Invest Like the Best with Patrick O'Shaughnessy
· Alex Karnal
[00:00:00] S1: If we are successful in mobilizing people around a health stack and we can move from reactively treating disease to helping people be as proactive about their health as possible. I think the unintended consequence of that is people live longer. Eventually, something's going to get us. The incidence of cancer being the issue that brings us down, the disease that brings us down, could rise. I think the unfortunate reality is that cancer is hard, both because we often identify it too late, and then when we do – cancer is like a sneaky devil. You might have an angle of attack to go and beat that cancer that presents itself early, and as soon as you're making progress with a medicine against that angle of attack, all of a sudden the cancer has a survival instinct and it redirects. Now, a medicine that was working incredibly well, that had shrunk a tumor completely to zero, is having no effect because while that medicine eliminated the cells that were most vulnerable to the medicine, guess what? The cells that were left behind – even if it's just a few – now had the advantage in growing rapidly and causing a new set of harm and setting a patient on a horrific direction. It's hard because we tend to identify cancer too late, and then when we do, it's shifty. Now, there's also the opportunity for optimism around it. I think it gets to the topic you and I have spent some time talking about, which is testing. The areas of testing today that I find most exciting are across being proactive, and early identification of the risk. And then once a cancer emerges, what do we do about it? And so, talking maybe across both of those modalities, and then come back to the medicines that are associated with that. In terms of identifying cancer early, there are companies like Exact Sciences and Guardant Health that have gone really hard at breakthrough innovations to help us screen for colorectal cancer. Now, of course, we have the gold standard that's available, which is a colonoscopy, and I have to go get one next year. But none of us are ever looking forward to that. Because it's something people don't look forward to, even though everybody should be getting them, and with regular periodicity, most people don't, and I think that's really tragic.
· Alex Karnal, Patrick O'Shaughnessy
Because by not getting your colonoscopy, you're putting yourself at risk for colon cancer, which is an incredibly slow-growing cancer, and if you just got the colonoscopy, I think we could very much live in a world today with very low incidence of colorectal cancer. Guardant Health and Exact Sciences went directly at this problem. Exact Sciences has a stool-based test that has incredible ability to predict people being at risk of cancer. Same thing for Guardant Health. Guardant Health took it to the next step in terms of knowing that you can go after markers that would predict colorectal cancer, but recognizing that the commercial model around being able to get people to not just receive the prescription for a stool-based test, but the complexity of people being able to complete the test and get that sample back, was one that just could never have the scale as a simple blood test. And so Guardant learned from Exact Sciences' advancement and then came up with a next-gen version that's a simple blood test that you can get done just about anywhere. And it's been amazing to see that not only are both of those markets continuing to grow, but the blood test is inflecting. That, to me, is exciting because it means that, again... [00:00:00] S0: People care.
· Alex Karnal
[00:00:00] S1: Doctors care. People care. They're getting it done, and that means we're going to be safer and safer from these. But I think it's important for people to realize that not all tests are created equally. When I look at a new diagnostic in this space, I care deeply about two metrics. One is the sensitivity, and the other is specificity. One of them tells us, of all the people that could have cancer, what percentage of those samples are we actually getting back that is an accurate diagnosis of cancer? So if there are a hundred cancers in a sample, what percentage of them actually get picked up as cancer? That's the sensitivity. And then the specificity is, if there's a hundred samples that don't have cancer, what percentage of those give us a false positive saying that you have cancer when you don't? I think both of those are really important metrics. And at the same time, I think that there's a whole other industry around multi-cancer early detection that's evolving right now and unfolding right before our eyes. These are companies moving from not just having single cancer tests, but having multi-cancer tests across large numbers of tumor types that can be really dangerous. When you think about how I describe the offensive and defensive side of the health stack, the defensive medicines that we can take to keep us maximally protected – what's not in there is anything to protect us directly from cancer. But that's because I tried to attack cancer from the screening perspective and made that part of offense. Over time, I think at a minimum, people should be doing a colonoscopy. I think that the next best-in-class version of that is colonoscopy married with either a blood test or a stool-based test with some regular periodicity to it. And I think over the next three to five years, particularly with how AI and the evolution of these tests are really converging to help them to move faster and faster and to be better and better, I think we're going to wake up within the next five years with really awesome multi-cancer early detection tests. And when we have them, then shame on us if we're not getting them and shame on us if we're not acting on the learnings that come from them. This will be obvious, but the earlier we know that we have a cancer, the greater the range of options are for us to go do something about it.
· Alex Karnal
And I think we're finding that across lots of different cancers, there's opportunities to have amazing results. Sadly, my brother-in-law's father passed from multiple myeloma, maybe almost a decade ago. If he had been diagnosed today with multiple myeloma, his outcome, his prognosis is dramatically different. Because not only is our ability to test and identify that people are developing cancers getting better, not only do we have other types of tests that we can look at what are the mutational drivers of that cancer, that help to connect not just cancer, but the type of cancer to the best medicine that we have today to go treat it. But the medicines are getting better and better. While cancer medicines began, as many medicines do, with just pills and injectable biologics, today we have an entirely new class of medicines that are these CAR T-cells, that are either cells that we take out of a patient's body and arm them with the ability to go attack the cancer directly. Or, companies like Capstan just came up with the next-gen version of that where they can inject, on an IV basis, that can attack the cancer cells directly without having to even take cells out of a patient's body and have that happen within the patient's own body. And what we're seeing from these medicines is dramatic efficacy. So we're seeing that they have the potential to reduce tumors by 100 percent and to do that in 70 percent plus of patients, and to keep them at bay for really long periods of time. While we haven't yet cured cancer, to me I think the slope of the line is really exciting, both from the testing angle and the earlier we can identify these cancers. And from the increasing range of modalities and options that we have to go after and destroy them.
· Patrick O'Shaughnessy
[00:00:00] S0: What about imaging? Both skin imaging, interesting companies doing that, like Neko. Deep body imaging, companies like Prenuvo. It's quite expensive, but as I think about the health stack as something that we could do that's preventative, how do you feel about those technologies which are relatively new but do try to take a picture worth a thousand words inside your body and identify a tumor early or something like that? Do you think that's worth it?
· Alex Karnal
[00:00:00] S1: To me, more data is worth it so long as you can put it in the right context. When we get the result of a colorectal cancer screening test, we know the context for that and we actually know whether we have something that's useful or not. The pictures that we can get from groups like Prenuvo and others are powerful because we can see progression over time and we can use that data, and particularly as AI is going to increasingly become our medical home. Arming our AI system with that information will be super helpful. The thing that I worry about, though, is as you measure more and more different dimensions, with each of them having a material false positive rate, the odds that you come out of that experience with a false positive that can be disruptive in life becomes material. It's not to discourage anybody from doing these. It's just to make sure that any data that we're collecting, make sure we put it into the right context set so that we can have a framework for how we deal with whatever information comes from taking that test. So for me personally, I'm not yet pursuing those. I'm very much focused on areas where if we're going to go and do a test, it's going to have a high probability of capturing what I'm testing for, and a low probability of giving me a false reading. And I think the more information that we can accumulate with really high fidelity, the better we'll be at being proactive about our health.