In real time to figure out what you're asking and be able to ask those in the end of the prepared remarks and the questions we have set for this call. I also want to thank Arvind and the IR team at Amgen for setting up this call so quickly after the call. I know we've already passed April 1, which probably created a bunch of head hook internally with the legal guy. And thank you for working through this and making this happen. So with that, I'm going to pass it over to David for some introductory remarks.
David?
Thank you, Ronny, and thanks, everyone, for getting together. Good morning. As we all know, we're in the middle of an unprecedented crisis, the biggest public health challenge in a century, certainly the biggest public health challenge that any of us have seen in our lifetimes. And we felt we being Adaptive and Amgen that given our technologies and given our existing relationship that this was an opportunity to see what we could contribute in the battle against COVID-nineteen. We have an ongoing collaboration for minimal residual disease in hematologic malignancies and it was really based on that scientific interchange and the knowledge that the companies had one another that led to a rapid series of discussions and the launch of this collaboration.
The intent here is really to marry the technologies of both organizations. So adaptive world class expertise in immune profiling. Of course, we'll go through that in much more detail in the course of the call with Amgen's expertise in genetics, immunology and then antibody engineering and manufacturing. We are focused on making progress as quickly as possible. We are trying to strike the right balance between getting the highest quality antibody or antibodies as therapeutic candidates with the shortest timeline that we can.
We will take advantage of frequent interactions with regulatory authorities. The FDA has been quite open about offering frequent touch points and certainly we will take advantage of that as we move through the development program. In addition, many of you have questions around scale up and manufacturing. And of course, we will be working on plans as we move along to ensure an appropriate supply of the therapeutic should it prove efficacious, while maintaining the supply on the Amgen side of our other protein and antibody therapeutics. We all know, but it bears repeating that cancer and heart disease don't go on vacation during an epidemic.
And of course, we're committed to maintaining supply of other vital medicines as well. We see these efforts as complementary to some of the other efforts that are going on in the industry. We really don't view this as a competition, but as an all hands on deck moment, where everyone is going to bend their efforts and expertise to coming up with an effective therapeutic. And with that, what I'd like to do is invite Harlan to make a few remarks on his side and then we'll open up the question part of the webinar.
Thanks, David. Good morning, everyone. My name is Harlan Robbins. I'm the Co Chief Scientific Officer of Adaptive Biotechnologies. Thank you for your time today.
We are looking forward to providing more insights into our partnership with Amgen to identify and develop neutralizing antibodies to COVID-nineteen. Adaptive is built on the premise that the Adaptive immune system is nature's most finely tuned diagnostic and therapeutic for most diseases. To translate these natural abilities of the Adaptive immune system into clinical products, we spent the past decade building a proprietary immune medicine platform that allows us to characterize key immune cells with scale, precision and speed to transform the way we detect and treat disease. Now, we are well poised to apply our platform to discover both diagnostics and therapeutic solutions to COVID-nineteen pandemic. On the diagnostic side, we are extending our partnership with Microsoft to decode the immune system's response to COVID-nineteen to complement diagnostic efforts that are focused on the virus itself.
On the therapeutic side, we are adding a new dimension to a multiyear working relationship with Amgen that David just mentioned to leverage our platform to identify neutralizing antibody candidates from the blood of patients who are actively fighting or have recently recovered from COVID-nineteen. The key to neutralizing antibodies is they have to be able to work alone or in small groups, meaning that they have to do the job of what normally hundreds of antibodies do in a typical immune response in the blood. This approach has been shown to be efficacious in some settings such as Ebola and is promising for SARS CoV-two, particularly because it is a slowly mutating virus. However, to find the truly effective antibody or what we like to say the Michael Jordan of antibodies is quite difficult. The search has to include the ability to scout every single high school basketball player in the entire country at the same time.
This is what Adaptive's platform is built to do. And together with Amgen, who is a world leader in antibody development, we see COVID-nineteen as a long term problem unfortunately, and there will be patients in need around the world for the foreseeable future. We are committed to applying our resources and expertise to help discover solutions. And on a personal note, Amgen is really a pleasure to work with and their scientists are quite extraordinary. So, we think together we'll be able to really progress in this effort.
So, thanks and I'll turn it back over to Ronny for questions.
Thanks, Alan. So before we attack the therapeutic chat yesterday as we kind of prepared for this call, we talked a little bit about the diagnostic approach, which looks really interesting. So can you just take us quickly for what you're trying to do there and the kind of insight that we potentially end up drawing from your ability to analyze kind of the progress and the variation between individuals' immune systems response to COVID-nineteen?
Yes. So, our diagnostic approach is primarily focused on the T cell response, not the B cell response. And it's basically co opting the same machinery, both technologically as well as including the software and machine learning that we've developed with Microsoft to be able to identify the specific T cell receptors, the part of the adaptive immune system that's focused directly on the disease and identify it for on a patient by patient level. And so basically what we're doing is trying to identify what each patient's immune response will look like and to answer a whole variety of questions. 1st, we think the immune response comes up the T cell response comes up quite quickly.
So it should be a very good early detection strategy. 2nd, the scale of your immune response, whether or not you have a really robust T cell response versus not, has a strong chance of being predictive of who's going to do well and who's going to have serious conditions in response to the virus. So it could be a way of determining who needs serious care and who doesn't. And then because you have immunological memory, it will persist and you will be able to assess later who actually had the virus and who didn't, the whole getting back to work campaign, etcetera. And it will hopefully be a complement to serology.
We don't yet know who's going to seroconvert. There's some evidence coming out that maybe certain patients who do particularly well, maybe even asymptomatic, don't even develop a neutralizing sorry, don't even develop an antibody response. So, serology might not pick those people up, but we think the T cell response might be able to cover at least some of those. So, that's what we're doing on the T cell side.
And the other thing that we kind of mentioned is this idea of looking at patients over time and being able to potentially predict how long the ability of the body to come to counter an immune response on the second exposure is. This goes to the question of it goes to the question of what's the length of immunity people have once they're exposed to the virus?
Yes. I mean, I think this is a super important question. And obviously, we don't know the answer yet. It ranges people's the length that a person is immune after being infected with a virus can range from lifetime immunity to a few months. So what's the answer for COVID-nineteen?
And so we will be assessing this as well. The idea would be that how long do your antibodies stay in your system and figuring out exactly what the level is to convey immunity is going to be challenging. But we can because we're going to be sequencing a huge array of of B cell receptors or antibodies from each person as part of our partnership with Amgen, we will also our IRB allows us to monitor these people over time, so we can continue to sequence their repertoires and see if they're maintaining the cells producing these antibodies over time or not. Okay.
It's a challenging question though. So switching over, it's almost like a perfect segue to the next question, Harlan, which is we are already having folks bringing convalescentera up and beginning to use it. What are the strengths of this approach and what are the
plasma from a patient that's the plasma from a patient that's recently recovered from COVID-nineteen, they have a whole set of antibodies that that person's immune systems develop to be in theory efficacious against the virus. And so what happens is that there's large efforts across the world where people are extracting large doses of Sarah from patients. It seems to be working and I think it's a great strategy. The negatives are that it's not really scalable. You only get maybe enough for 1 or 2 patients out of from each person that you get their plasma, you might get enough for 1 or 2 doses to different patients.
So you could imagine that's not a very scalable situation. And there's also obviously a lack of quality control because you could imagine that sometimes that Sarah is great and other times not so much and there's no real way to assess that. So there's some so there's I mean, I think this effort is great and will be useful to people and probably save many people's lives. On the other hand, it's not really a scalable solution that can be administered
worldwide. So, what is the neutralizing antibody approach at?
Yes. So, the neutralizing antibody approach, in this case, instead of looking for an anti this whole collection of antibodies, we're trying to find 1 or a handful of antibodies can kind of do the job of what the entire Cera could do by itself. And in order to do this, we have to find, as I mentioned earlier, truly find this special, Michael Jordan of antibodies where they have the capability of doing it by itself. This allows this to be scalable because Amgen can then produce develop and produce this therapy at scale and then we can administer it much more broadly.
Okay. So now talking to both of you. So as you kind of screen through the past experience we had with the antibody approach, They seem to be effective in various condition. We obviously have RSV therapy. There was clearly some success with Ebola.
Merz, though, never make it through. And in all of those cases, they were perfect. That is, it didn't just abrogate the disease. Can you talk a little bit about the past experience, what we learned from them and where are we going to improve as a science world this time around on those antibodies?
Sure. I'll start and then pass to Dave. So as you mentioned, there's been some success in the past with Ebola, RSV, even HIV. But there's been a couple of limitations. One is that these viruses are small RNA viruses that mutate quickly.
So we would expect that there is you're kind of trying to hit a moving target. So it's going to be a challenge to find really good neutralizing antibodies against those viruses. And in particular, the virus that the antibodies that have been found seem like they are able to neutralize, but probably aren't the superstars, aren't the very vast neutralizing antibodies, mostly because we haven't probably had as much effort as we're putting into COVID-nineteen across the world to find that. And so that's both hopeful and I consider that quite hopeful. We're getting some clinical efficacy even without necessarily the optimal neutralizing antibodies.
So just imagine how good we can be with a really good neutralizing antibody, especially against SARS CoV-two, which mutates at a much, much slower rate than these small RNA viruses, HIV and influenza, etcetera.
What I might add, Ronny, is that one of the things we clearly learned and I would say especially from the Ebola experience is that the time point at which you intervene has a huge effect on outcome. So administering the therapy earlier in the course of the disease gives it a much greater shot of efficacy as opposed to the very, very late stages of the disease and that will inform how we think about the administration of an antibody based therapeutic going forward. And there are a number of clinical settings where one can imagine it from patients who are very seriously ill to those who are earlier in the course of disease, for example, moderately to seriously ill, but not yet requiring ventilator support. Can you prevent them from traversing to that more serious clinical scenario? And then finally, potentially in the prophylaxis setting, Can you in fact prevent infection?
And this might be quite important as the epidemic evolves. And I think we're taking the view, as Harlan alluded, that this may be a 2 to 3 year event barring a vaccine intervention sometime earlier than that. And what that means is that there would be a clear role for prophylaxis. So one could imagine, for example, administering prophylaxis to healthcare workers in areas that are a hotspot, where an outbreak is developing to really try to protect frontline healthcare workers. So we're certainly thinking about a range of clinical spectrums, but but the experience that we have from other antibody therapies against viruses is that generally the earlier you go, the more effect
it. Got it. Alan, you mentioned a couple of times this issue that this virus is more of a slowing mutating virus. Talking to virologists, that at least the point we got was not as clear. So the question was whether the virus is a slowing mutating virus or simply a virus that did not have a lot of pressure on it from therapies and because the infectivity depend on the upper respiratory tract, even if there is more effect of their body's immune system in the lower alveoli, you are still infectious on the basic virus.
So the virus that move from patient to patient is the same, and thus you're not seeing a lot of mutations. But once you start applying drugs against that virus, you will see the virus mutating a lot faster. In your mind, do we have clarity on this question or is it still unknown?
I think it's clear that it mutates much slower. You can look within a person. So if you look within a person, even within that person, if you sequence influenza strain the influenza genomes or the HIV genomes, you get this huge diversity, whereas in this virus for SARS CoV-two, you get much, much less diversity. So it's and there's a good reason for this. The genome of SARS CoV-two actually carries a gene that corrects mutations.
The polymerase. Yes.
So it's it actually we know that it doesn't mutate at the same rate or it's almost close to 1,000 times less than the other genome. Does it meet it's still an RNA virus, it still will mutate. We've seen their different strains, but it's just vastly less than like HIV or influenza. So, what will happen when we put true selection pressure on it? I don't think we really know the answer, but looking with any individual people and knowing that everybody's immune system is actually putting that pressure on and seeing that there isn't huge variation is a very good sign.
So one of the options
sorry, I would add Ronnie that one of the things we're doing with gecogenetics, which is of course is participating in this collaboration as part of Amgen is actually generating a catalog of viral mutations along with all of the publicly available. There's an extensive molecular epidemiology study that Kari Stefansson and his team are conducting in Iceland. We hope that the first publication from that should be out very, very shortly. And that will inform some of our thinking as we move along here as well.
Okay. One of the arguments here, the one of the questions is I should go with a single monoclonal antibody or multiple ones. And the issue of how do you one of the advantages of monoclonal antibodies is that you attack every piece of the virus, here you'll be attacking a very specific epitope. How do you avoid this idea of the virus mutating away from you upon applying the pressure?
Well, I can start. I think there's 2 issues that are relevant. One is since we do have as David was saying from groups like DECODE, we have some information about what the different streams look like. So being able to show that you can find an antibody that's neutralizing against the different known strains of the virus, If it can neutralize a variety of strains, that's a good sign that whatever the virus is capable of mutating probably isn't away from this from that neutralizing antibody. But that there's no reason why we have to limit to 1, if we can and we've vetted this with the Amgen team yesterday basically is what's the capacity to handle a cocktail of 2 or 3 where we would avoid this problem even if there was escape.
So I can pass over to David to Amgen's perspective.
Yes. And that's certainly been part of our thinking from the beginning here, Ronnie, that while we would love to have a single antibody, it's possible that a tail of a handful or a little less will be required. And so as we move along, we're making plans to be able to handle that. The other question is, while of course most antibodies everyone anticipates will be directed against the spike protein. We are of course going to look at membrane envelope and that may the selection pressures may vary among those different targets.
And so these are things also that the decode work and the work that will go forward as part of this collaboration will inform.
Got it. How well were you able to come
up with antibodies that are likely to be fairly resistant to mutation by the virus? How well can you say identify sites which looks like they're pretty well conserved between coronavirus mutants? Or how well can you identify sites where it looks like if the virus were to mutate a way that would have significant implications for I guess viral fitness?
I mean, we need to let Viral Genetics tell us that answer. So this is just comparative genomics. We just line up all the viral sequences and ask where the assumption is the immune system inherently puts pressure on certain areas and the areas that don't mutate either one of two reasons there. But most likely those are the regions that can't mutate, they're needed for function of the virus. And so those are the areas that we would focus on.
But we also don't want to go into this with the assumption that we're that good at this. So we'd like to let the immune system tell us what the neutralizing antibodies are. So we plan to do a quite wide search without making too many assumptions externally about what the immune system latches onto to neutralize the antibody and hopefully screen very, very widely and let the immune system tell us what truly is neutralizing.
Is is going to be one that the virus can't really tolerate. And one can make pretty simple and basic predictions like that. But as Harlan indicated, we're really taking the approach here. We're going to let the rapidly emerging data that we're generating teach us as we go along. It's to sort of be our own adaptive immune response in a sense.
So coming back just to this issue of kind of the program that you have, I guess, Helen, you already mentioned that the differences between the antibodies is actually going to be critical in our success. If you kind of have to look at the kind of affinities or the kind of selection you guys are able to do versus previous efforts by other companies before your technology came around. I mean, how much better is it? Are we talking here about something will be 30% better or something where you can see the differences in terms of the antibody effectiveness being 1 in a 100 kind of thing, 100 times better than all the historical efforts in the space. I'm sure we have some experience from the cancer world and so forth.
So we expect to be able to screen a set of antibodies that's probably an order of magnitude or maybe 2 orders of magnitude larger pool. So how far that gets us in terms of
That is shocking.
Let's just say all the ability to neutralize comes on some kind of bell curve. And the more you can sample, the more likely you are to get farther out and get the super the really special one. But whether that really special one is twice as good or 20% better or 5 times better, I don't think we know the answer to that yet. But certainly, we're hoping that being able to search vastly more will get us to that needle in the hay, like the really special one, we'll be able to find it more likely. So David, that's important.
So David,
that's important. Even modest improvements may have a substantial may translate to a substantial effect in the clinic. So you may not need a log better antibody to actually have something 20% better may actually pull through to fairly substantive effect in the clinic.
So following up of that, so this is the kind of generating the leads. How much are the assays that we'll be able to tell you in vitro how likely the antigen is going to work in vivo? It feels like before this epidemic, we did not really invest that much in trying to correlate the efficacy of or the value of certain assays to the in vivo setup. Can you just talk a little bit about can we actually pick the right clone or are we just going to have a lot of clones and the selection process is going to throw everybody down?
So, a lot of the technology has been built up over the last decade, even though I don't think it ended up getting applied in the same way as it will in this case because the areas where we thought past pandemics were going to materialize, they didn't really ever get going in that way. So the initial SARS, even Ebola, which was a big scare a few years ago, it just never spread in the way that this is spreading. So I think there is some pretty nice technology that's been built up for screening. So I think we're going to do vastly better than in the past. Is it going to be perfect?
I'm sure not. It's going to be certainly vastly better in the past. I think we'll be able to narrow down quite effectively to a small set where we can then take into sort of truly live neutralizing the assays.
Yes. And I would add that in addition, animal models are coming up quickly. A number of groups are working on this and we believe that improvements in animal models will become available over the course of this project and of course we will make appropriate use of them.
Very good. So David, you obviously have the capacity for large company behind you. I guess the question is, can you just take us through the logic of how much do you think would be needed in terms of antibody manufactured and for each one of the potential use cases and what can Amgen do in that respect if you actually had the right clone selected and the right product?
Yes. So we want to be very careful to ensure that we can provide drug supply. You're hitting on an important point. We have the ability to scale relatively quickly. How much we will need is of course going to depend on the characteristics of the therapeutic itself.
What's the IC90? What is the biodistribution? Meaning what sort of dose do you need to really penetrate say mucosal surfaces? And other standard, the pharmacokinetics and pharmacodynamics of the antibody. Those are critical technical features.
I think the good news here is that we anticipate that you're only going to need a dose or 2, because it's really certainly in the treatment setting, you're going to need coverage for a couple of weeks in all likelihood. So we think 1 or 2 doses over a few week period should be sufficient. And we and others have done calculations. I'm sure you've seen them out there that the if we can get away with say something like a 10 milligram per kilogram dose that is feasible and something that you can handle. Obviously, as we select candidates and start to model what that dosing will look like, we'll have to think about production and capacity.
So, yes, so I'm going to push you on that one more David, which is okay, you get 10 gig per kg dose. You can figure out how much a person weighs. You can figure out what you have in terms of capacity. Roughly how many patient doses you would be able to provide assuming you got the right product with the right affinity and attending per kid, call it in the end of Q1 of 2021? I mean, if you're looking a year out, how much can you make?
Yes. I don't know that I want to give precise answer to that right now because of course we're mapping. I would say ballpark, we would be committed to trying to serve as much patient need as possible. It's very hard, I would say, at this early stage to give you a precise number of doses without understanding some of these parameters that we're talking about. Yes,
dollars 1,000,000, dollars 10,000,000, dollars 100,000,000 what are we talking about?
So, I can tell you that our thinking is what if we had to be able to administer tens of millions of doses, how would we do that? Now am I promising anything? Of course not, and I don't think anyone in the industry is, but we're not thinking that this is 10,000 doses,
if it's effective. So everything's got to work. You're not committing to success, obviously. But if you think about the product picture you're looking for, tens of millions is what Amgen will attempt. The direction is if things work properly, this is what we should be trying to achieve.
I would say that is the scale of our thinking now. Imagine a world where you had to provide that, can we get line of sight to doing it? Sure.
So this brings us to the next question. Is this essentially just a bridge to a vaccine? Or are you guys thinking based of our current understanding of the virus and the infection cycle that this antibody approach will be a viable approach or would be needed clinically for the foreseeable future beyond the 1st few years, which is roughly the rise when we probably start seeing vaccines coming through. How long would you take that one? So,
hopefully, we will have a great vaccine. It's hard to imagine that the 1st generation, especially with some of the really exciting, but sort of yet to be proven sort of RNA based vaccines, which are likely to hit first. I hope they have efficacy. I think there's a good chance they will, but I don't know that they're going to be truly protective across a broad swath of people. So I think there's going to be, for 2 issues.
1, I think it's going to take a while to get a vaccine that's like broadly works and then administering it across the whole world, which is now what the scale we need to be is also going to take a while even if it was a perfect vaccine. So I don't mean to be super pessimistic, but it's hard to imagine that we're eradicating this in less than a decade scale, not even with the development, David might have a different perspective, but sorry.
Yes. I mean, I would say, barring a vaccine, eventually, the likelihood based on everything we know about coronaviruses is that this will at some point transition from being epidemic or pandemic to endemic, meaning there would be ongoing need for a therapeutic over potentially a many years time horizon. Until such time, if there is long lasting immunity, you've infected a large chunk of people on earth. And so that again, as Harlan indicated, fits in the years, not months timeframe.
All right. Let's stop social distancing. It will be less than that. Otherwise, I'm going to personally consume most of the alcohol production in California. So moving just following up a little bit on this issue of pandemic becoming endemic.
It feels like an IV is a great product, but if we're going to try to move this away from just being a one time, let's give everybody an IV and eradicate the disease, but something more endemic, it seems like you might need this to be a subcutaneous injection or something that is much more accessible than IVR, just 100 of millions of IVs being administered on a semi regular basis, feels like technically very hard. Is this part of the development plan to take this to subcu or is this something that will stay at least in the 1st generation as an IV?
Yes, maybe I'll handle that. Certainly in the 1st generation IV and one thing that I think is an important consideration here in a therapeutic setting, meaning in the setting of an infection, one of the things that you're very likely to want is to get as high a Cmax as you can obtain to ensure biodistribution and penetration into target tissues. And so clearly, the intravenous approach would be preferred for that. I would also say that if this becomes an ongoing process and you say, hey, do you need over time 100 of millions of doses, the thing to remember is you don't need them all at once. That's spread out over some long period of time.
And what we would envision is a world where you have hotspots coming up and going down potentially, like a game of whack a mole. And the so then you see you would be targeting 2 discrete populations in a city or a region, for instance. And so in that way, the demand is not going to be all at once like we're facing now in a pandemic situation. And that makes it much more manageable.
Which kind of brings us to the question of, if you're going to go for prophy setting, it kind of makes sense hypothetically at least to go for a product will have higher than the natural life of a normal antibody, so try to move away from a biweekly or monthly infusion to something that is every 3 months or 6 months. Is that kind of in your features of the 1st generation product, are we thinking about an administration every 3 months or are we going on with native antibodies and a more of a shorter period of administration?
I would think the 1st generation certainly to try to get to the clinic as quickly as possible, one would envision a shorter infusion treatment cycle, if we want to call it that. We are thinking about some of the standard mutations you can make in the Fc domain and other standard engineering techniques that we apply to increase half life and that may change the efficacy profile somewhat. Obviously, we're going to be looking at that intensely as we go along. But I don't think the initial goal would be to say, hey, let's get a Q3 monthly Vincent
come in with a couple Vincent come in with a couple of questions, if he's down. But first, everybody seems to be developing IgG. I think you guys are the same. You talked to virologists to discuss IgA or maybe IgM as a preferred antibody type in terms of penetrating the lung epithelium. Can you talk a little bit about is this feasible?
Is it feasible at scale? Is it something you're looking at? Is IgG going to be good enough to prevent infectivity, not just prevent people from getting sicker by giving a dose IV?
Sure. So one of the advantages I think the virologists have here is they've never tried to produce metric tons of a product. So it's a little easier to speculate. There are reasons that the industry over 40 years has gravitated towards IgG. It's got the most favorable half life of the isotypes.
But then I think critically, IgA is essentially a dimer of dimers. And of course, IGM is pentamer or hexamer of dimers. They are much more complicated to produce at scale for a variety of technical reasons and simple things such as the glycosylation patterns start to become quite complex in IgA and IgM molecules, meaning that the process development and formulation are more challenging. Are they impossible? Requires a much longer timeline.
I think that we as an industry will get there towards making these sorts of antibodies, but the timeline that we're shooting for here, I think really leads us towards
IgG. So percentage exposure in the blood versus exposure in the lung epithelium, I mean, how much lower is the exposure in the lung epithelium? Is it 1 10th, 1%, 10ths of a percent? I mean, how much can you actually get in there?
I think that's what we're trying to we're going to be trying to understand, and there are a number of many groups around the world looking at that question right now. It's important to remember that the biodistribution into normal lung is likely to be very different tissue injury, a leaky vasculature, which may actually of tissue injury, a leaky vasculature, which may actually help promote biodistribution. So this is an important point and one that we're going to be taking a look at with our collaborators.
Okay. And last one, Vincent, before I proceed with Vincent, Vincent, let me just chug with one more. And it's the risk of antibody dependent enhancement. I mean, it was discussed in previous models, some of the physicians are quite concerned, some are not. Can you just give us your perspective of the risk of this with the monoclonal antibody approach?
Yes. I mean, I think a lot of folks here extrapolate from the experience with dengue, where there are 4 basically 4 flavors that have conserved domains and antibody dependent enhancement has been an issue. At least what we know about this virus to date, we are less concerned about this. And obviously, because we're using the immune system to teach us here in our antibody selection, we hope that we can avoid that issue. Maybe I'll ask Harlan to give his point of view here.
Yes. I mean, I agree. I don't see this as a huge risk. We will be screening for neutralization against the virus of interest. I mean, it would really be the question of we're asking about a strange off target effect that we have in a rare case, but we certainly wouldn't be the likely
safety concern. Got it. Vincent, can you jump in?
Yes. If I could just take that question on biodistribution earlier just a step further. I guess one of the things you've heard from some virologists is that IgG mostly that's the antibody of the bloodstream, the extracellular fluids. IGA is sort of where you have more of the mucosal immunity and so forth. And I guess folks have kind of wondered what does that mean in terms of the ability to get to the upper respiratory tract mucosa relative to, I guess, sort of the alveoli of the lower lungs.
What's your take there in terms of the ability of IgG to get to sort of the lower lungs and sort of where you get sort of deep pneumonia versus the potential nasal pharynx?
Yes. It's an open question in the field right now. When you talk about the normal biodistribution of antibodies, remember that's in intact tissues. And so again, certainly in a setting where you've got markedly compromised barriers within say lung alveoli, it's a different setting. And we also have experience with other antibodies.
I mean, we're developing tezepelumab for asthma and the inflammatory response that occurs essentially at the same site that we're discussing here in many ways for COVID-nineteen. So I think there is precedent here as well, certainly in an inflamed state.
Yes. I was
going to say, you guys might have more insight into more insight than most into where the antibodies go in the conditions for how this would work.
And maybe a second
one would simply be, if you think about the different so you alluded earlier to sort of like when do you need to treat? If you treat earlier versus you treat later, I know we won't know until we actually try this out. But from what you know right now, what would you say is help me handicap the odds of success in terms of early treatment versus later treatments? What's the point at which you say at this point slowing down? At this point, it's probably a little bit too late to impact the virus versus working to buy impact?
Yes. I mean, to me, so in a ventilated patient who's got poor oxygen saturation, that's probably too late. Now at what point is in the course of the disease is too late, too late? I don't think we know. I think we're actually going to have to understand that probably empirically in the clinic.
And I would say one of the challenges that we and the entire field faces right now is that we're going to be doing many things empirically in the weeks months ahead that we would otherwise prefer to march through scientifically, but we don't have the luxury of that time. But clearly earlier is better. I think that no quite there's no question. Is there some sort of threshold beyond which it's too late, I think is a critical clinical question right now. It's one that we would try to address going forward.
And then last one is
a corollary here. So one other thing we've heard from immunologists we've spoken to is that folks are pretty optimistic about the potential efficacy of neutralizing antibodies and preventing the progression from more mild to towards severe disease. I think the one that's a bit more of an open question and folks are falling different sides of the line It is how effective will this be in actually slowing transmission or will we simply have a situation where folks still transmit disease, but maybe they're not likely to then end up in the ICU, for example. What's your sense for the potential on the slowing transmission side?
So what I would say is that, if you're having an effect on the disease course, you will probably naturally have at least some effect on transmission. And remember, lowering your transmissibility even by 20%, the mathematics of an epidemic tells you that that actually plays through over time have a dramatic effect. And so you don't have to lower transmissibility a lot to ultimately have an effect. I do think a goal would be, again, preventing this progression from earlier stage disease to more serious disease. If you could do that even in an outpatient setting, for example, by identifying patients who are at higher risk of progressing the serious disease and administering the product and avoiding hospitalization that clearly helps slow transmission.
And so there are lots of knock on effects that one can envision here. Again, we're going to have to understand a lot of that empirically.
So with 10 minutes to go, I think we're going to ask that go to the next question. I'm pretty sure everybody wants to know, which is timelines. So Dave and I, I don't think you're going to put a Gantt chart up as part of this discussion. But as specific as you can get in terms of your kind of like the logic of the pipeline of the timeline? And Arvind, if you could chime in after them and let us know what do you think Amgen would like when do you think Amgen will likely put press release design around what steps it would be really appreciated?
Sure. So I'm not going to speculate on a timeline given that it's such early days. I would say that we're trying to work on a month, not years kind of timeframe. We're doing many things in parallel that we would do in a typical development program sequentially. Our goal would be to try to get into the clinic on a month's timeline, again balancing getting the highest quality antibody against speed.
And there's some tension inherent in those two attributes. This comes back I think also in what informs our thinking here is part of what you started with, which is if it's more than one antibody required or a cocktail of antibody, it may be all of ours or it may be a mixtures of ours and someone else's antibodies. One might also see a wave of products entering the clinic where some are less efficacious and we get better at understanding over time what makes a better antibody. So all of those things will affect our thinking as we move into development. But to be honest, I think it would be disingenuous to give timeline when we are moving forward with the research phase right now.
And Arvind will chime in here in a moment. But I think we'll commit to providing updates when we feel we have meaningful data. I've given the team a clear mandate here, which is let's worry about progress, not press releases. And progress will determine when we disclose things publicly, which will be when we have something meaningful to say.
David, I think that's very well said. We can't speculate on the time lines, Ronny. And as we get meaningful updates, of course, we'll provide those progress updates.
I'm going to pressure on this just a little bit and say that, David, if you're not in the clinic by the end of this year, would you be disappointed?
It depends what we ultimately enter the clinic with. And so again, that's that, as Arlen said, if you can pick the Michael Jordan of antibodies, I'd be happy to wait 2 or 3 more months to do that. I think you're likely to have a much greater impact. So again, we will be balancing optimizing antibody selection with speed as we go along.
Okay. I got a couple of questions on the cell on the emails, and I'm going to jump into them now. So one of the question is and we're going to dive into the science here a little bit, but the relative roles of B cell and T cell immunity in COVID-nineteen, I'm sure there's a lot we don't know yet, but to the extent we do can say certain things. Can you talk a little bit about the relevant role of both of those?
Yes. Just for so very roughly for sort of the way I would B cells prevent reinfection. So normally speaking, B cells prevent reinfection. So normally speaking, B cells or antibodies come up later and they're not playing a huge role in clearing the infection, which is why finding a neutralizing antibody is rare, where there you're actually looking for an antibody itself that can clear infection, which is not normally what they do. So that's a pretty special antibody.
And so for that's how we would think about most vaccines are trying to induce an antibody response that will convey long term immunity or protection. And the T cells are a necessary part because they coordinate the response, the helper T cells. And there's obviously some T cell memory as well. But primarily people think about antibodies as driving the protection.
Devin?
Yes. I don't think I have much to add to that. I think that's our understanding. Our understanding in the immune response to this virus is evolving very rapidly. And there are some strange features of the immune activation that appears to go on here with IL-ten spiking in ways that, for example, haven't been seen with some related viruses, macrophage and neutrophil engagement that seems a little bit odd.
I think we're in the early days of that understanding, but understanding that immunology will be critical to give us insights into how to optimize these therapies.
Alan, I got a couple of questions from a broader audience. The first one is, if you can comment on this issue of kind of like attenuated, kind of, live attenuated virus or kill virus is the ultimate, but what we should be aiming for in terms of getting immunity? And is this just being an immunologist and being so deep in this, is this really what we should be aiming for when you think about a vaccine? That's question 1. Scott, why don't you take that one first?
Yes. I think ideally, yes. The immune system is a system. So in order to be most efficacious, you need to engage the entire immune system. As David was just saying, there's even beyond the adaptive immune system, there's parts of the innate immune system that are playing a significant role.
But certainly, having a broad, well coordinated response will provide we believe will provide the best overall protection long term. So that would be an ideal. However, that's a longer road to toe than sort of these new methods of these RNA vaccines that can be made very, very quickly. So there's the balance there.
There's a trade off, yeah. Yes, I
would say it's early days. The SARS and MERS experience should be humbling to all of us because you could actually generate an immune response in some of the vaccine attempts there, but it was never really neutralizing and trying to understand why that was is very important right now. And are there things about this virus and there may be that actually lend itself a little more to vaccine development. But that's where I think the vaccine experts to comment more than me.
So David, I guess I want to follow on this because it's kind of interesting. Have you kind of looked it sounds like you've looked at the experience of us trying to develop vaccines against other coronavirus. And it sounds like you don't think that they would necessarily there's some issues with developing vaccines for coronavirus. Can you talk a little bit more about that just to educate us all about what had happened before and perhaps technically why this coronavirus is being paying for vaccine development?
Yes. I think the short answer is we don't know why it's been so challenging. Again, you can generate antibodies, for example, against the spike protein, but they ultimately do not seem to prevent infection. Now I would say there's one big caveat here, which is the effort that's being mounted now is on a scale far beyond what I think we have ever seen before for a coronavirus. And so the hope is that we can generate insights much more rapidly and that there are features of this virus that lend itself a bit more to a vaccine.
But I'm not a vaccinologist and I would defer to those folks on these sorts of questions.
And Harlan, I'm going to give you the last one here, which is a question from the audience to kind of describe a little bit about further how differentiated your approach is, what makes the differentiated versus otherwise speaking to kind of Michael Jordan antibody, which I guess is the reason why I'm just working with you guys. And give us your kind of assessment of where you guys are.
Yes. So, I mean, I think from our advantage is our ability to sequence and screen at scale. So we're able to go after a wider pool of potential antibodies. I know that there's a variety of other groups working in this direction and a lot of them have their own abilities as well in different areas. But that's our particular niche that's kind of proved successful on the T cell front and the same technology, which we developed over the last decade on the B cell side works at scale in the same way.
So I think we just from what we know basically, we think that should be a significant advantage. And but that I don't know enough about. And that most companies aren't super forthcoming about exactly what their techniques and technologies are. So I don't know that I could do a direct comparison across the board of what everybody else is able to do. Hopefully, there's a variety of successes because this is not one of the areas where we're rooting to win.
We're just rooting for a cure or so.
Vincent, last question for you, if you got something by email that you'd like to ask?
No, I think that's it from my side.
Very good. So first, I want to again, this is certainly one situation where we all wish you guys great success in this endeavor. It's very important for all of us. So really appreciate you getting on the phone with us today. And hopefully, hoping for some good news from you in the next in a few in the coming months.
Thank you very much guys. Thank you. Thank you.
Thank you.
Take care. Goodbye.