that they necessarily have to think about, you know, happening 20, 30 years from now. Some research will sit, you know, in journals, uh, in laptops, you know, hidden away with maybe very little impact. But I think what we're seeing is our science is is proving true to making a potential breakthrough for these patients.

SPEAKER_01

I think the Christiana message resonated with us too, and Kelly alluded to it very importantly. It's about the patient here, and I think that is lost sometimes in major institutions where the race is to develop the latest technology. We don't lose sight of the patient, and that's because Christiana's mantra is, you know, patient care, caregivers uh facing patients and helping them. So we've always believed in that, and that's been embedded in our DNA. I'll tell you an anecdotal story back to you know your question about how long this was. I pretty much came by Kelly's desk every day, every hour maybe, and said, Are we there yet? Are we there yet? And at some point she just put up a sign on a piece of paper that said, Not yet. So we kept so it it's it's I think her withstanding me and my anxiety about this, but I through the years I've learned this is the finest experimentalist I've ever seen to my right here. And her level of integrity and her ability to cut through a lot of the bad data, confusing data is extraordinary. Um she just demonstrated this again. The paper we're talking about today, the publication has been highly heralded, it's been quoted everywhere. We've had all kinds of people reach out to us, uh including patients that are willing for this. It took her a year to recraft that paper. And uh I used to come by her office and say, Are we there there yet? So it never stopped. So it was her withstanding my anxiety. But as a team, I think uh, you know, she she has uh has such a great set of hands to be able to conduct these experiments, and now with her own team, she has provided that. So it's a desire for discovery, the inspiration, and to see, to do what everyone else has done, but think what no one else has thought. That's that's really what what is at the core of what I think Kelly's team has developed. So it's been an honor to watch her grow and to develop into this team. And I still ask her, are we there yet?

SPEAKER_03

One day. One day, eventually. Let's talk about what that

Patient Impact And Quality Of Life

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will look like. You said a few short years from now, in the patient experience situation, if there's someone who's diagnosed with lung cancer, what could that potentially look like for them? What could this mean for them?

SPEAKER_00

Yes, this could mean um an increase in quality of life. It could mean less chemotherapy they have to undergo, lower doses of radiation, immunotherapy working. So maybe uh before our drug, our CRISPR drug being available, maybe they weren't qualified for immunotherapy. But what we're seeing with our data is that this could allow patients, you know, that new opportunity. So I think it just helps to add on to uh the the opportunities that the patients have. Um I think what we're trying to do is we're trying to augment standard of care to work a little bit better. We have these drugs that have been developed that do work, but at some point they fail. Uh so how can we reinvent what had previously worked to maybe work a little bit better or not have to put the patient under as much stress? Uh so we're really hopeful that, you know, those are those are the small, tangible moments. Big picture, we hope that, you know, this may provide patients with maybe a cure. That's really, you know, what what we hope for uh using CRISPR. I know that's you know the hot phrase that that gets thrown around and you know, CRISPR being the cure. And I I really do hope one day we're we're there. And I think we're looking at it from a realistic perspective. We we do want that to be a cure, but I think we want this to be impactful now. We don't want to wait for something. We want this to be impactful now. And so this is our way of making something that can potentially impact the patients currently at hand.

SPEAKER_01

Most of the drugs that patients take now that are effective require some sort of preconditioning. So for example, if you take uh immunotherapy, in many cases you have to take heavy doses of chemotherapy to suppress your own immune system so it doesn't reject the antibodies or the immune response that the you know the immune drug that's going forward. So to our surprise, based on Kelly's uh I think, you know, basic knowledge of this gene NRF2, we can kill the tumor cell without secondary treatment. And so that's been helpful. That will happen in a certain number of patients, we believe. But as Kelly mentioned, those that don't respond that way will be available to get chemotherapy, radiation, or essentially immunotherapy.

NRF2 Addiction And Tumor Biology

SPEAKER_01

But the idea here that um I should you know probably turn to Kelly to explain this uh this uh concept that she advanced about a year and a half ago uh that we all really, really fell in love with, and it's called the NRF2 addiction of tumor cells. So you might want to chat about that and then and how we think that we could stimulate the immune system alone without external drugs.

SPEAKER_00

Yeah, so our our gene of interest is NRF2, and it's a gene that's found in normal uh cells, but really this gene gets hijacked in cancer cells. So this gene is responsible for uh keeping your cells healthy, keeping the metabolism of the cells healthy, uh keeping any stress, outside stress, from impacting your healthy cell. However, in cancer cells, this gene gets turned on to the max. So that you can imagine, you know, this is a stress response. Well, in cancer cells, that stress is immense. And so they really need to amp up this NRF2 production to really prevent that stress from killing the cell. And so what has been seen across the literature and even in our own hands is that NRF2 really reshapes how that cancer cell behaves within the microenvironment. And that's where the term NRF2 addiction comes from. So this NRF2 gets built up in the cell and the set the cancer cell is able to reorganize its metabolism and essentially not have to rely on anything other than the NRF2 to really drive its growth and proliferation. So with our approach, we're trying to cut that at its root to really make the cell more susceptible to chemotherapy, to radiation, to immunotherapy, to any outside stress that would uh potentially keep the cancer cell growing. But in this case, without NRF2, those cancer cells don't really stand a chance. So from a basic level, that is what we're trying to do. We're trying to really cut it at its root where NRF2 is really driving the growth and keeping the cancer cell healthy.

SPEAKER_01

Yeah, the the tumor cell, uh, and then this is a concept that Kelly brought forward, as I said, a while ago. And it was fairly uh novel, but other people were considering it, and it has grown so rapidly that I think within the last six months there have been a plethora of papers which suggest that the level of NRF2 that exists in tumor cells, when it's upregulated because it's a tumor cell, uh suppresses your natural immune system for fighting the tumor. So regardless of how much immunotherapy you take or cell therapy, unless you get rid of this gene, that tumor cell is still going to survive. And even if it does so in a quiescent or a quiescent stem cell, uh cancer stem cell format, you'll never get rid of it and they will come back. So that's what we decided to go after. And that's 10 years of work on a very tough problem. But we're as you can tell and we're talking here today, we're we're we're closer. We're definitely close.

SPEAKER_02

So this has been 10 years in the making, and you kind of saw this as where you wanted to be. And and I know the focus is on helping patients now, but let's take that the next step and say another 10 years into

Platform Vision And Next Decade

SPEAKER_02

the future. Where are we headed? Where would you like to see this go?

SPEAKER_00

Yeah, uh, this is a platform approach. So we have always designed this with that in mind. So we're focused on lung cancer on head and neck, but really what we're doing is expanding this across different cancer backgrounds. So we know that right now our data supports, you know, these particular indications, but we hope that this really starts to set the stage for how we we look at, you know, treating cancer. Um, I think, you know, there are other genes just like NRF2, and we encourage, you know, our colleagues and and the field to start to look at this from a little bit of a different angle. I think the the push around oncology has been a little quiet from our colleagues. I'm hoping that this begins to set the stage for others to think creatively and really bring forward something to patients who don't have any other options or who have options and then are out of options. We're paving the way. For a platform approach by setting the stage of, you know, thinking from everything from the basic science mechanism all the way through manufacturing scale-up, patient recruitment and what this means, you know, for patients and potential investors on the business side. So we've spent the last 10 years really learning and, you know, putting on all of our different hats to hopefully make this something that is now transferable to the rest of the field. And so that we can have others, you know, jump in and help us fight alongside us for for this purpose.

SPEAKER_01

I think um just circling back to the first question you asked, um, you know, I think we see this as the hope of patients treating themselves at home with an inhaler. And that's it. You know, when they go get it refilled. Um one of the biggest things we just crossed over with our partners, Merksen and Inatarget, is making sure that the CRISPR drug is stable in the refrigerator. Sounds silly, right? But if it's not stable at four degrees in the refrigerator, a patient won't be active. So good news is it is, and we're, you know, and they would have to go down and get another inhaler. And I think in ten years uh we're hoping to eliminate those kind of, at least for lung cancer, the the massive amount of commitment it takes from the patient to be treated. We know, and this is a driving

Reducing Burden With At‑Home Care

SPEAKER_01

force, I think, for Kelly and I for years, and probably the whole I'm pretty sure the whole GI team is that a lot of patients stop their clinical trial after a while. They just they just give up. We were listening to yesterday to this uh uh visitor and and she was saying something about people even in kidney dialysis, they just can't take it anymore. They know they're gonna die in six months, but that's it. That happens a lot in in in trials. They just they just the the treatment is so severe, so devastating that they stop. And so if we could reduce that experience so it's not so devastating, and they can make it through and they can get on to the next uh treatment and make it easier on your body to take, they'll be healthier as they go through the trial. And that that's the goal, and one of the ways to do that is through this inhalation at home. Uh it it's picking up a fair bit of speed. There are clinical trials in Europe now where inhalation of chemotherapy is underway. So this is not a you know brand new idea. We're just advancing the ball closer and closer. The concept of where did we see this going? That's it. We saw it going with handing the ball over to somebody who can deliver this to patients, and we hope in the 10 years that the patients will just be inhaling CRISPR gene editing and help in the uh reduction of tumors and elimination of lung cancer.

SPEAKER_03

Eric and Kelly, thank you so much for being here. We look forward to having you back in a few short years to talk about the growth of this work. Thank you.

Closing And Where To Learn More

SPEAKER_01

Thanks.

SPEAKER_03

Check out the show notes for this episode for more information on this groundbreaking research we discussed today and other research being done at Christiana Care's Gene Editing Institute.

SPEAKER_02

You can also keep up with For the Love of Health on social media. Just search Christiana Care on your favorite platform.

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We'll be back in two weeks with another great conversation.

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Until then, thanks for joining us. For the Love of Health.

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