Patrick Short  0:03  
Hi, everyone, welcome to the first genetics podcasts of 2023. We're going to try something a little bit new today, something I've wanted to do for a little while. And I'm going to put my neck out a little bit here and make a couple of predictions for 2023. So I'm going to make four predictions. And I've done a little bit of work to do my research and try to make them specific think there's nothing more annoying than having somebody make predictions that are, they're just like reading somebody's poem. And they don't really mean anything. So I'm gonna give four predictions. And they're obviously broader themes that I'm interested in. And I think I'd have been worth watching anyway. So let's jump into it. The first one is about legislation of drug pricing. So you may have seen headlines over the last couple of months in August, the inflation Reduction Act in the US which which it sounds like has nothing to do with health. But if you know how US politics work, they cram all sorts of weird things into these broad bills. The inflation Reduction Act had a piece in there about legislation of drug pricing. And my prediction is that a there's going to be a huge amount of backlash from both patients and from drug developers from both sides. And I think that the legislation is going to be pretty comprehensively rewritten. So a little bit of background on the legislation itself. What it says is that it requires Medicare, which for those who don't know, is the US government's run government run insurance programme that's really focused on older Americans. It requires them to negotiate with drug manufacturers for a, quote, reasonable price when comparing with other costs other drugs on the market, and what the development costs for the drug are. So it's relatively broad and not particularly clear what it means. Importantly, for people listening this podcast are interested in genetics and in rare diseases in precision medicine, there is a carve out for orphan drugs, meaning that they're exempt from these negotiations. But this carve out only applies to orphan drugs that are labelled for a single disease. And as you may know, part of the rare disease and precision medicine playbook in general is that you develop a compound not just for a single disease, but you may get it initially approved for one disease. But if another disease has a common biological pathway or target, then that same drug can be used to treat a different disease. I mean, there's a great Wall Street Journal article, I'm going to put in the show notes that gives one example of Keytruda, which is a Merck drug that was initially approved seven or eight years ago in advanced melanoma, but it's now used in about 19 other cancers. So cancer is one great example of this, where if you've got a drug that is really effective, one of the first things they'll look to do is try in adjacent forms of cancer to other types of skin cancer, for example, in this case, and and other cancers defined by the same genetic marker. And another example, which was in the news relatively recently is there's a rare disease focused company called out nyalam. They do RNA interference based therapeutics. And traditionally, they've been very focused on rare disease, they've started to do a little bit more common disease, but they announced that they were cancelling a phase three for their Stargardt disease trial, which is a genetic eye disease. And interestingly, they cited this as the reason why they were cancelling the phase three, the drug they were going to test has already been approved in a different disease. And they were concerned that if the phase three trial and startup was successful, and they went to market that actually they would trigger this provision in the new bill, and that it would impact their pricing. And I've talked about this a lot on the podcast with different guests. But this whole issue of pricing with transformative therapies for Rare Disease is a massive one anyways, and my take on this is that the bill was well intended. I think the intention here is to prevent cases where people are taking advantage of having a cornered market where there's only one drug for a particular disease. And then the prices are sky high. And we've seen a lot of examples in the past where patients regulators, drug developers end up at a little bit of an impasse, because the drug developers feel they need to price the drug high in order to recover the enormous development costs patients if the drug can get paid for one to get access to it, because it's potentially transformative. But the regulators need to create some kind of semblance of fairness in the market. So um, that we don't have the million dollar drugs for all of the 6000 diseases that are yet to be cured. So this is, I think, a well, probably well, and like many things well intentioned, but is going to have enormous impacts. And I don't think it was intended to stop companies like Elon island from developing drugs for rare diseases. So my prediction is that this is going to be comprehensively rewritten, because they're going to be getting enormous pressure from patient advocacy organisations, as well as drug developers. And I don't think there's really anyone that is going to be a massive fan of this. They're going to be some people who probably appreciate the sentiment and the general direction. And I think there's a need for the general direction of having more clarity around how these things get priced. And if you just look at the difference in drug prices between the UK and the US for exam until the UK, which has a single payer system that has a lot of negotiating power. These drugs are priced significantly lower in the UK compared to the US where the market is a lot more fragmented. So I understand why they're doing this, but I think it's going to get rewritten because it was written in a very, very clumsy way. Okay, Prediction number two is about consolidation in the genetic testing market. So those who follow Illumina pack bio and other large scale sequencing organisations know that actually a merger between Illumina or acquisition between Illumina and PacBio was stopped by the antitrust regulators in the US and the UK, citing that it would be anti competitive that Illumina has market share, plus pack BIOS was was essentially too large for them to combine. I'm not predicting that Illumina is going to acquire pack bio, I think possibly that bridge has been burned until some point in the future. But what we've seen in the last couple of years is pack bio is getting a lot stronger, Oxford, nanopore is getting a lot stronger, they have a very different way of sequencing, then Illumina using nanopores, instead of chopping the DNA up, we've seen in 2022, and new sequencing technology called Ultimate that is going for an even lower cost sequencing than Illumina, they're, they're a little bit less mature in their earlier on, but they've come onto the scene. And at the same time, I think the recession that we find ourselves in in the changing economic climate means a lot of these companies that are not as financially secure as the 1000 pound gorilla in the room, Illumina are going to have potentially a tougher time. And also, this is a time when I think we're going to see many big companies acquiring smaller companies. So for that reason, I think we're going to my prediction number one is that we're going to see Illumina buy one of the other sequencing companies and a major one, one of the ones that I mentioned, there are one of the other major ones in the market. And my secondary prediction, if that one doesn't come true is that there's going to be a major acquisition of an adjacent technology, probably proteomics or something like that. So I'm thinking someone like Soma logic or olink. And when I think about Illumina and and where they're going, and also where the science is going, we're heading into a world where we are going to have large scale polygenic risk scores proteomic risk scores on the the last episode prior to this one with Vera, we talked about proteomics is a big theme. So as Illumina thinks about, eventually, probably in the next 10 years, we're going to be sequencing everyone from birth, we're going to be sequencing adults pretty soon for all sorts of different reasons. And they're gonna be looking at how do they not just compete in the sequencing market, but actually expand into other precision medicine applications beyond that. So prediction, one a is that they buy one of their competitors, either the low cost Ultima, to take them out of that competitive position, whether they're whether they're likely to sell, I don't know, there seems to be really well funded. And, and it's hard to say and I think for for those of us who by sequencing competition is always good, but I think it's likely to happen. And then number two is that they buy a major proteomics platform and work to add it into the workflow. Alright, my third prediction is that we're going to see positive news from a trial being done by Grail, which is a company that does early detection for cancer based on circulating tumour DNA in the blood. They've been running a trial in the UK, about 25,000 people, and a couple of different centres centred around Oxford. And importantly, these 25,000 people have suspected cancer. So they're running this early detection workflow alongside the standard of care. That trial is scheduled to read out this year. And I think we're gonna get positive news from that that's possibly not a surprise, because the people already have suspected cancer, the one that isn't going to read out this year, but I'm going to make it 2024 predictions, they're doing a larger study across the NHS, and about 140,000 people, which is now fully enrolled. And that's looking at people between ages of 50 and 77, who are currently healthy, so no, no reason to suspect they might have cancer or not, and actually believe there are people who have no prior diagnosis of cancer. So they're people who are ascertained for not being likely to have cancer right now. And they're measuring how many people they can detect with, with early stage cancer make a cancer diagnosis effectively through this broad population screening. So I predict we're going to get positive news from the Grail trial in the UK in people with suspected cancer. And I think in 2024, we're going to see positive news from the larger healthy volunteers study as well. What I'm going to I'm going to make two predictions on both of these first is they're going to meet the primary endpoints, which is going to be about making diagnoses. The second one is about health economics. So how, what are the total cost savings from implementing an early detection programme versus not and I think these are going to be positive as well. And these are going to be a lot more up for debate.

I think what most people believe about these technologies is that they're probably or possibly going to be good medically, but the jury is still out in terms of the Health Economics, if you screen 100 people to find one that has cancer or to find five that have cancer, how to the costs of that screening and all the additional tests that might be flagged up from false positive way against what you find, and again, not from a human or a medical perspective, but purely from an economics perspective. But I'm going to predict that in both cases, they, they come back positive, but I would not be surprised if the health economics are not a slam dunk. And that raises questions. But in any case, I think, hopefully, with the first one that I mentioned in the 25,000 people, if we get positive data on both of those pieces, it'll spark a really important conversation to do more of these studies, and to do them at a large scale. I think from a first principles perspective, we say, if the technology works, and if we can prove the economics work, it's an amazing way to rebuild the healthcare system in a way that is going to generate positive externalities far beyond the money that you can save. It's hard to quantify what detecting and early stage cancer does to somebody's life and well being. But those are, those are typically hard to capture in the calculation. So I'm hopeful on this one, and that's probably colouring my prediction, but um, I'm gonna predict that towards the middle to end of the year, we're gonna get some good news from this trial. All right, my final prediction here is is the most speculative one, and I'm predicting a big AI breakthrough, something bigger than alpha fold. I really don't have any inside info on this. I'm not entirely sure what it could be. This is the one where you're gonna have to hold me to it if something does happen. And you can say whether I was specific enough, but the reason for making this prediction is I was amazed by chat GPT, Dali, all of the non directly health relevant or genetics relevant breakthroughs in 2022. And it's been so in 2021, I believe was the big alpha fold paper. And they've been doing an enormous amount of work on that since then, but it feels like with all that progress happening in adjacent domains, the time is ripe for a big AI breakthrough. That's more directly relevant to this field. Chet GPT and Dali are obviously useful and interesting can be applied in many ways. I could see this going something building on top of alpha fold, for example, I think it's been it's been shown to work and it's been shown to be effective and and match many of the experimental findings. I wonder if they're they will take it a step further and apply it in some way to to drug discovery are another important problem focused on proteomics sport could be something entirely different. But I will be surprised if where we sit here next year, we haven't had a chat GPT or Dali type moment with AI and health and, and I could be wrong on this because health and life sciences is a very messy field, the data that we have is it's hard to take real world data and make sense out of it. And biology itself is messy. We're built up over hundreds of millions of years of layered evolution on top of one another. So it's a it's a challenging substrate to build on top of but based on what I've seen in other challenging fields like generating images, and, and text and so on. I think we might be in for some good surprises. So those are my four predictions for the year. If you have any others if you disagree, if you feel differently. We'd love to hear from you anytime you can email us at podcast at Senate genetics.com Or you can find me on Twitter at Patrick underscore J underscore short and let me know what you think. Thanks and happy new year.

Transcribed by https://otter.ai