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[Colin Miller] 

Hello, I'm Colin Miller, CEO at the Bracken Group, and this is Fractals: Life Science Conversations. Bracken is the professional services firm for life sciences and digital health organizations. Our intelligence ecosystem fulfils consulting, regulatory, marketing and analytics needs with an integrated and strategic approach. 

Today, we're diving into clinical development leadership, regulatory strategy, and the evolving role of medical affairs in both large pharma and innovative startups. I'm honored and delighted to be joined by Dr. David Krauss, an experienced pharmaceutical executive, physician and trusted advisor across the life sciences. And on a personal note, friend, colleague and collaborator, as I've had the opportunity to work with David many times over our careers. 

David is a board certified physician in internal medicine with additional qualifications in geriatrics and has spent more than 30 years leading clinical research and medical affairs at the highest levels. Over the course of his career, he has successfully filed multiple NDAs and BLAs across a range of therapeutic areas, led global clinical development teams at companies like SmithKline Beecham and GlaxoSmithKline, served as chief medical officer at both public and private companies, including Vicurion Pharmaceuticals and Genomind, a leader in pharmacogenetic testing. He's advised on business development strategy, served on scientific advisory boards, and also consulted at the Department of Defence. 

David is a fellow of the American College of Physicians and an author of numerous peer-reviewed publications. And as someone who holds a degree in both art history and psychology alongside his MD, he brings a rare interdisciplinary perspective to the science, business and human side of medicine. David, welcome to the program and thank you for joining me today. 

 

[David Krause] 

Colin, it's a pleasure to be here on this beautiful Friday. And thank you for that flattering introduction, where maybe it could be interpreted as checkered past, but that was very nice. Thank you. 

 

[Colin Miller] 

You're very welcome. And we don't get chance to often to sit down and discuss some of our past, some of the future, and I'm delighted today so that we're able to have this conversation. So you've had a remarkable career spanning large pharma, mid-sized companies and startups. 

How has your leadership style evolved across these different environments and over the course of time? 

 

[David Krause] 

A really interesting question, Colin, and I was very lucky when I got hired into SmithClineBeecham in 1990, that I had a mentor. There's a guy named Jerry Boccia. Jerry was just a tremendous mentor. 

I knew nothing at the time about drug development, clinical development, medical affairs, but Jerry really instilled a sense of critical thinking. And at every step of my career, large companies, small companies, I've been lucky to have great bosses and really never had a boss that I thought was a bad boss or didn't get along with. Obviously, there's personal connections that flourished. 

When I hired people, I always had that memory of being a mentor and I tried to mentor people along the way. And I was also really fortunate to hire good people along the way. In fact, in several instances, I hired people who subsequently became obvious successors to me. 

Because of the nature of the people that I hired, A, I could mentor them, but still allow them to do their jobs. And B, I didn't have to be down in the weeds, let's say. I hired people who were able to make good decisions. 

So I think a combination of, let's say, luck and aptitude come out when you get there. 

 

[Colin Miller] 

O'Reilly. 

 

[David Krause] 

Very good. 

 

[Colin Miller] 

I want to just pick up on one of the things that you commented on and always hiring people that you could see replacing you. I think succession planning is something that a lot of folks miss and is not necessarily thought through very much. And yet, it's a key critical part to business continuity and leadership. 

I wonder if you have any further thoughts to that. 

 

[David Krause] 

DeLong. In these instances that I talked about where I had hired people who became obvious successors to me, I can't say that there was forethought to a succession. It just occurred because of the people. 

But yes, I think succession planning is something that is not given enough thought. It's a little scary to think about playing your own successor because it requires that you have an idea for your next move in mind as well. In all of the places where I've worked, it was rarely mentioned. 

 

[Colin Miller] 

Oh, really? Interesting. And yet, in small companies, it's actually more critical in many respects because if anything happens...  

 

[David Krause] 

A lot of the institutional knowledge is instilled in a small number of people. So if it is more important at the smaller companies, yeah, it's a good point that I never thought about. 

 

[Colin Miller] 

As I was listening to you, I'm going, we touched it once in my prior career. We actually don't plan very well generally as an industry. 

And you're right. It's also quite frightening because you're really supposed to, with good succession planning, you've identified the next person to fill your shoes who should be better than you in many respects or can be groomed to be better than you. So at which point, unless you've got an exit, you're going to keep them down until you're ready to go or be booted off the planet, which is not what you want. 

So it is a strange one.  

 

[David Krause] 

You're making me think about things I haven't thought about in a long time. When I think back to that first job with SmithKline Beecham and my mentor, I think I became the obvious successor. I did succeed him. 

It also allowed him to move on to something completely different at which he was extraordinarily successful. That is the way that I would think about where I HR. 

 

[Colin Miller] 

O'Reilly. Very good. Very good. 

Thank you. 

 

[David Krause] 

DeLong. The sum total medical knowledge is doubling at an increasing rate. And now I read somewhere that the sum total medical knowledge doubles. 

I had in my mind 30 days, but I think it's maybe even faster than that. It may be like a week. So the balance of that is that now we have so much information as opposed to if you wanted to research something, you went to the library, you found an article, you read the article, you then looked at the references, then you went to the next article. 

And so you could spend the day in the library looking at five articles. But now it's all in my hands using AI. And of course, we know that AI is not perfect. 

It hallucinates. There still has to be a physician or learning intermediary, let's say, to interpret the results of the AI. But it's all there.

So that's the counterbalance between the sum total of new knowledge and the availability. And I think those things, to a large extent, balance each other. 

 

[Colin Miller] 

Good point about the balance there. To project forward, what you think how that's going to continue to change the environment? I'll narrow it down to pharmaceutical development here. 

 

[David Krause] 

Yeah, I think that genetics has changed a lot of things, genetics as well as epigenetics. And again, harking back to my medical school days, it was the genetics or environment. And we now know that it's both. 

It's the interaction of genetics and environment. And the interaction of those things, epigenetics, is really going to change the world. That's where the world is going. 

We're going to have much more in the way of personalized medicine. And so General Mind's whole mission is personalized medicine in the field of neuropsychiatry, but personalized medicine in the sense of drugs. So that's just one dimension, treating a patient. 

But this interaction of genetics, science, medicine, personalization is going to rule. 

 

[Colin Miller] 

Do you think it's cost-effective enough to be able to be driven that way? Or are we just at such an early stage in that pathway? We've got a couple more decades to go. 

 

[David Krause] 

Cost-effective, if you mean at the sense of at the payer level, if you get the right drug the first time, that's clearly going to. So we know that, for example, most patients with neuropsychiatric illnesses will not have success on the first drug. So with depression, the success rate for remission is probably less than 50% on the first drug. 

And then with each successive drug, success decreases. So that's a combination of the patient, maybe having refractory illness, but it's also get the tools that we have are imperfect, that they're not designed for the specific patient. We don't necessarily know what's going on at the neurotransmitter receptor level for that patient. 

Another really exciting area that one of our colleagues, Jim Gilligan, is working on is psychedelics. And I think psychedelics is really an exciting area for neuropsychiatry. And that has to do with total reprogramming of the neurocircuits. 

And that happens in a very rapid manner. Something that drugs, or at least conditional FSRIs, SNRIs, and so forth, really don't do. But the psychedelics actually, through a mechanism called neuroplasticity, are really rewiring the brain. 

And it can happen in very short order. So I think there are a lot of development challenges to psychedelics, but I think it's going to be very successful for a lot of neuropsychiatric illnesses, in particular, post-traumatic stress disorder, eating disorder, depression. We already see remarkable results with, for example, ketamine. 

So with traditional neuropsychiatric agents, you might have to wait 30 days or six weeks to see if the drug is effective. That's certainly, from a cost-effectiveness perspective, that's not very good, having to wait six weeks to see if you have success. But with drugs like ketamine, we know in a much more rapid fashion, I think there is success. 

So yes, I do think these things are going to be close to success. 

 

[Colin Miller] 

That makes a lot of sense. Now I hear it in that context. And I wanted to just follow in on that thesis that you presented a moment ago on getting the right drug first in psychiatry or in other neurological areas. 

Do you think, in your experience, does that spill over into other therapeutic areas? And if we were more targeted at getting the right drug first for the right patient, we'd have more efficacy, if you will, and patients would recover better because the second-line treatments are already failing, if that makes sense? 

 

[David Krause] 

I just thought of this. I was spent in vaccine development and anti-infectives. So for anti-infectives, if you have a bacterial infection, what do we do? 

We take a culture. We look at drug sensitivities. We have an answer in 24 hours. 

So in a way, it's psychiatry that's catching up to anti-infectives. 

 

[Colin Miller] 

And I also wonder, and this is a very naive question in many respects, whether as we become more targeted at cancers, the same thing, because of the runaround of cancer and the ability for metastatic cancer to occur and indifference, internal expression that essentially bypasses the first-line medication that's being given. 

 

[David Krause] 

There's no question that's happening. In the olden days, you had a drug that was indicated for lung cancer, pancreatic cancer. Now you have drugs that are indicated for cancers with very specific cell surface receptors. 

So a drug might be indicated for 10% of patients with lung cancer, depending upon their receptor expression. When my wife had breast cancer 12 years ago, we got an Alcatraz score, which looked at the expression of, I don't know, maybe 20 cell surface receptors. And you got an Alcatraz score, which suggested whether you may or may not benefit from chemotherapy. 

So I think that type of science is only going to accelerate. And there's no question that oncology drugs, psychiatry drugs are becoming more and more personal. In fact, I think oncology is probably the poster child for that type of personalized science. 

 

[Colin Miller] 

I would tend to agree with you, and a fascinating approach. So with the positive side of where we're going, just going back into the CNS drug development, where do you think we're still falling short? 

 

[David Krause] 

There's no question that the drugs that we have are blunt instruments. So as we previously mentioned, most patients with depression will respond to the first drug. There's, I think, six SSRIs, and you've got this whole trial and error approach to treatment. 

And again, personalized medicine, we need more and better drugs. And there was a fallow period in neuropsychiatric drug development, I think, in the early part of the century. But in the last 10 years, what looked to be a dead area is becoming common again, and more and more new drugs are coming on board. 

 

[Colin Miller] 

Yeah. Going back to the earlier conversation of precision medicine and the cost effectiveness of them, in part goes because of new technology and new development coming on. And I guess part of the challenge is if that slows down, it also slows this development process down as well. 

 

[David Krause] 

Fortunately, I think that the pharmaceutical industry is still vibrant, filled with people who are smart and have great ideas. And are, frankly, capitalists. I think, yes. 

So I think the industry is still vibrant. One of the other predictions that I made at the beginning of the year was that communication with the FDA would slow down. But I'm not sure that's happened. 

I think that the employees at the FDA are quite diligent. I have always said that the FDA was still with well-intentioned and smart people. That has been my experience, almost universally. 

Yes, I've had some bad experiences. But for the most part, I think the FDA is smart and well-intentioned. I also recall from a project that we've been working on together, the FDA has been pretty unique. 

And we have not had a problem in that area. 

 

[Colin Miller] 

I would echo that as well, David, over my career as well, watching the FDA work. Once you understand how they're constructed and frameworked and what they are charged to do, it makes a lot of sense. And yes, we've seen, I think our regulatory team at Bracken have seen no change in the responsive times, the connectivity with us. 

And as you've said, with some of the projects we're working on, the communication with our sponsors has been phenomenal. And I would also echo your commentary on the pharma industry being very robust. It's a global industry. 

It's not isolated to one country or one inflection point at one moment in time. It's just that the largest one that was driving some of the business was going through a speed bump at the moment, perhaps. 

 

[David Krause] 

It is global. And I just read something last night, Moderna. So obviously we have an issue with vaccines in this country right now. 

We are cleaved in different directions. So I just read something last night, Moderna just made a gigantic investment in China in the manufacturing facility. Yeah, the world is global and connected. 

It's not going backwards. The United States might choose to be an island, but the world's not going backwards. 

 

[Colin Miller] 

No, fantastic. Yep, no, onward and upward. So with that, perhaps you could give me what you consider one of the lowlights of your career and one of the highlights of your career. 

 

[David Krause] 

Well, that's a good question, Colin. The first decade of my career was doing vaccine development. And I was fortunate when I went to work at Smith Farm Beach in biologicals to land in an extremely spherical area that just had a very robust pipeline. 

And I worked, we submitted a bunch of DOAs. But one thing that stands out was we had a partnership with Echidna, which is Walter Reed's research branch, to develop a hepatitis A vaccine. And the IP came from Walter Reed for hepatitis A vaccine. 

Hepatitis A had affected every military operation of the United States throughout its entire history, from the Revolutionary War to the Vietnam. So we developed this hepatitis A vaccine with Walter Reed. Not only is there no more hepatitis A in the military, there's almost no hepatitis A in the United States. 

That was an extreme highlight that stands out above the others. As far as lowlights, there was a time when the FDA decided that it was going to regulate laboratory-developed tests, which had claimed that a laboratory-developed test is a test developed in one laboratory. And it originally meant like a lab would develop a test for a CBC. 

The lab would do that at test. The FDA chose not to develop it. As the world expanded, the FDA said they were going to choose to regulate laboratory-developed tests. 

That they had previously exercised regulatory discretion and that they chose not to regulate, but they had the right to it. At one point while we were working in general, the FDA asked us to remove all of the drugs from our title so that we would only report the genes. That had no meaning to a physician. 

If you tell a patient that your patient is SLA-C684, long, long, that doesn't have any meaning if you can't pair the drugs. And part of that, frankly, was due to the current administration. But eventually the FDA backed off of that. 

But it was a really poor decision by the FDA and that was slow. Yeah, there have been highs and lows along the way, but mostly drug development, it was a slog. And at the end of the day, you have to prove your mettle or not with your development program. 

 

[Colin Miller] 

Good point. Very good point. But congratulations on getting the hepatitis A vaccine out and being part of that team. 

That was a huge impact. So thank you. I really appreciate it. 

 

[David Krause] 

I just got an invitation from a colleague, or I would say a former colleague, an academic in Germany, who was having a reunion in September of people who developed DTAP. So a diphtheria, tetanus, and acellular pertussis vaccine that we developed in the early 90s, which is now the standard vaccine for diphtheria, tetanus, and pertussis in the United States and around the world. So we're having a reunion in September in Germany. 

So I thought that was a nice thing. 

 

[Colin Miller] 

That is, isn't it? Wow. Fantastic. 

So yeah, another real game changer, the early childhood vaccines, and that was one of them. So again, I hope you enjoy the reunion there. And congratulations to the team that pulled that one off. 

So thank you. Changing sort of shacks here and putting everything that we've just said aside, if you had something like $100 million to invest in industrial society, where would you invest it and why? Oh boy. 

 

[David Krause] 

That's a tough one that I haven't thought about. I think that gene therapy is evolving. It's been evolving fairly slow, but if you think about all the hundreds of millions of people who have genetic inborn organs, I mean, that is just gigantic. 

And with CRISPR technology, with vector technology, I think this is going to be the future. So it's obviously a very different and specialized area compared to drug development, but basically we're delivering genes instead of drugs. And I think that in the future, gene therapy will change the lives of many, many people. 

 

[Colin Miller] 

So you invest the money in a gene therapy program for these rare diseases and for the kids. It goes right back to the very beginning to your first mentor that said, focus on the patient. And I recognize the same ethos and philosophical approach. 

So appreciate the answer. So final question, if you could speak to yourself at the age of 25, what advice would you offer? 

 

[David Krause] 

I've already touched on it, right? Change more, do more. You mentioned something in the beginning that you said I have a degree in art history and psychology. 

Actually, I have a degree in art history and psychology. Oh, okay. Sorry. 

That's not the typical path that kids take today, right? My grandchildren are either in college or getting ready for college and they're all very focused. SAT scores, advanced placement courses in high school, blah, blah, blah. 

But I think that my liberal arts education really served me well. Yes, it took me a little longer to get there, but when I got to medical school, I thought I had some, or I would like to think that I had some humanist qualities that served me well. So these kids today are so driven and focused on the science and there's so many great kids, but I do worry that humanism is lost a little bit in their education. 

 

[Colin Miller] 

And you're seeing it now with your grandkids as well, directly. 

 

[David Krause] 

Yeah. 

 

[Colin Miller] 

Yeah, yeah. The arts part of it doesn't, unless people get to know you, then I appreciate perhaps that photography is still one of your, I would say a hobby, but it's, I've seen some of your art and it's just phenomenal. 

 

[David Krause] 

It's funny. I really like photography. And one of the things I like about it is that it's totally alone. 

It's just me. And I generally don't photograph people like landscape photographer or nature photographer. It's just me and the environment. 

For me, it's very fulfilling. 

 

[Colin Miller] 

It's great to hear. And what a great conversation today. Thank you so much for being part of this and just sharing a little bit about your insights over your career, but also thinking through where we might be going in the future. 

David, this has just been such a pleasure. Thank you so much. 

 

[David Krause] 

Well, let me say, Colin, I've joined Bracken about a year ago. It's really a remarkable group of people with expertise in many areas. Bracken's ability to create sort of virtual development teams has really been enjoyable to be a part of. 

 

[Colin Miller] 

It's been a pleasure to have you. And for us personally, just to be able to continue a friendship and a relationship over the years to collaborate again has been just outstanding. So I really appreciate it. 

Thank you again so much. And thank you for your time today. Fractals is brought to you by Bracken, the professional services firm for life science and digital health organizations. 

Subscribe to Fractals via your preferred podcast platform. Visit us at thebrackengroup.com or reach out directly on LinkedIn. We'll be delighted to speak with you. 

I'm Colin Miller wishing you sound business and good health. Thanks for listening.