Ask Me MD: Medical School for the real world

Ken Pienta, MD - Academic and Pharmaceutical Medicine

January 15, 2021 D.J. Verret, MD, FACS Season 1 Episode 27
Ask Me MD: Medical School for the real world
Ken Pienta, MD - Academic and Pharmaceutical Medicine
Chapters
Ask Me MD: Medical School for the real world
Ken Pienta, MD - Academic and Pharmaceutical Medicine
Jan 15, 2021 Season 1 Episode 27
D.J. Verret, MD, FACS

Dr. Ken Pienta, professor of Urology at Johns Hopkins University and acting CMO of Cue Biopharmaceuticals, talk about his experience in academic medicine and clinical trials. Dr. Pienta shares his thoughts on why physicians changing career focus isn't a negative but much for a positive. The discussion ends with a walk through of the process of clinical trial design and approval.

If you have questions or ideas for a show, send us an email at [email protected]. Hear the latest podcast at http://askmemdpodcast.com or through your favorite podcast directory.

Show Notes Transcript

Dr. Ken Pienta, professor of Urology at Johns Hopkins University and acting CMO of Cue Biopharmaceuticals, talk about his experience in academic medicine and clinical trials. Dr. Pienta shares his thoughts on why physicians changing career focus isn't a negative but much for a positive. The discussion ends with a walk through of the process of clinical trial design and approval.

If you have questions or ideas for a show, send us an email at [email protected]. Hear the latest podcast at http://askmemdpodcast.com or through your favorite podcast directory.

Announcer:

Ask me MD medical school for the real world with the MD Dr. DJ Verret

D.J. Verret, MD, FACS:

Greetings, and welcome to another edition of Ask me MD medical school for the real world. I'm Dr. DJ Verret and today we're talking with Dr. Ken Pienta, professor of oncology in urology at Johns Hopkins University and acting chief medical officer of Q biopharma about his experience in academics and pharmaceutical medicine. We'll talk to Ken right after this

Announcer:

Ask Me MD medical school for the real world.

D.J. Verret, MD, FACS:

Commerical Here Welcome back to ask me MD medical school for the real world. I'm Dr. D.J. Verret. And today we have the great pleasure of talking with Dr. Ken Pienta, professor of neurology and oncology at Johns Hopkins and acting CMO of Cue Biopharma. Ken, thanks for joining us.

Ken Pienta, MD:

I'm glad to be here. Thanks for inviting me.

D.J. Verret, MD, FACS:

So for all of our listeners out there who may not know, can you give us a little bit of history of your background and kind of how you got where you are today?

Ken Pienta, MD:

Sure, I trained in internal medicine at the University of Chicago and then went on to do an oncology fellowship at Johns Hopkins. And after that, I moved as an assistant professor to Wayne State, and then the University of Michigan where I spent 20 years running a translational research lab, basically focused on prostate cancer metastasis and therapeutics, and at the same time building up a practice in advanced prostate cancer. And then after 20 years of doing that, at the University of Michigan, I moved to Johns Hopkins, where I directed started to direct urology research, as well as develop the precision medicine program for Johns Hopkins. And that brings us here to today.

D.J. Verret, MD, FACS:

For for folks out there that may or may not really understand could you kind of explain what precision medicine is. I hear that term a lot. But I don't know if anyone's ever succinctly explained it to me.

Unknown:

Well, their their precision medicine is, you know, to use the tried and true definition is treating the right patient with the right drug at the right time. And now in 2020 at the right place. And that's especially true now with COVID. In that we have found that we need to be much smarter about how we treat people and where we treat people do we really need to bring them into the hospital to treat them. So part of precision is actually developing methods to do video medicine when it's appropriate and understanding when it's not appropriate. That's all about precision.

D.J. Verret, MD, FACS:

That's an interesting evolution. I hadn't thought about the the right place. But but it continues, I recently interviewed the CEO of a mostly rural hospital system. And he brought up the potential for virtual hospitals, that they're starting to talk about kind of in line with what you're you're talking about?

Unknown:

Yes.

D.J. Verret, MD, FACS:

What what kind of drew you to academic medicine? Why did you why'd you want to go in academics over some other practice opportunity?

Unknown:

Well, for me, I loved the research. And I loved the bench research part of it, the translation, and so to be successful, and that what I understood very early, was that I was going to have to narrow my clinical focus that it was going to if I was going to study prostate cancer in the lab, which is what I was trained to do. It made the most sense to work with prostate cancer patients, and therefore they became my clinical laboratory. And I would seamlessly do what I would look at what I was doing in the lab and then apply that to my patients in the clinic as I tried to develop therapies and then I would use their blood and bone marrow and biospecimens and tissue to take back to the lab to help me do better research and then as I was developing those resources programs, I realized it was very difficult to take any type of research, whether it be predictive biomarkers or clinical therapeutics, all the way across the finish line to an FDA approved product that would help actually help people across that sort of gap. And so they started working more and more with industry to to understand and translate what we were doing in the lab, to patients, and then from patients clinical trials, all the way to approval. And you can't do that alone anymore, maybe 30 years, 4050 years ago, you know, you've heard about people developing drugs at the bench and then taking them all the way to to, to the clinic and beyond. It takes a village, it takes a team it takes biotech by, you know, pharma, academic labs, etc, to do all that entire translation across the spectrum. And that's why I started also working over the years with, you know, biotech and pharma.

D.J. Verret, MD, FACS:

What do you find most rewarding about your involvement in the whole drug design and development process?

Unknown:

You know, I find the bottom line is we're here to help people and to try to make a difference and find ways that decrease morbidity and mortality. And I find that each step along the way, on any given day is really exciting. And I have the great privilege of being able to do that dance of of working in the lab, working in the in the clinic, but then, through my connections to biotech, actually develop those clinical trials into into large multicenter trials to work towards FDA approval. And I've been able to do that now in my life for not only drugs, but also imaging agents as well as bio biomarkers. Like for example, I was the guy that developed circulating tumor cells for prostate cancer as a diagnostic marker.

D.J. Verret, MD, FACS:

When we were talking earlier, I use the term non clinical medicine, which I think a lot of people would say, when you're involved in pharma, you're, you're in a non clinical job. But But you brought up a really good point that, that no, it's not non clinical. Can you kind of explain your thoughts on that?

Unknown:

Yeah, I, you know, I use that we were talking offline and you use that that term and I took some umbrage.

D.J. Verret, MD, FACS:

That's true. I was I was kind of put in a different way. But yes.

Unknown:

The reason why is because, you know, we need smart people in every step of this process of drug development, and, and what I tell my students, my, my PhD students, my clinical fellows, is that it's where you find your joy, but specifically, you know, for MDS, we need MDS who are trained to take care of people who understand illness, who recognize side effects, to work in industry, whether that's biotech or pharma, as we develop drugs, so, for example, is to be a medical director or a medical monitor, for a clinical trial of a first inhuman drug requires, you know, that you have expertise, that you can recognize what side effects are, and that you can recognize when your first inhuman drug might be having an adverse side effect or adverse event. And that's it. So you're you're taking care of people, and you're watching the drug develop. And you're and you Although you're not laying your hands on them, you are directly involved in their care, you are making lifetime decisions about whether they should continue on a drug. You know, the recent halt of the of the Merck study with COVID is because there was an MD in pharma. Not seeing patients but recognizing that there was a weird side effect. That that is that is clinical medicine to me. And I think folks who are switching over to industry potentially from academics or from private Practice to industry, because they they just don't want to do for example, the day to day clinical patient caridy anymore. They can, that's a very rewarding track to to be able to take care of people that way.

D.J. Verret, MD, FACS:

With your experience kind of being on the clinical side, the academic side, and then the pharma side now as an acting cmo with a with a biotech company in clinical trials, what advice would you give to physicians that may be looking to transition into some of these pharmaceutical jobs?

Unknown:

Yeah, my, my, I guess my number one piece of advice is to really clearly determine for yourself, what what you're interested in doing what you're excited to do every day. And they're the spectrum of, for example, biotech. That means that, you know, are you more interested in immunology? Are you more interested in Rheumatology? Are you more, you know, find fight, you can find there's so many companies out there. And so many opportunities, you can really find the type of position that you want to with the kind of drug you want to if you want to just dabble, you know, to say, is this interesting to me, that many of these companies have advisory boards that you can become involved in as they try to develop agents and they're looking for a, for example, how will this drug be used in the clinical practice you were in? Whether and it doesn't matter whether that was academics, or private practice or large groups, there's a lot of opportunity there. The other thing you have to think about is, do you want to be in biotech, which tends to be a small, you know, smaller organizations where you're going to be the MD, and they're going to be looking at you for your for clinical acumen. And understanding how a drug affects patients. Where or do you want to be part of a larger organization, like a pharma, a big drug company, where you might be asked to, you know, develop a particular agent across multiple countries or do it, you know, we already know the toxicities and what they need somebody to run a phase three, study. The, the also, the other thing you can do is, you know, depending on your training, you can get involved in, quite frankly, on the non clinical side, do you want to develop help develop FDA packages, you know, the the ind investigational new drug packages. And to do that, again, you can there, there are ways to do that, where you can sort of dip your toes in to say, this is something I want to learn, and figure out how to do.

D.J. Verret, MD, FACS:

I was interviewing a friend of mine from medical school who ended up going into hospital administration. And one of the things that he said that stuck with me was, when you're looking to leave a clinical practice for some other ground, always go towards the job, don't run away from a job. And so I wanted to get your thoughts on that. It sounds like you were kind of leaning towards towards that statement. So I wanted to get your thoughts on it.

Unknown:

Yeah, I think that's a beautiful, a beautiful way to put it. I think with any move, there's a push in a poll, and you have to make sure that you're aware of what, you know, put the pushes are number one, like why do I want to stop doing what I'm doing? And that doesn't have to be a negative. You know, people tend to think, Oh, you know, I'm burnt out, I got to get out. I'm working too many hours. The pay, you know, too many people are dying, or, or on the other end, I'm tired of taking care of diabetes and hypertension, and I'm bored. You know, those are all that doesn't have to be a negative statement. Right? It's just you're you're evolving in your life. You're, you're saying what I was doing for the last several years is not what I want to do. And some people come to that very quickly. I had a friend who was a fellow in oncology back when I was training, who jumped to industry in the space of about two years because he went, you know what, I made a wrong decision. I don't want to take care of cancer patients that every day, it's too much for me so So recognizing that is a powerful thing. It's not a negative. That push you that I think, you know, is not a is not a recognition of defeat. It's a recognition that your brain is evolving that you're thinking that differently. In fact, it's not a defeat, it's actually a powerful statement that says, I want to evolve, and I'm not going to accept who I am right now. And just put in the time, life's too short to just put in the time. So you have to find what you enjoy doing and what you're passionate doing. And whether you switch to an in you know, biotech or pharma, or to administration or to working in a law firm, working in patents, you know, firms working VC, all of those things can be fun, you just have to find out what's fun. And, and so what's the poll is very important. But I think even more important in the moment is understanding that the push is not a negative.

D.J. Verret, MD, FACS:

I think that's also a great expansion on what my friend was saying, just to be able to recognize where you want to be in and what you want to change, because I totally agree with you. It life's too short not to be in a job that you're happy with. A couple of the terms you use biotech versus pharma or biopharma? Can you kind of explain the differences in those because I hear those terms a lot as well.

Unknown:

Yeah, well, I'm sure there's official definitions, my definition basically, you know, a biotech a technology company is generally formed around a particular idea and is developing either diagnostics or therapeutics, based at least initially on a very narrow ideas. So, for example, q biopharma is an immuno oncology biotechnology company that was formed on technology out of Albert Einstein to develop specific molecules that we call immuno stats that are going to very selectively deliver an antigen to a protein that T cells should recognize for cancer therapy, is it at the same time, it is not developing a targeted agent for diabetes, for example, it is, you know, on a path based on this, this this drug platform, and that's important. So, biotech tends to be small, you know, the company, at least early tends to be, you know, companies with, you know, 10 to 100 people that are all working to get develop agents around a particular platform in a particular disease setting. As they get as, as they grow, they can take on other things, but they're basically formed around a specific IP, intellectual property and technology. And if they're, they're often developing first and human drugs, doing phase one. And phase twos. Farm pharma is a, you know, companies like Novartis and Bristol Myers are are large, multi 1000 member companies that are developing drugs and get delivering drugs that are already approved, as well as tending to run phase three trials where they're trying to develop more drugs. So you'll often see if if a company a biotech company has an agent that looks promising, they often get gobbled up, they get bought by a large company, who will then do the phase three trials, which often cost hundreds of millions of dollars. So the way I think about it is pharma. pharma is trying to do has multiple drugs 10s, if not hundreds of drugs in their portfolios across a wide variety of diseases, and generally are only running phase three, generally running phase three studies as well as giving drugs to people, you know, by prescription. So

D.J. Verret, MD, FACS:

what I'd like to use your your introduction into cue to talk a little bit about your acting cmo job and and just the thought process that goes into development of a drug trial. I think that's extremely interesting. And also just the process for the drug trial, because people hear a lot about phase one, phase two, phase three, but you don't hear a lot about all of the work before you can even start that phase one. So just to start, can you kind of describe what that pleat pre clinical work looks like in the development process, just from a 50,000 foot view?

Unknown:

Wow. Yeah. Well, that's that's an exciting area. area. And basically, that's what we did I did with Q, which was, you know, developed here we had this this molecule that we wanted to, to give to people. So to do that you have to do what are called ind enabling studies, which are investigational new drug studies. And that includes developing all the assays, outside of animals or people that demonstrate that your drug has activity, for example, does it bind to a T cell in a ditch, and then you have to do in vivo studies in in in basically in mice and in in rats to say, Oh, we have anti cancer activity. And then you have to do what's called tox, colic toxicology studies, where you have to prove that your drug was through a variety of doses is going to be safe for rats, as well as potentially dogs or monkeys, and demonstrate, and not only that the drug should be safe. But determine the starting dose for your drug in humans through a set of complex formulas that are complex, but easily learnable. You then take that in package, and simultaneously, you're developing your drug, you're putting it into vials under good manufacturing processes, to be able to say that it's sterile and not has the right pH and the right you the right vehicle that you can actually give it to people, whether it's IV or orally. And then as you're doing all those studies in parallel, you are also writing it all out and developing what's called the investigational new drug package, where you will present that whole body of evidence to the Food and Drug Administration to say, let us give this to people. It's a really exciting process.

D.J. Verret, MD, FACS:

When and then once you give it to the FDA, the FDA hopefully will tell you, okay, you can give it to people. But that's also the start of another whole process. Because the drug design in that phase one is is actually pretty important, right?

Ken Pienta, MD:

Yeah.

Unknown:

Right, so so once, as part of that package, you have to develop a phase one trial design. Yet generally, there are multiple phase one trial designs. But the most common is what's called the three by three design where you give three people a drug at a first dose, if it's safe, you then move you move up the dose and give it to another three. And if it's safe, you give it to another three. But if you find one, got one person gets sick, then you out of those three, enroll three more people. It's a it's a well known design that's been developed over the last 20 years that almost all phase one drugs use. And that's, again, it's all about determining safety and determining your ultimate dose for the next set of trials, phase two, where you're actually trying to determine efficacy.

D.J. Verret, MD, FACS:

But when you talk about the phase one, I know with q in particular, you not only you're giving it to the patients, but you're looking at data on the back end as well. To not only determine safety, but to try to get some information about how the drug works. Correct. Yeah,

Unknown:

yeah. Sorry. I didn't realize that's what you were looking for. Yes. So with with whenever you're getting a drug for the first time, you also look for two other effects pharmacokinetic effects or PK? Which is how fast is your drug? Get clear the system? Does it do it through the liver does do it through the kidney? What How long does it stay in the blood? Those kinds of questions, those pharmacology questions. The other thing that we're doing is you draw blood, so you have to draw blood from the patient and determine that and get tissue from them if you can. And the other part of that is the PD or pharmacodynamic effects, which is where gosh, you know, we're trying to turn on antigen specific T cells. So we're going to draw blood from patients after they've gotten our drug and from before they got their our drug and then put their their blood in with our naive T cells and see if we turn them off. And that that is basically the pharmacodynamic effects and and no matter what drug you're doing. Developing, whether it's an immunotherapy or a targeted agent, you're always looking for on the back end from your patients, the PK and PD assets.

D.J. Verret, MD, FACS:

And I also found it interesting that phase one isn't, you know, people say phase one. And you may think, Oh, it's it's pretty standard, as you mentioned, there are different trial designs, but also their different patient populations, you may give your drug to depending on what kind of drug it is, right?

Unknown:

Yeah, absolutely. And, and the cancer world as well as all medicine has really evolved or about that. They've just become more precise, right? So so we only give our drug, for example, and we had to work with the FDA for this. We were targeting HPV positive Human Papilloma Virus driven cancers, we could have picked head, neck, cervical, and you know, penile cancers. And so, we we specifically, you know, with the FDA, they said, Let's pick one disease type, and develop your drug and one disease type. And then as you get your dose move into other other treatment groups, so every time you're doing a phase one, it used to be that it was sort of like, oh, anybody who has nothing, no, no disease, no drug left to try for whatever their disease was, we were going to give them a phase one agent, because it was all about just determining the safety of that drug. That's really rare. Now, almost every agent that's going into clinical trial now is around a specific disease type. Looking at you because we want to look worse, even in the safety population, you're still looking for signal.

Ken Pienta, MD:

It's it,

D.J. Verret, MD, FACS:

it's a lot, you know, when I first kind of started getting involved with these companies, you think I always thought, oh, phase one, you just give the drug to somebody, but there's a lot that really goes into it. Where did you learn through that process? Did you start as an investigator for drug companies? Or was there some class you took? Or? I mean, how did that evolve? For you?

Ken Pienta, MD:

Wow, yeah, yeah. It's, it's, it's what you're always learning. And, and you can't be afraid to say what you don't know. But I, you know, I've started out first by, you know, an academic investigator running trials for companies drug because they had drugs I was interested in and, you know, understanding number one how to write a clinical trial. And that is something, you know, you you learn through training, although there are classes for it also. But the classic way back when I was doing it, you know, was here, go, right, this trial, here's a previous example, right? But there, you know, it's all on the web now, right. And then there's a lot of all the materials of how to what you need to do to develop a drug is all available from the like, the FDA websites. And then I also started to consult for companies and understand, you know, as they were developing there, as I was an investigator, they would ask me to come to an investigator meeting, and I would see the process they used to get there. And as I wanted to learn more about that, I would ask them questions and ask, could I be involved in that in any way so that I could learn the processes by which you go to the FDA, how you put together an ind package. And then again, lots of reading lots of learning, there's papers on this, there's books on it, there's websites on all this, and then every time we hit a, you know, sort of a roadblock of knowledge, you just, you can find the answers out there. And, and so it gets and it gets easier every time but also every drug has a little bit of a different, you know, weight that needs to be developed. But for example, the the tox studies are our standard, pretty much standard across the industry. You got to do two species, you got to do a rat and a monkey or a rat and a dog, you know it and, and so what you sort of do it once and it's like a bike, you know, you just have to plug your dragon and do it.

D.J. Verret, MD, FACS:

But I think the the important take home is it was an evolutionary process for you. It wasn't like you woke up one day and congratulations, you're acting CMO of a company.

Ken Pienta, MD:

Absolutely correct. Yeah.

D.J. Verret, MD, FACS:

What one one quick thing we didn't talk about in that phase process after you get your FDA approval. That's also part of the regulatory process, you still have to get if you stopped to get IRB approval at each one of your institutions as well, which is a whole nother process that involves more physicians, correct?

Unknown:

Yeah. So as we in, for example, for the FDA approval, and then, you know, you have to write the first write the the IRB template, so we have to write an IRB template. And we also have to write an investigators brochure. And we have to write a pharmacy manual. So there's three pieces of large pieces of work there, that you've written, the trial that you want to do, the IRB, that consent that goes with it, the investigators brochure that goes with it, which is sort of like a drug insert, and then the pharmacology manual, which is how you want them to give the drug. So you write all of those and you submit them to every place that you want to do the trial. They then modify it to their individual idiosyncrasies, which is a good way to put it. It's each institution and each IRB has their own idiosyncrasies, and, and that's how that process works.

D.J. Verret, MD, FACS:

Ken, this has been fascinating. I really appreciate the insight into I won't use the term non clinical medicine, just hire clinical medicine, but it really appreciate the time. Thanks for coming on.

Ken Pienta, MD:

Yeah, you bet. Take care.

D.J. Verret, MD, FACS:

We've been talking with Dr. Ken Pienta, professor of neurology and oncology at Johns Hopkins and acting chief medical officer of Cue Biopharma. You're listeni g to ask me MD medical school f r the real world. I'm Dr. J Verret. Thanks for joining u . Until next time, make it n awesome wee

Announcer:

Thank you for joining us for another episode of Ask me MD medical school for the real world with Dr. DJ Verret if you ave a question or an idea for a how, send us an email at uestions at Ask Me MD po cast.com.