WEBVTT - Stopping HIV Without a Vaccine 0:00:15.356 --> 0:00:23.956 Pushkin. So I'm curious in your own life when you 0:00:24.036 --> 0:00:29.196 first became aware of HIV and AIDS. 0:00:29.556 --> 0:00:34.116 Oh gosh, this is a great question to start interview. 0:00:35.396 --> 0:00:41.036 I am fifty I did one, so I do remember. 0:00:41.076 --> 0:00:44.036 I remember the first news stories as a you know, 0:00:44.036 --> 0:00:49.396 as a child. It's also been a driver of everything 0:00:49.396 --> 0:00:51.076 I've worked on and wanted to work on. 0:00:51.716 --> 0:00:56.236 I am also fifty one, coincidentally, and I you know, 0:00:56.476 --> 0:00:59.916 I vaguely remember the world before HIV and AIDS. I 0:00:59.996 --> 0:01:02.436 also remember, and I'm sure you remember this too, like 0:01:02.956 --> 0:01:06.276 coming of age at a time when if you got AIDS, 0:01:06.276 --> 0:01:08.716 you died, and you could get it from having sex. 0:01:09.156 --> 0:01:10.036 Uh. 0:01:10.196 --> 0:01:13.436 To me, that's the that's the big imprint it left 0:01:13.476 --> 0:01:16.876 on my own you know, narrowly, narcissistically on my own life. 0:01:17.116 --> 0:01:20.356 Yes, so much fear, right, so much, so much death, 0:01:21.316 --> 0:01:26.996 so much destruction, destruction of potential, and so much fear 0:01:27.076 --> 0:01:32.316 and surgainly for a generation to have fear and sex 0:01:32.596 --> 0:01:38.356 so coupled with each other, so intertwined. But it's always 0:01:38.396 --> 0:01:41.516 driven me to to to end HIV is to be 0:01:41.596 --> 0:01:44.956 able for you know, there to be a generation who 0:01:45.036 --> 0:01:48.036 didn't have that cloud of fear in their lives. 0:01:54.156 --> 0:01:56.556 I'm Jacob Goldstein and this is What's Your Problem, the 0:01:56.596 --> 0:01:58.596 show where I talk to people who are trying to 0:01:58.676 --> 0:02:03.316 make technological progress. My guest today is Jared Bayton. He's 0:02:03.396 --> 0:02:08.356 senior vice president in virology Achillead Sciences. Jared's problem is this, 0:02:09.156 --> 0:02:11.916 in a world without a vaccine, how do you prevent 0:02:11.996 --> 0:02:17.756 people from getting HIV. It's been clear for years that 0:02:17.836 --> 0:02:21.756 taking a daily pill dramatically reduces the risk of getting HIV, 0:02:22.356 --> 0:02:25.116 but as you'll hear, the vast majority of people who 0:02:25.156 --> 0:02:28.516 are at high risk for getting HIV just don't take 0:02:28.556 --> 0:02:32.236 a pill every day. Now, Jared and his colleagues are 0:02:32.236 --> 0:02:35.516 working on a new option, a drug called leni kapavir 0:02:35.716 --> 0:02:38.716 that you get as a shot once every six months. 0:02:39.036 --> 0:02:42.036 The drug has not yet been approved to prevent HIV, 0:02:42.596 --> 0:02:45.316 but there have been some really compelling results from a 0:02:45.316 --> 0:02:48.556 couple big clinical trials. There's a lot that's interesting in 0:02:48.596 --> 0:02:51.396 the show today, how medicine only works if it meets 0:02:51.396 --> 0:02:54.116 people where they are, and how what seemed like a 0:02:54.156 --> 0:02:57.076 big problem for Lena kapavir may turn out to be 0:02:57.276 --> 0:03:00.476 the key to its success. But we started with Jared's 0:03:00.476 --> 0:03:02.796 own career, which tracks a lot of the history of 0:03:02.996 --> 0:03:06.516 HIV and AIDS and the emergence of drugs that can 0:03:06.596 --> 0:03:10.556 prevent people from becoming infected. So when do you decide 0:03:10.636 --> 0:03:16.836 to make fighting HIV your career. 0:03:17.316 --> 0:03:20.156 When I went to graduate school and medical school, I 0:03:20.156 --> 0:03:22.876 was when I decided to work on HIV that I 0:03:22.956 --> 0:03:26.796 wanted to do health work that was meaningful to the world. 0:03:26.876 --> 0:03:29.716 That was that it was and it was immediately actionable. 0:03:30.356 --> 0:03:33.116 As a graduate student during medical school, I lived and 0:03:33.156 --> 0:03:38.036 worked on HIV prevention in Kenya. Obviously before there was 0:03:39.116 --> 0:03:44.436 medicine for prevention, and I remember very well, even before 0:03:44.516 --> 0:03:46.836 there was very good testing. I was a strain of 0:03:46.836 --> 0:03:50.636 thought at the time that testing was too scary to 0:03:50.676 --> 0:03:52.356 do because there was nothing to be done. 0:03:52.796 --> 0:03:53.236 Wow. 0:03:53.316 --> 0:03:55.916 I certainly had other doctors say that to me. I 0:03:56.156 --> 0:04:01.956 the hospital that I worked in Kenya, the only testing 0:04:02.196 --> 0:04:04.796 that was done was so people could stop spending money 0:04:04.876 --> 0:04:05.836 on their family members. 0:04:05.996 --> 0:04:08.476 Oh my god, So meaning, oh, don't spend any money 0:04:08.516 --> 0:04:11.396 on them. They have HIV, They're going to die. That's 0:04:11.476 --> 0:04:12.836 why they were doing the tests. 0:04:13.036 --> 0:04:15.596 Yeah, someone in the hospital extraordinarily sick. Let's do an 0:04:15.676 --> 0:04:18.596 HIV test. Okay, you can stop spending money. Jesus and 0:04:18.796 --> 0:04:22.236 then really importantly, I remember when medicines came. I remember 0:04:22.276 --> 0:04:25.476 when medicines came. I remember when I remember very well 0:04:25.476 --> 0:04:28.356 when the coffin makers who would work in the street 0:04:28.396 --> 0:04:30.276 outside the hospital start going out of. 0:04:30.236 --> 0:04:34.756 Business, the coffin makers, the coffin makers, yep, holy yahkah, 0:04:36.676 --> 0:04:42.636 which gosh, the Kenya's prevalence maybe at fifteen percent or 0:04:42.676 --> 0:04:44.956 something like that at some point, and it's. 0:04:44.756 --> 0:04:50.356 Not much lower to be able to see in that 0:04:50.396 --> 0:04:53.236 country and other countries what medicines can do. And that's 0:04:53.276 --> 0:04:56.396 actually that's what drove a lot of signs. I've always done, 0:04:56.436 --> 0:05:00.116 is HIV prevention and then HIV treatment, but making medicines 0:05:00.156 --> 0:05:02.556 that make a difference in people's lives, and like what 0:05:02.956 --> 0:05:06.756 good medicines did for HIV care here in the US 0:05:06.796 --> 0:05:09.316 where I live from, in many parts of Africa where 0:05:09.316 --> 0:05:14.876 I've worked, and how fundamentally transformed, how socially transformative, how 0:05:14.956 --> 0:05:20.636 something risked really destroying in fraction societies, and how good 0:05:20.676 --> 0:05:23.716 science was able to arrest that in averse. 0:05:23.756 --> 0:05:28.156 Then so okay, so that's what's happening, you know, around 0:05:28.156 --> 0:05:31.476 the turn of this century. And then there's this new 0:05:31.556 --> 0:05:34.956 idea that comes along after that right, and that is 0:05:35.516 --> 0:05:38.516 what if we can use these drugs to prevent people 0:05:38.556 --> 0:05:42.516 at high risk from getting HIV in the first place. Right, 0:05:42.596 --> 0:05:45.756 This idea called prep Where does that come from? 0:05:46.276 --> 0:05:48.596 So this idea of prep pre exposure, prople axis, you 0:05:48.596 --> 0:05:51.556 take a medicine. By having that medicine, your bloodstreams, your 0:05:51.556 --> 0:05:55.156 tissues or whatever, you if you expose to the virus, 0:05:55.396 --> 0:06:00.676 it doesn't take hold. Yeah, and the idea of propyle 0:06:00.676 --> 0:06:05.036 axis is not totally novel in infectious diseases. If you've 0:06:05.036 --> 0:06:07.436 ever traveled to a place with malaria, you've probably taken 0:06:07.476 --> 0:06:10.996 a malaria propyle axis that kind of idea, But they 0:06:11.116 --> 0:06:15.116 do prep for HIV was super surprising at the time. 0:06:15.236 --> 0:06:15.516 Huh. 0:06:15.556 --> 0:06:18.836 You have to have a medicine that would work to 0:06:18.876 --> 0:06:22.756 prevent HIV and HIV is very transmissible, so to avert 0:06:23.596 --> 0:06:26.916 infection would be a high bar. And then it has 0:06:26.916 --> 0:06:30.516 to be medicine itself that's very well tolerated, very safe 0:06:30.556 --> 0:06:34.476 because you're it would be given to healthy individuals who 0:06:34.516 --> 0:06:38.076 don't have affection, and the societal medical tolerance for side 0:06:38.076 --> 0:06:41.436 effects for treating HIV, just like treating any really serious 0:06:41.556 --> 0:06:44.916 dead latencies, is different than but for preventing. 0:06:44.516 --> 0:06:46.676 It, sure, it has to be lower risk. Right, if 0:06:46.716 --> 0:06:48.756 you already have HIV and you're going to die, you're 0:06:48.796 --> 0:06:51.636 willing to take a right medicine that has pretty severe 0:06:51.676 --> 0:06:55.036 side effects, whereas if you're healthy, you're not going to 0:06:55.116 --> 0:06:58.916 take some really harsh, risky drug just in case. 0:06:59.156 --> 0:07:03.276 Exactly exactly right and unfortunately for treating HIV. Just for 0:07:03.756 --> 0:07:06.516 your listeners, like the complexity and the side effects of 0:07:06.556 --> 0:07:09.476 the medicines from the late nineties and two thousand have 0:07:10.036 --> 0:07:12.836 changed dramatically in the last couple of decades, and so 0:07:12.956 --> 0:07:15.756 that most people these days actually take a single pill 0:07:16.076 --> 0:07:21.396 once a day, extremely well tolerated, and live what's expected 0:07:21.436 --> 0:07:23.036 to be a full lifespan lived as long as someone 0:07:23.036 --> 0:07:26.116 who doesn't have HIV and are on infections. So just 0:07:26.116 --> 0:07:29.276 so people know what's changing. But in early two thousands, 0:07:30.076 --> 0:07:31.436 medicine still had side effects. 0:07:31.436 --> 0:07:33.116 Were you working on PREP at this time? 0:07:33.316 --> 0:07:36.116 I worked on one of the two trials that formed 0:07:36.236 --> 0:07:40.796 the registrational package of PREP, one in mostly gave men 0:07:40.876 --> 0:07:45.796 and some transgender individuals, and then one in heterosexual individuals, 0:07:46.476 --> 0:07:49.596 women and men, And that was the second one was 0:07:49.596 --> 0:07:51.676 the study that I worked on with collaborators from all 0:07:51.716 --> 0:07:54.836 over the world. And based in Kenyan. You gotta it 0:07:54.996 --> 0:07:59.116 was almost five thousand couples where one person didn't have 0:07:59.236 --> 0:08:00.196 HIV and the other one did. 0:08:01.236 --> 0:08:03.556 So that's a very high risk setting, very. 0:08:03.516 --> 0:08:07.036 Higher setting, and also setting where there was tremendous motivation 0:08:07.716 --> 0:08:10.436 to have a different life experien for the couple it was. 0:08:11.036 --> 0:08:13.196 It was a really remarkable time because there was lots 0:08:13.196 --> 0:08:15.156 of questions where the park would work at all. There 0:08:15.156 --> 0:08:16.716 was not a question where it could be safe enough 0:08:17.276 --> 0:08:22.316 and go to the trials demonstrated both safety and HIV protection. 0:08:22.996 --> 0:08:26.036 Protection that was dependent on people taking it. Like all medicines, 0:08:26.076 --> 0:08:28.716 medicines only work if you take them, and there are 0:08:28.716 --> 0:08:31.316 all kinds of different motivations to take something, predict something 0:08:31.356 --> 0:08:33.956 that's every day, and some people really succeed and some 0:08:33.996 --> 0:08:36.636 people really struggle. As you can access. 0:08:36.396 --> 0:08:40.836 So you are, they're setting up the next turn in 0:08:40.916 --> 0:08:43.076 our story, which is the new drug we are here 0:08:43.116 --> 0:08:48.396 to talk about, right, But let's just do that for 0:08:48.436 --> 0:08:52.236 a minute more, because as you said that the drugs 0:08:52.276 --> 0:08:56.396 people can take to prevent getting HIV have gotten easier 0:08:56.436 --> 0:09:00.716 to take and better tolerated. And you know, if you 0:09:00.796 --> 0:09:02.556 can take one pill a day and you're in a 0:09:02.596 --> 0:09:05.316 high risk setting and that means you have a profoundly 0:09:05.316 --> 0:09:09.876 lower risk of getting HIV. Like, what's the problem? Like 0:09:09.916 --> 0:09:12.116 I feel like, great work, thank you for doing that 0:09:12.156 --> 0:09:14.796 good work, and like it seems like you're there. 0:09:18.196 --> 0:09:20.596 I'm sure there were moments where I thought, it seems 0:09:20.596 --> 0:09:23.316 like we're there. This seems obvious to me as well. Yeah, 0:09:23.396 --> 0:09:27.796 I remember well the first day. Its actually years after 0:09:28.156 --> 0:09:32.756 the first medication for PREP was approved, where it had 0:09:32.756 --> 0:09:37.116 never been something like this hadn't been rolled out in clinics, 0:09:37.116 --> 0:09:41.156 so like people doctors didn't have the conversation pieces to 0:09:41.196 --> 0:09:43.836 talk with this, patients or individuals who wanted PREP didn't 0:09:44.196 --> 0:09:48.796 always have heard about it or didn't have the practice 0:09:48.836 --> 0:09:52.876 and asking for it. And it was slow. It was 0:09:52.916 --> 0:09:55.636 slow going, slow going in this country, slow going around the. 0:09:55.596 --> 0:09:59.516 World, slow going meaning people just didn't take it that much. 0:09:59.556 --> 0:10:02.156 Healthy people didn't want to take a pill every day. 0:10:02.316 --> 0:10:04.356 Yeah, I was like, yes, this is hard, like new 0:10:04.476 --> 0:10:07.996 innovations and health are hard because none of us make 0:10:08.076 --> 0:10:11.436 health decisions, or at least I think most of us. 0:10:11.436 --> 0:10:13.436 Most of us do not make health decisions just because 0:10:13.476 --> 0:10:17.116 someone tells us to or because the science is really excellent. 0:10:17.156 --> 0:10:18.876 We make health decisions because we think it's going to 0:10:19.236 --> 0:10:21.316 be meaningful for us. So whether that's like what we 0:10:21.436 --> 0:10:24.196 eat or going to gym, or like what we buy 0:10:24.236 --> 0:10:28.156 off Instagram or whatever else for our health, Like, we 0:10:28.236 --> 0:10:30.716 make those decisions because we think it's meaningful for us. 0:10:30.716 --> 0:10:33.116 And something like PREP, which can be extorted and meaningful, 0:10:33.236 --> 0:10:35.556 it has to be extortedly meaningful for someone to want 0:10:35.596 --> 0:10:38.556 to make the effort to go to get it and 0:10:38.636 --> 0:10:42.116 to continue it. There are many many people who take 0:10:42.116 --> 0:10:44.636 PREP every single day. It fits into their lives. It 0:10:44.636 --> 0:10:47.676 brings benefit, and it brings meeting and they can make 0:10:47.716 --> 0:10:51.156 it workable within their lives. And then there have been 0:10:51.516 --> 0:10:55.396 many people who have tried and stopped or not tried 0:10:55.436 --> 0:10:58.676 at all. And that's like setting up for my rest 0:10:58.716 --> 0:11:04.076 for our discussion. Just because you have something that works 0:11:04.436 --> 0:11:08.516 for some people, that airing that bottle home or it 0:11:08.516 --> 0:11:12.116 could be found by an aunt, partner or brother or 0:11:12.116 --> 0:11:19.556 whatever is too much, too much disclosure, too much revealing. 0:11:20.236 --> 0:11:23.876 It means you're having sex, probably right, yeah. 0:11:23.556 --> 0:11:27.756 Exactly, Or the complexity of the of taking something every 0:11:27.836 --> 0:11:31.396 day when you've got two jobs and three kids or 0:11:31.396 --> 0:11:35.076 whatever the things are that for something that you don't 0:11:35.076 --> 0:11:36.196 really want to think about every day. 0:11:36.716 --> 0:11:40.116 Yeah, it's a very good qualitative description. Is there a 0:11:40.236 --> 0:11:44.356 quantitative piece like, have you estimated the population that you 0:11:44.396 --> 0:11:46.836 know might be relevant but doesn't want to take a 0:11:46.836 --> 0:11:48.036 pill every day in the first place. 0:11:48.316 --> 0:11:52.276 Yeah, In the US, CC is estimated that maybe about 0:11:52.276 --> 0:11:54.956 a third of the people who would most benefit from 0:11:54.996 --> 0:11:57.596 taking PREP, not even like benefit at all, but like 0:11:57.676 --> 0:12:00.996 most benefit from taking PREP are taking it sort of 0:12:00.996 --> 0:12:02.676 today we are taking it day to day. 0:12:02.716 --> 0:12:05.756 Wait, one third of the people who are at highest 0:12:05.876 --> 0:12:08.596 risk for getting HIV are taking it. So two thirds 0:12:08.596 --> 0:12:09.796 of the people are. 0:12:09.556 --> 0:12:12.596 Not exactly so, a third r a third arth, two 0:12:12.596 --> 0:12:13.116 thirds are not. 0:12:13.716 --> 0:12:19.316 So okay, So there is this idea that PREP is great, 0:12:19.356 --> 0:12:21.996 but most people who could most benefit from it don't 0:12:22.036 --> 0:12:26.516 take it. One thought as well, if instead of having 0:12:26.596 --> 0:12:28.996 to take a pill every day, it was less frequent, 0:12:30.156 --> 0:12:32.596 simple behavioral thing, maybe people would do it more often. 0:12:32.676 --> 0:12:35.036 And so so there's this search for a for a 0:12:35.076 --> 0:12:37.956 new drug that is longer lasting, right, that you in 0:12:37.996 --> 0:12:40.796 fact have found spoiler alert, But tell me about the 0:12:41.116 --> 0:12:41.956 search for that drug. 0:12:42.636 --> 0:12:47.276 The idea was that HIV has a structural element called 0:12:47.356 --> 0:12:50.156 it's capsid, where it encloses the nucleic acid of the 0:12:50.196 --> 0:12:52.236 virus within the virus. 0:12:52.076 --> 0:12:54.436 It's it's like it's the bag, right, It's the protein. 0:12:54.636 --> 0:12:58.556 It's yeah, it's a protein coming. It's like a yeah. 0:12:58.356 --> 0:13:00.476 And I always want to think it's stronger than the bag. 0:13:00.636 --> 0:13:01.956 It's stronger than a bag. 0:13:02.036 --> 0:13:06.836 It's like okay, it like akayas case flask okay, okay. 0:13:07.396 --> 0:13:09.836 And that's the virus is coming into the cell that 0:13:09.956 --> 0:13:11.876 opens and dumps the new class ass and out. So 0:13:11.916 --> 0:13:14.156 the virus is infecting and when it leaves it encapsulates 0:13:14.156 --> 0:13:18.036 the begin and floats away. And targeting that is particularly hard, 0:13:18.036 --> 0:13:21.716 and the work on it began a dozen years before 0:13:22.196 --> 0:13:25.236 took a dozen years from the work to start before 0:13:25.276 --> 0:13:27.316 we've even tested any human being for the first time, 0:13:28.796 --> 0:13:34.236 and four thousand molecules were synthesized and screened in test 0:13:34.236 --> 0:13:35.996 tubes and animals, selling them other things to be able 0:13:36.036 --> 0:13:38.636 to be able to bring forward one to be able 0:13:38.676 --> 0:13:41.116 to test in human beings, which then became a lot 0:13:41.116 --> 0:13:41.556 of capeer. 0:13:45.596 --> 0:13:46.916 We'll be back in a minute. 0:13:56.796 --> 0:13:59.876 A virus like HIV has a certain number of proteins 0:13:59.876 --> 0:14:03.116 that make it function right and caps it had not 0:14:03.196 --> 0:14:06.036 been targeted and as a result of a great question 0:14:06.076 --> 0:14:08.036 to say, could we target this part of the virus 0:14:08.036 --> 0:14:10.956 in a way that it's different. This is important for 0:14:11.116 --> 0:14:16.356 HIV broadly because what has been the success of treating 0:14:16.436 --> 0:14:19.476 HIV is being able to target the virus in multiple places, 0:14:20.676 --> 0:14:24.396 in multiple components of its life cycle, and that is 0:14:24.476 --> 0:14:28.796 what makes up a treatment cocktail for HIV. Multiple medications 0:14:29.316 --> 0:14:32.036 usually the target different parts of the virus life cycle 0:14:32.116 --> 0:14:34.996 at the same time, and from a safety point of view, 0:14:35.036 --> 0:14:38.076 actually ones that are very specific to the virus itself 0:14:38.236 --> 0:14:43.756 and don't have effects on us. And so a enzyme 0:14:43.796 --> 0:14:46.236 that only the virus makes, or in this case, protein 0:14:46.276 --> 0:14:48.756 protein interaction that only the virus has, is a great 0:14:48.996 --> 0:14:53.996 target because there's nothing that looks like that in our 0:14:54.396 --> 0:14:55.276 regular systems. 0:14:56.116 --> 0:14:58.836 So basically that means people are likely to have fewer 0:14:58.876 --> 0:15:01.636 side effects because our own cells aren't gonna be bothered. 0:15:02.076 --> 0:15:04.476 So it seems like a promising target because it's this 0:15:04.556 --> 0:15:06.836 weird thing that the virus does that we don't do. 0:15:07.596 --> 0:15:11.356 And then drug researchers find this, this molecule, right, this 0:15:11.556 --> 0:15:14.756 potential drug that will eventually be called len. 0:15:14.596 --> 0:15:15.276 A cap of bear. 0:15:15.956 --> 0:15:18.796 But but there's what seems like a problem with this 0:15:18.916 --> 0:15:21.556 with this molecule, right, and the problem is that it's 0:15:21.636 --> 0:15:25.716 not very soluble in water. It doesn't dissolve well in water. 0:15:26.196 --> 0:15:27.716 Tell tell me about that part of it. 0:15:28.756 --> 0:15:31.796 There people who work on it. Just sometimes you do 0:15:31.796 --> 0:15:33.436 a lot of work to try to figure out the 0:15:33.476 --> 0:15:36.756 best what's got the best attack on the virus itself 0:15:36.756 --> 0:15:38.876 around the end time you're trying to target itself. And 0:15:38.916 --> 0:15:42.636 then it's not particularly soluble problem because that like medicines 0:15:42.636 --> 0:15:45.996 that we take through our mouth, for example, like most 0:15:45.996 --> 0:15:49.796 medicine surge IVY need to dissolve an order for us 0:15:49.836 --> 0:15:52.436 to absorb them. And actually a lot of work goes 0:15:52.476 --> 0:15:55.276 into one one's doing drug development, and maybe you figure 0:15:55.276 --> 0:15:56.796 out the thing that targets best, and then you figure 0:15:56.796 --> 0:15:58.756 out how to modify it ever as best you can 0:15:59.196 --> 0:16:01.316 to be able to absorb it, because if you can't 0:16:01.316 --> 0:16:02.996 absorb it doesn't have an effect. 0:16:02.916 --> 0:16:05.516 Right you want you want it to dissolve in water. 0:16:05.556 --> 0:16:07.716 You want to take it and then it dissolves and 0:16:08.276 --> 0:16:10.956 goes off into your correct exactly. 0:16:11.716 --> 0:16:16.116 It's the tremendous advantage of Lena kaeper beer has been 0:16:16.556 --> 0:16:21.276 for what it eventually became is that when it's formulated 0:16:21.276 --> 0:16:25.356 as an injection, it forms a deepot of the drug, 0:16:25.476 --> 0:16:28.916 well deposit of the drug that dissolves slowly over time 0:16:28.956 --> 0:16:31.236 because it isn't immediately soluble. 0:16:31.316 --> 0:16:34.276 And like, was there a moment when somebody sort of 0:16:34.356 --> 0:16:37.756 just realized like, oh, this this bug could actually be 0:16:37.956 --> 0:16:40.236 you know, like an amazing feature. You know the fact 0:16:40.276 --> 0:16:42.636 that it's not soluble, like it might mean we could 0:16:42.676 --> 0:16:44.596 give this drug to people and it would last a 0:16:44.636 --> 0:16:45.556 really long time. 0:16:46.116 --> 0:16:47.996 I don't think that there's an exact moment. I think 0:16:47.996 --> 0:16:51.476 there's actually many moments along the way or a discovery 0:16:51.596 --> 0:16:54.516 like this, it's what do we have? How do we 0:16:54.556 --> 0:16:56.716 improve on that? Where could we get to? And I 0:16:56.716 --> 0:16:59.676 think the I will tell you the very first testing 0:16:59.716 --> 0:17:01.876 of lena caprier was not a six month injection. 0:17:02.516 --> 0:17:04.756 So over time, a lot of whiteboards, a lot of 0:17:04.796 --> 0:17:07.956 rooms full of people, you get to this idea of oh, 0:17:07.996 --> 0:17:10.436 we could do this as an injection that lasts four 0:17:10.436 --> 0:17:11.236 months and months. 0:17:11.516 --> 0:17:11.636 Right. 0:17:11.956 --> 0:17:12.156 Yeah. 0:17:12.396 --> 0:17:16.276 So there's two big sort of pivotal trials that you run, right, 0:17:16.276 --> 0:17:17.036 tell me about them. 0:17:17.316 --> 0:17:20.716 It's actually an entire program called Purpose And there are 0:17:20.756 --> 0:17:22.516 two trials, Purpose one in Purpose two. 0:17:23.156 --> 0:17:25.316 What's the acronym you say, Purpose? I got to ask 0:17:25.356 --> 0:17:25.996 you for the acronym. 0:17:26.076 --> 0:17:29.916 Oh, no, so the actually that acronym really is really complicated. 0:17:31.036 --> 0:17:36.636 It is not a clear pee you are, so, yeah, no, yeah, 0:17:36.636 --> 0:17:39.636 I don't make these up. But the trials are run 0:17:39.676 --> 0:17:44.796 across five continents, thousands of people, almost ten thousand people 0:17:44.796 --> 0:17:47.956 in total. And the two trials Purpose one and two 0:17:48.756 --> 0:17:53.596 were the trials that specifically are phase three pivotal trials 0:17:53.596 --> 0:17:55.596 for testing whether something is safe and effective. 0:17:56.956 --> 0:17:57.876 And what were the results? 0:17:58.836 --> 0:18:03.196 Yeah, so Purpose one is among Allison girls and young 0:18:03.236 --> 0:18:08.156 women in South Africa Uganda. It's almost five thousand people 0:18:08.196 --> 0:18:11.156 in the trial who were either taking the daily pill 0:18:11.316 --> 0:18:14.196 or taking the injection. And the among people who were 0:18:14.236 --> 0:18:17.476 assigned the injection, zero infections occurred for the primary d 0:18:17.516 --> 0:18:19.876 priant of the trial, which had never been seen before 0:18:19.916 --> 0:18:21.236 for an HIV prevention trial. 0:18:21.756 --> 0:18:26.036 So okay, so zero absolutely no. One of the two 0:18:26.116 --> 0:18:29.716 thousand or so people who got lenni kapavir, none of 0:18:29.756 --> 0:18:32.556 them got HIV in the control group. So they were 0:18:32.556 --> 0:18:36.956 taking in the control group of the anti retroviral pills 0:18:36.996 --> 0:18:40.596 that are standard. Now, how many of those people got HIV. 0:18:40.916 --> 0:18:44.276 For people who are getting the control pill, which is 0:18:44.516 --> 0:18:48.876 active prep, the approved active crap, sixteen out of about 0:18:48.916 --> 0:18:49.916 one thousand. 0:18:51.076 --> 0:18:53.036 So sixteen out of a thousand is kind of a lot. 0:18:53.196 --> 0:18:54.876 This is like over the course of what a year. 0:18:54.916 --> 0:18:58.996 Or something about a year a year follow and in 0:18:59.116 --> 0:19:02.956 almost all the cases of the sixteen it's because invested 0:19:03.036 --> 0:19:06.756 blood samples from those individuals they weren't using it, and 0:19:07.476 --> 0:19:11.196 a testament to for some people how challenging it can 0:19:11.276 --> 0:19:15.316 be to use something every day and how something that 0:19:15.756 --> 0:19:19.676 injection twice a year for many people both could be 0:19:19.716 --> 0:19:23.396 very effective, but also is something that they can make 0:19:23.436 --> 0:19:26.796 workable because you can set it and not think about. 0:19:26.556 --> 0:19:31.916 It, Okay, forget it. What's the other What was the 0:19:31.956 --> 0:19:33.796 result of the second pivotal trial. 0:19:34.196 --> 0:19:37.996 Yeah, the second pivotal trial was the more geographically diverse 0:19:38.556 --> 0:19:41.796 group and was men, transgender women, and men and gender 0:19:41.836 --> 0:19:45.716 non binary people in Asia, North and South America and Africa. 0:19:45.716 --> 0:19:50.116 It's really broad and global. Yes, And in that study, 0:19:50.276 --> 0:19:52.796 again among about two thousand people, there were only two 0:19:52.836 --> 0:19:58.676 infections that occurred compared to nine infections among about a 0:19:58.676 --> 0:20:02.916 thousand people who received the control so also quite a difference. 0:20:03.476 --> 0:20:07.076 Yes, I mean, presumably the larger audience or the larger 0:20:07.196 --> 0:20:09.676 patient population is the people who aren't taking oral prep 0:20:09.716 --> 0:20:13.316 at all. Precisely, and you can't randomize ethically to that. 0:20:13.516 --> 0:20:15.076 You can't have a control group where it's like we're 0:20:15.076 --> 0:20:16.556 not going to give them anything and we're going to 0:20:16.556 --> 0:20:18.756 see how they do. But in real life, that is 0:20:19.196 --> 0:20:21.876 probably the population you're looking for. 0:20:21.796 --> 0:20:22.476 Right exactly. 0:20:22.516 --> 0:20:26.756 So okay, congratulations on the successful outcome of the trials. 0:20:27.076 --> 0:20:27.796 Where are you now? 0:20:29.236 --> 0:20:32.716 Oh so you know, bigger mind we talked about before. 0:20:32.796 --> 0:20:35.756 You know, just because science can be the science may 0:20:35.796 --> 0:20:39.476 be fantastic, you may have a great publication or a 0:20:39.516 --> 0:20:41.836 great p value for science, it doesn't mean that people 0:20:41.876 --> 0:20:44.476 actually get medicine. And so the medicine when the cover 0:20:44.556 --> 0:20:48.796 has been submitted to regulatory agencies, because drug approvals. 0:20:48.276 --> 0:20:52.076 Are a necessary step for people to receive them, and 0:20:52.116 --> 0:20:57.636 that rigorous process is ongoing now and regulatory parentcies all 0:20:57.676 --> 0:20:58.356 around the world. 0:20:58.436 --> 0:21:01.796 From the beginning, the thought has been for loutic cover 0:21:01.876 --> 0:21:04.676 that's a medicine that can have a global impact, and 0:21:05.156 --> 0:21:10.236 then readying for being able to make it and distribute 0:21:10.236 --> 0:21:12.916 it for people all around the world. As we have 0:21:12.956 --> 0:21:15.396 been doing all of those steps, the dissemination of the science, 0:21:15.836 --> 0:21:21.116 the regulatory submissions, we've been simultaneously making plans for global 0:21:21.156 --> 0:21:23.996 access particularly access for low and lower middle income countries, 0:21:24.036 --> 0:21:26.276 and that part of the story is as important as 0:21:26.316 --> 0:21:30.996 everything else because success for ending HIV is it has 0:21:31.036 --> 0:21:32.116 to be a global success. 0:21:32.836 --> 0:21:35.236 Yeah, so let's talk about that. I mean, there's obviously 0:21:35.836 --> 0:21:41.436 an interesting history of getting HIV drugs to lower income 0:21:41.556 --> 0:21:44.476 countries that largely has been a success. Right, people don't 0:21:44.476 --> 0:21:47.356 talk about it that much anymore, but it's a good, 0:21:47.556 --> 0:21:52.556 happy story. Ultimately, what's happening with Lena kapavir that in 0:21:52.596 --> 0:21:54.876 that context, Yes, the the. 0:21:55.676 --> 0:21:57.716 You know, we talked back about my earlier history and 0:21:57.756 --> 0:22:00.476 I remember well when there were no medicines in lower 0:22:00.516 --> 0:22:03.876 middle income countries and then when there was, and that 0:22:04.476 --> 0:22:07.356 was a delay of years and years. And that's not 0:22:07.476 --> 0:22:10.956 unique to HIV. That is for innovations and health in general, 0:22:10.956 --> 0:22:14.156 that it can take years or decades for medicines to 0:22:14.236 --> 0:22:19.516 make it from when they're discovered to even approval and 0:22:19.556 --> 0:22:26.676 then availability in low income countries. For lenikapavier years ahead 0:22:26.716 --> 0:22:29.796 of results, truly years ahead before we had results. We 0:22:29.796 --> 0:22:34.876 were thinking about how we can compress that calendar, and 0:22:35.316 --> 0:22:40.316 that included within weeks of the Purpose trials reading out 0:22:40.716 --> 0:22:44.556 an announcement that we'd signed voluntary license agreements which are 0:22:44.676 --> 0:22:47.516 which allow a generic manufacturer to make a version of 0:22:47.556 --> 0:22:50.836 the medicine. So would volntarize de agreees with six generic 0:22:50.876 --> 0:22:56.356