Ep. 7 - 26MAY2020 

Simone Fishburn: Hello and welcome to another edition of BioCentury This Week I'm Simone Fishburn, editor-in-chief of BioCentury and I'm joined today by my colleagues. 

[00:00:10] Steve Usdin: Steve Usdin, Washington editor, BioCentury  

[00:00:14] Lauren Martz: Lauren Martz, senior editor of BioCentury, and I head up translation and clinical development.  

[00:00:19]Simone Fishburn: Well, we had another busy week in COVID-19 last week, but we are actually also starting to see some stories beyond that, especially with ASCO coming this week. 

[00:00:28] So we'll be discussing both areas, in today's podcast. Now, the thread that I think I see coming is that we're sort of entering a new phase, might be a long one in various areas. Steve, I want to talk about shuffling at the top of FDA. And the reason I think this is a new phase, you know, on this front is that FDA and or the government, rather, the White House, it's put in place Operation Warp Speed. 

[00:00:55] It's now trying to figure out how to manage this, how to do that, and do the FDA's day job. So maybe you can tell me how you think about what's going on.  

[00:01:06]Steve Usdin: So the two things that happened at FDA last week, that are really interesting. First, Janet Woodcock, the director of the Center for Drug Evaluation and Research, who for many people, I'm sure for many people who are listening, she is the FDA. 

[00:01:20]She has stepped away temporarily from her position as director of the Center for Drugs, and she's taken on the role of being the lead of therapeutics in Operation Warp Speed. That's the administration's, initiative to accelerate the development of diagnostics, drugs, and therapeutics for COVID-19. 

[00:01:41] And on the face of it, it's really hard to imagine anybody, in government, who would be better qualified to do that than Janet Woodcock. She understands drug development. She's been an advocate for master protocols, since before anybody knew what a master protocol was. And she understands the timelines that are involved in drug development and what's involved in manufacturing. 

[00:02:03] And she's also had experience doing this before she's stepped away from running CDER before and taking on different kind of challenges, and then, gone back to CDER.  

[00:02:12] Simone Fishburn: So, Steve, I don't know if you can answer whether she had a choice in this or not, but how do you think drug developers are gonna look at this if you're outside of COVID-19 is not having Janet Woodcock at the top of CDER, you know, a negative thing? 

[00:02:27] Steve Usdin: I don't think so. I think that people tend to personalize regulatory decisions, in the face of whoever's running CDER or whoever's running the FDA, and they get the credit or they get the blame for what's happening. But the reality is that, I think 90% of the decisions that affect companies that are developing drugs happen at a lower level. 

[00:02:49]Somebody like Janet Woodcock, is involved in setting the broad policies, which are really important, but I'm not sure that they're so important right now because I don't think there's a lot of policy development going on outside of COVID-19. And then they're are involved when something goes wrong, when there's a big controversy, then she would jump in. 

[00:03:06] But for most of what's happening. No, I don't think it's going to make much of a difference.  

[00:03:10] Simone Fishburn: Now what about Peter Marks going back in the other direction?  

[00:03:14] Steve Usdin: Well, that's an interesting one also. So Peter Marks, who's the head of the Center for Biologics Evaluation and Research had been involved for two months, at least behind the scenes, kind of semi secretly, in helping the government figure out how to ramp up vaccine development. And he was actually involved in creating Operation Warp Speed. I hope he wasn't involved in picking the name, which is abysmal, but anyway, the rest of it, you know, he was involved in that. And then he was named to head, the vaccine initiative within Operation Warp Speed when it was announced. 

[00:03:49] The thing about it is that, Operation Warp Speed already has an embarrassment of riches of vaccine expertise, of scientific expertise in vaccine development. Moncef Slaoui, who's heading Operation Warp Speed is a veteran of GSKs vaccine development projects. They've got someone who's, who's less well known, but no less, competent, named Matt Hepburn, who's been at DOD. The Department of Defense researching, and handling, logistics on vaccine and pandemic research for about 25 years. He was supposed to be the kind of co-head of vaccines and Peter Marks was going to be head of vaccines. In any case, I think the decision was made that Peter Marks could do more good by going back to the FDA and working on the regulatory issues, which are going to be quite thorny on vaccine development and leaving Moncef Slaoui and Matt Hepburn to run the vaccines part of Operation Warp Speed because there's a sense and I think that they hadn't really, the administration hadn't really thought this through in advance that you can't have the same person working on developing a therapeutic or developing a vaccine and then take that hat off and put another hat on and go back to FDA and be regulating it. There has to be some distance between those two roles.  

[00:05:09] Simone Fishburn: So, one of the other reasons I think that there's this thread of the beginning of the next phase is that companies are clearly starting to put into place practices for going back to work. Our colleague Amanda Micklus, senior biopharma analyst, did a survey for us last week, of biotechs. And I thought one of the really interesting things was that very, very few of them, 16% of them are actually requiring a negative virus test. 8% most of those actually overlap requiring a positive antibody test.  

[00:05:42] And, so people aren't really waiting for testing and among the reasons that they gave for that was that there's just too little known about the viral load or the antibody levels. There's not really a widely available one and people can't wait for it. One thing that was interesting was that 87% said that they wanted people to be symptom free before they went back, which of course raises the question about the other 13%, were they okay with people with symptoms going? So I'm not really sure about that. So, I think it does raise this whole critical question as I said, I think it is going to be a long way, but. We're starting to get vaccine data. Clearly people can't wait for vaccine to go back to work. I mean, that's been this dogma that's been put out by various governments actually, that we can't get back to normal until there's a vaccine. 

[00:06:33] But we're also now starting to see that actually it may not be that black and white. Lauren, our colleague, Selina Koch, executive editor, she did a story on Friday that really summarized the clinical data that we're starting, some of it's clinical actually and some of it sort of late preclinical. So monkey, preclinical, data. And I think what it really shows is how hard this is to compare it. I don't know if you've got comments, Lauren, on that.  

[00:06:58] Lauren Martz: Yeah, I think this is, this is just the tip of the iceberg for the vaccines data, and I think at this point it's going to be very hard to compare because we just don't have the information yet, we're getting these data on the antibody titers that are being produced by these vaccines, and there's just no way to really interpret that now. We know the level that the FDA wants to see for convalescent plasma, but then you have to take into account the differences between treating a virus that has a huge viral load and then preventing the virus. 

[00:07:31] So we just really don't know at this point what these data mean. And I think that's something that we'll start to learn a lot more. This is just one of the many things we'll keep learning about it as we understand the immune response to the virus going forward.  

[00:07:48] Steve Usdin: I think the other thing that we're going to learn and it's going to happen is that different vaccines are going to have different characteristics, and it's quite likely that some, and maybe all of the vaccines are not going to be a hundred percent effective in preventing the infection. 

[00:08:06] And it may be that we're going to have to live with something that's just, that, not just, but that, that reduces the severity of the symptoms that, reduces the number of people that go to the hospital. And then for the people that go to the hospital, it means that more of them survive. And that's going to unambiguously be a good thing. 

[00:08:23] But getting back to what you said, Simone, though, it isn't like flipping a light switch and you can say, okay, we've gone back to our lives before anybody had ever heard of COVID-19.  

[00:08:33] Simone Fishburn: I mean, I think that's important because frankly, I think most of us would say, you've got something as good as the flu vaccine, let's take it. It's better than nothing. And I think, you know, that's an important thing to convey, Steve, you've written about the importance of communication, of communicating and building trust. What we really don't want is, I think I'll let you say this yourself, we really don't want a backlash against it as not being perfect and people not taking it.  

[00:09:00] Steve Usdin: Yeah, the thing that I think that's really important along those lines is, for people to be educated and to have an understanding of what they can expect. So we don't get in a situation where we have response, like many people have to the flu vaccine where they say, Oh, well it's 50% effective it's 60% effective, and they say, well, what's the point then? It's just like flipping a coin and I'm not going to do it. That would be a tragic response, especially to something that's going to prevent people from dying. And I think that. Even more broadly, what's really needed is some people to take the bull by the horns or some organization to take the bull by the horns of educating the American people and people around the world and trying to develop understanding of what vaccines are likely to be able to do, what they're not likely to be able to do, and to build up that trust.  

[00:09:51] Because, if there isn't that trust, if you have a vaccine and nobody takes it or not very many people take it, then what was the point of all of this in the first place, it's not gonna work. So I think that's a terribly important thing, and I don't think that there's anybody who's, or any organization or entity that stepped forward and said and raised their hand and said, yeah, I'm going to be the one who's going to try to create that education and that trust.  

[00:10:18]Simone Fishburn: That's a good point, I think we'll continue to follow that. I want to switch to talking about ASCO, but I'm going to stay with this theme, of the beginning of a new phase. And I think it's particularly important with checkpoints, which are checkpoint inhibitors, PD1, of course being the most famous, although that came on the heels of CTLA-4. 

[00:10:38]Lauren, you wrote about this last week. Is this the dawning of the next generation of checkpoints?  

[00:10:46] Lauren Martz: I think it's possible, companies have been looking for this next checkpoint target since before PD1 was even around, I think I spoke with a company called CoStim, which was acquired by Novartis, like seven years ago, and they were trying to find this. 

[00:11:02] And what has happened with Genentech has done with TIGIT now is give us the first example of a checkpoint since PD1 and PDL1 that has produced results in a randomized placebo-controlled phase two trial, and that's something that just hasn't happened with the other checkpoint, the newer checkpoint targets to this point. 

[00:11:24] Simone Fishburn: Well, let me ask you, I mean, is it just that they designed the trial better, it takes time and we should expect to see a flood? Or is it gonna take another seven years before another checkpoint.  

[00:11:37] Lauren Martz: I don't know the answer to that. I think that they've done the right trial. It also might be a function of the target that they've chosen TIGIT has a couple of different anti-tumor mechanisms in it. But there are some other promising checkpoint targets that we just haven't seen this type of data from yet.  

[00:11:56] Simone Fishburn: Yeah. I mean, one of the things that you did write about is that this works by two different mechanisms, right? That we wrote about last week is that this target involves, maybe you can sort of elaborate more that it, it involves two different, ways of, of relieving the antitumor immunity. 

[00:12:12] Lauren Martz: Yeah, so we know that it's working by two different ways. I think that these checkpoint targets are all very complicated, and I think that we're probably going to learn that a lot of them work in different ways.  

[00:12:23]Simone Fishburn: Well. What about, you know, the other thing we're starting to see now, there's been a lot of talk about CAR-T cells over the last few years, but one of the things that you said is coming out at ASCO is bi-specifics now competing with CAR-T cells. 

[00:12:38]What does that look like? How are they competing? I mean, presumably, if they're equally efficacious, they would win. But is that necessarily true?  

[00:12:48] Lauren Martz: And it's always hard to compare across trials, but based on the data that we have, bi-specifics might not necessarily be as effective as CAR-T's, but they're all trying to accomplish the same goal of bringing the effector immune cells to the cancer cells to destroy them. 

[00:13:05] And you know, bi-specifics, they just have manufacturing benefits. They're easy to administer all of those things over CAR-T. So I think we'll start to learn when these, when everything gets to the market, where they each have their role.  

[00:13:21]Steve Usdin: Would you imagine that you would have a kind of fail first situation where, you know, patients would go on a bi-specific and hopefully that creates a kind of functional cure for them. 

[00:13:32] And if it doesn't, then they might, proceed from that to a CAR-T. And if that's the case, then whether it be implications for the pricing because they're both presumably going to be really expensive, you have to pile one on top of the other. That's going to be really rough.  

[00:13:45] Lauren Martz: Yeah. I'm not sure what that means for pricing, but I think that's exactly how some of these companies developing them are, are envisioning the landscape sorting out. 

[00:13:55] Simone Fishburn: So I want to just end with one last thing that you talked about that is coming out at ASCO, you talked a lot about myeloid cells. I think we've heard about those, we're starting to see data on those and then an saRNA, so it seems like every week there's a new kind of RNA. So there's an saRNA in the clinic. 

[00:14:13] Tell us about that. And, how did that creep up on us?  

[00:14:17] Lauren Martz: Sure. So saRNA is small activating RNA. So the idea here is that instead of knocking down a section of RNA to stop that gene expression, you're actually increasing expression of a certain target gene. I don't think this was the first time that we saw data for this particular product, but this therapy from MiNA Therapeutics is the first to come into the clinic. So it's just one example of these platform technologies that we've been following for the last decade or so as they've been developing, sort of coming of age and finally translating into the clinic. We'll likely see a lot of this type of data come out over the next few years. 

[00:14:57] Simone Fishburn: Well, I think that's about it for this week. I want to thank you both for joining today. Lots of things, I expect will come out this coming week. BioCentury's podcasts, webinars, and all our written content is available at biocentury.com. Our Coronavirus coverage, including an information center with a new tracker of clinical trials, which is interactive in addition to therapeutics and vaccines, diagnostics is available at bioCentury.com/coronavirus and our podcasts are available via Google, Spotify, Apple podcasts, and Stitcher.