YouSaid · the spoken record

Alex Telford

lines on the record: 61
first: 2024-01-30
most recent: 2024-01-30
sittings or episodes: 1
sources: podcast

Every line below is reproduced as it was said and linked to the record it came from. Nothing here is summarised or generated. Directory · Search · Corrections

“Think this has a pretty obvious answer in my case. Many people have done many kind things for me, right? But I think I just have to go with probably what is the most common answer, which is my parents have always been an unending well of support. And they bailed me out of many low points in my life. So I'm very thankful for that. And while other people have done me many kindnesses, nothing really compares to what my parents have done.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Much, and maybe you got too many for their managerial positions who are focused on the accounting aspect of it. They just want to milk existing products and copy the big ones that we know have an existing market, then you're not going to get the kind of meaningful breakthroughs like ITRUDA, these immuncology drugs, the GLP1 agonists that we're seeing now. So yeah, that's one thing I worry about.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“And use tricks and techniques to extend the patent life and make it harder to copy and try and extract as much value for as long as possible and maybe not invest in this fundamental research that really drives meaningful products that has this element of unpredictability to it. One thing I think is quite dangerous in the pharma industry is just this over-reliance on an accounting type mindset rather than a recognition that there's a science for an industry, it is an innovation driven industry. The commercial parts of Big Pharma should be in service to the R&D portion of the organizations or the ecosystem. And you should really be like hiring good people with good intuitions about what's worth developing and letting those scientists tinker for as long as they need to on some of these really challenging ideas at the forefront of what is possible and give them enough time, 10 or 20 years for these ideas to mature into actual products. And then you can commercialize them. And if the returns innovation are down to”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“To run and execute trials in an efficient way. And then what I'm worried about is there's a genuine worry that it's not going to be worthwhile for a lot of companies to continue to invest in developing new drugs. So I'm worried that if we don't get the balance, rewards innovation and incentives to innovation, we'll end up with a system where companies will decide, okay, I'm not actually incentivized to really invest in doing meaningful fundamental research and spending 30 years tinkering on some opportunity that may eventually bear fruit. I'm actually just going to market the drugs I already have that are old. I'm going to invest in drugs that are very hard to copy. So even though once they do go generic, no one will be able to copy me. So things like these radio radots talk about Cartes, they have a whole process associated with them, so they're quite hard to copy. And then you're just going to sit on existing treatments and try to milk them as much as possible.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“These external opportunities they're going to bring in. Maybe you'll see greater and greater externalization of more and more functions. Now we have an innovation RD externalized to little biotech. We have running clinical trials being externalized to these clinical research organizations that specialize in that. You can argue whether that's been a good thing or not, but it's just part of the externalization trend. And then you have more and more just pieces being externalized. So it'd be commercial analysis will be externalized in the future as well. So you may end up with pharma companies just being very specific IP holding companies plus just managing the finances of actually selling and distributing these drugs. Every little piece of the ecosystem is focused on some specific component of the process. And maybe that will help it be more efficient. So I'm interested in that. I think you can argue that it may not be helpful. Externalization hasn't been completely helpful. There's been some trade-offs there, but there's a lot of redundancy in the industry and if you're in a biotech who's getting ready to launch people having to build up redundant capacity.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“So, just a lot of improvements in tooling for how we intervene in biological systems to treat diseases and seemingly like an increase in the rate at which we're developing these tools and applying them to the clinic to solve biological problems and to treat diseases. So that general explosion in technology, our ability to control systems is really interesting. I'm interested in just general nearly new business models of the industry. So one trend you've seen over the past, I think it started probably in the 2000s is this greater externalization of research. So pharma companies, pharma companies used to do a lot of research in-house, they've mostly externalized that to smaller biotechs that are venture capital funded. So the big pharma companies are really just like commercialization machines all the time. And they do maintain some research labs, but the purpose of the research labs is in many cases just to validate external opportunities and test them in-house and have the expertise to actually meaningfully evaluate.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Of improving on the modalities that we do have. So you look at something like CRISPR. We just got our first CRISPR approved therapy in the UK and the US. But CRISPR is already in some ways becoming a bit of an outdated technology. You have a lot of investment in what's next. So instead of making cuts, you're going to have these base editors that are changing specific letters in the DNA sequence. And that's a more effective way of precisely treating certain genetic diseases than making cuts.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“I think what I'm most excited about is not a specific technology, but more this Cambrian explosion, if you like, of modalities in biotech. So for a while, I think back maybe 10, 20 years ago, there were that many different types of different treatment classes. And since the rise of biotech, you have all these different ways of treating disease that are becoming established and have a lot of potential. So you have CRISPR RNA interference, these CAR T cells we talked about, base editing, different variations of CRISPR. Our ability to control our biology is getting much better than it was, even just a few decades ago. So this increase in our ability to control our own biology and intervene in biological systems and very precisely use these molecular scoffles to push a system into a desirable state is really interesting. And just this why we...”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Preventative medicine, and they don't take up preventative medicine in many cases when it's offered to them. So it's the whole thing with the argument about Azempic and why don't people just practice diet and exercise? That's a more sustainable way of dealing with obesity. The reality is that people just don't do that. So they would rather just take ZenPIC when they are obese and have that treat their obesity. So I think this whole consumer attitude shift that needs to happen before preventative medicine ever becomes really established. It needs to be demand driven. So do you think about like the healthcare system? Who is really the end consumer of pharmaceuticals and healthcare system? I think you can make the argument that it's actually healthy people who are enrolling in the plans and are paying the majority of the money that goes into the system. And they want that system to represent value for money for when they do get sick. So you have to have the people who are healthy have a greater demand for products of prevention that then incentivize companies.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“I think prevention is difficult. People in the US often say that the reason why the US doesn't invest in prevention is because a lot of people are on these employee insurance plans and there's a lot of insurance plan turnover. So any insurance company that invests in prevention for its members is unlikely to reap the benefits of those investments when they switch to another employer and get a different plan. But the problem is that if you look at other countries that do have these nationalized healthcare systems like the NHS other European countries, they actually don't invest in that much in prevention either, even though they should in theory because it's a whole nationalized health system. They should be wanting to invest in those things. So it's a problem really that there's a lack of supply preventative treatments or is it really there's a lack of demand for preventative treatments? And I feel like the issue is probably more on the demand side where people unfortunately don't have a strong demand for”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“By cutting down even just a small number of these huge lottery winners, if you like. You have to accept a bit of a trade-off where you are trading off innovation for how much you're spending on drugs.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Real Pareto distribution in revenue. You need these lottery winners to make it a worthwhile investing in the system, which is an unfortunate reality that because drug development is so inefficient, you need high prices and you need these super blockbusters to make the economics work out. When you're doing R&D, you're paying money that you have now for revenues in 10 years. So from a temporally discounted point of view, you need to think you're going to get a really huge amount of money in the future to be worthwhile you paying hundreds of millions of dollars in the next few years. I think it's a really difficult problem. If you put pressure too much on drug prices, you can very easily remove the incentives for people to invest in the industry. Quite a fragile ecosystem that's built up once you start cutting down the tall poppies, you actually are removing a lot of the incentive to even develop any drugs. And there's just that you can do outsized damage.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Zero or very low return on invested capital. The industry as a whole is not that great of a business. It's very much like a lottery model that is just the type of lottery that's attractive to people with biomedical PhDs where most people are not making that much money, but a small number of drugs and companies are making super normal profits. And you can point to the examples of people who have very high prices and making super normal profits like Humira 20 billion seems like an incredible amount of money for a drug to make. And I think if you look at that isolated example, you can say just seems unreasonable that anyone is making 20 billion off this drug per year. It's way more than what someone should reasonably get for producing this drug. But you have to think more about the system of incentives. You want to be worth investing in developing drugs. And so the incentive needs to be very strong. And because such a smaller number of drugs produce so much of the revenue, it's like a”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Governments doing the negotiation on behalf of the population so they'll make assessments of the value of a drug based on metrics like how many quality adjusted life years does this drug give us, what's the benefit of this drug over the existing standard of care, and how much better is it and how much of a price premium can we give it on the existing drugs? So both systems have flaws. I don't think it's possible to find a perfect system that satisfied everyone. But if you look at the profit margins of drug makers, they make something like 10 to 20 percent profit after you take all their costs and the gross margins of something like 80%. But really, that's a distorted picture of the actual profitability of drug companies because there's distortions between when R&D expenses are paid and when the drug revenue comes in. So it's not necessarily a good picture of how much a drug company is getting for their investment. And if you look at how much drug companies are getting for their investment, actually most of them are pretty near.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“So I think drug pricing is really difficult. One thing I guess to say about the US is the US has by far the highest prices in the world. I think people recognize that. It's about twice as high as Europe on a net price basis. And the US market for drugs is something like 40% of the global market. And it's something like 60% by revenue of newer drugs. So drugs launched in the past 10 years or so. So the US, it accounts for outside share of the revenue that drug companies make. And part of that is because the US system is for the most part some of this is changing, but it is mostly a free pricing system where you can charge whatever you want. So when you're pricing a drug for the US market, you'll often, as a company, just try to charge whatever you think you could get away with, what do you think the market will bear. And in a reasonable world where all the incentives are aligned, what the market will bear is close to the actual value of that drug. In healthcare, you have all these strange incentives and markets that don't function properly. But in the rest of the world, you have systems where you have”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Where Big Pharma is only really interested in developing a drug if it can potentially become one of these blockbusters. Because anything else than that is just unlikely to recoup the investment. So you get a lot of these small markets that patients really would like to have drugs for. They could be really beneficial. And we know that we could potentially develop a drug against this disease. Do we have a good understanding of the mechanism? Like many small genetic diseases, but it's just not worth big pharma's time or even biochem to invest in developing these drugs because the economics don't work out. Even if you get through the whole process of developing this drug and it works and you get through clinical trials, you maybe make a few tens of millions a year and that's just absolutely not worth it because it will cost you 100, 200, 300 million just to get the drug through the whole development process. So there's a lot of, I think alpha that could be unlocked in making the process much cheaper in how drugs are tested and validated because it would mean that”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Have all this work that goes into developing a drug and it takes me 10 years to get it to market or 12 years to get it to market. And it launches and then it flops 55% of drugs that launch get through that process. They don't even recoup enough money to pay the average development cost of a drug. And then you have a very small number of drugs, blockbusters that 30 to 40 percent of revenue of the whole industry is made by these blockbuster drugs, which are quite a small fraction of all drugs. When I looked at the numbers, something like 170 blockbuster drugs that were actively generating revenue. And then the whole long tail of other drugs is making very small sums relative to blockbusters. So because the industry operates like a lottery type model where you just want to really hit a big, you have a venture capital, it distorts a lot of the incentives. So you see a similar thing in biotech investments that you do with”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, so a blockbuster drug is a drug that makes a billion dollars in annual revenue. So blockbusters are really, you have an outside imports in the pharmaceutical industry because they account for a huge proportion of the overall revenue of the industry. The way the economics operate is pretty analogous to venture capital and these long tail models where you have many losers who don't make much money or don't recoup the money who's invested in them. And a few really huge winners that will go off and generate billions and billions and billions of dollars and pay for all the failures many times over. So the industry is in many ways worth investing in for investors and for companies because there's always this potential of hitting it really big and having a mega blockbuster like Humera or Kitrudo or the COVID vaccines that generate tens of billions of dollars in revenue a year. Because if you look at all the drugs that get launched, it's sad that you”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Is where there's been too few patients to really do large scale randomized trials. And then you have these instances of super rare diseases where you may have just a handful of patients in the US, for instance. It's literally impossible to run an RCT and have any reasonable statistical outcome. You need to use things like digital twins or surrogates, single arm trials. You can't use RCTs. There's a lot of innovation in this digital twin idea and natural history cohorts.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“So, I think RCTs are always going to be the gold standard. And I think when we can do RCTs reasonably, we should do them because they just eliminate so many of these bias problems that you just aren't aware of. And that's the biggest, even if you control from the sources of bias that you think are likely to exist, there'll be hidden sources of bias that you just can't control for. So I think we want to keep RCTs as a conformatory method. But there are other tools in these instances where RCTs aren't feasible that have a lot of promise. So things like if you do a single arm study, which is just one treatment group, and you compare the ration of a disease with a matched digital twin of these patients, you can train with information from natural history data. We can make a good assumption about the rate at which these patients would have progressed had they not had the drug. So there's been a few approvals that have used some of these matched natural history data as an alternative cohort. And those have been in case.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Decent proxy marker for general health. So RCTs are just the most effective way we know of eliminating all these biases that you don't know exist from the start. Because otherwise it's just everything you try gets really confounded. You don't even know how it's confounded.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Randomly to groups, and they can supplementation for vitamin D. And then they measure outcomes and all these things like mortality and health. And then what they find is that actually vitamin D has very minimal or no effect on most of these outcomes, even though some of the data from retrospective analysis looks pretty strong. So how did that happen? What you find out is something like vitamin D is actually a marker for poor health in general. So vitamin D is produced by your body in response to sunlight. And if you are ill or poor health generally, you're less likely to go outside or you may be less mobile in general. So you make it less exposure to sun and then you'll see correlation between just general poor health and vitamin D. It's like with push-ups. They say if you can do less than 10 push-ups, then you're much more likely to die on literally the ability to do push-ups determines how likely you are to die is just that being able to do pushups.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Random allocation, you're going to see that people who take the drug die at a much higher rate or have a much worse illness than people who don't take the drug because you have this selection bias that doctors giving the drug to people who are less likely to have a good outcome. So you need to find a way to eliminate those biases. And you can do that with just total randomization. And so coming back to the vitamin D example, one thing in data and retrospective data that looks at vitamin D levels and outcomes is that you see people with low vitamin D levels have generally worse health outcomes. So they have higher rates of mortality. They have cardiovascular disease. I think it's probably been correlated with every bad thing you can probably get. And there's a natural inference there that we should just supplement fitamin D to the people who are low levels and then they'll have less rates of all these bad diseases. So then people do the trials and they do a randomized control trial when they”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“So, the big limitation to RCTs is they take time, they're complex to run, and then people don't want to be in the control group, essentially. So you have to expose patients to something that they don't want to take really. Because you're entering an RCT for a drug, you want the active drug. But maybe to take a step back. So the idea behind an RCT is that you have patients or people who are going to take some intervention and you want to figure out Does this intervention really work or not? you have to find some way of assigning the intervention randomly because if you rely on anything other than randomness there's going to be some bias that creeps into the study let's say you have this new drug and you take it to doctors and you say i want to test this new drug then the doctors may be more inclined to give the drug to patients who are sicker who really need it and they're less inclined to give us experimental drug to patients who seem like they're going to recover anyway so if you just do that”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Or not, if you're treating a disease that's eventually fatal, if you see that this biological response happens early on, then that's very highly predictive of improved variable down the line. And just finding more of these surrogates is a really, I think, valuable activity that something like the NIH and government agencies should invest a lot more money in developing. Because as soon as you have an established surrogate that the regulators could use, you really speed up how quickly you can iterate on developing drugs. You can take it into the clinic, you can see if it works in the surrogate, and then you can decide whether or not to continue or discontinue based on that. You don't have to wait five, 10 years to see if someone survives or not. So something like aging, we're never going to get drugs to prolong people's life until we figure out a surrogate for aging.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“To tell whether a disease is being treated effectively or not. So for cancer, what you really care about when someone has cancer is stopping them from dying. But you can get a proxy for that by looking at the size of the tumor. And it's not always a perfect correlation. You shrink the tumor most of the time. That's a good thing. Sometimes you shrink the tumor, but it doesn't actually help the patient survive longer in the end. So you're exposing them to toxicity and you're not helping them survive. So it's actually you're doing net harm with that drug. The idea of a surrogate is that you have a measure like tumor shrinkage that predicts benefit down the line and that helps you develop a drug much faster. A lot of drugs have been brought to market much faster in cancer than they otherwise would have been manyly effective drugs because they've used these surrogate markers of efficacy like tumor shrinkage. But it's harder to apply this principle in other conditions like more complex chronic conditions where you don't have an objective measure that's as simple as there's a tuberculosis.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“They really work. So there's been some instances of drugs that have got this accelerator's approval on some fairly flimsy evidence, but they seem promising. But then the company's meant to do a confirmatory trial to determine, okay, actually, we have a good reason to believe this drug is going to work, but we don't actually know that until we've collected this evidence over five, ten years or whatever. Companies drag their heels on doing the confirmatory study. I think the regulators should be much more stringent in forcing companies to collect that data and report it and takes the half the market. So this combination of being more open to approving drugs based on a lower standard of evidence when there's no good treatments and when it's just unfeasible to do a standard clinical trial coupled with more rigorous data collection and then taking things off the market but are not working. I think that will help increase the sort of rate of learning in the regulatory process. Surrogates as well, I think, are really important. So surrogates are measures like biomarkers that you can use as a proxy.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“So, I think in those conditions, you'll have to be able to say, look, we're just not going to be able to determine this in a trial. We have to, based on some principled reasoned evidence we've collected about how the drug works in animals and maybe some initial human testing and some preliminary biomarker evidence, we can then approve this drug and roll it out and then collect information more rigorously once it's on the market because you're just never going to get drugs for certain diseases. It's just uneconomical to achieve this vision of hyper-personalized medicine where you're developing a drug for everyone's individual condition and biology without some ability to make inferences about what is likely to work. based on early evidence and genetics and reasoning about the mechanism of action. So I think the second thing I would do is just be much more rigorous about data collection post-marketing. So you have a lot of drugs that go onto the market and then they're approved and then we're not really following up sufficiently to be able to tell if.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“I would make Fricotory changes. I think I would want to formalize the idea that different diseases require different standards of evidence and then pre-publishing the degree of evidence that we required for each different disease. So something like diabetes should have quite a high standard of evidence. So you should have to enroll very large numbers of patients and test mortality because we have extremely good drugs, different diseases where our standard of care is not as effective. We should formalize this idea of smaller trials, maybe approve drugs with a weaker standard of evidence. And we are seeing some moves towards that with rare diseases. So you have a lot of these conditions that are too small to really be able to tell. They maybe have too few patients, but they may have too few patients plus the disease of always over too long of a time for you to reasonably able to figure out a standard clinical trial whether or not these drugs are really working to any high level of”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“While I am optimistic about over the long term using things like AI to predict what drugs might be effective, to do drug discovery and drug candidate selection, I'm much more optimistic about using AI in the short term to help drugs get to market faster than they otherwise might have been. So things like can we use AI to help prepare regulatory documents quicker? Can we use AI to do things like help companies figure out what the markets for their drugs are and prioritize what opportunities they should invest in? How can we use AI to help identify patients who might be a good fit to enroll in a certain trial? So things like trial enrollment just takes away too much time. So just better tooling to identify patients who might be a good fit for a trial and only them seems pretty impactful.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Drug discovery is rate limited by our ability to design molecules and design new drugs. And that's not really true. Our ability is much more rate limited by the downstream clinical development and testing these drugs and gathering information. We need to actually justify approving these drugs for sale and marketing them.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Trying to make a drug against, an alpha fold can be a helpful starting point for that specific circumstance. But actually Alpha Fold has problems with the very granular predictions of the configuration of sites where drugs might bind. So it's not completely accurate. So we need more accurate models for it to be really useful for drug discovery and to improve alpha fold, we need more data. It just takes a long time to collect all this data. So alpha fold is trained on decades of protein structures that have been collected painstakingly by researchers growing crystals in dark rooms. It's definitely speeded up parts of that process, but a very small part. And I think the way it's going to impact the farm industry looks similar to that. A lot of little tools that are going to be very useful and aggregate, but they're going to take a long time to deploy and figure out how best to use them and work them into the process. One thing I should also mention is that there's this idea that”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Think I'm short term pessimistic, long term, optimistic when it comes to AI for drug discovery. And I'm much more optimistic in the short term about using AI to automate some of the processes along with drug development, not necessarily the designing of drugs itself, but all the steps to bring a drug to market. So if we start with drug discovery, like finding a drug, I think it's just very difficult to see how AI is anything more than just another tool in the expanding toolbox that drug developers use to produce and test molecules. Alpha Folds, an example where now you can predict the protein structure from a protein sequence, which is a problem that we didn't know how to do to a high degree of accuracy until before alpha fold. And a lot of people are saying, oh, alpha fold is going to revolutionize drug discovery. But in reality, it's just one little piece of the hugely complex puzzle where sometimes you'll have situations where you don't know the structure of a protein.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“You're testing even in the very earliest stages. You learn at a very slow rate about what works. And if you could just find ways to speed that up across the whole process, then you'll do a lot to, I think, address some of these problems with the pharma industry, like drug prices, just a huge healthcare spend, things like that.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Testing them, then you can tighten the feedback loop around the industry and maybe develop drugs a lot faster than you might otherwise be. So I think one of the big problems with pharmaceuticals in industry is that the iteration speed is super low compared to something like tech. Like in tech, if you have an idea for a product, you can spin up a demo in a few days and you can show it to some customers. You can get some feedback on that. You can then iterate it lere instantly encode effectively and then show the next demo to customers, get more feedback, you can do these A-B tests at massive scale. You can move super fast and learn very quickly. But pharma is a very hard domain to learn quickly because everything takes so long. Clinical trials will take around 10 years to get everything through clinical trials, even to do animal experiments takes weeks or months to do animal experiments in certain cases, making all these chemicals takes a long time.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Level in Super Mario much faster than people have been able to do so far, but no one knew it was possible. So until the software developer developed this tool called Scattershot, which simulates millions and millions of Marios jumping up this level in every possible configuration of jumps and starting positions, you managed to figure out there actually was a way to get up to the top of the castle they were trying to jump up and finish a level much faster than previously possible. It's changed this whole way that speed running is approached for that game. Free running itself is probably not of interest to that many people, but the general principle, I think, is interesting that you have this intuition that something is possible, which Janssen, when he was developing his drugs, he had an intuition that you could improve this compound pathadine to make a better drug, but he didn't exactly know how to modulate it to make it the best drug it could be. He was just tinkering around. So if you could use technologies to automate a scientist to feed this process of tinkering, trying out solutions.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Not very innovative, just doing insulin. But now they're like the 15th biggest company in the world or something, and everyone's excited about the GLPs, you would have necessarily predicted that would come out of Nova Nortis. But Nova Nortis was able to produce GLPs because they had this really longstanding interest in a specific area, metabolic diseases. They support the scientists there, and they've just been tinkering in this area for a long time. So to come back to the Mario idea, that post is about this idea that One of the ways you might productively use technologies like artificial intelligence and simulation tooling is to have an intuition about what areas of science might be promising and then use automation to do scalable tinkering around that nucleus of an idea. So the example in Super Mario was that there is this idea that you could do a specific type of jump to get through a”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Where you have scientists who are really passionate about an idea, they push through their management saying you should stop this. It's clearly not working. And they try to find ways to work on this without management finding out. They try to get resources wherever they can and champion despite lots of opposition. And then eventually it turns into this drug that becomes some mega blockbuster and helps a huge amount of patients. And then the management thinks they'll say that we do it all along or something in retrospect. You can't prospectively figure out what drugs are going to be really impactful a lot of the time. So I think it's quite dangerous in an industry like pharma, which is so innovation driven and science driven to impose these top-down pre-described notions of what people should invest in. You're very likely to be wrong. Until a few years ago, I think Nova Nordis was regarded as a pretty boring European pharma company.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, so I think if you look at how things get discovered in the pharma industry, it's often very serendipitous. So you'll have these stories of people tinkering away on some idea they think is promising for years and years. And then eventually that becomes a drug. So like the GLP ones is a good example where you had decades of the scientists at Nova Nordis pushing for this idea, tinkering around the boundaries of GLPs and trying to figure out how to actually take this idea from just a concept to an actual drug. So I think one way to help make the industry more effective is to try and find ways of promoting that artful tinkering because we just haven't proven to be very good at developing drugs to a pre-described positioning, if you like. They're really important.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Higher. So now what you've seen in the industry is regulatory arbitrage, where a lot of companies are investing in things that are easier to get past the regulators. You don't need to do all these really huge phase three trials because there isn't a good standard care where there's not so many patients. So you've seen a lot of this investment in cancers and rare genetic diseases. The requirement for evidence.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Treat diabetes similar to how they would treat AIDS. So after a lot of protesting by the AIDS community and a lot of patient advocacy, the FDA ended up speeding a number of these compounds through development. So AZT and DDI to the drugs. These turned out to not be particularly effective drugs, but you could argue that potentially by starting off that process of defining a pathway for how you treat AIDS, getting some drugs on the market, getting some initial revenue, you then spurred the process to iterate and invent drugs that are now very effective. So now there are very effective treatments for AIDS. This initial speeding of the regulatory process during the AIDS epidemic turned into what became the accelerator approval pathway. And that is for drugs that seem promising in disease a very high unmet need, like AIDS, like a lot of cancers are drugs can get through regulators with much less evidence than they can in other conditions like diabetes where the standards are.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“To jump to all these tubes, to do mortality studies, all these really onerous requirements. On the other hand, if you have a disease where there's no effective standard of care and patients are dying or suffering greatly from their condition, then it makes sense to potentially relax the regulatory burdens. Come back to the AIDS issue. When you had the AIDS epidemic, there were a number of drugs that seemed to be promising that pharmaceutical companies were developing at speed like they did with COVID, right? A lot of companies were developing all the anti-COVID drugs and vaccines. And the AIDS patients were quite rightly saying that we're going to die anyway. So we have a death sentence. You should let us try these drugs and see if they're effective because the alternative is death. And the FDA until that time didn't really have a process to deal with these differences in need between conditions. So they would.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“We had more rigorous testing. So there's no one size fits all solution to fix this tension. So you have to always make some compromises. And coming back to the issue about we're running out of low-hanging fruit, one of the biggest problems is that we already have so many good drugs for many conditions. So if you have diabetes or something, then we have insulin, we have many varieties of insulin, we have the GLP1 drugs now, we have a number of other drugs that treat diabetes effectively. And they're very effective drugs. So it's hard to make the case that you need to bring another drug to market with great haste to treat large number of patients who are being well treated by current drugs. So under that situation, you probably as a regulator are inclined to put really high burdens on drug makers. So you have to absolutely demonstrate that anything you bring to market is really safe.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Big tension in how you regulate drugs is how do you balance the need to develop drugs quickly while also keeping patients who are participating clinical trials safe and keeping people who take the drugs when it comes to market safe? So it's really difficult, I think, for regulators to find an appropriate balance. And it's almost an impossible problem because if you come down too hard on drugs and on manufacturers and make them jump through too many hoops, then it's just going to be uneconomical to develop drugs. And there's going to be a massive invisible graveyard of people who could have been saved had the drug come to market faster, but it was blocked by various regulatory processes. But then if you're too lenient on drug makers, some of them will take advantage and will push drugs onto market that shouldn't have been there. They may be acting completely good intentions and they'll test according to the process, the regulatory agency demands and bring the drug to market. And it turns out later that it causes some harm that we could have foreseen.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“That we want to eliminate or potentially down the line to insert new functional copies of genes. And then cell therapy is this idea that you can edit cells, immune cells in the body to program them in a way to do something that you others do. They might otherwise be inclined to do. So you take immune cells that are very good at killing other cells. They're very good at killing foreign cells and microbes. But the body has a lot of systems to prevent immune cells from killing your own cells. So what cell therapy is doing is taking out some of the immune cells and tweaking them so they'll bind and recognize pathogenic cells like cancer cells that may look to the unedited immune system similar to a normal cell and then redirecting the immune system towards removing those pathogenic cells.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“This idea that you can insert into the body to compensate for defective genes. If you have something like this spinal muscular atrophy example where patients who have that disease, they lack a functional copy of a gene called SMN1, which produces a protein that your motor neurons need to stay alive, essentially. And if you can package up that gene and deliver it into a cell, the cells that are missing this functional copy will then produce the protein. You can restore that function. That seems like quite a promising approach. But then, of course, a difficulty with fixing these mutations is actually getting the gene into the cells. So a lot of the innovation around gene therapy was figuring out how to deliver genes to cells. And the approach that we've landed on now is an industry, the dominant approach is to use a virus, essentially. So what CRISPR is doing is making specific, let's say, cuts to the DNA to either eliminate genes.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“If you can put in this antibody that binds this protein, takes it out, then you can treat some of these diseases that are pathologically too many of a certain protein. And if we want to treat cancer, cancers have a different composition of proteins on the surface than normal cells. You can put in antibodies that bind those cancer cells and kill them specifically. So where the monoclinal comes in is that a while back, there was some scientists figured out that you could take these immune cells that were producing antibodies and combine them with a cancer cell, essentially, and immortalize the cells that produces antibodies. That's how they make it into scalable. Manufacturing process. You have these cells that are artificially immortalized, that produce antibody anyway, and they just produce tons and tons of this antibody product that you can just grow them up in a big bioreactor vat and then after a certain level grow it and then you skim off the antibodies. Gene therapy is”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“Is always generating all the time, all these antibodies. And when a virus infects you, then if you have an existing antibody that binds that virus, it'll multiply within the body, and then it will bind to viral copies and it will stop the infection by just finding and neutralizing these viruses or bacteria. And that was recognized as if antibodies combined proteins on these foreign microbes, it can also probably be useful for binding other molecules or other proteins in the body that aren't necessarily foreign but may impact disease in certain ways. So we can use it to knock out proteins that we would want to knock out to treat diseases. So one example is Humiro, which is until recently the top-selling drug in the world, something like 20 billion in revenue. It's an antibody that binds to protein called”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“I'll start with this antibody, right? So when you get infected with some sort of virus or bacteria, your immune system will generate antibodies against the invading threat. And these antibodies are specific to foreign proteins”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source
“And these are compounds where you have a targeting element, let's say a cancer, and then you have a radio nucleide, which emits radiation. You infuse these drugs, it binds the cancer, it emits radiation, the radiation kills the cancer cell in a targeted way. And these are really complicated to deliver because the half-life of some of these radioactive compounds is something like seven days. You need to manufacture and deliver it to the patient within a few days before they lose efficacy. So these complex therapies are one way of pharmacies trying to build up moats to distribution products.”
2024-01-30 · Invest Like the Best · Alex Telford - Unlocking Innovation in Pharma - [Invest Like the Best, EP.360] · IDENTIFIED FROM THE TRANSCRIPT · source