Trials with Maya Z

  Hello and welcome to the next episode of Trials with Maya Z, brought to you by TrialHub, a data intelligence platform that helps clinical research organizations and sponsors plan clinical trials. This podcast is about how we can make clinical trials more successful and patient-friendly. Friendly, I am your host, Maya Z, and in every episode, I will be interviewing a leading expert from various industries to discuss some of the major challenges and brainstorm how we can solve them.

Let's get started.

 Hello, everyone. This is Maya from Trials with Maya Z. I hope everyone's okay and is looking forward to the next episode of my podcast. And today I have a dear friend of mine, joining me in an interesting conversation. A conversation that you wouldn't probably even expect.

I'm here today with Gretchen Knoll. Who actually spent quite some time in clinical research, she's an expert in clinical research, but not only that, and is looking clinical research from a very interesting angle. Gretchen, welcome to my podcast, can you please give us a few words about yourself and your background?

Hi, Maya. It's a pleasure to be here. It's really fun to be able to share this in a public forum. Our conversations and our creativity, why we created our companies, is to help patients and to help clinical patients.

trials and clinical treatments in the world. So I'm excited to do this today. Like you said I've got 27 years of background in clinical research, came to it a little bit like one of your former interviewees, Ross Jackson said, you know, you just come to clinical research through something else.

And that was me as well. So I worked in a small CRO, then I worked for the largest CRO, and now I've found my own little consulting company and work in biotech and a pleasure to be with you today.

It's a pleasure. Definitely. It's a pleasure. Just for my audience Gretchen and I had multiple conversations for the past probably two or even more years, Gret. And we've always enjoyed going wild in our ideas of what could research be like, not just research, but medicine in general.

And one of the main things I wanted to actually bring to. The audience to make it like for public is exactly your thoughts around clinical treatments in general, because clinical research is just the process of bringing new treatments available to the wider public

but then it's about. What kind of future we want to bring in, what is the future of, like, of treatment, of clinical treatments? I know you have quite some experience in oncology, and you and I, we both share the same opinion when it comes to how challenging it is, the clinical treatment of cancer.

In cancers and one of the things that you mentioned in the past but also recently is that this current classification of cancers, how this is actually a show blocker, let's put it that way, or like a blocker, or let's say a limitation that we currently have for the next future, like for the next future, next-generation treatment.

So, Gret, can you tell me actually? What is today this classification of cancers and why do you think that this should change and how do you see that changing in the future?

You're absolutely right. I think there's a lot of opportunities. We have a lot of transformation in how we're treating due to predictive analytics and the future of oncology, and this comes from, you know, something that came out of France, out of Gustave Roussy, the cancer institute here.

And I'd like to recognize, you know, that this information comes from Fabrice André. He published an article not so long ago On his frustration with how we are treating cancer, obviously, and we see this every day. Time is of essence when you have a cancer and to be able to get to a clinical trial and to get treatment fast is the difference between progression and sometimes outcome. Life and death. We're so in the last 20 years, I would say we, are now getting to precision oncology. The restructuring of medical oncology means that we're characterizing those tumors. So instead of treating by organ of origin, in other words, if you initially had lung cancer and it's spread and metastasized, they're treating you for your lungs. And instead of that, we should be characterizing the the tumor and what the origin of the tumor is and treating according to that, classification. So changing from an organ classification to a receptor classification that is just the molecular profiling of the tumor and of the immune cells. Is the future of oncology and I'm completely on board with that, but that transforms everything, you know, in terms of what you're doing, Maya, in terms of the way that we're going to be conducting clinical trials the way that we're going to treat and again, getting. The right treatment earlier. And I can give you a really specific example. There was a study that was done that identified a tumor and that was back, and I don't have all the numbers right in front of me, but that was back in like 2009. And then it was given to one organ for treatment. It was given to another organ for treatment. And then a third. Several years had gone by. So there was a potential there that that molecular targeting could have, you know if we had treated those patients for the molecular target instead of by organ class, that those patients would have had an opportunity much, much earlier.

No, I agree. I agree with you, Gret, and on our platform, FindMeCure. com where we support patients in their search for clinical trials and just trying to figure it out what clinical trials are, and how they fit into their treatment Like roadmap, let's put it that way. We get to work with a lot of people that are lost.

And are getting exactly like you said, like treatment on their organ cancer, but not necessarily knowing what's the profile of their tumor. Or maybe they do, but again, they still get a treatment that's been approved through research for a particular organ. And one thing I learned a few years ago is exactly that.

We have today these molecular testing like we have, I would call it personalized diagnostics. We have these tests that help you understand what is actually the origin of your tumor. What is this, what type of specific tumor do you have and what are all these treatments or even clinical trials that are available out there that are the most suitable for you and your tumor at the moment?

And actually what was eye-opening was that I was looking at such a test, like ready tests, like the results, let's put it that way. So I was looking at the results and then I could see some of the results of like these patients are, so this drug. But this drug is not approved for lung cancer, the one that you have, but let's say it's approved for breast cancer, for example, like imagine.

So they are even today there are drugs available on the market that can work on your tumor, but just because they haven't been approved Through research for this particular organ, they're not necessarily applied for the treatment. So actually, I just wonder why aren't we already applying this molecular testing on a scale?

What stops us from doing that? Any observations on it?

I think, so that's exactly where I think Professor Andre wants to go as well, is that currently what happens? We train our medical personnel by organ class. You have gastroenterologists, you

have pulmonologists, you have, we, all of our guidelines for ASCO, for EMSO, ESMO, they're based around the organs.

Hmm.

We have, even in the hospitals, we have the lung ward, we have the, we have the breast cancer ward. It's a paradigm shift that we need to put in place where, to be honest with you, when I was looking into this, I conducted a trial. We had a monoclonal antibody that I thought was brilliant.

We conducted it in a phase two study and it was just like throwing out a big fishing net.

Any solid tumor was allowed to be enrolled in that trial. But

we, I think we were doing it for different reasons 15 or 20 years ago. But that's where we should be going with clinical research is opening it up to, and when I was giving you that description, it was for.

PARP inhibitors. So,basically, PARP inhibitors, it was originally approved in ovarian, got the FDA approval. Then it got breast approval and breast cancer approval. Then it got approval for pancreatic cancer, then prostate. So that was what I was referring to before. You know, bringing All of any kind of tumor that would have a PARP inhibitor, for example, put them in a trial.

Now the challenge will be, how do you make those outcomes? What is success? What is efficacy across several different ranges of, cancer? You're going to have different scales, you're going to have different measurements. So that's where these brilliant people like Gustave Roussi and, you know, other statisticians and epidemiological experts are going to come in, have to come in and establish, okay, how do we measure this across so many different cancer types. and like you were saying the problem right now is that people aren't reimbursed for drugs when they're given off-label. So then this is going to be something that we're going to have to do with the industry. I also ran the trial where I did, for compassionate use and that was essential.

Again, that's essential For these patients because they're allowed to receive an investigational drug now. And it was on a case-by-case basis. It's within the pharmaceutical company We were signing them off, but it gave them an opportunity to be treated immediately So in response to your question, I mean, it's a huge mental shift across the entire world Healthcare industry that's going to be required. And I think it's on its way because it's so, convincing, you know, when you, obviously, if you have a drug that is allowing for a good response based on the receptors, then, it's just, it's daunting to me, the idea that there would be. A clinical trial where only one-fifth of the patients are responders, you know, and that's where we are

in oncology in some cases.

But , Gret, I'm happy that you're, like, very positive about it, that this mind shift is coming, but at the same time, I'm, maybe I'm less optimistic because literally in the past couple of weeks, I had to attend two different funerals, exactly because, the different organs were treated were treated differently.

I mean, it's not in oncology, but it doesn't matter. And I actually see what you're saying, around the education, the medical education, how we prepare doctors, for example, not only doctors, like any medical staff around the organs. I almost feel that medicine today looks at the human body, as a car, but at the same time, when we need to prepare the different mechanics, for example, it's almost like preparing them to treat the different parts of the car separately, no matter how these.

Parts fit together, no matter that these parts rely on each other. So we speak today about oncology, but I see that happening in the broader medicine, not just in oncology and all of these therapeutic areas. So, tell me what makes you so positive that at least in oncology, we'll

change this mentality. We will start actually looking at the cancer in a different way. We'll overcome this, classification by organs and we'll suddenly try to, look at the tumor, let's say profile. And, especially you also mentioned the whole problem starts with not just education, but also reimbursement.

So have you seen any successful initiatives or any companies that are already pushing, like being the leaders in this space?

understand. And I think you're realistic. Thank you for, the dash of realism there. , it's not all pie-in-the-sky happiness, is it? Especially when we're talking about oncology. And, I guess. I also have people around me who are confronted with complex complex situations.

In particular, you know, they have previous comorbidities or diseases So they can't be treated the way that you would typically be treated for their cancer So it we're really getting down to patient patient-specific and personalized medicine and I do think that that's the future I work a lot in geriatry and I also am my, you know, my heroes are the generalists. And so what you were saying is true. We have to treat the body as a whole. I've worked in cardiology for the past 20 years, I think. So there is no way that you can treat someone just for their heart disease. disease. You have to treat kidney disease. You probably need to think about CNS problems. You also have to think about metabolic syndrome.

I mean, it's across the board. And so we, yes, I think that we're going more towards personalized medicine and more towards holistic treatment, making sure that we're, that we are treating. Without adverse drug interactions because you get up to 80 years old. I was just with my, with a very dear friend who's 85, it's like 25 to 30 medicines she takes a day.

And I was just so concerned about drug interactions and does she really need all of these? Is one working contrary to the other?

No, I'm going to keep the cap. And I think it comes to. Like, everything starts with the education.

So we start with how we're educating our doctors and our medical staff. There does need to be that paradigm shift. But I think we've been preparing this. Like I said, predictive analytics and, everything that's going on in, in oncology right now, they've been working on this for the last 20 years. So I think we're actually

reaching the point where, and with all of the interactions that we're able to have, we're able to put together these databases much quicker.

So molecular targeting, for success and not for failure and

not just like you said, like throwing cisplatin at it and hoping that that will be the, solution, which.

Yeah. Unfortunately, it doesn't work like that.

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And now, back to my guest.

 Gret, let me bring you a few steps back. You mentioned that, in the past you did this, I think it was a breast cancer clinical trial, no, actually you mentioned the solid tumors and then you had to, uh, recruit patients with all sorts of organ cancers.

So from breast cancer lung cancer like different types of organ cancers, right?

Correct. Yes. You mentioned that one of the challenges in such a trial

is, how do you measure the outcomes after that? Are there any other challenges of such a trial?

For the time being, um, and that will be our job, right? Is to be able to raise physician knowledge enough to be able to inform their patients so that the patients have knowledge of what they're looking for. Okay. I have a PARP inhibitor mutation and I need to go to this type of trial.

So that becomes, you know, that becomes their key is to get, how do we get those patients in? How do we raise the awareness at every level so that, and this is true even with organ-based cancer trials. You and I have already had this conversation of how difficult even going on clinicaltrials. gov it is sometimes difficult to navigate and find a trial that corresponds to you for whatever your personal journey has been.

I've had a kidney transplant, um, I have heart disease and now I have cancer. What trial is offered to me and that won't, you know, that won't be adverse to me. So I think that there are, I think there are a number of challenges to get there, but starting with that paradigm shift and at all levels with the patients to be able to get that knowledge out. Because patient recruitment and even awareness of clinical trials or treatments, you know, even when it's, marketed is and I think, you know, I think you've had a conversation recently as well, physicians, they do, they get stuck in their ways. it's, I treat this way, it works more or less. If it ain't broke, don't fix it. And,

and how dynamic can we be? How much can we influence people to say, we have something new and we have an opportunity for your patients. And coming back to what we were saying about in oncology, it's really, it's urgent. Time is, time is of the essence. We don't have five years. In my example, the PARP inhibitor, the first FDA approval was only in 2014 for ovarian cancer and prostate cancer wasn't approved until six years later. Think about the 200, 000 deaths that were due to pancreatic and prostate cancer in the interim before that was approved to the market. So, yeah, you and I've also spoken previously about treatment, as a clinical trial and having opening that up as an option. But that takes insurer insurers, you know, that takes a lot of different. Shifts

, in how we deal with healthcare to allow us to skip some steps and not start with what the current guideline number one standard of care

treatment is. And if that fails, then you try this, then you try this, then you try that.

Yeah. Yeah. Well, it's a little bit complicated. Actually, not a little bit. It's a lot complicated because then, how do we, how do insurers make the decision? Okay. I'm not going to spend this, let's say 1000, but I will spend this hundred thousand on the treatment. And, it's their insurance that they won't spend this extra amount of time.

money to patients that could actually just be treated with the 1, 000, treatment. But I understand what you're saying. And, here I'm, a little bit left with these. I don't know about like you, Gret, or the audience, but does this paradigm shift come from the educators? Imagine the universities, the key opinion leaders, are they the ones to be, to lead this shift in our mindset, how we should treat cancer?

Or actually this should come from the payers, from the insurance companies that actually focus more on the value based healthcare, value based healthcare is something that I'm super, super big on, but like, would they be the innovators or they'll find a different business model because actually what you're saying, everything you're saying actually, Cries for a different business model in health care.

So who would be this institution? Either the universities, the company leaders or the payers and insurance companies that will actually be the leaders saying, Hey guys, we actually need to change how we think about health care, how we, reimburse like treatments, procedures, diagnostics, like everything.

Would it be the government? I don't know, but I do agree with you, Gret, that at the end of the day, We don't have a lot of time, if you see, all the stats on the country's expenditures. Healthcare, they're all increasing, I'm not sure that we even have the money anymore to afford this healthcare and it's getting worse even though like population is shrinking a lot more than the prevalence is actually increasing on a lot of other like diseases.

So, yeah. I agree with you that it's really pressing that we do, we need to change something.

So to answer your question, yes, regulatory agencies are starting. The FDA has already started. ASCO and

ESMO have already started. To shift it. And that's where it has to start. You're absolutely right. The only way insurance is going to reimburse it is if the regulatory agencies and the scientific guidelines mandate it or, or say this is the way to

go. And on top of that, just to close on that, the molecular testing is going to save money. That's the bottom line

is that if you're using tumor classification for TP53, EGFR, MET ALK translocations, things like that, according to the tumor type, you're ultimately going to save people money And that obviously speaks to regulators, that speaks to governments, that speaks to scientific societies, that speaks to patients. So you're absolutely right.

Thank you. Thank you for mentioning that you're absolutely right here. Like absolutely to the point that we will be saving money and we'll be also making more money because healthier people work more and pay more taxes at the end of the day. That's how governments think at the end of the day, also insurance companies.

So you're absolutely right here. Another very interesting area of research is Psychedelics. And that's the other type of research that we see very trendy lately, but, let's say that it's not that popular yet.

Let's put it that way. Also, I see the research is exploding in a way, but how much it's actually happening, treatment with psychedelics, like what's your observation, Gret?

Well, I don't work in CNS, but it's true that I have taken a profound interest in one company that's run like Google DeepMind, in conjunction with, EMBL-EBI which is, I think it's in Germany and its microbiology. I think I mentioned it before, it's called AlphaFold.

And so basically it's, it's like the human genome project for proteins.

Now when you think about the complexity of, life on Earth, we've only sequenced and identified the structure of probably a hundred thousand proteins. We only know of 200, 000 proteins. We're 8 billion people on the earth. So this is a huge endeavor that it's open source and they feel that they can bring new treatments. And one of them was a psychedelic for anti-depression that there's a possibility for that, and you're right. Between the COVID-19 pandemic, and increasing isolation due to us being in front of our devices all the time. I mean, I would dare to say we have a worldwide. Mental health crisis right now, my kids, went through COVID online, instead of being at school, my daughter missed out on some key moments, when we were like, 16 and going out and being together,

she was, you know, in isolation. And she's all the better for it.

I mean, she's fine, but I think that there's that associated risk. So you're right. I think that there is a big focus on mental health and how to treat it, whether that's therapy. Chemically, you know, medically, or non-medically, but that brought my attention to, AlphaFold because it's just powered by this incredible, the European Bioinformatics Institute and the European Molecular Biology Library. They have like 20 member states. It's all open source. In lockdown, they were just about to launch and then they had to go in lockdown. They

ended up sequencing the ORF8, which is the coronavirus, and looking at its structure while they were in, confinement. So that prediction of the protein folds, is going to help advance research And, you know, that could lead to what they claim to be a 2 percent gain in the drug efficacy. So 2 percent gain in drug efficacy in terms of selecting the models that will work, since we know that, 85 percent of all clinical trials fail, that's a big gain. That could be really of intrigue and importance to us. And, we're seeing other, monoclonal antibodies that. Are being repurposed. There's a monoclonal antibody called baricitinib, and it was for the treatment for, rheumatoid arthritis and autoimmune disease. And now they're seeing it as possibly a treatment for type 1 diabetes. So here we're repurposing or we're seeing the connections of the protein binding sites. There's a huge potential and that's The future of clinical research and the future of medicine is there as well

It feels like, from the first topic the organ based cancer, and now depression and psychedelics, it feels like that research kind of follows. It's not like. Changing the status quo, but more like following whatever changes in, let's say, in science and medicine in general. How quick is the industry to pick up on these changes, Gret?

Like, what's your observation? Yeah,

Well, increasingly, I think we're becoming, and this is to say what we said previously, is that we have to be more reactive. We have to be more on top of this. We have to catch up right now. I mean, what was voted like yesterday, they finally came through with the artificial intelligence, law, we're way ahead in terms of what we're capable of.

We, can't even regulate what we're discovering. So yes, in order the future truly to embrace this and be much more supple. And, you know, react. The word is reactive in French. I don't know if you can use that in English, but being able to respond to new innovation and adapt it and adopt it and integrate it more quickly. So, yes, I do see that happening. I definitely see that happening at least within my reach, which is in, innovation, and being ahead of the curve and, I see that now in large or small, mostly in large, because they have more income to support it, but all of the big pharma, they have their innovation.

They have their, finger on the pulse of innovation in terms of how to collect data, in terms of how to interpret that data, in terms of, new innovation, and how to, because it's, for everyone's interest. It's for theirs and it's also for the patients and, like now that we're doing more, much more patient-centric trials, I think that also there's, that attention to even gender-specific diversity. We're trying to increase our outreach so that more of the world population is involved. is treated and that we're not leaving orphan drugs. I work right now in orphan drugs. We're not leaving orphan drugs unaddressed, orphan diseases unaddressed, and we're making sure that we're not leaving, smaller populations, with less patients behind.

So, I actually wanna challenge you here. I'm, I agree with everything you said. Besides that research should be reactive, because, correct me if I'm wrong, but all science actually starts with research. Like all the scientific discoveries in any single category, any like, physics, math, everything starts with these, experiments with research and
Right now, what we do is we are exactly like you said, clinical search right now is reactive. We follow what basically payers and the regulators do and then it reacts. But at the same time, shouldn't we as The research actually be the leader in discovering what it actually is like that the human body, how it actually works like challenge what we know today and how much we don't know, and maybe go the extra mile with the next trial.

For example, yes, I know that clinical trials are trying to get evidence on a concrete hypothesis, but while doing that, pretty sure that we're discovering New areas that we don't know about. So shouldn't we speak loud about that and actually transform clinical research from the reactive industry that is today from a pro act to a proactive, network of people who push the boundaries of what's known, and what's unknown and actually drive real innovation?

no, I think that Every researcher, whether that be in the public industry or private, is interested in discovery and wants to assess there's a new treatment I worked on a molecule that there was a Princeton researcher who held onto this molecule for 30 years.

Brought it to phase two, again, a wide-sweeping six-armed or eight-armed trial, in psoriasis. Medium to, you know, not-so-great, outcomes. But there was something that was picked up in that phase two protocol, that was intriguing. So he had held on, personally, I mean, this is sort of like, the mRNA vaccine for COVID, right?

Personal, somebody that really is carrying the torch for this molecule. Well, the molecule was rapamycin. And Sirolimus, I mean, has made its way through. Immunosuppression, cardiovascular, oncology, it just seems like I see it for everything and it's still making its way through from the soil of Rapa Nui of Easter Island.

And it's, it expanded out. So I think you have to be open to to integrating new research. And, you know, at the time Wyeth took that molecule on, and because they, they saw potential in it. But they're always going to be, there's always going to be that weighing of, is this valuable? Is there potential for the future?

We can't accept all of them. And I think that's what we were talking about is that when you have some predictive analytics, when you know what the protein binding site is, what can we use? Can we use all of these incredible tools that are coming into our realm for predictive analytics, and precision medicine, to treat better and in order to have better outcomes for our trials and bring those wonderful new products to the market? Faster, and so when I say reactive, I mean it more in the sense of taking on. Yeah. And so really what it does mean is proactive of, being, but I agree with you. We have to have our finger on the pulse of what's coming up. We can't just be integrating something and then abandoning it, integrating something and abandoning it.

It's a delicate balance. We want to integrate things that have real potential, invest in that, and be able to bring them to fruition. But if we have tools that help us to anticipate the success rate, At a higher level, then we can make better decisions. I think we can make better decisions based on, that

And here I have to agree that, you definitely left me with a very positive, like feeling, because I do agree with you that, now it is probably one of the best times ever, to actually make a difference, and make a change, this paradigm shift that you mentioned, because, AI actually comes with.

Some really practical promise here, and we see that happening in drug discovery, a lot of the things that you now mentioned, the whole data, the integration, the structuring of data, understanding more, I do believe that now we have much more, much better chances than before to understand beyond what we've known, and thank you very much, Gret, for sharing this also story about this researcher, because these are the stories that give us this hope that, yeah.

We will get to solve the puzzle, one way or another. Great. Because we don't have much time anymore and, um, I'm enjoying this conversation, we can go on, like, discuss a lot of other topics, but I just want to make sure that I asked you this like a question, like one last question. Just to get your perspective, because that's what I'm trying to do with this podcast, to bring different perspectives from different people like you and to inspire people out there to be more open, but also see problems and challenges that we experience on a daily basis differently and probably find more sustainable and scalable solutions.

So from your perspective, Gret, what is this one thing that if we change it it will make clinical trials more successful and patient-friendly?

One thing, Maya?

Yeah, I know, I know, I know it's hard, I know it's hard, but like, what is this one thing that, at least now, for example, you think that if we invest time, money, resources, attention to, if we nailed it, then that will make tremendous impact on how successful clinical trials are and patient friendly.

Well, for me,

and, and this has been part of what our discussion today has been. For me, it comes right back down to the patient. Now I don't expect that every single patient is going to be 100 percent educated on their disease. They're invested. They want to get well. So they may have, spent the time. From my perspective, am medically trained with a large scientific background. Sometimes it's very hard for me to understand someone like my mother or my aunt or who doesn't have that background and how lost they are. They don't even want to ask questions to their doctor.

They don't even want to know, even so, you know How do we bridge that gap? Earlier in our in this podcast today? I was thinking, you know the patient advocacy groups for Lupus or other autoimmune diseases or cancer. They bring a voice of, we need this.

I've worked in mucoviscidosis, which is, cystic fibrosis. Those patient advocacy groups, have leverage. Look what, we were able to do with AIDS. Look what we were, we've been able to do with, you know, some cancers even. You know, we have a very good outcome for prostate cancer.

If it's not well if it's not too far advanced. So there is progress. And so I, my answer would be that giving, as much information and, empowerment and access to the patient is important. Because, ultimately, that's where it starts. If a patient refuses to be treated or doesn't understand, or doesn't have access to it, we're never going to get there. I would say that's a big piece. That's a very big piece, is the patient.

Yeah, and educating the patients and here I definitely see progress, but we need to do much more. Gretchen, thank you so much for your time and for all the inspiring stories today and keep doing work and pushing the boundaries on what's possible, and what's not possible. Thank you so much.

Thank you, Maya. Have a great day.