Naji Gehchan: Hello, leaders of the world. Welcome to “Spread Love in Organizations”, a podcast for purpose-driven healthcare leaders, striving to make life better around the world by leading their teams with genuine care, servant leadership, and love.
I am Naji, your host for this special episode in collaboration with MIT Sloan Healthcare and BioInnovations Conference, an event that brings the Healthcare Ecosystem Together. I have the pleasure to be joined by Michael McKeown acting CSO/head of research for a stealth start-up at the Pagliuca Harvard Life Labs. Michael started out in California getting his BS in Chemistry at UCSD and working in the Nobel Prize winning Tsien lab on fluorescent proteins. He then moved to Boston, earning a PhD in Chemical Biology from Harvard while working on novel cancer therapeutics at the DFCI. During this time, Michael contributed to several start-ups spun out the the lab, ultimately joining Syros Pharmaceuticals. As part of this work, he developed novel patient biomarker and pharmacodynamic markers to enable selection of the right patients and kinetic monitoring of response. With 10 years of industry drug discovery and development experience in the Boston area, Michael has contributed and led multiple successful programs. Most recently, he led pharmacology at Kronos Bio supporting combinations, biomarkers, and PD assays for the clinical programs as well as leading biology for their most advanced pre-clinical program generating an asset currently in IND enabling studies.
Michael, so good to have you with me today!
Michael McKeown: Thanks for having me on.
Naji Gehchan: Before we dig in “innovation and decentralization in clinical trials” the topic of your panel at SHBC, I am eager to hear more about your personal story. What brought you to the biotech industry and now heading research in biotechs?
Michael McKeown: Sure. Thanks. Um, Yeah, you know, I’ve always had a very strong interest in science, and, you know, I was very fortunate, uh, when I was at UCSD to be able to work with the Chen lab, um, you know, and getting to experience flexible proteins and imaging, um, and from there, you know, I moved to Boston, and, you know, Um, I got to hear a lecture in one of my classes from a professor, James Bradner, who was just starting out at the time, um, but he was so inspirational and so passionate about cancer therapeutics and helping patients, and especially as a physician scientist, that, um, I signed up and joined his lab, um, when he was at Zanf Harbor.
Um, of course, he went on from there to, to head up NIBR, and he’s now at Amgen. But it was just such a cool experience to be able to do, to be able to do research in a context where, you know, we were passing by patients, seeing them, you know, seeing the real effects of this every day when we were getting lunch and, and in the building.
Naji Gehchan: So going from there and from labs, as you said, to a startup word, several startups spinning out of labs, and now up to pre IND assets. So I’m, I’m intrigued by your leadership learning. What did you learn along the way moving from academia to entrepreneurship and building biotechs?
Michael McKeown: That’s a good question.
I mean, And I think part of the learning happens through, you know, classes and stuff. And there’s always, you know, like a little bit of the HR training and development at companies, but so much of it comes from, you know, mentorship. You know, I think the, the CSO at CIROS, um, when I was there, Eric Olson was really inspirational.
Um, you know, taught a lot about, you know, how to, how to manage organization that, you know, You know, people are important that, you know, one of the key things is, is, um, reducing unforced errors, right? Science is hard. So we’ve got to just reduce our incidents of mistakes that we could have prevented. Um, the other part is learning.
So, you know, in reading and actually my wife and I both, you know, we’re both in biotech. And so we purchased book series from like Harvard Business Review and, um, took classes at HBS and stuff. Um, I think that was really helpful, but yeah, yeah. I feel very fortunate that. There were some very good mentors and examples and leaders in some of the earlier organizations I was at to learn from.
Naji Gehchan: So if I double click on this, now that you’re acting CSO, is there one leadership behavior or one, one of the leaders who inspired you most that you would replicate what they have done as you are leading teams? And I loved how you framed it on the science part, right? Like science is hard. We need to reduce incidents of mistakes.
And as, so as you lead those teams with the ups and downs, this, this is where I’m asking these questions.
Michael McKeown: Yeah, so I think one of the one of the interesting features of science leadership in particular is that you’re trained to be a technical expert in your career, right? You go to grad school, you get a PhD, maybe do a postdoc and even work up in early levels of science and industry.
You are a technical expert and ever, ever deeper into your technical niche. And then suddenly. At some point, you start getting reports and you start to be more of a manager and a strategist and budgets and timelines and stuff, and you haven’t really had much training to prepare you for that. Um, so I think, you know, part of this is, you know, really embracing that, trying to learn, trying to learn from people around you, and especially some of the more senior people.
Um, you know, especially if you get some of the consultants that are actually like, you know, industry veterans that are semi retired. Um, the other one, I think a lot of scientists and, you know, I, I’ve struggled this with this. And so either colleagues or managers is that your skills will become obsolete someday.
And so, you know, your technical skills, like the way that I learned to do a Western blot is no longer how any of the labs do a Western blot, right? That’s okay. It’s much faster now. That’s wonderful. But, like, I have to be okay listening to the people who are now the technical exp, and, you know, understanding that my most important contributions aren’t micromanaging them.
It’s listening to them.
You know, the strategy and the value that we can create as a company and how it can help patients and helping to match that with what the scientists are telling me to make that fit into, you know, what we can actually accomplish with our budget and runway and timeline.
Naji Gehchan: I love this. And you’re framing it through practically unlearning sometime, uh, what we’ve learned before and also be humble enough, right?
On, on those aspects where you’re not an expert in managing teams. So that. I’m, I also have in my team scientists and physicians, so I, I relate to what you’re saying. And it’s an important piece of being humble and say, okay, I’m going to learn how to lead people and manage people. So I love how you frame both.
If we now go to your panel discussion, uh, I’d love first to hear your view, your personal view about innovation and decentralization in clinical trials from a broad perspective.
Michael McKeown: Yeah, so there were kind of two main things I was really trying to push, um, you know, in bringing to the panel and I want to make sure we covered for the discussion.
And one of them was getting the right drugs to the right patients. You know, there’s been a lot of talk about precision medicine, biomarkers. This has been driven by the ever, you know, cheaper ability to do NGS, for instance, you know, next generation sequencing, which used to be quite expensive and prohibitive, and now is actually quite commonplace for a lot of patients, at least at research hospitals.
Um, you know, so actually leveraging a lot of biomarkers to match the right patients with the right drugs, and then also getting more innovative, more Um, you know, as opposed to, you know, moving away from kind of the history of just, well, let’s get to MTD. Let’s do an all all comers advanced trial with the end stage patients.
They’ve seen a ton of prior therapies. Um, I just don’t think that that has a very high probability of success. And even more, I think it actually weeds out drugs. That would have value if they weren’t put through that process. So that’s kind of it at a high level.
Naji Gehchan: Great. So now let’s dig a little bit deeper.
If we take, because it’s a broad topic, and this is why I wanted to start at a high level, right? Like innovation and decentralization. So let’s now take the decentralization piece in clinical trials. A lot has been said, a lot is going on. COVID kind of reshaped or accelerated, I should say, some of those pieces.
How do you think of it today? And really behind this question, I’d love for you, if you can share, what are we trying to solve? With the city.
Michael McKeown: Yeah. So on the decentralized side, um, I’m actually a big fan of the investigator sponsored trials where, you know, this gets back to kind of hypothesis testing. So, you know, if you could open up your clinical trial, and there were some umbrella trials a few years ago, but they’re actually a bit less common now.
And I was hoping that trend would catch on more. But, you know, what I’d like to see is if you could open your trial and maybe the company or the original sponsor has an initial hypothesis they’re testing, but you just can’t possibly know everything. And so we’ve got to be able to, you know, capture the value of all these other scientists and physician scientists around the country and around the world that are coming up with innovative applications and ideas.
And so if they come to you with an IST. It would be nice if we could kind of bolt that onto the umbrella, figure out kind of the fastest way we can test this hypothesis, figure out if there’s a there there. And if you do get some traction, then, you know, expand out your path to try and cover that and get, you know, approval.
And this could work for, you know, maybe you find a new, Um, accelerated path to your first approval that you hadn’t even thought of. Or maybe this is an opportunity to expand. Um, and I think this is actually especially impactful in some of the smaller disease areas. Because maybe, you know, your, your original science had, couldn’t really model it.
There, there’s not as good modeling available. It’s not something that was originally on your radar, but, you know, if a really motivated physician scientist or patient community comes to you with this hypothesis, we’ve got to find a way to kind of, you know, decentralize, loosen up the structure to allow this sort of hypothesis testing.
Naji Gehchan: And as you’re thinking about those hypotheses from an investigator dance, uh, and from a company, then, so, uh, you’re trying actually this umbrella idea and then taking innovation from it from outside, say, say new indications or other pieces, put it in this one in like umbrella, uh, trial you’re thinking of, how do you think about, um, and did you discuss in the panel, the patient’s implication?
Of decentralized trial on their participation in those trials and how it’s done globally.
Michael McKeown: Yeah, that was discussed a bit. And, you know, particularly around, you know, matching people up. And so I think there, there is kind of some need for innovation there that. You know, if you, if you go to one of the main, you know, research hubs to a major research hospital, getting on a clinical trial is going to be a lot easier.
But if you’re not, you know, in 1 of those areas. it can be a lot harder to find. Now, I think one of the models that is really encouraging to me is with some of these patient groups. Um, so there’s, there’s some foundations and, you know, patient, patient disease centric organizations that have kind of taken this from a grassroots approach, and they will help connect patients with the trials, with the cutting edge research.
Give them a community of other people to talk to. Um, and that could be phenomenal. I’ve seen cases where, you know, they were concerned. Oh, that’s a rare disease. We’ll have really hard time enrolling it. And because there was a foundation and a patient group behind it, that actually became the fastest enrolling cohort on the trial.
Um, which, you know, nobody really expected, but that just shows the power of, you know, what we can do in the digital age and the power of, you know, the patient experience.
Naji Gehchan: Sure. And, and we’ve seen there’s tremendous work of patient advocacy group, uh, as you said, to help patients through their diseases and clinical trial, uh, can several times be actually the best treatment option for patients.
And so the working with advocacy group is certainly. impactful and we should all be grateful for what they do. Um, and you touch on something that was kind of my follow up question, uh, on some area, you said some areas might not have those trials and especially in your idea of, for example, IITs or IIS, it depends which academic group most probably will have the trial, et cetera.
So I’m thinking from a diversity and equity approach of those initiatives. Has this been discussed and how decentralized clinical trials or innovation in clinical trials can help improve diversity in clinical trials?
Michael McKeown: That’s a really interesting point. I mean, I think just being able to capture, um, more diverse geography helps that a lot.
You know, um, some of the research hospitals and hubs happen to be in cities that that may not capture the full diversity. Um, and so, you know, just being able to make sure you’re capturing, um. You know, potential patients from, you know, maybe, you know, rural areas. More in the South and Midwest. Um, you know, I live in Boston, and so we’ve got, you know, MGH and Dana Farber and Brigham and, you know, just the South or Mario Sloan Kettering, you know, multiple research hospitals in New York, but, um, you’ve got to have mechanisms to be able to boost awareness, um, and access.
And then, you know, the other thing I think has really helped there, Um, is um, you know, foundations have helped with patients getting to those sites. So maybe the only way to get that new treatment is to get to one of those research hubs. And if that’s the case, there’s got to be a way to help cover the costs.
Because I think that, that is one of the prohibitive things is, is just, can you afford to, you know, leave your hometown, get on a plane, fly, and put yourself up? In that area for, you know, an extended period of time, if you’re going through, you know, multiple infusions of a therapy. Um, so, yeah, you know, there’s got to be some mechanism to cover that.
And I don’t think that’s generally going to be coming from, like, insurance reimbursements as is currently structured.
Naji Gehchan: Yeah, those are those are great points from from a participant plans, right? Especially for underserved communities, how we work with advocacy group or other mechanism to, uh, to ensure the time, uh, the transportation, as you said.
So these are great examples. Uh, you’re giving. Uh, and then also community sites, I think, is one of the important pieces, uh, for, for diverse enrollment. Um, as you discuss those, I would love to hear your point of view. What excites you most from an innovation standpoint in clinical trial that you think will literally change the way we are, uh, from designing to executing our clinical trials in the future?
Michael McKeown: Yeah, I mean, I kind of touched on it earlier with the biomarkers, but, you know, it still feels like a very nascent application. The promise of NGS, of sequencing, of knowing exactly what the mutations are, what the What the condition is of the patient. Um, that’s still being rolled out, you know, and so I think some of the front front runners here and like, um, so in blood cancers, they’re actually restructure stratifying the disease based on your mutational profiling and linking that to what treatments you should get.
Um, so, you know, that’s starting to happen for, for standard care treatments, but even on new clinical trials, um, you know, there’s still so many trials out there that just go into the, the phase one advanced all comers, you know, solid tumor, for instance, and oncology or, or try to go for a very broad SWAT.
And I understand that, that, you know, capturing the broad SWAT, you know, has a potential potential implications for a larger market share down the road. And you know, also people say, well, it’s just a phase one that’s just supposed to be for. Um, and to set the dose. But, you know, a lot of investors and a lot of people are watching those trials now and do expect to show some sign of activity.
Um, you know, reason to believe that might be a bit unrealistic or optimistic in some cases, but, you know, nevertheless, that’s kind of what’s happening. So I just worry that, you know, by using these kind of older approaches that we’re actually missing stuff, it could be quite impactful if you were using them in the right patients.
And so. Yeah, I am a strong, strong advocate of leveraging all that science, you know, preclinically that we’re doing. And, you know, using biomarker approaches at the earliest stages of clinical work, at least as a correlate. So you can understand, well, did the people that were positive have a little bit higher activity than the ones that weren’t?
Um, this is actually what, what Ciros, the first company I was at did, you know, we showed that there was an enrichment of response in the biomarker positive patients. And then. When we go to the phase two and now phase three trial, we’re only looking at selected patients. And you have a really, really high response rate because you’ve pre enriched patients.
Um, and what that does is then that actually gets you a smaller trial because you don’t need as many patients because you’ve You know, essentially aren’t enrolling as many likely negative patients in terms of response. Um, and so, you know, if you need less patients, you can enroll faster and complete your trials faster, which is a huge component of the cost.
So, you know, a lot of the cost, you know, a huge portion of the cost in, um, new drug development happens during the clinical trials. And so anything you can do to shorten that and reduce the number of patients and not treat patients who are not likely to benefit. Is a good thing and, you know, furthermore, I look at even even older drugs, you know, you look at something like for septum, which is using her to breast cancer.
You know, that was going for the highest level of expression initially, and that got through and got an approval. And then subsequently, and partly because of real world evidence, and you know, what was happening in the clinics, they’ve since opened that up. And so they’ve figured out that there is benefit for, for an expanded, you know, swath of biomarker patients.
And I, I think that’s a really good way to go. You know, get your, get a fast tactical trial done, you know, um, relatively more efficient. In a selected population, and then open up exploration later, um, and potentially, you know, do more of these ISTs, get the community engaged and find out, well, where else can I use this?
Naji Gehchan: Can I ask a follow up question on biomarkers and your thought about, uh, what’s the hurdle to overcome to get where you’re saying we should go? Uh, and then your thoughts about. We’re hearing a lot about digital biomarkers. I’d love to hear also your thoughts about this.
Michael McKeown: So there’s a couple hurdles, right?
Um, you know, so, so technically, um, are patients able to get these assays done? Are they able to get sequencing done? That hurdles rapidly falling away. Um, you know, another one is, you know, if the samples exist, can you access them? So if you if a. company or another physician would like to run an assay on some of the, maybe some of the bank samples, maybe FFP blocks or, or frozen TBMCs or something from those patients.
Can you actually access the, those samples from the patient? Or will you have to go get that patient to get a new assay done? Because if you can access the archive stuff and that’s still relevant, then that’s going to be another acceleration. Um, the other is kind of on the corporate side with, with kind of with understanding, you know, Market, you know, there is pushback on, well, I don’t want to restrict what my potential, um, you know, uh, label will be down the road.
Uh, I still think that’s, I still think there’s, there’s kind of a double edged sword there that, you know, maybe you’re going for the widest possible label, but if that significantly reduces your probability of success, then I don’t think that’s actually. An advantage there. Um, and then maybe the last is, you know, if you have to run a diagnostic to prescribe a drug down the road, that could create an extra hurdle.
You’re going to have to get. Reimbursement, you’re going to have to make the, uh, diagnostic more available, but, you know, I actually think that also will go away because you look at how many patients, you know, particularly in cancer are getting sequencing or just the general population getting 23 million and stuff like that done is I think a lot of patients are already going to have sequencing done.
And so you’ll have a pretty good idea. Um, whether they’re going to be positive for your assay when you, when you run it, if you’d even need to, because, you know, if they’ve already had good quality sequencing done, maybe you don’t even need to, and I’m focusing, you know, on, on gene sequencing here, but, um, this would be true for some of the more complex, you know, flow cytometry and, and pathology, um, which are all having advances, um, lately.
So, you know, um, Yeah, so access accessing the samples, accessing the data, um, and then convincing people that this is a good way to go, even though it faces some restrictions. Um. You know, this is also, you know, doubly so for some of these rare diseases, because it’s, it’s how are we going to find these patients?
How are we going to find enough of them? Even if we have a good idea that they would be biomarker positive, but, um, that gets back to the trial design issue and the access to trials. And so I think, I think all this stuff’s getting solved. I think it will get better, um, especially with all the digital technologies and even social media that’s helping connect people.
Naji Gehchan: Any thoughts about digital biomarkers? Any thought on the digital biomarkers?
Michael McKeown: Um, you know, I think, I think it’s got promise, but I do worry about how good, you know, medical records you’ve got to get your medical records have to get up to car. So, you know, AI and all these, You know, computational techniques suffer from quality of data and, you know, I, like a lot of Americans have gone through multiple insurers as they change jobs have gone to multiple clinicians.
And so having all of your your own data in a coherent and systematized set that’s actually interpretable. It’s a big hurdle. Um, I was actually working on a project a while back where we were able to import a ton of medical records and anonymized ones to do some data analysis on. And the computational biologist came up to me, he’s like, yeah, I’m looking at this field and there’s 14 different string entries here.
And I look at them and it’s like, HIHI, HIGHIGH, you know, plus sign up, you know, it all meant the same thing, but. That’s actually a huge problem. And we had to create, you know, a database of synonyms just to to work on like one field of patient sample data. So I think that, you know, as we get better at this, as we get to more digital and systematized medical records, that’ll be a big help.
Naji Gehchan: So Michael, I want to now give you a word, and I would love your first reaction to it. Okay. So the first one is leadership.
Michael McKeown: Yeah, I mean, I think that that’s That’s important. Um, and, you know, it touches on, you know, what we started with here, which is You know, leadership really needs to be learned. Um, you know, they talk about natural born leaders, but I think there’s a lot of learning to be had both for mentorship and classes and books and reading.
Um, and to be a good leader. It means that you have to really take that seriously and take a commitment on yourself to you know, constantly be learning and becoming better as a leader.
Naji Gehchan: Drug development.
Michael McKeown: Man, it’s, it’s expensive, but um, you know, I think that these techniques that we were talking about, decentralization, biomarkers, I think there’s ways to accelerate this. And, you know, and make it a lot more efficient, which will make it more, more cost effective, cheaper and, and raise the probability of success, you know, overall, the, the probability that any single, you know, pipeline or, or discovery program actually gets to an approved drug is pretty low.
It could be that lowest 5 percent in some, some fields, but, um, I think we’ll be getting a lot better at that because of all things we were just talking about today.
Naji Gehchan: What about innovation?
Michael McKeown: It’s it’s an amazing time, you know, and I think, you know, especially being in a hub place like like Boston where I’m surrounded by all the amazing research coming out of Harvard and M.
I. T. Um, you know, I’m working out of. Harvard Innovation Lab, there’s ShareSpace, and you’re getting to hear all the amazing ideas that people are coming up with, um, either from bootstrap effort out of academia or working with venture funds, um, this is truly an amazing time for innovation, and kind of, I think, an unprecedented leap for, for life sciences, and especially as we’re coming, being in 2024, coming out of kind of the investment lull, um, you know, things are really roaring back.
Naji Gehchan: The last one is spread love in organizations.
Michael McKeown: Yeah, um, you gotta lead with heart and you’ve got to care and. You know, you care about your people, care about your mission, you know, I’ve mostly worked in, in oncology and small molecule oncology space and, you know, reminding people that you’re not just, you know, running an experiment today, you’re, you’re potentially taking a step forwards towards, you know, giving somebody another, another Christmas with their family or, or, you know, giving them more time with the loved ones.
And we work in, you know, I work in the life sciences, this has impacts on human health. And, um, But at the same time, don’t just grind your people and use that to make them work harder. Love the people in your organization and love your mission.
Naji Gehchan: I love how you framed it, uh, from caring for your people. To caring for the patients we serve, because this is exactly why you wake up every morning in this industry. Any final word of wisdom for healthcare leaders around the world?
Michael McKeown: Um, you know, listen, be humble, and you never stop learning.
Just because you’re, you’re at the top, you still have opportunities for growth and learning, and that is a constant, lifelong process.
Naji Gehchan: Well, what a great way to end this conversation. Michael, it was such a pleasure to have you with me today. Thank you.
Michael McKeown: Thanks so much for having me on. This was a lot of fun.
Naji Gehchan: Thank you all for listening to SpreadLove in Organizations podcast. Drop us a review on your preferred podcast platform
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