SIGA Technologies, Inc. (SIGA) Earnings Call Transcript & Summary

AGP's monkeypox virtual series in biotechnology and spec pharma. My name is Jim Molloy. I'm the biotech and spec pharma analyst here at Alliance Global Partners. Before we go any further, I'd like to point you to disclosure slides. It should be on your screen for the 3 companies that we have today: SIGA Technologies, Tonix Pharmaceuticals and Emergent BioSolutions. The format of today's webinar will be a 60-minute fireside chat with our guest panelists from EBS, SIGA and Tonix. All 3 of our panel companies are at the forefront of treatments and vaccines for monkeypox, smallpox and COVID-19, among other things. I'll be moderating the panel over the next 60 minutes. We'll have a hard stop at an hour. And our webinar attendees will be muted during the webinar. But if anyone has a question you would like to ask or get in, please feel free to utilize the chat room or e-mail me directly at [email protected], which should be right over my shoulder here as well. I'll try to get that question in for you. Propitious timing as well to have our webinar today. The World Health Organization is convening an emergency committee today to see if they're going to declare monkeypox a global health emergency with, I think, we got 3,417 cases over 58 countries. I think being caught flat-footed on COVID, the WHO doesn't want to have that happen again. Not that monkeypox is the same as COVID. We'll go through the differences, obviously. I'd like to start by asking our panelists to please introduce themselves, their company and their monkeypox, smallpox products and development candidates. And we'll go back to me, and I'll go through the discussion and get it rolling with some questions. So we have a lot to go over today. I'll go in alphabetical order of my company. We'll start with Adam and Atul at EBS for introductions, please.

Well, thanks, Jim. It's a pleasure to be here and good to see some of the panelists again. Excited to talk about the current situation. As you mentioned, my name is Adam Havey. I'm the Chief Operating Officer at Emergent BioSolutions. Emergent is a company that really lives in the life sciences space but focuses on public health threats. We've been partnering with the U.S. government and governments abroad to really deal with these types of issues over the last couple of decades. Our mission is really to protect and enhance lives, really have a meaningful impact in public health and really allow folks, our patients and customers to be prepared for when some of these unfortunate events occur. So giving folks a peace of mind when things are a bit uncertain, that's who we are and what we're all about and excited to be here to talk about the current situation. Atul, do you want to give them an overview of your background and what we're going to talk about?

Sure. Thanks, Adam. And I'm joining Adam here as the Chief Strategy and Development Officer for Emergent. I'm not going to reiterate what Adam said, but Jim, thanks so much for having us. Good to see all the panelists and looking forward to a lively discussion.

Thank you, gentlemen. Dennis and Phil at SIGA.

I'm Dennis Hruby. I'm the Chief Scientific Officer here at SIGA. I've been involved in the discovery and development of our antiviral drug TPOXX, and I continue to work with my R&D team to expand indications and bring other drugs along the pipeline. Phil?

Thanks, Dennis. Phil Gomez, I'm CEO here at SIGA Technologies. We're a company, as Dennis has described, that's been in the medical countermeasure of health security area for a long period of time, including long-standing collaboration with the U.S. government to develop TPOXX or tecovirimat, which is an oral drug that's approved for smallpox in the U.S. As we go into the discussion, just a little context. We've provided over 2 million courses of that drug to the U.S. Strategic National Stockpile. SIGA's had over $1 billion in contracts associated with development and stockpiling of that. And importantly, prior to the monkeypox outbreak, we did gain European Union approval under the animal rule for smallpox and monkeypox. And our team has been collaborating to do compassionate use treatment in Africa, in the Central African Republic through a collaboration with Oxford and the Institut Pasteur as I think all of us have come to realize this is a problem that has not just popped up overnight. It's been increasing over the years, unfortunately, in Central and Western Africa. So Jim, we appreciate the invite today. Look forward to the discussion. Back to you, Jim.

Thank you, Phil. Seth?

Thank you. I'm Seth Lederman, CEO of Tonix Pharmaceuticals. And we're in the development stage of a vaccine that we believe will be protective of smallpox and monkeypox. It's a live virus vaccine, and we think of it as potentially a next-generation product over the existing live virus vaccine that you'll hear about from Emergent. And we, so far, have just animal data, but our goal is to constantly improve, innovate on products with the goal that potentially changing the risk/benefit profile of vaccines might make it more appealing for governments and public health officials to think about more broad vaccination.

Well, thank you. And then in the effort of my trying to be seen but not heard, let's go back right around from Seth and we'll go back the other way. Let's talk about the World Health Organization meeting today. Your thoughts on what could come out of that and sort of what the implications might be for broadly and for Tonix in particular.

Well, thank you. It's hard to predict what the World Health Organization will do, but it is a sign that they're taking this very seriously. As you said in your introductory comments, Jim, this has now spread all over the world and more than 3,000 cases. There were some experts at the beginning who are saying that this might peter out, that it would be self-contained, that just isolation, case identification, case contact, that kind of measure would suffice. It seems like that is not sufficient. So I think now we are all very concerned that spread outside Africa will continue. There's a lot of concern in my hometown, New York City, where there's a pride event, a parade and other festivities scheduled for Saturday, which is 2 days from now. And this is concerning because there was a similar type of event in Spain that was one of the events that is believed to have contributed to some of the spread. So hopefully, there's been a lot of public health awareness. And hopefully, people take appropriate measures to keep safe. But now I think we all are prepared for an expansion of this. There already were 17 cases in New York City, according to New York Times last week. So if that's increased and then also there's probability that if there's 17 diagnosed cases, it's kind of like an iceberg where there presumably will be cases that are not yet diagnosed. So it's a big concern that this hasn't spread. But to echo your comments at the beginning, the other panelists, this has been growing in Africa for years. And it's really, on the one hand, it's unfortunate that we didn't take more care to pay attention what's going on in Africa. But on the other hand, we really have to congratulate BARDA in the United States for focusing on vaccines and antivirals and congratulate the other panelists and their companies for really getting ahead of this. We have vaccines and antivirals ready.

Yes. I'd love to echo Seth's last point in particular. I think there's no substitute for preparedness when it comes to a wide variety of public health threats. And I think certainly, smallpox, which was eradicated, has had a huge mortality, right, 3 out of 10 people died. And I think that's something that was tremendous that we were able to kind of eradicate through the appropriate vaccination and the preparedness since that time against accidental, intentional and naturally occurring sources of public health threats across the board is really important. I think it's really critical that we not focus just on one particular disease and kind of look at how preparedness efforts work across the spectrum. And I think it's also really important that the early warning and detection systems that we have with public health agencies like the CDC and with the World Health Organization are important to kind of gauge what the right response is at any point in time. So like Seth, we can't predict what's going to happen with the World Health Organization, but I think I'm comforted by the fact that they're focused on it. It is true that it's been endemic in Africa for a number of years in various African countries. But at this point, we're seeing over 3,000 cases in about 40 countries that we have not seen it historically. And so tracking it and trying to identify where it might spread and how to make sure that the world is prepared for it, I think, is important.

Phil, your thoughts on the virology today?

I'll defer to my colleague, Dennis, who's our Chief Scientific Officer and a long-standing pox virologist. Dennis, please.

Yes. Well, I've had a number of conversations with WHO over the last couple of weeks. So I know certainly they're taking this very seriously. Myself, I'm hoping they do declare a global emergency. As other panelists have noted, it's circulating in the population. Numbers are going up. We're probably only seeing the tip of the iceberg. And we have to remember that the longer this virus circulates in the human population, there's a greater chance for a mutation, so it spreads more easily. This is not going to be easy to stamp out because pox viruses like monkeypox have a long incubation period, 7 to 10 days with no symptoms. And so trying to do contact tracing is going to be a challenge. So I think this is serious. We have to pay attention to it.

Maybe, Dennis, could you walk through the similarities and differences? I know that the WHO, most people, I guess, were caught a little flat-footed by COVID and people obviously don't want to do that again. Can you walk through some of the similarities, differences between the monkeypox, smallpox versus, say, COVID in transmissibility and things like this.

Well, certainly, everyone is aware of the smallpox situation where, as pointed out, 3 out of 10 people would die, and it's highly infectious to the respiratory route. And so from that standpoint, it's kind of like super-COVID, much higher death rate. And as Phil noted, in most exercises that have been done modeling the spread of smallpox, it goes global and has a dramatic impact on morbidity and mortality. Monkeypox is a different disease. At least in Africa, the disease looks like smallpox. Hundreds of lesions, illness, 1% to 10% mortality depending on the strain, but it's not easily spread. It's really spread by direct contact or very close association with the patient. Now that could change. And hopefully, that won't happen. So I think as pointed out, we have the opportunity here. COVID, we did not have vaccines. We do not have drugs ready. In the case of monkeypox, we have both. And so it's really incumbent on the health agencies like the WHO and federal governments figuring out how to deploy those once it becomes epidemic.

Maybe a good segue over to EBS, Adam and Atul, on what you guys have ready because recently you did the Tembexa acquisition, walk through that and how that could be brought to use here.

Sorry about that. I'm happy to kick this off. And Adam, please feel free to chime in as well. I think going back to the comment I made earlier, we continue to focus overall broadly on public health threats. And the most relevant in terms of the preparedness and response is focusing on category A threat, and that includes things like smallpox, anthrax, botulism, where we have different types of products. And we've looked at both vaccines and therapeutics in order to be able to address those types of threats as they come up. In our portfolio, we have ACAM2000, which is the smallpox vaccine that is stockpiled in large numbers by the U.S. government in the event of a smallpox outbreak. And we also have a product called VIGIV, which is a plasma-based hyperimmune product that's also stockpiled by the U.S. government. And then as you mentioned, Jim, we signed a deal with Chimerix not too long ago, under which we would acquire the rights to Tembexa, which is a smallpox antiviral. That deal hasn't closed yet right now. So it's still Chimerix's product, but it kind of expands our ability to continue to work with the U.S. government on preparedness and response initiatives in order to make sure that there's appropriate availability in the case of any type of an outbreak in which it might be deployed. Adam, anything you want to add to that?

No. I think you covered the high points. I think no, nothing to add.

We're on the topic, going to back to SIGA, if we could, talking about you guys have TPOXX out there. You just had a nice press release this morning with another deal signed to have that stockpiled by some Asian and European countries. Can you walk through sort of your preparedness or your drugs that can be used and compare and contrast, if you would, maybe with some of the others that are out there.

Dennis, why don't you start, and I'll talk, Jim, about the commercial and availability questions that obviously come up. Dennis?

Our drug, which is called TPOXX here in the U.S. or tecovirimat SIGA in Europe, was developed in partnership with the U.S. government. And as a process of doing that, we conducted many, many animal studies, including monkeypox and nonhuman primates. And we know the drug is highly effective against multiple strains of monkeypox. It will protect an infected primate when given very late in the disease course. And we have very little doubt that it will be effective against monkeypox in humans. It has an excellent safety profile in multiple clinical studies. We have had no SAEs. Some very mild AEs are really consistent with the placebo. So it's a very, very safe drug, primarily because the target that it hits is simply not found in the human genome. It's very much limited to orthopoxviruses. Another safety signal is we've used the drug in a number of compassionate use cases with people infected with vaccinia, having vaccinia complications, cowpox and several monkeypox patients. And we've seen good effectiveness and no SAEs. So we believe the drug will be quite useful in the current monkeypox outbreak.

And Jim, maybe to bolt on to that. So with that data, another important program that's supported by the U.S. military is using our drug as a post-exposure prophylactic use. So the idea there is to give our drug to suspected exposed people. We're doing a clinical study now where we give the drug and we immunize with Jynneos, the replication incompetent MVA-based vaccine from Bavarian Nordic. And the idea there is it's a one-touch intervention. If they haven't been exposed to smallpox, the vaccine would provide long-term immunity. If they had been exposed, the antiviral drug TPOXX would provide a big benefit on not progressing to disease. In this outbreak, though, we had the press release today, $13 million in some initial orders we've gotten on monkeypox. We see this evolving in kind of 3 stages, which I think are really important to set context on how this is going. There's an initial reaction from governments certainly focused on vaccination, which makes sense, but it's also focused on getting antiviral drug for cases they have active. So the first call we typically have been getting is, I've got X number of cases. I need to get antiviral drug in case any of those have severe complications. The second phase of the discussion is, as you look at the WHO guidelines, and they highlighted that the use of antiviral drugs is expected to evolve, including the use for post-exposure prophylaxis. The U.K. has published, they're going to do a study for outpatient treatment to treat patients with monkeypox in an outpatient way, and they cited that tecovirimat was the only drug they were considering. So I think there's going to be an evolution as we learn more about drugs, vaccines, how the contact trace vaccination is going. That'll be the second phase of what we've learned in this outbreak in conversations about what the response will be. And then I'd come back to the one that Atul and Seth have both highlighted, which is ultimately the orthopox family contains smallpox with high mortality, high transmissibility. And it's great that the U.S. and, for our case, Canada have purchased our drug, had stockpiles, but no one else really globally has. And a big call to importance here is for the international organizations and countries to also stockpile these products in the event we did have a larger outbreak because there's no way to respond after the fact in the magnitude of vaccine, antiviral that countries would need. So hopefully that will be a lesson learned from this as well.

Seth, I'd love to get your thoughts. You are obviously early in development than SIGA and EBS and Bavarian Nordic out there as well. What are your thoughts on sort of the current landscape? And if this thing goes, certainly plenty of people who would need a vaccine or therapeutics going forward, so plenty of room in the pool. Would love to get your thoughts on the current players out there and then the development pipeline you guys are working on.

Thank you. And you can never be 100% prepared. And we are, to some extent, in the United States, somewhat back to our heels with how rapidly this has spread and the disappointment that it wouldn't just become self-limited. But it is great that we're sitting here with 2 companies making different antivirals and one of them making a vaccine. There's another vaccine approved. So this is somewhat encouraging. But I'm really focused on the longer term. Our product is in development. We've tested it on nonhuman primates and vaccinated nonhuman primates were protected against a lethal challenge with monkeypox. And we're impressed with the animal data in our drug. Our drug has not been in humans. But our idea is that if you look at the so-called real-world evidence, I think many experts believe that when smallpox vaccination was widely practiced, monkeypox was contained in the animal population. So that is probably a state where we should be heading, I think. The world is getting smaller, more populous. People are traveling more. So I don't know when that time is, but I think at some time, it would make sense to consider returning to so-called universal vaccination. But what a universal vaccination mean when it was practiced, it was really vaccinating healthy people, immunocompetent people who could tolerate a live virus vaccine and then benefit from getting a live virus vaccine. And obviously, Emergent has a great product, ACAM2000, is the pillar of our stockpile. And I think that as a live virus vaccine, it has a lot of the properties that we look for in live virus vaccines, which very importantly are durable immunity in people who studied the vaccinia protection. And there's even data 70 years later, people are protected. So it's phenomenal in that regard. And also the real-world data that it blocks forward transmission. And you started this off by talking about, what's the difference between smallpox and COVID. But one difference is, we know a lot about smallpox. We know a lot about monkeypox. When COVID hit, it was a big unknown and it was terrifying because it was so unknown. But one of the things about smallpox and monkeypox is we really know a lot about them. And we know that in a population, if you vaccinate the healthy immunocompetent people who are 5 years old or older, then you're protecting the pregnant people, the infants, the immunoincompetent people because it's the analogy of wetting the forest. It's just not going to spread if you've already vaccinated the healthy people. And also if you vaccinate people when they're healthy, they have a prolonged durable immunity for, for example, if they become less healthy in the future. So our goal as a company is to take on all the great properties of the existing live virus vaccines and potentially decrease the risk of getting them. What we're working on is called horsepox. It in tissue culture makes smaller plaque sizes. In mice seems to have less virulence and in monkeys was well tolerated. Our model goes back to we think that we're working on something very close to what Edward Jenner used in 1798. And there's a lot of evidence of sequencing older and older smallpox vaccines using the same kind of techniques that people used to look at Neanderthal DNA and the rest of it that all of the vaccines that have been sequenced from the 1800s were closer to horsepox than to the modern vaccine is. So our model is that if we could go back to something very, as if Edward Jenner had, had a master virus bank, our idea is that if you could go back to that, then you may get something that has better tolerability and preserve the features of the other live virus vaccines. So I think that we're really in for something with monkeypox, but monkeypox is really, the current monkeypox is really a warning. Someone brought up earlier this is the West African strain. The Central African strain has as much as a 10% mortality, and there's no reason why I know why that isn't the strain that we're confronting now, but so far it's not. Now a lot of the 10% mortality, the roughly 10% mortality in that group is infants. And this is not a situation you want to confront them on our heels. The other is smallpox is mentioned. I think that rogue nations, the terrorist groups, people looked and saw what COVID did to us. I think it may have encouraged people to think about these primitive weapons like smallpox. One of the general problems of our military is we're very, the United States military is very good at working with sophisticated threats. But if you look at us all over the globe, when we get involved in conflict, we're hurt by the primitive threats, the IEDs, the roadside bombs, these kinds of things. So I think that we really have to up our game and really have to consider more broad, maybe even mass vaccination with live virus vaccines. And our goal is to be innovating and possibly bring forward one with better tolerability.

I think Dennis or Atul, Seth introducing back Ed Jenner and back to Neanderthals, so a bit of history to walk through, but any thoughts on Seth's comments of development.

Yes. I mean, I'm one who is always a champion of good innovation in the biotech and pharmaceutical space. I think we can continue to look for better solutions across the board. And I commend Seth and Tonix for the work that they're doing. I think that's always great to see interesting technology brought forward, and we'll cross our fingers and hope that they're successful. In the meantime, as Seth mentioned, the ACAM2000 is derived from Dryvax, which actually was what was used to eradicate smallpox in the first place. It's stockpiled by the U.S. government. And at this point, in addition to the 3,000 patients or so that were used for the initial clinical trials and approval in the last -- between 2009 and 2017, there are nearly about 900,000 people who were vaccinated with it. And so we have some real-world data in the population to understand how it works and kind of make sure that it's the right thing. I did want to clear up, Jim, we were chatting beforehand. Sometimes there's a misimpression around what it means to be a live virus vaccine. And in this case, it's a vaccine that's based on vaccinia, which is the same virus that was used to eradicate smallpox. It is not variola, which is what causes smallpox. And so I've seen a lot of misinformation out there about, well, could you get smallpox because of this? And the answer is definitively no. They are 2 different viruses, and this one is used for vaccination purposes.

And the highlights from the comments about London finding polio in the wastewater and the value of something else. Dennis, any thoughts on this?

Yes. I think you never have too many vaccines or too many drugs. The safety profile of the vaccine to be used in different populations. Jynneos, for example, is a non-replicating virus. So it's definitely going to be reserved for immunocompromised. As far as antiviral drugs, I notice in the chat there's a question about resistance with TPOXX. We don't think that's an issue for acute use. In 40-some animal trials, we never saw a failure due to emergence of resistance. The spontaneous resistance rate is about 1 in 10 million. So that by the time that resistant mutant were to grow out, your immune system will be fully armed and take care of it. So we don't think resistance is an issue so. But having different drugs with different mechanisms to perhaps be used in combination, particularly immunocompromised individuals, that's a good thing.

I would add to that. I mean, I agree with where Dennis is coming from. I think I know there's a lot of apprehension in the public because of COVID and the pandemic. And I think it's important to understand that the orthopoxviruses tend to mutate more slowly than something that we see in COVID. It doesn't mean it can't mutate, but I do think it mutates more slowly. And so resistance developing is something that is probably a little differentiated. But what it really importantly highlights is the need to have multiple different approaches so that you can address if that situation arises. What you can't deal with is in the middle of an outbreak or an epidemic or a pandemic, there happens to be a mutation. What do you do at that point? The preparedness is absolutely critical across the board to make sure there's multiple ways that you can address an issue when it comes out.

We certainly saw some mutations with COVID that I think initially people weren't expecting. Any thoughts on, I would just go back to, you can never have too many drugs, Hunter S. Thompson couldn't have said it better. But any thoughts on potential mutations on monkeypox or smallpox and how to deal with those as the COVID variants came through?

As the pox virologist, I'll answer first. I mean, it's always a concern. I mean, the genomes of monkeypox and smallpox are more than 90% conserved. And I don't think anyone can predict what kind of mutations will change the host range, the pathogenicity or the transmissibility of monkeypox. So the longer it circulates in the human population, the greater the chance of that. So it's a risk that we have to keep our eyes on. Now whether or not it might mutate to being resistant to other vaccines or to the drugs that's doubtful, but we'll see.

Yes. And the question comes in, is it known how the Central Africa's more deadly strain, Seth, how that is for resistance versus the one that you're not sure it is the Central one.

Yes. I'll echo what Dennis said that, by and large, orthopox mutate more slowly, but one of the huge advantages of Emergent's product, ACAM2000, is that the vaccine is grown in cell lines and doesn't mutate. And that was one of the weaknesses of Dryvax and the rest of it. So I think that one of the concerns about monkeypox is that if it really gets spread out, if you have 2 strains in the population that I think with crossing over a recombination is quite a bit more frequent than mutation. So I think that if you can keep something clonal and there's just one monkeypox around like in the cell culture grown vaccines, and so far, I'm not aware of mutations in what people are seeing in this non-African outbreak of the West African monkeypox. I think we're okay. But again, as it gets more and more broadly spread out and particularly when you start getting people maybe infected with both, it's hard to predict.

Maybe a question for Adam or Phil. I think back when I just covered EBS and BioThrax, you were looking at government contracts in the $1 billion range. Is this something that the U.S. government is going to be stepping up to SIGA and EBS and Bavarian Nordic, and then hopefully down the road towards Tonix with sort of these vastly larger orders than what we've seen to date?

You want me to go, Phil?

Yes. Go ahead, Adam.

Sure. I mean, I don't know about changes in preparedness. I think, Jim, to how we started the conversation, I think the government has been preparing for those category A threats. Fortunately, in this case, smallpox is in that orthopox family. So I think in the context of the current contracts, I would think that there might be additions to and some other development exercises like Phil's team has done at SIGA where you can expand the indication. I think there could be some discussions around what would it take for ACAM to have a monkeypox indication or an orthopox broad indication. But I think from just a basic preparedness standard, the contracts right now are typically longer standing and the government has been behind them, at least for ACAM2000, for VIGIV for SIGA and Tembexa and Jynneos. So I think that framework of preparedness works for orthopox, at least for today. Obviously, I would expect some additional prioritization around funding from a development perspective, but I don't think the materiality, maybe the requirement grows a little bit, but I don't think we're talking a 2x change. We're talking probably maybe an increase of X percent or Y percent. I actually think from a broader preparedness perspective, Jim, it's not the U.S. government stance. It's what Phil said earlier, it's the global community and other countries either taking a more aggressive preparedness posture around these category A threats, I think that's what's needed. It's countries in Europe, countries in Southeast Asia, countries in the Middle East taking and being more proactive like the United States has been.

Yes. Adam, I'd like to echo that. And I look back at the G7 publication of the 100-day plan. The U.K. has published that. The Biden administration came out with a post-COVID strategy that really focuses on families of viruses. So if we look at COVID, I happened to be at NIH many years ago and worked with the team that developed the first SARS vaccine, in retrospect, probably should have focused on a pan-coronavirus vaccine development back in 2003. And I'm very happy to say that I think people have coalesced around this idea that we should prepare for orthopox broadly. Prepared doesn't mean we've discovered and developed drugs. Prepared means we have them deployed and we're ready to use them if there was ever an outbreak. And that is what happened in the U.S. with limited resources. There's been a lot of debate about that if the spending is commensurate with the risk. For us, at SIGA, that's meant Canada has purchased our drug. And Jim, I would reiterate, as we see this, as we think about the commercial opportunity, unfortunately, the rest of the world had not stockpiled our antiviral drug before the outbreak. But the incoming calls are kind of the immediate, can we get some drug in case we have severe cases? The next part, though, they think about is that, what is the intervention in this outbreak going to be? Seth, we've all talked about the fact that if this spins out of control and we do have endemic, that would really be a lost opportunity because we have antiviral drugs and vaccines that could be used to interrupt transmission. And I've been talking to people in public health that worked in the early days of the HIV outbreak, which unfortunately didn't have a fast response because people said, hey, it's a targeted population, not really clear what the impact is. There's a window here to use the tools that we have to really aggressively try and intervene here. And that could be being able to use chemoprophylaxis as the Hong Kong strategy highlighted, or as WHO talked about, post-exposure prophylaxis, thinking about ways to combine all the tools in our toolbox to potentially intervene here. But I also agree that then the third level is that broader preparedness and thinking about smallpox, what could happen to monkeypox. And so the commercial opportunity for us, Jim, is going to be driven by the virus and the response. We're in a mode where we're trying to respond to and help public health agencies, educate them on the data that Dennis has described, make sure we support any randomized controlled trials that are going to look broadly at treatment of prophylaxis. So we're making sure we're a good public health partner and going to be ready should those larger orders come in and those conversations come to fruition. So a lot of work going on there.

Jim, if I can just add to what Phil and Adam said. The United States government actually has a very comprehensive approach that it uses. It's got something called the Public Health Emergency Medical Countermeasures Enterprise, PHEMCE, which coordinates a whole of government approach for medical countermeasures. And you specifically see the leadership within Department of Health and Human Services of the Assistant Secretary for Preparedness and Response as kind of a lightning rod to kind of coordinate a lot of those activities. I think that's been very powerful to kind of calibrate what are the right threats and what is the right level of preparedness across that. And I think as we look at other countries across the world, developing those infrastructures to ensure that within those countries there's an appropriate whole of government response as they evaluate the threats for those countries is actually kind of a really critical set of infrastructure that needs to develop. And it's kind of at different stages in different places. You're starting to see it develop a little bit more in the EU post-COVID pandemic. But I think that's where the actual growth needs to be, and that will kind of determine what those needs will be in the various countries.

Maybe a question for SIGA and EBS now and a question for Tonix in the development. How do you guys stand on production? How quickly can you ramp up SIGA and EBS currently if the demand is there and the need is there? And are supply chain issues still an issue? And then for Seth, in your development, how the supply chain issue is trying to develop things? But we'll start with the SIGA and EBS on ability to turn on the faucets.

Jim, yes, absolutely. So thanks for the question. So we've been fortunate. We've been manufacturing this product for delivery to the Strategic National Stockpile since 2011. It is a U.S.-based supply chain. We've worked very hard to work with our colleagues at BARDA and ask for the Assistant Secretary for Preparedness and Response to make sure we have as much of that supply chain broadly, including raw materials in the U.S. For the past several years, we've supplied over 360,000 courses to the Strategic National Stockpile. We've also been supported by BARDA to create a second active pharmaceutical ingredient manufacturing site. So we do outsource our supply chain, that's listed on our website, our great partners that help us with that. So we do have an ability to scale up in response to needs. And certainly, we, as Atul mentioned, have a great partner in the U.S. government to work with to think about manufacturing planning, scale-up opportunities. So as we think about those 3 phases, the initial response for cases, then what's the actual intervention going to be, we certainly are in very good position even globally to deliver on the first 2. The longer-term question of what is smallpox preparedness broadly, that will be a broader question for us. But fortunately, we're a small molecule, orally available capsule. And so we can scale our supply chain.

Yes. So a similar story on our front. I think, again, the benefit of preparedness and time, we've got a U.S.-based supply chain that's robust. We've been delivering about 18 million doses a year to the stockpile. And that's kind of the standard run rate for us right now, Jim, in alignment with what Atul said, PHEMCE and SNS requirements. We do have a surge kind of component to our programs, as most of the government contracts do. So we have the ability to probably double that or maybe get a little bit higher than that if we needed to. But like with COVID, those things take time. So those things don't happen immediately. But if the government was to need it, we could start implementing those plans. There's probably a 6-month lag between when you say go from when you start really seeing the benefits of that increased throughput in production. And the good news is, again, in the preparedness stance, I mean, there are quite a few doses in the Strategic National Stockpile. So immediate kind of initial response and intervention, I think we're in a pretty strong across the board in most of these cases having the products where they need to be and we can get them where they need to be if needed for today. And then it's more about how do we just maintain and sustain those capabilities over time. And in good times when things aren't, if there aren't as many outbreaks and things that these dollars get challenged, and I think our voice would like to argue that, hey, in those times, don't forget what's happening now and make sure we continue to prioritize the funding around these category A threats.

Seth, any thoughts on any supply chain issues for you as you're working on your development?

Yes. So again, we're just in development. So we're not as mature in the sense of these other 2 great companies. But we did just 2 days ago celebrate the opening of a facility in New Bedford, Massachusetts, which is capable of producing GMP vaccine. And our estimates right now is we can, we expect to be able to, each run would be about 10,000 vials. And very similar to ACAM2000, we expect to have 100 doses per vial. So it will have substantial capability, but nothing like the capability of the more mature products. We're in the planning stage of a commercial manufacturing facility in Montana, but that would be several years away.

And you've made a big push over the last year or so, in the last 2 years, to bring everything into the U.S. So SIGA just said the same thing and EBS I presume. Is onshoring a vital component for an SNS product like this?

I mean, I think it's not 100% essential. I think you can have manufacturing in different places. That's actually very common for pharmaceutical products. That said, I think there is a general bias and a preference for the U.S. government to minimize supply chain risk issues. And certainly, if there's geographic limitations that could come up in a outbreak or pandemic situation, I think they tend to favor those that have fewer supply chain risks, especially if you need it in a surge situation.

I'll just add that getting anything done in the pandemic was very challenging. Borders closed, supply chains are broken. And even now, the supply chains are not normal. Just getting things like PBS can be challenging. Just for those of you who don't know a common material that you need to make things. So I think not only do you need, I think it may be more important than a completely domestic supply chain that you need warehouse space and protocol to test products from your warehouse for stability over time. But I think that particularly in this line of business, one shouldn't count on borders being open or supply chains being flowing freely in order to deliver these life-saving products.

I think domestic is important to the Atul's point, not critical. But I think what Phil was alluding to, I think having partners and making sure we're doing things to have proper risk mitigation, so backup suppliers, all of those things are critically important especially when things kind of escalate quickly. Like the key there, I think, is having some of those contingencies well thought out and well in hand.

Dennis, please go ahead.

Yes. I would just say to echo Seth, the supply chain issues are still a problem. I mean, they can be trivial in the sense that we've had trouble getting labels. We've had trouble getting vials, the proper boxes. So even having the drug manufactured, being able to put it in the vials and get it shipped to where it needs to be remains to be a challenge with the supply chain as it is.

I know if anyone out there listening has a plum or 2, please feel free to e-mail me. Well, we're around the home stretch here coming into the last, coming into the finish. Let's go through and talk about next-generation products at SIGA and EBS and then, Seth, obviously, you get the earlier stage. Dennis, how is ST-357 or what's the jewel or the crown, so the next thing from SIGA?

Well, for TPOXX work, that still is, we're quite busy. One, we've been thinking the post-exposure prophylaxis indication approved will be vital for preparation and that will allow people to use it. We're developing a pediatric formulation, a powder for reconstitution to be used in very small patients. That's very important to us. Then as you highlighted, we have another molecule, ST-357, that is a potent antiviral. It hits all the orthopoxviruses. It's a mechanism distinct from either Tembexa or TPOXX, and we think it'll be important to bring that along. We're currently seeking federal government support to bring that forward. So that still is ongoing for other products, bringing the portfolio, and we'll do that when it makes sense.

Yes. And I'd highlight, Jim, as well, we do have a collaboration with Cipla that has an antibiotic that could, a novel antibiotic that's licensed that could be used for biothreats that we've teamed with them for future, what we anticipate will be request for proposal from BARDA on that space. And there's the question that came in on the chat that I do think monkeypox is bringing up a question of what is the ultimate sales channel for these products. So for example, we have FDA approval for smallpox in the U.S., but in Europe, we got monkeypox, smallpox, vaccinia and cowpox. We certainly will be looping back with FDA and having a conversation. It comes down to is approval through animal rule, which means it's unethical or impossible to do efficacy testing in the virus or is it through efficacy tests that'll be going on very likely in Europe and Canada and elsewhere on that. So we'll certainly loop back with FDA. Clearly, the vaccine division of FDA thought monkeypox could be approved on animal data when they approved Jynneos. The drug division did not take that stance as we had conversations with them, but we'll continue to do that. And for all the products that we're talking about, if monkeypox would unfortunately become endemic, it does bring up a question of how would they go through the sales channel. Right now, they're all stockpiled and could be distributed by governments kind of like COVID-19 vaccines. But unfortunately, it became endemic, would it be something that you would want to have in STD clinics? Is it something that travelers may want to use? Is it something that maybe like HIV prep that you may want to give to exposed people? So there's a whole lot of evolution that we anticipate to see with the virus and the response. Hard to predict where it's going to go and how it's going to go. But certainly, at SIGA, we've been thinking broadly about those things and doing long-range planning. So we'll continue to monitor it closely.

Yes. Thanks, Jim, for the question. If you don't mind, I'll just broaden it a little bit because we continue to focus on kind of the broader sense of public health threats. And we have a number of different initiatives from an R&D perspective that we're continuing to pursue across a pretty wide spectrum of threats. I'll highlight 3. First is on the smallpox, monkeypox question because it is acute right now. We've been looking across ACAM2000, VIGIV. And then once the transaction closes, Tembexa, to be really looking at, are there spaces where it makes sense to try to expand the label for those programs to other orthopox situations. As was noted earlier on the call, there was a point when there was full vaccination that you saw a reduction in other orthopox transmission human to human. And I think that is something that we're in the process of evaluating, particularly given the data that we have historically. The second thing I would highlight is that we continue to focus on anthrax preparedness across the board. BioThrax has been used and approved for many years, but we have been developing a new anthrax vaccine that's currently designated AV7909. And we're seeking registration of that with the FDA at the moment. So continuing to advance that, and that's being procured in the Strategic National Stockpile, but we're continuing to advance hopefully towards registration. And then the third thing I would highlight is that as we look at the infectious disease space more broadly, we're seeing kind of an increase in mosquito-borne illnesses, particularly chikungunya right now. We've got a vaccine candidate that's in Phase III of development that we're continuing to advance and bring forward. So we're really looking across a very wide spectrum of where there might be an opportunity to address different sorts of public health threats, and those are kind of the 3 that are top of mind at the moment for me.

Seth?

Thanks. For us, the TNX-801, which is our horsepox vaccine that we discussed for potentially protecting against monkeypox and smallpox is also the platform technology for a broader platform that we call RPV, recombinant pox vaccine. And essentially, what we're doing in that is cloning in antigens from other viral illnesses, pathogens, for example, COVID, where we've cloned in the spike protein for COVID-19 or CoV-2. And we've protected monkeys from challenge with CoV-2, for example. We think that this is a really great platform. And again, it's quite similar to vaccinia or to the basis of the ACAM2000. But for us, it's a platform into which we expect to make a number of products for other conditions. We think that they're really unique characteristics about a live virus vaccine, the kind of stimulation it provides to the innate immune system, the durable immunity it creates, the cell-mediated response, it creates humoral immunity. So we think it's really something that could be used for a number of different conditions. One of the problems about SARS-CoV-2 is that there are many aspects of the SARS-CoV-2 virus itself that actually turns off the innate immune response. And that's one of the reasons why many people believe it's more deadly to older people. They tend to have less of an innate immune response. So we think that instead of looking at, for example, just using a live virus vaccine in a traditional sense like a weakened SARS-CoV-2, to move important antigens onto the backbone of, in our case, horsepox could really change the durability of the vaccine response to SARS-CoV-2 and also potentially block forward transmission. For example, in the monkeys that we vaccinated with our spike protein vaccine, we sterilize the upper airway, which we think could be a marker of blocking forward transmission in humans, although it hasn't been in humans yet. So we see a lot of ways to go. There are general aspects of this. The way it stimulates the immune system, the fact that it's known not to integrate into DNA is very, you can put a number of genes into it. It has more human experience than any other vaccine. It's the most successful vaccine. As was pointed out before, it eradicated smallpox. So we think that there's a lot of room to go with this and we see expanding this platform. And also to conform with the American Pandemic Preparedness Plan of potentially being able to make new clones of this within 100 days of getting sequenced. That's one of the reasons we've set up an R&D center in Frederick, Maryland, this process manufacturing and GMP manufacturing facility in New Bedford and then ultimately a commercial scale manufacturing facility to be able to meet the goal set out of having a vaccine within 100 days.

Well, maybe a quick lightning round here. I know you highlighted some of the things you guys -- that EBS is looking at. But Dennis, what do you see past monkeypox? What keeps you up at night going, oh my gosh, worry about this thing next.

Well, certainly, the -- any respiratory virus that comes to our population, and there's a lot of them out there, I mean, before COVID, there were people who thought hantavirus might be the next great thing. But certainly, any of these respiratory viruses that come out of animals and jump into humans could cause huge problems. And that keeps me up. I mean I think the time has come where we have the science and technology to make vaccines for a lot of these things to develop drugs. And hopefully, we now have the will to do that, to have them on the shelf and ready to go.

Phil, any thoughts?

I'd certainly agree with Dennis. And I do think, going back to the last mile of pandemic preparedness, I've talked to a lot of folks in the kinetic space that said smallpox broadly, and orthopox is a great example of having drugs and vaccines prepositioned, ready to go in an outbreak. Unfortunately, globally, we didn't get to that last mile. And so this really requires political will. It requires leadership on the folks that do the funding for this, both in the U.S. and broadly. I think Adam highlighted this that this is an important issue for the U.S. Most of the experts, as we started to do lessons learned from COVID said we didn't have enough of a lot of the stuff we should have had in the Strategic National Stockpile, and that was based on the limitations and funding in that area. So I do hope these types of things will also make sure we look back and say if there really was an outbreak, and we know what outbreaks would look like, do we have enough of this product? Because the worst thing would be we would have developed them, put them in a stockpile and then not had enough when we actually had an outbreak. So I do think there's a lot of work still to do in this area, but where we were with COVID and being able to rapidly respond was based on a lot of science and work on by people on this call and people by this R&D areas in the U.S. government of NIH and BARDA and DoD. So we have some great success stories. We just have to make sure we get over that finish line. Thanks, Jim.

Same questions to Atul and then Adam. So the last, what keeps you guys up at night for next things to worry about.

Yes. I would say 3 things. One is, I would echo what Dennis said about respiratory pathogens. I think that is definitely an area of particular concern. I would say a second one would be things that are vector-borne, particularly mosquito-borne viruses. And then the third thing that I would highlight as kind of an overall public health threat is antimicrobial resistance. And I think we're starting to see that in a variety of different places. And the investment across the board in terms of both vaccines and therapeutics that could be helpful in dealing with situations where we are seeing types of bacteria, viruses, others that are developing forms of resistance, I think, is actually a risk that's quite large. So I think I would highlight those 3 things.

Adam?

I don't know if this is a keep you up at night. It's more of a, I think it may be a passion, Jim. I think we've got to do more to address kind of the things that Phil and all the other panel members have said about attacking some of these classes of viruses instead of just attacking the individual and again, continuing to be willing to lead from a global perspective in the United States around innovation and putting some dollars and leadership behind that. So just doing everything we can as a company and as individuals or as a collective in this space to drive that message forward.

Seth, any final comments?

Yes. I agree with everything people have said. I'm still very concerned about COVID. I think it's very novel. We have successive overlapping waves of mutants. The amount of mutation going on in this is unprecedented. Maybe it's the furin cleavage site, maybe it's other things but highly infectious. And I think Bill Gates on his book tour put it at a 5% chance, it's probably a good number, for COVID taking a really bad turn even now. I don't think there's any reason a priori why successive mutants should be less dangerous. And in fact, there's evidence that Omicron was more deadly than Delta, at least to older people in the United States. So I don't, COVID keeps me up. I think we should really be more ahead of it. I think that we're really struggling with COVID fatigue in the United States. People don't want to hear about it. Journalists don't want to write about it. Politicians don't want to fund it. But it's out there and it's a big problem. But to end with where we start at the beginning, monkeypox is a real problem. We don't want it to become endemic. We don't want it to go fallow. We don't want it to get into the rodent population in the United States. So this is, I agree with everything that's been said on this call. We should be jumping on this as quickly as possible to try to contain it. And I just hope there's the political will and the public health will to do it.

Well, I can't thank you, gentlemen, enough for your generosity with your time this afternoon. We're coming up on the 1-hour time. And as my father always told me, you have to speak up to be heard, stand up to be seen and sit down to be appreciated. So we're going to wrap up our call here at the 60-minute mark. And thanks to all our attendees for dialing in and all the excellent questions that came through. Take care, everyone.

Thanks, Jim. Appreciate it.

Thanks, Jim.

Thanks, everybody.